Third

Edition

Manipal
Prep Manual of
Medicine
As per CBME Guidelines | Competency Based Undergraduate Curriculum for the Indian Medical Graduate

Manthappa M
MBBS, MD (Internal Medicine)
Associate Professor
Department of Medicine
JSS Medical College
JSS Academy of Higher Education and Research
Mysuru, Karnataka
Former Associate Professor, Department of Medicine
Kasturba Medical College, Manipal University (now MAHE)
Manipal, Karnataka
Email: [email protected]

CBS Publishers & Distributors Pvt Ltd

New Delhi • Bengaluru • Chennai • Kochi • Kolkata • Mumbai
Hyderabad • Jharkhand • Nagpur • Patna • Pune • Uttarakhand

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 to
my brother MK Swamy
and
my daughter Prathiksha

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 Preface to the Third Edition

I am very happy to place before you the third edition of Manipal Prep Manual of Medicine. There was
an overwhelming response to the first and second editions of this book because medical students liked
the simple, compact, and lucid presentation of the subject. The third edition has been revised thoroughly
to make the book up-to-date. Each and every paragraph of the third edition has been given full attention
and many new pictures have been added. Many new topics as specified in the CBME (competency based
medical education) syllabus have been incorporated in this book. The presentation of subject matter in
this book is very simple and easy to grasp without any scope for confusion.
I have noticed that, to get clarity on some topics, medical students have to refer multiple textbooks or
other sources of medical literature because no single book is perfect in all the aspects. For example, definition
of a disease may be good in one book, clinical features in another book. It is very difficult for medical
students to refer multiple books on all the occasions due to lack of time and huge medical syllabus. I have
referred several standard medical textbooks and recent medical literature while writing this book so that
up-to-date information with maximum clarity is available to you.
This book is not a substitute for standard medicine textbooks. It has been written with the intention of
helping the students grasp the subject matter easily and provide for the actual requirements of students.
Read this book at least twice before your exams. Higher the number of revisions, the better it is. Remember
that intelligence and memory are not the same. A genius can have poor memory, and an idiot can have
photographic memory. Albert Einstein was a genius but had poor memory. So even if you are very
intelligent, it does not mean that you always have good memory. Good memory depends on the number
of revisions, and the trick is to revise the subject matter more times, to remember better.
The purpose of the book is served if it makes you a better student and a better doctor by making you
more knowledgeable. Write to me if you have any queries or suggestions to improve the book. I have
provided my email address below. Wish you happy reading and happy learning.

Manthappa M MBBS, MD (Internal Medicine)

Email: [email protected]

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 Contents
Foreword to the Third Edition by Dr H Basavana Gowdappa vii
Foreword to the First Edition by Dr Raviraja V Acharya ix
Preface to the Third Edition xi
Preface to the First Edition xiii

1. Infectious Diseases 1
2. Diseases of Respiratory System 98
3. Diseases of Cardiovascular System 148
4. Gastrointestinal System 249
5. Diseases of Nervous System 298
6. Diseases of Blood 375
7. Diseases of Liver and Biliary System 433
8. Diseases of Kidney and Urinary Tract 474
9. Endocrinology and Diabetes Mellitus 501
10. Diseases of Immune System, Connective Tissue, and Joints 544
11. Nutritional Disorders 572
12. Psychiatric Disorders 585
13. Fluid and Electrolyte Disorders 598
14. Oncology 608
15. Genetic Disorders 620
16. Diseases of the Skin 631
17. Poisoning, Venomous Bites and Environmental Diseases 645
18. Emergency Medicine and Critical Care 668
19. Case Scenario Based Discussion 677
20. Role of Physician in the Community, Medicolegal and Ethical Issues in
Health Care 694
Index 705

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 1

Infectious Diseases

Q. Define the terms colonization, infestation, infection, – Enzyme-linked immunosorbent assay (ELISA)
bacteremia, sepsis and septic shock. – Rapid immunochromatographic test
 Colonization: It is the simple presence of potentially – Western blot (immunoblot) test
pathogenic microbes on a body surface (like on the – Immunofluorescence test
skin, mouth, intestines or airway) without causing – Complement fixation test
disease. However, colonization may progress to – Agglutination test
infection.
– Immunodiffusion
 Infestation: Refers to presence of parasites inside
– Immunoelectrophoresis
or on the host.
 Infection: Invasion and multiplication of patho-
Enzyme-linked Immunosorbent Assay (ELISA)
genic microorganisms in a body part or tissue,
which may produce subsequent tissue injury and  ELISA or the enzyme immunoassay (EIA) makes
progress to overt disease through a variety of use of enzyme-labelled immunoglobulin to
cellular or toxic mechanisms. Infection can be detect antigens or antibodies. It is a sensitive and
localized, as in pharyngitis, or widespread as in specific test for the detection and quantification of
sepsis. antigens or antibodies.
 Bacteremia: Presence of bacteria in the bloodstream  ELISA tests are usually performed in microwell
is called bacteremia. It can result from day do day plates. Microwells in ELISA plates are coated with
activities such as toothbrushing or can be a result antibodies to the target proteins (antibodies or
of an infection in the body. Bacteremia usually does antigens). Clinical sample is added into these
not cause any symptoms such as fever and often microwells. If a specific antigen or antibody is
usually resolves on its own. However, rarely it can present in the clinical specimen it is captured by
progress to sepsis and septic shock. the coated antibodies on the ELISA plate. A second
 Sepsis: It is presence and multiplication of micro- antibody to the target protein conjugated with an
organisms in the blood which triggers an immune enzyme is then added which is captured by the
response and makes the patient symptomatic. target protein. The unbound material is washed out.
Sepsis is usually associated with fever, weakness, A chromogenic substrate (to the enzyme) is then
tachycardia, tachypnea and multiorgan dysfunction. added. Development of color by the action of
 Septic shock: Sepsis that causes dangerously low
hydrolyzing enzyme on chromogenic substrate
blood pressure is called septic shock. It carries high indicates the presence of the specific antigen or
morbidity and mortality. antibody. Colour intensity is measured by the
spectrophotometer.
 There are many variations of ELISA, but the basic
Q. Discuss the serological (immunological) methods
used in the diagnosis of infectious diseases. principle remains the same as described above. In
the first-generation ELISAs either crude antigen or
 Serological (immunological) methods involve detec- single antigen is used for the test. In the second-
tion of antigen or antibody of a microorganism in a and third-generation ELISAs multiple antigens or
given sample. These are as follows. recombinant antigen or/and specific peptides are
1
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2 Microbial protein is run on gel electrophoresis to
separate the ligands, which are then transferred on
to a nitrocellulose membrane strip. Patient’s serum
is added to this nitrocellulose strip. If there are
antibodies to a specific microorganism, they bind
to antigens present on the strip. Enzymatically
labelled anti-immunoglobulins can be added now
which bind to the antibodies and visualised by the
addition of an enzyme substrate to produce
coloured bands. This test is commonly used to
confirm the diagnosis of HIV infection.

Immunofluorescence Test
 This test makes use of immunoglobulin (antibody)
labeled with fluorescent dye to detect antigens or
antibodies. It requires a fluorescent microscope to
read the signal. It is commonly used to detect infec-
tions with herpes virus, dengue virus and rabies
virus.

Direct Immunofluorescence
 Direct immunofluorescence or direct fluorescent
antibody (DFA) test uses a single antibody labelled
with fluorescent dye to detect the presence of a
specific antigen. If a specific antigen of a micro-
organism is present in patient’s serum, it combines
with the antibody labelled with a fluorescent dye
which can be detected as a fluorescent signal. This
test is highly sensitive and specific.

Indirect Immunofluorescence
Figure 1.1 ELISA  Here two antibodies are used. The first antibody
recognizes the target antigen and binds to it, and
the second antibody, which is labeled with a
used, which improves the sensitivity and specificity
fluorescent dye recognises the first antibody and
of the test.
binds to it.
 ELISA is routinely used to detect antibodies against
 This test is more complex than the direct immuno-
HIV and hepatitis A virus.
fluorescence test and takes more time but allows
Rapid Immunochromatographic Test more flexibility. Patient’s serum is incubated
with a specific microbial antigen. If specific anti-
 Here, the principle is same as ELISA, but the tech-
bodies are present in the patient serum, they
nique is embedded in a nitrocellulose membrane
combine with the antigen. Next, fluorescent-
of a test strip. This allows rapid detection of antigen
Manipal Prep Manual of Medicine

labelled antisera is added and the fluorescent signal

or antibodies in patient’s body fluids such as blood
or serum. The presence of specific proteins is is looked for.
indicated by the development of coloured bands
Complement Fixation Test
on the strip. These diagnostic strip tests are simple,
rapid, cheap and reliable and can be used at home  This test is used to detect presence of specific
and clinics. Such kits have been developed for antibodies to a microorganism. It depends on the
dengue; malaria, etc. Urine pregnancy test kit is also antigen antibody reaction which uses complement.
an example of immunochromatographic test which Patient’s serum is heat treated to remove any free
uses specific antibodies to selectively identify hCG complement. It is then mixed with a specific antigen
in urine. and sensitized sheep RBCs are added. Complement
is added next. If antibodies are present in the


Western Blot (Immunoblot) Test patient’s blood, there is formation of antigen

1  In Western blot, antibodies to multiple specific

proteins are detected. Hence, it has high specificity.
antibody complex and complement is used up. If
there is no antibody, complement remains unused

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 and it lyses the sensitized sheep RBCs. Absence of Q. Discuss the molecular methods used in the 3
hemolysis means complement fixation test is diagnosis of infectious diseases.
positive which means that specific antibodies are
 Molecular methods involve detection of RNA or
present. This test has been largely superseded by
DNA of a microorganism. These are polymerase
other methods such as ELISA and PCR.
chain reaction (PCR), southern blotting and
northern blotting.
Agglutination Test
Direct Agglutination Polymerase Chain Reaction (PCR)
 Here, the patient’s serum is added to a known  This is the most specific and sensitive test of all
antigen. If antibodies are present in the patient’s molecular techniques. Here the nucleic acid
serum, it leads to agglutination. Weil-Felix test for sequence of a microorganism is amplified so that it
scrub typhus and direct agglutination test for becomes easily detectable. Since each micro-
visceral leishmaniasis are examples of this test. organism has unique DNA/RNA sequences, it is
possible to select a PCR primer that specifically
Indirect (Passive) Agglutination Test identifies a particular microorganism.
 Here, carrier particles such as RBCs, latex, or gelatin  Multiple microorganisms can be identified in single
are coated with a soluble antigen and are mixed clinical sample using ‘multiplex’ PCR.
with patient’s serum. These particles agglutinate if  Fluorescent dyes can be attached to different
the patient’s serum contains antibodies. primers and the final nucleic acid polymers
 In latex agglutination test, latex particles coated examined by light spectroscopy.
with specific antibody are mixed with patient’s  Reverse transcriptase (RT)–PCR amplifies very
serum. If there are specific antigens in the patient’s small amounts of any kind of RNA (mRNA, rRNA)
serum, there is agglutination of antibody coated and makes complementary DNA, which is then
latex particles. This test is used to detect toxins of amplified with conventional PCR. HIV viral copies
Vibrio cholerae and staphylococci. are estimated by this method.
 In haemagglutination test, RBCs are coated with  Real-time PCR is used to quantify the organisms
known antigens. If mixed with serum containing and is used in estimation of HIV viral load.
specific antibodies, there is agglutination of RBCs.  The disadvantages of PCR are its high cost and false
This is used in the diagnosis of syphilis and herpes positive results. False positive results happen if
virus infections. there is any contamination from laboratory or other
sources.
Immunodiffusion
Southern Blotting
 Immunodiffusion is a diagnostic test which
involves diffusion through a substance such as agar  Southern blot is a method for detection of a specific
gel. Here a specific antigen or antibody is placed in DNA sequence in DNA samples. Southern blot
one well and patient’s serum or body fluid is placed is named after biologist Edwin Southern who
in another well and left for 48 hours. The antigen developed this technique.
and antibody diffuse through the agarose gel  DNA fragments are separated by gel electro-
towards each other and a precipitation line is phoresis and transferred on to a blotting paper. A
formed between the two wells. DNA probe (this is a piece of single stranded DNA
with known sequence labeled with a radioactive
Immunoelectrophoresis isotope or a fluorescent signal) is then added to the
 Immunoelectrophoresis is a general name for a blotting paper. DNA probe will bind to its comple-
number of biochemical methods where proteins are mentary DNA if present. This is then washed to
separated by electrophoresis and identified using remove any unbound DNA probe.
specific antibodies. This test is conducted on  Even after washing if there is radioactivity or
fluorescence, it means that a specific DNA


agarose gel. Four types of immunoelectrophoresis

Infectious Diseases

(IEP) have been used: Electroimmunoassay (EIA complementary to DNA probe is present. Since each
also called rocket-immunoelectrophoresis), classical microorganism has specific DNA sequences, it
immunoelectrophoresis (IEP), immunofixation indicates the presence of that particular micro-
electrophoresis (IFE) and immunoprecipitation of organism in the clinical specimen.
proteins after capillary electrophoresis. The proce-
dure used in most laboratories is immunofixation Northern Blotting
electrophoresis (IFE). IFE is widely used for  This is same as Southern blotting except that RNA
identifying Bence Jones proteins seen in multiple
myeloma.
fragments are used here to detect microbial RNA
instead of DNA. 1
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4 Q. Define fever of unknown origin (FUO). Enumerate  Hospital associated FUO is defined as a tempera-
the causes of FUO. How do you approach a case ture of ≥38.3°C (≥101°F) on several occasions in a
of FUO? hospitalized patient in whom infection was not
manifest or incubating at the time of admission
 Fever of unknown origin (FUO) or pyrexia of
which remains undiagnosed even after 3 days of
unknown origin (PUO) is prolonged febrile illness
without an established etiology despite intensive investigation, including at least 2 days incubation
evaluation and diagnostic testing. of cultures.
 Neutropenic FUO is defined as a temperature of
Definition of FUO ≥38.3°C (≥101°F) on several occasions in a patient
FUO can be classified into following categories: whose neutrophil count is <500/L that remains
1. Classic FUO undiagnosed after 3 days of investigation, including
2. Nosocomial FUO at least 2 days incubation of cultures.
3. Neutropenic FUO  HIV associated FUO refers to HIV positive patient
4. FUO associated with HIV infection with fever of ≥38.3°C who have been febrile for
 Classic FUO is defined as fever of >38.3°C (>101°F) 4 weeks or more as an outpatient or 3 days as an
on several occasions which remains undiagnosed inpatient, in whom the diagnosis remains uncertain
even after 3 outpatient visits or 3 days of hospitali- even after 3 days of investigation, including 2 days
zation. incubation of cultures.

Causes of FUO

TABLE 1.1: Causes of FUO

Infections (most common cause of FUO) • Rocky Mountain spotted fever
Bacterial • Scrub typhus
• Tuberculosis (very common cause of FUO) Fungal
• Typhoid • Candidiasis
• Brucellosis • Histoplasmosis
• Infective endocarditis • Mucormycosis
• Syphilis • Blastomycosis
• Melioidosis • Cryptococcal disease
• Sinusitis
Neoplasms (second most common cause of FUO)
• Osteomyelitis
• Lymphoma
• Prostatitis • Leukaemia and other hematologic malignancies
• Dental abscesses • Liver involvement with hepatoma or metastases
• Cholangitis • Renal cell carcinoma
• Intra-abdominal abscesses (subphrenic, renal, • Colon carcinoma
retroperitoneal, and paraspinal abscesses) • Atrial myxoma
Viral Inflammatory and connective tissue disorders
• HIV • Rheumatoid arthritis
• Chronic hepatitis (B, C, D) • Systemic lupus erythematosus (SLE)
• Infectious mononucleosis • Sarcoidosis
Manipal Prep Manual of Medicine

• Inflammatory bowel disease (IBD)

Parasitic • Polyarteritis nodosa (PAN)
• Malaria • Giant cell arteritis (common in elderly patients)
• Amebiasis • Polymyalgia rheumatica
• Leishmaniasis • Crohn’s disease
• Malaria • Granulomatous hepatitis
• Strongyloidiasis • Kikuchi disease
• Toxocariasis Miscellaneous
• Toxoplasmosis • Drug fever
• Trichinellosis • Factitious fever
• Babesiosis • Periodic fever (familial meditarranean fever)
Rickettsial infections


Undiagnosed
• Q fever • Even after extensive workup some FUOs may remain
1 • Rickettsialpox undiagnosed. Some of them may resolve spontaneously

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Approach to a Case of FUO disseminated process such as TB involving bone 5
Clinical History marrow), jaundice (points to hepatobiliary disease),
sternal tenderness (hematological malignancy),
 Get a detailed history of general symptoms (e.g. spinal tenderness (Pott’s spine, epidural abscess),
fever, weight loss, night sweats, headache, rashes). clubbing (TB, chronic suppurative lung disease) and
 Enquire about the pattern of fever [Tertian fever for signs of meningeal irritation like neck stiffness
(occurring every third day) in malaria, step ladder and kernigs sign (meningitis).
type fever (typhoid), undulant fever (evening fevers
 Carefully examine heart for any murmurs (infective
resolving by morning in brucellosis), week-long
endocarditis), abdomen for any tenderness (deep
fever with week-long remission (relapsing fever in
abdominal infections) hepatosplenomegaly (enteric
borreliosis), week-long high fevers with week-long
fever, malaria, hepatitis, hemolytic anemia) or spleno-
remissions (known as Pel-Ebstein fever seen in
megaly (malaria, hematological malignancies).
Hodgkin disease).
 Always examine the fundus and retina (papillo-
 Inquire about symptoms involving all major organ
edema in meningitis, retinal lesions in CMV
systems.
infection, disseminated candidiasis, tuberculosis).
 Itching after a hot bath (lymphoma)
 Painful nodules on shins (tuberculosis, fungal Investigations
infections, lymphoma)
 Common things are common. First rule out common
 Contact with infection (tuberculosis) or animals (cat diseases such as enteric fever, tuberculosis, malaria,
scratch disease, brucellosis) or birds (psittacosis). UTI, HIV infection, etc. and then only think of rare
 High risk sexual behaviour (HIV, hepatitis B, illnesses.
hepatitis C).
 Order routine investigations like Hb, total WBC
 Travel history (suspect infections endemic in places count, RBC count, differential count, platelet count,
visited). ESR and peripheral smear study. Cytopenias may
 Drug therapy (suspect drug fever). suggest a pathologic process involving bone marrow
 Occupation (e.g. farmers prone for leptospirosis, such as disseminated tuberculosis, hematological
veterinary workers prone for brucellosis). malignancies, etc. A high leucocyte count is common
 Recent dental treatment (possibility of endocarditis). in infections. A very high leucocyte count may
 History of immunosuppression such as HIV suggest leukemia. A very high ESR (>100 by
infection or steroid therapy (suspect opportunistic Westergren method) often indicates active tuber-
infections). culosis, collagen vascular disease or malignancy.
 History of previous abdominal surgery, trauma,  Urine microscopy and culture sensitivity (to R/O
endoscopy, or gynecologic procedures increase the UTI).
likelihood of an occult intra-abdominal abscess.  If there is cough and sputum production send it
for Gram’s stain, fungus stain, AFB, malignant cells
Clinical Examination
and culture/sensitivity.
 Do a complete physical examination.  Blood culture and sensitivity for both aerobic and
 Document the height and pattern of fever. Measure anerobic organisms (infecting organism may be
the fever more than once and in the presence of a picked up by this).
nurse to exclude factitious fever.  Complete LFT and RFT to look for any liver and
 Document BP, pulse, respiratory rate and SPO2. BP renal involvement.
may be low in septic shock and myocarditis. Pulse  Culture and examination of the stool for any ova,
rate usually increases by 10 per degree celsius rise parasites and occult blood.
in temperature. Relative bradycardia (i.e. pulse rate
 Chest radiograph (tuberculosis, pneumonia,
does not correspond to the raise in temperature)
sarcoidosis).
may be seen in enteric fever, brucellosis and some
viral infections. Relative tachycardia, i.e. pulse rate  Mantoux test can help in diagnosing TB.
ECG, echocardiogram (to look for signs of infective


more than expected to the raise in temperature may 

Infectious Diseases

be seen in myocarditis, sepsis, hypovolemia and endocarditis).

thyrotoxicosis. High respiratory rate usually points  Ultrasound abdomen and pelvis to R/O any intra-
to some respiratory pathology such as pneumonia, abdominal pathology. Ultrasound can help in many
empyema, ARDS, etc. ways. It can document any organomegaly, intra-
 Look for lymphadenopathy (tuberculosis, infectious abdominal lymphadenopathy or masses, ascites,
mononucleosis, HIV, lymphoma, malignancy), skin any change in the texture of organs, any intra-
and mucosal lesions (skin rashes in connective abdominal collections of pus.
tissue diseases, oral ulcers in behcets disease), pallor
(may point to hematological malignancy, or a
 Lumbar puncture and CSF examination if suspect-
ing meningitis. 1
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6  Serological investigations (WIDAL test, ASO titre, trial may be indicated. For example, antituberculosis
HIV-Elisa, VDRL, TPHA, rheumatoid factor, therapy (ATT) in suspected tuberculosis and steroid
antinuclear antibodies, viral antibody titres, Paul- therapy in suspected connective tissue diseases.
Bunnell test, brucella agglutination test).  Periodic review is very important in cases of FUO
 CT/MRI scanning (intra-abdominal lymphadeno- as development of new signs and symptoms may
pathy, tumours, abscesses). help in identifying the underlying cause. In some
 Tissue diagnosis (lymph node FNAC/biopsy, liver cases a ‘second opinion’ by another physician can
biopsy, bone marrow examination). also be very helpful as different people think from
 Diagnostic surgical procedures like laparoscopy, different angles.
exploratory laparotomy, etc. may be required in  Many undiagnosed cases of FUO will sponta-
undiagnosed cases. neously resolve.
Treatment
Q. Chemoprophylaxis.
 Treatment depends on the underlying cause.
 Until a diagnosis is made, it is better to use only  Chemoprophylaxis is the administration of drug to
symptomatic treatment. Blind antibiotic therapy prevent the development of a disease.
may make diagnosis of an occult infection more  For example, antibiotics may be administered to
difficult, and empirical steroid therapy may mask immunocompromised patients to prevent opportu-
an inflammatory response without treating the nistic infections. Antibiotics may also be given to
underlying cause. healthy individuals to limit the spread of an epi-
 Sometimes when all the tests are negative and the demic, or to patients with recurrent infections (such
cause of fever remains undiagnosed, a therapeutic as urinary tract infections) to prevent recurrence.

Common Situations where Chemoprophylaxis is Used

TABLE 1.2: Common situations where chemoprophylaxis is used
Situation Goal Chemoprophylaxis
Rheumatic fever To prevent recurrence and further cardiac Phenoxymethyl penicillin 250 mg twice daily
damage or inj Benzathine penicillin once a month for
many years as recommended

Meningitis
• Due to meningococci
• Due to H. influenzae type b To prevent infection in close contacts Rifampicin 600 BD for 2 days
Alternatives (single dose) ciprofloxacin 500 mg
orally or inj ceftriaxone 250 mg IM
Rifampicin 600 mg daily for 4 days

Tuberculosis To prevent infection in exposed tuberculin- Oral isoniazid 300 mg daily for 6 months
negative individuals, infants of infected
mothers and immunosuppressed patients

Valvular heart disease To prevent infective endocarditis in dental, Amoxicillin, 2 g orally.

Prosthetic heart valves oral, or upper respiratory tract procedures: If allergic to penicllin, clindamycin 600 mg or
cephalexin 2 gm or azithromycin 500 mg can
Manipal Prep Manual of Medicine

be used.
Antibiotic should be given 1 hour before the
procedure orally.
If patient is unable to take orally any of
these can be given parenterally.
Malaria Prevention of malaria Chloroquine one double strength tablet per
week or mefloquine 250 mg once a week.

HIV infected patient with CD4 Prevention of Pneumocystis jiroveci Trimethoprim-sulfamethoxazole, one double-
count below 200 cells/mcL pneumonia strength tablet (960 mg) daily

HIV infected patient with toxo- Prevention of toxoplasmosis Trimethoprim-sulfamethoxazole, one double-
plasma IgG antibody positive and strength tablet (960 mg) daily
CD4+ T cell count <100/mcL


1
HIV infected patient with CD4 Prevention of Mycobacterium avium Azithromycin (1200 mg orally weekly) or
count below 50 cells/mcL complex infection clarithromycin (500 mg orally twice daily)

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Q. Opportunistic infections (Table 1.3). – Steroid therapy – 7
Chemotherapy for cancer –
 Opportunistic infection is an infection by a micro-
organism that normally does not cause disease, but Immunosuppressing agents for organ transplant
becomes pathogenic when the body’s immune recipients
system is impaired. Opportunistic infections are – Malnutrition
common in following conditions: – Prolonged antibiotic therapy
– Primary immune deficiency disorders  Opportunistic infections can be due to bacteria,
– HIV infection viruses, protozoa or fungi.

TABLE 1.3: Common opportunistic infections

Organism Disease Treatment
Pneumocystis Pneumonia Sulphomethoxazole + trimethoprim
Toxoplasma gondii Encephalitis, pneumonia Sulphadiazine + pyrimethamine
Alternative clindamycin
Cryptosporidium Diarrhea Nitazoxanide
Strongyloidiasis Diarrhoea Thiabendazole
Herpes simplex virus Encephalitis Acyclovir
Varicella zoster virus Disseminated herpes zoster Acyclovir
Cytomegalovirus Retinitis, pneumonia Gancyclovir
Candida Mucocutaneous and esophageal candidiasis Fluconazole, itraconazole, amphotericin B
Cryptococcus Meningitis Amphotericin B + flucytosine


Infectious Diseases

Figure 1.2 Common opportunistic infections 1

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8 Q. Nosocomial infections (hospital-acquired  Intravenous canula should be removed if there is
infections). inflammation at the insertion site.
 Indwelling urinary catheter should be removed if
 The term nosocomial infection or hospital acquired
possible.
infection is a newly acquired infection that is con-
 Surgical-site infections should be managed with a
tracted within a hospital environment. Infections
combination of surgical care and antibiotic therapy.
are considered nosocomial if they first appear
48 hours or more after hospital admission or within Prevention
30 days of discharge.
 Nosocomial infections increase medical expendi-
 The most common sites of infection are the blood-
ture and also cause significant morbidity and
stream, lungs, urinary tract, and surgical wounds.
mortality. Hence all efforts should be made to
Organisms prevent them.
 Patients with infections should be isolated.
Though any organism can cause a nosocomial infec-
 Aseptic measures should be enforced in wards,
tion, there is an increasing incidence of multidrug-
operation theatres and labour rooms, by arranging
resistant (MDR) pathogens causing hospital-acquired
clean air, clean linen, adequate airspace, etc. There
infections. This rise can be explained by indiscriminate
should be adequate space between beds.
use of antibiotics and lack of hygienic measures among
 Wound dressings and minor procedures like
healthcare professionals. Some common organisms
lumbar puncture, pleural and peritoneal tapping,
causing nosocomial infections are as follows.
etc. are better done in a separate procedure room
 Bacteria: Staphylococcus epidermis is the most
and not bedside.
common organism causing nosocomial infection.
 Pharmacy should check all intravenous fluids
It most often causes wound infection. Other bacteria
before supplying to wards.
are Escherichia coli, Klebsiella pneumonia, Pseudomonas
aeruginosa, Acinetobacter, methicillin resistant  The hospital kitchen staff should observe strict
Staphylococcus aureus (MRSA). hygienic habits and should have periodic medical
check up to detect and treat any infection.
 Viruses: Hepatitis viruses (A, B, C), cytomegalo-

virus, influenza, respiratory syncytial virus, etc.  Every hospital should have an infection control
committee which should monitor and control
 Fungi: Candida, Aspergillus.
infections in the hospital.
Transmission
Q. Food poisoning.
 Transmission usually occurs via health care workers,
patients, hospital equipment, or interventional  Food poisoning is defined as an illness caused by
procedures. the consumption of contaminated food or water.
Food or water can be contaminated with bacteria,
Clinical Features viruses, parasites, toxins, and chemicals. Green
 Any new onset fever or any unexplained clinical leafy vegetables are the most common cause of food
deterioration in a hospitalized patient may be due poisoning, followed by dairy items and poultry.
to hospital-acquired infection.  Food poisoning should be suspected when many
 Clinical features depend on the site of infection. people develop the illness after ingesting the same
food and the illness bears a temporal relationship
 Any new infiltrate on chest X-ray may due to
to food intake.
hospital-acquired pneumonia.
Manipal Prep Manual of Medicine

Causes
Investigations
 Complete blood count: Usually shows leukocytosis. TABLE 1.4: Causes of food poisoning
 Blood culture and sensitivity: To diagnose blood Infective Non-infective
stream infection. Toxin mediated Plant toxins (flava beans),
 Urine examination: To diagnose urinary tract Preformed toxin: Staphylo- paralytic shellfish toxin,
infection. coccal enterotoxin, bacillus ciguatera fish poisoning,
cereus scombrotoxic fish poisoning,
 Chest X-ray: To diagnose pneumonia.
Toxin produced in the intestine: heavy metals (arsenic,
 Other tests as per clinical suspicion. Clostridial spp. Vibrio cholerae, thallium and cadmium)
enterotoxigenic E. coli
Treatment Mucosal involvement


 Treatment will be based on the type of hospital- Rotavirus, Norwalk agent, Shigella,

1 acquired infection. However, pending investigation giardiasis, Campylobacter jejuni,

Yersenia enterocolitica
reports, broad spectrum antibiotics can be started.

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Clinical Features Clinical Features 9
 The commonest manifestation of food poisoning is  Following ingestion of contaminated food, nausea,
a mixture of nausea, vomiting, fever, abdominal vomiting and abdominal cramps develop within
pain and diarrhea. 1–6 hours. Fever and/or diarrhea may also occur
 Usually symptoms occur in many persons who in a minority of patients.
ingest the same food.  Most cases improve rapidly. Rarely severe dehydra-
 Symptoms usually develop within 48 hours after tion can occur which can be fatal.
ingestion of food. In case of preformed toxins and
noninfective food poisoning symptoms develop Management
within minutes to hours.  Fluid replacement and antiemetics (domperidone,
 Specific etiologic agent can be identified by examin- ondansetron) should be given. Suspected food
ing the suspected food, vomitus, stool or blood. should be tested for the presence of enterotoxin and
Staphylococcus, if feasible. Public health authorities
Management should be notified if food vending is involved.
 Most cases of food poisoning are self limiting.
 Intravenous fluids and electrolytes should be given Q. Toxic shock syndrome (TSS).
to patients with severe vomiting and diarrhea.
 Antidiarrheal agents (codeine phosphate, loper-  Toxic shock syndrome (TSS) is a toxin-mediated
amide) can be used to control diarrhea. However, acute life-threatening illness, usually caused by
they should be avoided in young children, elderly, infection with either Staphylococcus aureus or group
and patients who have fever and pain abdomen A Streptococcus (GAS, also called Streptococcus
suggesting infective diarrhea. pyogenes).
 Antibiotics are not routinely indicated unless a  TSS was first described in a small group of children
specific pathogen is suspected. with acute febrile illness. Subsequently, it was
found in young, menstruating women who were
Prevention of Food Poisoning using a highly absorbent tampon that was newly
introduced to the market. This was due to
Following precautions can decrease the chances of multiplication of vaginally colonized S. aureus and
food poisoning. production of an exotoxin known as TSST-I and
 Do not drink raw (unpasteurized) milk or foods that
enterotoxin B. However, tampon associated cases
contain unpasteurized milk. of TSS have come down, and most cases are now
 Wash raw fruits and vegetables thoroughly in secondary to S. aureus infections of skin or other
running water before eating. sites.
 Use precooked, perishable, or ready-to-eat food as

soon as possible. Clinical Features

 Avoid cross contamination; keep raw meat, fish,
 TSS usually begins with nonspecific flu-like
and poultry separate from other foods.
symptoms such as fever and myalgia. In menstrual
 Thoroughly cook raw food from animal sources.
cases, the onset is usually 2 or 3 days after the start
Seafood and shellfish should be cooked thoroughly of menstruation.
to minimize the risk of food poisoning.
 As the severity of illness increases, patients develop
 Refrigerate foods promptly. Never leave cooked
diffuse erythematous rash, hypotension, and
foods at room temperature for more than two hours.
multiple organ dysfunction. Multiple organ dys-
function manifests as vomiting and diarrhea (GIT
Q. Staphylococcal food poisoning. involvement), renal failure (kidney involvement),
 Staph. aureus is a common commensal of the ARDS (lung involvement), liver enzyme elevation
anterior nares. Staph. aureus is coagulase positive (hepatitis), thrombocytopenia (hematological
and is the most virulent of all staphylococcal species. involvement), confusion, drowsiness (CNS involve-


ment), conjunctival erythema (mucosal involve-

Infectious Diseases

All other staphylococci have been collectively

designated as coagulase negative staphylococci and ment), etc.
are less virulent.  Desquamation of the skin occurs during convale-
 Food handlers may transfer the bacteria via hands scence, usually 1–2 weeks after the onset of illness.
to foodstuffs such as dairy products, meats, eggs,
and salads. Investigations
 After the food is left at room temperature, the  Investigations typically show leucocytosis, thrombo-
organisms multiply and can produce a substantial
quantity of enterotoxin.
cytopenia, increased urea creatinine, hypoalbumi-
nemia and liver function abnormalities. 1
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10  Gram staining and culture sensitivity of the infected Clinical Features
specimen.  Scarlet fever is characterized by exudative pharyn-
 Blood culture may show causative organism such gitis, fever, and scarlatiniform rash. Initially patient
as Staphylococcus or Streptococcus. develops fever, headache, vomiting and sore throat,
followed within 24 hours by a punctate erythe-
Treatment matous rash. Erythematous rash is caused by
 Patient should be admitted immediately to the erythrogenic toxin.
hospital.  Initially, the exanthem is seen on the tongue which
 Local measures (e.g. decontamination, debride- becomes bright red with prominent red papillae.
ment). This appearance is called strawberry tongue. The rash
 Fluid resuscitation and circulatory support. then appears on the neck and spreads to trunk and
 Empiric antibiotic therapy (e.g. clindamycin plus extremities. These rashes enlarge and join together
vancomycin) pending culture results. In addition to form a generalized erythema. Usually the rash
to antibacterial effect, clindamycin also reduces the does not affect nose, lips, palms and soles. Since
synthesis of toxin. the lips are not affected it remains pale and stands
 For patients with group A Streptococcus infection, a out against the red background of flushed cheeks.
combination of penicillin-G (4 million U IV q4h) Rash is more prominent in the skin folds and is
and clindamycin (600–900 mg IV q8h) is used. called Pastia’s lines. Usually the rash becomes
Intravenous immune globulin can be considered for maximum by 2 days and fades by 7 days.
streptococcal toxic shock syndrome (specific anti-
Differential Diagnosis
body to streptococcal exotoxins).
 Duration of antibiotic treatment is 10 to 14 days.  Includes other causes of fever with generalized
rash, such as,
Q. Enumerate the infections caused by streptococci. – Rubella, measles, and other viral exanthems
Write briefly on scarlet fever and erysipelas. – Kawasaki disease
– Toxic shock syndrome
Streptococci are Gram-positive bacteria arranged in – Systemic allergic reactions (e.g. drug eruptions).
chains. They cause a variety of infections in man which
are as follows. Complications
 Skin and soft tissue infections; cellulitis, erysipelas,
 Otitis media, pneumonia, septicemia, osteomyelitis,
necrotising fasciitis toxic shock syndrome, rheumatic fever, and acute
 Bone and joint infections
glomerulonephritis.
 Tonsillitis

 Scarlet fever Investigations

 Glomerulonephritis  Complete blood count shows leucocytosis.
 Rheumatic fever  Throat culture is the most important test to confirm
 Puerperal sepsis the diagnosis.
 Endocarditis  Direct antigen detecting kits allow immediate
 Urinary tract infection diagnosis but have less sensitivity.
 Neonatal infections including meningitis  Anti-deoxyribonuclease B and antistreptolysin-O
 Female pelvic infections titers (antibodies to streptococcal extracellular
 Peritonitis products).
Manipal Prep Manual of Medicine

 Dental infections
Treatment
 Liver abscess.
 Penicillin is the drug of choice and is given for
Scarlet Fever 7–10 days. Cephalosporins can also be used instead
of penicillin. Erythromycin is an alternative for
 Scarlet fever is a syndrome characterized by exuda-
patients allergic to penicillin.
tive pharyngitis, fever, and bright-red exanthema
(scarlet means bright red). Scarlet fever is caused by
toxin producing group A beta hemolytic strepto- Erysipelas
cocci (GABHS). GABHS is found in secretions and  It is an infection of skin and soft tissue.
discharge from the nose, ears, throat, and skin.  Erysipelas usually involves the face and head but
 Exotoxin-mediated streptococcal infections range other areas may also be involved.


from localized skin infection (e.g. bullous impetigo)  The skin becomes red, oedematous and firm to hard
1 to the widespread eruption of scarlet fever to the
highly lethal streptococcal toxic shock syndrome.
in consistency due to cuticular lymphangitis. It may
spread to adjacent parts and involve large areas.

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 The margins of the erythematous areas are raised Q. Discuss the etiology, pathogenesis, clinical features 11
and sometimes vesicles are also seen. The patient and complications of diphtheria. How do you
may appear sick. investigate and manage a case of diphtheria?
 Erysipelas of the face has to be differentiated from
cellulitis. Since cellulitis is an infection of sub- Etiology
cutaneous tissues, it does not involve the external  Diphtheria is a localized infection of mucous mem-
ear which has no subcutaneous tissue, while facial branes or skin that is caused by Corynebacterium
erysipelas can involve external ear (Millian’s sign). diphtheriae. It is associated with a characteristic
 Penicillin is the drug of choice for erysipelas. pseudomembrane at the site of infection.
 C. diphtheriae is a gram-positive bacillus and
Q. Listeriosis. resembles Chinese letter patterns on Albert’s stain.
 There are 3 strains of C. diptheriae; mitis, inter-
 Listeriosis is a serious infection caused by Listeria
medius and gravis. Gravis causes the most severe
monocytogenes. Listera monocytogenes is an aerobic,
disease.
gram-positive rod. It is an intracellular organism
and is capable of invading several cell types. Epidemiology
Listeriosis is a rare infection and primarily affects
pregnant women, newborn infants, elderly, and  Diphtheria affects people all over the world. But
immunocompromised patients. now it is uncommon due to immunization practices.
It is more common during winter. It is mainly a
Transmission disease of children.
 Humans are the main reservoir of C. diphtheriae.
 The main route of acquisition of Listeria is through
However, some cases have also occurred due to
the ingestion of contaminated food products. Other
transmission from livestock.
modes of transmission are contact with infected
 Spread occurs in close-contact settings through
animals such as rodents or ruminants. Venereal
respiratory droplets or by direct contact with respi-
transmission occurs occasionally. Mother to child
ratory secretions or skin lesions. Fomite trans-
transmission can occur during perinatal period.
mission can also occur.
Clinical Features Pathogenesis
 The disease is seen mainly in neonates and young  Diphtheria is initiated by entry of C. diphtheriae into
children. Mother can get infected in late pregnancy the nose or pharynx. It multiplies locally without
which can lead to stillbirth. It presents as a febrile blood stream invasion.
illness. The mother recovers after delivery but,
 It produces a powerful exotoxin which causes local
occasionally, the organism persists in the genitalia
tissue necrosis and formation of a tough, adherent
to cause habitual abortions. If the neonate survives,
pseudomembrane, composed of a mixture of fibrin,
the picture is one of severe infection. Neonates die
dead cells, and bacteria. The membrane usually
in about three days but survivors develop suppura-
begins on the tonsils or posterior pharynx and can
tive meningitis.
spread to fauces, soft palate, and into the larynx,
 Listeria infection in healthy adults is uncommon which may result in respiratory obstruction. Toxin
but affects immunocompromised persons like AIDS entering the blood stream causes tissue damage at
patients, diabetics, alcoholics and those with distant sites, particularly the heart (myocarditis),
debilitating diseases. Listeria is an opportunistic
infection in AIDS. Meningitis is often the clinical
manifestation.

Investigations
 Organism can be isolated by blood culture, and
culture of any infected body fluid such as CSF.

Infectious Diseases

Treatment
 The treatment of choice is intravenous ampicillin often
in combination with an aminoglycoside. Penicillin
G can be used as an alternative to ampicillin.
 Trimethoprim-sulphamethoxazole is second line
drug and can be used if the patient is allergic to


ampicillin or penicillin.
The response to treatment is slow. Figure 1.3 Diptheria bacilli 1
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12 nerves (demyelination), and kidney (tubular Treatment
necrosis).  The goals of treatment are to neutralize the toxin,
 Nontoxigenic strains may cause mild local respira- eliminate the infecting organism, provide suppor-
tory disease, sometimes including a membrane. tive care, and prevent further transmission.
Clinical Features Antitoxin
Respiratory Diphtheria  Diphtheria antitoxin is a hyperimmune antiserum
 Nose infection presents as a chronic serosangui- produced in horses, which binds to and inactivates
neous or seropurulent discharge without fever or the diphtheria toxin.
significant toxicity. A whitish membrane may be  The antitoxin is only effective before toxin enters
observed on the septum. the cell and thus must be administered as early as
 The faucial (pharyngeal) form is most common. possible.
After an incubation period of 1 to 7 days, the illness  There is risk of allergic reactions to antitoxin since
begins with sore throat, malaise, and mild to it contains horse serum. Hence, a test dose should
moderate fever. Grayish membrane may be present be given before administration.
that is tightly adherent and bleeds on attempted  The dose of antitoxin depends upon the site and
removal. In severe cases, the patient appears toxic. severity of infection. 20,000 to 40,000 units for
Cervical lymphadenopathy and soft tissue edema pharyngeal/laryngeal disease, 40,000 to 60,000
may occur, resulting in the typical bull neck appea- units for nasopharyngeal disease, and 80,000 to
rance and stridor. 120,000 units for severe disease with “bull-neck”.
 Laryngeal involvement presents as hoarseness, The dose should be administered intravenously
stridor, and dyspnea. over 60 minutes.
 Myocarditis presents with signs of low cardiac
output and congestive failure. Conduction distur- Antibiotics
bances, ST-T wave abnormalities, arrhythmias, and
 They decrease toxin production indirectly by killing
heart block can occur.
the organisms.
 Neurologic involvement manifests as cranial nerve
 Penicillin is the drug of choice. Penicillin G (25,000
palsies and peripheral neuritis. Palatal and/or
to 50,000 units/kg IV q12 h until the patient can
pharyngeal paralysis occurs during the acute phase.
take orally) followed by oral penicillin V (250 mg
Cutaneous Diphtheria QID) for a total of 14 days.
 Erythromycin 500 mg QID for 14 days is an
 Cutaneous diphtheria lesions are classically
alternative.
indolent, deep, punched-out ulcers, which may
have a grayish white membrane.
Diphtheria Toxoid
Invasive Disease  Patients should be given diphtheria toxoid immuniza-
 This is rare and may cause endocarditis, osteo- tion during their convalescence since natural
myelitis, septic arthritis, and meningitis. Frequently, infection does not induce immunity.
these patients have underlying immunosuppression.
Prevention
Investigations  Isolate the patient.
Gram’s stain: A presumptive diagnosis of C. Non-immunised contacts should be given both
Manipal Prep Manual of Medicine

 
diphtheriae can be made by identifying gram- antibiotics and diphtheria antitoxin.
positive rods in a “Chinese letter” distribution on  Immunised contacts are given a booster dose
Gram’s stain. of diphtheria toxoid.
 Cultures from beneath the membrane, from the
nasopharynx, and from suspicious skin lesions. Q. Describe the etiology, pathogenesis, clinical
Cultures may be negative if the patient has received features and management of tetanus. Add a note
antibiotics. on prevention of tetanus.
 Toxigenicity testing should be performed on all C.
diphtheriae isolates.  Tetanus is a serious illness caused by Clostridium
 Polymerase chain reaction test may allow both tetanus organism. It is characterized by an
detection of the organism and determination of acute onset of hypertonia and painful muscle


toxigenicity. spasms.

1  ECG may show ST-T wave changes, heart block,

and dysrhythmia.
 Tetanus has been described by Hippocrates and in
the Indian medical writings of Sushruta.

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 – In women after illegal abortion due to unsterile 13
handling of the genital tract through which
organisms gain entry.
– Intramuscular injections given with
contaminated needles.
– Necrotic or gangrenous tissues due to
peripheral vascular disease or any other cause.

Pathogenesis
 Spores inoculated into the wound develop into
bacteria. These bacteria multiply locally and pro-
duce neurotoxin tetanospasmin which is respon-
sible for the clinical manifestations of tetanus.
Figure 1.4 Tetanus bacilli  Toxin released in the wound is disseminated
throughout the body and binds to motor neuron
Etiology terminals in muscles, and ascends up the axon to
 Cl. tetanus is a gram-positive, spore-forming, reach nerve-cell body in the brainstem and spinal
anaerobic bacillus. It has a drumstick appearance cord. The toxin then migrates across the synapse to
due to the presence of terminal spore. It is a normal presynaptic terminals where it blocks release of the
commensal of human and animal gastrointestinal inhibitory neurotransmitters glycine and gama-
tracts and is widely distributed in soil. Its spores aminobutyric acid (GABA). As a result, minor
can survive for many years even in adverse condi- stimuli result in uncontrolled spasms, and reflexes
tions. are exaggerated.
 Tetanus can occur in following situations: –  The time taken for the toxin to ascend from nerve
Neonatal tetanus: Occurs when the umbilical endings to CNS depends on the length of nerves.
cord is cut with an unsterile instrument Since cranial nerves are short, effect is first seen in
or smeared with cowdung after cutting as is cranial nerve territories such as face, head and neck
the (like lock jaw).
practice in some areas.
Clinical Features
– After road traffic accidents where wounds may
get contaminated easily with tetanus spores.  The incubation period is 4 days to 14 days. It can
Even a seemingly trivial injury may be able to be shorter or longer than this in rare cases.
cause tetanus.  Tetanus can present in one of four clinical patterns:
– People with otorrhoea may develop tetanus if – Generalized
the ear is probed with a wire or match stick which – Localized
may carry spores on it.


Infectious Diseases

Figure 1.5 Pathogenesis of tetanus 1

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14 – Cephalic Differential Diagnosis
– Neonatal  Inflammatory lesions inside the mouth can induce
trismus (lockjaw).
Generalized Tetanus  Drug induced dystonic reactions (e.g. phenothia-
 This is the most common and most severe form. zines, metoclopramide).
 The classical clinical triad consists of trismus (lock  Strychnine poisoning,
jaw), muscle rigidity, and reflex spasms.  Hypocalcemic tetany.
 Tetanic spasms mainly affect the muscles of the
trunk, back and proximal parts of the limbs, and Treatment
spare the peripheries.  The goals of therapy are to eliminate the source of
 The patient first notices difficulty in opening the toxin, neutralize unbound toxin, prevent muscle
jaw due to increased tone in the masseter muscles spasms, and support the patient until recovery.
(trismus, or lockjaw). Dysphagia or stiffness or pain Patient should be kept in a quiet room to minimize
in the neck, shoulder, and back muscles appears stimulation. Patient should be continuously moni-
concurrently or soon thereafter. Abdominal and tored for any signs of deterioration especially
limb muscle involvement produces a rigid respiratory compromise.
abdomen and stiff limbs. Sustained contraction of
the facial muscles results in a grimace or sneer (risus Antibiotic Therapy
sardonicus), and contraction of the back muscles
 Antibiotics are given to kill tetanus bacilli so that
produces an arched back (opisthotonus).
further production of toxin is prevented.
 Chest muscle spasms impair breathing. Laryngo-
 Penicillin is the drug of choice (10 to 12 million units
spasm may produce asphyxia.
intravenously, in divided doses daily for 10 days).
 These spasms occur repetitively and may be sponta-
Metronidazole is an alternative. Clindamycin and
neous or provoked by even the slightest stimulation.
erythromycin can be used in those allergic to
 Tetanic spasms cause contraction of both agonist penicillin.
and antagonist groups of muscles together.
 Patient remains fully concsiuos and alert through- Antitoxin
out, even during spasms.  Antitoxin is given to neutralize the free circulating
 Autonomic dysfunction is seen in severe cases and and unbound toxin. It does not have any action on
is characterized by labile or sustained hypertension, the bound toxin.
tachycardia, dysrhythmia, hyperpyrexia, profuse  Human antitetanus globulin (ATG) is the choice
sweating, peripheral vasoconstriction, and and is given in a dose of 3000 to 6000 units intra-
increased plasma and urinary catecholamine levels. muscularly, usually in divided doses because the
 Due to repetitive muscle spasms and dysphagia, volume is large. Human antitetanus immuno-
patient may develop many complications like globulin has a long half life; hence repeated doses
aspiration pneumonia, fractures, muscle rupture, are not required.
rhabdomyolysis, deep-vein thrombophlebitis,  Equine antitetanus immunoglobulin can also be
pulmonary embolism. used but carries risk of allergic reactions. However,
 Death can occur due to respiratory failure (most it is cheaper.
common cause) or cardiac arrest due to hypoxia.  The value of injecting antitoxin proximal to the
wound or infiltrating around the wound is unclear.
Localized Tetanus
Antitoxin does not penetrate the blood–brain
Manipal Prep Manual of Medicine

 Uncommon form in which manifestations are restricted barrier. The value of intrathecal administration is
to muscles near the wound. The prognosis is excellent. still not clear.

Cephalic Tetanus Control of Muscle Spasms

 Rare form of local tetanus, follows head injury or  Benzodiazepines like diazepam, lorazepam and
ear infection. Trismus and dysfunction of one or midazolam can be used to control muscle spasms.
more cranial nerves, often the seventh nerve, are  Uncontrolled spasms even after giving benzo-
found. Cephalic tetanus may remain localized or diazepines may require paralysis with a non-
may progress to generalized tetanus. The incuba- depolarizing neuromuscular blocking agent and
tion period is a few days and the mortality is high. mechanical ventilation.
 General anesthesia with propofol may be required


Neonatal Tetanus for continuous spasms.

1  Neonatal tetanus (tetanus neonatorum) is genera-

lized tetanus that results from infection of a neonate.
 Dantrolene and intrathecal baclofen can also be
considered in severe spasms.

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Supportive Measures feeding honey to infants. Honey may contain 15
 Respiratory support with endotracheal intubation botulism organisms which may proliferate in the
or tracheostomy, and mechanical ventilation, may gut to produce toxin. Wound botulism usually
be required. occurs due to contamination of wound with
 IV fluids should be given to maintain hydration. organisms.
 Hypertension due to autonomic dysfunction may
Investigations
be controlled by beta-blockers, clonidine, and
morphine sulfate. Intravenous magnesium sulphate  Toxin can be identified in serum, stool, vomitus,
also has a stabilizing effect and is useful in auto- gastric aspirate, and suspected foods.
nomic dysfunction.  C. botulinum may be grown on selective media from
 Hypotension or bradycardia may require volume samples of stool or foods.
expansion, use of vasopressors.  Wound cultures that grow C. botulinum suggest
 Wound should be kept clean by debridement and wound botulism.
removing any necrotic or foreign material.
Clinical Features
Prevention of Tetanus  Symmetric descending paralysis is characteristic
Immunization and usually starts in the extraocular muscles, and
spreads to the pharynx, larynx, and respiratory
 All partially immunized and unimmunized adults muscles before inducing a generalised flaccid
should receive vaccine, as should those recovering paralysis. Patient may have symptoms like ptosis,
from tetanus. The primary series for adults consists blurred vision, diplopia, pooling of secretions,
of three doses—the first and second doses are given dysphagia and breathlessness.
4 to 8 weeks apart, and the third dose is given 6 to  Nausea, vomiting and diarrhea may occur if the
12 months after the second. A booster dose is source of toxin is intestine. Paralytic ileus may
required thereafter every 10 years. develop due to intestinal muscles paralysis.
 For persons with unclean and major wounds, give  Fever is unusual.
tetanus immunoglobulin 250 units IM and also a
 Patient is conscious and alert.
dose of tetanus vaccine.
 Sensory findings are usually absent.
Wound Care  Respiratory paralysis may lead to death in un-
treated cases.
 Wounds should be washed thoroughly and any
dead tissue and slough should be excised.  A diagnosis of botulism must be considered in
patients with symmetric descending flaccid
paralysis without sensory deficits, who are afebrile
Q. Discuss the etiology, pathogenesis, clinical features,
and mentally intact.
diagnosis and treatment of botulism.
 Botulism is a paralytic disease caused by botulinum Treatment
toxin, which is produced by Clostridium botulinum.  Botulinum antitoxin should be given intravenously
 C. botulinum is an anaerobic gram-positive as early as possible.
organism that forms subterminal spores. It is found  Antibiotics are recommended for wound botulism
in soil and marine environments throughout the along with incision and thorough debridement of
world. Botulinum toxin is the most potent bacterial the infected wound. Penicillin G or metronidazole
toxin known. can be used.
 The immediate threat to life is respiratory failure.
Pathogenesis
Close monitoring for respiratory failure is impor-
 Under anaerobic conditions, the spores germinate tant. If respiratory failure develops, endotracheal
and the bacteria multiply and release the exotoxin. intubation and mechanical ventilation should be


Botulinum toxin inhibits release of acetylcholine at started. Tracheostomy is required if the patient
Infectious Diseases

the neuromuscular junction and causes flaccid needs mechanical ventilation for a long time.
paralysis. Botulinum toxin is extremely potent and
is capable of killing a person even in minute Q. Gas gangrene.
quantities. It can be used as an agent of bioterrorism.
 Naturally occurring botulism occurs in one of three  Gas gangrene (also known as clostridial myonecrosis)
forms: Food-borne botulism, infant botulism, or is a bacterial infection that produces gas in tissues
wound botulism. Food-borne botulism is caused by in gangrene. It usually occurs as a complication in
ingestion of preformed toxin present in canned
foods. Infant botulism occurs due to the practice of
devitalised and devascularised tissues. It is a medical
emergency. 1
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16 Etiology difficile (formerly called Clostridium difficile). The name
 80% of cases are caused by Clostridium perfringens, has been changed after finding out that this
while C. novyi, C. septicum, and C. histolyticum cause organism has many characteristics different from
the remaining cases. These organisms are true other Clostridium species.
saprophytes and are ubiquitous in soil and dust.  Broad spectrum antibiotics such as clindamycin and
 C. perfringens grows in anaerobic conditions and ampicillin have been implicated most often, but
also produces a toxin, and enzymes like collagenases tetracyclines and cephalosporins are other causal
and hyaluronidases which destroy the connective agents.
tissue and allow the infection to spread.
Pathogenesis
Clinical Features  C. difficile colonizes the intestinal tract after the
 The incubation period of gas gangrene is usually normal gut flora has been altered by antibiotic
short; less than 3 days. therapy.
 The first symptom is pain, along with numbness of  After colonization, C. difficile elaborates two large
the affected limb. There may be swelling around toxins: Toxin A an enterotoxin, and toxin B a cyto-
the wound, with pale surrounding skin. Serosan- toxin. These toxins initiate an inflammatory process
guinous foul-smelling discharge may be there from in the intestinal mucosa resulting in the disruption
the wound. Crepitus can be elicited on palpation of epithelial cell barrier function, diarrhea, and
in and around the wound due to gas formation. pseudomembrane formation.
 Constitutional symptoms are severe with tachy-
Clinical Features
cardia and hypotension and the patient may be
stuporous. Mild to moderate fever may be there.  Diarrhea usually begins 5 to 10 days after starting
 Sometimes uterine infection can occur following antibiotics. Stools may contain blood.
criminal abortion or poor aseptic technique during  Fever and abdominal pain may be present.
labor.  Signs of dehydration may be there due to diarrhea.
 Toxic megacolon and colonic perforation (rigid
Laboratory Findings abdomen and rebound tenderness) can occur in
 Gas gangrene is a clinical diagnosis, and empiric very severe cases.
therapy should be started if the diagnosis is
suspected. Investigations
 X-rays may show presence of gas in the tissues.  Stool examination may show presence of WBCs and
 The smear shows the presence of gram-positive RBCs.
rods.  Culture for C. difficile is slow and expensive, hence
 Anaerobic culture confirms the diagnosis. not recommended.
 Stool assay for C difficile toxins (mostly toxin B). It
Treatment is considered positive when cultured cells undergo
 Wounds should be thoroughly cleansed and cytopathic changes when exposed to stool which
debrided. contains toxin.
 Traditionally, the antibiotic of choice for clostridial  Enzyme-linked immunoabsorbent assay (ELISA)
infection has been penicillin G (4 million units every for toxin A.
four hours IV). Recently clindamycin has been  Sigmoidoscopy may reveal erythematous mucosa
shown to be superior to penicillin G. Combination covered by adherent membranes over the colonic
Manipal Prep Manual of Medicine

of clindamycin and penicillin is superior to mucosa.

penicillin alone. Metronidazole can be used instead
of clindamycin. Treatment
 Antitoxin is of doubtful value.  All antibiotics should be stopped and this alone
 Hyperbaric oxygen may relieve constitutional may halt the diarrhoea.
symptoms but its effect on mortality is not clear.  Vancomycin (125 mg orally 4 times daily for
14 days) is the drug of choice. Fidaxomicin is an
Q. Describe the etiology, pathogenesis, clinical features alternative (200 mg BD for 10 days). Metronidazole
and treatment of pseudomembranous colitis. is no longer the drug of choice but can be used if
vancomycin or fidaxomicin is not available.
Etiology  Probiotics such as lactobacillus may be considered


 Pseudomembranous colitis is inflammation of the but benefit is doubtful.

1 colon that occurs in some people who have taken

antibiotics. It is usually caused by Clostridioides
 Surgery may be required for complications such as
toxic megacolon, perforation and necrotizing colitis.

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Q. Anthrax (malignant pustule, woolsorters’ disease, Investigations 17
Siberian ulcer, charbon).  Chest X-ray may show mediastinal widening in
 Anthrax is a zoonotic infection caused by Bacillus inhalational anthrax.
anthracis. Anthrax is also known by various names  Gram stain—gram positive rods seen.
like malignant pustule, woolsorters’ disease,  Culture may grow B-anthracis.
Siberian ulcer, charbon, etc.  Direct fluorescent antibody (DFA) test and polymerase
chain reaction (PCR) assay may identify anthrax
Etiology bacillus.
 B. anthracis is a spore forming gram-positive rod.
Treatment
 Actually it is a zoonotic infection which affects
sheep, cattle, horses and goats. Humans are affected  Cutaneous anthrax: It is treated with any one of the
when spores are ingested or inhaled or inoculated following antibiotics—ciprofloxacin, levofloxacin,
into broken skin. This can happen either by direct doxycycline.
contact with these animals or contact with their  Other forms of anthrax: Require therapy with 2 or
products. 3 antibiotics. Antibiotic choices are ciprofloxacin,
 Recently anthrax has attained notoriety because of levofloxacin, meropenem, vancomycin, penicillin
its possible use in biological warfare. G, and doxycycline.
 Monoclonal antibodies and IV anthrax immune
Pathology globulin can also be considered for treatment of
inhalation anthrax along with antibiotics.
 After entry into the body, the spores germinate into
vegetative bacteria and multiply locally. Postexposure Prophylaxis
 Spores entering the lungs are ingested by macro-
phages and carried via lymphatics to regional  Exposed individuals should be given ciprofloxacin
lymph nodes, where they rapidly multiply and or levofloxacin, or doxycycline and anthrax vaccine.
cause hemorrhagic lymphadenitis. In addition to these, monoclonal antibodies can be
considered for people exposed to inhalation anthrax.
 Invasion of the bloodstream leads to sepsis, killing
the host.
Q. Gonorrhea; Gonococcal urethritis.
Clinical Features  Gonorrhea is a sexually transmitted disease (STD)
 The incubation period is from 1 to 5 days. characterized by purulent infection of the mucous
 Depending on the route of entry anthrax occurs in membrane surfaces.
three forms: Cutaneous, inhalational, and gastro-  It is one of the commonest STD world over.
intestinal forms.
 Cutaneous anthrax is the most common presenta- Etiology
tion (95%). Spores inoculate a host through skin  It is caused by a gram-negative diplococcus Neisseria
lacerations, abrasions, or biting flies. This form most gonorrhoea which infects the epithelium of the uro-
commonly affects the exposed areas of the upper genital tract, and less frequently of the rectum and
extremities. Initially the cutaneous lesion appears the conjunctivae. Gonococci are kidney shaped, and
as a small erythematous, maculopapular lesion, occur in pairs, hence the name gonococcus.
which subsequently undergoes vesiculation and
ulceration to form a black eschar (malignant pustule).
Sometimes sloughing of the eschar is associated
with hematogenous spread, sepsis, and shock.
 Respiratory involvement (woolsorters’ disease) is
due to inhalation of spores, resulting in nonproduc-
tive cough, fever and retrosternal discomfort.
Occasionally initial clinical improvement is follo-

Infectious Diseases

wed by severe dyspnea, stridor, cyanosis and death.

Neck and chest wall edema may develop.
 Gastrointestinal infection occurs after ingestion of
spores and presents as diarrhea and vomiting,
which can be bloody.
 Cutaneous anthrax may be transmitted from person
to person by direct contact or fomites but gastro-
intestinal and inhalation anthrax are not transmitted
from person to person. Figure 1.6 Gonococci 1
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18 Clinical Features  Quinolones like ciprofloxacin (500 mg) or levo-
 The incubation period is 1–5 days. The common age floxacin (250 mg) are alternatives but resistance is
group affected is 15–30 years. emerging.
 Asymptomatic infections can occur and more
common in females. Asymptomatic individuals Q. Chancroid.
contribute more to transmission of infection than  Chancroid also known as “soft chancre,” is a
actual cases. sexually transmitted disease (STD) characterized by
 Gonococcal infection in males results in acute painful genital ulcers that may be accompanied by
urethritis with symptoms of dysuria and purulent inguinal lymphadenopathy. It is highly contagious
urethral discharge. Some patients may have mucoid but curable infection.
urethral discharge. It may spread and cause
epididymitis and prostatitis. Etiopathogenesis
 In females, cervix is infected more often than the  Chancroid is caused by Haemophilus ducreyi which
urethra. Vaginal discharge, dyspareunia (painful is a small gram-negative bacillus. When examined
intercourse), and dysuria are common symptoms. by Gram stain, organisms from culture often clump
Genitourinary infection can progress to pelvic in long parallel strands, producing a so-called
inflammatory disease and lead to fever and lower “school of fish” appearance.
abdominal pain.  It is pathogenic only in humans, with no inter-
 Rectal gonorrhoea (proctitis) occurs in homosexual mediary host. H. ducreyi is transmitted sexually by
males and heterosexual females as a result of ano- direct contact with purulent lesions and by
genital sex. The symptoms vary from mild anal autoinoculation to nonsexual sites, such as the eye
pruritus and mucopurulent discharge to symptoms and skin. H. ducreyi enters the skin through
of severe proctitis with rectal pain and tenesmus. disrupted mucosa and causes a local inflammatory
 Pharyngeal gonorrhea (pharyngitis) may occur as reaction. It produces a cytotoxin which plays a role
a consequence of oro-genital sex and may be seen in epithelial injury and development of an ulcer.
in either sex. This is generally asymptomatic.
 Ocular gonorrhea is rare in adults. It occurs in
neonates as a result of contact of eyes with the
infected maternal birth canal. It presents as acute
purulent conjunctivitis that may affect deeper
structures of the eye and may occasionally result
in panophthalmitis.
 Disseminated gonococcal infection can occur in
both males and females leading to septic arthritis,
pustular skin lesions, and meningitis. Knee is the
most common site of septic arthritis.
Figure 1.7 School of fish appearance of H. ducreyi

Investigations Epidemiology
 Gram stain: Presence of typical gram-negative  Chancroid is seen worldwide, and is associated
intracellular diplococci establishes a diagnosis of with low socioeconomic and poor hygienic condi-
gonorrhea. tions. It predominantly affects young sexually
 Culture is the most common diagnostic test for active people (20–30 years of age). Chancroid is
Manipal Prep Manual of Medicine

gonorrhea. most often seen in uncircumcised men. In women

 DNA probe is a test that uses a probe to detect it may be asymptomatic.
gonorrhea DNA in specimens.
 Polymerase chain reaction (PCR). Clinical Features
 Incubation period is 4–7 days.
Treatment  The ulcer is seen on the prepuce in men and on the
 Ceftriaxone 250 mg intramuscular (IM) single dose labia in women. It begins as a papule with
PLUS azithromycin 1 g PO single dose. Doxycycline surrounding erythema which ruptures and forms
100 mg PO twice a day for 7 days can be used an ulcer. Ulcers are usually multiple, very painful,
instead of azithromycin. non-indurated and soft, have undermined edges
 Disseminated gonococcal infection should be with a base of granulation tissue and slough.


treated by parenteral antibiotics (ceftriaxone 1 g IM  Tender inguinal lymphadenopathy occurs in about

1 or IV OD) initially followed by oral therapy for a

total of 7 days.
half the patients. These lymph nodes may become
fluctuant (bubo) and rupture spontaneously.

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Diagnosis the site of attachment, the organism multiplies, 19
 Gram stain of material from a bubo or biopsy from producing a variety of toxins that cause local
ulcer reveals large numbers of gram-negative mucosal damage and systemic effects. There is local
coccobacilli, arranged in a ‘school of fish’ pattern. cellular invasion, but systemic dissemination does
not occur. Systemic manifestations are due to
 Culture is the most definitive method of diagnosis,
toxins.
but the organism is fastidious.
 It is not exactly known what causes the paroxysmal
 Immunofluorescence test and serologic assays for
cough that is the hallmark of pertussis. Pertussis
antibodies are newer laboratory tests.
toxin may be responsible for cough. Local mucosal
 Polymerase chain reaction (PCR) can rapidly detect damage may contribute.
H. ducreyi in clinical samples and may supersede
 Bronchopneumonia can develop in some persons.
culture in future.
 Seizures and encephalopathy can occur and are due
Differential Diagnosis to hypoxia from coughing paroxysms or apnea.

 Chancroid ulcer has to be differentiated from genital Clinical Features

ulcer due to syphilis, lymphogranuloma venereum,
herpes simplex virus-2, and granuloma inguinale.  The incubation period is 7 to 14 days.
 Classically, there are three stages: Catarrhal,
Treatment paroxysmal and convalescent.
 A single 1-g oral dose of azithromycin will cure The Catarrhal Stage
most people.
 Lasts 1–2 weeks. It resembles common cold and is
 Alternative regimens include ceftriaxone (250 mg
characterised by running nose, fever and mild
intramuscularly as a single dose), or ciprofloxacin
cough.
(500 mg orally twice a day for 3 days), or
erythromycin (500 mg orally three times a day for
The Paroxysmal Stage
7 days).
 Fluctuant lymph nodes may require  Lasts for 2–6 weeks or longer. The cough becomes
needle aspiration or incision and drainage. more frequent and spasmodic with repetitive bursts
of 5 to 10 coughs, often within a single expiration.
The episode may be terminated by an audible
Q. Pertussis (whooping cough).
whoop, which occurs due to rapid inspiration
 Pertussis (per—intensive, tussis—cough) is an acute against a closed glottis at the end of a paroxysm.
respiratory tract infection caused by Bordetella Post tussive vomiting is frequent.
pertussis, a gram-negative coccobacillus.  During a spasm, there may be impressive neck-vein
 A severe bout of cough is followed by a deep distension, bulging eyes, tongue protrusion, and
inspiration with characteristic sound (whoop). cyanosis.
Hence the name “whooping cough.”  Paroxysms may be precipitated by noise, eating,
 The Chinese name for pertussis is “the 100-day or physical contact
cough,” which accurately describes the course of  The whoop may be absent in infants, partially
the disease. immune older children, and adults, which makes
the diagnosis difficult in them. Most complications
Epidemiology occur during the paroxysmal stage
 Pertussis occurs worldwide but the incidence has
come down due to vaccination. Periodic epidemics
The Convalescent Stage
however continue world over.  Decrease in intensity and frequency of the cough
 The infection is more common and serious in over 1–2 weeks.
infancy and early childhood. It is highly comm-


unicable. Differential Diagnosis

Infectious Diseases

 Even with the decline after vaccination, pertussis  Includes conditions with severe cough lasting more
still continues to be a major health hazard. than 2 weeks. These are adenovirus infection, endo-
bronchial tuberculosis, inhaled foreign body, and
Pathogenesis hyperreactive airway disease.
 The organism is spread by droplets from patients.
 Infection is initiated by attachment of the organism Complications
to the ciliated epithelial cells of the nasopharynx.
Attachment is mediated by surface adhesions. At
 Infants and young children have more complica-
tions. 1
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20  Respiratory complications: Otitis media, pneumonia Q. Discuss the etiology, pathogenesis, clinical
due to B. pertussis itself or secondary bacterial features, diagnosis and management of typhoid
infection, atelectasis, emphysema, bronchiectasis, fever (enteric fever).
pneumothorax and pneumomediastinum.
Q. Rose spots.
 Neurological complications: Seizures and
encephalopathy. Q. Complications of typhoid fever.
 Severe cough leads to marked increase in pressure
in various body compartments, which may cause  Typhoid is a systemic infection caused by Salmonella
epistaxis; retinal, subconjunctival and intracranial typhi or paratyphi.
hemorrhage; inguinal hernia; rectal prolapse;  The disease was initially called typhoid fever because
rupture of the diaphragm; rib fracture. of its clinical similarity to typhus. Since the primary
 Malnutrition can occur due to prolonged disease. site of infection is intestine, the term enteric fever
was proposed as an alternative name. However, to
Laboratory Findings this day, both names are used interchangeably.

 Pertussis is mainly a clinical diagnosis. Etiology

 There may be lymphocytic leucocytosis.
 Salmonella are gram-negative motile bacilli. Salmo-
 Confirmation of diagnosis depends on culture of
nellae are present worldwide but cause disease only
B. pertussis from a nasopharyngeal swab or cough
where poor hygiene and overcrowding exist.
plate in Bordet-Gengou medium. Cultures are often
positive in the catarrhal and early paroxysmal stage.
Pathogenesis
 Direct fluorescent antibody and counterimmuno-
electrophoresis are other methods for rapid  Humans are the only reservoir of S. typhi. Organisms
diagnosis. originate from patients with typhoid, or from
 Chest X-ray may show lung infiltrates. carriers excreting organisms in their stools. Human
hands, flies, or insects then transfer these organisms
Management to food or drink. Since S. typhi survive freezing and
drying, infection can also occur through ice or
 Patient should be admitted to hospital if there is canned food. Shellfish from polluted waters may
respiratory distress, neurological signs and transmit the disease. Decreased stomach acidity is
dehydration a risk factor for infection to occur.
 Antibiotics: Purpose is to eradicate the infecting  Once salmonellae reach the small intestine, the
bacteria from the nasopharynx. Antibiotics should bacteria penetrate and traverse through the
be given early to reduce the risk of prolonged intestinal wall through phagocytic cells that reside
disease. Macrolide antibiotics (azithromycin, within Peyer’s patches. After crossing the epithelial
clarithromycin) are the drugs of choice for treat- layer of the small intestine, S. typhi and S. paratyphi
ment of pertussis. Trimethoprim-sulfamethoxazole are phagocytosed by macrophages.
is an alternative for individuals allergic to
 Once phagocytosed, salmonellae disseminate
macrolides.
throughout the body in macrophages via the
 Supportive measures: These include providing lymphatics and colonize reticuloendothelial tissues
adequate nutrition and hydration and avoiding (liver, spleen, lymph nodes, and bone marrow)
factors aggravating cough such as excessive crying. where they start multiplying. Patients have
Complications are managed as per standard guide- relatively few or no symptoms during this initial
lines. incubation stage.
Manipal Prep Manual of Medicine

 Once the number of bacteria reaches a critical stage,

Prevention
they invade blood stream and rest of the body. At
 Isolate the patient for 4–5 days after starting this stage, signs and symptoms, such as fever and
antibiotics to prevent spread to others. abdominal pain appear. Peyer’s patches can get
 Chemoprophylaxis: With azithromycin or erythro- enlarged and necrosed due to mononuclear cell
mycin should be given to all household contacts infiltration. Bacteria also reach gallbladder via
whether they have been vaccinated or not. blood stream and multiply there. From the gall
 Vaccination: All children under 7 years of age should bladder, bacteria reach the intestine and are
be vaccinated. Vaccination against pertussis is part excreted in the stool which can spread to others via
of standard childhood vaccination. For adults, a contaminated foods. Some patients become chronic
single booster with Tdap (containing lower doses carriers carrying the bacteria in their gallbladder


of the diphtheria and pertussis components than and are responsible for much of the transmission

1 the childhood DTaP) is recommended after age

19 years.
of the organism. Carriers remain asymptomatic, but
may shed bacteria in their stool for decades.

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Clinical Features noninvasive duodenal string test) can be positive 21
 The incubation period averages 10 to 14 days. despite a negative bone marrow culture. If blood,
 The onset of the disease is insiduous, with bone marrow, and intestinal secretions are all
headache, malaise, anorexia and fever. The fever is cultured, the yield of a positive culture is >90%.
remittent (does not touch the baseline) sometimes Stool cultures, can be positive during the third week
increasing in a step-like manner (step ladder fever) of infection in untreated patients.
to reach a peak towards the end of the first week.  The Widal test is very helpful in diagnosis. There
Thereafter, it plateaus and remains for two to three can be false positive and false negative results. The
weeks. Accompanying chills are common but frank test is positive if O antigen titer is more than 1:160.
rigors are rare. Headache is present and often A four-fold rise in serum agglutinins against the
disabling. somatic (O) antigen of the bacillus is diagnostic
 With the passing days debility sets in and in some rather than a single test. Titres against the flagellar
cases progresses to mental dullness and delirium, (H) antigen are less specific. Usually it becomes
characterized by muttering and picking at bed positive after the 1st week of illness. Early anti-
clothes. microbial therapy may dampen the immunologic
response.
 Abdominal discomfort with mild bloating and
constipation usually occurs, but diarrhea can also  Typhidot-M test is a new test which detects IgM anti-
occur. Stools may have a ‘pea soup’ appearance. body against typhoid bacilli. It has high sensitivity
and specificity and is better than WIDAL test.
 Hepatosplenomegaly may develop by the end of
the first week. Mild jaundice may be present.  Relative bradycardia and leukopenia may be a clue
to diagnosis.
 The typical rash of typhoid (rose spots) develops
in the second week but is seldom seen in Indian  LFT may show mild elevation of AST and ALT.
patients. “Rose spots” are pink macules, 2–3 mm  Polymerase chain reaction tests and DNA probe
in size, occur in small crops on the chest and assays are being developed.
abdomen, blanch on pressure and last for 2–3 days.
Treatment
 In the absence of complications, typhoid fever
usually subsides.  Third generation cephalosporins are currently the
drugs of choice. Ofloxacin and levofloxacin are also
Complications effective, but quinolone resistance is now emerging.
 Ceftriaxone (1 to 2 g intravenously or intramuscu-
 Complications are uncommon now due to availa- larly) for 10 to 14 days is the treatment of choice in
bility of effective antibiotics. severe typhoid.
 Bleeding: Erosion of blood vessels in necrotic Peyer’s  Azithromycin is also an alternative to quinolones
patches or in the intestinal wall can initiate (1 g orally once a day for 7 days or 500 mg orally
bleeding. for 10 days).
 Intestinal perforation: Typhoid ulcers can perforate.  Paracetamol can be used to control fever, headache
Usually happens in 3rd week of illness. and myalgia.
 Typhoid can affect almost all the organs. Hence,  Supportive measures include good nutrition and
pneumonia, meningitis, nephritis, cholecystitis, hydration. Soft and bland diet should be given
hepatitis, myocarditis, osteomyelitis, encephalitis because of inflamed bowel. Laxatives and enemas
can occur. should be avoided because of the same reason.
 Involvement of the central nervous system can  In cases of severe typhoid fever (fever, altered
present as stupor, delirium, convulsions, encepha- sensorium or septic shock; and a positive culture
litis, cerebellar ataxia, extrapyramidal signs, for S. typhi or S. paratyphi A), dexamethasone
myopathy and deafness. treatment should be considered. One trial showed
 Acute renal failure and disseminated intravascular that treatment with dexamethasone decreased the
coagulation are rare complications. mortality rate.


 About 1 to 4% patients become chronic carriers of

Infectious Diseases

Investigations typhoid bacilli. They can be a source of infection to

 The diagnostic “gold standard” for enteric fever is others (remember Typhoid Mary). Carrier state can
culture of S. typhi or S. paratyphi. Blood cultures are be treated with oral amoxicillin, TMP-SMX,
positive in 90% during the first week of infection ciprofloxacin, or norfloxacin. Antibiotics should be
but decrease to 50% by the third week. Cultures of given for 6 weeks. However, in cases of anatomical
stool and urine may also be positive. Bone marrow abnormality (e.g. gallstones or kidney stones),
culture is highly (90%) sensitive and may remain eradication of the infection often cannot be achieved
positive even with up to 5 days of antibiotic therapy.
Culture of intestinal secretions (best obtained by a
by antibiotic therapy alone and requires surgical
correction of the abnormalities. 1
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22 Prognosis  About 2–5% of patients become chronic carriers
 The mortality rate of typhoid fever is less than 1% after Salmonella typhi infection, and the rate is higher
in treated cases. Elderly or debilitated persons are in patients with cholelithiasis or other biliary tract
likely to do poorly. With complications, the prog abnormalities.
nosis is poor. Relapses occur in up to 10% of cases.  Chronic urinary carriage of S. typhi is rare and is
usually associated urinary tract abnormalities such
Q. Typhoid vaccines. as urolithiasis, prostatic hypertrophy or Schistosoma
haematobium infection.
 Vaccination against typhoid is recommended for,  Chronic carriers do not develop recurrent sympto-
– Persons traveling to developing countries matic disease. They develop high level systemic
– People who have intimate or household contact immunity so that they and do not develop clinical
with a case or chronic carrier disease but excrete large numbers of organisms in
– Laboratory workers who frequently work with the stool.
S. typhi.  Chronic carriers act as source of infection to others,
 Following typhoid vaccines are currently available. particularly if involved in food preparation. Hence,
None of the typhoid vaccines protect against eradication of carrier state should be done if such
paratyphoid fever. individuals are identified.

1. Ty21a (oral vaccine) Diagnosis

 This is an attenuated live S. typhi vaccine. The
 Stool culture is the gold standard test to detect
vaccine is supplied as a packet of four enteric- carrier state but has low sensitivity.
coated capsules that must be kept refrigerated.
 Detection of antibodies against Vi antigen is also
It should be given as one capsule every other day
used for carrier diagnosis.
until all four capsules have been taken. Booster
doses are given every 5 years. Vaccine-elicited
Treatment
immunity occurs 14 days after receipt of the last
dose, with an efficacy of 50 to 80 percent. It  Fluoroquinolones are the drugs of choice to eradi-
maintains its efficacy for 4 years. It is well tolera- cate carrier state (e.g. ciprofloxacin 500 to 750 mg
ted. Ty21a is commonly used vaccine because it orally twice daily or ofloxacin 400 mg orally twice
can be given orally and has fewer side effects. daily for 4 weeks). Cholecystectomy should be
 It is contraindicated in considered if there is any abnormality such as
 Pregnant women
cholelithiasis.
 Children below 6 years.
 Alternatives antibiotics are ampicillin, trimethoprim-
 People with immunodeficiency.
sulfamethoxazole, and chloramphenicol.

2. ViCPS Q. Shigellosis.
 It consists of purified Vi polysaccharide from the

bacterial capsule. Etiology

 It is given as 0.5 ml intramuscularly (single dose)  Shigellosis refers to infection of the intestinal tract
and is well tolerated. It maintains its efficacy for by Shigella species.
2 years. Booster dose is given after 2 years  There are 4 species; Shigella dysenteriae, Sh. flexneri,
 It should not be used below 2 years. Sh. sonnei and Sh. boydii.
3. Typhoid conjugate vaccine (TCV)  Shigella dysenteriae type 1 is the most virulent of
Manipal Prep Manual of Medicine

the shigellae. It has been responsible for many

 This vaccine consists of Vi polysaccharide bound
epidemics during war, famine and natural disasters.
to a nontoxic protein such as tetanus toxoid or
diphtheria toxoid, etc. Linkage of a protein
Epidemiology
moiety results in T cell dependent differentiation
of B cells. Thus, TCVs are highly immunogenic  Shigellosis occurs mainly in the developing
and suitable for use in children below 2 years. countries.
 Two injections of the vaccine have to be given  Shigella infection is associated with the ‘gay bowel
with 6 weeks interval between the doses. syndrome’ of homosexuals, and travellers’ diarrhea
of tourists to the developing countries.
Q. Typhoid carrier.  The disease spreads by feco-oral route. Infection is
transmitted by fingers and flies. Food and water


 A person waho excretes Salmonella organism in contamination can cause epidemics as in refugee
1 stool or urine for more than 12 months after the
acute infection is called chronic carrier.
camps where population densities are high and
hygienic standards are low.

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 Bacillary dysentery is also a hazard in institutions TABLE 1.5: Differential diagnosis between bacillary dysentery 23
where hygiene is difficult to maintain, as in homes and amebic dysentery
for the mentally handicapped, geriatric nursing Bacillary dysentery Amebic dysentery
homes, and day-care centres for children.
Ulcers are distributed trans- Ulcers are distributed in the long
versely to long axis of gut. axis of gut; flaskshaped. Shape
Pathogenesis and Pathology Ulcers are serpiginous with is oval with regular edges. Ulcers
 Shigella first multiplies in the small intestine and ragged undermined edges are deep and involve all layers
initially, it may cause a secretory diarrhea. Thereafter communicating with other of intestine
ulcers
it rapidly localizes to the colon, where inflamma-
tion with hemorrhage, microabscesses, ulceration, Rarely perforate May perforate
and mucus production results. Mucous membrane is Mucous membrane not inflamed.
inflamed. Bowel wall not inflamed. Bowel wall thickened
thickened
Clinical Features
Stool scanty in quantity but Stools are lare quantity, mixed
 Symptoms usually start 2–3 days after exposure. very frequent; bright blood with blood and mucus, dark
 The onset is sudden with fever, malaise, abdominal red, gelatinous viscid mucus, brown, foul smelling
pain and watery diarrhea. This early phase reflects odourless (red currant jelly
appearance)
small intestinal involvement.
 Later when the colon gets involved there will be Tenesmus common Tenesmus uncommon
dysentery characterized by loose stools mixed with Stool microscopy: RBCs RBCs numerous and in clumps.
numerous and discrete. WBCs scanty. E. histolytica
blood and mucus. There may be tenesmus. Severe
WBCs plenty. Bacteria may trophozoites containing ingested
cramping abdominal pain may be present. be visible red cells present
 Nausea, vomiting, headache may occur.
 In children convulsions may occur due to the effect Treatment
of neurotoxin.
 Fluid and electrolyte replacement: Oral rehydration
 Sigmoidoscopy reveals hyperaemic and inflammed
salt can be used and if the patient is unable to take
mucosa, with transversely distributed ulcers with
orally use intravenous fluids.
ragged undermined edges, a picture which is
indistinguishable at times from inflammatory  Antibiotics: A fluoroquinolone (such as ciprofloxacin
bowel disease. 500 mg po q 12 h for 5 days), or azithromycin
500 mg daily for 4 days, or ceftriaxone 2 g/day IV
 Reactive arthritis and hemolytic–uremic syndrome
for 5 days. Trimethoprim-sulfamethoxazole can
(HUS) are rare complications.
also be used but shigella is likely to be resistant to
Differential Diagnosis this antibiotic. Fluoroquinolones are contraindi-
cated in pregnancy.
 Shigella dysentery has to be differentiated from  Antimotility drugs such as loperamide may worsen
other causes of dysentery such as: the condition and are better avoided.
– Inflammatory bowel disease
– Entamoeba histolytica Q. Describe the etiology, epidemiology, clinical
– Salmonella features, diagnosis and management of cholera.
– Entero invasive E. coli Add a note on its prevention.
– Yersinia –
Campylobacter jejuni –  Cholera is an acute
Vibrio parahaemolyticus diarrheal illness caused
by Vibrio cholerae. The
– Clostridium difficile
hallmark of the disease
 Clinically it is difficult to distinguish between these
is profuse secretory
and laboratory tests may be needed. Viral gastro-
diarrhea. Cholera can
enteritis is not usually associated with fever and
be endemic, epidemic,


the stool does not usually contain blood or pus.

or pandemic.
Infectious Diseases

Differential diagnosis between Shigella (bacillary)

and amoebic dysentery Etiology
 Vibrio cholerae is a
Laboratory Findings
comma shaped, motile,
 Stool shows many WBCs and RBCs. gram-negative bacillus
 Stool culture is positive for shigellae in most cases. that colonizes the human
 Serological tests are used mainly during epi-
demics.
small intestine. It has a
single flagellum at one Figure 1.8 Vibrio cholerae 1
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24

end. Its antigenic structure consists of flagellar H transported into Europe, Japan, and Australia have
antigen and somatic O antigen. based on the type caused localized outbreaks.
of O antigen, Vibrio cholera are divided into various
serogroups. Currently V. cholerae O1 and V. cholerae Pathogenesis
O139 are the principal ones associated with  Cholera is spread by feco-oral route. After inges-
epidemic cholera. Other serotypes such as non-O1, tion, cholera bacilli colonize the small intestine, and
non-O139 can cause mild infection. produce an exotoxin which is responsible for the
 Serotype O1 exists in two biotypes, classical and disease features.
EI Tor, and EI Tor biotype is further divided into
 The exotoxin has A and B subunits. The B subunit
three serotypes, Inaba, Ogawa, and Hikojima.
binds to the epithelial cell wall. The A subunit is
 V. cholerae can survive in water for up to 3 weeks
responsible for actions. A subunit activates intra-
and on moist linen for about a week.
cellular adenylate cyclase, which causes increase in
Epidemiology cyclic adenosine monophosphate (cAMP). cAMP
in turn inhibits sodium absorption and stimulates
 Its natural habitat is salt water. secretion of chloride. The net effect is accumulation
 Cholera has 2 main reservoirs, humans and water. of sodium chloride in the intestinal lumen. Water
V. cholerae is rarely isolated from animals, and moves passively to maintain osmolality, and when
animals do not play a role in transmission of disease. this volume exceeds the capacity of the gut to
 Transmission occurs by the faeco-oral route usually reabsorb fluid, watery diarrhea ensues.
through contaminated food and water.
 Cholera causes bicarbonate loss in stools and
 V. cholerae belonging to O1 serogroup (classical
increase in lactate because of diminished perfusion
biotype) has been so far responsible for many
of peripheral tissues which can cause metabolic
epidemics and pandemics. It has been endemic in
Manipal Prep Manual of Medicine

acidosis. Hypokalemia results from potassium loss

the Ganges Delta of West Bengal and Bangladesh.
in the stool.
It has been responsible for several epidemics and
pandemics in the world.  The organisms themselves do not damage the
 In 1991, epidemic EI Tor struck South America. epithelial cells of the gut. Since the organisms do
 In 1993 an outbreak of cholera occurred in India not invade the intestinal wall, stool does not contain
and Bangladesh for the first time with a non O1 blood.
V. cholerae. This organism is now designated as  Malnutrition increases susceptibility to cholera.
O139 Bengal. A close watch is being kept on O139 Because gastric acid can quickly inactivate V. cholerae,
B, as it has a potential to cause epidemics and hypochlorhydria or achlorhydria of any cause
pandemics. Mild infection is much more common (including Helicobacter pylori infection, gastric
with the currently predominant EI Tor biotype and surgery, vagotomy, use of H2 blockers and proton


with non-O1, non-O139 serogroups of V. cholerae. pump inhibitors) increases susceptibility. For

1  In 2010, an outbreak occurred in Haiti which later

spread to the Dominican Republic and Cuba. Cases
unknown reasons, incidence of cholera appears to
be twice as high in people with type O blood.

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Clinical Features dehydration, with a cold, clammy skin, tachycardia, 25
 Cholera is predominantly a disease of children with hypotension and peripheral cyanosis. The patient
attack rates highest in the 1 to 5 years age group. usually remains alert but appears weak. Muscle
Classically there are three disease phases. cramps can occur due to dehydration and hypo-
 Evacuation phase: Occurs after an incubation natermia. Children may present with convulsions
period of 1–2 days. There is sudden onset of due to hypoglycemia. Acute renal failure and
painless, profuse, watery diarrhea. There may be metabolic acidosis may develop due to hypo-
vomiting in severe cases. Stool appears like ‘Rice volemic shock. If the patient survives this stage, the
water’ because of mucus flecks floating in the recovery phase sets in.
watery stools (resemblance to the water in which  Recovery phase: Diarrhea episodes come down and
rice has been washed). If treatment is not given at there is gradual recovery of clinical and biochemical
this stage, the patient passes onto the next stage. parameters.
 Collapse phase: This is characterized by severe  Cholera sicca: Refers to severe disease in which
dehydration with sunken eyes, hollow cheeks, massive amount of fluid and electrolytes collect in
‘washer woman’s hands’, and decreased urine the dilated intestinal loops. Diarrhoea and vomiting
output. Circulatory shock may develop due to do not occur and the mortality is high.

Assessment of Dehydration

TABLE 1.6: Assessment of dehydration

Normal (No dehydration) Mild to moderate dehydration Severe dehydration (if the
(if the patient has two or more patient has two or more signs,
of the following signs, including at least one sign
including at least one sign marked with star*)
marked with star*)
General condition Well, alert *Restless, irritable* *Lethargic or unconscious;
floppy*
Eyes Normal Sunken Very sunken and dry
Tears Present Absent Absent
Mouth and tongue Moist Dry Very dry
Thirst Drinks normally, not thirsty *Thirsty, drinks eagerly* *Drinks poorly or not able to
drink*
Skin pinch Goesback quickly *Goes back slowly* *Goes back very slowly*

Investigations ORS (Oral Rehydration Salt)

 The diagnosis is largely clinical. It should be  Replacement of fluid by ORS is highly effective and
suspected in patients with painless diarrhea has saved countless lives. ORS takes advantage of
without fever and abdominal pain. Stool does not a co-transport mechanism not affected by cholera
contain blood. toxin wherein sodium (Na+) moves across the gut
 Gram’s stain of a stool sample may show gram- mucosa along with actively transported glucose.
negative comma shaped organisms. Sodium loss in stool in cholera is high, so that an
 Examination of stool under dark field illumination oral replacement solution containing 90 mmol/L
may show motile organisms. Inhibition of their Na+ is the WHO recommendation.
movement with type-specific antisera is diagnostic.  Content of WHO ORS in grams (to be added to
 Stool and rectal swabs should be taken for culture. 1 litre of water)
 Serotyping and biotyping: Specific antisera can be


NaCl 3.5
used in immobilization tests to identify the sero-
Infectious Diseases

NaHCO3 2.5
type. This is useful for epidemiologic studies.
KCI 1.5
 Hematocrit and serum proteins are elevated in
Glucose 20
dehydrated patients because of hemoconcentration.
 Rice-based ORS is also available. It contains rice
Treatment powder instead of glucose. It has less osmolality,
 Cholera is simple to treat. Rapid replacement of provides more nutritional benefits and may also
fluid and electrolytes is enough in most of the
cases.
reduce the amount of diarrheal stool, an effect not
seen with ordinary ORS. 1
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26 Intravenous Fluids O1 and O139. These are administered in 2 doses
 The ORS is necessary for the severely dehydrated. 14 days apart in adults and children older than
Ringer lactate is the best choice as it contains all 1 year. A booster dose is recommended after 2 years.
the electrolytes. The total fluid deficit, which is  CVD 103-HgR (VAXCHORA) is a recently FDA
usually estimated as 10% of body weight, can be approved cholera vaccine. This vaccine is highly
infused within 4 hours and half of this within the protective against moderate and severe cholera and
first hour. Oral fluid can usually be substituted is recommended for adults aged 18 to 64 years
thereafter but patients with continued large-volume traveling to high risk areas. It is given as single oral
diarrhea require intravenous fluid until diarrhea dose.
stops. Hypokalemia may develop and can be
corrected by potassium supplements. Fluid Q. Describe the etiology, epidemiology, pathogenesis,
replacement is monitored by urine output. clinical features, diagnosis and management of
plague.
Antibiotics
Etiology
 Although not necessary for cure, the use of an
antibiotic to which the organism is susceptible will  Plague is an acute febrile zoonotic disease caused
diminish the duration and volume of fluid loss and by infection with Yersinia pestis. Yersinia is named
will hasten clearance of the organism from the in honor of Alexander Yersin, who first isolated this
stool. Single-dose tetracycline (2 g) or doxycycline bacterium.
(300 mg) is effective in adults but is not  Y. pestis is a gram-negative coccobacillus in the
recommended for children <8 years of age because family Enterobacteriaceae. It has bipolar staining
of possible deposition in bone and developing teeth. pattern and appears like a safety pin.
Antibiotics can be continued for 3 to 5 days, though  Plague is one of the most virulent and potentially
single dose is enough for most of the cases. In areas lethal bacterial diseases known.
where tetracycline resistance is prevalent, cipro-
floxacin or erythromycin can be used for adults. For Epidemiology
children, furazolidone has been the recommended  Foci of plague are present on most continents except
agent and trimethoprim-sulfamethoxazole the second Australia. Multiple stable foci exist in Africa, Asia,
choice. Erythromycin is also a good choice for children. and South America.
 Plague has been known for many centuries. It was
Prevention described as Mahamari (great destroyer) in India.
 Hygienic measures should be implemented. Avoid The latest outbreak occurred in India in 1994 and
unboiled water, food from street vendors, raw or affected Maharashtra (earthquake-affected areas)
undercooked seafood, and raw vegetables. Water and Surat of Gujarat.
can be treated with chlorine or iodine, by filtration,  Low atmospheric temperature and humidity favor
or by boiling. epidemics, which occur mostly from September to
May.
Antibiotic Prophylaxis
 All the age groups and both sexes are affected.
 Not routinely recommended. WHO recommends  Plague is a zoonosis primarily affecting rodents.
prophylaxis only if an average of one household Humans are accidental hosts who play virtually
member in a family of five becomes ill after the first no role in the maintenance of Y. pestis in the eco-
case. Mass chemotherapy of entire communities is system.
not effective and is not recommended.
Manipal Prep Manual of Medicine

Vaccines
 Cholera vaccination is no longer officially required
for any international traveler but can be used by
travelers going to endemic areas. WHO has
identified 3 oral vaccines which can be used.
 The first vaccine is a killed whole-cell V. cholerae O1
with recombinant B subunit of cholera toxoid (rBS-
WC). Two doses have to be taken one week apart.
It provides ~70% protection over a 3-year period.
It can be used to prevent cholera in populations at


risk of an epidemic.

1  Other vaccines are SHANCHOL and ORCVAX

which are bivalent vaccines based on serogroups Figure 1.9 Plague bacilli

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 The reservoir of infection is Rattus norvegicus in  There is rapid onset of fever associated with 27
western countries. In India, wild rats like Tatera headache, backache and bodyache. If not treated
indica and Bandicota bengalensis varius are the early, plague can follow a toxic course, resulting in
reservoirs of infection. Domestic rats get infected shock, multiple-organ failure, and death.
by coming in contact with wild rats. When domestic  In humans, plague presents mainly as three forms;
rats die or come in contact with the human bubonic, septicemic, and pneumonic. Bubonic
population, the disease spreads. The chief vector plague is most common type and is usually caused
of the disease is the flea Xenopsylla cheopis. Farmers, by the bite of an infected flea. Septicemic and
rat catchers and those who eat rats may contract pneumonic plague can be either primary or
plague from the wild reservoir. When fleas feast secondary to spread from other sites.
on dead rats they ingest plague bacilli which
multiply and block proventricularis. This blocked Bubonic Plague
flea inoculates the host and thus spreads the  Initially patient experiences fever, chills, headache,
disease. Infection can also take place by the bite of myalgia and arthralgia. These symptoms are
a rat and by handling infected material. Pneumonic followed usually within 24 hours by pain and
plague spreads from man to man by droplet swelling in one or more regional lymph nodes
infection. Dogs and cats can become infected with proximal to the site of inoculation of the plague
Y. pestis by eating infected rodents and possibly by bacillus. Since most of the flea bites are on legs,
being bitten by infective fleas. Both dogs and cats femoral and inguinal nodes are most commonly
may transport infected fleas from rodent-infested involved; axillary and cervical nodes are next most
areas to the home environment. commonly affected. Within hours, the enlarging
bubo becomes painful and tender. The patient
Pathogenesis usually guards against palpation, pressure, stretch
 Y. pestis is highly invasive and pathogenic. It and limits movements around the bubo. The
produces many virulence factors and also a surrounding tissue often becomes edematous, and
lipopolysaccharide endotoxin which is important the overlying skin may be erythematous, warm, and
in sepsis, triggering the systemic inflammatory tense. At the site of flea bite, there may be a papule,
response syndrome and its complications. pustule, or ulcer. The ulcer may be covered by an
 Y. pestis organisms inoculated through the skin or eschar.
mucous membranes are carried to regional lymph  If treated early, bubonic plague usually responds
nodes via lymphatic channels, although direct quickly, with resolution of fever and other systemic
bloodstream inoculation and dissemination may manifestations. Without treatment, patients become
take place. Phagocytes, which can phagocytize increasingly toxic, and secondary plague sepsis may
Y. pestis, may play a role in dissemination of the result in DIC, bleeding, shock, and multiorgan
infection to distant sites. Plague can involve almost failure.
any organ, and untreated plague generally results
in widespread and massive tissue destruction. Septicemic Plague
Infected lymph nodes (buboes) contain huge  Here primary septicemia develops in the absence
numbers of infectious plague organisms and show of a bubo. Septic patients often present with gastro-
distorted or obliterated lymph node architecture intestinal symptoms like nausea, vomiting, diarrhea,
with loss of vascular integrity, hemorrhage, and abdominal pain, which may be confused with
necrosis, infiltration of neutrophils, and extensive some abdominal disease. If not treated early with
serosanguineous effusion. Primary septicemic appropriate antibiotics, septicemic plague can be
plague consists of sepsis in the absence of a bubo; fulminant and fatal. DIC may develop which will
secondary septicemic plague is a complication of manifest as petechiae, ecchymoses, bleeding from
bubonic or pneumonic plague. DIC can occur in puncture wounds and orifices, and gangrene of
severe cases. Vascular damage may lead to wide- limbs. Shock may develop which manifests as
spread ecchymoses and petechiae. Acral ischemia refractory hypotension, renal shutdown, and


and gangrene may sometimes develop.

Infectious Diseases

obtundation. Acute respiratory distress syndrome

 Primary plague pneumonia is lobar or multilobar. (ARDS) can occur at any stage of septicemic plague.
Secondary plague pneumonia begins more
diffusely. The affected lung tissue is characterized Pneumonic Plague
by edema, hemorrhagic necrosis, and infiltration  Pneumonic plague is often secondary to bacteremia
by neutrophilic leukocytes. in bubonic or septicemic plague. However, primary
pneumonic plague can occur, being acquired from
1
Clinical Features inhalation of Y. pestis from another patient or
 Incubation period is 2–8 days. animal or laboratory specimens.

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28  Pneumonic plague develops more rapidly and is recovery. Patients initially given intravenous
more fatal than other two forms. Incubation period antibiotics may be switched to oral regimens upon
is usually 3 to 5 days. The onset is often sudden, clinical improvement.
with fever, headache, bodyache, and weakness.  Chloramphenicol may be used to treat plague
Pulmonary signs, including tachypnea and dys- meningitis, pleuritis, endophthalmitis, and myo-
pnea, cough with expectoration, and chest pain, carditis because of its superior tissue penetration;
usually start on the second day of illness. Respira- it is used alone or in combination with streptomycin
tory failure may develop. Usually one lobe is or another first-line agent.
involved in early stages and later on it may spread  Complications like DIC, ARDS, and sepsis require
to other lobes and other lung also. treatment as per standard guidelines.
 Buboes may require surgical drainage.
Rare Presentations
 Plague meningitis, plague pharyngitis, endophthal- Prognosis
mitis, and lymphadenitis at multiple sites.  If not treated, plague is fatal in >50% of cases of
bubonic disease and in nearly all cases of septicemic
Diagnosis
and pneumonic disease. Prognosis has improved
 Plague should be suspected in any patient with now with the availability of antibiotics.
fever and painful lymphadenopathy. Patient should
be questioned about travel to areas of endemic Prevention
disease, and potential exposure to animal or rodent  Avoid exposure to live or dead rodents and use
vector. insect repellants in endemic areas.
 Culture and staining: This will confirm the  Face to face contacts of patients with known or
diagnosis. Blood, aspirates from buboes, sputum suspected pneumonic plague should be provided
and CSF can all be cultured and stained with chemoprophylaxis with doxycycline (100 mg two
Wright-Giemsa or Wayson’s stain. Wayson’s stain times daily for 2 to 3 weeks). In pregnant women
demonstrates the typical bipolar staining, which and children under the age of 8, trimethoprim
resembles a “closed safety pin.” Gram’s stain shows sulfamethoxazole has been recommended for five
small gram-negative coccobacilli. to seven days. Ciprofloxacin is also effective.
 Serology: Demonstration of antibodies supports the  Vaccines are being tested.
diagnosis.
 Rapid diagnostic tests: A new rapid diagnostic test Q. Describe the etiology, clinical features, diagnosis
(RDT) capable of detecting F1 antigen of the Y. pestis and treatment of melioidosis.
within 15 minutes has been developed. This test
holds considerable promise for rapid diagnosis of Etiology
plague.
 Melioidosis is an infectious disease caused by
 Chest X-ray: May show bronchopneumonia, Burkholderia pseudomallei (previously known as
consolidation, pleural effusions and hilar or Pseudomonas pseudomallei). It is a gram-negative
mediastinal lymphadenopathy. organism showing bipolar staining (safety-pin
Treatment appearance) like plague bacillus. It is found in the
soil and stagnant waters of the tropical and
 Patients should be isolated subtropical regions of Asia and Australia.
 Streptomycin is considered the drug of choice.
However, gentamicin has been shown to be equally
Manipal Prep Manual of Medicine

Epidemiology
efficacious, cheaper and easier to administer.
 Melioidosis is found predominantly in Asia,
Hence, in many places gentamicin has replaced
Australia, and China. It is rare in the United States.
streptomycin as the drug of choice. Other antibiotics
which are effective include tetracycline, doxycycline  The routes of infection are through skin abrasions,
(100 mg PO or IV twice daily), chloramphenicol, by ingestion, and inhalation.
and trimethoprim-sulfamethoxazole (160/800 mg  Percutaneous inoculation during exposure to wet
twice daily). Antibiotics should be given for season soil or contaminated water is the predomi-
10 days. nant mode of acquiring the infection. Hence,
 Antibiotics are given orally but can be given majority of melioidosis cases occurs in the monsoon
parenterally in critically ill patients and to patients wet season.
who cannot tolerate oral medication. In general,


antimicrobial treatment should be continued for Clinical Features

1 7 to 10 days or for at least 3 days after the patient

has become afebrile and has made a clinical



Incubation period ranges from 1 to 20 days.
Most infections are asymptomatic.

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 Immunocompromised states such as diabetes for 3 to 5 weeks. Complications like meningitis, 29
mellitus, malignancy, chronic renal failure and transverse myelitis, encephalitis, hepatitis and
cirrhosis of the liver predispose to infection. osteomyelitis can occur.
 The most common manifestation is an acute pulmo-
nary infection (pneumonia). Localized suppurative Investigations
infection can occur in almost any organ but is most  Serologic testing or PCR testing.
common at the site of inoculation in the skin.  Lymph node biopsy: Reveals characteristic granulo-
Typical metastatic sites of infection include the liver, matous inflammation with stellate necrosis.
spleen, kidneys, prostate, bone, and skeletal muscle.
Most of the patients have multiple abscesses. Treatment
Septicemia may occur in some patients which may
 Cat-scratch disease is generally benign and self-
cause death. Acute or chronic fever may be present.
limiting. Antibiotics are not required except in
Pathology immunocompromised patients and patients with
encephalitis or other serious manifestations. It can
 Initially lesions begin as granulomas resembling be treated with azithromycin or doxycycline.
tuberculosis, with giant cells but without acid-fast
bacilli. Later these lesions become microabscesses. Q. Trench fever.
Microabscesses enlarge to become big abscesses.
Etiology
Diagnosis
 Trench fever, also known as 5-day fever or quintan
 Melioidosis should be considered in patients with
fever, is a febrile illness caused by Bartonella quintana,
fever and multiple abscesses. Multiple abscesses,
a gram-negative bacillus. It was first reported in
especially those in the liver or spleen, should alert
soldiers hiding in trenches during World War I.
the physician to the possibility of melioidosis.
Hence, it was called trench fever.
 Confirmation of the diagnosis is by demonstration
of typical safety pin-shaped organisms in smear and Epidemiology
culture of abscesses. Pus may occasionally be sterile;
hence, repeated samples should be cultured. In  Trench fever is seen worldwide. It is more common
severe cases, blood culture may be positive. in the United States.
 Humans are the only reservoir of this Bartonella
Treatment infection. Human body louse is the carrier of B.
quintana which is transmitted to humans when feces
 The drug of choice is ceftazidime or carbapenems
from infected lice are rubbed into abraded skin or
such as imipenem or meropenem for a minimum
the conjunctiva.
of 2 weeks and preferably for 4 weeks. Thereafter,
combination of chloramphenicol, TMP-SMX, and
Clinical Manifestations
doxycycline or with the single agent amoxicillin/
clavulanate is recommended for 6 weeks to  Trench fever is characterized by the sudden onset
6 months to eradicate infection. of fever, headache, bodyache, malaise, weight loss
 Abscesses should be drained by surgical procedures. and aseptic meningitis.
 Untreated, the case fatality may be 90% or more.  Some patients may have minimal symptoms.

Diagnosis
Q. Cat-scratch disease.
 The infection is diagnosed by finding Bartonella
Etiology quintana in blood. In cultures, it is slow to grow.
 Cat-scratch disease is caused by Bartonella henselae, The infection can also be detected serologically by
a gram-negative bacillus. demonstration of antibodies.
 It occurs throughout the world and is seen
commonly in children. Treatment

Infectious Diseases

 Gentamicin for 2 weeks plus doxycycline for

Clinical Features 6 weeks.
 Domestic cat is the animal reservoir of this micro-
organism. It is caused by scratch, bite, or lick of a Q. Describe the etiology, epidemiology, pathogenesis,
cat and by close contact. diagnosis and treatment of brucellosis.
 Usually 3 to 5 days after exposure, patient develops
a papule that later crusts. Still later tender regional Etiology
lymphadenopathy develops. There may be mild
fever and malaise. The lymphadenopathy persists
 Brucellosis is a zoonotic infection transmitted to
human beings from infected animals. It is also 1
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30 known as undulant, Mediterranean, Malta or TABLE 1.7: Clinical features of brucellosis
Gibraltar fever. It is called undulant fever because Organ system Clinical features
of its remittent character.
Musculoskeletal system Myalgia, arthralgia, low back
 It is caused by brucella organisms which are small, pain, spine and joint pain, and,
non motile, gram-negative rods. rarely osteomyelitis, suppurative
 There are many species of Brucella. Out of these, arthritis
Brucella melitensis is the commonest cause of disease Haematologic Hemolytic anemia, thrombocyto-
in humans and is found in sheep, goats, and camels. penia, pancytopenia
B. abortus is usually acquired from cattle or buffalo. Nervous system Depression, lethargy, dizziness,
B. suis is usually acquired from swine. B. canis is tinnitus, meningitis, encephalitis
commonly acquired from dogs. Eyes Visual disturbances, keratitis,
uveitis, optic neuritis
Epidemiology Respiratory system Cough, pneumonia, chronic
 Brucellosis occurs worldwide. The disease is more pulmonary granuloma
common in young persons and six times more CVS Palpitations, endocarditis, myo-
common in men than in women. carditis, cardiac failure
 Human brucellosis is usually associated with Genitourinary system Epididymitis, orchitis
occupational or domestic exposure to infected GIT Hepatosplenomegaly, diarrhea,
animals or their products. cholecystitis, sub-diaphragmatic
 The route of entry is by ingestion or inhalation or abscess
through mucosal or percutaneous exposure.
 Farmers, shepherds, goatherds, veterinarians,  Constitutional symptoms include anorexia, asthenia,
workers in slaughterhouses and meat-processing fatigue, weakness, and malaise, and weight loss.
plants are commonly exposed to infection.  Lymphadenopathy and splenomegaly are seen in
Laboratory workers handling cultures or infected 50% of the cases
samples are also at risk. Others may acquire the  Brucellosis is a multisystem disease and affects
infection through consumption of contaminated almost all the organs. Clinical features depend on
foods. The most common food items implicated are the system involved (Table 1.7).
dairy products like cheese, unpasteurized milk, and  Prolonged fever with a history of contact with
ice cream. Raw meat and cosmetic products have animals or animal products and without any
been reported to spread the infection rarely. specific diagnosis should arouse a suspicion of
 Person-to-person transmission is extremely rare, as brucellosis.
is transfer of infection by blood or tissue donation.
Investigations
Pathology  The diagnosis of brucellosis is difficult to confirm
 After gaining entry into human body (via ingestion, because the organism is difficult to culture and
inhalation, percutaneous or mucosal exposure) secondly, even casual contact with infected animals
organisms are taken up by macrophages and other may induce positive serological tests in persons
mononuclear cells and get disseminated to local even without disease.
lymph nodes and different organs. Brucella then  Routine biochemical tests are usually within normal
replicate in the lymph nodes and various organs. limits, although sometimes LFTs may be abnormal.
Since the organism is intracellular, it is protected WBC count is usually normal or low (relative
from antibiotics and antibodies. Cell mediated leukopenia). Mild anemia and thrombocytopenia
Manipal Prep Manual of Medicine

immunity plays an important role in clearing the may be present. ESR can be elevated.
infection. The host response to infection is charac-  Blood, bone marrow and lymph node culture may
terized by tissue granulomas with B. abortus and grow organisms.
microabscesses with B. melitensis and B. suis.  Serologic tests: May demonstrate antibodies to
brucella. Tube agglutination test is the most
Clinical Features common test done to detect antibodies. In endemic
 The incubation period varies from 1 week to several areas agglutinin titers of ≥1:320 to 1:640 are
months. considered diagnostic; in nonendemic areas, a titer
 Acute or insidious onset fever which is low or high of ≥1:160 is considered significant. Repetition of
grade, remittent or intermittent, with chills and tests after 2 to 4 weeks may demonstrate a rising
sweats, without localizing signs in most cases. Fever titer.


can be characteristically undulant, i.e. it may dis-  Polymerase chain reaction (PCR) shows promise for

1 appear and again appear. Fever can be associated

with a relative bradycardia.
the detection and rapid diagnosis of Brucella spp.
in human blood specimens.

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Treatment Diagnosis 31
 At least two antibiotics should be used. Mono-  Klebsiella granulomatis is very difficult to culture
therapy is not recommended. The “gold standard” because it is extremely fastidious.
for the treatment of brucellosis in adults is intra-  The easiest method to visualize the organism is via
muscular streptomycin together with doxycycline. smears from the base of the ulcer. The organisms
The alternative regimen (current WHO recommen- are seen within the cytoplasm of macrophages.
dation) is rifampicin plus doxycycline for 6 weeks. They exhibit bipolar staining with safety-pin
For patients in whom tetracyclines are contra- appearance, and are referred to as Donovan bodies.
indicated (children, pregnant women) trimethoprim  A diagnostic PCR test has been recently developed
sulphomethoxazole can be used instead of tetra- and can be used for the detection of C. granulo-
cyclines. matis.
 There is evidence that other aminoglycosides can  Serologic tests are also available.
be used instead of streptomycin, e.g. netilmicin or
gentamicin. Treatment
 Surgery in cases of infection of prosthetic heart  The recommended antibiotic for granuloma
valves and prosthetic joints (replacement required). inguinale is either trimethoprim/sulfameth-
If abscesses develop they need to be drained. oxazoleor doxycycline. Alternatives include cipro-
floxacin, erythromycin, or azithromycin. Treatment
Prevention is given for 3 to 5 weeks.
 Live attenuated vaccine is available for use in
animals but none is available for human beings. Q. Actinomycosis.
Using gloves and mask while handling animals,
drinking pasteurized milk may protect against  Actinomycosis is a chronic suppurative granulo-
acquiring infection. matous infection characterised by abscess formation
and multiple draining sinuses. The main patho-
Q. Granuloma inguinale (donovanosis) (granuloma logical feature is formation of purulent material
venereum). containing granules with a yellow sulfur like
appearance (termed sulfur granules).
 Donovanosis is a chronic, progressively destructive
bacterial infection of the genital region. It is a Etiology
sexually transmitted infection.  The disease is caused by actinomycetes bacteria.
Actinomyces israelli is the commonest pathogen caus-
Etiology
ing actinomycosis. Though actinomycetes resembles
 It is caused by a Gram-negative intracellular fungus, actually it is a bacterium. It is Gram-positive,
bacterium, Klebsiella granulomatis. The organism nonmotile, nonsporing, noncapsulated.
responsible for granuloma inguinale was initially
described by Donovan (hence known as dono- Pathogenesis
vanosis) and subsequently the bacterium was  Actinomyctes are normal commensals in the mouth,
classified as Calymmatobacterium granulomatis. Later, colon and vagina.
it was found that the molecular structure of this
 Entry into tissues happens when there is a breach
organism was similar to Klebsiella species and pre-
of the mucous membrane or from aspiration into
sently it is named Klebsiella granulomatis. It is an
the lung.
intracellular bacteria and has a capsule with bipolar
 Infection spreads by direct extension to contiguous
staining, which gives it a ‘safety pin’ appearance.
tissues. Hematogenous spread to distant areas,
Clinical Features particularly to the bone and brain, can happen.
 The organisms form visible microcolonies in the
 Incubation period is 1 to 4 weeks.
tissues called grains (sulphur granules). Sulphur
Common sites of infection are genitals, and perianal



granules are in vivo matrix of bacteria, calcium
Infectious Diseases

region.
phosphate, and host material.
 The primary lesion is a painless nodule which
slowly enlarges and erodes to produce bright-red Clinical Features
ulcers with pearly rolled edges. Ulcer bleeds easily.
The lesions progress slowly and heal with fibrosis. Cervicofacial Actinomycosis
There is no lymph node involvement.  Most common type. Painful swelling in the angle
 Extragenital lesions occur in some cases and may of jaw is the usual initial symptom. The swelling
involve oral cavity, lips, and bones. Lesions in the
inguinal region may resemble lymph nodes.
is purplish, firmly indurated, and feels woody or
lumpy (hence, also known as lumpy jaw). There 1
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32 can be multiple such swellings which break to the Treatment
surface, forming multiple sinus tracts discharging  Requires prolonged antibiotic therapy (6–12 months).
pus with yellowish white granules. It may spread  Penicillin is the drug of choice; 10 to 20 million units
to tongue, salivary glands, thorax, cervical spine, intravenously daily for 2–6 weeks followed by oral
cranial bones and brain. penicillin or amoxicillin for 6–12 months.
 Erythromycin, tetracycline, and clindamycin are
Thoracic Actinomycosis
alternatives.
 Results from aspiration of pharyngeal contents or
dental plaques into the lungs or spread from cervico- Q. Nocardiosis.
facial actinomycosis. Patients usually c/o mild fever
and cough with expectoration. Sputum can be  Nocardiosis is an acute, subacute, or chronic infec-
blood-stained. Multiple abscesses may develop in tious disease that occurs in cutaneous, pulmonary,
the lungs which may break open into the exterior and disseminated forms.
through multiple discharging sinuses. Chest X-ray  Members of the genus Nocardia are ubiquitous
shows consolidation bilaterally in the lower lung saprophytes in soil, decaying organic matter, and
fields. fresh and salt water. Nocardia organisms are
branching, beaded, filamentous, gram-positive
Abdominal Actinomycosis bacteria. They are weakly acid-fast except Nocardia
 Results from diseased appendix. It can involve any madurae which is non acid-fast.
organ in the abdomen. The disease usually presents  Reproduce by branching.
as an abscess or mass lesion that is often fixed to  N. asteroids and N. Brasiliensis cause pulmonary
underlying tissue and mistaken for a tumor. Sinus infections, meningitis, and brain abscess. N. madurae
tracts may form in the abdominal wall. causes mycetoma.

Pelvic Actinomycosis Clinical Features

 Involves uterus and cervix. It has become common  Cutaneous nocardiosis can present in three clinical
with the use of intrauterine contraceptive devices. forms: (1) Cutaneous infection, (2) lymphocutaneous
infection and (3) subcutaneous infection. Cutaneous
CNS Actinomycosis infection presents as ulceration, abscess, and
cellulitis. Lymphocutaneous nocardiosis manifests
 Rare. Can present as meningitis or multiple brain as a nodule/ulcer at the site of injury, lymphangitis,
abscesses. and regional lymphadenopathy. Subcutaneous
infection (also known as mycetoma) presents as pus
Musculoskeletal and Soft-Tissue Actinomycosis
discharging sinuses which may contain yellow
 Skin, subcutaneous tissue, muscle, and bone coloured granules.
involved alone or in various combinations.  Pulmonary nocardiosis is the most common clinical
 Multiple cutaneous sinus tracts. presentation of nocardiosis. It occurs due to inhala-
tion of nocardia. Pulmonary nocardiosis is usually
Disseminated Disease seen as opportunistic infection in immunocompro-
 Multiple organ infections. mised patients. Patients present with fever and cough
with expectoration. X-ray shows lung infiltrates.
 Lungs and liver most commonly involved.
 Extrapulmonary infections commonly involve
 Presentation: Multiple nodules mimicking dis- brain. Cerebral nocardiosis presents as space-
Manipal Prep Manual of Medicine

seminated cancer. occupying lesion. Purulent meningitis may result

if an abscess ruptures into the ventricles.
Diagnosis
 Microscopic identification of sulfur granules in pus Diagnosis
or tissues. Sometimes granules may be visible to  Microscopy
the naked eye.  Culture of pus and tissue specimens for Nocardia.
 Sulfur granules may also be found in mycetoma. If
any doubt is there, identification of actinomycetes Treatment
by microscopy and culture of pus or tissue speci-  Long term antibiotic therapy is required (at least
mens will confirm the diagnosis. However, because 6 months). Sulfonamides are the drugs of choice
these organisms are part of the normal flora, their for nocardiosis. Sulfadiazine or sulfisoxazole can


identification in the absence of sulfur granules in be used. Trimethoprim sulfamethoxazole (TMP-SMZ)

1 sputum, bronchial washings, and cervicovaginal
secretions is of little significance.
is also effective. Additional or alternative parenteral
therapies include carbapenems (imipenem or

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 meropenem), third-generation cephalosporins Treatment 33
(cefotaxime or ceftriaxone), and amikacin alone or  Differentiation between actinomycetoma caused by
in combination. Combination therapy is recom- bacteria and eumycetoma caused by fungi is
mended for serious infections. important because treatment is different for both.
 For actinomycetoma (caused by bacteria), surgical
Q. Mycetoma (Madura foot or Maduromycosis). debridement followed by prolonged antibiotic
therapy is required. A combination of antibiotics
 Mycetoma is a chronic infection of the skin and
are used including trimethroprim sulpha-
subcutaneous tissue characterized by a triad of
methoxazole, streptomycin, dapsone and rifampicin.
tumefaction, sinus tract formation, and grains
 For eumycetoma (caused by fungi), surgery
(sulfur granules). It is also known as Madura foot
followed by antifungal therapy (amphotericin B or
because it was first described in the Indian town of
itraconazone or ketoconazole) is used.
Madura region in the mid-19th century.

Etiology Q. Discuss the etiology, epidemiology, pathogenesis,

clinical features, diagnosis and treatment of leprosy
 Mycetoma is caused by filamentous bacteria and
(Hansen’s disease).
true fungi.
 Mycetoma caused by filamentous bacteria is termed  Leprosy (Hansen’s disease) is a nonfatal, chronic
actinomycetoma. These filamentous bacteria are infectious disease caused by Mycobacterium leprae.
Nocardia species such as Nocardia brasiliensis, To minimize the prejudice against those with leprosy,
Nocardia madurae, and Actinomyces israelii. the condition is also referred to as Hansen disease,
 Mycetoma caused by true fungi is termed eumyce- named after GA Hansen who discovered M. leprae.
toma. Eumycetoma can be caused by Pseudallescheria  First described in ancient Indian texts from the sixth
boydii, Phialophora jeanselmei, Madurella mycetomi, century BC.
Madurella grisea, Cephalosporium falciforme, and  Mainly affects skin, peripheral nervous system,
Cephalosporium recifei. upper respiratory tract, eyes, and testes.
 Associated with social stigma.
Clinical Features
 Mycetoma commonly affects young adults, Etiology
particularly males aged between 20 and 40 years,
 Mycobacterium leprae is the causative agent of
mostly in developing countries. People of low
leprosy.
socioeconomic status and manual workers such as
 It is an acid-fast and obligate intracellular organism.
agriculturalists, labourers and herdsmen are
commonly affected. Organisms enter the skin
through minor trauma.  The organism grows best at 27–30°C; therefore, skin
lesions tend to develop in the cooler areas of the
 Mycetoma is a chronic, deep, progressively destruc-
body, with sparing of the groin, axilla, and scalp.
tive, and deforming infection of skin, subcutaneous
tissues, bone, and muscle. Most of the cases involve  Cannot be cultured in vitro.
foot but any part of the body can be involved. It
Epidemiology
manifests as a tumor like area of localized edema
or massive enlargement, with erythema and  99% of leprosy cases are found in Asia, Africa and
multiple draining sinus tracts. In a typical case, a Latin America. Highest number of cases is in
triad of tumefaction, sinus tract formation, and India.
grains (sulfur granules) is seen. The color of the  Affects all age groups. Peak onset is in the second
grains varies depending on the pathogen. and third decades of life.
 Note that mycetoma is different from actinomycosis.  Leprosy is associated with poverty and rural
Actinomyces israeli can cause both actinomycosis and residence.
mycetoma. Its incidence is not increased by AIDS unlike


tuberculosis.
Infectious Diseases

Investigations  Recently there has been a dramatic decline in leprosy

 Gram’s stain of secretions can show filamentous cases because of effective multi-drug therapy.
gram-positive bacteria or gram-negative fungi.
 Biopsy: Shows suppurative granulomas surround- Pathogenesis
ing characteristic grains in the subcutaneous tissue.  Incubation period is long, 5–10 years.
Causative filamentous bacteria or fungi can be seen  It spreads by droplet infection when an infectious


in Gram’s stain.
Culture of the secretions or biopsy specimens.
(lepromatous) patient releases the organisms by
coughing and sneezing. The organism enters the 1
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34 body through skin, mucous membranes of the skin gives rise to convoluted folds, which give the
respiratory tract and possibly the gut. The infecti- face a lion-like appearance (hence called ‘leonine
vity of the disease is low and large percent of people facies’).
exposed to the infection do not get infected.  Infiltration of eyebrows leads to loss of eyebrows,
 Leprosy has 2 classification schemes: The 5-category initially lateral third.
Ridley-Jopling system and the simpler 2-category  Nose can get involved which can cause nasal bridge
WHO system. collapse and epistaxis. Nasal septum can get
 Ridley-Jopling system divides leprosy into five perforated.
clinical categories (2 polar forms and 3 borderline  Patients with LL leprosy have late involvement of
forms). Two polar forms are; tuberculoid (TT) and nerves which presents as distal symmetric peripheral
lepromatous leprosy (LL). Tuberculoid leprosy neuropathy. Neural involvement predisposes to
occurs in people with good immunity. Lepromatous painless burns and trophic ulcers, deformities and
leprosy occurs in people with low immunity. resorbed digits of the hands and feet.
Between these forms lies a large group of patients  Systemic involvement causes lymphadenopathy,
described as the borderline group. In this group, hepatosplenomegaly, testicular involvement and
patients showing features closer to lepromatous gynecomastia, and bacillemia. Smears from lesions
leprosy are designated borderline lepromatous (BL) show large number of bacilli. Lepromin test is
leprosy and those with features closer to negative in LL leprosy.
tuberculoid form are designated as borderline  The disease runs a slow and progressive course.
tuberculoid (BT) leprosy; patients with features Patients may die of intercurrent infections, renal
lying midway between the two are classified as failure or amyloidosis all of which are complica-
borderline (BB) leprosy. tions of leprosy.
 WHO classifies leprosy into two types, i.e.
paucibacillary and multibacillary types. This Borderline Group
classification is important for treatment purpose.  In the BT form, the lesions show features closer to
tuberculoid form of the disease. Lesions may be
Clinical Features more or a tuberculoid lesion may have a satellite
Tuberculoid (TT) Leprosy lesion close to it. In BL form, the lesions show
features closer to the lepromatous form. Genuine
 Occurs in people who possess a high degree of cell borderline (BB) cases have features midway
mediated immunity. between tuberculoid and lepromatous leprosy.
 More often affects brown and black people.
 The skin lesions of tuberculoid leprosy are only one Primary Neuritic Leprosy
or few hypopigmented macules or plaques that are  Here nerve involvement is seen without any skin
sharply demarcated and hypoaesthetic. Lesions lesions. Nerves are thickened and may be tender
usually have erythematous or raised borders, and with associated loss of sensations. Facial palsy can
are devoid of sweat glands and hair follicles and also be a presentation.
thus are dry, scaly, and anhidrotic.
 The regional or local nerve is thickened and may Indeterminate Leprosy
be tender. Most commonly affected nerves are  This is often a single hypopigmented macule which
ulnar, posterior auricular, peroneal, and posterior may be atrophic and may be hypoasthetic. Acid-
tibial nerves. fast bacilli may or may not be seen. At this stage it
 Histology of the lesions shows granulomatous is difficult to tell which way the lesion will progress
Manipal Prep Manual of Medicine

infiltrate consisting of macrophages, lymphocytes whether towards the lepromatous end or tuber-
and giant cells. The infiltrate is more prominent culoid end.
around the nerves and the skin appendages. Differences between tuberculoid and lepromatous
 Smears from lesions show absent or very few AFB. leprosy are given in Table 1.8.
 Lepromin test is positive in TT leprosy.
Diagnosis
Lepromatosus (LL) Leprosy  Currently, the diagnosis of leprosy is based on
 Occurs in people who have less cell mediated clinical features. Examination of skin smears and/
immunity. or biopsy can confirm the diagnosis.
 It more often affects white people.
 The skin lesions are multiple, bilaterally symme- Clinical Features


trical, hypopigmented macules, plaques, nodules  In an endemic country or area, an individual should

1 or diffuse skin infiltration. The margins are ill

defined, and diffuse. Diffuse infiltration of facial
be regarded as having leprosy if he or she has one
of the following features:

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TABLE 1.8: Differences between tuberculoid leprosy and lepromatous leprosy 35
Feature Tuberculoid leprosy (TT) Lepromatous leprosy (LL)
Skin Lesions Up to 3 in number; sharply defined asymmetric Multiple symmetric lesions with ill-defined
macules or plaques with elevated borders and margins, multiple infiltrated nodules and
a tendency toward central clearing. Hypo- plaques or diffuse infiltration; leonine facies
esthesia an early sign and loss of eyebrows. Hypoesthesia a late sign
Nerve lesions Peripheral nerves involved early. Only few nerves Nerves are involved late in the disease. Symme-
are involved. Nerves are thickened and may be tric involvement common
tender
Acid-fast bacilli (bacterial 0 to 1+ 4 to 6+
index)
Lymphocytes 3+ 0 to 1+
Lepromin skin test Positive Negative
IgM antibodies to PGL-1 Found most often Found less often

 Hypopigmented or reddish skin lesion(s) with  Currently, most leprosy programmes classify and
definite loss of sensation. choose the appropriate regimen for a particular
 Involvement of peripheral nerves, as demonstrated patient using clinical criteria, which uses the
by loss of sensation and weakness of the muscles number of skin lesions and nerves involved to
of hands, feet or face. classify leprosy patients into paucibacillary single-
 Skin smear positive for acid-fast bacilli. lesion leprosy (one skin lesion), paucibacillary
leprosy (2–5 skin lesions) and multibacillary leprosy
Skin Smears and Biopsy (more than five skin lesions).
 Skin smears may be taken from lesions on the ears,  When skin smears are available and reliable, any
elbows, and/or knees. A biopsy should be taken patient with a positive skin smear, irrespective of
from entirely within a lesion. the clinical picture, must be classified as multi-
bacillary leprosy and treated with the regimen for
Other Diagnostic Tests multibacillary leprosy.
 Measurement of anti-phenolic glycolipid-1 (PGL-1) anti-  The WHO recommends that paucibacillary adults
bodies: This is a specific serologic test based on the be treated with 100 mg of dapsone daily and
detection of antibodies to phenolic glycolipid-1. 600 mg of rifampicin monthly (supervised) for
This test yields a sensitivity of 95% for the detec- 6 months. For patients with single-lesion pauci-
tion of lepromatous leprosy but only 30% sensitive bacillary leprosy, the WHO recommends as an
for tuberculoid leprosy. alternative a single dose of ROM (rifampin 600 mg,
 Polymerase chain reaction (PCR): This can be used to ofloxacin 400 mg, and minocycline 100 mg).
identify the Mycobacterium in biopsy samples, skin  Multibacillary adults should be treated with 100 mg
and nasal smears, and blood and tissue sections. of dapsone plus 50 mg of clofazimine daily
 Lymphocyte migration inhibition test (LMIT): As (unsupervised) and with 600 mg of rifampicin plus
determined by a lymphocyte transformation and 300 mg of clofazimine monthly (supervised).
LMIT, cell-mediated immunity to M. leprae is absent Originally, the WHO recommended that multi-
in patients with lepromatous leprosy but present bacillary patients be treated for 2 years or until
in those with tuberculoid leprosy. smears became negative (generally in ~5 years).
However, current WHO recommendation of dura-
Treatment of Leprosy tion of therapy is 1 year. While 1 year of treatment
is enough for most cases, concern has been
 There are 3 main drugs for the treatment of leprosy. expressed that it is not sufficient for higher bacterial
These are dapsone, clofazimine, and rifampicin. Of index (BI) cases.
these drugs, only rifampicin is bactericidal but


dapsone is the most important.

Infectious Diseases

TABLE 1.9: WHO treatment of leprosy

 Other agents which are effective against leprosy are Form of leprosy WHO recommended regimen (1982)
minocycline, ofloxacin and clarithromycin. Paucibacillary Dapsone (100 mg daily, unsupervised)
 WHO has made recommendations for the treatment (tuberculoid) plus Rifampicin (600 mg/month, super-
of leprosy. For treatment purposes, the WHO vised) for 6 months
classifies leprosy patients as paucibacillary and Multibacillary Dapsone (100 mg/d) plus Clofazimine
multibacillary. Previously, patients without demon- (lepromatous) (50 mg/d), unsupervised; and Rifampicin
strable AFB in the dermis were classified as pauci-
bacillary and those with AFB as multibacillary.
(600 mg) plus Clofazimine (300 mg)
monthly (supervised) for 1–2 years 1
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36 Complications of leprosy  Testes: M. leprae can invade testes and cause
 Extremities: Distal myopathy, claw hand, loss of aspermia or hypospermia. Erythema nodosum
digits, foot drop, trophic ulcers. leprosum can also cause orchitis.
 Nose: Destruction of nasal cartilage with resultant  Amyloidosis: Secondary amyloidosis is a complica-
saddle nose deformity and anosmia, epistaxis. tion of LL leprosy.
 Eye: Corneal ulcerations and development of
 Nerve abscesses: Seen in TT and BT forms of leprosy
opacities due to loss of sensation of cornea. Uveitis
and can cause rapid nerve destruction which may
due to direct bacterial invasion with consequent
cataracts and glaucoma. be permanent.

Q. Write briefly about antileprosy drugs (Table 1.10).

TABLE 1.10: Antileprosy drugs

Drug Mechanism of action Features Dosage Side effects
Dapsone Inhibition of folic acid Bacteriostatic. Inexpensive 100 mg daily Agranulocytosis hemolytic
synthesis and relatively non-toxic anemia in patients with
G6PD deficiency
Rifampicin Rifampicin binds the Most bactericidal drug 600 mg monthly Renal failure, bone marrow
DNA-dependent RNA available for the treatment suppression, “flu-like” syn-
polymerase complex of leprosy drome, hepatitis
uncoupling transcription
Clofazimine Binds preferentially to Weakly bactericidal against 50 mg daily Skin pigmentation
mycobacterial DNA and M. leprae
inhibits Mycobacterium
leprae growth
Ofloxacin Interferes with bacterial Bactericidal 400 mg single dose Nausea, diarrhea and other
DNA replication by as part of ROM single gastrointestinal complaints
inhibiting DNA gyrase dose regimen CNS effects such as insomnia,
headache, dizziness, nervous-
ness, and hallucinations
Clarithromycin Inhibits bacterial protein Bactericidal for M. leprae 500 mg daily Gastrointestinal irritation,
synthesis by binding to nausea, vomiting, and
50S ribosomal subunit diarrhea
Minocycline Inhibits protein synthesis Bactericidal for M. leprae 100 mg daily Discoloration of teeth in
by binding to 30S infants or children
ribosomal subunit

Q. Lepra reactions. neuritis, and rarely fever. Ulnar nerve is usually

affected at elbow, which may be painful and
 Lepra reactions are immunologically mediated exquisitely tender. Foot drop may result due to
inflammatory states. They occur due to abrupt peroneal nerve involvement. If patients with
change in immunological response of the body affected nerves are not treated promptly with
against M. leprae. steroids, irreversible nerve damage may occur.
Manipal Prep Manual of Medicine

 They can cause considerable suffering to the patient

and sometimes can be life threatening. Type 2 lepra reaction (erythema nodosum leprosum,
ENL)
 Two types of lepra reactions are usually seen.
 Type 2 lepra reaction occurs in patients with high
Type I reaction (reversal reaction) load of leprosy bacilli as in multibacillary/infiltra-
 Type I reactions occur in borderline forms of tive type of leprosy. Type 2 reaction can involve
leprosy as a result of increased activity of the body’s multiple organs and systems, causing generalized
immune system against M. leprae. Usually the BL symptoms.
form changes to BT form with treatment due to  It occurs when large number of leprosy bacilli are
increase in immunity, hence this type of reaction is killed with release of their antigens. These antigens
also known as reversal reaction. Cell mediated provoke an arthus type allergic reaction producing
immunity plays a major role here. It occurs both in antigen antibody immune complex reaction (type


paucibacillary and multibacillary leprosy. III hypersensitivity) in the presence of complement

1  Manifestations include signs of inflammation in

pre-existing lesions, appearance of new skin lesions,

system. Immune complexes are deposited in the
tissues (skin, eyes, joints, lymph nodes, kidneys,

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 liver, spleen, bone marrow, endothelium and testes) Treatment of Lepra Reactions 37
as well as in the circulation.  For mild type 1 lepra reaction, analgesics, such as
 Most cases of ENL follow the initiation of chemo-
acetylsalicylic acid or paracetamol are enough. For
therapy, usually within 2 years. Rarely it may occur severe type 1 lepra reactions with evidence of
even before the diagnosis of leprosy and may in neuritis (pain, loss of sensation or function), steroids
fact point towards leprosy diagnosis. such as oral prednisolone should be used. The usual
 Patients usually present with multiple painful dose of prednisolone is 40–60 mg daily (1 mg/kg)
erythematous papules that resolve spontaneously initially followed by a gradual tapering. The
in a few days but may recur. Patients may also have duration of steroid therapy is 3 months.
fever, arthritis, myalgia and epididymo-orchitis,  Therapy for type 2 reaction includes analgesics,
iridocyclitis and lymphadenopathy. There can be such as acetylsalicylic acid or paracetamol, and
anemia, leukocytosis, and abnormal liver function steroids (oral prednisolone). In patients with severe
tests. Skin biopsy of erythematous papules reveals type 2 reactions, who do not respond to steroids or
vasculitis or panniculitis. Rarely severe ENL can in whom steroids are contraindicated, clofazimine
result in death. at high doses or thalidomide may be used under close
Differences between type 1 and type 2 lepra medical supervision. Clofazimine often requires
reactions are given in Table 1.11. 4–6 weeks before an effect is seen, and, therefore,
initially it should be combined with steroids.
TABLE 1.11: Differences between type 1 and type 2 lepra
reactions Q. Syphilis.
Type 1 reaction Type 2 reaction
 Syphilis is an infectious venereal disease caused by
It occurs both in paucibacillary Occurs mainly in multibaci-
the spirochete Treponema pallidum.
and multibacillary leprosy llary (lepromatous) leprosy
 It is characterized by episodes of active disease
Occurs due to increase in cell Occurs due to antigen anti-
mediated immunity (delayed body (immune complex) de-
interrupted by periods of latency.
type hypersensitivity) position
Etiology
Localised More generalized
Skin lesions: Inflammation in Existing skin lesions remain
 Syphilis is caused by pallidum subspecies of
pre-existing lesions, appea- unchanged and new red, Treponema which belongs to spirochete group.
rance of new skin lesions painful, tender, cutaneous/  It is spiral in shape. Live organisms can only be seen
subcutaneous nodules appear under dark-ground illumination because of poor
(ENL) resolution with conventional light microscopy.
Nerve involvement common Uncommon Treponema organisms have characteristic to-and-
Little or no fever and other Prominent fever and other fro, undulating, corkscrew-like and angulating
constitutional symptoms constitutional symptoms movements.
Eye involvement in the form Internal eye disease (iritis,  Syphilis is becoming a rare disease now after the
of weakness of eyelid muscles irido-cyclitis) occurs, lepro- discovery of penicillin. However, efforts to
leading to incomplete closure matous nodules are seen eradicate this disease have been unsuccessful.
may occur (nerve involved)
Other organs not affected Multiple organs may be
affected

Lucio’s Phenomenon
 This rare reaction is seen exclusively in patients of
Caribbean and Mexican origins.
 It is seen with lepromatous leprosy. It affects most
often those who are untreated.


 Patients develop recurrent, large, ulcerative

Infectious Diseases

lesions—particularly on the lower extremities.

Ulcers may develop all over the body. Secondary
infection and consequent sepsis can be fatal. Ulcers
happen due to ischemic necrosis of skin, which in
turn is due to thrombus formation in blood vessels
supplying skin due to heavy parasitism of endo-
thelial cells with AFB, and endothelial proliferation.
Immune complex deposition may also play a role
in thrombus formation. Figure 1.10 Treponema pallidum 1
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38 Pathophysiology Primary Syphilis
 The only known natural host for T. pallidum is  Primary syphilis is characterized by the develop-
man. ment of a painless chancre at the site of entry after
 Almost all cases of syphilis are acquired by sexual an incubation period of 3–6 weeks. The lesion has
contact. Less commonly it is acquired by nonsexual a punched-out base and rolled edges and is highly
personal contact, infection in utero (congenital infectious. It has a firm consistency. In heterosexual
syphilis), and blood transfusion. 1 in 2 persons men the chancre is usually located on the penis,
exposed to infection gets infected. whereas in homosexual men it is often found in the
 Syphilis is usually classified into 4 stages: primary, anal canal or rectum, in the mouth, or on the
secondary, latent, and tertiary. It can be acquired external genitalia. In women, it is usually found on
or congenital. the cervix and labia. Regional lymphadenopathy
 Primary syphilis: In acquired syphilis, after exposure, is usually seen. Lymph nodes are firm, non-
T. pallidum penetrates intact mucous membranes or suppurative, and painless.
microscopic dermal abrasions and enters the
Secondary Syphilis
lymphatics and blood to produce systemic
infection. At the site of entry, a painless ulcer  Secondary syphilis has protean manifestations.
develops which is called chancre. Histologically, the These include skin and mucous membrane lesions
chancre is characterized by local inflammation with and generalized painless lymphadenopathy. The
infiltration by macrophages and lymphocytes. In healing primary chancre may be still present in
this stage, the spirochete can be isolated from the some cases. The skin lesions are macular, papular,
surface of the ulceration or the overlying exudate. papulosquamous rashes, and occasionally pustules.
Whether treated or not, healing occurs with residual The rahes may be very subtle and may be missed.
fibrosis. Initial lesions are bilaterally symmetric, pale red or
 Secondary syphilis develops several weeks or months pink, nonpruritic, discrete, round macules that
after the appearance of the primary lesion. During measure 5 to 10 mm in diameter and are distributed
this stage, the spirochetes multiply and spread on the trunk and proximal extremities. After many
throughout the body. Secondary syphilis has days or weeks, red papular lesions appear. These
numerous clinical manifestations. Common lesions may progress to pustular lesions.
manifestations include malaise, fever, myalgias,  In warm and moist areas like perianal area, vulva,
arthralgias, lymphadenopathy, and rash. scrotum, etc. papules can enlarge and become
 Latent syphilis is characterized by resolution of skin eroded to produce moist, pink or gray-white, highly
lesions and other clinical manifestations. However, infectious lesions called condylomata lata. Mucosal
serologic tests are positive for T. pallidum. lesions include erosions, called mucous patches and
 Tertiary or late syphilis develops years after the initial occur on lips, oral mucosa, tongue, palate, pharynx,
infection (5–10 years later) and can involve any vulva and vagina, glans penis. The mucous patch
organ system. The most dreaded complications are is painless with a red periphery.
neurosyphilis and involvement of the aortic valve  Constitutional symptoms may accompany secon-
and root. Initially syphilis mainly involves dary syphilis and include fever, weight loss, malaise,
meninges and vasculature of CNS (meningo- anorexia and headache. Meningitis can occur rarely.
vascular syphilis), later the parenchyma of brain  Less commonly there can be hepatitis, nephropathy,
and spinal cord is involved. arthritis, periostitis, iritis and uveitis.
 Regardless of the stage of disease and location of
lesions, histopathologic hallmarks of syphilis are Latent Syphilis
Manipal Prep Manual of Medicine

endarteritis and a plasma cell-rich infiltrate. The  In latent syphilis serologic tests for syphilis are
syphilitic infiltrate is actually a delayed-type hyper- positive but there are no clinical manifestations. In
sensitivity response to T. pallidum, and can result latent syphilis T. pallidum is present in the body.
in gummatous ulcerations and necrosis seen in Latent syphilis can get transmitted to the fetus in
tertiary syphilis. Antigens of T. pallidum induce utero and to others through blood transfusion.
treponemal antibodies and nonspecific reagin
antibodies. Tertiary Syphilis
 Tertiary syphilis is characterized by a persistent
Clinical Features low-level burden of pathogens, against which a
 Acquired syphilis has predictable stages though potent and self-destructive immune response is
there may not be clear cut demarcation between mounted. It is usually very slowly progressive and


the stages. Four stages can usually be recognized noninfectious. Any organ of the body may be

1 and include: (1) Primary, (2) secondary, (3) latent, and

(4) tertiary syphilis.
involved, but three main types are: Neurosyphilis,
cardiovascular syphilis and gummatous (late) syphilis.

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Neurosyphilis Gummas may be single or multiple and size varies 39
 Traditionally, neurosyphilis was considered to be from microscopic to many centimeters. The most
a late manifestation of syphilis, but this not true commonly involved sites are skin, mucous
and CNS can get affected anytime. CNS involve- membranes and skeletal system. Gummas of the
ment can be asymptomatic or symptomatic. skin produce painless and indurated nodular
Asymptomatic neurosyphilis refers to patients lesions which may breakdown to form punched-
without any neurological signs and symptoms but out ulcers with vertical edges. The ulcer heals in
have CSF abnormalities or a positive VDRL test. the middle with an atrophic tissue-paper scar and
Such asymptomatic patients should be treated spreads peripherally. The base of the lesion is dull
because untreated patients may progress to red and appears like ‘wash-leather’. Nocturnal bone
symptomatic neurosyphilis. pain may occur due to bone involvement.
 Neurosyphilis can be meningeal, meningovascular,
Congenital syphilis
and parenchymatous syphilis. Meningeal syphilis
 Transmission of T. pallidum from a syphilitic woman
occurs usually within 1 year after infection,
meningovascular syphilis occurs 5 to 10 years after to her fetus across the placenta may occur at any
infection, general paresis after 20 years, and tabes stage of pregnancy, but the lesions in fetus develop
dorsalis after 25 to 30 years. after the fourth month of gestation.
 Treatment of the mother before 4th month of
 Meningeal syphilis presents with typical signs and

symptoms of meningitis like headache, nausea, gestation can prevent fetal damage. Untreated
vomiting, neck stiffness, and alteration of mental maternal infection may lead to abortion, stillbirth,
status. prematurity, neonatal death, or nonfatal congenital
syphilis.
 Meningovascular syphilis involves meninges and also
 Among infants born alive, congenital syphilis may
blood vessels leading to stroke.
or may not be clinically apparent.
 Parenchymatous syphilis involves brain and spinal
 All women should be screened for syphilis in early
cord and manifests as General paresis and tabes
dorsalis. General paresis happens due to wide- pregnancy. In areas of high prevalence serologic
spread brain parenchymal damage and includes screening should be repeated in the third trimester
abnormalities corresponding to the mnemonic and at delivery.
PARESIS: Personality disturbances, Affect abnor-  The manifestations of congenital syphilis can be

malities, Reflex hyperactivity, Eye abnormality divided into three types:

(Argyll Robertson pupils), Sensorium changes, – Early manifestations: Appear within the first
Intellectual impairment and Slurred speech. In 2 years of life. These are due to infection of
tabes dorsalis there is demyelination of the posterior various organs by Treponema pallidum and
columns, dorsal roots, and dorsal root ganglia. resemble secondary syphilis in the adult. These
Symptoms include ataxia, paresthesia, bladder include rhinitis (snuffles), bullae (syphilitic
disturbances, impotence, areflexia and loss of joint pemphigus), vesicles, petechiae, papulosqua-
position, deep pain, and temperature sensations. mous lesions, mucous patches, and condylomata
Argyll Robertson pupil can be seen in both tabes lata. The most common early manifestations are
dorsalis and general paresis. It reacts to bone changes including osteochondritis, osteitis,
accommodation but not to light. Optic atrophy also and periostitis. Hepatosplenomegaly, lympha-
occurs frequently in tabes. denopathy and jaundice are also common.
Cardiovascular syphilis – Late manifestations: Appear after 2 years and are
noninfectious manifestations. These include
 Cardiovascular manifestations are due to end-
interstitial keratitis, eighth-nerve deafness,
arteritis obliterans of the vasa vasorum, which
recurrent arthropathy and bilateral knee effusion
provide blood supply to large vessels. This results
known as Clutton’s joints. Neurosyphilis and
in weakening of tunica media and formation of
gummatous periostitis can also occur.
aneurysm, aortitis (with linear calcification of the


ascending aorta on chest X-ray), aortic regurgita- – Residual stigmata: These include Hutchinson’s
Infectious Diseases

tion, or coronary ostial stenosis. Symptoms usually teeth (centrally notched, widely spaced, peg-
appear 10 to 40 years after infection. The most shaped upper central incisors) and “mulberry”
common finding on cardiovascular examination is molars (molars with multiple, poorly developed
a diastolic murmur with a tambour quality, secon- cusps). There can be abnormal facies like frontal
dary to aortic dilation with valvular insufficiency. bossing, saddle nose, and poorly developed
maxillae. Saber shins, characterized by anterior
Gummatous syphilis (late syphilis) tibial bowing, are rare. Rhagades are linear scars
 Gummas are nothing but areas of granulomatous

inflammation with a central area of necrosis.

at the angles of the mouth and are caused by
healing of early facial eruption. 1
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40 Diagnosis Treatment
 The diagnosis of syphilis is suspected based on  The treatment of choice in all stages of syphilis is
history and clinical features. Since the clinical long acting preparation of penicillin (benzathine
features are protean, lab confirmation of diagnosis penicillin) except in neurosyphilis where aqueous
is required. penicillin is used.
 Benzathine penicillin 2.4 million units IM (1.2 million
Dark Field Microscopy units to each buttock) cures primary, secondary,
 This is the most specific technique for diagnosing and early (<1 year) latent syphilis. Additional doses
syphilis and can demonstrate Treponema pallidum of 2.4 million units should be given 7 and 14 days
in samples taken from chancre and condylomata later for late (>1 year) latent syphilis.
lata. But dark-field microscopy is not widely avail-  Neurosyphilis should be treated with intravenous
able. aqueous penicillin G (3 to 4 million units IV Q 4h
for 10 to 14 days) followed by benzathine penicillin
Non-treponemal Tests 2.4 million units deep IM once a week for 3 weeks.
 For penicillin allergic patients doxycycline 100 mg
 These include venereal disease research laboratory
BD for 1 month should be given. Doxycycline is
(VDRL) test and rapid plasma reagin (RPR) test.
contraindicated in pregnant women and children.
 Syphilis leads to the production of non-specific In such cases penicillin should be administered after
antibodies that react to cardiolipin. This reaction is desensitization. Ceftriaxone1 gm daily IM/IV for
the basis of VDRL and rapid plasma reagin (RPR) 8 to 10 days is an alternative. At 6 and 12 months
test. Nontreponemal tests are widely used for after treatment, patients with primary syphilis
syphilis screening. should be reexamined and undergo repeat serologic
 With nontreponemal tests, false-positive reactions testing.
can occur because of pregnancy, autoimmune  Congenital syphilis: Aqueous penicillin 50,000 units/
disorders, and other infections. In addition, these kg IV q 12 h for the first 7 days of life and q 8 h
tests may show a “prozone” phenomenon in which thereafter for a total of 10 days.
large amount of antibody blocks the antibody-
antigen reaction, causing a false-negative test in the Q. VDRL (Venereal Disease Research Laboratory) test.
undiluted sample.
 These tests may be negative in early primary  VDRL is a nontreponemal antibody test to diagnose
syphilis and late syphilis in up to one-third of syphilis. It is quite sensitive but not very specific
patients. for syphilis. VDRL is reactive in 78% of patients
 After adequate treatment of syphilis, nontrepo- with primary syphilis. It becomes positive within
nemal tests eventually become nonreactive. 4 to 6 weeks after infection or 1 to 3 weeks after the
appearance of the primary lesion. Thus, these tests
 Titers are not interchangeable between different test
can be negative in early syphilis. VDRL can also be
types. Hence, the same nontreponemal test should
negative in some untreated patients in late syphilis.
be used for follow-up evaluations.
Hence, VDRL cannot be relied on for diagnosis in
very early or late stage of syphilis.
Treponemal-specific Tests
 False positive VDRL test can occur in infections (TB,
 Treponemal-specific tests detect antibodies to HIV, Lyme disease, infectious mononucleosis,
antigenic components of T. pallidum. These tests malaria), pregnancy, connective tissue diseases,
are used primarily to confirm the diagnosis of liver disease, and malignancy.
Manipal Prep Manual of Medicine

syphilis in patients with a reactive nontreponemal  Because of frequent false positive and false negative
test. VDRL test, all positive tests and all negative tests
 Treponemal-specific tests include T. pallidum enzyme in patients in whom syphilis is strongly suspected
immunoassay (TP-EIA), T. pallidum hemagglutina- clinically, should be verified by a specific trepo-
tion (TPHA) test, microhemagglutination assay for nemal test.
antibodies to T. pallidum (MHA-TP), fluorescent  The nontreponemal tests are quite useful for
treponemal antibody-absorption (FTA-ABS) test, monitoring the patient’s response to treatment,
chemoluminescence immunoassays (CLIA). because the titers reflect disease activity. When
 Unlike nontreponemal tests which show a decline these tests are used for this purpose, it is important
in titers or become nonreactive with effective to use the same test (either VDRL or RPR) for serial
treatment, treponemal-specific tests usually remain measurements because the two tests can differ


reactive for life. Therefore, treponemal-specific significantly in their titers. When possible, it is
1 test titers are not useful for assessing treatment
efficacy.
also recommended to do the test in the same labora-
tory.

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Q. Yaws.  Pinta is a Spanish word used to describe a spotted 41
or mottled appearance. The lesions of pinta have a
 Yaws is a chronic, relapsing, nonvenereal infection peculiar pigmented appearance on the skin.
caused by Treponema pallidum pertenue. Yaws,
 Transmission is non-venereal by contact with skin
endemic syphilis (bejel), and pinta collectively
lesions. Various biting and sucking arthropods have
constitute the endemic treponematoses.
also been implicated.
Clinical Features Clinical Features
 The incubation period is 9 to 90 days (average  It is predominantly a disease of childhood. After
20 days). infection, 2–3 weeks later, a primary lesion at the
 It predominantly affects children with peak site of inoculation appears. Secondary lesions appear
incidence between 5 and 9 years of age. after a month or a year. These secondary lesions are
 It spreads through close contact and the presence erythematous papules which become scaly and
of minor skin lesions, abrasions and scratches which pigmented. These lesions gradually regress and
facilitate penetration and infection by the become depigmented. Lesions are found mainly on
treponemae. distal extremities. Trunk and face may also be
 Initially patient develops constitutional symptoms involved. The lesions have to be differentiated from
like bodyache, malaise and fever with rigors for a other depigmented lesions like leprosy, yaws,
week. Then the initial yaws may start as a maculo- syphilis, psoriasis, tinea versicolor, and vitiligo.
papular eruption and then may develop into a
papilloma. Initial lesion usually appears on the leg. Investigations
Several weeks to months later generalised papillo-  Same as those described under yaws.
matous eruptions may appear. Bone and joints can
get affected and take the form of periostitis and Management
osteitis. Gondou is a hypertrophic osteitis of the  Penicillin is the drug of choice. Tetracycline or doxy-
nasal process of the maxilla. Hyperkeratosis of soles cycline are alternatives.
and palms develops late. In late stages highly
destructive ulcers may develop in the skin, bones Q. Leptrospirosis.
and cartilages.
 Gangosa is the result of extensive destruction of Q. Weil’s syndrome.
nasal bones and cartilages. In severe cases, the
whole of the palate may be destroyed, so that the Etiology
nose and the mouth become one space.  Leptospirosis is an infectious disease of humans
and animals that is caused by pathogenic spiro-
Investigations chetes of the genus Leptospira. It is considered the
 Dark field microscopy of the specimens from early most common zoonosis in the world.
lesions may show spirochaetes.  Leptospira are coiled, thin, highly motile spiro-
 Serological tests are similar to those of syphilis chaetes.
(VDRL, RPR, FTA-ABS, etc.) and become positive
at an early stage of infection, but tend to become
negative later. Serological tests cannot differentiate
yaws from other treponemal infections.

Treatment
 Benzathine penicillin is the drug of choice.
 The recommended dose is 6 lakh units for those
under 10 years of age, and 12 lakh units for those


above 10 years of age.

Infectious Diseases

 In patients allergic to penicillin, tetracycline or

doxycycline can be used.

Q. Pinta.

Etiology
 Pinta is an endemic treponematosis caused by
Treponema carateum. Figure 1.11 Leptospira 1
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42  Human infection is caused by L. icterohaemorrhagica,  Headache may be intense.
L. canicola and L. hardjo serotypes.  Physical examination shows fever, conjunctival
suffusion, muscle tenderness, and hepatospleno-
Epidemiology megaly. Mild jaundice may be present. Sometimes
 It is a zoonosis and the reservoir of infection is rats a rash also may be noted.
(L. icterohaemorrhagica), dogs (L. canicola) and pigs
(L. hardjo), respectively. These animals shed Immune Phase (Second Phase)
spirochaetes in the urine.  After a gap of 1 to 3 days, fever reccurs in many cases.
 Infection occurs by direct contact with urine or This second phase coincides with the development
blood of an infected animal or by indirect contact of antibodies. Fever and myalgias may be less severe
with contaminated water, soil or vegetables. in the second phase. Aseptic meningitis, iridocyclitis
Human-to-human transmission is rare. and uveitis may develop during second phase. Most
 The organism enters the body through cuts, mucous patients become asymptomatic within a week.
membrane or even unabraded skin.
 The disease is more common in veterinary Severe Leptospirosis (Weil’s Syndrome)
personnel, agricultural workers, sewers, slaughter  Weil’s syndrome, the most severe form of lepto-
house workers and fisher men. spirosis, is characterized by jaundice, renal failure,
hemorrhagic tendency, and a high mortality rate.
Pathogenesis  It is most often caused by leptospira icterohaemorr-
 The organism spreads through the blood stream to hagica serogroup.
all organs. Multiplication takes place in blood and  Initially symptoms are same as that of uncompli-
tissues. cated leptospirosis. However, later, jaundice, renal
 Leptospires damage the wall of small blood vessels and vascular dysfunction develop. Jaundice is very
leading to vasculitis. Vasculitis causes leakage of deep and gives an orange tinge to the skin. Tender
plasma, hemorrhage and volume depletion. Vascu- hepatomegaly is usually present. Splenomegaly
litis is responsible for most of the manifestations of may also be present.
leptospirosis.  Dialysis may be required for renal failure. Renal
 Although any organ may be involved kidneys and function usually recovers completely with treat-
liver are involved mainly. Kidney involvement ment.
leads to renal failure and oliguria. Liver involve-  Pulmonary involvement occurs frequently and
ment leads to jaundice and liver function abnorma- results in cough, dyspnea, hemoptysis and rarely
lities. Muscle involvement leads to prominent respiratory failure.
myalgia and elevated CK levels. Lung involvement  Hemorrhagic manifestations include epistaxis,
can lead to ARDS and pulmonary hemorrhage. petechiae, purpura, and ecchymoses. Severe GI
 Meningitis can develop when there is rise in bleeding and adrenal or subarachnoid hemorrhage
antibody titers. This association suggests that an occur rarely.
immunologic mechanism may be responsible for  Complications of Weil’s disease include rhabdo-
meningitis. myolysis, myocarditis, pericarditis, congestive
heart failure, cardiogenic shock, ARDS, necrotizing
Clinical Features pancreatitis, septic shock and multiorgan failure.
 The incubation period varies from 2 to 20 days.
 More than 90% of patients have mild and anicteric Laboratory Features
Manipal Prep Manual of Medicine

form of leptospirosis.
Presumptive Diagnosis
 Severe leptospirosis with deep jaundice (Weil’s
syndrome) develops in 5 to 10% of patients.  A positive result of a rapid screening test such as
 Leptospirosis is characteristically biphasic and has IgM ELISA, latex agglutination test, lateral flow,
an initial septicemic phase followed by immune dipstick, etc.
phase. The distinction between the first and second
phases is not always clear, and mild cases may not Confirmatory Diagnosis
have the second phase.  Isolation of pathogenic leptospires through culture
of blood or other clinical samples.
Septicemic Phase  A positive PCR result (for blood in the early stages
 It presents as an acute influenza-like illness, with of infection).


fever, chills, headache, nausea, vomiting, and  Fourfold or greater rise in titre or seroconversion
1 
myalgias.
Muscle pain is an important clinical feature.
in microscopic agglutination test (MAT) on paired
samples obtained at least 2 weeks apart.

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Other Tests nausea, vomiting, and sleeplessness. Patients may 43
 Blood examination shows anemia, increased WBCs, also develop a generalized petechial or ecchymotic
decreased platelet count, and high ESR. rash, hepatosplenomegaly, jaundice, hemorrhagic
 LFT shows elevated direct bilirubin, elevated AST tendency and hemoptysis. Meningitis can occur
and ALT and prolonged prothrombin time. rarely.
 Renal function tests (RFT) show elevated blood urea  Although patients can completely recover from the
and creatinine. initial stage, majority will develop one or more
relapses. Louse-borne fever has more chances of
 CK levels are high due to muscle damage.
relapse than tick borne fever. Relapses result from
 Urine examination may show proteinuria, RBCs,
antigenic variation of the spirochete’s outer-surface
and cellular and granular casts.
proteins.
 ECG may show low voltage, prolonged QT and
 Untreated, one-third of patients may die.
nonspecific ST and T wave changes.
 Chest X-ray may show patchy bronchopneumonia Diagnosis
or ARDS.  Diagnosis can be confirmed by direct observation
Differential Diagnosis of spirochetes in peripheral blood smears during
episodes of fever.
 Leptospirosis should be differentiated from other  Direct or immunofluorescence staining may also be
febrile illnesses associated with headache, muscle used to visualize spirochetes using a fluorescence
pain and jaundice, such as dengue, severe malaria, microscope.
enteric fever, viral hepatitis, hantavirus infections,
 Motile spirochetes can be seen when specimens are
sepsis and rickettsial diseases.
examined by dark-field microscopy.
Treatment Treatment
 Crystalline penicillin 1.5 million units IV 6th hourly  Treatment with doxycycline (or tetracycline), or
daily for 7 days OR ceftriaxone 1 gm IV BD for 5 to erythromycin, or chloramphenicol is effective. For
7 days is the drug of choice for severe cases. Mild children <8 years of age and for pregnant women,
cases can be treated with oral antibiotics such as erythromycin or penicillin is preferred, because of
ampicillin or amoxicillin or erythromycin or doxy- side effects of tetracyclines.
cycline.  A severe Jarish-Herxheimer reaction may occur
 Fluid and electrolyte balance should be maintained after antibiotics are given and should be carefully
and supportive measures provided. watched for.
 Dialysis may be required for renal failure.  Public health measures are needed to control the
louse and tick populations.
Q. Relapsing fever.
Q. Rat-bite fever.
 The condition is so named because it is characterized
by recurring fever separated by afebrile periods.  Two organisms, Spirillum minus and Streptobacillus
 Relapsing fever is endemic in Africa, India, Middle moniliformis can cause rat bite fever. Both are
East and South America. spirochetes.
 Human cases occur as a result of a bite or scratch
Etiology (direct contact) from an infected rat. Infection may
 The infection is caused by several species of the also occur from exposure to infected rat urine or
spirochete Borrelia. by eating food or water contaminated with rat feces.
 Relapsing fever is an arthropod-borne infection  Patient develops fever, inflammation, ulceration at
spread by lice (Pediculus humanus) and ticks the bite site, and regional lymphadenopathy. Arthritis
(Ornithodoros species). Two main forms of this and periodic fever can occur for several weeks.
infection exist: Tick-borne relapsing fever (TBRF)  Diagnosis is by demonstration of spirochaete in


and louse-borne relapsing fever (LBRF). fluid from the ulcer, lymph node, or joint effusion.
Infectious Diseases

 TBRF is caused by many Borrelia species (e.g. Borrelia  Treatment is by penicillin or tetracycline.
hermsii, Borrelia duttonii, etc.), while LBRF is caused
solely by Borrelia recurrentis. Q. Lyme disease (lyme borreliosis).
Q. Erythema migrans.
Clinical Features
 After an incubation period of 7–10 days, the illness Etiology
starts with high grade fever with chills and rigors,
headache, body ache and joint pain. There can be
 Lyme disease is a zoonosis caused by the spiro-
chaete Borrelia burgdorferi. 1
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44 Epidemiology (polyneuropathy, encephalopathy) or dermato-
 The disease is transmitted by the bite of the Ixodes logical (acrodermatitis chronica atrophica)
tick which normally infects dogs, deer and sheep. symptoms occur. Lyme arthritis is the hallmark of
 The disease is seen mainly in western countries. stage 3 Lyme disease. It tends to involve large joints
(knee is involved in 90% of cases).
 Most cases occur in summer months in rural areas.
Children and women are affected more commonly.
Investigations
Clinical Features  Lyme disease is usually diagnosed by the clinical
features with serologic confirmation by testing for
Localized Infection (Stage 1) serum antibodies. The most frequently used test is
 Borrelia organisms are injected into the skin when the enzyme immunoassay (EIA) or enzyme-linked
a tick bites. immunosorbent assay (ELISA). Positive results can
 From the injected site, the spirochaete migrates be confirmed by Western blot test. However, there
outwards, producing a red macule or papule that are many limitations to serological tests. Thirty
expands slowly to form a large annular lesion called percent (30%) of acute cases are seronegative;
erythema migrans (EM) which is the characteristic positive tests may reflect past rather than current
rash of Lyme disease. As the lesion increases in size, infection.
it develops a bright red outer border and central  PCR testing of joint fluid is helpful in arthritis.
clearing. Without therapy, EM typically fades  More sophisticated immunological tests are being
within 3–4 weeks. EM usually is round or oval, but developed.
can be triangular or linear. Often, a central punctum
is present at the bite site. EM enlarges by a few Management
centimeters per day; single lesions typically achieve  B. burgdorferi is sensitive to beta-lactam antibiotics
a diameter of approximately 5–6 inches. Since ticks (penicillins and cephalosporins) and to the tetra-
tend to bite the areas where natural barriers impede cyclines. For severe cases, IV benzylpenicillin or
their forward motion, rash location is usually on the ceftriaxone is given. For less severe cases oral
popliteal fossa, axillary or gluteal folds, areas near doxycycline or amoxycillin for 3 weeks is effective.
elastic bands in bra straps or underwear. In children,
the scalp, face, and hairline are especially common Q. Epidemic typhus fever.
locations. Some patients with EM may have
secondary EM lesions due to hematogenous spread.  Typhus refers to a group of infectious diseases that
These lesions generally are smaller than the primary are caused by rickettsial organisms that result in
one, lack the central punctum, and tend to be more acute febrile illness. Arthropod vectors transmit the
uniform in morphology than the primary lesion. rickettsial organisms to humans. The main diseases
Location of secondary lesions can be anywhere. of this group are epidemic typhus, murine typhus,
 Fever, chills, and malaise are also present in this and scrub typhus.
stage.  Epidemic typhus is the prototypical infection of
the typhus group of diseases, and the pathophysio-
Disseminated Infection (Stage 2) logy of this illness is representative of all typhus
 From the local site, organisms spread hemato- fevers.
genously to many sites within days or weeks after  Epidemic typhus is caused by the organism
the onset of erythema migrans. Patients have severe Rickettsia prowazekii.
headache, neck stiffness, fever with chills,
Manipal Prep Manual of Medicine

Transmission
arthralgias, and fatigue.
 One or more organ systems become involved as  It is spread by the vector Pediculus corporis (body
hematologic or lymphatic spread disseminates louse).
spirochetes to distant sites. Musculoskeletal  Organisms enter through abraded skin or mucous
(arthritis) and neurologic symptoms are the most membrane when an infected louse is crushed on
common. Neurologic manifestations include cranial the body surface.
nerve palsy especially facial nerve palsy (Bell’s
palsy), meningitis and encephalopathy. Cardiac Clinical Features
involvement presents as dizziness, syncope,  Incubation period is ~1 week.
dyspnea, chest pain, and palpitations.  Typhus is a multisystem vasculitis and may cause
a wide array of clinical manifestations.


Persistent Infection (Stage 3)  Main features are high fever, severe headache, and
1  After months or years of latency the articular
(oligoarticular arthritis in large joints), neurological
maculopapular rash. Cough is noted frequently.
There is severe generalized myalgia.

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 Rash begins on the upper trunk, usually on the fifth Clinical Features 45
day, and then becomes generalized, involving all  The site of chigger bite is marked by an eschar and
of the body except the face, palms, and soles. is accompanied by regional lymphadenopathy,
Initially, rash is macular, then it becomes maculo- which may later become generalized. Other clinical
papular, petechial, and confluent. features are high fever, intense headache, diffuse
 Photophobia and conjunctival congestion are myalgias, and, sometimes a rash. Severe infection
frequently present. The tongue may be dry and may be complicated by interstitial pneumonia,
coated. Confusion and coma are common. Skin pulmonary edema, congestive heart failure, circula-
necrosis and digital gangrene may be seen in severe tory collapse, and signs and symptoms of CNS dys-
cases. function, including delirium, confusion, and seizures.
 Patients may also develop hemodynamic collapse, Death may occur as a result of these complications,
multiorgan involvement including renal failure. usually late in the second week of illness.
 Brill-Zinsser disease, a mild recrudescence of
epidemic typhus, can occur years after the initial Investigations
infection if host defenses falter.
 Weil-Felix OX-K strain agglutination test is the
oldest test available. It is inexpensive, but lacks
Investigations specificity and sensitivity.
 Indirect immunofluorescence assay (IFA) or  Demonstration of antibodies against Orientia
enzyme immunoassay (EIA) testing can be used to tsutsugamushi using indirect fluorescent antibody
evaluate for a rise in the immunoglobulin M (IgM) (IFA) test or indirect immunoperoxidase (IIP) test.
antibody titer, which indicates an acute primary IFA is the gold standard test. These tests are more
disease. sensitive and specific than Weil-Felix.
 The complement fixation (CF) test is a serological  Molecular detection using polymerase chain
test that can be used to demonstrate which specific reaction (PCR) is possible from skin rash biopsies,
rickettsial organism is causing disease by detection lymph node biopsies or blood.
of specific antibodies.
Treatment
Treatment
 Drug of choice is doxycycline (100 mg bid PO for
 Doxycycline is the drug of choice. It is given as 7–15 days). Alternative is chloramphenicol 500 mg
200 mg once followed by 100 mg bid for at least qid PO for 7–15 days.
7 days. Alternative is chloramphenicol 500 mg qid
orally for 7–15 days. Intravenous administration Q. Q fever.
of antibiotics is indicated in very sick patients.
Supportive treatment is provided as needed.  Q-fever is so named because when an outbreak
occurred in Australia, it was unknown what type
Q. Scrub typhus. of fever it was. Hence, it was named Q (for query)
fever. But later the micro-organism responsible for
Etiology Q fever was isolated.
 Scrub typhus is a mite-borne infectious disease  Q fever is caused by infection with Coxiella burnetii,
caused by Orientia tsutsugamushi (previously called a small gram-negative bacillus.
Rickettsia tsutsugamushi), an intracellular gram-  Q fever is a zoonotic disease found in wild
negative bacterium. (mammals, birds, and ticks) and domestic animals
(cattle, sheep, and goats).
Transmission of Infection  It is transmitted among animals by ticks. Infected
animals shed it through their milk and conceptional
 Scrub typhus is found in areas with heavy scrub
products during delivery into soil.
vegetation, e.g. where the forest is regrowing after
being cleared and along riverbanks. Hence, it is  Human disease is acquired by inhalation of infected


dust, handling infected animals, and by drinking

Infectious Diseases

called scrub typhus.

contaminated milk. Veterinarians are at increased
 Seen in India, Asia, Australia, New Guinea, and
risk of infection. It can also be acquired through
Pacific Islands.
blood transfusion.
 Orientia tsutsugamushi is present in trombiculid
mites. The organism is transmitted to humans
Clinical Features
through the bite of larval stage of mite called
chiggers. Infected chiggers feeds on animal hosts,  Incubation period is 3 to 30 days.
mainly rodents and infect them. Human infection
is acquired by accident.
 It presents as flu like illness with moderate fever,
headache, myalgia, malaise and anorexia. 1
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46  Multiorgan involvement leads to pneumonia,  Molecular methods such as real time PCR have high
hepatitis, pericarditis, myocarditis, endocarditis sensitivity and specificity and can be used for rapid
and meningoencephalitis. Endocarditis commonly diagnosis.
affects aortic valve.  Culture is difficult and hazardous to laboratory
personnel.
Diagnosis  X-ray reveals patchy shadows, most often in the lower
 Polymerase chain reaction (PCR) on a blood sample lobes.
can be used for rapid diagnosis.
 Serologic methods: Indirect immunofluorescence (IIF) Treatment
(method of choice), complement fixation and  Oral doxycycline 100 mg twice daily for 21 days is
enzyme-linked immunosorbent assay (ELISA). A curative.
fourfold increase in IgG antibody titer by immuno-  Erythromycin is the second line therapy when
fluorescent assay (IFA) of paired acute and convale- tetracyclines are contraindicated.
scent specimens is the diagnostic gold standard to
confirm the diagnosis of Q fever. Q. Lymphogranuloma venereum (LGV).
 Immunohistochemistry or culture of affected tissue can
provide definitive confirmation of infection by  LGV is a sexually transmitted disease caused by
Coxiella burnetii. certain L1, L2, and L3 serotypes of Chlamydia tracho-
matis. These serotypes can invade and reproduce
Treatment in regional lymph nodes.
 Chloramphenicol and tetracyclines (doxycycline) Clinical Features
are effective against Q fever.
 In pregnancy, trimethoprim sulfamethoxazole is  The peak incidence of LGV corresponds to the age
recommended for treatment. of greatest sexual activity: The second and third
decades of life.
 Quinolones are also effective.
 It is characterized by a painless genital lesion with
bilateral inguinal lymphadenopathy (buboes).
Q. Psittacosis (parrot fever).
 These buboes may break down to form multiple
 Psittacosis, also known as parrot fever, is caused discharging sinuses with extensive scarring.
by Chlamydia psittaaci which is an intracellular  Anal intercourse may lead to hemorrhagic proctitis
bacterium. with regional lymphadenopathy.
 Many birds are known to harbour the organisms,  Systemic symptoms like fever and leukocytosis are
but psittacine species (parrots), poultry, and seen. Meningoencephalitis can develop rarely.
pigeons are the main sources of human infection.  Genital elephantiasis (due to lymphatic obstruc-
 Organisms are transmitted to humans through contact tion), strictures, urethral and rectal fistulas may
with infected animals or birds or their faecal materials. occur as a late complication.
Organisms enter human body through inhalation. It is
common among pet bird (pigeon and parrot) Diagnosis
owners and poultry (chicken and duck) farmers.  Direct microscopic examination of tissue scrapings
shows typical intracytoplasmic inclusions or
Clinical Features elementary bodies.
 History of bird contact present. Incubation period is  Detection of chlamydial antigens or antibody in
1 to 2 weeks. It presents as atypical pneumonia with serum or in local secretions.
Manipal Prep Manual of Medicine

fever and tachypnea. Examination may show  Nucleic acid amplification testing (NAAT) of
relative bradycardia. Chest examination may show specimens.
crepitations and signs of consolidation. Lung
lesions are more extensive than the clinical features Treatment
suggest. Respiratory failure can occur.  Recommended treatment is doxycycline 100 mg bd
 Rarely extrapulmonary complications can occur and for 21 days. Macrolides (erythromycin or azithro-
include myocarditis, encephalitis, meningitis, mycin) are alternatives.
pancreatitis, glomerulonephritis, and disseminated  Surgical drainage for suppurative bubo may be
intravascular coagulation. required.
Diagnosis
Q. Influenza.


 Serological methods are preferred. These include

1 complement fixation (CF) and microimmuno-
fluorescent antibody test (MIF).
 Influenza is an acute respiratory illness caused by
influenza viruses. Influenza viruses are encapsula-

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 ted, single-stranded RNA viruses of the family  Systemic examination is usually normal. 47
Orthomyxoviridae.  Most patients recover in 1 week, although cough
may persist for 1 to 2 weeks longer. In some patients
Epidemiology weakness may persist for several weeks.
 There are 3 influenza viruses; A, B and C. Influenza-  Complications include secondary bacterial pneumonia,
A viruses are further subdivided (subtyped) on the Reye’s syndrome, myocarditis, encephalitis, trans-
basis of the surface hemagglutinin (H) and verse myelitis and, rarely, Guillain-Barré syndrome.
neuraminidase (N) antigens. H1N1 is a type of
influenza A virus. Diagnosis
 In addition to humans, influenza also infects a  Laboratory diagnosis is accomplished by the
variety of animal species. More than 100 types of detection of virus or viral antigen in throat swabs,
influenza A infect most species of birds, pigs, nasal washes, or sputum.
horses, dogs, and seals. Influenza B has also been  Rapid diagnostic tests: These employ immuno-
reported in seals. In this context, the term avian logical and molecular techniques. Options include
influenza (or “bird flu”) refers to zoonotic human immunofluorescence (IF) assays, enzyme immuno-
infection with an influenza strain that primarily assays (EIA), and polymerase chain reaction (PCR)-
affects birds. Swine influenza refers to infection based testing.
from strains derived from pigs.  Serology: Diagnosis can be established retrospecti-
 Type A is responsible for major epidemics and B vely by serologic methods such as hemagglutination-
for localized outbreaks. Epidemics usually occur inhibition.
during the winter months. Influenza A pandemics
also occur and cause considerable school and work Treatment
absenteeism. Influenza B causes less severe  Most cases of influenza resolve spontaneously
outbreaks mostly in schools and military camps. without any complications. Symptomatic therapy
Influenza C rarely causes human disease. with paracetamol for fever and myalgia, codeine
 A remarkable feature of influenza virus A is it can syrup for dry cough are enough for such cases.
undergo periodic antigenic variations. Major Aspirin should be avoided because of the risk of
antigenic variations, called antigenic shifts, are Reye’s syndrome. Patients should be advised to rest
associated with pandemics and are seen with and maintain hydration during acute illness.
influenza A viruses only. Minor variations are  Antiviral drugs are available to treat influenza:
called antigenic drifts. Antigenic shift happens due amantadine and rimantadine for influenza A and the
to re-assortment of gene segments between viral neuraminidase inhibitors zanamivir and oseltamivir
strains and ‘antigenic drift’ from point mutations. for both influenza A and influenza B. Antiviral
drugs are recommended for high-risk patients.
Pathogenesis
 Antibiotics are indicated for secondary bacterial
 The disease is acquired by inhalation of droplets infections.
generated by coughs and sneezes.
 It can also spread through hand-to-hand contact, Prevention
personal contact, and fomites.
 Influenza vaccine is recommended for all persons
 The infection involves the ciliated columnar aged 6 months or older every year if there are no
epithelial cells, but can also involve alveolar cells, contraindications.
mucous gland cells and macrophages. The infected  Inactivated influenza vaccine (IIV): This is given as
cells of the tracheobronchial tree eventually become
0.5 mL intramuscularly.
necrotic and desquamate.
 Live-attenuated influenza vaccine (LAIV): This is
 The host response to influenza involves both cell administered as intranasal spray.
mediated and humoral immunity.
 Systemic symptoms in influenza such as fever and
Q. Discuss the etiology, clinical features, diagnosis and
myalgia are due to the induction of cytokines.


management of H1N1 influenza (Swine Flu).

Infectious Diseases

Clinical Manifestations
 Swine influenza is a highly contagious respiratory
 The incubation period varies from 18 to 72 hours. disease in pigs caused by one of several swine
 Initially respiratory symptoms like dry cough and influenza A viruses. In addition, influenza C viruses
rhinorrhea are present but are later overshadowed may also cause illness in swine. The current virus
by systemic symptoms. is a novel influenza A (H1N1) virus not previously
 Systemic symptoms include fever, chills, headache, identified in humans (H = hemagglutinin, N =
myalgia, arthralgia and loss of appetite. Rigors are
rare. Fever may last for as long as a week.
neuraminidase). Outbreaks of H1N1 influenza
(swine flu) are common in pigs year-round. 1
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48  Transmission of swine influenza viruses to humans Management
is uncommon. However, transmission can occur to
Supportive Therapy
humans via contact with infected pigs or environ-
ments contaminated with swine influenza viruses.  Patients should be isolated to prevent spread of infec-
Once a human becomes infected, he or she can then tion to others. Bedrest, increased fluid intake, cough
spread the virus to other humans. suppressants, antipyretics and analgesics (e.g aceta-
 In 2009, cases of influenza like illness were first minophen, nonsteroidal anti-inflammatory drugs)
reported in Mexico on March 18; the outbreak was for fever and myalgias. Severe cases may require
confirmed as H1N1 influenza A. During this intravenous hydration and ventilator support.
outbreak, nearly 100,000 were hospitalized, and
about 3,900 died. On June 11, 2009, WHO raised Antiviral Agents
the pandemic alert level to phase 6 (indicating a  Serious patients should be treated with antiviral
global pandemic) because of widespread infection agents. Drugs of choice are oseltamivir (Tamiflu)
beyond North America to Australia, the United or zanamivir. These two drugs inhibit neuramini-
Kingdom, Argentina, Chile, Spain, and Japan. dase on the surface of influenza virus that destroys
Currently WHO and Centre for Disease Control and an infected cell’s receptor for viral hemagglutinin.
Prevention (CDC) are monitoring the situation all By inhibiting viral neuraminidase, these agents
over the world. decrease the release of viruses from infected cells
and, thus, viral spread.
Clinical Features  Antiviral drugs reduce the risk of pneumonia a
 Manifestations of H1N1 influenza (swine flu) are leading cause of death in H1N1 and the need for
similar to those of seasonal influenza. Patients hospitalization. Oseltamivir should be started as
present with symptoms of acute respiratory illness, early as possible (preferably within 48 hours) in a
such as fever, chills, fatigue, cough, sore throat, dose of 75 mg BD for 5 days. Where oseltamivir is
body aches, and headache. In addition, diarrhea unavailable or cannot be used for any reason,
and vomiting may occur. zanamivir may be given. Zanamivir is given by
 Clinical deterioration is characterized by primary inhalation in a dose of 10 mg BD for 5 days.
viral pneumonia, which destroys the lung tissue Pregnant women and patients with underlying
and does not respond to antibiotics, and multi- medical conditions are at higher risk of developing
organ dysfunction including the heart, kidneys, and complications and should be given antivirals as
liver. Patients with severe disease have dyspnea, soon as H1N1 is suspected even before laboratory
cyanosis, dehydration, and altered mental status. confirmation.

Diagnosis Reducing the Spread of Infection

 Clinicians should consider the possibility of H1N1  Patients who develop flulike illness (i.e. fever with
infection in patients who present with febrile either cough or sore throat) should be strongly
respiratory illness. The CDC criteria for suspected encouraged to self-isolate in their home for 7 days
H1N1 influenza are as follows: after the onset of illness or at least 24 hours after
– Onset of acute febrile respiratory illness within symptoms have resolved, whichever is longer.
7 days of close contact with a person who has a  While in home isolation, patients and other
confirmed case of H1N1 influenza A virus household members should be given infection
infection, or control instructions, including frequent hand
– Onset of acute febrile respiratory illness within washing with soap and water. Patients with H1N1
Manipal Prep Manual of Medicine

7 days of travel to a community (within the influenza should wear a face mask when within
United States or internationally) where one 6 feet of others at home.
or more H1N1 influenza A cases have  If the patient must go into the community (e.g. to
been seek medical care), he or she should wear a face
confirmed, or – mask.
Acute febrile respiratory illness in a person who  Patients should call the physician before meeting
resides in a community where at least one H1N1 and should avoid mixing with other OPD patients
influenza case has been confirmed. at clinic or hospital.
If H1N1 is suspected, the clinician should obtain  Prophylaxis with antiviral agents should be consi-
a respiratory swab and send it for H1N1 testing. dered for close household contacts of a confirmed
or suspected case who are at high risk for complica-


Laboratory Confirmation of Diagnosis

 Real-time RT-PCR is the recommended test for tions (e.g. chronic medical conditions, persons

1 confirmation of H1N1 cases. This is done on swab

sample from the nose or throat.
>65 years or <5 years, pregnant women), school
children at high risk for complications who have

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 been in close contact with a confirmed or suspected  There may be a prodrome of low grade fever, 49
case, health care providers who were not using headache and malaise lasting 1–2 days before the
appropriate personal protective equipment during onset of rash.
close contact with a confirmed or suspected case.  Rash appears first on the face and trunk and then
Antivirals should not be used for postexposure spreads to other parts of the body. Lesions can also
chemoprophylaxis in healthy children or adults. be found on the mucosa of the pharynx and vagina.
 School closure should be considered upon a Rashes may be pruritic and centripetal with relative
confirmed case of H1N1. sparing of the peripheries. To start with rashes are
 Public gatherings should be avoided in a place maculopapular and in a few hours become vesicles.
where there has been a confirmed case of H1N1. Vesicles become pustules which later form crusts.
New lesions continue to appear for 2 to 4 days so
Vaccine that all stages of the eruption are present simulta-
 Vaccine stimulates active immunity to influenza neously (pleomorphic rash). Rashes usually heal
virus infection by inducing production of specific without scarring. Lesions can get secondarily
antibodies. H1N1 vaccine is available as an IM infected with bacteria, usually Streptococcus pyogenes
injection and as an intranasal product. or Staphylococcus aureus.
 Intramuscular vaccine contains monovalent,
inactivated influenza A virus. It is given as 0.5 mL Diagnosis
IM in deltoid muscle. Two doses are required for  Diagnosis is mainly based on clinical features.
children younger than 10 years (initial dose  Diagnosis can be confirmed where necessary by
followed by a booster several weeks later). Single isolation of virus in tissue culture, demonstrations
dose is recommended for adults and children of high titres of antibodies or the detection of VZV
10 years and older. Intranasal vaccine is given as DNA by PCR. Tzanck smear made by scraping of
0.2 mL/dose (0.1 mL per nostril) intranasally the base of the lesions may show multinucleated
(1 dose). A quadrivalent vaccine containing four giant cells.
strains of influenza viruses including H1N1 is
available now which can be used. Treatment
 Vaccination is recommended for all pregnant
 Most people recover with supportive treatment.
women, adults, and children over 6 months of age.
 Antiviral agents like acyclovir, famciclovir and
Prognosis valacyclovir are recommended for adolescents and
adults with chickenpox of ≥24 hours duration.
 H1N1 influenza tends to cause high morbidity but
low mortality rates (1–4%). Complications are more  Antibiotics may be used for secondary bacterial
likely in children, elderly, pregnant women and infection of skin lesions.
people with other co-morbid illness.
Complications
Q. Varicella (chickenpox) (HHV-3).  CNS involvement in the form of cerebellar ataxia,
meningitis, encephalitis, transverse myelitis, and
Etiology Guillain-Barré syndrome
 The causative agent of varicella or chickenpox is  Involvement of other organ systems can produce
Varicella-zoster virus (VZV; human herpes virus-3). varicella pneumonia, myocarditis, nephritis,
It is a DNA virus belonging to herpes viridae hepatitis and arthritis.
family.  Reye’s syndrome (hepatic encephalopathy),
 It produces two clinical entities: Varicella (chicken- another complication, is associated with aspirin
pox) and herpes zoster (shingles). therapy.
 Chickenpox is the primary infection, and usually
occurs in childhood. Chickenpox rarely occurs Q. Herpes zoster (shingles).


twice but the virus remains latent in the dorsal root

Infectious Diseases

ganglia and cranial nerve ganglia. Years later it may Etiology

be reactivated to cause vesicular eruption in the
 Etiologic agent is varicella-zoster virus (VZV) which
relevant sensory dermatomes which is known as
is the same virus causing chickenpox. After an
herpes zoster (shingles).
attack of chickenpox VZV remains latent in the
dorsal root ganglia and cranial nerve ganglia. Years
Clinical Features later it may be reactivated to cause vesicular



Chickenpox affects children commonly.
Incubation period is 10 to 21 days.
eruption in the relevant sensory dermatomes which
is known as herpes zoster (shingles). 1
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50 Clinical Features  Infectious mononucleosis (IM) is also known as
 The first symptom is severe burning or shooting glandular fever or kissing disease. Later it was called
pain in the affected dermatome followed by infectious mononucleosis because it is characterized
erythematous maculopapular eruption in 2 to by absolute lymphocytosis and atypical mono-
3 days. These eruptions turn into vesicles and start nuclear cells in the blood.
crusting. The skin eruption is usually unilateral.  It is characterized by a triad of fever, pharyngitis,
 The total duration of disease is generally between and lymphadenopathy.
7 and 10 days.
Pathogenesis
 Local skin hyperalgesia is a clue to the neural origin
of pain.  In humans it spreads commonly through saliva
 The dermatomes from T3 to L3 are commonly (‘the kissing disease’) and rarely by blood
affected. transfusion.
 In ophthalmic herpes the gasserian ganglion  After entry into the body the virus multiplies
(trigeminal ganglion) is affected and the ophthalmic primarily in B lymphocytes but also may replicate
branch of the trigeminal nerve is involved. Lesions in the epithelial cells of the pharynx and parotid
develop on the nose, conjunctiva and cornea of the duct. Infected B cells are responsible for the
affected side. Corneal lesions heal leaving behind dissemination of infection throughout the lympho-
opacities causing blindness. reticular system, i.e, liver, spleen, and peripheral
lymph nodes. Infected B lymphocytes produce
Treatment antibodies against the virus. Cytotoxic T cells are
also produced by the body against the EBV-infected
 Antiviral drugs are indicated for the treatment of B lymphocytes.
shingles. Drugs used are same as for varicella
(aciclovir or famciclovir or valacyclovir). Clinical Features
 Herpes zoster causes severe pain which may be
 Incubation period is 4–8 weeks. Infectious mono-
difficult to control. NSAIDs and opioid analgesics
nucleosis is a disease of childhood, adolescence and
can be used along with neuron modulator drugs
low socioeconomic groups.
such as carbamazepine, gabapentin, amitriptyline
and lidocaine patches to control pain.  Initially there is a prodrome of fatigue, malaise, and
myalgia.
Complications  Prodrome is followed by typical features such as
 Postherpetic neuralgia: In postherpetic neuralgia fever, sore throat, and lymphadenopathy.
pain persists even after the lesions have healed. Pain  Fever is usually low grade. Lymphadenopathy
of postherpetic neuralgia may be sharp and most often affects the posterior cervical nodes but
intermittent or constant and may be debilitating. It may be generalized. Rarely hepatosplenomegaly
may persist for months or years or permanently. may be found.
Treatments for postherpetic neuralgia include  A generalized maculopapular rash is occasionally
gabapentin, pregabalin, cyclic antidepressants, seen. Rash may develop if ampicillin is taken.
topical capsaicin or lidocaine ointment, and  IM should be suspected in an adolescent or young
botulinum toxin injection. adult with fever, sore throat and lymphadenopathy
 CNS complications include meningoencephalitis (especially posterior cervical lymphadenopathy).
and transverse myelitis. Sometimes weakness and The illness usually lasts 2–4 weeks but weakness
Manipal Prep Manual of Medicine


wasting in segments supplied by the nerve root may can persist for a long time.
occur due to motor neuritis.
 Complications include splenic rupture, thrombo-
 Immunocompromised patients can develop severe cytopenia, autoimmune hemolytic anemia,
disease with multiorgan involvement. meningitis, encephalitis, and GB-syndrome.

Q. Infectious mononucleosis (glandular fever). Investigations

 Blood tests show raised leukocyte count with
Etiology
atypical lymphocytosis.
 Infectious mononucleosis (IM) is a disease caused
 Liver enzymes may be raised but jaundice is rare.
by Epstein-Barr virus (EBV). EBV is a DNA virus
belonging to the family Herpesviridae. EBV also  Paul Bunnell test and Monospot test (detect


causes many tumors in human beings like naso- heterophile antibodies) are usually positive.

1 pharyngeal carcinoma, Burkitt lymphoma, and

Hodgkin lymphoma.
 Demonstration of antibodies to viral capsid antigen
(i.e. VCA-IgG and VCA-IgM).

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Differential Diagnosis Diagnostic Criteria for Chronic Fatigue Syndrome 51
 Other infections which produce fever and lympha-  Severe fatigue lasting >6 months.
denopathy: Streptococcal pharyngitis, cytomegalo-  Postexertional malaise.
virus, acute HIV, or toxoplasma.  Unrefreshing sleep.
 Lymphoma.  Cognitive impairment or orthostatic intolerance.

Treatment Treatment
 There is no specific treatment for infectious  There is no specific therapy.
mononucleosis. Antiviral drugs do not have much  Cognitive behavioral therapy and graded exercise
benefit. programs have been shown to be beneficial.
 Supportive measures, rest and antipyretics are  Low dose of a tricyclic antidepressant may help
given as required. most patients.
 Ampicillin should be avoided in suspected  Treatment of co-morbid illness such as depression,
infectious mononucleosis because it causes rash. sleep disturbances, etc.
 Corticosteroids can be helpful for complications
Q. Human papillomavirus infections.
such as impending airway obstruction, severe
thrombocytopenia, and hemolytic anemia.  Human papilloma viruses are DNA viruses belong-
ing to the family Papillomaviridae.
Q. Chronic fatigue syndrome.  They infect the skin and mucous membranes.
Infections produce warts or may be associated with
 Chronic fatigue syndrome (CFS) is a disorder a variety of benign and malignant neoplasms. Some
characterized by unexplained, persistent, and HPV infections (such as 16, 18, 31, 33, and 45) cause
sometimes debilitating fatigue. cervical cancer.
 It can be difficult to diagnose because there are no  Most of the infections are seen in children and
objective clinical or laboratory findings associated young adults. Warts can be common warts (verruca
with this disorder. vulgaris), plantar warts (verruca plantaris) or ano-
genital warts (condyloma acuminatum). Anogenital
Etiology warts are sexually transmitted.
 The exact etiology of CFS is unknown and is likely  Complications of warts include itching and
to be multifactorial including a genetic pre- bleeding with secondary infection. Warts in the
disposition, and exposure to microbes, toxins, and respiratory tract may obstruct the airway.
other physical and/or emotional trauma.  Many HPV lesions resolve spontaneously. Treat-
 Various immunologic abnormalities have been ment options are cryosurgery, application of caustic
reported in CFS patients. These include low levels agents, electrodesiccation, surgical excision, and
of IgG, abnormal IgG, decreased lymphocytic ablation with a laser. Topical antimetabolite, such
proliferation, circulating autoantibodies and as 5-fluorouracil is also effective.
immune complexes, etc. Relatives of patients with
CFS have an increased risk of developing the Q. Measles (rubeola).
disease, suggesting a genetic component.  Measles (also known as rubeola) is a highly conta-
gious, acute, viral exanthematous disease.
Clinical Features
 CFS is more common in young and middle-aged Etiology
adults, in women and in Caucasians.  Measles is caused by measles virus which is a RNA
 Persistent fatigue is the hallmark of CFS. Fatigue virus belonging to the family of paramyxoviruses.
often follows an infection such as upper respiratory
infection or infectious mononucleosis. Patient is left Epidemiology

Infectious Diseases

with overwhelming fatigue even after he recovers  It most commonly affects preschool children.
from the initial illness. Physical activity worsens Incidence of measles has come down after the
fatigue. Many patients with CFS also have other introduction of measles vaccine.
symptoms such as feeling feverish, muscle and joint  Measles virus is transmitted by inhalation of
aches, intermittent tenderness or swelling in the respiratory droplets. It can also spread through
lymph nodes. Physical examination is normal, with direct contact with larger droplets.
no objective signs of muscle weakness, arthritis,  The virus is present in nasopharyngeal secretions,
neuropathy, or organomegaly.
 Many patients have underlying depression.
blood and urine during the prodromal period and
for a short time after the rash appears. 1
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52  Patients are contagious from 1 or 2 days before the Complications
onset of symptoms until 4 days after the appearance  Respiratory tract complications: Laryngitis, croup,
of the rash. Infectivity is maximum during the or bronchitis, otitis media, pneumonia.
prodromal phase.  CNS complications: Encephalitis, transverse
myelitis, subacute sclerosing panencephalitis
Clinical Features (SSPE). SSPE is a chronic, rare form of measles
 Incubation period is 10 to 14 days. encephalitis. It is common in children who have
 Measles starts with a prodrome of malaise, cough, measles before the age of 2 years. SSPE is now rare
lacrimation, nasal discharge, and fever. At this stage due to widespread vaccination against measles.
it resembles influenza. Clinical features are progressive dementia which
 Just before the onset of the rash, Koplik’s spots evolves over several months.
appear as 1 to 2 mm blue-white spots on a bright  Gastrointestinal complications: Hepatitis, appen-
red background. Koplik’s spots are usually seen on dicitis, and mesenteric adenitis.
the buccal mucosa alongside the upper second  Others: Myocarditis, glomerulonephritis, postinfec-
molars. They are characteristic of measles because tious thrombocytopenic purpura and reactivation
they are not seen in any other disease. The spots of tuberculosis.
disappear after the onset of rash.
 Rash appears 3–4 days after the onset of fever. Rash Prevention
begins first at the hairline and behind the ears, and  Immediate protection can be obtained by giving
then spreads to the trunk and limbs. Rashes do not immunoglobulin within 6 days of exposure to the
spare the palms and soles, are erythematous, non- disease. Measles vaccine given within 72 hours of
pruritic, and maculopapular. Rash is monomorphic, exposure may also protect against disease.
i.e. all rashes have similar morphology. Rash begins  Active immunization with measles vaccine is
to fade by the fourth day, in the order in which it included in the national immunization programme.
appeared. A single dose of vaccine is given at 8 to 9 months of
 The entire illness lasts about 10 days. The disease age. It provides lifelong immunity. Giving MMR
tends to be more severe in adults than in children. vaccine at 15 to 18 months takes care of occasional
failure of measles vaccine given at 8 to 9 months of
Diagnosis age. However, if there is an epidemic of measles,
 Measles is diagnosed mainly by clinical features. vaccination may be given at 6 months of age
 Diagnosis can be confirmed by detecting serum followed by another dose at 15 months of age.
anti-measles IgM antibody. IgM antibody is
detectable three days after the appearance of rash. Q. Mumps.
Anti-measles IgG antibody appears 7 days after the
appearance of rash.  Mumps is an acute, communicable, systemic viral
 A quick diagnosis of measles can be made by infection whose most distinctive feature is swelling
demonstration of measles antigen by immuno- of parotid glands. It can involve other salivary
fluorescent staining of a smear of respiratory glands, meninges, pancreas, and the gonads.
secretions.
 Measles virus can be cultured and isolated from Etiology
respiratory secretions or urine.  Mumps is caused by mumps virus which is a
 PCR for measles virus RNA can also diagnose member of the paramyxovirus group. It is a RNA
Manipal Prep Manual of Medicine

measles. virus.

Treatment Epidemiology
 There is no specific treatment for measles.  Mumps occurs worldwide but the incidence has
 Patient should be isolated. decreased after the introduction of MMR vaccine
 Most people recover spontaneously and only which contains mumps component also.
supportive treatment is necessary.  Mumps occurs mainly during winter and spring.
 Ribavirin may be considered for use in immuno- It is mainly a disease of childhood, but nowadays
compromised individuals. adults are getting affected more commonly. Both
 Administration of vitamin A has been shown to sexes are affected equally.
prevent complications especially in malnourished  Epidemics occur in close populations, such as in


children. schools and military services.

1  Secondary bacterial complications are treated with

appropriate antibiotics.
 Mumps is highly infectious and spreads rapidly
among susceptible people living in close quarters.

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 Mumps virus is transmitted by droplet nuclei,  Virus isolation by culturing appropriate clinical 53
saliva, and fomites. Fomites contaminated by specimens.
infected saliva and possibly also by urine transmit  PCR.
the infection. Transmission of infection occurs a day
before the appearance of the parotid swelling and Treatment
for about three days after the swelling disappears.  Symptomatic treatment; analgesics and antipyretics
 One attack of mumps or vaccination confers lifelong for fever and pain, cold compresses for parotid
immunity. swelling.
 Patients with meningitis or pancreatitis may require
Clinical Features hospitalization.
 Incubation period is 2–3 weeks.  Patients with orchitis are also treated symptomati-
 Mumps starts with a prodrome of fever, malaise, cally with bedrest, nonsteroidal antiinflammatory
myalgia, and anorexia. agents, support of the inflamed testis and ice packs.
 Parotitis may develop within the next 24 h or may
Prevention
be delayed up to a week. Parotitis is usually
bilateral, although sometimes only one side is  Patients should be isolated to prevent transmission
affected. Parotid glands are involved most to others.
commonly and submaxillary and sublingual glands  Passive immunization using immunoglobulin is not
are involved rarely. Parotid gland becomes swollen effective to prevent infection in close contacts and
and tender. Gland swelling increases for a few days is not recommended.
and then gradually subsides within a week.  Active immunization is routinely given as MMR
 Other than parotitis, orchitis is the most common vaccine (measles, mumps, rubella) subcutaneously
manifestation. Testis becomes swollen, painful and at 15 months of age or later; repeat dose may be
tender. Testicular atrophy develops in half of the necessary after 5–10 years. MMR vaccine is also
affected men. However, since orchitis is usually recommended for susceptible older children,
unilateral and other testes remains unaffected, adolescents, and adults, particularly adolescent
sterility is rare. Oophoritis can occur in women but males who have not had mumps. Vaccine should
less common than orchitis and does not lead to not be given to pregnant women, immuno-
sterility. suppressed patients, or persons with advanced
 Aseptic meningitis is a common manifestation of malignancies.
mumps in both children and adults. Mumps
meningitis is usually self-limiting, although cranial Q. Rubella (German measles).
nerve palsies are rarely seen. Rarely, encephalitis
 Rubella is an acute viral exanthematous disease
can occur, which presents as high fever with altered
caused by rubella virus, a RNA virus.
sensorium. Other CNS problems occasionally seen
 It is also known as German measles because it was
are cerebellar ataxia, facial palsy, transverse
first recognized to be different from measles in
myelitis, Guillain-Barré syndrome, and aqueductal
Germany.
stenosis leading to hydrocephalus.
 Other clinical manifestations are pancreatitis, myo- Epidemiology
carditis, mastitis, thyroiditis, nephritis, arthritis,
and thrombocytopenic purpura.  Humans are the only natural hosts for rubella
infection.
Differential Diagnosis  It spreads by respiratory droplets or is maternally
transmitted to the fetus causing congenital infection.
 Mumps has to be differentiated from other causes
 The peak incidence of the disease is in children of
of parotid gland swelling, such as
5 to 12 years of age.
– Influenza, parainfluenza and coxsackie virus
infections Clinical Manifestations


– Bacterial parotitis due to staphylococcal

Infectious Diseases

 Incubation period is usually 2–3 weeks.

infection
 The disease is characterized by fever, rash, and
– Obstruction of Stenson’s duct by a calculus
lymphadenopathy.
– Parotid tumor  It is more severe in adults than children.
– Sarcoidosis
 There is usually a prodrome of low grade fever,
– Sjögren’s syndrome. malaise, anorexia and sore throat, followed by
lymphadenopathy and appearance of skin rash.
1
Diagnosis
 Diagnosis is mainly by clinical features. Rash often begins on the face and spreads down
 Serological detection of IgM antibodies. the body. It is maculopapular but not confluent. It

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54 disappears in the same order. Lymphadenopathy  Live rubella vaccine is contraindicated during
usually affects suboccipital, cervical and post- pregnancy and it is recommended that pregnancy
auricular nodes but rarely axillary nodes can also be avoided for at least 3 months after rubella
be involved. Complications are rare and include vaccination.
arthritis (in women), encephalitis and thrombo-
cytopenia. Q. Discuss the etiology, epidemiology, pathogenesis,
 Congenital rubella: Maternal infection in early clinical features, diagnosis and treatment of rabies.
pregnancy can lead to fetal infection, leading to
Q. Prevention of rabies.
teratogenic effects and congenital rubella.
Sensorineural hearing loss is the most common Q. Post-exposure prophylaxis of rabies.
manifestation of congenital rubella syndrome.
 Rabies is an acute lethal viral infection of the central
Other signs of congenital rubella are cataract, heart
nervous system caused by rabies virus. It is a
disease (patent ductus arteriosus), deafness, and
preventable zoonotic disease.
many other defects like mental retardation,
microcephaly, and thrombocytopenic purpura.  Rabies is one of the oldest, best known, and most
Infection in the first trimester leads to more severe feared human diseases. It has the highest case
congenital rubella in the fetus. fatality rate of any infectious disease.

Etiology
Investigations
 Rabies virus is a bullet shaped virus, with a single-
 Most cases are mild and are difficult to diagnose
stranded ribonucleic acid (RNA) nucleocapsid core
on clinical grounds.
and lipoprotein envelope. It belongs to the family
 Rubella can be diagnosed by specific IgM rubella
of Rhabdoviridae and genus Lyssavirus.
antibody and also by virus isolation.
Epidemiology
Treatment
 Rabies has a worldwide distribution except
 Isolate the patient for 7 days after the onset of rash Antarctica, New Zealand, and Japan.
to prevent spread of infection to others.  Mammals are the main reservoir of rabies virus.
 There is no specific treatment. Most cases recover  Rabies exists in two forms: (1) Urban rabies, found
spontaneously. in unimmunized domestic dogs and cats, (2) sylvatic
 Antipyretics like paracetamol can be used to treat rabies, found in skunks, foxes, raccoons, mongooses,
fever. wolves, and bats.
 The main reservoir of rabies throughout the world
Prevention is the domestic dog. Domestic animals usually
 Presently all infants are routinely immunized acquire infection from sylvatic reservoirs of infection.
against rubella by giving MMR vaccine at 12–15  Human infection occurs through contact with
months of age. Live rubella virus vaccine containing unimmunized domestic animals or from exposure
RA 27/3 strain, and a recombinant DNA vaccine is to wild animals.
now available.  Mandatory vaccination of domestic dogs against
 Vaccine is administered in a single dose of 0.5 ml rabies has resulted in decreased incidence of rabies.
subcutaneously. Immunity wanes after 10–15 years
and hence the vaccine may have to be repeated at Pathogenesis
10–15 years of age. Rubella vaccine may also be Rabies is a highly neurotropic virus that evades
Manipal Prep Manual of Medicine


administered to anyone who is thought to be immune surveillance by its sequestration in the
susceptible to the infection. nervous system.
 Rabies is transmitted by the bite of infected animals,
commonly dogs or cats. The saliva of these animals
is the reservoir of infection. Rarely, transmission
takes place through transplantation of infected
tissues such as cornea or inhalation of aerosol
containing virus.
 After the entry of live virus through saliva following
a bite, viral replication starts in striated muscle cells.
The virus then spreads centripetally up the nerve


to the CNS, via peripheral nerve axoplasm, at a rate

1 Figure 1.12 Rabies virus
of ~3 mm/h. Once the virus reaches the CNS, it
multiplies there and then passes centrifugally along

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 somatic and autonomic nerves to other tissues— they are interspersed with lucid intervals, but as 55
the salivary glands, adrenal medulla, kidneys, the disease progresses the lucid periods get shorter
lungs, liver, skeletal muscles, skin, and heart. In the until the patient lapses into coma. Hyperaesthesia,
salivary glands virus can multiply again and with excessive irritation to bright light, noise, touch,
secreted into saliva which is infective to others. and breezes are often seen. Abnormalities of the
 The most characteristic pathologic finding of rabies autonomic nervous system include dilated pupils,
in the CNS is the formation of cytoplasmic increased sweating, lacrimation, salivation and
inclusions called Negri bodies within neurons. postural hypotension. There may be fever at this
Negri body is an eosinophilic mass of fibrillar stage. Evidence of upper motor neuron paralysis,
matrix and viral particles. Negri bodies are not with weakness, exaggerated deep tendon reflexes,
found in at least 20% cases of rabies, hence, their and extensor plantar responses, is always found.
absence does not rule out the diagnosis of rabies. Paralysis of the vocal cords may produce dysphonia.
Brain stem dysfunction begins shortly after ence-
Clinical Features phalitic phase. Brainstem dysfunction manifests as
diplopia, facial paralysis, and dysphagia with
Incubation Period excessive salivation. The combination of excessive
 The incubation period of rabies ranges from 10 days salivation and difficulty in swallowing give the
to over 1 year (mean 1–2 months). Rarely, cases of appearance of “foaming at the mouth.” Attempt to
human rabies with an extended incubation period swallow liquids produces painful, violent, involun-
(2 to 7 years) have been reported. The incubation tary contraction of the diaphragmatic, accessory
period depends on the amount of virus introduced, respiratory, pharyngeal, and laryngeal muscles-
host defense mechanisms, and the distance that the called hydrophobia. Hydrophobia is seen in only
virus has to travel from the site of inoculation to ~50% of rabies cases. Even blowing air can produce
the CNS. violent spasms (aerophobia)
 Incubation period is less than 50 days if the patient  Paralytic (dumb) rabies presents as quadriparesis
is bitten on the head or neck or if a heavy amount with sphincter involvement, mimicking Guillain-
of virus is inoculated. A person with a scratch on Barré syndrome. Encephalitis occurs late in the
the hand may take longer to develop symptoms of course.
rabies than a person who receives a bite to the head.
 The rabies virus is segregated from the immune Stage of Coma and Death
system during this period, and no antibody  This begins within 10 days of onset, and the dura-
response is observed. tion varies. The patient soon lapses into coma, and
dies of respiratory failure. After the onset of brain-
Prodromal Period stem symptoms, patient survives for only 4–5 days
 Prodromal stage: This stage lasts 1–4 days and is and rarely for 20 days maximum. If artificial
characterized by fever, nausea, vomiting, headache, supportive measures are instituted, patient may
myalgia, sore throat and dry cough. There may be survive longer but many complications may appear
complaint of paresthesia, fasciculations or intense like hypotension, cardiac arrhythmias, ARDS, etc.
itching at the site of virus inoculation which is which can kill the patient.
pathognomonic of rabies and occurs in 50% of cases
during this phase. These sensations are due to the Diagnosis
multiplication of virus in the dorsal root ganglion  Diagnosis is usually made based on clinical features
of the sensory nerve supplying the area. Except for and history of exposure to rabies source (dog bite).
these sensations/fasciculations, all other symptoms  Routine blood tests are nonspecific.
resemble any other viral prodrome.  Detection of rabies antigen: Rabies antigen can be
detected in cutaneous nerves by direct fluorescent
Acute Neurologic Period antibody (DFA) test. Skin biopsy from the nape of


 Two acute neurologic forms of rabies are seen in the neck can be obtained for this purpose. Rabies
Infectious Diseases

humans: Encephalitic (furious) in 80% and paralytic virus antigen is detected in cutaneous nerves at the
(dumb) in 20%. base of hair follicles. DFA can be done on corneal
 Encephalitic rabies presents with hydrophobia, smear also but skin biopsy is more sensitive.
aerophobia, pharyngeal spasms, and hyperactivity.  Detection of rabies virus RNA: Detection of rabies
This is the most common form. This stage is charac- virus RNA by RT-PCR (reverse transcriptase-
terized by periods of excessive motor activity, polymerase chain reaction) is highly sensitive and
excitation, agitation, hallucinations, confusion, specific. This technique can detect virus in fresh
muscle spasms, meningismus, opisthotonic
posturing, seizures, and focal paralysis. Initially
saliva and CSF samples. Real time PCR is even more
sensitive than RT-PCR. 1
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56  Virus isolation from infected tissue: Virus isolation Pre-exposure Prophylaxis
from infected tissue can be carried out by inoculat-  It should be given to all those at risk of developing
ing the sample into mice (mouse inoculation test) rabies like veterinarians, animal handlers and
or in cell culture. The specimens collected for this laboratory workers.
purpose can be saliva samples, throat swabs, swabs  3 doses of vaccine (preferably HDCV: Human
of the nasal mucosa, corneal smears and CSF. diploid cell vaccine) are administered intramuscu-
Disadvantage of this test is it is time consuming. larly on days 0, 7, and 21 or 28.
 Demonstration of antibodies against rabies virus:
This is not a very useful test because rabies virus– Postexposure Prophylaxis
specific antibodies may be found in serum as a
 Exposure is considered to be a bite that breaks the
result of previous vaccination against rabies.
skin or any contact between mucous membrane or
However, detection of antibodies in the serum or
broken skin and animal saliva. Persons exposed to
CSF of a previously unimmunized patient is
rabies should be given 5 doses of rabies vaccine
diagnostic of rabies.
preferably HDCV (human diploid cell vaccine).
 After death the diagnosis of rabies can be confirmed
Doses are administered on 0, 3, 7, 14, and 28 days.
by demonstration of Negri bodies in brain.
A booster dose may be given at day 90. Persons
Treatment who have already received pre-exposure prophyl-
axis need to receive only two doses of rabies vaccine
 There is no specific treatment for rabies. Medical 3 days apart.
management is supportive and palliative. Death is
 In addition to vaccine, human rabies immune
inevitable once clinical signs develop.
globulin (20 IU/kg) or equine rabies immuno-
 The bite wound should be cleaned, debrided and
globulin (40 IU/kg) should be given. Out of the total
carefully examined for any foreign body (e.g.
dose of required immunoglobulin, as much as
broken tooth). Generally, leave wounds to heal by
possible should be injected at the site of the bite,
secondary intention to permit drainage of wound
and the remaining should be injected intramuscu-
fluids and prevent infection. The following therapy
larly at a distant site, e.g. in the deltoid opposite
has been recommended though there is no proof
the vaccine site. Immunoglobulin can be given up
that they are effective.
to day 7 after the exposure. After day 7, it is not
– Rabies vaccination to accelerate the immune necessary to give rabies immune globulin because
response. endogenous antibodies are being produced and
– Intramuscular human rabies immune globulin exogenous antibodies may actually be counter-
(HRIG) to promote clearance of the infection. productive.
– Intravenous and intraventricular ribavirin –  Tetanus toxoid should be given if not given in the
Intravenous and intraventricular IFN-α – last 5 years.
Intravenous infusion of ketamine, a dissociative
 Wound should be cleaned with water and antiseptic
anesthetic agent and a noncompetitive antagonist
lotions. Wound should not be sutured.
of the N-methyl-D-aspartate receptor has been
shown to inhibit virus replication at high
Q. What are arboviruses? List common arboviruses and
concentrations.
the diseases caused by them.
Prevention of Rabies
 Arboviruses are a group of viruses transmitted by

 Since there is no treatment for rabies, all efforts arthropods to vertebrate hosts like man. The word
should be made to prevent rabies. Prevention of arbovirus is an acronym (arthropod-borne virus).
Manipal Prep Manual of Medicine

rabies can be divided into pre exposure prophylaxis The arthropods which transmit the infection are
and post-exposure prophylaxis. called vectors and include mosquito, tick, sandfly

TABLE 1.12: Common arboviruses and the diseases caused by them

Arbovirus Disease Transmitted by (vector) Clinical manifestations
Chikungunya Chikungunya fever Aedes mosquito Fever, arthritis
Dengue virus Dengue fever Aedes mosquito Fever, rash, hemorrhagic fever
Yellow fever virus Yellow fever Aedes mosquito Fever, jaundice, hemorrhagic fever
Japanese encephalitis virus Japanese encephalitis Culex mosquito Encephalitis
West Nile virus West Nile fever, encephalitis Culex mosquito Fever, rash, hepatitis, encephalitis


Kyasanur forest disease virus Kyasanur forest disease Tick Encephalitis, hemorrhagic fever

1
Colorado tick fever virus Colorado tick fever Tick Fever, myalgia, encephalitis, hemorr-
hagic fever

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 or midge. These infections generally occur during  Disseminated intravascular coagulation (DIC), 57
warm weather months, when mosquitoes and ticks induced by liver dysfunction, leads to consumption
are active. of platelets and clotting factors.
 Clinical manifestations of arbovirus infections  Tachypnea and hypoxia with impending respira-
include fever, rash, arthritis, encephalitis, or tory failure may develop as a consequence of sepsis
hemorrhagic fever. and acute respiratory distress syndrome (ARDS).
 Identification of infecting virus can be done by  In late stages of disease, shock and multiorgan
isolation of virus from blood, CSF (if there is dysfunction syndrome (MODS) dominate the
encephalitis) or other specimens. Serological clinical picture.
diagnosis can be made by demonstrating rising
antibody titres usually by complement fixation or Diagnosis
hemagglutination inhibition. IgM capture ELISA  LFT shows raised bilirubin, AST, ALT and pro-
permits early diagnosis. longed prothrombin time.
 Complete blood count usually shows leucopenia
Q. Yellow fever. and thrombocytopenia.
 Serology: Enzyme-linked immunosorbent assay
Etiology (ELISA) can identify IgM antibody against yellow
 Yellow fever is a viral hemorrhagic fever caused fever virus.
by yellow fever virus which is a flavivirus. The  Detection of yellow fever antigen using monoclonal
disease was labeled “yellow” because of profound enzyme immunoassay in serum specimens.
jaundice observed in affected individuals. It is a  Detection of viral genome sequences in tissue or in
disease of monkeys found in Africa and South blood or other body fluid using polymerase chain
America. It has not been reported from Asia. reaction (PCR) assay.
 The infection is transmitted by Aedes aegypti  Histopathology: Liver biopsy is contraindicated
mosquito from monkeys to humans. due to risk of hemorrhage. However, it can be done
 Yellow fever is an internationally notifiable disease. for postmortem confirmation of diagnosis. Findings
include mid-zone necrosis, fatty degeneration and
Pathogenesis intracellular hyaline necrosis (Councilman bodies).
 The virus is transmitted via the saliva of an infected  Urine analysis: Usually shows severe albuminuria
mosquito. Local replication of the virus takes place which is a constant feature in yellow fever and its
in the skin and regional lymph nodes with subse- presence helps differentiate yellow fever from other
quent dissemination to all parts of the body. Liver causes of viral hepatitis.
is the most important organ affected in yellow fever.
Hepatocellular damage is characterized by lobular Treatment
steatosis, necrosis, and apoptosis with subsequent  There is no specific treatment. Only supportive
formation of Councilman bodies (degenerative treatment is required. Bedrest, analgesics, and
eosinophilic hepatocytes). Other important organs maintenance of fluid and electrolyte balance are
affected are kidneys, lymph nodes, spleen, brain important.
and bone marrow. The terminal phase is marked  Fresh frozen plasma is given to actively bleeding
by delirium, stupor, and coma due to cerebral patients due to prolonged prothrombin time.
edema and microscopic perivascular hemorrhage.  A nasogastric or orogastric tube may be required
to provide nutritional support.
Clinical Features  Patients with renal failure or refractory acidosis
 Yellow fever is a hemorrhagic fever with hepatic may require dialysis.
necrosis. The incubation period varies from 3 to
6 days. Prevention


 Patients present with high fever, headache,  It is easily prevented using 17-D chick embryo
Infectious Diseases

retrobulbar pain, arthralgia, a flushed face and vaccine, which provides protection for 10 years. It
conjunctival suffusion. Relative bradycardia (Faget is contraindicated in infants of less than 1 year, preg-
sign) is present from the second day onwards. The nant women, and immunocompromised persons.
patient then makes an apparent recovery and feels
well for many days. Thereafter again patient Q. Describe the etiology, pathogenesis, clinical
develops increasing fever, jaundice and hapato- features, diagnosis and management of dengue
megaly. Hemorrhages, hematemesis, melena, and fever.
encephalopathy occur due to extensive hepatic
involvement.
Q. Dengue hemorrhagic fever. 1
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58 Etiology  A maculopapular rash may appear in over 50% of
 Dengue fever is a viral hemorrhagic fever caused cases. Rash spares palms and soles. Petechiae may
by dengue virus which belongs to flavivirus family. appear all over the body but more prominent on
There are four closely related dengue viruses the extensor surface of the limbs.
(dengue 1–4).  The fever subsides after 3–4 days for a couple of
 Dengue is the most common arthropod-borne viral days, and returns again in a mild form and subsides.
(arboviral) illness in humans. Dengue Hemorrhagic Fever
Epidemiology  Severe form of dengue fever.
 It is believed to be due to sequential infection with
 It is mainly found in Asia and Africa and is trans-
two different dengue serotypes. First infection
mitted by the daytime-biting Aedes aegypti mosquito.
sensitizes the person against dengue. Second
 Occurs mostly during and shortly after the rainy
infection in a sensitized person leads to severe
season.
dengue with hemorrhagic manifestations.
 Most often affects children.
 Dengue hemorrhagic fever typically begins like
 Humans are infective during the viraemic stage classic dengue fever. The initial fever lasts approxi-
which lasts for 3 days. mately 2–7 days. However, in persons with dengue
 Mosquitoes become infective about 2 weeks after hemorrhagic fever, the fever reappears, giving a
feeding on an infected individual, and remain so biphasic or saddle back fever curve.
for the rest of their lives.  The critical feature of dengue hemorrhagic fever is
plasma leakage. Plasma leakage is caused by
Pathogenesis
increased capillary permeability and may manifest
 Primary infection leads to classic dengue fever. as hemoconcentration, as well as pleural effusion
Dengue hemorrhagic fever (DHF) and dengue and ascites. Bleeding is caused by capillary fragility
shock syndrome (DSS) are due to reinfection by a and thrombocytopenia and may manifest in various
different serotype of dengue virus. Prior infection forms, ranging from petechial skin hemorrhages to
with a serotype leads to antibody production and life-threatening gastrointestinal bleeding. Hypo-
sensitizes the person to reinfection. Reinfection with tension occurs due to hemorrhages.
a different serotype leads to enhanced antibody-
mediated macrophage activation. Macrophages Dengue Shock Syndrome
produce vasoactive inflammatory mediators which  As the term implies, dengue shock syndrome is
result in vascular leak. Severe vascular leak results essentially dengue hemorrhagic fever with
in shock. progression into circulatory failure, with ensuing
 Endothelial damage also leads to hemorrhagic hypotension and shock. This is an even more severe
manifestations. Hemorrhage is often widespread form of the disease.
and associated with pleural effusions and ascites.  Aggressive fluid replacement is required to correct
Focal hepatic necrosis, immune complex–mediated the intravascular fluid deficits.
glomerulonephritis, and transient bone marrow
suppression may be seen. Investigations
 Low WBC counts, thrombocytopenia and altered
Clinical Features LFT. Thrombocytopenia is an important feature.
Clinical manifestations can be of 3 types:  Isolation of dengue virus from serum, plasma, and
 Classic dengue fever leukocytes
Manipal Prep Manual of Medicine

 Dengue hemorrhagic fever (DHF)  Serological tests: Demonstration of IgM and IgG
 Dengue shock syndrome (DSS) antibodies by ELISA in the serum sample.
 Detection of the specific viral protein NS1 (non-
Classic Dengue Fever structural protein) by ELISA is diagnostic during
 Presents as a nonspecific biphasic (saddle back the first few days of infection.
fever) febrile illness.  Immunohistochemistry for antigen detection in
 Incubation period is 4–5 days. tissue samples can also be used.
 Disease is more severe in adults than children.  Detection of viral genomic sequences in serum, or
About 80% of infected infants and children remain cerebral spinal fluid (CSF) samples via polymerase
asymptomatic. chain reaction (PCR).
 The disease starts with sudden onset fever, chills,  Chest X-ray may show pleural effusion.


headache, conjunctival suffusion, myalgia, joint pain,  Ultrasound: May show pleural effusion, ascites,

1 and severe backache. Because of severe muscle, joint

and bone pains, it is also called “breakbone” fever.
pericardial effusion (polyserositis), and a thickened
gallbladder wall.

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Treatment  People remain infectious as long as their blood and 59
 There is no specific treatment for dengue. Treatment body fluids including semen and breast milk
is mainly supportive. Paracetamol is used to treat contain the virus. Men can transmit the virus
fever and body aches. IV fluids and blood trans through their semen for up to 7 weeks after recovery
fusions are given to replace intravascular volume from illness.
loss. Platelet transfusions may be required to correct
severe thrombocytopenia (<20,000/cumm). Pathogenesis
 Ebola virus replicates well in virtually all cell types,
Q. Ebola virus disease. including endothelial cells, macrophages, and
parenchymal cells of multiple organs. Viral replica-
 Ebola virus disease (formerly known as Ebola tion is associated with cellular necrosis. In addition
hemorrhagic fever) is a severe, often fatal illness, to sustaining direct damage from viral infection,
with a case fatality rate of up to 90%. It is one of the patients infected with Ebola virus have high
world’s most virulent diseases. circulating levels of proinflammatory cytokines,
which contribute to the severity of the illness. The
Etiology final effect of all this is widespread inflammation,
 Ebola is a RNA virus. It is a member of the family DIC and tissue necrosis.
Filoviridae, taken from the Latin “filum,” meaning
thread-like, based upon their filamentous structure. Clinical Manifestations
Marburg virus is also a Filovirus and causes illness  Incubation period is approximately 7–10 days.
similar to ebola virus. Humans are not infectious until they develop
 The genus Ebola virus is currently classified into symptoms.
5 species: Sudan ebolavirus, Zaire ebolavirus, Tai Forest  Initial symptoms are sudden onset of fever, fatigue,
(Ivory Coast) ebolavirus, Reston ebolavirus, and muscle pain, headache and sore throat. This is
Bundibugyo ebolavirus. The 2014 outbreak of Ebola followed by vomiting, diarrhea, rash, symptoms of
virus disease in West Africa is due to Zaire impaired kidney and liver function, and in some
ebolavirus. cases, both internal and external bleeding (e.g.
oozing from the gums, epistaxis, blood in the
Epidemiology stools).
 Additional findings include edema of the face, neck,
 Ebola virus disease (EVD) first appeared in 1976 in
and/or scrotum, hepatomegaly, flushing, conjunc-
2 simultaneous outbreaks, one in Nzara, Sudan, and
tival injection, and pharyngitis.
the other in Yambuku, Democratic Republic of
Congo. The latter occurred in a village near the  Patients without any complications may recover
Ebola River, from which the disease takes its name. 10–12 days after the onset of disease.
In addition to causing human infections, Ebola virus
Investigations
has also spread to wild nonhuman primates, such as
macaques, chimpanzee and gorilla in Central Africa.  Leukopenia and thrombocytopenia is common.
This has also triggered some human epidemics due  Liver enzymes and serum amylase level may be
to handling of and/or consumption of sick or dead elevated.
animals by local villagers as a source of food.  Antigen-detection by ELISA.
 Electron microscopy.
Transmission  Virus isolation by cell culture.
 It is thought that fruit bats of the Pteropodidae  Real-time PCR is extremely useful for rapid
family are natural Ebola virus hosts. Ebola is diagnosis.
introduced into the human population through  The indirect fluorescent antibody test with paired
close contact with the blood, secretions, organs or sera is also an effective diagnostic tool.
other bodily fluids of infected animals such as


chimpanzees, gorillas, fruit bats, and monkeys.

Infectious Diseases

Treatment
 Human to human transmission occurs through  No virus-specific therapy is available, and at
direct contact (through broken skin or mucous present treatment is mainly supportive. Supportive
membranes) with the blood, secretions, organs or care with oral or intravenous fluids and treatment
other bodily fluids of infected people, and with of specific symptoms improves survival.
fomites contaminated with these fluids.  Experimental therapies include inhibitor of factor
 Burial ceremonies in which mourners have direct VIIa/tissue factor or with activated protein C, direct
contact with the body of the deceased person can
also play a role in the transmission of Ebola.
intervention against viral replication with small
interfering RNA (siRNA), inhibitors of cell entry 1
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60 (since the membrane fusion mechanism of Ebola Clinical Features
virus resembles that of retroviruses) and  Japanese encephalitis resembles any other viral
monoclonal antibodies that have neutralizing encepahalitis.
capacity.  Incubation period is 5–15 days.
 All ages can be affected though children are affected
Prevention
more frequently.
 No vaccine or antiviral drug is currently available.  The encephalitis mainly involves the thalamus and
 Reducing the risk of human-to-human transmission the substantia nigra.
from direct or close contact with people with Ebola  Patient presents with a prodrome of fever, vertigo,
symptoms, particularly with their bodily fluids. sore throat, and respiratory symptoms. Headache,
Barrier nursing precautions should be used while meningeal signs, photophobia, vomiting and
treating a patient with Ebola. altered mental status follow quickly. Patient may
 Reducing the risk of wildlife-to-human trans- be disoriented and comatose. Cranial nerve palsies,
mission from contact with infected fruit bats or hemiparesis, monoparesis, difficulty in swallowing,
monkeys/apes and the consumption of their raw and frontal lobe signs are all common. Convulsions
meat. and focal signs may appear during the course of
 Vaccines are under development. the disease.
 Avoid visiting endemic areas.  The acute encephalitis usually lasts from a few days
to as long as 2 to 3 weeks. Complete recovery may
Complications take weeks to months.
 Death due to multiorgan failure and DIC or hemorr-
hage. Investigations
 Late hepatitis, uveitis, and orchitis have been  Initial leukocytosis followed by leukopenia.
reported, with isolation of virus from semen or  CSF analysis shows a lymphocytic pleocytosis.
detection of PCR products in vaginal secretions for  MRI or CT scan: Both show abnormalities in the
several weeks. thalamus, basal ganglia, midbrain, pons, and
medulla.
Q. Japanese encephalitis.  EEG (electroencephalography) may show genera-
lized slowing, and epileptiform activity.
Etiology
 The diagnosis of Japanese encephalitis can be made
 This is encephalitis caused by Japanese encephalitis by demonstration of IgM antibody by capture
(JE) virus which is a flavivirus. immunoassay of CSF, a four-fold rise in serum
 JE virus is the most important global cause of antibody titers against JE virus, or isolation of virus
arboviral encephalitis. or demonstration of viral antigen or genomic
 It is found throughout Asia, including Russia, sequences in tissue, blood, or CSF.
Japan, China, India, Pakistan, and Southeast Asia.
 In India it occurs in epidemics, mostly affecting Treatment
children in Tamil Nadu, West Bengal, Bihar and
 There is no specific therapy for Japanese encephalitis.
Assam.
Management is mainly supportive.
Transmission  Elevated intracranial pressure, respiratory failure,
and convulsions should be managed as per stan-
JE virus is transmitted in an enzootic cycle between
Manipal Prep Manual of Medicine


dard protocols.
mosquitoes and vertebrate hosts, primarily pigs and
 Nutrition should be maintained by Ryle’s tube
birds such as herons and egrets. Mosquitoes get
feeds. Bladder should be catheterized, if the patient
infected when they feed on these animals and then
is in altered sensorium or comatose. Fluid and
transfer the virus to humans. It is spread by Culex
electrolyte balance should be maintained.
mosquitoes (most often by Culex tritaeniorhynchus).
Vaccination of these animals may reduce the
Prevention
transmission of the virus.
 Humans are considered dead-end hosts in the JE  Japanese encephalitis is the most common vaccine-
virus transmission cycle because they do not preventable cause of encephalitis in Asia. A vaccine
develop a level or duration of viremia sufficient to is available for human use. It is given as two
infect mosquitoes. JE virus is not spread from doses administered intramuscularly (IM) on days


person to person through direct contact. JE virus 0 and 28.

1 transmission through blood transfusion has been

documented in a JE-endemic area.
 Pig population and mosquitoes should be
controlled.

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Q. Kyasanur forest disease (KFD). Q. Chikungunya fever. 61

 Kyasanur forest disease (KFD) is an acute febrile  Chikungunya is a mosquito-borne viral disease.
illness caused by KFD virus which is a flavivirus. Chikungunya virus is an RNA virus that belongs
It is named Kyasanur forest disease because the to the family Togaviridae. The name ‘chikungunya’
disease was first recognized in the Kyasanur forest derives from a word in the Kimakonde language
of Shivamogga district, Karnataka. of an ethnic group in southeast Tanzania, meaning
“to become contorted” and describes the stooped
Epidemiology appearance of sufferers with joint pain (arthralgia).
 It is found in Shivamogga, Mangaluru, Udupi,  Chikungunya is found mainly in tropical Africa and
Uttara Kannada and Chikkamagalur districts of Asia.
Karnataka state.  It is transmitted by the bite of an infected Aedes
 Monkeys (black faced langur and bonnet) are the mosquito.
reservoirs of this virus.  A large epidemic occurred in southern India in 2006
 Man gets infected when the tick: Haemophysalis due to the emergence of a new viral variant in
spinigera bites man after feeding on monkeys. Bites immunologically naive population.
happen usually during summer when people visit
the forest area to collect wood. Clinical Features
 Human is the dead end in natural cycle of the virus.  Self-limiting illness.
There is no human to human transmission of KFD.  Incubation period is 2–4 days.
 Characterized by sudden onset of fever, headache,
Clinical Features malaise, arthralgias or arthritis, myalgias, and low
 Incubation period is 4 to 6 days. back pain.
 Sudden onset of fever with chills and rigors, severe  Joint symptoms can be quite painful and usually
headache, bodyache, backache, orbital pain and involve small and large joints. Patient may not be
weakness. Vomiting and diarrhea can also be there. able to walk.
There can be bleeding manifestations like epistaxis,  A generalized maculopapular skin rash is seen in
gum bleeding, hematemesis and melaena. approximately half of cases on the second to fifth
 Examination usually reveals relative bradycardia, day of illness.
hypotension and conjunctival congestion. Lympha-  Fever subsides within seven days, but joint pain
denopathy may be noted in the neck and axilla. may persist for weeks to months.
 Fever usually subsides in 10–12 days. However,
some patients can have recurrence of fever. Laboratory Features
 Leukopenia, anemia, thrombocytopenia, and
Investigations elevated liver enzymes.
 Leucopenia and thrombocytopenia.  Serological tests, such as enzyme-linked immuno-
 Diagnosis can be confirmed by isolation of virus sorbent assays (ELISA) can detect the presence of
from the blood during fever. IgM and IgG anti-chikungunya antibodies.
 Detection of IgM antibodies against KFD virus by  Virus can be isolated from the blood during the first
ELISA. few days of infection.
 RT-PCR or real time RT-PCR can be used for rapid  Various reverse transcriptase–polymerase chain
diagnosis of KFD. reaction (RT–PCR) methods are also available to
detect the viral genome.
Treatment
 There is no specific treatment. Only symptomatic Treatment
and supportive measures are required. The condi-  There is no specific antiviral treatment. Only
tion usually resolves without any sequelae. The supportive treatment is required such as NSAIDs


mortality is 5 to 10%. for fever and joint pain.

Infectious Diseases

 Mosquito protection should be used to prevent

Prevention spread of disease.
 A formalin inactivated vaccine is available for use.
 People should avoid visiting forests when there is Q. Discuss the transmission, pathogenesis, clinical
death of monkeys. Those visiting the forest area features, investigations and management of human
should wear protective clothing and apply insect immunodeficiency virus (HIV) infection.
repellants (dimethyl phthalate) and take bath on
return.
Q. Enumerate the AIDS indicator conditions. 1
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62  Human immunodeficiency virus (HIV) is a single (vertical transmission). >70% of infections occur
stranded RNA virus belonging to retroviridae because of unsafe sexual practices. Transmission
family and lentivirus genus. It is spherical in shape through blood transfusion has largely been
and has a lipid membrane lined by a matrix protein eliminated by the universal screening of blood
that is studded with glycoprotein (gp)120 and gp41 products for HIV.
spikes surrounding a cone-shaped protein core. The
core contains two copies of the single-stranded Pathogenesis
RNA genome and viral enzymes.  HIV infects mainly cells of immune system such as
 HIV infection leads to AIDS (acquired immuno- helper T cells (CD4+ T cells), macrophages, and
deficiency syndrome) a condition in which the dendritic cells. HIV enters into these cells by
immune system begins to fail, leading to life- binding to CD4 receptor through its gp-120
threatening opportunistic infections. Immune molecule. The virus replicates itself by generating
deficiency is due to destruction of CD4 lympho- a DNA copy by reverse transcriptase. Viral DNA
cytes. Most of the AIDS cases are caused by HIV-1. becomes incorporated into the host DNA, enabling
HIV-2 causes a similar illness but is less aggressive further replication.
and is seen mainly to Western Africa.  HIV infection leads to fall in CD4+ T cells by three
 AIDS was first recognized in the United States in main mechanisms: direct viral killing of infected
1981 in male homosexuals. Since then, it has grown cells; increased rates of apoptosis of infected cells;
to become a major pandemic in the world. It and killing of infected CD4+ T cells by CD8 cytotoxic
has become the second leading cause of disease lymphocytes that recognize infected cells. When
burden worldwide and the leading cause of CD4+ cell count declines below a critical level, cell-
death in Africa. In 1983, HIV was isolated from a mediated immunity is lost, and the body becomes
patient with lymphadenopathy, and by 1984 it more susceptible to opportunistic infections and
was demonstrated clearly to be the causative agent various neoplasms.
of AIDS.  Progressive failure of immune system leads to
 Till now more than 25 million deaths have been development of AIDS characterized by develop-
attributed to AIDS. The current estimate of world- ment of opportunistic infections and malignancies.
wide disease prevalence is more than 33 million The speed of progression of HIV infection to AIDS
HIV infections. Two-thirds of these cases are in is variable depending on viral load, host, and
developing countries, mainly sub-Saharan Africa environmental factors. Most will progress to AIDS
and Southeast Asia. within 10 years of HIV infection.
 Most AIDS cases occur in adults aged 25–49 years
(70% of cases). Clinical Stages and Natural History of HIV Infection
 Clinical HIV infection undergoes 3 distinct phases:
Transmission of HIV Acute HIV infection, chronic HIV infection, and
 Transmission of HIV occurs through almost any AIDS.
body fluid such as blood, vaginal fluid, or breast
milk. Within these bodily fluids, HIV is present as Acute HIV infection (Acute seroconversion)
both free virus particles and virus within infected  This stage is characterized by rapid viral replication
immune cells. leading to an abundance of virus in the peripheral
 The four major routes of transmission are unsafe blood with levels commonly approaching several
sex, contaminated needles, breast milk, and trans- million viruses per mL. There is a marked drop in
mission from an infected mother to her baby at birth the number of circulating CD4+ T cells. It usually
Manipal Prep Manual of Medicine

occurs 2–6 weeks after exposure to HIV and lasts

an average of 28 days. The immune system
responds to the replication of virus by activation
of CD8+ T cells, and antibody production against
the viral antigens. Hence, this phase is also called
seroconversion phase.
 Most people develop flu-like illness during this
stage. Common symptoms are fever, lymphadeno-
pathy, pharyngitis, rash, myalgia, malaise, apthous
ulcers, hepatosplenomegaly, oral candidiasis, and
weight loss. All these signs and symptoms are not


specific for HIV infection and can be seen in many

1 Figure 1.13 HIV virus

other infectious diseases. Hence, diagnosis may be
missed at this stage.

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 During the acute HIV infection stage, the level of or are indicative of a defect in cell-mediated immunity; 63
HIV in the blood is very high, which greatly or (2) the conditions are considered by physicians
increases the risk of HIV transmission. to have a clinical course or to require management
that is complicated by HIV infection.
Chronic HIV Infection (Asymptomatic Infection) Examples include, but are not limited to, the
 During this stage, strong immunity reduces the following:
viral load and patient may remain asymptomatic – Bacillary angiomatosis –
except for the possible presence of persistent Oropharyngeal candidiasis
generalised lymphadenopathy (PGL, defined as (thrush)
enlarged glands at ≥2 extra-inguinal sites). But HIV – Vulvovaginal candidiasis, persistent or resistant
remains active within lymphoid organs, and also – Pelvic inflammatory disease (PID)
as free viral particles. Patient remains infective – Cervical dysplasia (moderate or severe)/cervical
during this stage also. CD4 count decreases usually carcinoma in situ
at a rate between 50 and 150 cells/year. Asympto-
– Hairy leukoplakia, oral –
matic infection lasts for a variable period (can last
Herpes zoster (shingles), involving two or more
from two weeks to ten years or more).
episodes or at least one dermatome
AIDS Stage – Idiopathic thrombocytopenic purpura
– Constitutional symptoms, such as fever
 This stage (stage 3 in CDC classification) is charac-
(>38.5°C)
terized by signs and symptoms of various opportu-
or diarrhea lasting >1 month
nistic infections. The CD4 count is usually below
 – Peripheralofneuropathy
Candidiasis bronchi, trachea, or lungs
200/mm3.
 Candidiasis, esophageal
Category C (AIDS Indicator Conditions)
 Cervical cancer, invasive
CDC Classification of HIV Infection (2014 Classification)
 Coccidioidomycosis, disseminated or extrapulmo-
 Category A: Asymptomatic HIV infection without
nary
a history of symptoms or AIDS-defining conditions.
 Cryptococcosis, extrapulmonary
 Category B: HIV infection with symptoms that are
 Cryptosporidiosis, chronic intestinal (>1 month’s
directly attributable to HIV infection (or a defect in
T-cell–mediated immunity) or that are complicated duration)
 Cytomegalovirus disease (other than liver, spleen,
by HIV infection.
 Category C: HIV infection with AIDS-defining or nodes)
 Cytomegalovirus retinitis (with loss of vision)
opportunistic infections.
 Encephalopathy, HIV-related
These 3 categories are further subdivided on the basis  Herpes simplex: Chronic ulcer(s) (>1 month’s
of the CD4+ T-cell count, as follows: duration); or bronchitis, pneumonia, or esophagitis
 >500/μL: Categories A1, B1, C1
 Histoplasmosis, disseminated or extrapulmonary
 200–499/μL: Categories A2, B2, C2
 Isosporiasis, chronic intestinal (>1 month’s duration)
 <200/μL: Categories A3, B3, C3
 Kaposi’s sarcoma

 Lymphoma, Burkitt’s (or equivalent term)

Clinical Categories of HIV Infection
 Lymphoma, primary, of brain

Category A  Mycobacterium avium complex or M. kansasii,

 Consists of one or more of the conditions listed disseminated or extrapulmonary

 Mycobacterium tuberculosis, any site (pulmonary or
below in an adolescent or adult (>13 years) with
documented HIV infection. Conditions listed in extrapulmonary)
categories B and C must not have occurred.  Mycobacterium, other species or unidentified

– Asymptomatic HIV infection – species, disseminated or extrapulmonary

 Pneumocystis jiroveci pneumonia
Persistent generalized lymphadenopathy –


 Pneumonia, recurrent
Infectious Diseases

Acute (primary) HIV infection with accom

 Progressive multifocal leukoencephalopathy
panying illness or history of acute HIV infection
 Salmonella septicemia, recurrent

Category B  Toxoplasmosis of brain

 Consists of symptomatic conditions in an HIV-  Wasting syndrome due to HIV

infected adolescent or adult that are not included

among conditions listed in clinical category C Investigations
and that meet at least one of the following criteria:
(1) The conditions are attributed to HIV infection



HIV ELISA and Western blot test.
CD4 count. 1
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64  Viral load.  The availability of antiretroviral agents has drasti-
 Hepatitis B surface antibody (HBsAg). cally improved the prognosis of HIV infected
 Hepatitis C IgG antibody. patients. Patients who receive successful ART have
 Hepatitis A IgG antibody. stabilization or improvement of their clinical
 Toxoplasma antibody. condition, improved life expectancy and decrease
 Cytomegalovirus (CMV) IgG antibody. in AIDS-related complications.
 Treponema serology (VDRL and TPHA).
 Chest X-ray. When to Initiate ART (Anti-retroviral Therapy)
 Latest guidelines recommend that ART should be
Treatment of the HIV Infection started immediately for all people with a confirmed
 The aims of HIV treatment are to: Decrease viral HIV diagnosis regardless of CD4 count. This is
load to an undetectable level (<50 copies/ml) for called rapid ARTinitiation and should be started
as long as possible and improve the CD4 count to on the same day of diagnosis or within 3 days of
above 200 cells/mm3. diagnosis of HIV.

Antiretroviral Drugs
TABLE 1.13: Antiretroviral drugs
Drug Main side effects
Nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs)
Zidovudine Anemia, neutropenia, myopathy, lactic acidosis, hepatomegaly with steatosis
Lamivudine Rash, peripheral neuropathy
Didanosine Peripheral neuropathy, pancreatitis, hepatitis, lactic acidosis
Zalcitabine Peripheral neuropathy, pancreatitis, hepatitis, lactic acidosis, hepatomegaly with steatosis
Stavudine Peripheral neuropathy, pancreatitis, hepatitis
Emtricitabine Hepatitis
Abacavir Hypersensitivity reaction (can be fatal), fever, rash
Tenofovir Renal toxicity

Nonnucleoside reverse transcriptase inhibitors (NNRTIs)

Nevirapine Skin rash, hepatotoxicity
Efavirenz Skin rash, hepatitis, drowsiness, abnormal dreams, depression
Delavirdine Skin rash

Protease inhibitors
Indinavir Renal calculi, fat redistribution, lipid abnormalities
Saquinavir Diarrhea, nausea, fat redistribution, lipid abnormalities
Ritonavir Nausea, abdominal pain, hyperglycemia, fat redistribution, lipid abnormalities
Nelfinavir Diarrhea
Atazanavir Hyperbilirubinemia

Entry inhibitors
Enfuvirtide Injection site pain and allergic reaction, increased rate of bacterial pneumonia
Maraviroc Cough, fever, rash
Manipal Prep Manual of Medicine

Integrase strand transfer inhibitors (INSTIs)

Raltegravir Diarrhea, nausea, rash
Dolutegravir Hepatotoxicity, insomnia, fatigue, and headache
Elvitegravir Nausea, vomiting, diarrhea,suicidal ideation

CYP3A inhibitor
Cobicistat This drug increases the serum concentration of atazanavir and darunavir by CYP3A enzyme present in liver

First-line ART Regimens of three drug classes: An integrase strand transfer

 Combinations of 2, 3, or 4 drugs from different inhibitor (INSTI), a non-nucleoside reverse trans-
classes are usually necessary to fully suppress criptase inhibitor (NNRTI), or a protease inhibitor
replication of HIV. (PI) with a pharmacokinetic enhancer (i.e. cobicistat
or ritonavir).


 Recommended ART regimens generally consists of

1 two nucleoside reverse transcriptase inhibitors

(NRTIs) in combination with a third drug from one
Some of the popular regimens are as follows:
 Dolutegravir/abacavir/lamivudine (DAL)

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 Dolutegravir/tenofovir/emtricitabine (DET)  Opportunistic infections usually occur when CD4 65
 Darunavir/ritonavir plus tenofovir/emtricitabine count is below 200. However, certain opportunistic
(DRET) infections in HIV infected person indicate that the
person is having AIDS irrespective of the CD4 count.
Alternative Regimens  An opportunistic infection may be caused by various
 Efavirenz/tenofovir/emtricitabine (ETE) pathogens—bacteria, viruses, fungi, or protozoa.
 Atazanavir/cobicistat/tenofovir/emtricitabine

(ACTE) Common Opportunistic Infections in HIV

Viral
Reduction of HIV Transmission (Mother-to-Child and
Person-to-Person)  Cytomegalovirus (CMV): CMV retinitis.

 Human herpes virus 8 (HHV-8): Kaposi’s sarcoma.

Prevention of Mother to Child Transmission  Human papillomavirus (HPV): Cervical cancer.
 Transmission of HIV from mother to child can occur  Epstein barr virus (EBV): Primary CNS lymphoma.
during pregnancy, labor and delivery, or breast
feeding. During antenatal period, HIV-infected Bacterial
women who are pregnant should start antiretro-  Mycobacterium tubercrulosis: Pulmonary or extra-
viral treatment with at least three medications. pulmonary tuberculosis.
Recommended regimens are tenofovir plus  Mycobacterium avium complex (MAC): Disseminated
lamivudine plus efavirenz (TEL). During labor, infection with multi organ involvement.
intravenous administration of ZDV, 2 mg/kg
loading dose, followed by a continuous infusion of Fungal
1 mg/kg per hour until delivery should be given.  Candida: Oropharyngeal and esophageal candi-
 After delivery, the neonate should be given daily diasis.
nevirapine from birth for minimum 6 weeks.  Pneumocystis jirovecii: Pneumonia.
 Because HIV can be transmitted in breast milk,
 Cryptococcosis: Usually manifests as meningitis.
women with HIV should not breastfeed their  Histoplasmosis: Disseminated infection.
babies. Baby milk formula is a safe and healthy
 Coccidioidomycosis: Disseminated infection.
alternative to breast milk in such situations.
 Microsporidia: Causes diarrhea.

Prevention of Person to Person Transmission

Protozoal
 Precautions regarding sexual practices and injection
 Toxoplasm gondii: Toxoplasmosis of brain.
drug use.
 Cryptosporidiosis: Intestinal infection leading to
 Universal screening of donor blood and blood
diarrhea.
products for HIV.
 Isosporiasis: Intestinal infection leading to diarrhea.
 Infection control practices in the health care setting.

 Vaccines are under development.

Prophylaxis for Common Opportunistic Infections
 Postexposure prophylaxis if there is accidental

exposure to a known source of HIV.  Every attempt should be made to prevent opportu-
nistic infections in HIV infected patients as they
Q. Opportunistic infections in AIDS. cause significant morbidity and mortality.
 Prophylaxis of opportunistic infection is usually
 Opportunistic infections are those which usually based on the CD4 count. If the CD4 count increases
occur in a person with weakened immune system above the levels that are used to initiate prophylaxis—
such as patients with AIDS. prophylactic therapy can be discontinued.

TABLE 1.14: Prophylaxis for opportunistic infections

CD4 count Opportunistic infection against Drugs used for prophylaxis
which prophylaxis is indicated


All HIV-infected patients with positive Mycobacterium tuberculosis Isoniazid, 300 mg daily, plus pyridoxine 50 mg
Infectious Diseases

PPD reactions (defined as >5 mm of orally daily, for 9 months

induration for HIV-infected patients)
CD4 counts ≥200 cells/mcL Pneumocystis jiroveci pneumonia Trimethoprim-sulfamethoxazole, one double-
strength tablet (960 mg) daily or dapsone
50–100 mg daily
CD4 counts <100 cells/mcL with a Toxoplasmosis Trimethoprim-sulfamethoxazole (one double-
positive IgG toxoplasma serology strength tablet daily)

1
CD4 counts <50 cells/mcL Mycobacterium avium complex Azithromycin (1200 mg orally weekly) or
(MAC) infection clarithromycin (500 mg orally twice daily)

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66 Treatment of Opportunistic Infections in HIV (Table 1.15)
TABLE 1.15: Treatment of opportunistic infections and complications of HIV
Opportunistic infection or complication Treatment
Mycobacterium tuberculosis Standard 4 drug anti-tubercular therapy for 6 to 9 months. ART is delayed for a
period of 2–8 weeks following initiation of antitubercular therapy toprevent IRIS
(Immune reconstitution inflammatory syndrome)
Pneumocystis jiroveci infection Trimethoprim-sulfamethoxazole, 15 mg/kg/d (based on trimethoprim component)
orally or intravenously for 14–21 days OR pentamidine or trimethoprim, 15 mg/kg/d
orally, with dapsone, 100 mg/d orally, for 14–21 days OR Primaquine, 15–30 mg/d
orally, and clindamycin, 600 mg every 8 hours orally, for 14–21 days.
Mycobacterium avium complex infection Clarithromycin, 500 mg orally twice daily with ethambutol, 15 mg/kg/d orally
(maximum, 1 g). Therapy may be stopped when CD4 count is >100/μL for 3–6
months.
Toxoplasmosis
Sulfadiazine and pyrimethamine combined with leucovorin for 4 to 6 weeks
minimum. Maintenance therapy with same drugs may be required as long as CD4
count is <200/μL.
Cryptococcal meningitis
Amphotericin B with or without flucytosine intravenoulsy for 2 weeks, followed
by fluconazole orally.
Cytomegalovirus infection
Valganciclovir or ganciclovir or foscarnet
Esophageal candidiasis or recurrent vaginal Fluconazole, 100–200 mg orally daily for 10–14 days.
candidiasis
Q. Postsimplex
Herpes exposure prophylaxis
infection (PEP)
and herpes for HIV.
zoster Q. Immune
Aciclovir or famciclovir reconstitution
or valacyclovir or foscarnet.inflammatory syndrome
(IRIS).
 Immediate decontamination: Wash the area with

soap and water. Small wounds and punctures may  The term “immune reconstitution inflammatory
be cleansed with an antiseptic such as alcohol, iodo- syndrome” (IRIS) refers to a collection of inflamma-
phors, or chlorhexidine. For mucous membrane tory disorders associated with paradoxical
exposure, irrigate the area with water or sterile worsening of pre-existing infectious processes
saline. following the initiation of antiretroviral therapy
 Testing of source of exposure: Voluntary testing for (ART) in HIV patients. IRIS has been reported in
HIV antibody, hepatitis C virus antibody, and 10 to 32% of patients starting ART.
hepatitis B surface antigen (HBsAg); if HIV test is
positive, confirmatory Western blot and CD4 count. Pathogenesis
If the source patient’s rapid HIV test is negative  As the immunefunction improves following the
but there has been a risk for HIV exposure in the initiation of ART, systemic or local inflammatory
previous 6 weeks, plasma HIV RNA testing is reactions may occur at the sites of preexisting
recommended infections. The syndrome appears to result from an
 Testing of exposed person: Testing for HIV unbalanced immune reconstitution of effector and
antibody, HCV antibody, HbsAg, and hepatitis regulatory T cells in patients receiving ART. Macro-
B surface antibody (HBsAb); in females of phages and natural killer cells are also suspected
childbearing age, pregnancy testing. to play a role in IRIS.
Manipal Prep Manual of Medicine

· Recommended regimen: Three-drug PEP  Presence of opportunistic infection at the time of

regimens are now the recommended regimens initiation of ART is a clear risk factor for the develop-
for all exposures due to the safety and ment of IRIS. A variety of mycobacterial, viral, fungal
tolerability of new HIV drugs. The preferred 3-drug and parasitic opportunistic infections are associated
PEP regimen with IRIS. Mycobacterium tuberculosis (TB) is one of
is as follows: Tenofovirplusemtricitabineplus the commonest pathogen known to cause IRIS.
atazanavir or lopinavir (TEA or TEL). The duration  Determining whether clinical deterioration is
of treatment is 1 month. Effect of atazanavir caused by treatment failure, IRIS, or both requires
 or
PEPlopinavir
should be can be boosted
initiated by adding
as soon ritonavir.
as possible, ideally assessment of the persistence of active infections
within 2 hours of exposure; a first dose of PEP with cultures and can be difficult.
should be offered to the exposed worker while the


evaluation is underway. Clinical Features

1  Repeat HIV testing should be done at 4 and 12

weeks postexposure.
 Patient usually presents with worsening or

appearance of new clinical or radiological features.

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 Manifestations depend on the underlying opportu- China at the end of 2019. This virus is a beta corona- 67
nistic infection. virus (same group as SARS virus). This has been
 Mycobacterium tuberculosis (TB) is among the most named SARS-CoV-2 as it is very similar to the one
common pathogen associated with IRIS. TB IRIS that caused the SARS outbreak (SARS-CoVs). The
presents with worsening of the pulmonary or disease caused by SARS-CoV-2 virus has been
extrapulmonary symptoms of TB. There is return designated as COVID-19 (which stands for corona-
of fever, lymph node enlargement or suppuration. virus disease 2019). This virus subsequently spread
Chest X-ray may show appearance of fresh infil- throughout China and then became a pandemic
trates, mediastinal lymphadenopathy, worsening spreading all over the world, becoming a global
pleural effusion and pericardial effusion. Pre- health emergency.
existing CNS tuberculosis may worsen due to  The exact origin of SARS-CoV-2 is unknown but it
inflammation and present with worsening of is probably of animal origin from bats. There is
headache and altered mental status. speculation that it has spread from bats to other
 Pneumocystis jiroveci associated IRIS may present mammals and then to human beings.
as worsening pulmonary symptoms and high
fever. Chest X-ray may show worsening of lung Structure of COVID-19
infiltrates.  SARS-CoV-2 is round in shape and has an envelope.
Envelope has spike proteins and conjugated
Treatment proteins (glycoproteins). Spike proteins play a
 Opportunistic infections should be optimally crucial role in binding to angiotensin-converting
treated. Non-steroidal anti-inflammatory drugs enzyme 2 (ACE2) receptors of host cells to enter
(NSAIDS) can be used for milder manifestations of the cell by endocytosis.
IRIS and steroids for cases with severe inflamma-  SARS-CoV-2 is a single-strand RNA virus. The
tion. ART should be continued unless there is life genome contains sequences for proteases, replicases,
threatening IRIS. helicases, endoribonuclease, and spike proteins.

Prognosis
 Majority of patients with IRIS have a self-limiting
disease course. However, significant morbidity and
mortality may be seen with ARDS and CNS
involvement.

Prevention
 ART should be initiated before the onset of severe
immunodeficiency and after the treatment of oppor-
tunistic infections. In the case of HIV-TB co-infection,
Figure 1.14 Corona virus
WHO recommends that TB should be treated first
and after 2 to 4 weeks, ART to be initiated.
Pathophysiology
Q. Coronavirus infection.  The route of transmission of SARS-CoV-2 is
coughing and sneezing via respiratory droplets.
 Coronaviruses are RNA viruses whose name The virus enters the lungs through the respiratory
derives from their characteristic crown-like appea- tract and attacks alveolar epithelial type 2 (AT2)
rance in electron microscope. Coronaviruses are cells. AT2 produces a surfactant to decrease the
important human and animal pathogens. They can surface tension within alveoli. The virus binds to
cause upper and lower respiratory tract infections ACE2 receptors on alveolar epithelial cells through
which can be severe. its spike protein. ACE2 receptors are also found in
The coronaviruses are classified into four genera: Alpha, kidneys, heart, intestine, pancreas, and endothelial



Infectious Diseases

beta, gamma, and delta coronaviruses. The human cells. Once inside the host cell, the virus releases its
coronaviruses (HCoVs) are in two of these genera: RNA. The RNA uses the host cell ribosome to
alpha coronaviruses and beta coronaviruses. Beta produce viral proteins. It also uses RNA dependent
coronaviruses include Middle East respiratory RNA polymerases to duplicate its RNA.
syndrome coronavirus (MERS-CoV), and the severe  The virus then leads to an inflammatory response
acute respiratory syndrome coronavirus (SARS- activating macrophages and CD4+ T helper cells
CoV). which in turn release cytokines (IL-1, IL-6, and
 A novel coronavirus was identified as the cause of
a cluster of pneumonia cases in Wuhan, a city in
TNFα) and chemokines into the bloodstream.
Excessive release of these cytokines can lead to 1
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68 cytokine storm. The release of these molecules  Antigen test: Antigen tests provide rapid results but
causes vasodilation and increased capillary permea- have a higher chance of missing an active infection.
bility. The leakage of plasma into the interstitial These tests also require a nasal swab or nasopharyn-
spaces of the alveoli cells will lead to alveolar geal swab.
collapse and impaired gaseous exchange. In the  Antibody test: detection of IgM or IgG antibodies
later stages of the disease, all these steps cause against SARS-CoV-2 indicates Covid-19. But these
difficulty in breathing, hypoxemia, and respiratory tests take time to become positive and hence are
failure. All these abnormal inflammatory responses not useful in early diagnosis.
can lead to septic shock and multiorgan failure.
Management
Clinical Features  The possibility of COVID-19 should be considered
 Incubation period is within 14 days following expo- in patients with fever and/or lower respiratory tract
sure, with most cases occurring approximately five symptoms who reside in or have recently traveled
days after exposure. to China or who have had recent close contact with
 The clinical spectrum of COVID-19 varies from a confirmed or suspected case of COVID-19.
asymptomatic cases to severe pneumonia charac-  Patients with suspected or confirmed COVID-19
terized by respiratory failure requiring mechanical who require hospitalization should be cared for in
ventilation, to multiorgan failure and death. a facility that can provide an airborne infection
 Mild disease presents with symptoms of an upper isolation room.
respiratory tract viral infection, including mild  Supportive care for sepsis and acute respiratory
fever, cough (dry), sore throat, nasal congestion, distress syndrome is required
malaise, headache, and muscle pain. New loss of  Guidelines recommend dexamethasone (6 mg per
taste and/or smell, diarrhea, and vomiting are day for up to 10 days) for patients who are
usually present. mechanical ventilator or require oxygen. Other
 Severe disease manifests as pneumonia charac- steroids (methylprednisolone, hydrocortisone) can
terized by fever, fatigue, dry cough, dyspnea, low be used instead of dexamethasone. Steroids are not
oxygen saturation (SpO 2 <94%), and bilateral recommended for patients who do not require
infiltrates on chest imaging. Approximately 20% of oxygen.
the infected patients develop complications such  Remdesivir injection is recommended for 5 days in
as respiratory failure, septic shock, or other organ patients who require oxygen (O2 saturation <94%
failure requiring intensive care. Mortality rate is on room air).
around 3%. Most of the deaths have occurred in  Anticoagulants: COVID-19 patients have a higher
patients with underlying medical comorbidities. incidence of thrombotic complications (venous
 Children seem to be less affected than adults. thromboembolism, MI, stroke). Hence anticoagu-
 Complications and death rate are more among lant therapy with heparin or LMWX is recommen-
elderly people and those with comorbid illness such ded for all admitted patients for 5 to 10 days.
as diabetes mellitus, hypertension, heart disease,  For patients with severe respiratory failure, extra-
and pre-existing lung diseases. corporeal membrane oxygenation (ECMO) may be
considered.
Diagnosis
 There are insufficient data to recommend drugs
 Bilateral infiltrates on chest X-ray. such as azithromycin, chloroquine, and ivermectin.
 High-resolution CT (HRCT) of chest is one of the
most important test in the diagnosis of COVID-19 Prevention
Manipal Prep Manual of Medicine

pneumonia. Most common findings are multifocal  Early recognition of suspect cases, immediate isola-
bilateral “ground glass opacities” associated with tion, and institution of infection control measures.
consolidation areas with patchy distribution,  Individuals with suspected infection in the comm-
mainly in the peripheral/subpleural areas. unity should be advised to wear a medical mask to
 Lymphopenia or elevated neutrophil-to-lympho- contain their respiratory secretions and seek
cyte ratio (NLR). medical attention.
 Elevated D-dimer.  WHO advises general measures to reduce trans-
 Increased liver enzymes and LDH. mission of infection, including diligent hand
 RT-PCR (real-time reverse transcriptase-polymerase washing, respiratory hygiene, and avoiding close
chain reaction) to detect viral RNA: Specimens contact with ill individuals.
should be collected from both the upper respiratory  WHO also advises exit screening for international


tract (naso- and oropharyngeal samples) and lower travelers from areas with ongoing transmission of
1 respiratory tract such as expectorated sputum,
endotracheal aspirate, or bronchoalveolar lavage.
COVID-19 virus to identify individuals with fever,
cough, or potential high-risk exposure.

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 Quarantine is meant to separate and restrict the  Live, attenuated SARS-CoV-2 vaccines: Another type 69
movement of close contacts who were exposed to of vaccine consists of live attenuated SARS-CoV-2;
COVID-19 case to see, if they become sick. The the virus is still infectious and can cause an immune
recommended duration is based on the incubation response.
period, which is up to 14 days for the SARS-CoV-2  Inactivated SARS-CoV-2 vaccines: These vaccines use
virus. Quarantine is recommended for 14 days after SARS-CoV-2 virus that has been inactivated with
their last exposure for asymptomatic close contacts heat, radiation, or chemicals, which terminate the
either testing negative or not tested. pathogen’s ability to replicate.
 Isolation is meant to separate COVID-19 patients  Protein-based vaccines: These vaccines contain SARS-
from others. Isolation is recommended for people CoV-2 proteins or protein fragments (subunits) that
with COVID-19 symptoms and those who are stimulate a protective immune response. The viral
COVID-19 positive. Isolation is usually recommen- protein can be produced by recombinant techno-
ded for 10 days from the day of symptom onset or logy, in which genes that encode the viral protein.
from the day of positive test for asymptomatic  Noninjectable vaccines: Intranasal and inhaled
patients. vaccines are also undergoing clinical trials. These
 Strict adherence to these measures has been success- vaccines could stimulate local mucosal immunity
ful at controlling the spread of infection in select areas. in the respiratory tract, in addition to systemic
immunity.
Vaccines
 The SARS-CoV-2 vaccines can be classified into two Q. Discuss the etiology, pathogenesis, clinical features,
broad categories: Gene-based and protein-based diagnosis and management of malaria.
 Gene-based vaccines include RNA, DNA, virus
Q. Life cycle of malarial parasite.
vector, and live attenuated SARS-CoV-2 virus
vaccines. Q. Tests to diagnose malaria.
 Protein-based vaccines include inactivated SARS- Q. Chemoprophylaxis for malaria.
CoV-2 virus and viral protein or protein fragment
(subunit) vaccines.  Malaria is a protozoan disease caused by Plasmodium
 The spike protein, which studs the surface of the species of protozoa.
SARS-CoV-2 virus is responsible for fusion of the
Etiology
virus to host cell membranes. Antibodies that bind
to the spike protein and block viral entry into host  Five species of Plasmodium namely, Plasmodium
cells are thought to be most important for protection vivax, P. falciparum, P. ovale, P. malariae and P. knowlesi
from disease. Hence spike protein is a key target are responsible for almost all human infections. Out
for all COVID-19 vaccines in clinical development. of these, P. falcifarum causes severe infection and is
 mRNA vaccines: SARS-CoV-2 is an RNA virus. responsible for most of the deaths due to malaria.
Several COVID-19 vaccines use the gene (in the
Epidemiology
form of messenger RNA or mRNA) that encodes
the spike protein and are encapsulated in a lipid  Malaria is the most important of the parasitic
nanoparticle to deliver the viral gene into the diseases of humans. It has been eliminated from
vaccine recipient’s cells. The recipient’s cells then the United States, Canada, Europe, and Russia.
use this gene to synthesize the spike protein that Malaria is very common in tropical countries. P.
stimulates a protective immune response. Two falciparum predominates in Africa, New Guinea,
doses spaced 3 or 4 weeks apart are required. Two and Hispaniola. P. vivax is more common in Central
mRNA vaccines are currently being used to America. Both falciparum and vivax are common
vaccinate people in multiple countries. in South America, the Indian subcontinent, eastern
 DNA vaccines: One SARS-CoV-2 vaccine uses DNA Asia, and Oceania. P. malariae and P. ovale is mainly
plasmids (small circles of double-stranded DNA) confined to Africa.
that encode the spike protein, which are introduced  P. knowlesi has been identified on the island of


directly into the vaccine recipient’s cells using an Borneo and Southeast Asia.
Infectious Diseases

intradermal injection device. The recipient’s cells

then produce the spike protein. Pathogenesis and Life Cycle of Malarial Parasite
 Viral vector vaccines: In viral vector vaccines, the  It is transmitted by the bite of infected Anopheles
SARS-CoV-2 spike protein gene is inserted into a mosquitoes.
harmless carrier virus that delivers the gene to the  Human infection begins when a female anopheles
vaccine recipient’s cells, which in turn read the gene mosquito bites man and inoculates sporozoites into
and assemble the spike. The spike protein is the blood. These sporozoites are motile forms of
presented on the surfaces of the recipient’s cells,
provoking an immune response.
the malarial parasite and are carried via the
bloodstream to the liver. 1
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70

Figure 1.15 Malaria life cycle

 In the liver sporozoites invade hepatic parenchymal Clinical Features

cells and start multiplying there to produce  The incubation period for vivax, ovale and
schizonts. Schizonts contain merozoites. This initial falciparum infections is 8–24 days. For P. malariae
replication in the liver is called the exoerythrocytic it is 15–30 days.
cycle. In P. vivax and P. ovale infections, some of  The initial symptoms of malaria are nonspecific and
these schizonts may remain dormant (hypnozoites) include malaise, nausea, vomiting, headache,
for up to a year or longer. These dormant forms fatigue, body ache and fever. Some cases may also
are the cause of relapses in vivax and ovale. have abdominal pain, arthralgia, or diarrhea.
 After 8–14 days, the swollen liver cell containing Though myalgia may be prominent, it is not as
merozoites (schizont) bursts, releasing motile severe as in dengue fever or leptospirosis. Muscle
merozoites into the bloodstream. Each merozoite tenderness is absent unlike in leptospirosis or
can invade an RBC and start multiplying there. typhus fever. Classic malarial symptoms with inter-
Attachment to RBC is mediated by a receptor on mittent fever, chills, and rigors are usually seen with
the RBC. In the case of P. vivax, this receptor is P. vivax or P. ovale infection but not in all cases.
related to the Duffy blood group antigen. Those  Fever in vivax and ovale comes once in 3 days
who have Duffy-negative blood group (West (tertian malaria) and once in 4 days P. malariae
African) are resistant to P. vivax malaria. (quartan malaria). However, this time pattern may
 Inside the RBCs, the merozoites develop into ring- not be seen in all cases of malaria. In falciparum
stage trophozoites. Some trophozoites mature into fever comes daily and does not follow any pattern.
schizonts and some trophozoites differentiate into The fever can rise above 40°C.
gametocytes. Schizonts contain many merozoites.  Children can have febrile convulsions at the time
When the RBC ruptures, these daughter merozoites of fever.
are released, each capable of invading a new RBC Cerebral malaria should be suspected in any-
Manipal Prep Manual of Medicine


and repeating the cycle. Gametocytes (sexual forms) body with falciparum malaria presenting with
are picked up by mosquitoes when they bite human seizures.
beings. Inside the mosquito’s midgut the male and  Physical examination is essentially normal except
female gametocytes join to form a zygote. This fever, mild anemia, mild jaundice and mild spleno-
zygote becomes an ookinete which penetrates and megaly. Anemia and jaundice are due to destruction
develops in the mosquito’s gut wall to become of RBCs (hemolysis) by the parasites. Splenomegaly
oocyst. Oocyst develops by asexual division and is common in malaria-endemic areas and reflects
bursts to release motile sporozoites, which migrate repeated infections. Mild hepatomegaly may also
to the salivary gland of the mosquito to await be seen particularly in young children.
inoculation into another human at the next feeding.  Severe malaria especially falciparum can present
 Malaria can also develop after blood transfusion with features of sepsis with multiorgan dysfunction.


without any incubation period. The hepatic phase Patients may present with impaired consciousness
1 is absent as the erythrocytic infection is directly
transmitted.
or coma, renal failure, liver impairment, low platelet
counts, and ARDS.

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TABLE 1.16: Differences in malaria caused by different plasmodium species 71
P. vivax P. ovale P. falciparum P. malariae
Incubation period 8–24 days 8–24 days 8–24 days 15–30 days
Fever pattern Tertian Tertian No periodicity Quartan
Exo-erythrocytic cycle Yes Yes No No
Relapses Yes Yes No No
Red cell preference Young RBCs Reticulocytes Young RBCs (but can Older cells
invade cells of all ages)
Morphology Large ring forms and Infected erythrocytes, Small ring forms; banana- Band forms of tropho-
trophozoites; Schüffner’s enlarged and oval with shaped gametocytes zoites
dots tufted ends; Schüffner’s
dots

 Serious renal damage may occur due to progressive matic activities. Assays may involve detection of a
glomerulonephritis in Plasmodium malariae infection histidine-rich protein 2 (HRP-2) associated with
due to deposition of immune complexes. The glo- malaria parasites (especially P. falciparum) and
merulonephritis does not respond to antimalarial detection of plasmodium-associated lactate dehydro-
drugs or corticosteroids. genase (pLDH). These tests are rapid and almost
as sensitive as thick smear but do not quantify the
Causes of Anemia in Malaria severity of infection and remain positive for weeks
after infection.
 Destruction of RBCs by parasites.
 Enlarged spleen causing sequestration of RBCs and  HRP-2 based tests: Histidine-rich protein-2 (HRP-2)
hemolysis. based serologic assays can detect parasite anti-
gens in blood from a fingerprick sample. PfHRP2
 Dyserythropoiesis.
dipstick or card test can detect only falciparum.
 Folate deficiency due to depletion of stores.
 Drug-induced (chloroquine, primaquine) hemolysis  Plasmodium LDH based tests: The pLDH-based
in patients with G6PD deficiency. assays specifically detect the parasite lactate de-
hydrogenase enzyme using a panel of monoclonal
Investigations antibodies. Different species can be identified.
Example is OptiMAL test.
 It is difficult to diagnose malaria clinically with
accuracy; hence treatment should be started on Fluorescent Technique (MP-QBC)
clinical grounds pending laboratory confirmation.
 The quantitative buffy coat (QBC) is a technique
Peripheral Smear that is as sensitive as thick smear.
 The diagnosis of malaria can be easily made by  Blood is collected in a glass micro tube containing
demonstration of asexual forms of parasites in the acridine orange stain, anticoagulant, and a float.
peripheral blood smear. If initial smears are This is centrifuged to concentrate the parasitized
negative, repeat smears should be made preferably cells around the float. Malarial parasites take up
at the time of fever. Thick and thin smears are made fluorescent stain and can be easily detected under
and stained with Giemsa stain. The level of parasi- fluorescence microscopy. This test is ideal for
temia is expressed as the number of parasitized processing large numbers of samples rapidly. But
erythrocytes per 1000 RBCs, or per 200 white blood this test cannot identify the species of malaria.
cells (WBCs), and this figure is converted to the
number of parasitized erythrocytes per microliter. Other Tests
A parasite index of 2% or more is associated with  In addition to the tests listed above, new molecular
techniques, such as PCR assay testing and nucleic


an increased risk of severe malaria. Thick smear can

Infectious Diseases

detect parasites even if there is lower levels of acid sequence-based amplification (NASBA) are
parasitaemia. Gametocytes may persist for days or also available for diagnosis. They are more sensitive
weeks after clearance of asexual parasites. Presence than thick smears but are expensive and unavailable
of gametocytes without asexual forms does not in most developing countries.
indicate active infection.
Other Laboratory Findings
Rapid Diagnostic Tests (RDT)  There may be normochromic normocytic anemia,
 Rapid diagnostic tests for malaria are based on the
presence of certain plasmodium antigens or enzy-
increased WBC count, neutrophilia, and increased
ESR. In severe falciparum malaria there may be 1
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72 metabolic acidosis, increased bilirubin, elevated – Renal failure (serum creatinine >3 mg/dl)
liver enzymes, thrombocytopenia, increased urea – Jaundice (serum bilirubin >3 mg/dl)
creatinine, and hypoglycemia. – Severe anaemia (Hb <5 g/dl)
– Pulmonary edema/acute respiratory distress
Treatment (Refer to Table 1.17)
syndrome
TABLE 1.17: Regimens for the treatment of malaria – Hypoglycemia (plasma glucose <40 mg/dl)
Chloroquine-sensitive strains Chloroquine (10 mg of base/kg – Metabolic acidosis –
of all species of malaria stat followed by 5 mg/kg at 12, Circulatory collapse/shock (systolic BP <80 mm
(P. vivax, P. falciparum, 24, and 36 h) Hg) –
P. malariae, P. ovale, OR Abnormal bleeding and DIC –
P. knowlesi) Amodiaquine od 3 days)
In addition to above, prima-
Hemoglobinuria –
quine (0.5 mg of base/kg per Hyperthermia (temperature >104°F)
day) should be given for 14 days – Hyperparasitemia (>5% parasitized RBCs in
to prevent relapses in vivax and low endemic and >10% in hyperendemic areas)
ovale. Primaquine kills the
hypnozoites present in liver and Supportive
 Include Measures
IV fluids, antipyretics, blood transfusion
prevents relapses. Tafenoquine
to correct severe anemia, and bedrest.
300 mg single dose is an alterna-
tive to primaquine in adults ≥16 Relapses
years. Primaquine should not be
 Relapses occur in vivax and ovale malaria due to
given in severe G6PD deficiency
hepatic hypnozoites. Since hepatic hypnozoites are
Chloroquine-resistant un- Quinine sulfate (10 mg/kg 3 absent in falciparum malaria, relapses do not occur
complicated Plasmodium times a day for 3 or 7 days) plus
in falciparum malaria.
vivax and falciparum Doxycycline 100 mg twice a day
(suspect this in areas known for 7 days
Prevention of Malaria
to harbor resistant strains. OR
Ovale and malraiae are Artemether-lumefantrine (BD for Decreasing the Mosquito Population
usually sensitive) 3 days with food)
OR  Spraying of insecticides
Atovaquone/proguanil 4 adult  Biological methods such as use of mosquito larva
tablets once a day for 3 days eating fish in water reservoirs.
Primaquine or Tafenoquine
should be given to prevent Personal Protection
relapses as mentioned above.
 Use of clothes extending up to the wrists and ankles
Severe malaria, all Plasmo- Severe malaria is an emergency
when outdoors and mosquito nets when indoors
dium species including and parenteral artemisinin
falciparum derivatives or quinine should be
to avoid mosquito bites. Application of insect-
used irrespective of chloroquine repellant creams on the exposed body surfaces like
sensitivity. legs and hands.
IV artesunate2.4 mg/kg body
weight at 0, 12, 24, and 48 hours Chemoprophylaxis
followed by one of the following  Recommended for nonimmune visitors to endemic
a. Artemether-lumefantrine areas and to pregnant women living in endemic
(BD for 3 days with food)
areas.
OR
Travelers should start taking antimalarial drugs at
Manipal Prep Manual of Medicine


b. Atovaquone/proguanil 4 adult
tablets once a day for 3 days least 1 week before visiting the area and continue
OR for 4 weeks after returning from the endemic area.
c. Doxycycline100 mg twice a  Chloroquine 500 mg per week or mefloquine 250 mg
day for 7 days orally per week or doxycycline 100 mg orally once
Primaquine or tafenoquine should daily can be used for prophylaxis. Doxycycline is
be used to prevent relapses
contraindicated in pregnant women and children
if
less than 8 years.
P. vivax or P. ovale is likely or
Criteria for Severe Malaria confirmed Malaria Vaccine
 Malaria is considered to be severe when patients  Malaria vaccines are under development.
have ≥1 of the following. Severe malaria is most
often due to P. falciparum.


Complications of Malaria
– Impaired consciousness/coma
1 – Repeated generalized convulsions
 Complications usually happen in severe falciparum
malaria.

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• Cerebral malaria  Although the exact mechanism is uncertain, evidence 73
• Severe anemia suggests that repeated or chronic exposure to malaria
• Renal failure elicits exaggerated stimulation of polyclonal B
• Pulmonary edema
lymphocytes, leading to excessive and partially
• Acute respiratory distress syndrome (ARDS), and respiratory
uncontrolled production of immunoglobulin M
failure (IgM) as the initiating event. IgM is polyclonal and
• Hypoglycemia is not specific for any particular malarial species.
• Circulatory collapse  By an unclear mechanism, the malarial parasite
• DIC causes proliferation of B lymphocytes due to
• Acidosis
defective control of B lymphocytes by suppressor
• Hemoglobinuria
or cytotoxic T lymphocytes, T cell infiltration of the
hepatic and splenic sinusoids accompanies this
• Jaundice
process. There is increase in serum cryoglobulin,
autoantibody levels and high-molecular-weight
Q. Cerebral malaria.
immune complexes. The result is anemia, deposi-
 Cerebral malaria is the most severe complication tion of large immune complexes in Kupffer cells in
of falciparum malaria with high mortality rate. It the liver and spleen, reticuloendothelial cell hyper-
is more common in children, pregnant women, plasia, and hepatosplenomegaly.
splenectomised and in non-immune individuals.  In some cases refractory to therapy, clonal lympho-
 The main pathology in cerebral malaria is sequestra- proliferation may develop and then evolve into a
tion of parasitized red cells in brain micro- malignant lymphoproliferative disorder.
vasculature. Inflammatory mediators may also play
a role in the pathogenesis. Clinical Features
 Patients with tropical splenomegaly present with
Clinical Features an abdominal mass or a dragging sensation in the
 Cerebral malaria manifests as diffuse encephalo- abdomen. Occasionally sharp abdominal pain may
pathy and presents as impaired state of conscious- be noted due to perisplenitis.
ness and/or seizures, and can result in coma and  Anemia and pancytopenia are usually present, but
death. Focal neurologic signs are unusual. Although malarial parasites cannot be found in peripheral-
some passive resistance to head flexion may be blood smears in most cases.
detected, frank neck rigidity is absent. This feature  These patients are prone for respiratory and skin
can differentiate cerebral malaria from meningitis. infections and many die due to infection and
The corneal reflexes are preserved except in deep secondary sepsis.
coma. Flexor or extensor posturing may be seen.
Some patients have retinal hemorrhages, Treatment
papilledema, and cotton wool spots. Convulsions  Chloroquine and proguanil appear to be equally
can occur and are usually generalized. effective. Eradication of parasitemia may be the
 Cerebral malaria is universally fatal if untreated, underlying mechanism. Pyrimethamine may be an
and even with treatment mortality is high. About alternative.
10% of patients who survive cerebral malaria have
Q. Describe the etiology, life cycle, pathogenesis,
persistent neurologic abnormalities even after
clinical features and treatment of amebiasis.
recovery.
 Amebiasis is an infection caused by the intestinal
Treatment protozoan Entamoeba histolytica. The diseases pro-
 Same as that of severe malaria (see above). duced by amoeba include dysentery and abscesses
in the liver and other organs.
Q. Tropical splenomegaly (hyperreactive malarial
Epidemiology


splenomegaly syndrome).
Infectious Diseases

 Amebiasis is found all over the world.

 Hyperreactive malarial splenomegaly syndrome  Amebiasis is more common in the developing
(HMSS) is prevalent in native residents of regions world, where overcrowding, poor sanitation and
where malaria is endemic and visitors to those regions. economic backwardness are common. In developed
countries, it is an important infection among male
Pathogenesis homosexuals, intravenous drug users and patients
 Patients with HMS have high levels of antimalarial with AIDS.
antibody. Chronic antigenic stimulation may be an
important factor in the development of HMS.
 90% of infections are asymptomatic and only 10%
produce clinical symptoms. 1
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74 Life Cycle of Ameba and Pathogenesis mainly of blood and mucus. Fever is uncommon
 The infection is transmitted through the feco-oral unlike bacterial diarrhea. Almost all patients have
route. blood in the stools.
 Man is the only reservoir of infection and excretes  Severe intestinal infection may present with severe
the cystic form of the organism in the feces, which abdominal pain and high fever. Some patients may
can survive in the environment for several weeks. develop toxic megacolon where there is severe
Man acquires infection by ingestion of viable cysts gaseous dilation of colon. Rarely patients develop
from fecally contaminated water, food, or hands. chronic amebic colitis, which can be confused with
Less commonly it is acquired through oral and anal inflammatory bowel disease.
sexual practices. Once ingested, cysts are able to Extraintestinal Amebiasis
resist the acidic gastric juice, and reach small
 Extraintestinal infection by E. histolytica most often
intestine, where the cysts develop into motile
trophozoites. Trophozoites remain as harmless involves the liver. Other sites include the brain,
commensals in the colon in most patients. However, spleen, lungs and pelvic organs.
 Patients present with fever and right-upper-
in some patients, the trophozoites invade the bowel
mucosa, and cause colitis which presents clinically quadrant pain. Pain is dull or pleuritic in nature
as dysentery. and may radiate to the right shoulder. Point
 There are usually mucosal ulcers which typically have tenderness over the liver and right-sided pleural
the shape of a flask in cross-section (wide base and effusion is common. Hepatomegaly is usually seen,
but jaundice is rare. Although the initial site of
narrow neck). Amebic ulcers occur most commonly
infection is the colon, most patients do not give a
in the rectum but may occur anywhere in the colon.
history of dysentery. Most abscesses occur in the
 Trophozoites can also enter the bloodstream and
right lobe of liver. Amebic liver abscess can present
get carried to different organs like liver, lungs, or as FUO and should be considered in the differential
brain where they may produce abscesses. The diagnosis of fever of unknown origin.
necrotic contents of a liver abscess appear like
“anchovy sauce”. Some trophozoites undergo Complications
encystation and produce infectious cysts which are
 Perforation of amebic ulcers and toxic megacolon.
shed in the stool and the life cycle can get repeated
again.  Liver abscesses may become big and rupture into
adjacent structures such as the pleural cavity, lungs,
 Trophozoites if ingested cannot cause infection
pericardium and peritoneum which can be fatal.
because they are rapidly killed by exposure to air
or stomach acid. Investigations
Clinical Features  Stool examination: This is the best test to diagnose
amebic dysentery. A saline preparation of freshly
 Amoebic infections are clinically classified as passed stool is examined for motile trophozoites.
intestinal and extraintestinal. Cysts also may be seen. Stool can be cultured for
Entamoeba histolytica and other bacteria.
Intestinal Amebiasis
 Colonoscopy and sigmoidoscopy: These are useful
 Most patients with intestinal amebiasis are to see the typical ulcers and also to distinguish it
asymptomatic. Those who become symptomatic from other ulcerative and inflammatory lesions like
present with dysentery. Lower abdominal pain, acute bacillary dysentery and ulcerative colitis, and
malaise and mild diarrhea develop gradually. to obtain swabs and biopsies for appropriate
Abdominal pain is usually colicky. Patients may examinations.
pass up to 10 to 12 stools per day. The stools appear
Manipal Prep Manual of Medicine

 Ultrasonography: Useful to identify amebic liver

dark brown, contain little fecal material and consist abscess. It gives an assessment of the size and
location of the abscess.
 Serological tests: Demonstration of presence of
anti-amebic antibodies in the serum is an important
way of diagnosing amebic infections. Enzyme-
linked immunosorbent assays (ELISAs) and indirect
hemagglutination test are used for this purpose.

Treatment
 Metronidazole 400 mg thrice a day for 7 days is
effective. Tinidazole can also be used.


 Newer agents like tinidazole, secnidazole or

1 Figure 1.16 Life cycle of ameba
ornidazole are equally effective and allow less
frequent dosing.

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 Along with above agents, it is useful to give luminal is an important cause of travellers’ diarrhea and is 75
amebicides like diloxanide furoate or iodoquinol also an important cause of diarrhea in immuno-
or Paromomycin which act in the gut lumen and suppressed individuals.
have minimal systemic absorption. Asymptomatic
cyst passers do not require treatment. Clinical Features
 Liver abscess requires the above drugs at a higher  Giardia infection can be asymptomatic.
dosage. If liver abscess does not respond to medical  Acute giardiasis may manifest as diarrhea,
therapy, it can be aspirated under ultrasound abdominal pain, bloating, belching, flatus, nausea,
guidance by introducing a pig-tailed catheter. and vomiting. This illness is usually self-limiting.
Chloroquine has also been used for patients with Patients may also present with dyspeptic symptoms
hepatic amebiasis. with nausea and anorexia.
 Complications such as perforation, toxic megacolon  Chronic giardiasis may present with malabsorption,
and stricture require appropriate surgical treatment. steatorrhea and weight loss. Such patients usually
have villous atrophy, with malabsorption of fat,
Q. Describe the etiology, clinical features, diagnosis carbohydrates, vitamin B12 and lactose intolerance.
and treatment of giardiasis. Children with chronic giardiasis may have growth
impairment.
 Giardiasis is one of the most common parasitic
diseases worldwide and is due to giardia lamblia  Giardiasis can be life-threatening in patients with
which is a protozoan. It causes intestinal disease hypogammaglobulinemia.
and diarrhea. Diagnosis
 Giardia lamblia is a flagellated protozoan and has a
pair of nuclei which give it an owl-eyed appearance.  Giardiasis is diagnosed by the detection of parasite
Flagellae are responsible for its motility. antigen, cysts or trophozoites in the feces.
 Endoscopic sampling of duodenal fluid and biopsy
Pathogenesis of the mucosa may be required to detect the parasite.
 Infection spreads through feco-oral route and is Treatment
acquired by ingestion of cysts present in food or
water. The cysts excyst in the intestine and become  Metronidazole is the drug of choice and is given either
trophozoites which have owl-eyed appearance. as 200 mg thrice daily for 7 days or as a single dose of
Giardia colonises the mucosa of upper small 2.4 g. Tinidazole or secnidazole are alternatives. All
intestine but does not invade the mucosa. infected symptomatic persons should be treated.
 Giardia attach to the mucosa of duodenum and
jejunum with the help of their ventral suction disc. Q. Trichomonas vaginalis.
They interfere with gut function by mechanical  Trichomonas vaginalisis is a pear shaped protozoan and
covering of the mucosa by a large number of causes infection of the vagina, urethra and prostate.
parasites and causing villous atrophy in the jejunal
 It spreads through sexual contact.
mucosa leading to a reduced absorptive surface. In
most infections the gut morphology is normal, but Clinical Features
in a few cases there may be changes resembling
tropical sprue and gluten-sensitive enteropathy on  In women, it causes vaginitis which presents as
histopathology. The pathogenesis of diarrhea in yellow and frothy vaginal discharge with burning
giardiasis is not known. and itching. They may also complain of dysuria,
 Both trophozoites and cystic forms are excreted in increased urinary frequency and dyspareunia.
the stool, but only cysts are infective to others. High  In men, trichomoniasis presents with urethritis and
levels of secretory IgA in breast milk are believed prostatitis, but may be asymptomatic.
to protect suckling infants from infection. Giardiasis
Diagnosis
 The diagnosis is made by detection of motile


trichomonads in wet smears prepared from vaginal,

Infectious Diseases

urethral or prostatic secretions. Direct immuno-

fluorescent antibody staining is more sensitive test
than microscopy.

Treatment
 Metronidazole is the drug of choice and is given as
200 mg thrice a day for 7 days or as a single 2 g

Figure 1.17 Giardia lamblia

dose. Tinidazole also can be used. Both partners
should be treated to prevent reinfection. 1
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76 Q. Describe the etiology, clinical features, diagnosis
and treatment of leishmaniasis.
 The term leishmaniasis refers collectively to various
clinical syndromes caused by intracellular protozoa
of the genus Leishmania. The name leishmaniasis
comes from the scientist Sir William Leishman who
first discovered the organisms in a patient who died
of leishmaniasis. It is a vector-borne (sandfly)
zoonosis, with rodents and canids as reservoir hosts
and humans as incidental hosts.
 The clinical spectrum of leishmaniasis ranges from
self-healing cutaneous ulcers to fatal visceral
disease. These syndromes fall into three broad
categories:
– Visceral leishmaniasis (VL)—this is also known
as kala-azar and is the most serious form of the
disease.
– Cutaneous leishmaniasis (CL)—this is the Figure 1.18 Lifecycle of leishmaniasis
most common type.
 There is inflammatory response against leishmania
– Mucocutaneous leishmaniasis (ML).
organisms with increased production of gamma
Etiology interferon (IFN), tumor necrosis factor alpha
(TNFα), and other proinflammatory cytokines. In
 The various species of leishmania causing human addition to these proinflammatory cytokines and
disease are as follows. chemokines, patients with active disease also have
 Visceral leishmaniasis—Leishmania donovani, L. markedly elevated levels of IL-10 in serum as well
infantum as in lesions. IL-10 inhibits the killing of amastigotes
 Cutaneous leishmaniasis—L. tropica, L. major, L. by inhibiting macrophages. This inflammation
aethiopica and L. mexicana along with inhibition of killing of amastigotes
 Mucocutaneous leishmaniasis—L. braziliensis. causes nodules, necrosis, ulceration and destruction
of tissues seen in leishmaniasis.
Epidemiology
 Leishmaniasis mainly occurs in tropical and Clinical features
temperate regions. India and neighboring Nepal, Visceral Leishmaniasis (Kala-azar)
Bangladesh, Sudan, and Brazil are the four largest  Potentially lethal widespread systemic disease
foci of visceral leishmaniasis. characterized by darkening of the skin as well as the
 Cutaneous leishmaniasis occurs mainly in pentad of fever, weight loss, hepatosplenomegaly,
Afghanistan, Pakistan, Ethiopia, Kenya, and pancytopenia, and hypergammaglobulinemia.
Uganda.
Cutaneous Leishmaniasis (CL)
Life Cycle and Pathogenesis  A few days or weeks after the bite of a sandfly, a
 Leishmania parasites are transmitted to man by the papule develops and grows into a nodule that
bite of sandflies (Phlebotomus and Lutzomyia). ulcerates. The base of the ulcer, which is usually
Manipal Prep Manual of Medicine

Visceral leishmaniasis can also be transmitted by painless, consists of necrotic tissue and crusted
blood transfusion or needle sharing. serum. Satellite lesions and local lymphadenopathy
 Leishmania exists in the sandfly as a motile, spindle- may be present.
shaped promastigote with an anterior flagellum. As  In diffuse cutaneous leishmaniasis, multiple, wide-
the flies feed on hosts including man, they spread non-ulcerating cutaneous papules, nodules
regurgitate the promastigote stage into the skin. and infiltration is seen.
Promastigotes are phagocytized by macrophages  Post-kala-azar dermal leishmaniasis (PKDL):
and inside the macrophages develop into the Develops months to years after the patient’s
nonflagellated amastigote stage. This amastigote recovery from visceral leishmaniasis. Cutaneous
multiplies by binary fission and are released after lesions include hypopigmented macules, erythe-
rupture of macrophages. Released amastigotes are matous papules, nodules and plaques.
phagocytized by other macrophages and start


multiplying there. Some amastigotes can be Mucocutaneous Leishmaniasis (ML)

1 ingested by sandflies where they transform back

into promastigotes and ready to infect other hosts.
 Lesions in or around the nose or mouth are the
typical presentation of ML. Patients usually give

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 history of self-healed CL preceding ML by 1–5 Pathogenesis 77
years. Typically, ML presents as nasal stuffiness and  Infection begins in macrophages at the inoculation
bleeding followed by destruction of nasal cartilage, site as described above and disseminates through-
perforation of the nasal septum, and collapse of out the reticuloendothelial system. Reticulo-
the nasal bridge. Subsequent involvement of the endothelial cells undergo hyperplasia which leads
pharynx and larynx leads to difficulty in swallow- to enlargement of the spleen, liver, lymph nodes,
ing and phonation. The lips, cheeks, and soft palate and bone marrow. Bone-marrow infiltration,
may also be affected. Secondary bacterial infection hypersplenism, autoimmune hemolysis, and
is common, and aspiration pneumonia may be fatal. bleeding all lead to pancytopenia.

Diagnosis Clinical Features

 The diagnosis is established by demonstration of  The incubation period varies from weeks to months
parasites. Amastigotes can be demonstrated by but can be as long as years.
light-microscopic examination of a specimen  Males are affected more than females and children
(smear, biopsy) obtained from the infected site. are affected more than adults.
 Culture can be done in Novy-MacNeal-Nicolle  Patients usually present with daily fever. Some
(NNN) blood agar. patients have 2 fever spikes per day (double quoti-
 Immunologic methods for diagnosis include dian fever) with rigors. Occasionally continuous
serologic assays and skin testing for delayed-type fever can occur.
hypersensitivity reactions. Traditional serologic  Skin manifestations in VL are frequent. Kala-azar
methods like indirect fluorescent testing do not means “black sickness” and refers to characteristic
reliably distinguish past from current infection. darkening of the skin seen in this condition.
 Other methods of parasitological confirmation  Hepatosplenomegaly is often present and spleno-
include animal inoculation, and polymerase chain megaly can be massive. Lymphadenopathy is also
reaction (PCR). present.
 Anemia is present in most patients due to hemolysis,
Treatment hypersplenism, and bone marrow suppression.
 Three groups of drugs are commonly used in  Jaundice, hypoalbuminemia, edema and ascites can
the treatment of leishmaniasis. be there due to liver involvement.
– Pentavalent antimonials—sodium stibogluconate  Death occurs due to secondary infections.
and meglumine antimoniate
– Pentamidine is etheonate and pentamidine Diagnosis
methanosulphonate  Kala-azar can be diagnosed by demonstration of
– Amphotericin B the parasite in smears or cultures of a tissue aspirate
 All these drugs have to be given parenterally (IM or a biopsy specimen (e.g. of spleen, liver, bone
or IV) for effective cure. marrow, or lymph node).
 Miltefosine: This is the first oral compound approved  Antibody detection by direct agglutination test (DAT)
for the treatment of leishmaniasis. It has a long half- and ELISA are the tests of choice for field diagnosis.
life (150–200 h) and its mechanism of action is not  PCR is a sensitive test and can also identify the
clearly understood. species. It can be performed on almost any tissue.
 Allopurinolhas also been used to treat leishmaniasis. It is not widely available.

Q. Visceral leishmaniasis (kala-azar, Dumdum fever). Treatment

 Pentavalent antimonials (sodium stibogluconate)
Etiology are the first-line drugs used to treat visceral
 Visceral leishmaniasis (kala-azar) is caused by leishmaniasis. Other choices include amphotericin
Leishmania donovani and L. infantum. Kala-azar means B, Pentamidine isethionate and allopurinol. All
‘black fever’ in Hindi which refers to characteristic these drugs are given parenterally.

Infectious Diseases

darkening of the skin seen in this condition.  Recently miltefosine has been found to be highly
effective and can be given orally. Sitamaquine,
Epidemiology another oral agent, is also being field-tested.
 Most cases of visceral leishmaniasis occur in
Bangladesh, northeastern India (particularly Bihar Prevention
State), Nepal, Sudan, and northeastern Brazil.  Sandflies should be controlled by spraying insecti-
 Visceral leishmaniasis is transmitted by sandflies. cides such as pyrethroids.
 It can also spread by blood transfusion or needle
sharing.
 Cases should be treated adequately to remove the
reservoir of infection. 1
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78  Insecticide-impregnated mosquito net and Clinical Features
repellants can be used for personal protection  An indurated inflammatory lesion called “chagoma”
against sandfly bites. often appears at the site of parasite entry.
 Vaccines are being developed.  If the bite occurs near the eye, unilateral painless
edema of palpebrae and periocular tissues
Q. Trypanosomiasis. associated with preauricular lymphadenopathy
(Romana’s sign) occurs. These initial local signs are
Q. American trypanosomiasis (Chagas disease).
followed by malaise, fever, and anorexia.
Q. African trypanosomiasis (sleeping sickness).  Cardiac abnormalities are the most frequent
manifestations of chronic Chagas disease. Conges-
 Trypanosomiasis is caused by protozoans belong- tive heart failure is the first sign of chagasic heart
ing to the genus Trypanosoma. disease. Other features are arrhythmias and heart
 There are mainly two types of trypanosomiasis, blocks (commonly RBBB-right bundle branch
American trypanosomiasis and African trypano- block). Death usually occurs due to heart failure.
somiasis.  Involvement of GI tract produces dysphagia, regurgi-
 American trypanosomiasis (Chagas disease) is tation, hiccups, constipation, and abdominal pain.
caused by Trypanosoma cruzi. African trypanosomiasis  Muscle involvement leads to myositis and myalgia.
(sleeping sickness) is caused by Trypanosoma brucei  Nervous system involvement leads to meningo-
gambiense and T. brucei rhodesiense. encephalitis.

American Trypanosomiasis (Chagas Disease) Diagnosis

 Chagas disease is caused by the hemoflagellate  Microscopic examination of anticoagulated blood or
of the buffy coat can show the motile trypanosomes.
protozoan Trypanosoma cruzi. T. cruzi is found only
in the America. It is the leading cause of congestive  Giemsa-stained blood smears can also show
heart failure in areas of Latin America where it is trypanosomes.
endemic.  Polymerase chain reaction (PCR).
 Blood culture in specialized media.
Pathogenesis  Detection of specific antibodies.
 It is transmitted to man by the bite of triatomines Treatment
(a type of reduvid bug also known as kissing bug).  There is no satisfactory treatment for Chagas’
These bugs ingest organisms while sucking blood disease. Only two drugs—nifurtimox and benznida-
from infected animals or humans. Ingested zole are available for treatment and these drugs
organisms multiply in the gut of the bugs, and cause severe side effects. Nifurtimox, a nitro-
infective forms are passed in the feces at the time furantoin derivative, is given for 3 or 4 months. New
of bite. Transmission occurs when breaks in the drugs are being developed.
skin, mucous membranes, or conjunctivae become
contaminated with bug feces. African Trypanosomiasis (Sleeping Sickness)
 T. cruzi can also be transmitted by blood transfusion, Etiology
organ transplantation and from mother to fetus.
 African trypanosomiasis (sleeping sickness) is
 A nodular swelling or chagoma develops at the site
caused by Trypanosoma brucei complex, transmitted
of entry. Lymphatic spread then carries the
to man by the bite of tsetse flies. Trypanosoma brucei
organism to regional lymph nodes. When the
gambiense infection is prevalent in West Africa and
histiocytes or other inflammatory cells ingest the
Manipal Prep Manual of Medicine

T. brucei rhodesiense is prevalent in East Africa.

parasites, they transform into amastigotes. After
local multiplication, the organisms can assume the Life Cycle
trypomastigote form and invade the bloodstream,  The tsetse fly becomes infected when it bites
carrying the infection to all parts of the body. Cells infected mammalian hosts. After multiplication in
of the reticuloendothelial system; cardiac, skeletal, the midgut of the tsetse fly, the parasites migrate
and smooth muscles; and neural cells are pre- to the salivary glands. Parasites are transmitted to
ferentially parasitized. another mammalian host when the tsetse fly bites.
 During the acute phase of illness, the parasite is The injected trypanosomes multiply in the blood of
believed to directly destroy host cells. The patho- new host and invade all the organs causing illness.
genesis of the cardiac and GI alterations typical of
the chronic phase is not well understood. Loss of Clinical Features


ganglionic neurons and nerve fibers along with  A painful chancre may appear in some patients at
1 inflammatory reaction are important pathological
findings.
the site of bite associated with enlargement of the
regional lymph nodes.

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 Enlargement of the nodes of the posterior cervical Life Cycle and Pathogenesis 79
triangle is known as ‘Winterbottom’s sign’and is  The nymphal stage of the deer tick Ixodes scapularis
characteristic of T. brucei gambiense infection. is the primary vector for transmission of B. microti.
 Hematogenous and lymphatic dissemination is Transmission occurs from May through September
marked by the onset of fever, headache, arthralgia, with three-fourths of cases presenting in June and
lymphadenopathy and hepatosplenomegaly. July. The incubation period is 1–6 weeks. Babesiosis
 If untreated, CNS gets involved, producing sleepi- can also be acquired through blood transfusion.
ness during the day (hence called sleeping sickness), There are case reports of congenital babesiosis also.
nighttime insomnia, mental confusion, coma and
death. CNS involvement occurs weeks to months Clinical Features
after the initial infection.
 Babesiosis causes malaria-like illness with fever and
 In rhodesience infection, death from myocarditis
hemolytic anemia. Patients present with fever
and intercurrent infection can occur before sleeping
associated with chills, sweats, headache, myalgia,
sickness.
anorexia, dry cough, arthralgia, and nausea.
Diagnosis  Physical examination is usually normal except for
fever. Occasionally, hepatosplenomegaly may be
 Microscopic examination of fluid expressed from seen. Rarely jaundice, pharyngeal erythema, retinal
the chancre or wet blood film may show trypano- infarcts, and retinopathy with splinter hemorrhages
somes. Thick and thin blood smears will also show is seen.
trypanosomes. Concentration methods like
 Severe babesiosis can occur in immunocompro-
centrifugation can be used if trypanosomes are not
mised states such as asplenia, HIV/AIDS, malig-
seen by the above methods. Lymph node aspirate
nancy, and immunosuppression. Complications
and CSF can also show the parasites. CSF
such as ARDS, disseminated intravascular coagula-
examination should be done in all cases of African
tion, congestive heart failure, and renal failure can
trypanosomiasis.
occur in severe babesiosis. Splenic infarcts and
 Serological tests have not become popular because rupture have also been reported.
of variable sensitivity and specificity.
 PCR techniques are not yet commercially available. Diagnosis
Treatment  Babesiosis should be considered in patients who
presents with flu-like symptoms and has recently
 Drugs used in the treatment of African trypano-
resided in or traveled to an endemic area.
somiasis include pentamidine, suramin, eflornithine,
and melarsoprol.  Babesiosis is diagnosed by identification of Babesia
in a peripheral blood smear. Babesia species appear
Prevention as round or pear-shaped organisms inside RBCs.
 Avoid areas which harbor tsetse flies, wear  Polymerase chain reaction (PCR) can be used to
protective clothing and use insect repellents. identify RNA of Babesia.
Chemoprophylaxis is not recommended, and no  Serological tests such as indirect immunofluorescent
vaccine is available at present. antibody test is useful to identify antibodies against
Babesia.
Q. Babesiosis.
Treatment
 Babesiosis is a tick-borne infectious disease caused  Treatment is indicated in symptomatic patients
by parasites of the genus Babesia. These protozoans with positive Babesia tests.
are obligate intracellular parasites of red blood cells  Mild B. microti illness: Oral atovaquone plus azithro-
(RBCs). Wild and domestic animals are the natural mycin for 7–10 days. Clindamycin plus quinine is
reservoirs of Babesia. Transmission to humans is the second choice.
incidental.


 Severe B. microti illness: IV clindamycin plus oral

Infectious Diseases

 There are many species, but Babesia microti is quinine is given for 7–10 days.
responsible for most of the infections.
Q. Toxoplasmosis.
Epidemiology
 Most of the cases occur in the United States.  Toxoplasmosis is a disease caused by an intracellular
Sporadic cases are reported in Europe and the rest parasite Toxoplasma gondii. Toxoplasmosis can be
of the world including India. The number of cases congenital or acquired.
of B. microti illness has increased steadily over the
last decade.
 Congenital toxoplasmosis is transmitted from the
mother to the fetus during pregnancy. 1
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80  Acquired infection is due to ingestion of cysts Acute Toxoplasmosis
excreted in the feces of infected cats or from eating  Majority of acute infections are asymptomatic.
undercooked meat (especially lamb and pork). Some patients may present with non-tender cervical
 Infection can also be acquired through blood or axillary lymphadenopathy. There may be fever,
transfusion and organ transplantation. pharyngitis, maculopapular rash and hepato-
splenomegaly (hence mistaken for infectious mono-
Life Cycle and Pathogenesis nucleosis).
 The cat is the definitive host in which the sexual
phase of the cycle takes place. Asexual cycle occurs Central Nervous System (CNS) Toxoplasmosis
in other mammals (including humans). Oocysts are  Symptomatic CNS disease is mainly seen in
formed in the cat and shed in feces. Vegetables immunocompromised patients such as AIDS
or grass contaminated by cat feces can be ingested patients. It presents as encephalitis and ring-
by animals, birds, and humans. Ingested oocysts enhancing intracranial lesions seen on CT or MRI
become cysts (bradyzoites) in the muscle of scans. Clinical features are headache, altered mental
animals. status, seizures, coma, fever, and sometimes focal
 Human infection occurs by ingestion of oocysts in neurologic deficits.
food or water contaminated with cat feces (most
common mode of infection) or by eating raw or Congenital Toxoplasmosis
undercooked meat containing cysts, most commonly  Infected children develop neurologic complications
lamb, pork, or rarely beef. Toxoplasmosis can be such as hydrocephalus, microcephaly, mental
transmitted transplacentally if the mother becomes retardation, chorioretinitis and epilepsy.
infected during pregnancy.
 After ingestion of oocysts or tissue cysts, tachyzoites Ocular Toxoplasmosis
are released and spread throughout the body. This  Presents with retinitis and choroiditis. Symptoms
acute infection is followed by the formation of tissue are ocular pain, blurred vision, and sometimes
cysts in many organs especially in CNS, eyes, heart, blindness.
lungs, and adrenals. The cysts can reactivate later
in immunocompromised patients such as AIDS Disseminated Disease
patients.  Usually seen in immunocompromised patients.
They may present with pneumonitis, myocarditis,
Clinical Features polymyositis, diffuse maculopapular rash, and high
Infections may manifest in several ways as follows: fevers. This may occur with or without CNS disease.
 Acute toxoplasmosis

 CNS toxoplasmosis
Investigations
 Congenital toxoplasmosis  Serological tests like detection of antibodies are
 Ocular toxoplasmosis helpful in the diagnosis. A rise in the titre of IgM
 Disseminated disease. antibodies indicates acute infection. Antibodies
persisting in an infant beyond 6 months of age
imply congenital toxoplasmosis.
 Biopsy of a lymph node may show tachyzoites or
histological changes.
 Contrast CT or MRI of brain should be done in
Manipal Prep Manual of Medicine

suspected CNS toxoplasmosis which will show

multiple ring enhancing lesions. Toxoplasma may
also be demonstrated in the CSF of immuno-
compromised patients.
 PCR techniques have high sensitivity and specificity
and are recent developments.

Management
 Immunocompetent persons do not require specific
treatment as the infection usually resolves sponta-
neously. But infants, immunosuppressed patients


and those with eye involvement require treatment.

1 Figure 1.19 Life cycle of toxoplasmosis

 A combination of pyrimethamine plus either
sulfadiazine or clindamycin is used for treatment.

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 For immunocompromised persons (such as HIV Clinical Features 81
patients), trimethoprim–sulfamethoxazole (TMP–  The incubation period is 1–2 months.
SMX) can be used as an alternative to above  Patients with pneumocystis pneumonia present
treatment. AIDS patients who are seropositive with fever, dyspnea, and dry cough. Physical
for T. gondii and who have a CD4+ T lymphocyte findings include tachypnea, tachycardia, and
count of <100/mcL should receive trimethoprim- cyanosis, but there are few lung findings (i.e.
sulfamethoxazole (TMP-SMX) as prophylaxis symptoms are more than signs). Pneumothorax
against toxoplasmosis. may occur sometimes and management is difficult.
 Although pneumocystis usually remains confined
Toxoplasmosis and Pregnancy
to the lungs, disseminated infection can occur and
 If a seronegative woman acquires toxoplasmosis in involves lymph nodes, spleen, liver, and bone
first trimester of pregnancy, there is a high risk of marrow. Eye lesions (choroiditis) also occur and
fetal damage. Hence, termination of pregnancy may be confused with CMV retinitis.
should be considered in such women.
 If a woman is already seropositive before becoming Investigations
pregnant, then there is no risk of fetal damage.  Chest X-ray shows bilateral diffuse infiltrates mainly
 Spiramycin 1 g qid for 4–6 weeks is safe for use in the perihilar regions.
during pregnancy.  ABG (arterial blood gas) analysis shows reduced
arterial oxygen pressure (PaO2), and respiratory
Q. Describe the pathogenesis, clinical features, investiga- alkalosis. There is increased alveolar-arterial
tions and treatment of Pneumocystis infection. oxygen gradient (PAO2 – PaO2). PAO2 – PaO2 of
Q. Pneumocystis jiroveci pneumonia (Pneumocystis >35 mmHg indicates poor prognosis.
carinii).  Pulmonary function tests show reduced diffusing
capacity of the lung (DLCO) and an increased
 Pneumocystis jiroveci (formerly known as Pneumo- uptake of tracer with nuclear imaging (gallium-67
cystis carinii) is an opportunistic fungal pulmonary citrate scan).
pathogen and is an important cause of pneumonia  Serum lactate dehydrogenase (LDH) levels are usually
in the immunocompromised individuals. elevated due to lung parenchymal damage.
 Pneumocystis is now classified as a fungus.  Since there is little sputum production, sputum can
However, unlike fungi, pneumocystis lacks ergo- be induced by inhalation of 3% saline and stained
sterol and is not susceptible to antifungal drugs. with methenamine silver and toluidine blue which
 Pneumocystis has worldwide distribution and most selectively stain the wall of P. carinii cysts. Fiber-
people are exposed to the organism in childhood optic bronchoscopy with bronchoalveolar lavage
itself. (BAL) is more sensitive (>90%) than induced
sputum.
Pathogenesis
 Transbronchial biopsy and open lung biopsy are per-
 Pneumocystis infection develops usually in immuno- formed only when the diagnosis remains in doubt.
compromised individuals. HIV patients who have
CD4+ counts below 200/μL have high chances of Treatment
developing Pneumocystis jiroveci infection. Other
 Treatment should be started as soon as the
persons at risk are patients on immunosuppressive
diagnosis is suspected.
therapy (particularly glucocorticoids) for cancer,
organ transplantation, and other disorders; children  Trimethoprim–sulphamethoxazole (TMP–SMX) is
with primary immunodeficiency diseases; and the drug of choice for all types of pneumocystis
premature malnourished infants. infections and is given for 14 days in non-HIV
infected patients and 21 days in HIV-infected
 After being inhaled, pneumocystis reaches the
patients. Other effective drugs include clindamycin,
alveoli, and attaches to type I alveolar cells. The
pentamidine and trimetrexate. Intravenous therapy


main defence against pneumocystis is alveolar

may be switched over to oral after improvement.
Infectious Diseases

macrophages, which ingest and kill the organism.

If the immune system of the host is compromised,  High-dose steroids improve the prognosis in HIV
Pneumocystis multiplies and damages the type I infected patients with pneumocystosis. However,
alveolar cells, alters surfactant, and increases one should be cautious about associated tuber-
alveolar capillary permeability. Lung sections culosis or fungal infection.
stained with hematoxylin and eosin, show the
alveoli filled with a foamy exudate. In severe Prevention
disease, there is interstitial edema, fibrosis, and
hyaline membrane formation.
 Primary prophylaxis is indicated for HIV-infected
patients with CD4 counts less than 200 cells/cumm. 1
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82 Secondary prophylaxis is indicated for patients with Q. Taenia saginata (beef tapeworm).
prior pneumocystosis.
 T. saginata (also called the cattle or beef tapeworm)
 TMP–SMX (one double strength tablet once daily)
is the drug of choice. Dapsone (100 mg OD) is an occurs in all countries where raw or undercooked
alternative. beef is eaten. This worm can reach 8 metres in length.

Q. Name the different tapeworms which infest human Life Cycle

beings.  Humans are the only definitive host for the adult
stage of T. saginata and cattle are intermediate hosts.
It lives in the upper jejunum. It attaches to jejunal
mucosa through a scolex which has four suckers.
Eggs are passed in the feaces and can live for
months to years on vegetation. Cattle may ingest
these eggs while grazing. Inside the cattle intestine,
the embryo is released which invades the intestinal
wall, carried to striated muscle, where it becomes a
cysticercus. When raw or undercooked beef is eaten
by humans, this cysticercus can grow into adult
worm.

Figure 1.20 Tapeworm Clinical Features

 Cestodes or tapeworms, are segmented worms.  Patients may notice worm segments (proglottids)
 Adult worms reside in the gastrointestinal tract, but in their feces. The proglottids are often motile.
the larvae can be found in any organ.  Abdominal pain or discomfort, nausea, decreased
 Humans are either the definitive hosts where the appetite, weakness, and weight loss can occur.
adult worms reside in GIT (Taenia saginata,
Diphyllobothrium, Hymenolepis, and Dipylidium Diagnosis
caninum) or the humans are intermediate  Detection of eggs or proglottids in the stool. Eggs
hosts where larval-stage parasites are present in may also be present in the perianal area; thus, if
the tissues (echinococcosis, sparganosis, and proglottids or eggs are not found in the stool, the
coenurosis). perianal region should be examined with use of a
 For Taenia solium, humans can be both definitive cellophane-tape swab.
and intermediate hosts.
 Eosinophilia and elevated serum IgE levels may be
 An adult tapeworm consists of a head (scolex), a
present.
neck, and a chain of individual segments
(proglottids). The scolex is the attachment organ
Treatment
through which tapeworm attaches to the intestinal
mucosa. Neck is the narrow part behind scolex from  Praziquantel, given as a single dose (10 mg/kg) is
which proglottids (segments) form. Mature effective against this tapeworm. Niclosamide (2 g)
proglottids produce eggs. Proglottids are is an alternative.
hermophrodites and cross-fertilisation between
proglottids occurs. Big worms can be several metres Prevention
Manipal Prep Manual of Medicine

in length. The entire worm is covered with an elastic  Proper cooking of beef and pork, inspection of beef
cuticle. Tapeworms absorb nutrients directly before cooking, and proper disposal of human
through the cuticle since they do not have any GI feces are measures which can prevent T. saginata
tract. infestation.
 Five tapeworms commonly infect humans. These
are: Q. Taenia solium and cysticercosis (pork
Large tapeworms Small tapeworms
tapeworm).
Taenia saginata Hymenolepis nana  T. solium is the pork tapeworm.
(beef tapeworm) (dwarf tapeworm)
 It can cause two forms of infection. In humans,
Taenia solium Echinococcus granulosis infection can be with adult tapeworm in the
(pork tapeworm) (dog tapeworm)


intestine or with larval forms in the tissues

(cysticercosis).
1
Diphyllobothrium latum
(fish tapeworm)
 It has worldwide distribution.

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Life Cycle Diagnosis 83
 Humans are the only definitive hosts for T. solium;  Stool examination may show eggs or worm segments.
pigs are the usual intermediate hosts. The adult  Definitive diagnosis of cysticercosis is difficult
tapeworm usually stays in the upper jejunum. It because it requires biopsy and histopathological
has a scolex with two sucking disks through which studies which are sometimes difficult to obtain as
it attaches to the mucosa. The adult worm is about in brain infection. However, a clinical diagnosis can
3 m in length and may live for years. Proglottids be made based on clinical features, imaging studies,
(segments) contain eggs and are passed in the feces. serologic tests, and exposure history.
Eggs can survive in the environment for many
months. These eggs are infective to humans and Treatment
animals. If eggs are ingested by animals and man,
the larvae are released in the intestine, penetrate Intestinal Infection
the intestinal wall, and are carried to many tissues.  Praziquantel (10 mg/kg) as a single dose is effec-
In the tissues, larvas become encysted in 2–3 months tive. Niclosamide (2 g) is an alternative.
(cysticerci). These cysticerci can survive for months
to years. Humans also acquire infection by ingesting Neurocysticercosis
undercooked pork containing cysticerci. In this case
 Praziquantel 50 to 60 mg/kg daily in three divided
ingested cysticerci develop into adult tapeworms
in the intestine. Autoinfection may occur if an doses for 15 days or albendazole (15 mg/kg per day
individual ingests eggs from his own feces. for 8 to 28 days) hasten the resolution of cysticercosis.
 Both drugs can exacerbate the inflammatory
Clinical Manifestations response due to dying parasites which may be
 Intestinal infection with T. solium is usually prevented by addition of steroids.
asymptomatic or produces epigastric discomfort,  Antiepileptics for seizures.
nausea, weight loss, and diarrhea. Worm segments  Obstructive hydrocephalus is treated by the
(proglottids) may be noted in feces. removal of the cysticercus via endoscopic surgery
 In cysticercosis, the clinical manifestations depend or by ventriculoperitoneal shunting.
on the location of cysticerci. Cysticerci are
commonly found in the brain, skeletal muscle, Prevention of T. solium Infection
subcutaneous tissue, and eye.  Same as for T. saginata infection.
 Cysticerci in the brain act like space occupying
lesions. Seizures, hydrocephalus (due to obstruction
of CSF flow by cysticerci), signs of raised intra- Q. Diphyllobothriasis.
cranial pressure including headache, nausea,  Diphyllobothrium latum (fish tapeworm) a parasite
vomiting, changes in vision, dizziness, ataxia, or
of freshwater fish. D. latum is the largest parasite
confusion, may be present. Patients with hydro-
of humans (up to 10 m in length).
cephalus may develop papilledema or display
altered mental status. Chronic meningitis and
Life Cycle
strokes can also occur.
 In the eye they may cause blindness.  The adult tapeworm lives usually in the ileum and
occasionally in the jejunum. The adult worm has
3000 to 4000 proglottids (segments) which release
eggs daily into the feces. If an egg reaches water, it
hatches and releases a free-swimming larva which
is eaten by Cyclops. Inside the Cyclops the larva
develops into a procercoid which is swallowed by
a fish. Inside the fish, the larva migrates into the
fish’s flesh and grows into a sparganum larva.
Humans acquire the infection by ingesting infected
raw fish. Inside the human intestine, the larva

Infectious Diseases

matures into an adult worm. Diphyllobothriasis

occurs worldwide, especially where lakes are
contaminated by sewage.

Clinical Manifestations
 Most D. latum infections are asymptomatic. Some
may have abdominal discomfort, diarrhea, vomit-

Figure 1.21 Life cycle of Taenia solium

ing, weakness, and weight loss. Rarely worm can
cause intestinal obstruction, cholangitis or chole- 1
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84 cystitis. Because the tapeworm absorbs vitamin B12,
vitamin B12 deficiency can develop which manifests
as megaloblastic anemia.

Diagnosis
 Stool examination may show eggs or worm seg-
ments (proglottids) in the stool. Eosinophilia may
be present.

Treatment
 Praziquantel, 5 to 10 mg/kg as a single dose is
highly effective. Niclosamide (2 g) is an alternative.

Q. Hymenolepis nana (dwarf tapeworm).

 This is the most common and smallest tapeworm
(2–4 cm in length) infesting human beings. H. nana
is endemic all over the world. Infection is spread
by feco-oral contamination.
Figure 1.22 Life cycle of dog tapeworm (hydatid cyst)
Life Cycle
eggs are ingested by intermediate hosts—sheep,
 H. nana is the only tapeworm which does not
cattle, humans, goats, camels, and horses either
require an intermediate host. Both the larval and
through vegetables or while grazing. Eggs develop
adult phases take place in the humans. The adult
into cysts in the muscles of intermediate hosts.
worm resides in the proximal ileum. The eggs are
When a dog ingests beef or lamb containing cysts,
released into the feces and when ingested by a new
they develop into adult worms in dogs and life cycle
host, the oncosphere is freed and penetrates the
is completed.
intestinal villi, becoming a cysticercoid larva. Larva
migrates back into the intestinal lumen, attaches to  When humans ingest the eggs, embryos escape
the mucosa, and matures into adult worm. Eggs from the eggs, penetrate the intestinal mucosa, enter
may also hatch before passing into the stool, causing the portal circulation, and are carried to various
internal autoinfection. organs, most commonly the liver and lungs where
they develop into fluid-filled unilocular hydatid
Clinical Manifestations cysts. These cysts consist of an external membrane
 Infection is usually asymptomatic. Occasionally ano- and an inner germinal layer. Daughter cysts and
rexia, abdominal pain, and diarrhea may be seen. brood capsules develop from the inner germinal
layer. New larvae, called protoscolices, develop
Diagnosis within the brood capsule. The cysts expand slowly
over a period of years.
 Detection of eggs in the stool.
 The life cycle of E. multilocularis is same except that
Treatment the intermediate hosts are rodents.
 Praziquantel (25 mg/kg once) is the drug of choice. Clinical Manifestations
It is effective against both the adult worms and the
Echinococcal cysts remain asymptomatic until their
Manipal Prep Manual of Medicine

cysticercoids. Niclosamide (2 g) is an alternative. 

expanding size elicits symptoms in the involved

Q. Echinococcosis (dog tapeworm) (hydatid cyst). organ. Liver and lungs are involved commonly.
Patients with liver cysts often present with
 Echinococcosis is an infection caused in humans abdominal pain or a palpable mass in the right
by the larval stage of Echinococcus granulosus, upper quadrant. Compression of a bile duct can
E. multilocularis, or E. vogeli. cause biliary obstruction and jaundice. Involvement
 E. granulosus produces unilocular cystic lesions. of bone leads to pathologic fractures, CNS
E. multilocularis causes multilocular lesions. E. vogeli involvement leads to seizure, neurological deficits
causes polycystic hydatid disease. and raised ICT. Involvement of the heart leads to
conduction defects and pericarditis.
Life Cycle  Rupture or leakage of hydatid cyst fluid may


 Like other cestodes, echinococcal species have both produce fever, pruritus, urticaria, eosinophilia, or
1 intermediate and definitive hosts. The definitive
hosts are dogs that pass eggs in their feces. These
anaphylaxis. Lung hydatid cysts may rupture into
the bronchi or peritoneal cavity and produce cough,

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 chest pain, or hemoptysis. Rupture of hydatid cysts communicating with the biliary tree. Albendazole 85
may lead to dissemination of protoscolices, which (15 mg/kg daily in two divided doses) should be
can develop into additional cysts. Rupture can given for at least 4 days before the procedure and
occur spontaneously or at surgery. continued for at least 4 weeks afterward.
 The larval forms of E. multilocularis present as  For complicated E. granulosus cysts (e.g. those
slowly growing mass in the liver with destruction communicating with the biliary tree), surgery is the
of hepatic parenchyma. These cysts may lead to treatment of choice. Pericystectomy is the procedure
obstruction of biliary tree leading to obstructive of choice, where the entire cyst and the surrounding
jaundice, or invade adjacent structures like fibrous tissue are removed. There is a risk of spillage
diaphragm, kidneys and lungs. of cyst contents during surgery. Albendazole
should be given for several days before resection
Diagnosis and for several weeks after resection. Praziquantel
 MRI, CT, and ultrasound can define the site and (50 mg/kg daily for 2 weeks), may hasten the death
size of echinococcal cysts. of the protoscolices.
 Examination of aspirated fluid from cyst for proto-  Medical therapy with albendazole alone for
scolices or hooklets can make a definite diagnosis 12 weeks to 6 months results in cure in ~30% of
of E. granulosus infection, but is not usually cases and improvement in another 50%.
recommended because of the risk of fluid leakage  Surgical resection remains the treatment of choice
resulting in either dissemination of infection or for E. multilocularis infection.
anaphylactic reactions.
 Serologic studies for antibodies can be useful, but Q. Name the different intestinal nematodes that infest
negative result does not rule out the diagnosis. man.

Treatment Intestinal Nematodes

 For uncomplicated E. granulosus cysts, PAIR  Intestinal nematodes are roundworms. Their length
(percutaneous aspiration, infusion of scolicidal varies from 1 mm to many centimetres. There are
agents, and respiration) is now the treatment of more than a billion people worldwide who are
choice. PAIR is contraindicated for superficially infected with intestinal nematodes. Though
located cysts (because of the risk of rupture), for nematode infections are not usually fatal, they can
cysts with multiple internal septae, and for cysts cause malnutrition and diminished work capacity.

TABLE 1.18: Intestinal nematodes infesting man

Ascaris Hookworm (Necator Strongyloides Trichuris trichiura Enterobius
lumbricoides americanus, stercoralis (whipworm) vermicularis
(roundworm) ancylostoma (pinworm)
duodenale)
Endemic areas Worldwide Hot, humid regions Hot, humid regions Worldwide Worldwide
Infective stage Egg Filariform larva Filariform larva Egg Egg
Route of infection Oral Percutaneous Percutaneous Oral Oral
Gastrointestinal Jejunum Jejunum Small intestine Cecum, colon Cecum, appendix
location of worms
Adult worm size 15–35 cm 0.7–1.2 cm 2 mm 3–5 cm 0.8–1.3 cm
Pulmonary passage Yes Yes Yes No No
of larvae
Incubation period 60–75 40–100 17–28 70–90 35–45
(days)
Lifspan 1 – 2 years 2 – 8years Decades (owing to 5 years 2 months
autoinfection)

Infectious Diseases

Main symptoms Usually asympto- Iron-deficiency Gastrointestinal Gastrointestinal Perianal pruritus

matic. Rarely anemia symptoms, symptoms, anemia
gastrointestinal or malabsorption
biliary obstruction
Diagnosis Detection of eggs Detection of eggs Detection of larvae Detection of eggs Detection of eggs
in stool in fresh stool, in stool or duodenal in stool from perianal skin on
larvae in old stool aspirate cellulose acetate tape
Treatment Mebendazole Mebendazole Ivermectin Mebendazole Mebendazole

1
Albendazole Albendazole Albendazole Albendazole Albendazole
Pyrantel pamoate Pyrantel pamoate Thiabendazole Pyrantel pamoate

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86 Q. Describe the, lifecycle, clinical features, diagnosis  In heavy infections, a large number of worms can
and treatment of intestinal. get entangled and cause intestinal obstruction.
Single worm may migrate into and occlude the
 Ascaris is a nematode seen worldwide. biliary tree, causing biliary colic, cholecystitis,
 It is transmitted through feco-oral route and is cholangitis, and pancreatitis. Sometimes worms
common in areas of poor sanitation. may come out of mouth or nose.
 The length of adult ascaris is 15–35 cm.
Diagnosis
Life Cycle
 Detection of ascaris eggs in the stool sample.
 Adult worms live in the small intestine for 1 to  Detection of larvae in sputum or gastric aspirates
2 years. Female Ascaris worms produce eggs which when they migrate through the lungs.
are passed in the stools. These eggs mature in the
 Eosinophilia may be found in the blood in early stages.
soil and become infective after several weeks. Eggs
 The large adult worm shadows may be visualized
can remain infective for many years. When a person
occasionally on contrast studies of the gastro-
swallows these eggs, eggs hatch in the intestine and
intestinal tract. A plain abdominal X-ray may show
produce larvae. These larvae invade the intestinal
masses of worms in gas-filled loops of bowel in
mucosa, reach lungs through circulation, break into
patients with intestinal obstruction.
the alveoli, ascend the bronchial tree, and are
swallowed. They reach small intestine and develop  Pancreaticobiliary worms can be detected by
into adult worms. About 2 and 3 months are ultrasound and endoscopic retrograde cholangio-
required from swallowing of eggs to development pancreatography (ERCP).
of adult worms
Treatment
Clinical Features  Albendazole (400 mg once), or mebendazole (500
 Most infected individuals are asymptomatic. mg once) is effective against ascariasis. These drugs
Symptoms arise due to larval migration through are contraindicated in pregnancy and instead
the lungs or adult worms in the intestines. pyrantel pamoate (11 mg/kg once; maximum, 1 g)
 When the larvae migrate through the lungs, patients can be used in pregnancy. Intestinal obstruction
may develop a dry cough and burning substernal requires surgery.
discomfort worsened by coughing or deep
inspiration. Sometimes dyspnea and blood-tinged Q. Describe the epidemiology, lifecycle, clinical
sputum may be seen. Low grade fever and weight features, diagnosis and treatment of hookworm
loss may be present. All these features may be infestation.
mistaken for pulmonary tuberculosis. Eosinophilia
develops during this symptomatic phase and Epidemiology
subsides slowly over weeks. Chest X-ray may show  Human hookworm disease is predominantly caused
eosinophilic pneumonitis (Löffler’s syndrome) with by the nematode parasites Necator americanus and
round or oval infiltrates. Ancylostoma duodenale; and rarely by Ancylostoma
ceylonicum, Ancylostoma braziliense, and Ancylostoma
caninum.
 Ancylostoma duodenale is found in Mediterranean
countries, Iran, India, Pakistan, and the Far East.
Necator americanus is found in North and South
Manipal Prep Manual of Medicine

America, Central Africa, Indonesia, and parts of

India. Both are found in many tropical regions,
particularly Southeast Asia.
 It is common in rural areas where defecating in
open fields is common. Barefoot walking is a risk
factor for infection.
 Older children are affected commonly.
 Ancylostoma caninum and Ancylostoma braziliense
are animal hookworms and can cause cutaneous
larva migrans (“creeping eruption”).


Life Cycle

1 Figure 1.23 Life cycle of ascariasis

 Adult hookworms are about 1 cm long. They attach
to the intestinal mucosa through buccal teeth

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  Eosinophilia may be present. 87
 Microcytic hypochromic anemia, occasionally with
eosinophilia is characteristic of chronic hookworm
infestation.

Treatment
 Albendazole (400 mg single dose), or mebendazole
(500 mg single dose), or pyrantel pamoate (11 mg/
kg for 3 days) are highly effective.

Q. Strongyloidiasis.

 Strongyloidiasis is due to Strongyloides stercoralis

which is a helminth.
 In contrast to other helminthic parasites, S.
stercoralis can complete its entire life cycle within
the human host. This unique capacity leads to
repeated cycles of autoinfection and thus
Figure 1.24 Life cycle of hookworm
strongyloidiasis can persist for decades in the
host.
(Ancylostoma) or cutting plates (Necator) and suck
blood (0.5 ml/day per Ancylostoma and 0.03 ml/ Epidemiology
day per each N. americanus) and interstitial fluid.
 S. stercoralis is found in tropical areas and is particu-
The adult hookworms produce thousands of eggs
larly common in Southeast Asia, sub-Saharan
daily. The eggs are passed with feces into the soil,
Africa, and Brazil. It is also found in some parts of
where rhabditiform larvae hatch and develop over
United States.
a 1 week period into filariform larvae. These
filariform larvae penetrate the skin and reach the Life Cycle
lungs through bloodstream. In the lungs, they
invade alveoli and ascend the airways, get Adult female worms of S. stercoralis are about
swallowed and reach the small intestine. In the 2 mm long. Parasitic adult males do not exist and
small intestine they develop into adult worms. It female worms produce eggs by parthenogenesis.
takes about 6 to 8 weeks from skin invasion to Eggs hatch in the intestine itself, releasing rhabditi-
appearance of eggs in the feces. Adult hookworms form larvae which are passed with the feces into soil.
live about 6 to 8 years (A. duodenale) or 2 to 5 years These rhabditiform larvae transform into infectious
(N. americanus). filariform larvae either directly or after a free-living
phase of development in the soil. Humans acquire
Clinical Features strongyloidiasis when filariform larvae penetrate the
skin or mucous membranes and enter the body. These
 Most hookworm infections are asymptomatic. filariform larvae reach the lungs through bloodstream.
 Filariform larvae may cause pruritic maculopapular In the lungs, they invade alveoli and ascend the
dermatitis (“ground itch”) at the site of skin airways, get swallowed and reach the small intestine.
penetration as well as serpiginous tracks when they In the small intestine, larvae mature into adult worms
migrate through subcutaneous tissue (similar to that penetrate the mucosa of the small intestine.
cutaneous larva migrans). Alternatively, rhabditiform larvae in the intestine can
 Larvae migrating through the lungs may cause develop directly into filariform larvae that penetrate
transient pneumonitis. the colonic wall or perianal skin and enter the blood
 Mild epigastric pain or diarrhea may be seen some- stream to repeat the migration that establishes ongoing
times. internal reinfection (autoinfection).


Chronic hookworm infection leads to iron defi-

Infectious Diseases

ciency anemia. Clinical Features

 Most patients are asymptomatic or have mild
Diagnosis cutaneous and/or abdominal symptoms.
 Detection of oval hookworm eggs in the feces. In  Recurrent urticaria is the most common cutaneous
light infections, stool-concentration procedures manifestation.
may be required to detect eggs. Eggs of the two  Migrating larvae can elicit a pathognomonic
species cannot be differentiated by light micro-
scopy.
serpiginous eruption, larva currens (“running
larva”), a pruritic, raised, erythematous lesion that 1
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88 advances as rapidly as 10 cm/h along the course of Epidemiology
larval migration.  It is found all over the world both in the tropics
 Adult worms burrow into the duodenojejunal and subtropics.
mucosa and can cause abdominal (usually  It most commonly affects poor children.
epigastric) pain, which resembles peptic ulcer pain.
Nausea, diarrhea, gastrointestinal bleeding, and Life Cycle
weight loss can occur.
 The adult worms live for many years in the colon
 Immunosuppressed states can lead to disseminated and cecum. Their anterior ends are embedded into
infection where larvae may invade the central the mucosa. Adult female worms produce
nervous system, peritoneum, liver, and kidney. thousands of eggs per day which are passed with
the feces, mature in the soil and become infective.
Diagnosis
After ingestion, infective eggs hatch in the
 Finding rhabditiform larvae in feces is diagnostic. duodenum, releasing larvae which mature and
Since the eggs hatch in the intestine, they are not migrate to the colon. The full cycle takes about
usually found in the feces. Repeated stool examina- 3 months.
tions can improve the sensitivity of stool diagnosis.
 If stool examinations are negative, strongyloides Clinical Features
can be detected by sampling of the duodenojejunal  Most infected persons are asymptomatic.
contents by aspiration or biopsy.  Heavy infections can cause abdominal pain,
 Detection of antibodies against Strongyloides is a anorexia, and diarrhea. Rectal prolapse and growth
sensitive method of diagnosing uncomplicated retardation can happen in children.
infections.
 Eosinophilia is common. Diagnosis
 The characteristic lemon-shaped whipworm eggs
Treatment
may be detected on stool examination. Adult worms
 Ivermectin (200 μg/kg daily for 1 or 2 days) is the can occasionally be seen on proctoscopy.
drug of choice and is more effective than albenda-
zole (400 mg daily for 3 days, repeated at 2 weeks) Treatment
and is better tolerated than thiabendazole (25 mg/kg  Mebendazole (500 mg once for mass treatment or
twice daily for 2 days). Ivermectin should be given 100 mg BD for 3 days for individual patient) or
for at least 5 to 7 days in disseminated strongyloidiasis. albendazole (400 mg daily for 3 doses) or ivermectin
200 μg/kg orally once a day for 3 days are effective
Q. Trichuriasis(whipworm). against whipworm.
 Trichuriasis is caused by infection with the
nematode, Trichuris trichiura. Q. Pinworm infestation (Enterobiasis, Oxyuriasis).
 It is about 4 cm long and has a thin anterior  Pinworm (Enterobius vermicularis) is a small
end and a broad posterior end which gives it a nematode about 1 cm long. It is more common in
characteristic whiplike appearance (hence called temperate countries than in the tropics. School
whipworm). children are affected commonly.

Life Cycle
Humans are the only natural host for enterobius.
Manipal Prep Manual of Medicine

Adult worms live in the terminal ileum and colon.

The female worm migrates out at night into the
perianal region and lays up to 10,000 eggs. Self-
infection results from perianal scratching and trans-
port of eggs by the hands to the mouth. The larvae
hatch and mature within the intestine. This life cycle
takes ~1 month, and adult worms live for ~2 months.
It can spread easily from one person to another.

Clinical Features
 Most pinworm infections are asymptomatic.


Perianal itching is the cardinal symptom. The

1 Figure 1.25 Whipworm
itching is worse at night and is due to the nocturnal
migration of the female worms.

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 Heavy infections can cause abdominal pain and microfilariae, and (4) the pathological syndromes 89
weight loss. they cause.
 Rarely, pinworms invade the female genital tract
and cause vulvovaginitis. Q. Describe the etiology, epidemiology, pathogenesis,
clinical features, diagnosis and treatment of
Diagnosis lymphatic filariasis.
 Since the eggs are deposited in the perianal region,
Q. Wuchereria bancrofti.
they can be detected by the application of clear cello-
phane tape to the perianal region in the morning.  Lymphatic filariasis is caused by Wuchereria bancrofti,
Eggs get attached to the sticky cellophane tape Brugia malayi, and Brugia timori. The thread like
which is then transferred to a slide and examined adult worms live in lymphatic channels or lymph
under microscope for characteristic pinworm eggs, nodes for many years. World Health Organization
which are oval and flattened along one side. (WHO) has identified lymphatic filariasis as one of
the major cause of permanent and long-term dis-
Treatment ability in the world.
 A single dose of mebendazole (100 mg), or albenda-
zole (400 mg), or pyrantel pamoate (11 mg/kg base), Epidemiology
is effective against pinworms. Treatment should be
 W. bancrofti is the most common human filarial
repeated after 2 weeks. All family members should
infection seen all over the world. Humans are the
be treated to eliminate asymptomatic reservoirs of
only definitive host for this parasite. W. bancrofti is
infection.
nocturnally periodic (microfilariae are found in peri-
pheral blood mainly at night). Vectors for W. bancrofti
Q. Emumerate the different filarial species which cause are Culex fatigans mosquitoes in urban settings and
infection in man. anopheles or Aedes mosquitoes in rural areas.
 Filariasis is a group of parasitic infections due to  B. malayi occurs mainly in China, India, Indonesia,
filarial worms (nematodes) (Table 1.19). Filariasis Korea, Japan, Malaysia, and the Philippines.
is transmitted by mosquitoes or other arthropods.  B. timori is seen only on islands of the Indonesian
 Eight filarial species infect humans. Out of these, archipelago.
four: (1) Wuchereria bancrofti, (2) Brugia malayi,
(3) Onchocerca volvulus, and (4) Loa loa—are Pathology
responsible for most infections.  Female adult worms are 8 to 10 cm long; males are
 Adult filarial worms reside in either lymphatic or about 4 cm long. Gravid adult females produce
subcutaneous tissues of humans. Adult worms live microfilariae that circulate in blood. Adult worms
for many years and produce offsprings called live in afferent lymphatics or sinuses of lymph
microfilariae, which either circulate in the blood or nodes and cause dilatation and thickening of
migrate through the skin. lymphatics. An inflammatory reaction develops in
 Microfilariae are ingested by the arthropod vector the lymphatics due to the presence of worms which
and there develop into new infective larvae. further damages lymphatics and their valves
 All filarial worms have similar life cycles but differ leading to tortuous and blocked lymphatics.
in: (1) their vector, (2) the final dwelling place of Blocked and damaged lymphatics lead to
the adult worms, (3) the circadian periodicity of the lymphedema with hard or brawny edema in the

TABLE 1.19: Filarial species causing disease in humans

Worm species Periodicity Vector Dwelling place of Dwelling place of
adult worm microfilariae
Wuchereria bancrofti Nocturnal Mosquitoes Lymphatic vessels Blood

Infectious Diseases

Brugia malayi Nocturnal Mosquitoes Lymphatic vessels Blood

B. timori Nocturnal Mosquitoes Lymphatic tissue Blood
Oncocercus valvulus None Simulium (blackflies) Subcutaneous Skin
Loa loa Diurnal Chrysops (deerflies) Subcutaneous Blood
Mansonella ozzardi None Midges Retroperitoneal Blood and skin
Mansonella perstans None Midges Retroperitoneal Blood
Mansonella streptocerca None Midges Skin Skin 1
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90 overlying skin. Death of the adult worm leads to be collected based on the periodicity of the
increased inflammatory reaction and fibrosis of microfilariae. Nighttime blood sample should be
lymphatics which may be permanent. examined in case of nocturnal periodicity.
 Microfilariae do not have much role in the develop-  Antigen test for W. bancrofti: Antigens of W. bancrofti
ment of lymphedema. can be detected by enzyme-linked immunosorbent
assay (ELISA) and immunochromatographic card
Clinical Features test. There are currently no tests to detect antigens
 Patients with lymphatic filariasis usually present of brugian filariasis.
with subclinical microfilaremia, acute adenolymph-  Antibody tests: Enzyme immunoassay tests for
angitis (ADL), and chronic lymphatic disease. antifilarial antibodies.
 In areas where W. bancrofti or B. malayi is endemic,  Molecular diagnosis: Polymerase chain reaction
most infected individuals are clinically asympto- (PCR) based assays for DNA of W. bancrofti and
matic. Investigations may show microfilariae in the B. malayi in blood have been developed. PCR tests
blood or microscopic hematuria and/or protei- have high sensitivity and can detect infection in
nuria, dilated and tortuous lymphatics on imaging. almost all infected subjects.
Scrotal lymphangiectasia may be detectable by  Elevated eosinophils and serum IgE support the
ultrasound. diagnosis of lymphatic filariasis.
 Only very few of these asymptomatic individuals
develop acute and chronic stages of infection. Acute Differential diagnosis
stage of infection leads to adenolymphangitis which
 Acute filarial lymphangitis and lymphadenitis has
is characterized by fever, lymphangitis, lympha-
to be differentiated from bacterial lymphangitis.
denitis, and transient local edema. Lymphangitis
 Chronic filarial lymphedema must be distinguished
is inflammation of lymphatic vessels and is retro-
from the lymphedema of malignancy, postopera-
grade extending from the lymph node to periphery.
tive scarring, trauma, chronic edematous states, and
In bacterial lymphangitis ascending lymphangitis
congenital lymphatic abnormalities.
is seen. Lymphadenitis is inflammation of lymph
nodes which become enlarged and painful. The
lymphangitis and lymphadenitis can involve both Treatment
the upper and lower limbs. Genital lymphatics  Diethylcarbamazine (DEC) is the drug of choice for
involvement occurs almost exclusively with W. filariasis. It has action on adult worms as well as
bancrofti infection and manifests as funiculitis, microfilariae. It is given in a dose of 6 mg/kg/day
epididymitis, and scrotal pain and tenderness. in three divided doses for 12 days. A single dose of
Hydrocele and scrotal elephantiasis may develop. 6 mg/kg also has equivalent efficacy in reducing
Renal lymphatic involvement leads to rupture of levels of microfilariae. For tropical pulmonary
the renal lymphatics and chyluria. eosinophilia (TPE), a longer DEC treatment course
 Chronic filarial disease develops insidiously after of 14–21 days is generally recommended.
many years and is due to severe lymphatic damage.  Ivermectin is a semisynthetic macrolide antibiotic
This leads to elephantiasis characterized by non- and a single oral dose of 150 μg/kg is useful to
pitting edema due to thickening of the subcuta- clear microfilaria. Ivermectin does not kill adult
neous tissues and hyperkeratosis. Recurrent worms.
infections of these edematous tissues lead to further  A single dose of albendazole plus either DEC or
swelling. ivermectin has been found to be more effective than
Tropical pulmonary eosinophilia (TPE) is another single drug. Recently single dose of a 3-drug
Manipal Prep Manual of Medicine

rare manifestation which causes low grade fever regimen of ivermectin plus diethylcarbamazine and
and wheezing. Blood eosinophil count is usually albendazole has been shown to be more effective
high. It is most likely due to hypersensitivity than the 2 drug combination.
reactions to microfilariae.  Early treatment of asymptomatic persons is
recommended to prevent permanent lymphatic
Diagnosis damage. For adenolymphangitis (ADL), supportive
 Definitive diagnosis can be made by detection of treatment with antipyretics and analgesics is given
adult filarial worms. But this is difficult. Imaging and antibiotics are also indicated if secondary
techniques like ultrasound and Doppler can some- bacterial infection is suspected. In persons who
times identify motile adult worms in the dilated have chronic lymphedema, good local hygiene
lymphatics. should be maintained, and secondary bacterial


 Microscopic examination of blood samples: Micro- infections should be prevented. Hydroceles are
1 filariae can be demonstrated in the blood, hydrocele
fluid, or rarely in other body fluids. Blood should
managed by repeated aspiration or surgical
intervention.

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Prevention and Control  Idiopathic hypereosinophilic syndrome. 91
 Avoidance of mosquito bites by using insect  History of filarial exposure, nocturnal cough and
repellents and mosquito nets reduce the chances of wheezing, high levels of antifilarial antibodies, and
infection. a rapid response to DEC help in differentiating TPE
 Mass treatment with either DEC or ivermectin every from other conditions.
year suppress microfilaremia and interrupts Treatment
transmission.
 Community use of DEC-fortified salt dramatically  DEC should be given at a dosage of 4 to 6 mg/kg
reduces microfilarial density. of body weight divided into 2 or 3 doses per day
for 3 weeks. DEC plus albendazole is more effective
than DEC alone.
Q. Tropical pulmonary eosinophilia.
 Tropical pulmonary eosinophilia (TPE) is a distinct Q. Onchocerciasis (river blindness).
syndrome that develops in some individuals with
lymphatic filariasis.  Onchocerciasis (river blindness) is caused by the
 Males are affected commonly often during the third filarial nematode Onchocerca volvulus. Humans
decade of life. Most cases occur in India, Pakistan, acquire onchocerciasis through the bite of Simulium
Sri Lanka, Brazil, and Southeast Asia. blackflies. Because the fly develops and breeds in
flowing water, onchocerciasis is commonly found
Etiology along rivers and is sometimes referred to as river
blindness.
 Wuchereria bancrofti and Brugia malayi are the main  This disease is seen mainly in Africa.
causes of TPE. It is due to an exaggerated immune
 It affects mainly the skin and eyes. Onchocerciasis
response to microfilariae trapped in the lungs.
is the second leading cause of infectious blindness
worldwide.
Clinical Features
 Patients are usually from filaria-endemic areas. Life Cycle and Pathogenesis
 They usually present with nocturnal dry cough  Man acquires infection by the bite of an infected
and wheezing (probably due to the nocturnal blackfly. Infective larvae of O. volvulus are deposited
periodicity of microfilariae), low-grade fever, and into the skin during bite. The larvae develop into
high blood eosinophil counts (usually >3000 adults worms, which are found in subcutaneous
eosinophils/μL). nodules. The adult female worm releases
 The clinical symptoms are due to allergic and microfilariae that migrate to all tissues. Infection is
inflammatory reactions elicited by the microfilariae transmitted to other persons when a female blackfly
in the lungs. ingests microfilariae from the host and these
 Interstitial fibrosis and lung damage can happen if microfilariae then develop into infective larvae.
this condition is not treated properly. Adult female worms are about 40 to 60 cm in length
and males 3 to 6 cm in length. These worms can
Investigations live up to 18 years.
 Eosinophil count is high (usually >3000 eosino-
Clinical Features
phils/μL).
 Chest X-ray may show increased bronchovascular  In onchocerciasis, tissue damage occurs due to
markings, diffuse miliary lesions or mottled microfilariae and not due to adult worms.
opacities.  In the skin, pruritus and papular rash are the most
 Pulmonary function tests show both restrictive and frequent manifestations. Subcutaneous nodules form
obstructive defects. around the adult worms and are seen commonly
over bony prominences. Chronic inflammatory
 Serum IgE levels and antifilarial antibodies are
changes in skin result in loss of elasticity, atrophy,
elevated.


fibrosis and premature wrinkling.

Infectious Diseases

Differential Diagnosis  In the eye, the most common early finding is con-
junctivitis with photophobia. Corneal inflammation
 Asthma (keratitis) occurs due to microfilaria which leads to
 Allergic bronchopulmonary aspergillosis neovascularization, corneal scarring and formation
 Löffler’s syndrome of opacities. This leads to blindness. Inflammation
 Allergic granulomatosis with angiitis (Churg- in the anterior and posterior chambers frequently
Strauss syndrome) results in anterior uveitis, chorioretinitis, and optic



Systemic vasculitis (Wegener’s granulomatosis)
Chronic eosinophilic pneumonia 
atrophy.
Lymphadenopathy is usually present. 1
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92 Diagnosis Life Cycle
 Diagnosis can be confirmed by the detection of an  Humans are the definitive hosts and Cyclops (a
adult worm in an excised nodule or microfilariae crustacean) are intermediates hosts.
in a skin snip.  Humans acquire infection by drinking water
 Ultrasound can also visualize worm in the sub- containing infected microcrustaceans (Cyclops).
cutaneous nodules. containing infective larvae. The larvae are released,
 Eosinophils and serum IgE levels are elevated. penetrate the bowel wall, and mature in the
 Antibody detection: – Ov16 card test: abdominal cavity into adult worms. After mating,
Antibodies against this antigen adult male worm dies, but gravid female worm
have been shown to yield high sensitivity migrates through the subcutaneous tissue, usually
(approximately 80%) and specificity to lower limb.
(approximately 85%).  A blister forms in the skin and breaks down to form
– An ELISA-based test using a cocktail of 3 an ulcer through which the worm can come out and
antigens (Ov7, Ov11, Ov16) has also been used release motile, rhabditiform larvae into water.
to detect antibodies. It has 97% sensitivity and These rhabditiform larvae are ingested by cyclops
100% specificity. where they develop into infective larvae. Cyclops
 PCR to detect onchocercal DNA in skin snips are release the infective larvae into the water thus
highly sensitive and specific but not available completing the cycle.
everywhere.
 Diethylcarbamazine (DEC) patch test (Mazzotti Clinical Features
reaction): Topical application of DEC in a cream  Guinea worm infection is usually asymptomatic.
base (DEC patch) elicits localized cutaneous But just before blister formation, there is fever and
reactions (pruritus, maculopapular eruptions, allergic symptoms like periorbital edema, wheez-
dermal edema) in response to dying microfilariae ing, and urticaria. The emergence of the worm is
which is highly suggestive of onchocerciasis. associated with local pain and swelling. Sometimes,
the worm is visible to the naked eye when it comes
Treatment out. Fever and local symptoms subside when the
 Ivermectin is the drug of choice for onchocerciasis. blister ruptures releasing larva-rich fluid. The ulcer
It is given as a single oral dose of 150 μg/kg, slowly heals but can become secondarily infected.
repeated at 6- to 12-month intervals for at least Occasionally, the adult worm does not emerge but
10–12 years. Ivermectin kills microfilaria and does becomes encapsulated and calcified.
not kill the adult worms. Ivermectin is contra-
indicated in pregnant or breastfeeding women. Treatment
 Doxycycline can kill the adult worms by killing  Emerging adult worm can be gradually extracted
endosymbiont bacteria Wolbachia which O. by winding a few centimetres on a stick every day.
volvulus requires for survival and embryogenesis. Worms may be excised surgically. Niridazole can
 Moxidectin is a new drug that has been approved be used but not very effective.
for use in onchocerciasis. It has been shown to be  Guineaworm infestation can be prevented by the
superior to ivermectin. provision of safe drinking water.
 Subcutaneous nodules near the head should be
excised (because the adult worms are nearer to the Q. Describe the etiology, lifecycle, clinical features,
eye). investigations and management of schistosomiasis
Manipal Prep Manual of Medicine

(bilharziasis).
Prevention
 Vector control. Etiology
 Community-based administration of ivermectin  Schistosomiasis is also known as bilharziasis after
every 6 to 12 months to interrupt transmission. Theodor Bilharz who first identified the parasite.
It is caused by infection with parasitic blood flukes
Q. Dracunculiasis (guinea worm infection). known as schistosomes. Schistosomes are trema-
todes (flat worms) which belong to the phylum
Etiology Platyhelminthes.
 Dracunculiasis is a parasitic infection caused by  The organisms infect the vasculature of the
Dracunculus medinensis. Female Dracunculus worm gastrointestinal or genitourinary system. Human


is very thin but length is up to 1 meter. schistosomiasis is caused by five species. These are
1  Its incidence has declined dramatically due to global
eradication efforts. But cases still occur in Sudan.
Schistosoma mansoni, S. japonicum, S. mekongi, S.
intercalatum and S. haematobium. S. haematobium

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 causes urinary tract disease and others cause Pathogenesis 93
intestinal disease.  The clinical manifestations seen in schistosomiasis
are due to inflammatory reaction to eggs in the
Epidemiology
tissues. Chronic inflammation leads to granuloma
 Schistosomiasis is found in South America, the formation and irreversible fibrosis.
Caribbean, Africa, the Middle East, and Southeast
Asia. People between 15 and 20 years age group Clinical Features
are affected commonly. It is less common in older
 Most people with intestinal schistosomiasis are
age groups probably due to less water exposure.
asymptomatic. In contrast, most people with urinary
Life Cycle schistosomiasis are symptomatic.
 In general, disease manifestations of schisto-
 Human infection is acquired when infective
somiasis occur in 2 stages: Acute and chronic stages.
cercariae in fresh water penetrate the skin and reach
the subcutaneous tissue. In the subcutaneous tissue,
Acute Infection
cercariae transform into schistosomula which travel
through the bloodstream to the liver, where they  During the phase of cercarial invasion, a form of
mature into adults worms. dermatitis called swimmers’ itch may be seen. It is
 The mature adult worms then migrate through the seen 2 or 3 days after invasion as an itchy maculo-
veins to their ultimate home in the intestinal veins papular rash.
(typically S. japonicum and S. mansoni) or the venous  Acute shistosomiasis syndrome (also called
plexus of urinary bladder (typically S. haematobium). Katayama fever) is seen during worm maturation
Adult worms measure 1 to 2 cm in length. In these and is characterized by a serum sickness-like
organs worms mate and gravid female worms syndrome with fever, generalized lymphadeno-
produces eggs. Eggs can penetrate the venous wall pathy, hepatosplenomegaly and increased eosino-
by enzyme secretion and reach the lumen of the phil counts.
intestine or urinary bladder from where they are
passed with stools or urine. Some eggs are carried Chronic Infection
by venous blood flow to the liver and other organs  The clinical manifestations of chronic schisto-
(e.g. lungs, central nervous system, spinal cord). somiasis are species-dependent. Egg deposition
Excreted eggs hatch in freshwater, releasing in the intestinal wall (S. mansoni, S. japonicum,
miracidia (first larval stage) which enter snails. S. mekongi, and S. intercalatum) causes colicky
After multiplication in snail, thousands of free- abdominal pain and bloody diarrhea. Eggs can
swimming cercariae are released which are ready penetrate the bowel adjacent to mesenteric vessels
to infect humans. where adult worms are residing. Unshed eggs,


Infectious Diseases

Figure 1.26 Lifecycle of schistosomiasis 1

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94 which are swept back to the portal circulation Prevention and Control
induce granulomatous reaction in the portal tracts  Travelers should avoid fresh water contact espe-
leading to presinusoidal blockage and portal cially in endemic areas.
hypertension. Portal hypertension can lead to  Application of molluscicides, provision of safe
esophageal varices and splenomegaly. Right and water and disposal of sewage, chemotherapy, and
left upper-quadrant “dragging” pain may be health education are all effective in reducing the
experienced due to hepatomegaly and splenomegaly prevalence of schistosomiasis.
respectively. Bleeding from esophageal varices may
cause hematemesis and malena and may be the first
Q. List the important fungi affecting human beings.
manifestation of the disease. In late-stage disease,
cirrhosis and liver failure may develop.  Fungi are universally present in nature but only a
 Deposition of eggs in the urinary bladder (S. few fungi belonging to Eumycetes group are
haematobium) causes inflammation and granuloma pathogenic to man.
formation in the urinary bladder leading to dysuria,  The eumycetes group can be divided into:
increased frequency, and hematuria. Obstruction 1. Moulds (filamentous, mycelial fungi), e.g. the
of the lower end of the ureters results in hydroureter ringworm fungi, actinomycetes.
and hydronephrosis. Bladder granulomas undergo
2. Yeasts (unicellular fungi), e.g. Cryptococcus
fibrosis and result in typical sandy patches visible
neoformans.
on cystoscopy. Squamous cell carcinoma has been
3. Yeast-like fungi, e.g. Candida albicans.
observed to develop in damaged bladder; hence,
S. haematobium has now been classified as a human 4. Dimorphic fungi, e.g. Histoplasma capsulatum,
carcinogen. Blastomyces dermatitidis, Sporothrix schenckii
 Lungs can also get affected in schistosomiasis.
Embolized eggs lodge in small lung arterioles, and Q. Describe the etiology, clinical features,
produce acute necrotizing arteriolitis and granu- diagnosis and treatment of candidiasis.
loma formation. Later, fibrosis leads to endarteritis
obliterans, pulmonary hypertension, and cor Etiology
pulmonale.  Candidiasis is a fungal infection caused by yeasts
 CNS schistosomiasis occurs when eggs which are that belong to the genus Candida. Out of many
carried to the brain induce a granulomatous species of candida, Candida albicans is the most
response and fibrosis. Patients may present with common yeast causing human disease.
epilepsy. Transverse myelitis may also be seen due  Candida albicans is a normal oropharyngeal and
to eggs traveling to the venous plexus around the gastrointestinal commensal.
spinal cord. Patients with transverse myelitis  Candida species reproduce asexually by budding.
present with lower limb weakness accompanied by
bladder dysfunction. Clinical Features
 Oropharyngeal candidiasis (thrush) is common in
Diagnosis
neonates, patients with diabetes mellitus, HIV
 History of travel to endemic areas and exposure to infection, dentures, patients treated with antibiotics,
freshwater bodies is central to diagnosis. chemotherapy, or radiation therapy, patients with
 High blood eosinophil count and presence of xerostomia and those treated with inhaled cortico-
schistosomal antibodies is highly suggestive of steroids. Oral candidiasis (thrush) presents as well
infection. Schistosomal antibodies can be detected defined, painless adherent white patches in the
Manipal Prep Manual of Medicine

by indirect fluorescent antibody test and ELISA. mouth, tongue and pharyngeal mucosa. HIV
 Examination of stool or urine may show eggs of infection should be ruled out in unexplained oro-
schistosoma. pharyngeal candidiasis.
 Plain X-ray of the abdomen or CT scan may reveal  Cutaneous candidiasis usually occurs in macerated
intramural calcification in the wall of the bladder skin, such as diapered area of infants, under
or colon. pendulous breasts. It presents as red macerated
 Schistosome infection can also be diagnosed by areas, paronychia, balanitis, or pruritus ani. Partial
examination of tissue samples, usually rectal alopecia can occur in scalp infections.
biopsies and rarely liver biopsy.  Vulvovaginal candidiasis is especially common in the
third trimester of pregnancy. It causes pruritus, white
Treatment discharge, and sometimes pain on intercourse.


 Infections with all major Schistosoma species can be  Esophageal candidiasis can cause substernal pain

1 treated with praziquantel. Steroids can be given

along with praziquantel to suppress inflammation.
or dysphagia. Most lesions occur in the distal third
of the esophagus.

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 Systemic candidiasis and septic shock can occur Q. Describe the etiology, clinical features, diagnosis 95
especially in immunocompromised persons. It can and treatment of Aspergillosis.
invade almost any organ. Hematogenous seeding
is particularly common in the retina, kidney, spleen,  The term “aspergillosis” refers to illness due to
and liver. Kidney involvement causes cystitis, allergy, colonization, or tissue invasion by species
pyelitis, or papillary necrosis. Retinal infection of Aspergillus.
appears as unilateral or bilateral small white retinal  Aspergillus species are A. fumigatus (most
exudates. The vitreous humor becomes cloudy, and common), A. flavus, A. niger, A. nidulans, A. terreus,
the patient notices blurring, ocular pain, or a and many other species.
scotoma. Retinal detachment can occur. Infection  Aspergillus is a mold with septate branching
of liver and spleen can occur in patients with acute hyphae. Aspergillus is ubiquitous in the environ-
leukemia recovering from profound neutropenia. ment, and is present on dead leaves, stored grain,
Candida pneumonia is very rare. Candida compost piles, hay, and other decaying vegetation.
endocarditis can occur in previously damaged or  Infection is seen most often in immunocompro-
prosthetic heart valves. The source is often an mised and diabetic persons. Aspergillus can
intravascular catheter or illicit drug injection. Other colonize the damaged bronchial tree, pulmonary
manifestations include arthritis, subacute perito- cysts, or cavities. Balls of hyphae within cysts or
nitis, brain abscess and chronic meningitis. cavities (aspergillomas) may form and can reach
several centimeters in diameter.
Diagnosis
Clinical Manifestations
 Pseudohyphae are seen on a wet KOH smear
prepared from the scrapings of lesion. Diagnosis  Allergic bronchopulmonary aspergillosis (ABPA)
can be confirmed by culture. can occur in patients with asthma and cystic fibrosis
and lead to worsening of wheezing and breathless-
 Since candida is a normal commensal, positive
ness.
cultures of urine, sputum, abdominal drains,
endotracheal aspirates, or the vagina is not  Invasive aspergillosis pneumonia can occur in
diagnostic. immunosuppressed individuals and is difficult to
treat. Aspergillus may invade immunosuppressed
 Blood cultures are useful in the diagnosis of patients through the skin at a site of minor trauma
Candida endocarditis. Serologic tests for antibody or through the upper airway mucosa. Rapid
or antigen are not useful. extension into the adjacent paranasal sinus, orbit,
or face is common. Patients usually have a history
Treatment of chronic allergic rhinitis, and present with painless
 For cutaneous candidiasis, topical antifungals are proptosis, nasal obstruction, or dull aching pain.
effective. Nystatin powder or ciclopirox cream or CT or MRI scan shows a solid mass pushing out
an azole is useful. Clotrimazole, miconazole, the lateral wall of the ethmoid sinus or the medial
econazole, and tolnafate are available as creams or wall of the maxillary sinus.
lotions.  Aspergillus can grow on cerumen and detritus
 For vulvovaginal candidiasis, azoles are better than within the external auditory canal and is called
nystatin preparations. All azoles are equally otomycosis.
efficacious. A single dose of 150 mg fluconazole is  Other manifestations include aspergillus keratitis,
more convenient to use for vulvovaginitis than endophthalmitis, and infection of intracardiac or
topical treatment but is contraindicated in preg- intravascular prostheses.
nancy.
 For oral candidiasis clotrimazole troches can be Diagnosis
used five times a day. Oral fluconazole (150 mg  Detection of hyphae in clinical specimens suggests
daily) can also be used. infection.
For esophageal candidiasis, oral fluconazole (150 mg Fungus ball in the lung is detectable by chest


 
Infectious Diseases

once daily for 2–3 weeks) is the treatment of choice. X-ray.

Itraconazole is an alternative. For azole-resistant  IgG antibody to Aspergillus antigens is found in
oropharyngeal or esophageal candidiasis a 2-week many colonized patients and almost all patients
course of intravenous amphotericin B or caspo- with fungus ball. Serum IgE antibody is raised in
fungin is effective. allergic bronchopulmonary aspergillosis.
 For invasive candidiasis, intravenous amphotericin  Biopsy is required for the diagnosis of invasive
B is the drug of choice. Candida endocarditis aspergillosis of the lungs, nose, and paranasal
requires valve replacement along with long-term
fluconazole administration. 
sinuses, etc.
Blood cultures rarely yield positive results. 1
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96 Treatment  Infection takes place when the organism is
 Fungus ball of the lung usually requires lobectomy. inoculated into the skin—usually on the hand, arm,
 Allergic bronchopulmonary aspergillosis responds or foot, especially during gardening. Pulmonary
to short courses of steroids. infection develops after inhalation. Invasive infec-
tion can occur in immunocompromised persons.
 Invasive aspergillosis is treated with voriconazole,
or itraconazole or liposomal or conventional  Lymphocutaneous sporotrichosis is the commonest
amphotericin B. form seen. A nodule develops at the site of inocula-
tion. This later becomes adherent to the overlying
skin and ulcerates. Within a few days to weeks,
Q. Mucormycosis: Zygomycosis.
similar nodules develop along the lymphatics
Q. Rhinocerebral mucormycosis. draining this area, and these may ulcerate as well.
The lymphatic vessels become indurated and are
 Mucormycosis (zygomycosis, phycomycosis) refers easily palpable.
to opportunistic infections caused by members of  Diagnosis is by culture of the organism. Detection
the genera Rhizopus, Mucor, Absidia, and Cunning- of antibody is useful for diagnosis of disseminated
hamella. disease, especially meningitis.
 Predisposing factors are:  Treatment for localized disease is by itraconazole,
– Diabetic ketoacidosis 200–400 mg orally daily for several months.
– Chronic renal failure Terbinafine, 500 mg twice daily, is also effective.
– Desferoxamine therapy Systemic infection is treated by intravenous
– AIDS amphotericin-B.
– Corticosteroids or cytotoxic drugs  Prognosis is good in lymphocutaneous
 Infection commonly involves sinuses, orbits, and sporo-trichosis, and bad in systemic disease.
the lungs. Disseminated infection can occur in
immunocompromised and those receiving chemo- Q. Adult immunization (vaccination).
therapy
 Immunization enables the body to better defend
Clinical Features itself against diseases caused by certain bacteria or
 The most common clinical presentation of mucor- viruses. When people are immunized against a
mycosis is rhinocerebral infection. Here the disease, they usually do not get the disease or get
infection involves the nose, paranasal sinuses and only a mild form of the disease. However, because
then spreads to orbit and adjacent brain. It should no vaccine is 100% effective, some people who have
be suspected in patients with black necrotic lesions been immunized still may get the disease.
of the nose or sinuses with cranial nerve palsies.  Many diseases have been eradicated by immuniza-
Prognosis is poor in rhinocerebral mucormycosis. tion practice. Example is smallpox which has been
eradicated. Polio is also about to be eradicated by
Diagnosis polio vaccination programmes.
 There are two types of immunization:
 Diagnosis is by demonstrating characteristic fungal
hyphae in secretions and biopsy specimens. – Active immunization (by using vaccines)
Cultures are frequently negative. – Passive immunization (by using antibodies)

Treatment Adult Vaccination

Routine immunization against various diseases is
Manipal Prep Manual of Medicine

 Treatment is by high-dose amphotericin B (1–1.5 

mg/kg/d intravenously) or a lipid preparation of given for all children. Similarly, adults are also at
amphotericin B for prolonged periods. Posacona- risk of developing many diseases and many
zole is also effective. Control of diabetes and other vaccines are recommended for them also.
underlying conditions is important. Extensive
Vaccines may be made from one of the following:
surgical removal of necrotic involved tissue is
 Non-infectious fragments of bacteria or viruses (e.g.
essential for cure.
hepatitis B vaccine).
 A toxin that is produced by a bacteria but has been
Q. Sporotrichosis.
modified to be harmless called a toxoid (e.g. tetanus,
 Sporotrichosis is a chronic fungal infection caused toxoid).
by Sporothrix schenckii.  Weakened (attenuated), live whole organisms that


 It is seen worldwide but most cases occur in do not cause illness (e.g. oral polio vaccine).

1 Americas and Japan. It is found in soil, sphagnum

moss, and decaying wood.
 Following vaccines are recommended for all adults

unless there are contraindications. Certain vaccines

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TABLE 1.20 97
Disease Who should be vaccinated Dose and administration Major brands available
Chickenpox (varicella) All adults who have not had 2-dose series 4–8 weeks apart Varilrix
the vaccine or the disease
Varicella zoster or herpes All adults above 50 years It is given as a 2-dose series, Shingrix
zoster with the second shot admini-
stered 2 to 6 months after the
first shot
Tetanus and diphtheria All adults as a combination booster Every 10 years TENIVAC
vaccine with tetanus. Tetanus Given IM into deltoid TDVAX
vaccine alone can be given if
there is a contaminated wound
Pertussis (whooping cough) All adults (usually given as a Given IM into deltoid BOOSTRIX (this is a 3 in
combination vaccine with tetanus one vaccine)
and diphtheria (Tdap—tetanus,
diphtheria, and acellular pertussis)
if they have not already been
vaccinated
Pregnant women during each
pregnancy
Haemophilus influenzae type b Adults who have not been vacci- Single dose given IM into deltoid HIBERIX
infections (such as meningitis) nated and who are at increased
risk, such as the following:
• People who do not have a
functioning spleen
• People who have a weakened
immune system (such as those
with AIDS)
• People who have had chemo-
therapy for cancer
• People who have had stem cell
transplantation
Hepatitis A All adults who have not been 2-dose series 6–12 months apart Havrix
vaccinated
Hepatitis B All adults who have not been 3 doses at 0,1, and 6 months. ENGERIX-B
vaccinated Booster dose every 5 years. SHANVAC-B
Given IM into deltoid
Influenza All people over age 6 months Given IM into deltoid every year
Pneumococcal infections Adults at increased risk, such as Single dose IM deltoid PRENVAR-13
(such as meningitis and those aged 65 and above, those
pneumonia) with COPD, chronic heart disease,
and diabetes.
Typhoid vaccine Adults at increased risk especially Given as IM injection into deltoid. SHANTYPH
travellers Can be repeated evry 2 to 4 years. TYPBAR
Oral vaccine is also available TYPHERIX
(TYPHORAL) and is given as Typhoral capsules
one capsule on alternate day
for 3 doses

are recommended routinely for all adults at certain vaccines (e.g. rabies, typhoid, yellow fever) are not
ages who have not previously been vaccinated or routinely given but are recommended only for


have no evidence of previous infection. Other specific people and circumstances.

Infectious Diseases

1
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 4

Gastrointestinal System

Q. Define the terms nausea, vomiting, retching,  Indigestion is a nonspecific term that encompasses
regurgitation, rumination and indigestion. a variety of upper abdominal complaints including
nausea, vomiting, heartburn, regurgitation, and
 Nausea is the subjective feeling of need to vomit. It dyspepsia (upper abdominal discomfort or pain).
precedes vomiting and may happen alone, with
retching or vomiting.
Q. Discuss the causes and mechanism of vomiting. How
 Vomiting (or emesis) is the forceful ejection of upper do you approach and manage a case of
gastrointestinal contents through the mouth vomiting?
resulting from contractions of gut and thoraco-  Vomiting (or emesis) is the forceful ejection of upper
abdominal muscles. gastrointestinal contents through the mouth
 Retching is voluntary muscle activity of the resulting from contractions of gut and thoraco-
abdomen and thorax without discharge of gastric abdominal wall musculature.
contents through the mouth.  Vomiting can be projectile or non-projectile. In

 Eructation (belching) is the expulsion of swallowed projectile vomiting, vomiting is not preceded by
gastric air. nausea, whereas in non-projectile vomiting, there
 Regurgitation is effortless return of gastric or is preceding nausea. Projectile vomiting is seen in
esophageal contents into the mouth without nausea. CNS diseases which increase intracranial pressure
It occurs without abdominal, thoracic, or gastro- such brain tumor, meningitis, and intracranial
intestinal muscle contractions. bleed.
 Rumination (merycism) is effortless but purposeful  Most common causes of nausea and vomiting are

regurgitation of food from the stomach into the acute gastroenteritis, systemic febrile illnesses and
mouth, where it is re-chewed and re-swallowed. medications.

TABLE 4.1: Causes of vomiting

Causes Examples
Gastrointestinal diseases Gastritis, cholecystitis, appendicitis, gastroenteritis, intestinal obstruction, peptic ulcer,
pancreatitis, peritonitis
Drugs and toxins Digoxin, levodopa, opiates, anticancer drugs, alcohol excess
Acute infections Hepatitis, influenza, malaria, urinary tract infection
CNS diseases Raised intracranial pressure, meningitis, migraine
Reflex In intense pain (myocardial infarction, ureteric stone)
Psychogenic Unpleasant taste or smell, psychogenic stress, seeing fearful scenes
Labyrinthine disorders Motion sickness, space sickness, viral labyrinthitis, acoustic tumors, and Ménière’s disease
Metabolic causes Uremia, diabetic ketoacidosis, hypercalcaemia, Addison’s disease
Pregnancy
Postoperative

249
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250 Mechanism of Vomiting colicky abdominal pain suggests biliary, ureteric or
 Vomiting is coordinated by the brainstem and is intestinal obstruction. History of missed period in
effected by neuromuscular responses in the gut, a woman of child bearing age suggests pregnancy.
pharynx, and thoracoabdominal wall. There are  Past medical and surgical history: The past medical
three phases of vomiting; nausea, retching and history will reveal the presence of any GI disease
actual act of vomiting. or previous surgeries. History of past abdominal
 There is no single vomiting center as believed surgery may suggest recurrence of the previous
earlier. There are many nuclei in the lateral reticular disease or intestinal obstruction due to peritoneal
formation of the medulla which are stimulated by adhesions.
the chemoreceptor trigger zones (CTZs) in the floor
Physical Examination
of the fourth ventricle, and also by vagal afferents
from the gut. Many causes of vomiting act through  Assessment of the patient’s hydration status and
stimulation of CTZs or vagal afferents. Several vital signs. Tachycardia and hypotension may be
other brainstem nuclei integrate the responses of present if there is hypovolemia. Fever can be
the gastrointestinal, respiratory, pharyngeal, and present in infections.
abdominal muscles during the act of vomiting.  Abdomen should be examined for any abnormality
 During vomiting, thoracic and abdominal muscles such as distension (seen in intestinal obstruction,
contract, producing high intrathoracic and intra- peritonitis), tenderness, guarding (seen in abdominal
abdominal pressures which expel the gastric contents. infections), bowel sounds (increased in intestinal
The gastric cardia herniates through the diaphragm, obstruction and decreased in peritonitis and para-
there is intense salivation and the larynx moves lytic ileus).
upward to promote oral propulsion of the vomitus.  Other systems should be examined for any
There is reversal of peristaltic waves which assist abnormality.
in the oral expulsion of small-intestinal contents.  Red flags: The following findings are of particular
concern and require immediate evaluation
Approach to a Case of Vomiting and treatment:
– Signs of hypovolemia (immediate hydration
History
required).
 Duration: Acute vomiting refers to vomiting of few – Headache, stiff neck, or mental status change
hours or few days. Causes of acute vomiting include (suggest CNS infection).
obstruction, ischemic, toxic, metabolic, infectious, – Peritoneal signs (suggest peritonitis).
neurological and postoperative reasons. Chronic
– Distended, tympanitic abdomen (suggest acute
vomiting refers to vomiting lasting more than
abdomen, intestinal obstruction, etc).
1 month. Causes of chronic vomiting include partial
intestinal obstruction, motility disorder, chronic Investigations
neurological conditions (such as chronic meningitis,
brain tumor), pregnancy or functional reasons.  CBC: If Hb and hematocrit are high, it indicates
dehydration. Leukocytosis is seen in infections.
 Time of onset: Early morning vomiting seen in raised
intracranial tension, pregnancy, and uremia.  Serum electrolytes: To rule out hypochloremia,
hypokalemia, etc.
Vomiting 1 hour after eating suggests gastric outlet
obstruction or gastroparesis. Vomiting few hours  Urea, creatinine: Renal failure can cause vomiting
after eating suggests gastric or intestinal obstruc- due to uremia. On the other hand vomiting itself
tion. can cause renal failure, if there is dehydration.
Manipal Prep Manual of Medicine

 Content of the vomitus: If bilious then gastric outlet  Urine pregnancy test: In women of childbearing age
obstruction can be ruled out since bile from to rule out pregnancy.
duodenum cannot come back to stomach if there is  Serum amylase, lipase: Elevated in pancreatitis which
gastric outlet obstruction. Undigested food suggests can present with vomiting and abdominal pain.
achalasia or stricture. If hematemesis suspect upper  Liver function tests: To rule out hepatitis. Acute
GI bleed with its causes. If fecal matter is present hepatitis can cause nausea and vomiting.
suspect distal bowel obstruction.  Erect abdomen X-ray: If any intra-abdominal patho-
 Associated symptoms: Chronic headache associated logy suspected. Dilated bowel loops with multiple
with vomiting is seen in intracranial lesion and air fluid level seen in peritonitis and intestinal
migraine. Vomiting without preceding nausea obstruction.
(projectile vomiting) is typical of central nervous  Ultrasound abdomen: To rule out any intra-abdominal


system pathology. Vertigo suggests a labyrinthine pathology.

4 or vestibular problem. Associated diarrhea suggests

gastroenteritis. Fever suggests an infection. Severe
 Upper GI endoscopy: If peptic ulcer or gastric outlet
obstruction is suspected or if hematemesis is present.

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 CT abdomen: If the cause of vomiting is not clear  Diarrhea is defined as abnormal increase in stool 251
from above investigations. liquidity, frequency, and quantity. Typically a stool
 Other tests as indicated. weight >200 g/d or frequency more than 3 times
per day is considered to indicate diarrhea.
Complications of Vomiting  Depending on the duration, diarrhea may be
 Aspiration: Vomiting in a patient with altered mental classified as acute if <2 weeks, persistent if 2 to
status, low or depressed level of consciousness, or 4 weeks, and chronic if >4 weeks in duration.
persistent vomiting can lead aspiration of vomitus  Diarrhea should be differentiated from pseudo-
to the lungs and cause asphyxia or aspiration pneu- diarrhea, and fecal incontinence. Pseudodiarrhea
monia. is frequent passage of small volumes of stool. It is
 Mallory-Weiss syndrome: Due to severe and repetitive seen in irritable bowel syndrome and anorectal
retching and vomiting a partial tear of the mucosa disorders such as proctitis. Fecal incontinence is
and sub-mucosa in the stomach and gastroesophageal involuntary discharge of fecal matter and is seen
junction can occur and lead to hematemesis. in neuromuscular disorders and structural
 Boerhaave’s syndrome: This is a full thickness tear of anorectal problems.
all the layers of the esophagus, commonly in the
lower part of the esophagus due to repetitive, bouts Causes of Acute Diarrhea
of retching and vomiting. It is a medical emergency.
 Hypovolemia: Recurrent vomiting can cause dehydra- TABLE 4.3: Causes of acute diarrhea
tion and hypovolemia due to loss of water content. Bacterial
 Electrolyte imbalance: Hypokalemia occurs due to Preformed enterotoxin production
hypovolemia which stimulates renin angiotensin • Staphylococcus aureus
aldosterone system (RAAS) leading to sodium • Bacillus cereus
• Clostridium perfringens
absorption and potassium excretion in the urine.
Enterotoxin production
 Hypochloremic metabolic alkalosis: This occurs due to
• Enterotoxigenic E. coli (ETEC)
loss of hydrogen ions and chloride which are • Vibrio cholerae
present in the gastric juice in the vomitus. Cytotoxin production
• Enterohemorrhagic E. coli O157:H5
Treatment of Vomiting
• Vibrio parahaemolyticus
 Underlying cause should be treated. • Clostridium difficile
 In severe persistent vomiting, patient should be Mucosal invasion
kept nil by mouth and IV fluids administered. • Shigella
 Antiemetics can be used for symptomatic control • Salmonella
of vomiting. Examples: Domperidone 10 mg TID, • Campylobacter jejuni
metoclopramide 10 mg TID, ondansetron 4 mg TID. • Enteroinvasive E. coli (EIEC)
Metoclopramide and ondansetron can be given • Yersinia enterocolitica
parenterally and are useful in persistent vomiting. • Chlamydia
• Neisseria gonorrhoeae
• Listeria monocytogenes
Q. Causes of loss of appetite.
Viral
TABLE 4.2: Causes of loss of appetite • Noroviruses
• Rotavirus
• Infections: Viral fever, tuberculosis or any other infection
• Cytomegalovirus
• Gastrointestinal diseases: Peptic ulcer, pancreatitis
Protozoal
• Liver diseases: Hepatitis, cirrhosis • Giardia lamblia
• Renal diseases: Renal failure • Cryptosporidium


• Endocrine causes: Hypothyroidism, Addison’s disease, • Cyclospora

Gastrointestinal System

hyperparathyroidism • Entamoeba histolytica

• Malignancies: Carcinoma stomach, pancreas or any other
malignancy, leukemias, lymphomas Pathophysiology of Diarrhea
• Psychiatric disorders: Depression, anorexia nervosa  Diarrhea is the reversal of the normal net absorptive
status of water and electrolyte absorption to
Q. Define diarrhea, pseudodiarrhea and secretion. Such a derangement can be the result of
fecal incontinence. either an osmotic force that acts in the lumen to
Q. What are the causes of acute diarrhea? How drive water into the gut (osmotic diarrhea) or the
do you evaluate and manage a case of acute
diarrhea?
result of an active secretory state induced in the
enterocytes (secretory diarrhea). 4
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252  Example of osmotic diarrhea is lactulose-induced  History of animal exposure: Exposure to young dogs
diarrhea. In secretory diarrhea, the epithelial cells’ or cats is associated with Campylobacter organisms.
ion transport processes are turned into a state of Exposure to turtles is associated with Salmonella
active secretion. Example of secretory diarrhea is organisms.
bacterial infection of the intestine. Pathogens can
Examination
induce secretory diarrhea through multiple
mechanisms such as production of enterotoxins or  Look for any signs of dehydration. Assess pulse,

cytotoxins, release of cytokines, etc. BP, postural hypotension, skin turgor, dryness of
mucous membranes.
Evaluation of a Patient with Acute Diarrhea  Assess conscious level as patient can be in altered

History sensorium due to electrolyte imbalance.

 Examine the abdomen for any distension, tender-
 Residence.
ness and bowel sounds.
 Occupational exposure.
 Recent and remote travel (suspect diseases endemic Investigations in Acute Diarrhea
in the area of travel).  Most cases of acute diarrhea improve spontaneously
 Duration of diarrhea (whether acute or chronic, with supportive treatment and do not require
because the causes are different). investigations. However, acute diarrhea should be
 Frequency and quantity of stools (to assess the investigated if it is severe with dehydration, associa-
severity of diarrhea). ted with bloody stools, fever, lasts more than 2 days
 Appearance of stools: Rice water stool is seen in cholera, without improvement, new community outbreaks,
pea soup appearance in enteric fever, brown colored severe abdominal pain and in immunocompro-
in amebiasis, red currant jelly stools in shigella. mised patients.
 Presence of blood and/or mucus (suggests invasive
infection. Fresh blood and mucus is seen in large
Complete Blood Count CBC)
intestinal diarrhea).  Hemoconcentration and leukocytosis is commonly

 Any associated vomiting (suggests food poisoning seen. High leukocyte count suggests infectious
or gastroenteritis). diarrhea.
 History of pain abdomen (suggests invasive Urea/Creatinine, Serum Electrolytes
infection).
 Urea and creatinine may be elevated due to prerenal
 Urine output (to assess dehydration).
azotemia. Electrolyte disturbances such as hypo-
 History of fever (suggests infection with invasive
natremia and hypokalemia occur in severe diarrhea.
organisms).
 Food history can give clue about food poisoning Stool Analysis
and possible pathogen.  Stool should be sent for bacterial and viral cultures,
 Recent antibiotic use (may suggest antibiotic- microscopy for ova and parasites, immunoassays
induced diarrhea due to Clostridium difficile). for bacterial toxins (C. difficile), viral antigens
 History of immunocompromised state (suspect (rotavirus), and protozoal antigens (Giardia, E.
diarrhea due to unusual organisms such as Crypto- histolytica). Pathogens can also be identified by
sporidia, Isospora belli, etc). detecting their DNA sequences.

TABLE 4.4: Assessment of dehydration

Feature Mild dehydration Moderate dehydration Severe dehydration
Manipal Prep Manual of Medicine

General appearance Well Restless Lethargic

Oral mucosa Moist Dry Very dry
Skin Normal Cool Cool
Skin turgor Normal Reduced Markedly reduced
Capillary refilling Normal Slow Very slow
Eyes Normal Sunken Markedly sunken
Pulse rate Normal Tachycardia Markedly increased
JVP Normal Collapsed Collapsed
BP Normal Postural drop or reduced Hypotension/shock
Respiration Normal Normal Increased
Urine output Normal Reduced Markedly reduced


Urine specific gravity <1.020 >1.020 >1.035

4 Blood urea Normal Normal or high High

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Ultrasound Abdomen  Empirical treatment with metronidazole can also 253
 Useful if there is severe abdominal pain or be given for suspected giardiasis or amebiasis
abdominal distension or any mass is felt. (400 mg TID for 5–7 d).
 Antibiotic therapy may be modified when specific
GI Scopy pathogen is identified.
 If stool analysis does not reveal the cause of  Antibiotics should also be given to patients who
diarrhea, then flexible sigmoidoscopy with biopsies are immunocompromised, have mechanical heart
and upper endoscopy with duodenal aspirates and valves or recent vascular grafts, or are elderly even
biopsies may be indicated. if the organism is not identified.
 Colonoscopy may be indicated to identify any
growth, or to exclude inflammatory bowel disease. Q. Traveler’s diarrhea
 Traveler’s diarrhea refers to diarrhea occurring in
CT Scan Abdomen
persons traveling from resource-rich to resource-
 It is useful in the evaluation of ischemic colitis, poor regions of the world. It is common among
diverticulitis, or partial bowel obstruction. travelers to developing countries.
 Food and water contaminated with fecal matter are
Treatment
the main sources of infection. Bacteria such as
Fluid and Electrolyte Replacement enterotoxigenic Escherichia coli, enteroaggregative
 This is very important in acute diarrhea since de- E. coli, Campylobacter, Salmonella, and Shigella are
hydration is the major cause of death. If the patient common causes of traveler’s diarrhea.
is able to take orally, oral fluid replacement (in the  Most cases are benign and self-limited, but occasio-
form of ORS or any other fluid) can be given in mild nally can be severe enough to cause dehydration
to moderate dehydration. Intravenous rehydration and other complications.
is required if the patient is not able to take orally,
Causes
in severe dehydration, in infants, and elderly.
TABLE 4.5: Causes of traveler’s diarrhea
Antimotility Agents
Bacteria
 Agents like loperamide, diphenoxylate/atropine • Enterotoxigenic Escherichia coli
combination decrease the frequency and quantity of • Campylobacter jejuni
diarrhea. They can be used in diarrhea without fever • Salmonella
and without blood in stools. These agents should • Shigella
be avoided in infective diarrhea (febrile dysentery), • Vibrio parahaemolyticus
which may be exacerbated or prolonged by them. • Vibrio cholerae
• Yersinia enterocolitica
Antisecretory Agents
Viruses
 Example is racecadotril.
• Rotavirus
 Inhibits secretion of water and electrolytes into the • Norwalk virus
intestinal lumen.
Parasites
 It acts by inhibition of the enzyme neutral endo-
• Giardia lamblia
peptidase (also known as enkephalinase), a cell
• Entamoeba histolytica
membrane peptidase enzyme found on the
epithelium of the small intestine.
 Dose is 100 mg TID.  These organisms are often transmitted by food and
 It is useful in acute watery diarrhea. water.
 It is contraindicated in renal failure, pregnancy and  More than 90% cases are due to bacteria; the most


breastfeeding. common being enterotoxigenic Escherichia coli

Gastrointestinal System

(ETEC).
Antispasmodics
Clinical Features
 Such as dicyclomine, hyoscine, etc. can be used in
patients with crampy abdominal pain.  Most cases occur within first 2 weeks of travel.
 Abdominal cramps followed by sudden onset,
Antibiotics watery diarrhea, lasting 2–5 days.
 Moderately to severely ill patients with febrile  Malaise, anorexia, nausea, vomiting, and fever.
dysentery may be empirically treated with a  Diffuse tenderness over abdomen.
quinolone, such as ciprofloxacin (500 mg bid for
3 to 5 d).
 Additional specific features may be present depend-
ing on the organism. 4
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254 Treatment Q. Enumerate the parasites causing diarrhea.
 Fluid replacement: Most cases are self-limited and  Amebiasis
resolve on their own within three to five days of  Giardiasis
treatment with fluid replacement only. Oral fluid
 Trichuriasis
replacement is enough in most cases. Broth, fruit
 Strongyloidiasis
juice, or similar fluids may be used. ORS is
especially useful in severe diarrhea.  Balantidiasis
 Antibiotics: Shorten the disease duration to about  Coccidioses
one day. Antibiotics are indicated in patients with  Schistosomiasis
severe diarrhea associated with fever, blood, pus,  Capillariasis
or mucus in the stool. Ciprofloxacin or norfloxacin
may be used. Bismuth subsalicylate can also be Q. Define chronic diarrhea. What are the causes of
used. chronic diarrhea? How do you investigate and
 Antimotility agents: Antimotility agents such as manage a case of chronic diarrhea?
loperamide (Imodium) or diphenoxylate (Lomotil)
 Chronic diarrhea is defined as diarrhea lasting for
can be used to reduce severity of diarrhea.
more than 4 weeks.
However, caution should be exercised in using
these agents in bloody diarrhea.
TABLE 4.6: Causes of chronic diarrhea

Prevention Secretory diarrhea

• Hormonally mediated: VIPoma, carcinoid, medullary
 Improving food and drink selection: Avoid raw food carcinoma of thyroid (calcitonin), Zollinger-Ellison syndrome
items such as chutney, salads, buttermilk, and (gastrin)
curds. Use only boiled or bottled water. Avoid fresh • Villous adenoma
fruit juices with ice. Inflammatory conditions
 Prophylactic antibiotics: Not routinely necessary. • Inflammatory bowel disease (ulcerative colitis and Crohn’s
Quinolones or doxycycline 100 mg/day for a few disease)
weeks. Bismuth subsalicylate 60 mL four times a • Radiation enteritis
day is an alternative. Rifaximin may prove to be Malabsorption syndromes: Celiac sprue, tropical sprue,
the preferred antibiotic because it is not absorbed Whipple’s disease, eosinophilic gastroenteritis, small bowel
and is well tolerated. resection (short bowel syndrome), chronic pancreatitis, lactose
 Probiotics: Such as Lactobacillus and Saccharomyces intolerance
boulardii have been shown to decrease the incidence Chronic infections
of diarrhea in travelers. • Giardiasis
• Chronic amebiasis
• Intestinal tuberculosis
Q. Enumerate the indications for stool cultures
• HIV related infections by Mycobacterium avium complex,
and blood cultures in patients with acute diarrhea.
microsporida, cryptosporidium, Isospora belli
Motility disorders
Indications for Stool Cultures in Acute Diarrhea
• Blind loop with bacterial overgrowth
 Fever • Diabetes mellitus
 Blood in stools • Hyperthyroidism
 Leukocytes in stool • Irritable bowel syndrome
Manipal Prep Manual of Medicine

 Pain resembling that associated with appendicitis Malignancy: Lymphoma of intestine, adenocarcinoma colon
(Yersinia) Medications: Laxatives, angiotensin receptor blockers
 Diarrheal illness associated with partially cooked
hamburger (cytotoxigenic E. coli O157:H7) Investigations in Chronic Diarrhea
 Prolonged diarrhea (more than 4 to 7 days)
 In contrast to acute diarrhea, most cases of chronic
 Immunocompromised host
diarrhea are noninfectious.
 For epidemiologic purposes, such as cases involv-
 All the tests described for acute diarrhea are
ing food handlers.
required for chronic diarrhea.
 24-hour stool fat estimation, testing for presence of
Indications for Blood Cultures in Acute Diarrhea
laxatives, and estimation of stool osmolality (normal
 Fever osmotic gap in secretory diarrhea, increased in


 Pain abdomen osmotic diarrhea) should be done.

4 


Patients with sepsis, shock
Immunocompromised patients.
 Intestinal aspirates and quantitative cultures to rule
out small bowel bacterial overgrowth.

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 If suggested by history or other findings, hormonal  Risk factors for constipation include female sex, older 255
excesses should be ruled out by appropriate tests age, inactivity, low caloric intake, low fiber diet, and
(serum gastrin, VIP, calcitonin, thyroid function taking a large number of medications. The incidence
tests, etc.). of constipation is three times higher in women.
 Low fecal pH suggests carbohydrate malabsorp-
tion; lactose malabsorption can be confirmed by Approach to a Case of Constipation
lactose breath testing or by a therapeutic trial History
with lactose exclusion and observation of the effect  Confirm what exactly the patient means and whether
of lactose challenge. there is really constipation. A constipated patient
 Pancreatic disease should be excluded by secretin- may be otherwise totally asymptomatic or may
cholecystokinin stimulation test, or by assay of fecal complain of one or more of the following: Straining,
chymotrypsin activity or a bentiromide test. lumpy or hard stools, sensation of anorectal obstruc-
 Ultrasound abdomen to rule out pancreatitis, malig- tion, sensation of incomplete defecation, manual
nancy, and pancreatitis. maneuvering required to defecate, abdominal
 Colonoscopy to rule out ileocecal TB, ca colon, bloating, pain on defecation, and rectal bleeding.
inflammatory bowel disease, etc.  Ask about the frequency of stools, consistency
 CT abdomen if malignancy or pancreatitis or (lumpy/hard), excessive straining, or prolonged
abdominal TB is suspected. defecation time.
 Presence of blood in the stool and weight loss should
Treatment of Chronic Diarrhea be taken seriously as it can indicate carcinoma
 Treatment of chronic diarrhea depends on the colon. Similarly presence of vomiting, inability to
specific etiology. For example, elimination of lactose pass flatus and pain abdomen indicates intestinal
containing foods in lactase deficiency or gluten in obstruction.
celiac sprue, use of steroids or anti-inflammatory  Ask about the symptoms of any underlying disease
agents in inflammatory bowel diseases, etc. (see the causes above).
 Ask about food habits, activity, and drug intake.
Q. Define constipation. Enumerate the causes of
constipation. How do you investigate and treat a Examination
case of constipation?  Do a complete physical examination and rectal
examination.
 Constipation may be defined as infrequent stools  Look for any hernias which can cause constipation
(less than 3 times in a week), hard stools, excessive or the result of chronic constipation.
straining, or a sense of incomplete evacuation.  Look for any mass in the abdomen.
 Look for any evidence of endocrine (hypothyroidism)
TABLE 4.7: Causes of constipation in adults or neurological abnormalities.
Common causes Inadequate fiber or fluid intake, seden-
tary lifestyle, irregular bowel habits Investigations
GI diseases Intestinal obstruction, colonic neoplasm,  Based on the history and examination findings
colonic stricture, anal fissure, painful investigations are ordered as follows.
hemorrhoids, anal sphincter spasm,
pelvic floor dysfunction, descending Blood tests
perineum syndrome, rectal mucosal  Serum calcium, blood sugar, thyroid and para-
prolapse, rectocele, Hirschsprung’s thyroid function tests, etc. if clinically indicated.
disease, Chaga’s disease, irritable
bowel syndrome
Stool examination
 Look for occult blood (presence of blood may
Endocrinopathies Hypothyroidism, hyperparathyroidism,
suggest ca colon)


hypercalcemia, diabetes mellitus

Gastrointestinal System

Psychiatric disorders Depression, eating disorders Sigmoidoscopy, barium enema, colonoscopy

Neurologic disease Parkinsonism, multiple sclerosis, spinal  These are indicated to rule out local anorectal

cord injury, paraplegia, autonomic abnormalities. Colonoscopy is especially important

neuropathy in patients above 40 years with history of weight loss,
Myopathic diseases Systemic sclerosis, myotonic dystrophy rectal bleeding, or anemia to rule out colonic cancer.
Metabolic Hypokalemia, hypercalcemia, uremia, Colon transit time
porphyria
 This is measured by performing an abdominal radio-
Drugs Calcium channel blockers, anti- graph 120 hours after ingestion of radio-opaque
4
depressants, opioids, anticholinergics,
markers. Retention of >20% of the marker indicates
clonidine, calcium and iron supplements
prolonged transit.

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256 Balloon expulsion testing, anal manometry, and Q. Enumerate the causes of occult blood in the stool.
defecograph
 Occult bleeding refers to positive fecal occult blood
 These tests can be used to assess pelvic floor dys-
test without visible fecal blood either to the patient
function and anorectal disorders.
or physician.
Treatment
TABLE 4.8: Causes of occult blood in the stool
 General measures: Increase fluid intake, high fiber
Upper GI lesions
diet and physical activity. • Esophagitis
 Bulk laxatives: These include psyllium (ispaghulla), • Peptic ulcer disease
methylcellulose, and calcium polycarbophil. They • Gastritis/erosions
exert their laxative effect by absorbing water and • Duodenitis/erosions
increasing fecal mass. They are well tolerated. They • Angiodysplasia
may be used alone or in combination with dietary • Esophageal or gastric varices
changes. Side effects are impaction above strictures, • Gastric cancer
gas and bloating. • Gastric or duodenal polyps
 Emollients (stool softeners): Include docusate sodium Lower GI lesions
and liquid paraffin. Docusate sodium acts by • Colon polyps
lowering the surface tension of stool, thereby • Colon cancer
allowing water to easily enter the stool. Liquid • Angiodysplasia
paraffin works by lubricating the stool. They are • Colonic ulcers
• Hemorrhoids
generally inferior to bulk laxatives, but more useful
• Anal fissure
in patients with anal fissures and hemorrhoids
which cause painful defecation. They are gene- Worm infestation
rally well tolerated. Liquid paraffin can cause • Hookworm
depletion of fat soluble vitamins if used for long Drugs
time. • Aspirin or other NSAIDs
 Osmotic laxatives: Include magnesium sulfate,
lactulose, polyethylene glycol, sorbitol, and Q. Enumerate the causes of weight loss.
glycerine. These agents are poorly absorbed and
act as hyperosmolar solutions which retain water TABLE 4.9: Causes of weight loss
in the intestinal lumen. Magnesium sulfate can Involuntary weight loss
cause hypermagnesemia in patients with renal • Endocrine disorders (hyperthyroidism, pheochromocytoma,
failure. Other agents can cause flatulence and adrenal insufficiency)
abdominal bloating. • Uncontrolled diabetes mellitus
 Stimulant laxatives: These include castor oil, • Malignancy
bisacodyl and senna. They increase intestinal • Chronic infections (tuberculosis, HIV, subacute bacterial
motility and secretion of water into the bowel. They endocarditis)
can cause electrolyte imbalance such as hypo- • GI disorders (malabsorption syndromes, chronic pancreatitis,
kalemia. IBD, parasitic infestation)
• COPD
 Prokinetic agents: Metoclopramide and mosapride.
They increase intestinal motility. • Chronic renal failure
• Psychiatric disorders (depression, mania, anorexia nervosa,
 Enemas: Enemas act within 5–15 min and are given
Manipal Prep Manual of Medicine

schizophrenia)
rectally. These include tap water enema, soap water
• Chronic alcoholism
enema and sodium phosphate enema, etc. Rarely
• Drugs (opiates, amphetamines, digoxin, metformin, NSAIDs,
if stools are impacted, digital evacuaton has to be anticancer drugs)
done.
Voluntary weight loss
 New agents: Newer therapies for constipation
• Treatment of obesity
include prucalopride, a prokinetic agent that stimu-
• Anorexic drugs—amphetamines and derivatives
lates colonic motility and decreases transit time, and
• Distance runners, models, ballet dancers, gymnasts
the osmotic agents lubiprostone and linaclotide,
• Marked increase in physical activity
which stimulate intestinal fluid secretion by acting
• Prolonged fasting
on the intestinal mucosa. Lubiprostone and linaclo-
tide are useful in chronic idiopathic constipation and
Q. Aphthous ulcers.


constipation caused by irritable bowel syndrome.

4 Naloxegol and methylnaltrexone are useful in

opioid induced constipation.
 These are painful oral ulcers which are localized,
shallow, round to oval, with a grayish base.

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 Aphthous ulcers are common in childhood and Q. S/N. Paraesophageal or rolling hernia. 257
adolescence and become less frequent in adulthood.
They usually heal within 10 to 14 days without  Hiatus hernia is herniation of a part of the stomach
scarring. into the thoracic cavity through the esophageal hiatus
of the diaphragm. There are two types: (1) Sliding
Etiology hiatus hernia and (2) para-esophageal or rolling hernia.
 Exact cause of aphthous ulcers is not well known.
Sliding Hiatus Hernia
Alterations in local cell mediated immunity may
play a role in the causation.  Here, the gastroesophageal junction and fundus of
 A genetic basis exists for some recurrent aphthous the stomach slide upward through the hiatus and
ulcerations. This is shown by a positive family lie above the diaphragm.
history in about one-third of patients with recurrent
aphthous ulcerations. Etiology
 Recurrent aphthous ulcers are seen in stress,  Incidence increases with increasing age.
infections, food allergy, HIV infection, celiac sprue,  Weakening of the anchors of the gastroesophageal
gluten sensitive enteropathies, inflammatory bowel junction to the diaphragm and longitudinal
diseases, Behcet’s disease and vitamin and mineral contraction of the esophagus.
deficiencies (B vitamins, iron, folic acid, and zinc).  Increased intra-abdominal pressure (ascites,
Drugs like methotrexate may induce oral ulcers. pregnancy, obesity).
 Trauma.
Treatment  Congenital malformation.
 Local corticosteroid application (triamcinolone gel
and hydrocortisone pellets) and other topical Clinical Features
analgesics are adequate. These are applied to the  It does not produce symptoms on its own; symptoms
ulcer two to four times daily until the ulcer is occur because of associated gastroesophageal reflux.
healed.  Symptoms are epigastric or substernal pain, post-
 Chlorhexidine gluconate mouth rinses reduce prandial fullness, nausea, and retching.
the severity and pain of ulceration but not the
frequency. Investigations
 Oral corticosteroids are indicated for severe disease.  Chest X-ray: May show retrocardiac air fluid level
 Colchicine, dapsone, pentoxifylline, interferon or intrathoracic stomach.
alpha, and levamisole are beneficial in severe  Barium swallow will demonstrate the presence of
recurrent aphthous ulcers. gastroesopahgeal junction in the thorax.
 Thalidomide is useful for severe recurrent aphthous  Endoscopy.
ulcers especially in patients with HIV infection.
Management
Q. What is hiatus hernia? Discuss the causes, clinical  Asymptomatic sliding hiatus hernia does not
features, diagnosis and management of hiatus require any treatment.
hernia.
 Symptomatic large hiatus hernia requires either
Q. S/N. Sliding hiatus hernia medical or surgical treatment. Surgical treatment


Gastrointestinal System

Figure 4.1 Hiatus hernia 4

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258 involves repair of the diaphragmatic defect, and  It becomes pathological, when the antireflux mecha-
fixing the stomach in the abdominal cavity nisms fail sufficiently to allow gastric contents to
(fundoplication) combined with an anti-reflux make prolonged contact with the lower esophageal
procedure. mucosa causing damage (GERD). Reflux esopha-
gitis is the commonest form of GERD, most often
Paraesophageal or Rolling Hernia recognized by recurrent heartburn.
 Here, the gastroesophageal junction remains fixed
in its normal location but a small part of the fundus Etiology of GERD
of the stomach rolls up through the hiatus alongside  Pregnancy, obesity, ascites and weightlifting act by
the esophagus. increasing intra-abdominal pressure.
 Fat, chocolate, smoking, coffee, large fatty meals
Etiology or alcohol ingestion reduce lower esophageal
 Idiopathic sphincter tone.
 Postsurgical (e.g. after antireflux procedures,  Drugs: Calcium-channel blockers, nitrates reduce
esophagomyotomy, or partial gastrectomy). sphincter tone.
Clinical Features  Systemic sclerosis reduces sphincter tone and
esophageal motility.
 Clinical features are same as sliding hiatus hernia.
 After treatment for achalasia (reflux increases).
 Complications are common in this variety and
include dysphagia, gastritis, ulceration, volvulus  Sliding hiatus hernia predisposes to reflux because
and strangulation. Respiratory complications can the gastroesophageal junction lies above the
occur due to compression of the lung by the diaphragm and hence the sphincter effect of
herniated viscera. diaphragm is lost.

Investigations Pathophysiology
 Same as sliding hiatus hernia.  Esophagus is a 25 cm conduit whose upper third is
skeletal muscle and lower two-thirds are smooth
Treatment muscle. There is a sphincter in the lower esophagus
 Involves, reduction of the herniated stomach into (LES) formed by the lower 4 cm of esophageal
the abdomen, herniotomy, herniorraphy combined smooth muscle. It relaxes after swallowing to allow
with an antireflux procedure and gastropexy food to enter the stomach and closes after swallow-
(attachment of the stomach sub-diaphragmatically ing, thereby preventing reflux. Sphincter tone can
to prevent reherniation) increase in response to rises in intra-abdominal and
intragastric pressures. Reflux is also prevented
by contraction of the crural diaphragm which
Q. What is gastroesophageal reflux disease (GERD)?
surrounds lower end of esophagus and exerts a
Describe the etiology, pathophysiology, clinical fea-
‘pinchcock-like’ action at the LES.
tures, investigations, complications and treatment
of reflux esophagitis.  When these mechanisms fail, abnormal acid reflux
occurs and damages the lower end of esophagus.
 Gastroesophageal reflux is the movement of gastric Damage to esophagus produces mild esophagitis
contents into the esophagus. It occurs in everyone, (mild erythema) and erosive esophagitis (mucosal
multiple times every day. damage, bleeding, superficial linear ulcers, and
Manipal Prep Manual of Medicine


4 Figure 4.2 Pathology in GERD

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 exudates). Erosive esophagitis may heal by intes-  Bernstein test can tell whether the symptoms are due 259
tinal metaplasia (Barrett’s esophagus), which is a to acid reflux. This test is done by perfusing acid
risk factor for adenocarcinoma. (0.1 N HCl, pH 1.1) or saline (control) through a
catheter positioned in mid-esophagus. If symptoms
Clinical Features develop during acid, but not saline perfusion, the
 Regurgitation of sour material into the mouth and test is considered positive for GERD.
heartburn are the main features of GERD. Angina  Resting and stress ECG to rule out angina.
like pain can occur in some patients. Heartburn is
due to contact of refluxed material with the Complications of GERD
sensitized or ulcerated esophageal mucosa. The  Esophagitis.
correlation between heartburn and esophagitis is  Peptic stricture.
poor. Patients with severe esophagitis may have
 Barrett esophagus.
mild pain and patients with mild esophagitis may
 Carcinoma of esophagus.
have severe pain. The burning is aggravated by
bending, stooping or lying down and on drinking  Aspiration pneumonia.
hot liquids or alcohol. It is usually be relieved by  Iron deficiency anemia due to chronic blood loss
antacids. from esophageal ulcers.
 Reflux into the pharynx, larynx, and tracheobronchial
tree can cause chronic cough, bronchoconstriction, Treatment
pharyngitis, laryngitis, bronchitis, or pneumonia. General Measures
 Dysphagia may develop due to stricture of lower  Weight reduction if overweight, head end elevation
end of esophagus or development of adeno- of the bed at night, reduction in alcohol consumption
carcinoma in Barrett’s esophagus. and cessation of smoking help all patients with GERD.
 Mucosal erosions may produce bleeding, hema-
temesis and anemia. Medical Management
 This is the preferred treatment. The goal of treatment
TABLE 4.10: Differentiating GERD from angina is to relieve symptoms and prevent complications.
GERD Angina Most patients obtain symptom relief with the
• Burning pain • Gripping or crushing pain following treatment, but symptoms usually return
• Pain produced by bending, • Pain produced by exercise when treatment is stopped and long-term therapy
stooping or lying down is then required.
• Pain relieved by antacids • Pain relieved by rest and  Antacids: Antacids neutralize the acid in the stomach
nitrates and immediately relieve heartburn. Most antacid
• Radiates to retrosternal area • Pain radiates into neck, preparations contain combination of magnesium
and not to shoulders and arms shoulders and both arms sulphate and aluminium hydroxide. Magnesium
• No dyspnea, sweating and • Accompanied by dyspnea, sulphate tends to cause diarrhea while aluminium
tachycardia tachycardia and sweating
hydroxide causes constipation. Combining both of
them will have neutral effect on bowel movements.
Investigations Antacids are available in both liquid and tablet
 A history of recurrent heartburn and response to forms. These preparations can be taken as and when
antacids or acid-suppressant medication is required (10 mL 3 to 6 times daily). Alginate-
adequate to diagnose GERD. Investigations are containing antacids form a gel or ‘foam raft’ on top
reserved for patients with alarm symptoms such of gastric contents and thereby reduce reflux.
as dysphagia, weight loss, or gastrointestinal  H2-receptor antagonists (e.g. ranitidine, famotidine
bleeding. and nizatadine) are used for acid suppression
 Endoscopy is used to confirm damage to esophagus along with antacids. They should be given for


or to rule out other alternate pathology. 6–8 weeks.

Gastrointestinal System

 Barium swallow followed by X-rays in the head-  Proton pump inhibitors (PPIs) (e.g. omeprazole,
down position can detect movement of barium from rabeprazole, lansoprazole, pantoprazole, esome-
stomach to esophagus suggesting reflux. prazole): They inhibit gastric hydrogen/potassium-
 24-hour esophageal pH monitoring is the gold standard ATPase and reduce gastric acid secretion by 90%.
test for identifying reflux. This is done by fixing a These are more effective than H2 blockers and are
small pH probe in the esophagus, 5 cm above the preferred over them. 8 weeks of therapy can heal
LES, and recording all episodes of acid reflux (drop erosive esophagitis in up to 90% of patients. Patients
in pH <4) over a 24-hour period. Total number and with severe symptoms need prolonged treatment,
duration of each reflux event yield a total eso-
phageal acid contact time.
often for years. Rebound increased acid secretion
is a problem with these agents. 4
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260  Prokinetic agents (metoclopramide, mosapride, endoscopic mucosal resection are being evaluated
cintapride and domperidone): They increase lower as alternatives.
esophageal sphincter tone and speed gastric  There is no evidence that treatment with PPIs or
emptying. They are only occasionally helpful. antireflux surgery leads to Barrett’s regression.
Cisapride increases QT interval and predisposes to
cardiac arrhythmias. It has been withdrawn from Q. Define dysphagia. What are the causes of dys-
market. Acotiamide is a novel prokinetic agent phagia? How do you approach a case a dysphagia?
which acts by increasing acetylcholine release from
enteric neurons through acetylcholinesterase  Dysphagia means difficulty in swallowing.
(AChE) inhibition.  Odynophagia is pain while swallowing.
 Swallowing is a process governed by the swallow-
Surgery ing center in the medulla, and in the mid-esophagus
 Antireflux surgery can be considered for patients and distal esophagus by a largely autonomous
with severe reflux symptoms confirmed by pH peristaltic reflex coordinated by the enteric nervous
monitoring and with esophagitis on esophago- system.
scopy. But even these patients respond to medical
therapy which should be reinforced. Surgery can TABLE 4.11: Etiology of dysphagia
also be an alternative for patients who require long- Causes in the esophagus
term, high-dose PPIs. • Congenital stenosis of esophagus
 In antireflux surgery, the gastric fundus is wrapped • Tracheoesophageal fistula
around the esophagus (modified Nissen fundo- • Congenital web
plication), which increases lower esophageal • Strictures
sphincter pressure and prevents reflux. Laproscopic • Carcinoma esophagus
fundoplication is another procedure for GERD. • Diverticulum
 Complications of GERD-like stricture require • Esophagitis (reflux, candida)
repeated dilatations or surgical resection. • Achalasia cardia
• Plummer-Vinson syndrome
Q. Barrett’s esophagus. • Scleroderma
Causes outside the esophagus
 This is metaplasia of esophageal squamous epithe-
lium to columnar epithelium. • Thyroid swelling
• Secondaries in the neck
 It is a complication of long standing severe reflux
• Mediastinal mass, lymphadenopathy, or abscess
esophagitis and is a risk factor for developing
esophageal adenocarcinoma. Barrett’s epithelium • Aortic aneurysm
progresses through a dysplastic stage before • Left atrial enlargement
developing into adenocarcinoma. • Osteophytes in cervical spine
 Metaplastic columnar epithelium develops because Painful diseases of mouth and pharynx
it is more resistant to acid-pepsin damage than • Stomatitis
squamous epithelium. • Tonsillitis
 It is more common in men and older age groups. • Pharyngitis
 Endoscopically, Barrett’s epithelium may be seen • Retropharyngeal abscesses
as a continuous sheet, a finger-like projection into • Diphtheria
the esophagus or as islands of columnar mucosa. Motility disorders
Manipal Prep Manual of Medicine

 An indocarmine spray down the endoscope can • Achalasia cardia

detect intestinal metaplasia and possibly dysplasia. • Scleroderma
Biopsies should be obtained from all four quadrants • Diffuse esophageal spasm
of the Barrett’s segment. • Hypertensive lower esophageal sphincter
Neuromuscular disorders
Treatment
• Bulbar paralysis
 Regular endoscopy can detect dysplasia before • Pseudobulbar palsy
development of adenocarcinoma. Hence, endoscopic • Myasthenia gravis
surveillance every 2 to 3 years, with four-quadrant • Multiple sclerosis
biopsies of Barrett’s segment is recommended. • Parkinson disease
 If high-grade dysplasia is found on biopsy, • Rabies


esophagectomy of the involved segment is advised

Functional
4 before it turns into adenocarcinoma. Photodynamic
laser or thermocoagulative mucosal ablation and
• Functional dysphagia

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Approach to a Case of Dysphagia Investigations 261
 Hemoglobin and peripheral smear to check for
History
anemia (iron deficiency causes anemia and
 The type of food causing dysphagia gives useful Plummer-Vinson syndrome).
information. Dysphagia only for solids implies  Barium swallow detects tumors as filling defects
mechanical dysphagia with partial obstruction. and strictures as rat tail appearance. Corkscrew
Dysphagia for both solids and liquids occurs in appearance is seen in achalasia.
neuromuscular and severe obstructive lesions.  Endoscopy and biopsy of any lesions.
 History of difficulty in initiating swallowing suggests  Esophageal motility studies.
oropharyngeal dysphagia. History of food “sticking”  Chest X-ray to rule out mediastinal mass or
after swallowing indicates esophageal dysphagia. bronchogenic ca.
 The duration and course of dysphagia are also  CT scan of neck and chest to rule out any mass lesions.

helpful in diagnosis. Transient dysphagia is usually

Q. Plummer-Vinson syndrome (Paterson-Kelly syndrome).
due to an inflammatory process. Sudden onset
dysphagia occurs due to obstructive foreign bodies.  The combination of esophageal webs, dysphagia,
Progressive dysphagia may be due to carcinoma and iron-deficiency anemia is called Plummer-
esophagus or scleroderma or achalasia. Intermittent Vinson syndrome.
dysphagia is seen in esophageal spasm.  It is usually seen in middle-aged women.
 Dysphagia with nasal regurgitation is seen in  Esophageal webs are thin, diaphragm-like mem-
pharyngeal paralysis. branes of squamous mucosa. They are usually seen
 History of regurgitation of old food and halitosis in the upper esophagus and may be multiple.
suggests Zenker’s diverticulum.  Most cases are asymptomatic. Solid food dysphagia
 Tracheobronchial aspiration with dysphagia is seen may occur. Dysphagia is intermittent and not pro-
gressive.
in tracheoesophageal fistula.
 Investigations include barium esophagogram and
 Weight loss and progressive dysphagia in elderly endoscopy.
is highly suggestive of carcinoma. When hoarseness  Treatment involves passage of a large (>16-mm-
precedes dysphagia, the primary lesion is usually diameter) bougie dilator to disrupt the lesion.
in the larynx. When hoarseness appears after Repeated dilations are required in many patients.
dysphagia, it suggests involvement of the recurrent Underlying iron deficiency should be treated.
laryngeal nerve by extension of esophageal
carcinoma. Sometimes hoarseness may be due to Q. Define hiccups (singultus). What are the causes of
laryngitis secondary to gastroesophageal reflux. hiccups? Add a note on its treatment.
 Chest pain with dysphagia occurs in diffuse eso- Definition
phageal spasm and related motor disorders.
 A prolonged history of heartburn preceding  A hiccup is an involuntary, intermittent contraction
dysphagia indicates peptic stricture. of the diaphragm and the inspiratory intercostal
 If odynophagia is present, it suggests esophagitis. TABLE 4.12: Causes of hiccups
CNS diseases
Physical Examination • Neoplasms, infections, cerebrovascular accident, trauma.
 Pallor is present in Plummer-Vinson syndrome due Toxic and metabolic problems
to iron deficiency. • Alcohol intoxication, uremia, diabetic ketoacidosis,
hyponatremia.
 Neck should be examined for thyromegaly,
lymphadenopathy or any other abnormality. Irritation of the vagus or phrenic nerve
• Sudden temperature changes (hot then cold liquids, hot then
 Mouth and pharynx should be examined for any cold shower)
local pathology. • Foreign body in ear


 Skin should be examined for evidence of sclero- • RS: Pneumonia, empyema

Gastrointestinal System

derma. • CVS: Myocardial infarction, pericarditis, aneurysm, reflux

esophagitis
 Neurological examination should be done looking
• Abdomen: Subphrenic abscess, hepatitis, pancreatitis, chole-
for evidence of bulbar or pseudobulbar palsy. cystitis, gastric or pancreatic malignancy, sudden gastric
 Abdomen should be examined for any distension, distension (carbonated beverages, air swallowing, overeating).
mass. Surgical
 Cancer spread to lymph nodes and liver may be • General anesthesia, postoperative
evident. Psychogenic
 Respiratory system examination may reveal • Excitement, stress, laughing
complications of dysphagia such as aspiration
pneumonia.
Idiopathic
• Unknown cause 4
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262 muscles that results in a sudden inspiration and  Pancreatic diseases: Pancreatitis, pancreatic carci-
ends with abrupt closure of the glottis. noma.
 Hiccups have no known physiological function.  Biliary tract disease: Cholelithiasis.
They are usually benign and self-limiting.  Other conditions: Diabetes, renal insufficiency,
However, occasionally they may be a sign of serious myocardial ischemia, hiatus hernia and pregnancy.
underlying illness.  Drugs: NSAIDs, metformin, corticosteroids, erythro-
mycin.
Investigations  Functional dyspepsia (also known as nonulcer dyspepsia):
 Most cases of hiccups are benign and require no No identifiable cause.
investigations.
 Persistent hiccups (lasting >48 hr) require detailed Differential Diagnosis
neurologic examination, serum creatinine, liver
Peptic Ulcer Disease
function tests, and a chest X-ray.
 If the cause is still not clear, CT of the head, chest,  Discomfort occurs predominantly in the epi-
and abdomen, echocardiography, bronchoscopy, gastrium, but can also occur in the right or left
and upper GI scopy may help. Chest fluoroscopy upper quadrants.
helps in studying diaphragmatic movement and  Pain is usually burning type or hunger-like in
diagnosing unilateral hiccups. quality. It can be vague or cramping.
 Gastric ulcer pain is aggravated by food while
Treatment duodenal ulcer symptoms occur 2 to 5 hours after
meals or on an empty stomach. Symptoms
 Idiopathic hiccups can often be terminated by
also occur at night, between 11 pm and 2 am,
simple measures such as stimulation of naso-
when the circadian stimulation of acid secretion is
pharynx, pressure on eyeballs, breath holding,
maximal.
Valsalva’s maneuver, sneezing, or rebreathing into
a bag, stimulation of the vagus by carotid massage.  Antacids, H2 blockers and proton pump inhibitors
relieve the pain.
 If there is gastric distention, it should be relieved
by belching or insertion of a nasogastric tube. Gastroesophageal Reflux Disease
 Drugs: Many drugs can help to control hiccups.
 Most common symptoms of GERD are heartburn
– Chlorpromazine, 25–50 mg orally or intra-
and regurgitation.
muscularly.
 Symptoms are aggravated by stooping or lying flat
– Baclofen 10 mg TID.
and relieved by antacids.
– Other useful drugs are metoclopramide,
dom- peridone, phenytoin, diazepam, and Gastric Malignancy
gabapentin.
 Usually occurs in patients over 50 years of age.
Q. Define dyspepsia. What are the causes of  Other features include progressive dysphagia,
dyspepsia? How do you investigate and manage a weight loss, hematemesis, anemia, persistent vomit-
case of dyspepsia? ing and abdominal mass.
 Dyspepsia is pain or discomfort in the upper

abdomen especially in the epigastrium. Patient may Biliary Tract Disease

describe it as abdominal fullness, early satiety,  Dull aching pain in the epigastrium or right upper
burning, bloating, belching, nausea, retching, or quadrant. Pain may radiate to the back or scapula.
Manipal Prep Manual of Medicine

vomiting.
 Dyspepsia may be functional dyspepsia (without Pancreatitis
any identifiable cause) or secondary dyspepsia  Pain is mainly in the epigastric region, severe and
(with an identifiable cause). dull aching. It often radiates to back and associated
 Functional dyspepsia accounts for the majority of with nausea and vomiting. It increases on lying
cases. down and decreases by bending forward.

Causes of Dyspepsia Irritable Bowel Syndrome

 Food related: Overeating, eating high-fat foods,  Chronic abdominal pain and altered bowel habits
drinking too much alcohol or coffee. is characteristic of IBS.
 GI tract problems: Gastritis, peptic ulcer, GERD,


gastric cancer, gastroparesis (in diabetes mellitus), Drug-induced Dyspepsia

4 infections (Helicobacter pylori, giardia, strongy-

loides).
 Dyspeptic symptoms appear after the intake of
offending drugs.

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Investigations  Symptoms of irritable bowel syndrome such as 263
 If the patient is less than 50 years, he is likely to be pellet-like stools and feeling of incomplete evacua-
having functional dyspepsia hence empiric therapy tion after defecation may be present.
with H2 blockers (ranitidine, famotidine) or proton  Examination is usually normal except for epigastric
pump inhibitors (omeprazole, pantoprazole) may tenderness. There is no weight loss. Patients often
be tried. appear anxious.
 However, if the history or examination is pointing  A drug history (NSAIDs) should be taken and
towards any specific cause listed above, investiga- depressive illness should be ruled out.
tions should be done to rule out the same. Rome IV criteria for functional dyspepsia
 Ultrasound abdomen and CT abdomen is helpful  Functional dyspepsia is defined by the presence of
to rule out pancreatic or biliary tract disease. one or more of the following symptoms in the
 Esophageal pH monitoring may help if gastro- absence of structural disease using imaging or
esophageal reflux is suspected. endoscopy.
 Noninvasive tests for H. pylori (IgG serology, fecal
• Epigastric pain or burning
antigen test, or urea breath test) help in ruling out
• Early satiety
H. pylori infection.
• Postprandial fullness
 Upper GI scopy should be done in patients above
50 years with persistent dyspepsia and in all
Investigations
patients with “alarm” features such as weight loss,
dysphagia, recurrent vomiting, evidence of bleeding,  All organic causes should be ruled out by appro-
or anemia to rule out carcinoma stomach. priate tests.
 Alarming features which merit thorough investiga-
Treatment tions include dysphagia, anemia, weight loss,
anorexia, dysphagia and hematemesis or melena.
 If any underlying cause is found, it should be
 In women, pregnancy should be ruled out by urine
treated.
pregnancy test and ultrasound.
 For functional dyspepsia, 2 to 4 weeks of therapy
 Upper GI scopy to rule out peptic ulcer, malignancy
with H2 blockers (ranitidine, famotidine) or proton
and hiatus hernia.
pump inhibitors (omeprazole, pantoprazole) may
be tried.  Ultrasound abdomen if required to rule out gall-
stone disease and other mass lesions.
 Tests to rule out H. pylori infection.
Q. Discuss the etiology, clinical features, investigations
and management of functional dyspepsia (non- Management
ulcer dyspepsia; idiopathic dyspepsia).
 Explain the nature of illness and reassure.
 Non-ulcer dyspepsia is defined as chronic dys-  Address any underlying psychological stress.
pepsia (pain or upper abdominal discomfort) in the  Avoid cigarette smoking and alcohol abuse. Reduce
absence of organic disease. intake of fatty foods.
 The first-line treatment is with a proton pump
Etiology inhibitor or H2 receptor antagonist for at least
Exact etiology is unknown. However, following 4 weeks. Then, if symptoms persist, treatment with
factors have been implicated. tricyclic antidepressants, or prokinetic agents are
 Abnormal gastric motor function (delayed gastric tried. Prokinetic agents include itopride, metoclo-
emptying, reduced gastric compliance) pramide (10 mg 8-hourly) and domperidone (10 mg
 Visceral hypersensitivity 8-hourly). Acotiamide is a new upper gastro-
 Helicobacter pylori infection
intestinal motility modulator useful in functional
dyspepsia.


 Psychosocial factors (anxiety, somatization, neuro-

Gastrointestinal System

ticism, and depression)  H. pylori should be eradicated if the tests are

positive.
Clinical Features
 Patients are usually young (<40 years) and women Q. Describe briefly esophageal motility disorders.
are affected twice as commonly as men. Q. Achalasia.
 Patients care of postprandial fullness, early satiety,
and epigastric pain. Any one or more of these Esophageal motility disorders include:
symptoms may be present.  Achalasia

 Morning symptoms are characteristic and pain or

nausea may occur on waking.
 Diffuse esophageal spasm

 Nutcracker esophagus
4
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264  Hypertensive lower esophageal sphincter  Nitrates and calcium channel blockers provide
 Scleroderma (systemic sclerosis) short-term benefit. Nitroglycerin, 0.3 to 0.6 mg, or
isosorbide dinitrate, 2.5 to 5 mg sublingually or 10
Achalasia (Esophageal Aperistalsis; Megaesophagus) to 20 mg orally is used before meals. The calcium
channel blocker nifedipine, 10 to 20 mg orally or
 Achalasia (a Greek term which means “does not
sublingually before meals, is also effective.
relax”) is neurogenic esophageal motility disorder
characterized by impaired esophageal peristalsis  Endoscopic injection of botulinum toxin into LES
and a lack of lower esophageal sphincter (LES) can provide temporary relief. Botulinum toxin
relaxation during swallowing. relaxes LES by blocking cholinergic excitatory
nerves in the sphincter.
Etiology
Diffuse Esophageal Spasm
 There is loss of inhibitory neurons in the distal
esophagus leading to impaired relaxation of smooth  Diffuse esophageal spasm is characterized by non-
muscle. peristaltic contractions of long duration. This
 Primary idiopathic achalasia accounts for most of happens due to dysfunction of inhibitory nerves.
the patients. There is patchy degeneration of nerve cell processes
 Secondary achalasia occurs due to malignant in the esophagus.
infiltration of the esophagus, lymphoma, Chagas’
Clinical Features
disease, eosinophilic gastroenteritis, and neuro-
degenerative disorders.  Diffuse esophageal spasm presents with chest
pain and dysphagia. Chest pain is retrosternal and
Clinical Features may radiate to both arms, and the sides of the
 Achalasia occurs at any age but usually begins jaw mimicking the pain of myocardial ischemia.
between ages 20 and 60. However, presence of dysphagia should help
 Dysphagia, chest pain, and regurgitation are the distinguish the pain from myocardial ischemia.
main symptoms. Dysphagia is if insidious onset and
Investigations
gradually progressive over months to years.
Dysphagia occurs with both liquids and solids.  Barium swallow shows uncoordinated simulta-
Aspiration may occur due to regurgitation of neous contractions that produce the appearance of
retained food and saliva in the esophagus. Weight “corkscrew” esophagus.
loss is also common.  Esophageal manometry shows increased luminal
pressure.
Investigations
Treatment
 Esophageal manometry is the preferred investigation
of choice. It shows elevated resting esophageal  Smooth muscle relaxants such as sublingual nitro-
pressure and failure of LES to relax on swallowing. glycerin (0.3 to 0.6 mg) or longer-acting agents such
Cholecystokinin (CCK), which causes relaxation of as isosorbide dinitrate (10 to 30 mg orally before
LES in normal people, causes contraction of the LES meals) and nifedipine (10 to 20 mg orally before
in achalasia. This happens because of loss of meals) are helpful.
inhibitory neurons.
 Barium swallow shows proximal esophageal dilation Nutcracker Esophagus
and beaklike narrowing of terminal esophagus.  This refers to hypertensive esophageal peristaltic
Manipal Prep Manual of Medicine

 Chest X-ray may show absence of the gastric air contractions. Hypertensive peristaltic contractions
bubble. An air-fluid level in the mediastinum in the may be due to cholinergic or myogenic hyper-
upright position represents retained food in the activity.
esophagus.  Patients present with chest pain, dysphagia, or both.
 Fluoroscopy shows loss of peristalsis in the lower Chest pain usually occurs at rest but may be
two-thirds of the esophagus. brought on by swallowing. Dysphagia for solids
 Endoscopy is helpful to exclude other causes of and liquids may occur.
dysphagia, particularly gastric carcinoma.  Investigations and treatment is same as diffuse
esophageal spasm.
Treatment
 Balloon dilatation and laproscopic Heller’s myotomy Hypertensive Lower Esophageal Sphincter


of the LES.  This refers to spastic contraction of LES and failure

4  Endoscopic myotomy is also an effective proce-

dure.
to relax. This leads to dysphagia. Investigations and
treatment are same as diffuse esophageal spasm.

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Scleroderma  Most duodenal ulcer patients have increased acid 265
 Esophageal involvement is present in up to 90% of secretion, whereas acid secretion is normal or even
patients with scleroderma. Scleroderma primarily decreased in patients with gastric ulcer. Hence,
involves the smooth muscle layer of the gut wall, increased acid may play an important role in the
resulting in atrophy and sclerosis of the distal two- causation of duodenal ulcer and impaired mucosal
thirds of the esophagus. This produces aperistalsis defense may play an important role in the causation
or low amplitude contractions, and low or absent of gastric ulcer.
lower esophageal sphincter pressure.  NSAIDs inhibit the synthesis of protective prosta-
 The proximal esophagus (striated muscle) is spared glandins which play an important role in the mucosal
and exhibits normal motility. defense, and lead to ulcer formation.
 Patients commonly present with dysphagia.  H. pylori infection is associated with increased gastric
acid secretion and decreased duodenal mucosal
Treatment bicarbonate secretion. This leads to duodenal ulcer.
H. pylori infection causes chronic inflammation of
 Prokinetic drugs such as metoclopramide and
gastric mucosa which overwhelms the gastric
mosapride increase esophageal sphincter pressure,
mucosal defense mechanisms and leads to gastric
improve peristalsis, and enhance gastric emptying.
ulcer formation.
 Erythromycin is also beneficial in scleroderma. It acts
as a motilin agonist which increases gastric contrac- Clinical Features
tions and lowers esophageal sphincter pressure.
 Epigastric pain (dyspepsia) is the most common
symptom of peptic ulcer. However, some patients
Q. Discuss the etiology, clinical features, investigations
may have silent ulcers which come to attention due
and management of peptic ulcer disease.
to bleeding or perforation. Pain is well localized,
 Peptic ulcer is a break in the gastric or duodenal felt in the epigastrium and not severe. It is usually
mucosa that penetrates through the muscularis burning type but can also be gnawing, dull, aching,
mucosae. or “hunger-like.”
 Peptic ulcer arises when there is decrease in  Pain occurs in episodes (periodicity), lasting 1–3 weeks
mucosal defensive factors or increase in ulcerogenic every time, 3–4 times a year. In between, patient is
factors such as acid and pepsin. free of pain.
 Peptic ulcers occur more commonly in duodenum  The typical pain pattern in duodenal ulcer occurs
than stomach but can also occur in the jejunum after 2 to 3 hours after a meal and is frequently relieved
anastomosis to stomach and ileum adjacent to by antacids or food, whereas gastric ulcer pain is
Meckel’s diverticulum. worsened by intake of food. Pain that awakes the
 They are more common in men than women. patient from sleep (between midnight and 3 am) is
 Duodenal ulcers occur commonly between 30 and the most discriminating symptom, and is seen in
55 years of age, whereas gastric ulcers occur two-thirds of duodenal ulcer patients and one-third
commonly between 55 and 70 years of age. of gastric ulcer patients.
 Nausea and weight loss are common in gastric
Etiology ulcer, whereas weight gain may be present in
duodenal ulcer patients because pain relief from
TABLE 4.13: Etiology of peptic ulcer food makes them eat more frequently.
• H. pylori infection (produces mucosal damage)  Epigastric pain which becomes constant, and
• NSAIDs and aspirin radiates to the back may indicate ulcer penetration
• Gastrinoma (Zollinger-Ellison syndrome) into pancreas.
• Malignancy (gastric, lymphoma)
 Sudden onset of severe, generalized abdominal pain
• Vascular insufficiency including crack cocaine use (produces
mucosal ischemia and damage)
may indicate ulcer perforation with consequent


peritonitis.
Gastrointestinal System

• Radiation therapy (mucosal damage)

• Carcinoid syndrome  Pain worsening with meals, nausea, and vomiting
• Crohn’s disease of undigested food suggest gastric outlet obstruc-
• Stress (acute illness, burns, head injury) tion.
• Smoking and alcohol intake  Tarry stools or coffee ground vomitus indicate
• Idiopathic bleeding from ulcer.
 Physical examination is often normal in uncompli-
Pathophysiology cated peptic ulcer except mild epigastric tenderness.
 Most cases of peptic ulcer are due to Helicobacter Sometimes pallor may be present due to chronic
pylori infection and use of nonsteroidal anti-
inflammatory drugs (NSAIDs).
blood loss from ulcer. In peptic ulcer perforation
board like rigidity of abdominal wall is found. 4
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266 TABLE 4.14: Differences between gastric and duodenal ulcer
Factors Gastric ulcer Duodenal ulcer
Age 55–70 years 30–55 years
Sex Equal in both sexes More in males
Acid secretion Normal or decreased Increased
Course of the illness Less remittent More remittent
Episodes of pain Immediately after food Occur 1 to 3 hours after a meal
Antacids Inconsistent relief of pain Prompt relief of pain
Food Provokes the pain Relieves the pain
Night pains Rare Common
Effect on weight Weight loss Weight gain

Investigations Acid Neutralizing/Inhibitory Drugs

Blood tests Proton pump (H+, K+-ATPase) inhibitors
 Anemia may be present due to acute or chronic  Proton pump inhibitors (PPIs) are the most potent

blood loss from the ulcer. Increased WBC count and acid inhibitory agents available and are the drug
increased amylase and lipase suggests ulcer pene- of choice to treat peptic ulcer. They covalently bind
tration into the pancreas. Serum gastrin levels may and irreversibly inhibit H+, K+-ATPase which is the
be high in patients with Zollinger-Ellison syndrome. final pathway in acid secretion. These are given for
Upper GI scopy 4 to 6 weeks.
 Examples are omeprazole, esomeprazole, lanso-
 This is the procedure of choice for the diagnosis of

duodenal and gastric ulcers. Biopsy can also be taken prazole, rabeprazole, and pantoprazole.
during endoscopy. Duodenal ulcers are virtually H2 receptor blockers
never malignant and do not require biopsy.  These agents decrease acid secretion. Examples are

Barium swallow ranitidine, famotidine, and nizatidine. All are

 Can be used for screening patients with uncompli-
equally effective. They are less commonly used now
cated dyspepsia. However, it is less commonly used because of availability of PPIs.
 These agents are given for 4 to 6 weeks.
now because of wide availability of endoscopy.
Tests for H. pylori Antacids
 They relieve the pain by neutralizing the acid. They
 Mucosal biopsies can be obtained during endoscopy

for rapid urease test and for histologic examination. are mainly used for symptomatic relief of epigastric
Noninvasive tests for H. pylori include stool antigen pain.
 Commonly used antacids are mixtures of aluminum
test and urea breath test.
hydroxide and magnesium hydroxide. Aluminum
Complications of Peptic Ulcer hydroxide can produce constipation and phosphate
 Hemorrhage. depletion; magnesium hydroxide may cause loose
stools. Combining both will neutralize the side effects
 Perforation.
of each other.
 Penetration into adjacent structures.
 Dose is 15–30 ml 4 to 6 times per day.
 Gastric outlet obstruction due to scarring.
 Calcium carbonate and sodium bicarbonate are
Manipal Prep Manual of Medicine

Differential Diagnosis other potent antacids.

 Peptic ulcer disease must be distinguished from Mucosal Protective Agents
other causes of epigastric distress (dyspepsia).
Sucralfate
Treatment  Sucralfate is a complex sucrose salt which becomes

a viscous paste within the stomach and duodenum

 The goal of treatment is to provide relief of symp-
in acidic pH. Thus it forms a coating on ulcers and
toms (pain or dyspepsia), promote ulcer healing,
helps in healing. It does not act in alkaline pH.
and ultimately prevent ulcer recurrence and
Hence, giving it along with other acid suppressing
complications.
agents may render it ineffective.
General Measures Bismuth-containing preparations


 Avoid smoking and spicy food.  These agents coat the ulcer, prevent further pepsin/

4 


Cut down or quit alcohol intake.
Avoid aspirin and NSAIDs
acid-induced damage and stimulate prostaglandins,
bicarbonate, and mucus secretion.

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 Colloidal bismuth subcitrate (CBS) and bismuth sub- Pathogenesis 267
salicylate (BSS) are the most widely used prepara-  Erosions begin to develop within hours of major
tions. These compounds are commonly used as one trauma or serious illness. They are thought to result
of the agents in an anti H. pylori regimen. from derangements in the balance between gastric
Prostaglandin analogues acid production and mucosal protective mecha-
 These agents enhance mucosal defense and repair.
nisms. Hypersecretion of acid due to excessive
They also enhance mucous bicarbonate secretion gastrin stimulation of parietal cells is seen in
and stimulate mucosal blood flow. Example is patients with head trauma.
prostaglandin E1 derivative misoprostal.  In critically ill patients, increased concentrations of
 Misoprostol is contraindicated in pregnant women
refluxed bile salts or the presence of uremic toxins
because it can cause uterine bleeding and contrac- can denude the glycoprotein mucous barrier and
tions. lead to ulcer formation.
 Ischemia in shock, sepsis, and trauma can lead to
H. pylori Eradication impaired perfusion of the gut and lead to ulcer
 H. pylori should be eradicated in patients with docu- formation.
mented peptic ulcer disease. H. pylori eradication Clinical Features
prevents the recurrence of peptic ulcer and also
helps in remission of gastric MALT lymphoma. The  The most common presentation of stress ulcers is
agents used with the greatest frequency include the onset of acute upper GI bleed like hematemesis
amoxicillin, metronidazole, tetracycline, clarithro- or melena in a patient with an acute critical illness.
mycin, and bismuth compounds. Combination  Hypotension may occur due to severe bleeding and
therapy should be used to eradicate H. pylori. there may be drop in hemoglobin concentration
Treatment should be given for 10–14 days. requiring blood transfusions.

Surgical Treatment Evaluation

 Less commonly used now because of the availa-  Gastric lavage can identify the presence of blood
bility of effective medical therapy. in the upper GI tract.
 Partial gastrectomy with Bilroth I anastomosis for  Upper GI scopy will show the ulcers.
gastric ulcer. Treatment
 Options for duodenal ulcer are truncal vagotomy
plus pyloroplasty, selective vagotomy plus pyloro-  H2 blockers (ranitidine, famotidine, nizatidine).
plasty, and highly selective vagotomy.  Proton pump inhibitors (omeprazole, pantoprazole,
 Emergency surgery is indicated in penetrating or esomeprazole).
perforating peptic ulcers.  Sucralfate.
 Prostaglandin analogs (misoprostol).
Q. Stress ulcers.  Bleeding ulcers require endoscopic therapies
(epinephrine injection, electrocauterization, or
 Stress ulceration is defined as ulceration of the upper clipping of the bleeding vessels).
gastrointestinal (GI) tract (esophagus, stomach,
duodenum) that occurs due to hospitalization. Prevention of Stress Ulcers
 They are usually shallow but deeper lesions can  Antacids.
cause massive hemorrhage and/or perforation.  H2 blockers (ranitidine, famotidine, nizatidine).
 Stress ulcers are the most common cause of gastro-  Sucralfate.
intestinal (GI) bleeding in intensive care unit (ICU)  Proton pump inhibitors (omeprazole, pantoprazole,
patients. esomeprazole).
Prostaglandin analogs (misoprostol).



TABLE 4.15: Risk factors for development of stress ulcers
Gastrointestinal System

• Shock
 Early enteral nutrition.
• Sepsis
• Liver failure Q. Role of Helicobacter pylori in peptic ulcer.
• Renal failure Q. Tests to detect Helicobacter pylori.
• Multiple trauma
• Head or spinal trauma (Cushing’s ulcer)
Q. Helicobacter pylori eradication regimens.
• Burns (Curling’s ulcer)  H. pylori is a spiral-shaped, flagellated, gram-
• Organ transplant recipients negative, urease-producing bacterium. It lives in the
4
• Prior history of peptic ulcer disease or upper GI bleeding mucus layer of stomach. Some bacterial cells are
• Mechanical ventilation
found adherent to the mucosal cells.

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268  It has several acid resistance mechanisms of which  H. pylori colonization increases the lifetime risk of
the most important is production of urease enzyme peptic ulcer disease, gastric cancer, and B cell non-
which hydrolyses urea to produce buffering Hodgkin’s gastric lymphoma. Smoking increases
ammonia. ulcer and cancer risk in H. pylori positive indivi-
duals.

Diseases Caused by H. pylori

 Gastroesophageal reflux disease and dyspepsia
 Gastritis
Figure 4.3 H. pylori  Peptic ulcer disease
 Gastric adenocarcinoma
Epidemiology
 MALT (mucosal-associated lymphoid tissue)
 Helicobacter pylori is the most common chronic lymphoma
bacterial infection in humans.
 Prevalence of H. pylori is more in developing coun- Tests to Detect H. pylori Infection
tries and low socioeconomic groups. Prevalence is Non-invasive Tests
high in the older population—presumably acquired
 Urea breath test (UBT): This is a quick and simple
in their childhood when hygiene was less good than
test which can be used as a screening test. The urea
today.
is labeled with isotope 13C (Carbon-13). The patient
 Humans are the only important reservoir of H.
drinks a solution of this labeled urea and then blows
pylori. Colonization is common in childhood
into a tube. If H. pylori urease is present, the urea is
institutions suggesting direct person-to-person
hydrolyzed and labeled carbon dioxide is detected
spread.
in breath samples. The test is very sensitive (97%)
 It spreads by fecal-oral or oral-oral route. and specific (96%). The breath test is also used to
demonstrate eradication of the organism following
Pathogenesis
treatment.
 H. pylori does not invade the mucosa. Instead, it  H. pylori fecal antigen test: H. pylori antigen can be
damages the mucosa by disrupting the mucous detected in the stool by immunoassay. This is less
layer, liberating enzymes and toxins, and adhering accurate than urea breath test but useful in children.
to the gastric epithelium. Urease is an important Can be used to detect post-treatment eradication.
enzyme secreted by it. Urease converts urea into
 Serological tests: Detect IgG antibodies by enzyme-
ammonia, thus alkalinizing the surrounding acidic
linked immunosorbent assay (ELISA) or immunoblot.
medium so that H. pylori can survive, but simulta- These tests may be positive even after eradication
neously produces ammonia-induced mucosal therapy and therefore are not useful for confirming
damage. eradication or the presence of a current infection.
 H. pylori produces toxins, Vac A (vacuolating toxin) These are especially useful for epidemiological
and Cag A (cytotoxic associated protein) as well as studies.
urease and adherence factors. H. pylori infection
produces superficial gastritis characterized by Invasive Tests
inflammatory cell infiltration of the mucosa. These
 These tests require endoscopy.
inflammatory cells release cytokines which damage
 Biopsy urease test: Gastric biopsies are added to a
the mucosa.
urea solution containing phenol red. If H. pylori are
Manipal Prep Manual of Medicine

 Effects of H. pylori infection depend on the location

present, the urease enzyme splits the urea to release
within the stomach. The antral predominant
ammonia which raises the pH of the solution and
infection results in increased gastrin production,
causes a rapid colour change.
probably via local impairment of somatostatin
 Culture: Biopsies specimens can be cultured and
release. Increased gastrin stimulates increased acid
antibiotic sensitivity ascertained.
production leading to duodenal ulcer formation.
Body predominant infection leads to diffuse  Histology: Biopsy specimens can be stained (Giemsa)
gastritis, gastric atrophy and decreased acid and looked for the presence of H. pylori.
production. Patients with body-predominant
Treatment
infection are predisposed to gastric ulcer and gastric
adenocarcinoma. Some patients have mixed  There are many triple drug regimens for eradication
infection of both antrum and body with varying of H. pylori infection. These are as follows.


clinical effects. The mucosa appears red endo-  Omeprazole, amoxicillin, and clarithromycin (OAC).

4 scopically, and histologically there is epithelial cell

damage.
 Bismuth subsalicylate, metronidazole, and tetra-
cycline (BMT).

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 Lansoprazole, amoxicillin, and clarithromycin TABLE 4.16: Etiology of GI bleeding 269
(LAC). Etiology of upper GI bleeding (hematemesis)
 These triple drug combinations come as kits and • Peptic ulcers (responsible for the majority of cases)
are given for 10 to 14 days. • Esophageal varices due to portal HTN
• Portal hypertensive gastropathy
Q. Define hematemesis. What are the causes of hema- • Mallory-Weiss tears
temesis? How do you investigate and manage a • Vascular anomalies (hereditary hemorrhagic telangiectasia)
case of hematemesis? • Ca esophagus
• Ca stomach
Q. Causes of upper gastrointestinal (GI) bleeding. • Erosive gastritis (due to NSAIDs, alcohol, or severe medical
Q. Causes of lower GI bleeding. or surgical illness)
• Erosive esophagitis (due to GERD)
Q. Describe the approach to a case of acute GI • Aortoenteric fistulas
bleeding. How do you differentiate between upper • Post-surgical (anastomosis)
and lower GI bleeding based on clinical features? • Systemic causes; hemophilia, thrombocytopenia
Etiology of lower GI bleeding
 Hematemesis is vomiting of blood which may be
• Dysentery (bacillary, amebic)
obviously red or have an appearance similar to
• Lower GI malignancy (Ca colon, Ca rectum)
“coffee-grounds”. Usually the source of bleeding • Inflammatory bowel disease (Crohn’s disease, ulcerative colitis)
in hematemesis is GI tract above the ligament of • Hemorrhoids
Treitz. Ligament of Treitz corresponds to the • Diverticulitis
junction of duodenum and jejunum. • Necrotizing enterocolitis
 Lower GI bleeding is described as bleeding that • Mesenteric vascular disease
occurs below the level of ligament of Treitz. • Angiodysplasia
 Hematochezia refers to presence of fresh blood in • Radiation-induced telangiectasia
stool. • Radiation enteritis
 Melena refers to passage of black, tarry, and foul • Polyp
smelling stool. • Post-biopsy or polypectomy

 Guaiac test can be performed if there is doubt

whether red color is due to blood or some other sub-
stance. It will be positive in the presence of blood.
 History of syncopal attack (due to hypotension)
may be present if there is massive bleeding.
 NSAID use or previous history of peptic ulcer or
dyspepsia suggests peptic ulcer.
 History of heavy alcohol ingestion or retching
before hematemesis suggests a Mallory-Weiss tear.
 History of chronic liver disease with portal hyper-
tension suggests esophageal varices as the cause of
hematemesis.
 History of dysphagia and weight loss prior to hema-
temesis suggests esophageal or gastric malignancy.
Figure 4.4 Ligament of Treitz
 History of constipation or pain while passing stool
suggests hemorrhoids or anal fissure as the cause
Clinical Presentation
of blood in stool.
History


 Vomiting of red blood or coffee ground vomitus. Examination Findings

Gastrointestinal System

Red blood indicates fresh bleeding and coffee  Heart rate and blood pressure can give an idea of
ground indicates bleeding sometime back. Other amount of bleed. Significant bleeding leads to
causes of red colored vomitus are food coloring, tachycardia and postural hypotension. A systolic
colored gelatin or drinks, red candy, beets, and blood pressure less than 100 mm Hg suggests
tomato skins. severe bleeding. Pallor may be present.
 Patient may give history of melena. Melena refers  Patient may present in a state of shock with
to black, tarry, foul smelling stool. It indicates hypotension, cold peripheries, excessive sweating,
bleeding in upper GI tract. Other causes of black in severe bleeding.
colored stool are bismuth or iron preparations,
spinach, blueberries, black grapes, and licorice.
 Signs of liver disease such as jaundice, and ascites
may be present. 4
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270 TABLE 4.17: Differences between upper and lower GI bleeding
Upper GI bleeding Lower GI bleeding
Site of bleed Above ligament of Treitz Below ligament of Treitz
Common causes Peptic ulcer, esophageal varices, erosive Diverticulosis, hemorrhoids, carcinoma colon,
gastritis, carcinoma stomach, Mallory-Weiss inflammatory bowel disease
tear
Presentation Vomiting of blood (fresh blood or coffee Fresh blood in stool
ground) melena
Bowel sounds Increased Normal
Nasogastric aspiration Shows blood Clear
Investigation of choice Upper GI endoscopy Lower GI endoscopy
BUN/creatinine ratio Increased Normal
Proton pump inhibitors Useful in treatment No benefit

Investigations Management of Hematemesis

Complete Blood Count with Differential Count Initial Stabilization
 Hb, PCV are important to know the amount of  In patients with significant bleeding, two intra-
bleed. Hemoglobin does not fall immediately after venous lines should be inserted. Blood should be
bleeding because hemodilution takes some time (up sent for grouping and cross-matching for 2 to 4 units
to 72 h). MCV (mean corpuscular volume) may be or more of packed red blood cells.
low due to development of iron deficiency anemia  Aggressive fluid replacement with normal saline
due to recurrent blood loss. or Ringer lactate should be started till blood is
available. In mild to moderate bleeding fluid
Coagulation Profile
replacement is enough and blood transfusion is not
 Bleeding time, clotting time, and prothrombin time. required.
Sometimes, a bleeding diathesis may be the cause  A nasogastric tube (Ryle’s tube) should be placed
of hematemesis or it may exacerbate bleeding due in all patients with hematemesis. The aspiration of
to other causes. red blood or “coffee grounds” confirms an upper
gastrointestinal source of bleeding. Periodic aspira-
Blood Grouping and Crossmatching
tion of the nasogastric tube can identify ongoing
 This is required because patient may require blood bleeding or rebleeding.
transfusion in case of massive hematemesis.  In actively bleeding patients, platelets are trans-
Liver Function Tests and Renal Function Tests fused if the platelet count is below 50,000/mcL.
Uremic patients (who have platelet dysfunction)
 To rule out liver disease and renal failure. Renal with active bleeding are given three doses of
failure (prerenal azotemia) can occur in case of desmopressin (DDAVP), 0.3 μg/kg intravenously,
massive hematemesis and hypotension. Pre-existing at 12-hour intervals. Fresh frozen plasma is given
renal failure can cause uremic gastropathy and if prothrombin time is prolonged and INR
cause hematemesis. (international normalized ratio) is >1.5.
Endoscopy
Pharmacological Measures to Control Bleeding
Upper GI endoscopy is the investigation of choice in
Manipal Prep Manual of Medicine


Octreotide or vasopressin infusion
hematemesis. It is diagnostic as well as therapeutic.
 Continuous intravenous infusion of octreotide (100
 Colonoscopy is useful to identify the causes of
μg IV bolus, followed by 100 μg/h) reduces
lower GI bleed.
splanchnic blood flow and bleeding pending
 Endoscopy can identify the source of bleeding, endoscopy. Octreotide is especially useful for
determine the risk of re-bleeding and render endo- variceal bleed, but can also be used for upper GI
scopic therapy. bleeding of any cause. Vasopressin can also be used
Ultrasound Abdomen but not as effective as octreotide.
To identify liver disease such as cirrhosis and any GI Proton pump inhibitors (PPIs)
malignancy.  Intravenous proton pump inhibitors (omeprazole,

lansoprazole, or pantoprazole) reduce bleeding in



Angiography patients with peptic ulcer. They can be used in

4 If bleeding persists and endoscopy fails to identify a
bleeding site.
bleeding due to other causes. PPIs also reduce the
recurrence of bleeding after endoscopic therapy.

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Endoscopic Therapy  Causes vasoconstriction. 271
 Urgent endoscopy is done in patients with active  Reduces portal vein pressure.
bleeding not responding to conservative measures.
Uses of Octreotide
Otherwise, it can be done once the patient is hemo-
dynamically stable, usually within 24 hours after  Treatment of growth hormone producing tumors
admission. (acromegaly and gigantism), when surgery is
 Hemostasis can be achieved in actively bleeding contraindicated.
lesions with endoscopic therapies such as cautery,  Treatment of diarrhea and flushing episodes
injection, or ligation. Actively bleeding varices can associated with carcinoid syndrome.
be treated with sclerosant injection or rubber band  Treatment of diarrhea in people with vasoactive
ligation of the bleeding varix. Actively bleeding intestinal peptide secreting tumors (VIPomas).
ulcers, angiomas, or Mallory-Weiss tears can be  Treatment of mild cases of glucagonoma when
controlled with either injection of epinephrine, surgery is not an option.
cauterization, or application of an endoclip.  Bleeding esophageal varices (given as intravenous
 Colonoscopy should be done in lower GI bleed and infusion, acts by reducing portal venous pressure).
appropriate endoscopic therapy should be done to  Radiolabeled octreotide is used in nuclear medicine
stop bleding (application of clips, epinephrine imaging to noninvasively image neuroendocrine and
injection, or laser photocoagulation). other tumors expressing somatostatin receptors.
 Radiolabeled octreotide can also be used in the
Intra-arterial Embolization or Vasopressin treatment of unresectable neuroendocrine tumors
 Angiographic treatment is used rarely in patients with expressing somatostatin receptors.
persistent bleeding even after endoscopic therapy.  Hypoglycemia: Octreotide is also used in the treat-
ment of refractory hypoglycemia in neonates and
Transvenous Intrahepatic Portosystemic Shunts (TIPS) sulphonylurea-induced hypoglycemia in adults.
 Placing a stent from the hepatic vein to the portal
vein through the liver reduces portal venous pressure Adverse Effects
and helps in control of acute variceal bleeding. It is  Gastrointestinal side effects are common and
used when endoscopic modalities have failed. include diarrhea, nausea, abdominal discomfort,
gallbladder abnormalities, such as cholelithiasis
Surgery and microlithiasis.
Surgery is indicated in:  Bradycardia, conduction abnormalities, and
 Severe, life-threatening hemorrhage from peptic arrhythmias.
ulcer not responsive to other measures.  Hypoglycemia and hyperglycemia occur due to
 Coexisting reason for surgery (e.g. perforation, alteration in glucose metabolism.
obstruction, malignancy)  Hypothyroidism.
 Aortoenteric fistula.  Skin itching.
 Pain at the injection site.
Q. Octreotide.  Headache and dizziness.
 Octreotide is a long acting analogue of somato-  Rare side effects include acute anaphylactic
statin. Its pharmacological actions are similar to reactions, pancreatitis and hepatitis.
somatostatin which is a natural hormone.
Q. Discuss the etiology, classification, clinical features,
Pharmacokinetics investigations and management of malabsorption
 Octreotide acts on somatostatin receptors. It is syndrome.
administered through a subcutaneous or intra- Q. What are the disorders causing malabsorption?


venous route. It is absorbed quickly and completely

Gastrointestinal System

How do you approach a case of suspected mal-

after subcutaneous and intravenous injection. absorption?
Pharmacological Actions  Malabsorption refers to impaired absorption of
 Inhibits secretion of many hormones, such as gastrin, nutrients.
cholecystokinin, glucagon, growth hormone,  Malabsorption occurs mainly due to diseases of
insulin, secretin, pancreatic polypeptide, TSH, and small intestine since this is the major site of
vasoactive intestinal peptide. absorption of nutrients.
 Reduces intestinal and pancreatic secretion.  Fat is the most difficult to absorb and hence most mal-
 Reduces gastrointestinal motility and inhibits
contraction of the gallbladder.
absorption syndromes have steatorrhea. A stool test
for fat is the best screening test for malabsorption. 4
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272  There are three stages of nutrient absorption: Steatorrhea
Luminal, mucosal, and postabsorptive.  Steatorrhea is due to fat malabsorption.
– The luminal phase involves mechanical mixing
 The hallmark of steatorrhea is the passage of pale,
and digestive enzymes.
bulky, and foul smelling stools, which float on top
– The mucosal phase requires a properly of the toilet water and are difficult to flush. Also,
functioning mucosal membrane for absorption. patients find floating oil droplets in the toilet
– The postabsorptive phase becomes facilitated by following defecation.
an intact blood supply and lymphatic system.
 Malabsorption can occur due to problems in any of Weight Loss and Fatigue
these three phases.
 Weight loss is due to protein energy malnutrition
from malabsorption. Fatigue is due to weight loss
TABLE 4.18: Causes of malabsorption
plus coexisting anemia.
Disorders of luminal phase
• Enzyme deficiency: Chronic pancreatitis, cystic fibrosis.
Flatulence and Abdominal Distention
• Enzyme inactivation: Zollinger-Ellison syndrome.
• Diminished bile salt synthesis: Parenchymal liver diseases.  Bacterial fermentation of unabsorbed food sub-
• Impaired bile secretion: Bile duct obstruction, chronic stances releases gases, such as hydrogen and
cholestasis. methane, causing flatulence.
• Increased bile salt loss: Ileal disease or resection.  Flatulence often causes uncomfortable abdominal
• Reduced luminal availability of specific nutrients: Intrinsic factor distention and cramps.
deficiency in pernicious anemia causing Vit B12 deficiency.
• Bacterial consumption of nutrients: Bacterial overgrowth Edema
causing vitamin B12 deficiency.
 Protein malabsorption causes hypoalbuminemia
Disorders of mucosal phase
which causes peripheral edema.
• Defects in brush border hydrolysis: Sucrase-isomaltase
deficiency, lactase deficiency.  With severe protein depletion, ascites may
• Defects in mucosal absorption (villous atrophy): Celiac sprue, develop.
tropical sprue, lymphoma, Whipple’s disease, radiation
enteritis, AIDS, giardiasis, Crohn’s disease. Anemia
Disorders of postabsorptive, processing phase  Anemia develops due to iron deficiency (microcytic
• Defects in enterocyte processing: Abetalipoproteinemia. anemia), folic acid or vitamin B12 deficiency (macro-
• Defects in lymphatic transport: Intestinal lymphangiectasia, cytic anemia). Iron deficiency is common in celiac
intestinal tuberculosis. disease. Vitamin B12 deficiency is common in Crohn’s
Systemic diseases causing malabsorption disease with ileal involvement or ileocecal TB.
• Thyrotoxicosis (rapid transit through gut)
• Hypothyroidism (impaired intestinal motility, bacterial Bleeding Disorders
overgrowth)
 Bleeding tendency is due to vitamin K malabsorp-
• Diabetes mellitus (impaired intestinal motility, bacterial
overgrowth) tion and decreased production of Vit K dependent
• Scleroderma (impaired intestinal motility, bacterial clotting factors. Ecchymosis is usually seen but
overgrowth) patient can also have melena and hematuria.
Drugs causing malabsorption
• Antibiotics (vitamin B12 and vitamin K deficiency)
Bone Pain and Pathologic Fractures
Manipal Prep Manual of Medicine

• Methotrexate (folic acid antagonist, causes inhibition of crypt  This is due to vitamin D deficiency causing osteo-
cell division) penia or osteomalacia.
• Cholestyramine (binds bile salts)  Malabsorption of calcium can lead to secondary
• Laxatives (rapid transit through gut) hyperparathyroidism.
• Liquid paraffin causes fat soluble vitamin deficiency
Neurologic Manifestations
Clinical Features
 Electrolyte disturbances, such as hypocalcemia and
Diarrhea hypomagnesemia, can lead to tetany, manifesting
 Diarrhea is the most common complaint. It is due as the Trousseau’s sign and the Chvostek sign.
to the osmotic load received by the intestine because  Vitamin malabsorption can cause generalized
of unabsorbed carbohydrates and solutes. motor weakness (pantothenic acid, vitamin D) or


 Bacterial action producing hydroxy fatty acids from peripheral neuropathy (thiamine, Vit B12), a sense
4 undigested fat also can increase fluid secretion from
the intestine, further worsening the diarrhea.
of loss for vibration and position (Vit B12), night
blindness (vitamin A), and seizures (biotin).

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TABLE 4.19: Summary of features of specific nutrient mal-  Measurement of fat soluble vitamin levels in the 273
absorption blood (A, D, E, K); prothrombin time.
Carbohydrates: Watery diarrhea, flatulence, acidic stool pH,  Near infrared reflectance analysis (NIRA): This may
milk intolerance. become the procedure of choice in future. NIRA
Protein: Edema, muscle atrophy, amenorrhea. can simultaneously measure fecal fat, nitrogen, and
carbohydrates in a single sample.
Fat: Pale, bulky, foul smelling stool which floats on water and
difficult to flush. Diarrhea without flatulence. Weight loss.  14C-triolein breath test: The test involves measure-
ment of breath CO2 after ingestion of the radiolabeled
Vitamins
• Vitamin A: Follicular hyperkeratosis, night blindness.
triglyceride triolein, and provides a measure of fat
• Vitamin B 12 : Anemia, neuropathy, subacute combined absorption.
degeneration of the spinal cord.
• Vitamin B1, B2: Cheilosis, painless glossitis, Tests for Carbohydrate Absorption
acrodermatitis, angular stomatitis.  Oral glucose tolerance test: There will be failure of
• Folic acid: Megaloblastic anemia. blood glucose levels to rise after glucose loading.
• Vitamin D: Tetany, pathologic fractures due to osteomalacia,
 D-xylose test: Patient ingests 25 g of D-xylose, and
muscular irritability.
• Vitamin K: Bleeding tendency.
urine is tested for the presence of D-xylose.
Excretion of lesser amounts of D-xylose suggests
Minerals and electrolytes
abnormal absorption (as in celiac sprue).
• Iron: Anemia, glossitis, pica.
 Lactose tolerance test: After ingestion of 50 g lactose,
• Calcium: Tetany, pathologic fractures due to osteomalacia,
muscular irritability. blood glucose levels are monitored. Insufficient
• Zinc: Anorexia, weakness, tingling, impaired taste. increase in blood glucose plus the development of
symptoms is diagnostic of lactose intolerance.
Investigations Another test is measurement of breath hydrogen
after lactose ingestion. An increase in breath
Imaging Studies hydrogen is diagnostic.
 Endoscopy: Upper GI scopy is helpful to visualize  Breath tests: Breath tests using hydrogen, 14CO2, or
stomach, duodenum and upper jejunum. A 13CO2 can be used to diagnose specific forms of
cobblestone appearance of the duodenal mucosa is carbohydrate malabsorption (e.g. lactose, fructose,
seen in Crohn’s disease. Reduced duodenal folds sucrose isomaltase and others). All of these breath
and scalloping of the mucosa may be seen in celiac tests rely on bacterial fermentation of nonabsorbed
disease. Small bowel biopsy can also be taken carbohydrate and therefore concurrent antibiotic
during endoscopy. administration often alters the results.
 CT and ultrasound abdomen: May be helpful in the
diagnosis of chronic pancreatitis and other abnor- Tests for Protein Absorption
malities in the abdomen.
 Serum albumin will be low.
 Barium studies: An upper gastrointestinal series with
 Intravenous radioactive chromium is used to label
small bowel follow-through or enteroclysis (a
circulating albumin. In case of protein losing
double contrast study performed by passing a tube
enteropathy radioactivity appears in stools.
into the proximal small bowel and injecting barium
 Measurement of nitrogen in the stool will be more
and methylcellulose) can provide information about
than 2.5 gm.
the gross morphology of the small intestine. For
example, small bowel diverticula and mucosal  Excretion of alpha-1 antitrypsin in the stool
abnormalities can be identified. (normally it is absent in the stool).
 Wireless capsule endoscopy: Wireless capsule endo-
Tests for Absorption of other Substances
scopy allows for visualization of the entire small
bowel. Because of the risk of retention, it should be  Complete blood count (anemia), serum iron, ferritin,


avoided in patients with suspected small bowel folate, vitamin B12 level, Schilling test (for Vit B12
Gastrointestinal System

strictures. malabsorption), serum calcium, sodium, potassium,

β-carotene, and prothrombin time should be obtained
Tests for Fat Absorption in all patients with suspected malabsorption.
 Fecal fat estimation: Increase in stool fat excretion
is known as steatorrhea. A 72-hour fecal fat estima- Tests for Bacterial Overgrowth
tion can detect steatorrhea. More than 6 g/day of  The gold standard for diagnosis of bacterial over-
fat in stool is pathologic. growth is the direct quantitative measurement of
 Sudan III stain: Sudan stain on a spot stool bacterial counts from aspirated intestinal fluid.
sample can detect more than 90% of patients with
steatorrhea.
However, this is invasive and hence the following
tests are used more commonly. 4
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274  Hydrogen breath test: This is used to detect bacterial  A 24-hour urine is then collected for determination
overgrowth in the intestine. Oral lactulose or of the percent excretion of the oral dose. Normally
glucose is metabolized by bacteria with the at least 10% of the radiolabeled vitamin B12 is
production of hydrogen. An early rise in the breath excreted in the urine. In patients with pernicious
hydrogen indicates bacterial overgrowth in the anemia or impaired absorption, less than 10% of
small intestine. the radiolabeled vitamin B12 is excreted.
 14C-glycocholic acid breath test: It is rarely done now  Next, the above step is repeated after the addition
and has been replaced by the hydrogen breath test. of intrinsic factor. If this second urine collection is
Patient is given radiolabelled bile acid (14C- normal, it proves intrinsic factor deficiency or
glycocholic acid) orally. Bacteria in the intestine pernicious anemia.
deconjugate the bile acid, releasing [14C]-glycine,  If urinary excretion of Vit B12 is still less than 10%
which is metabolized and appears in the breath as after adding intrinsic factor, then the test is repeated
14CO2. after a course of antibiotics. Small intestinal bacterial
overgrowth is suggested if an abnormal test is
Serologic Tests normalized after a course of antibiotics. If the absorp-
 IgA endomysial antibody and IgA anti-tTG antibody tion is abnormal even after addition of intrinsic
both are found in celiac disease. IgG or IgA anti- factor and exclusion of bacterial overgrowth, it
gliadin antibodies are also present in celiac sprue. suggests terminal ileal disease. The Schilling test
can also be abnormal in pancreatic insufficiency and
Intestinal Mucosal Biopsy and Histopathology celiac disease. Normalization after pancreatic
 Villous atrophy is seen in celiac disease, and tropical enzyme substitution or a gluten-free diet is useful
sprue. for diagnosis of these causes of malabsorption.
 The Schilling test can also be used to determine the
Treatment functional integrity of the ileal mucosa after
treatment of ileal Crohn’s disease.
 Treat the underlying cause.
 Many labs have stopped doing the Schilling test,
 Avoid milk and milk products in lactose intole-
due to lack of production of radiolabeled Vit B12
rance.
test substances. Also, the treatment remains same
 Gluten-free diet in celiac disease. (i.e. injection of Vit B12), even if the exact cause was
 Pancreatic enzyme supplements in pancreatic identified. Moreover, upper GI scopy can detect
insufficiency. many causes of Vit B12 deficiency. Hence, Schilling
 Reduction of long chain fatty acids and low fat diet test it is not being performed now.
in fat malabsorption.
 Antibiotics are the therapy for bacterial overgrowth. Q. Celiac sprue (celiac disease, gluten-sensitive
 Corticosteroids, anti-inflammatory agents such as enteropathy).
mesalamine, are used to treat inflammatory bowel Q. Dermatitis herpetiformis.
disease such as Crohn’s disease.
 Replacement of specific nutrients which are  Celiac disease is an inflammatory condition of the
deficient such as folic acid, iron and Vit B12, Vit D, small intestine precipitated by the ingestion of
etc. wheat, rye, and barley in individuals with genetic
 Caloric and protein replacement. predispositions.
 It occurs throughout the world but common in
Northern Europe. There is increased incidence of
Manipal Prep Manual of Medicine

Q. Schilling test.
celiac disease within families but the exact mode of
 This test is performed to determine the cause for inheritance is unknown.
vitamin B12 malabsorption. Vitamin B12 is absorbed
in the terminal ileum. Etiology
 Causes of vitamin B12 malabsorption are intrinsic  Inflammatory damage to the intestinal mucosa is
factor defficiency, atrophic gastritis, small intestinal due to gluten protein of wheat. Gluten is also
bacterial overgrowth, exocrine pancreatic insuffi- present in barley, rye and oats. The toxic component
ciency, and ileal disease. in gluten is gliadin.
 Schilling test is performed by administering 1 μg  Over 90% of patients will have HLA-DQ2. However,
of radiolabelled Vit B12 orally, followed by an environmental factors also play an important role.
intramuscular injection of 1000 microgram of


Vit B12 one hour later to saturate Vit B12 binding Pathogenesis

4 sites so that absorbed radiolabelled B12 is excreted

in the urine.
 Glutens are partially digested in the intestinal
lumen to release gliadin and other peptides.

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 Gliadin is rich in glutamine. Some of the glutamines  Extraintestinal manifestations of celiac disease 275
in gliadin are deamidated by the enzyme tissue include rash (dermatitis herpetiformis), neurologic
transglutaminase (tTG), generating negatively disorders (myopathy, epilepsy), psychiatric dis-
charged glutamic acid residues. orders (depression, paranoia), and reproductive
 These altered gliadin peptides are recognized by disorders (infertility, spontaneous abortion).
local intestinal T cells as foreign, thereby stimulat-
Investigations
ing an immune response. B cells are also activated
and produce various antibodies such as antigliadin,  Duodenal/jejunal biopsy: It shows characteristic
antiendomysial, and anti-tissue transglutaminase changes of celiac sprue.
(tTG) antibodies.  Serologic markers: Useful in supporting the diagnosis.
 This immune response causes damage to intestinal An IgA anti-tissue transglutaminase antibody (IgA
mucosa resulting in mal-digestion and malabsorp- TTG), detected by ELISA is the best first test for
tion of nutrients. suspected celiac sprue. Antigliadin IgA and IgG
antibodies are sensitive but not specific. Antiendo-
Pathology mysial IgA antibodies are highly sensitive and
specific for celiac disease.
 The mucosa of the jejunum is predominantly  Tests for malabsorption of proteins, carbohydrate, fat and
affected, and the damage decreases towards the vitamins: All patients with celiac disease should be
ileum. screened for vitamin and mineral deficiencies and
 There is absence of villi, making the mucosal surface have bone densitometry.
flat. Histological examination shows crypt hyper-
plasia with chronic inflammatory cells in the lamina Treatment
propria and subtotal villous atrophy. In the lamina  Treatment consists of a lifelong gluten-free diet.
propria there is an increase in lymphocytes and Wheat, rye, and barley should be excluded from
plasma cells. the diet.
 A lactose-free diet is also recommended until symp-
toms improve because of secondary lactase deficiency.
 Any deficient vitamins and minerals should be
replaced. Women of childbearing age should be
given folic acid supplements.
 90% of patients on gluten-free diet experience
symptomatic improvement within 2 weeks. A small
Figure 4.5 Normal and abnormal villi percentage of patients do not improve on a strict
gluten-free diet (refractory sprue). Such patients
may have atrophic mucosa. Lymphoma should be
Clinical Features
ruled out in refractory sprue. Steroids may be of
 Celiac disease can present at any age but usually in help in refractory sprue if there is persistent
infancy after weaning on to gluten-containing inflammation.
foods. It has a female preponderance.
 Many patients present with anemia or osteoporosis Complications
without gastrointestinal symptoms. These indivi-  Intestinal lymphoma.
duals usually have proximal intestinal disease that  Ulcerative jejunitis.
impairs iron, folate, and calcium absorption.
 Patients with significant mucosal involvement Dermatitis Herpetiformis
present with diarrhea, abdominal distension and  Dermatitis herpetiformis is the most common skin
bloating after eating, weight loss or growth retarda- disorder associated with celiac disease. The pre-


tion, and features of vitamin and mineral defi- sence of dermatitis herpetiformis is pathognomonic
Gastrointestinal System

ciencies. Absorption of all nutrients, electrolytes, of celiac sprue.

fat-soluble vitamins, calcium, magnesium, iron,  It is characterized by an itchy papular vesicular
folate, and zinc, is affected. Diarrhea is due to eruption on the skin. These blisters rupture due to
decreased surface area for water and electrolyte scratching, dry up, and leave an area of pigmenta-
absorption and the osmotic effect of unabsorbed tion and scarring.
luminal nutrients.  The diagnosis can be confirmed by the demonstra-
 There is an increased incidence of other auto- tion of granular IgA deposition in the skin in an
immune diseases, like thyroid disease, type-1 area not affected by blistering.
diabetes, primary biliary cirrhosis and Sjögren’s
syndrome.
 Treatment includes dapsone in addition to gluten
free diet. 4
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276 Q. Tropical sprue. Clinical Features
 Tropical sprue is a chronic diarrheal disease, The disease is common in middle-aged men and affects
possibly of infectious origin, that involves the small multiple systems. Onset is insidious and features
intestine and is characterized by malabsorption of include diarrhea, steatorrhea, abdominal pain, weight
nutrients, especially folic acid and vitamin B12. loss, migratory large-joint arthropathy, fever,
 It was called tropical sprue because it is common dementia and ophthalmologic symptoms. It is a major
in residents or visitors of a tropical area. Tropical cause of culture negative endocarditis.
sprue is endemic in most of Asia, some Caribbean Investigations
islands, Puerto Rico and parts of South America.
Biopsies from the small intestine and other involved
In India, it is mainly seen in south India. Epidemics
organs show presence of PAS-positive (periodic acid-
of tropical sprue occur, lasting up to 2 years in these
Schiff) macrophages containing the characteristic
areas.
small bacilli.
Etiology Treatment
 Etiology is unknown, but is likely to be due to Ceftriaxone or penicillin initially followed by tri-
an infectious agent because it responds to anti- methoprim/sulfamethoxazole for minimum 1 year.
biotics. Combination of doxycycline and hydroxychloroquine
 Some of the implicated bacteria include E. coli, can be used in patients with sulpha allergy.
Klebsiella and Enterobacter.
Q. Protein-losing enteropathy.
Clinical Features
Protein-losing enteropathy is not a specific disease but
 Patients present with diarrhea, anorexia, abdominal
refers to many disorders characterized by excess
distension and weight loss which can be acute or
protein loss into the gastrointestinal tract.
insidious in onset.
 Steatorrhea is common. Nutritional deficiencies, TABLE 4.20: Causes of protein-losing enteropathy
especially of folate and vitamin B12 develop after
Gastrointestinal mucosal diseases causing protein loss into GIT
several months to years. Patient may also have • Ulcerative colitis
glossitis, stomatitis, and peripheral edema. • Gastrointestinal carcinomas
• Peptic ulcer
Investigations • Amyloidosis
 Endoscopy and mucosal biopsy: Endoscopy shows • Celiac sprue
flattening of duodenal folds and “scalloping.” • Whipple’s disease
• Ménétrier’s disease (hypertrophic gastropathy)
The jejunal mucosal biopsy show partial villous
atrophy which is usually less severe than celiac Lymphatic dysfunction
disease. Changes are seen in whole of small • Intestinal tuberculosis
• Obstruction (enlarged mesenteric nodes or lymphoma)
intestine.
• Lymphangiectasia
 Other causes of diarrhea must be excluded
Cardiac disorders
particularly Giardia, which can mimick tropical
• Heart failure
sprue.
• Chronic pericarditis
Treatment
Clinical Features
Manipal Prep Manual of Medicine

Broad-spectrum antibiotics and folic acid can cure the

condition, especially if the patient leaves the tropical  There is peripheral edema, low serum albumin and
area and does not return. Antibiotic treatment involves globulin levels in the absence of renal and hepatic
tetracycline 1 g daily for up to 6 months. Doxycycline disease.
can be used instead of tetracycline.  Both albumin and globulin are low in protein losing
enteropathy. If only albumin is low with normal
Q. Whipple’s disease. globulin, search for renal and/or hepatic disease
 Whipple’s disease is a chronic multisystem disease  Patients with increased protein loss into the gastro-
caused by the gram-positive bacteria Tropheryma intestinal tract from lymphatic obstruction often
whippelii. Tropheryma whippelii has high infectivity have steatorrhea and diarrhea.
but low virulence.
 Although the first descriptions of the disorder
Diagnosis


described a malabsorption syndrome with small  Loss of protein into the gastrointestinal tract can be

4 intestinal involvement, the disease also affects the

joints, CNS, and CVS.
demonstrated by giving radiolabeled proteins and its
quantification in stool during a 24 or 48 hours period.

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Treatment Investigations 277
 Underlying disease should be treated. For example, Lactose Tolerance Test
gluten-free diet in celiac sprue or mesalamine for  50 gm of lactose is given orally and blood glucose
ulcerative colitis. levels are measured at 0, 1 and 2 hours. An increase
in blood glucose by less than 20 mg/dL plus the
Q. Discuss the etiology, clinical features, investiga- development of symptoms is diagnostic.
tions, and management of lactose intolerance.  This test is cumbersome and time consuming, and
 The term lactose intolerance refers to the develop- has largely been replaced by the lactose breath
ment of GI symptoms such as abdominal pain, hydrogen test.
bloating, flatulence, diarrhea, and vomiting after
Lactose Breath Hydrogen Test
the ingestion of lactose. It is due to lactase deficiency
which hydrolyses lactose into glucose and galactose.  This is the most common test done. Oral lactose is
 Intolerance to lactose-containing foods (e.g. dairy given in the fasting state, at a dose of 2 gm/kg
products) is a common problem worldwide. (maximum dose, 25 g). Unabsorbed lactose is
fermented by intestinal bacteria leading to release
Etiology of Lactose Intolerance of hydrogen gas that is absorbed into the blood and
excreted by lungs. Breath hydrogen is sampled at
Primary lactase deficiency baseline and at 30-minute intervals after the
• Racial or ethnic ingestion of lactose for three hours.
• Developmental
 Baseline and post-lactose values are compared. A
• Congenital lactase deficiency
breath hydrogen value of more than 20 ppm is
Secondary lactase deficiency diagnostic of lactose malabsorption.
• Bacterial overgrowth
• Infectious enteritis Genetic Test for Primary Lactose Malabsorption
• Giardiasis
 Missing gene coding for lactase may be identified.
• Mucosal injury
• Celiac disease
Intestinal Biopsy and Measurement of Lactase Enzyme Levels
• Inflammatory bowel disease (especially Crohn’s disease)
• Drug- or radiation-induced enteritis  This is the “gold standard” test for lactose mal-
absorption. However, it is not routinely required.
Pathophysiology
Treatment
 Lactose is hydrolyzed by intestinal lactase to
glucose and galactose in the intestine which are then
Dietary Lactose Restriction
absorbed. If there is lactase deficiency, lactose  Initially complete restriction of lactose-containing
cannot be hydrolyzed and absorbed. The un- foods should be tried till the symptoms improve.
absorbed lactose creates an osmotic load in the Improvement of symptoms confirms the diagnosis
intestine, which draws fluid into the intestine. also.
Excess fluid in the intestine causes dilatation of  Small quantities of lactose may subsequently be
intestine and diarrhea. In the colon, free lactose is reintroduced into the diet, with careful monitoring
fermented by colonic bacteria to yield short-chain of symptoms. Many patients will tolerate graded
fatty acids and hydrogen gas. The combined increase in lactose containing foods.
increase in fecal water, intestinal transit, and
generated hydrogen gas accounts for abdominal Enzyme Replacement
pain, bloating, flatulence, and diarrhea.  Commercially available “lactase” preparations are
actually bacterial or yeast beta-galactosidases. They
Clinical Features can be taken with food and reduce symptoms in


 Among adults, the age of presentation is 20 to many lactose intolerant subjects.

Gastrointestinal System

40 years.
 Abdominal pain: May be crampy in nature and is often Probiotics
localized to the periumbilical area or lower quadrant.  Lactase-containing probiotics may be beneficial.
 Bloating However, studies have shown mixed results.
 Flatulence
 Diarrhea: Stools are usually bulky, frothy, and Calcium Supplementation
watery.  Avoidance of milk and other dairy products can
 Vomiting lead to reduced calcium intake, which may increase
 Borborygmi may be audible on physical examina-
tion and to the patient.
the risk for osteoporosis and fracture. Hence,
calcium supplementation should be given to all 4
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278 patients. A dose of 1200–1500 mg/day is necessary Clinical Features
for adolescents and young adults.  Constitutional symptoms like anorexia, fatigue,
 In addition, the vitamin D status should also be fever, night sweats, and weight loss.
monitored. If necessary, Vit D supplementation  Nonspecific chronic abdominal pain, diarrhea,
should also be given. constipation, or blood in the stool.
 A doughy mass may be palpable in right lower
Q. Abdominal tuberculosis. quadrant of abdomen.
 Abdominal tuberculosis (TB) refers to tuberculosis  Abdominal distension due to ascites.
of intestine, peritoneum and abdominal lymph nodes.  Patients may also present acutely with small
One or more of these structures may be affected. intestinal obstruction and colonic perforation.
 The most common site of intestinal involvement is
the ileocecal region. The affinity of M. tuberculosis Complications of Abdominal Tuberculosis
for this site may be due to its relative stasis and  Intestinal perforation
abundant lymphoid tissue.  Abscess formation
 Tuberculosis is being seen more frequently in  Fistula formation (between intestinal loops and into
patients with HIV infection. the exterior through skin)
 Malabsorption
Etiology
 Massive bleeding
 Mycobacterium tuberculosis.  Intestinal obstruction.
Routes of Spread
Differential Diagnosis
 Intestinal tuberculosis occurs due to swallowing of
 TB must be differentiated from other diseases
infected sputum, or hematogenous spread from active
affecting ileocecal region such as Crohn’s disease,
pulmonary or miliary TB, or ingestion of contami-
Yersinia enterocolitica, Y. pseudotuberculosis infection
nated milk or food, or spread from adjacent organs.
and cecal carcinoma.
Pathology
Diagnosis
Intestinal Tuberculosis
 Routine laboratory tests reveal mild anemia, increased
 The macroscopic appearance of the intestinal TB ESR and hypoalbuminemia.
can be categorized into 3 types.  Chest X-ray may show evidence of active or old
Ulcerative (60%) tuberculosis.
 This is characterized by multiple superficial ulcers.  Plain X-ray abdomen may show calcified lymph
 Ulcers are perpendicular to the long axis of intestine.
nodes and dilated bowel loops.
Healing may result in scarring and stricture formation.  Tuberculin skin test is positive in most patients.
 This pattern has been associated with a virulent  Ascitic fluid analysis
clinical course. – High leukocyte count of 150 to 4000/mm3, with
predominant lymphocytes.
Hypertrophic (10%) – Fluid is exudative (protein content is >3.0 mg/dL).
 This is characterized by scarring, fibrosis, and
– AFB stain and culture may be positive but have
hypertrophic mass (pseudotumor). low yield rate.
Ulcerohypertrophic (30%) – Polymerase chain reaction (PCR) assay can
Manipal Prep Manual of Medicine

 This is characterized by an inflammatory mass rapidly detect mycobacteria.

centering around the ileocecal valve with thickened – Adenosine deaminase (ADA) levels in ascitic
and ulcerated intestinal walls. fluid has high sensitivity and specificity for
 It is common in ileocecal TB compared to other detecting tuberculosis.
segments of intestine. – Cartridge based nucleic acid amplification
test (CB-NAAT/GeneXpert) of ascitic fluid.
Peritoneal Tuberculosis  Barium meal and small bowel follow-through may
 Peritoneum is studded with tubercles. show mucosal ulcerations, strictures (string sign),
 Wet type presents with ascites which develops due and hypersegmented bowel loops.
to “exudation” of proteinaceous fluid from the  Barium enema may show deformed cecum, a gaping
tubercles. Most patients have this type. and incompetent ileocecal valve with narrowing of


 Dry type is characterized by fibro adhesive form of terminal ileum (inverted umbrella sign).

4 
the disease.
Patients may have combination of both of the above.
 Ultrasound abdomen may show ascites, thickened ileo-
cecal region, ileocecal mass and lymphadenopathy.

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 CT scan: May show concentric mural thickening of population. There is increased concordance for IBD 279
the ileocecal region, with or without proximal in monozygotic twins than dizygotic twins.
intestinal dilatation. Adjacent mesenteric lympha-  Environmental factors: Good domestic hygiene has
denopathy may be seen on CT. been shown to be a risk factor for CD but not for
 Colonoscopy shows ulcers, strictures, nodules, UC. It is suggested that in a clean environment,
pseudopolyps, fibrous bands, fistulas, and intestinal immune system is not exposed to many
deformed ileocecal valves. pathogens and hence, may not be able to handle an
 Laparoscopy: Laparoscopy examination is an infection. Hence, even minor infections trigger
effective method of diagnosing peritoneal tuber- prominent inflammation.
culosis because it can directly visualize tubercles  Psychosocial factors: Major life events such as illness
and biopsy of the peritoneum can be taken. Biopsy or death in the family, divorce or separation, inter-
specimens may be tested for AFB by staining, personal conflict, or other major loss are associated
culture and PCR. with an increase in IBD symptoms.
 Nutritional factors: High sugar and fat intake is
Treatment
suspected to be associated with IBD, but more
 Treatment is similar to that for pulmonary TB. studies are needed to confirm it.
Conventional antitubercular therapy for at least  Smoking: Patients with CD are more likely to be
6 months including initial 2 months of HREZ (e.g. smokers, and smoking has been shown to exacer-
isoniazid, rifampicin, ethambutol and pyrazina- bate CD. In contrast, there is an increased risk of
mide) followed by 4 months HR is recommended UC in nonsmokers and nicotine has been shown to
in all patients. be an effective treatment of UC.
 Surgery is required for complications such as  Appendicectomy: Appendicectomy is protective for
intestinal perforation, abscess or fistula, massive the development of UC, particularly if performed
bleeding, and intestinal obstruction. before the age of 20. In contrast, appendicectomy
may increase the risk of development of CD.
Q. What are inflammatory bowel diseases (IBD)?  Intestinal microflora: IBD is characterized by an over-
Discuss the etiology of IBD. aggressive immune response to luminal bacterial
 Inflammatory bowel disease (IBD) is an immune antigens and other products, occurring against a
mediated chronic intestinal inflammation. There are background of genetic susceptibility. There is an
two major types of IBD—ulcerative colitis (UC) and alteration in the bacterial flora, with an increase in
Crohn’s disease. anaerobic bacteria in CD and an increase in aerobic
 Ulcerative colitis (UC) affects only the colon and bacteria in UC.
Crohn’s disease (CD) can affect any part of the GI  Immunological factors: Many immunological abnor-
tract. There is overlap between these two conditions malities have been described in IBD patients. Many
in their clinical, histological and radiological patients lack the ability to appropriately down
features and sometimes differentiation between the regulate antigen-specific or antigen non-specific
two is not possible. It is possible that these condi- inflammatory responses to endogenous luminal
tions represent two aspects of the same disease. antigens. There is upregulation of macrophages and
T helper lymphocytes in IBD which release pro-
Epidemiology inflammatory cytokines. There is also activation of
 IBD occurs worldwide but more common in the other cells (eosinophils, mast cells, neutrophils and
West. Both Crohn’s disease (CD) and ulcerative fibroblasts) which leads to excess production of
colitis (UC) have an incidence of approximately chemokines (lymphokines, arachidonic acid meta
5 to 10 per 100,000 annually. Whites are affected bolites, neuropeptides and free oxygen radicals),
more commonly than non-white races. Jews are all of which can lead to tissue damage.
more affected than non-Jews, and the Ashkenazi


Jews have a higher risk than the Sephardic Jews. Q. Describe the etiology, pathology, clinical features,
Gastrointestinal System

investigations and treatment of Crohn’s disease.

Etiology (Common for Both Crohn’s Disease and
Ulcerative Colitis)  Crohn’s disease is an idiopathic, chronic inflamma-
 The exact etiology of IBD is unknown. But the tory disease of the gastrointestinal (GI) tract that can
pathogenesis involves three factors: Genetic affect any part of the tract from the mouth to the anus.
susceptibility, environmental factors and host It is characterized by exacerbations and remissions.
immune response. Many risk factors have been
identified which are as follows. Epidemiology
 Familial and genetic factors: IBD is more common
amongst relatives of patients than in the general
 Crohn’s disease is slightly commoner in females
(M: F = 1:1.2). 4
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280  Its incidence has a bimodal distribution with the  It can be complicated by anal and perianal disease
onset occurring most frequently between ages 15 and can be the presenting feature, often preceding
to 30 years and 40 to 60 years old. colonic and small intestinal symptoms by many
 It is more common in Western population and in years.
urban areas than rural areas.  Enteric fistulae, e.g. from intestine to bladder or
vagina occur in some cases.
Etiology  Examination may show weight loss and general ill-
 Refer previous question on IBD. health. Right iliac fossa tenderness and mass are
occasionally found. The mass is due either to
Pathology inflamed loops of bowel that are matted together
Macroscopic Changes or to an abscess. Anal fissures or perianal abscesses
may be present. Extra-intestinal features such as
 Crohn’s disease can affect any part of the gastro-
arthritis may be present.
intestinal tract from the mouth to the anus but
commonly affects the terminal ileum and ascending Investigations
colon (ileocolonic disease).
 Blood tests: Anemia is common due to blood loss.
 The disease is characterized by skip lesions (normal
ESR, CRP, and WBC counts are raised indicating
areas in between affected areas).
inflammation. Hypoalbuminemia is present in
 The involved small bowel is usually thickened and
severe disease due to protein loss from intestine. Pre-
narrowed. There are deep ulcers and fissures in the
sence of antisaccharomyces cerevisiae antibodies
mucosa of the intestine, producing a cobblestone
(ASCA) with absence of anti-neutrophil cytoplas-
appearance.
mic antibodies (pANCA) is seen in Crohn’s disease
 Fistulae and abscesses may be seen in the colon. and can distinguish Crohn’s from ulcerative colitis.
Microscopic Changes  Stool examination: This should be done to exclude
infective causes of diarrhea.
 In Crohn’s disease the inflammation extends
 Fecal calprotectin: This is high in IBD. Calprotectin
through all layers (transmural) of the bowel.
is a protein released by neutrophils. When there is
 There is an increase in chronic inflammatory cells inflammation in the intestine due to IBD neutro-
and lymphoid hyperplasia. phils infiltrate intestine and release calprotectin,
 Non-caseating granulomas may be seen. resulting in an increased level in the stool. This test
can help distinguish between IBD and IBS (irritable
bowel syndrome).
 Barium meal follow-through: Examination may show
an asymmetrical alteration in the mucosal pattern
with deep ulceration, and areas of narrowing or
stricturing (string sign). Changes are commonly
seen in terminal ileum. Skip lesions with normal
bowel in between.
 Ultrasound, CT or MRI abdomen: These are used to
Figure 4.6 Skip leisons in Crohn’s disease
define the thickness of the bowel wall and mesen-
tery as well as intra-abdominal and para-intestinal
Clinical Features
abscesses and also used to rule out alternate patho-
 It is a chronic disease with remissions and exacerba- logy in acute presentations.
Manipal Prep Manual of Medicine

tions.  Radionuclide scans: With radiolabelled leucocytes are

 The disease may present insidiously or acutely. used to identify small intestinal and colonic disease
 The major symptoms are diarrhea, abdominal pain, and to localize extra-intestinal abscesses.
and weight loss.  Colonoscopy: Superficial or deep ulceration with
 Constitutional symptoms of malaise, lethargy, cobblestone appearance and deep fissures. Skip
anorexia, nausea, vomiting and low-grade fever lesions. Rectal sparing.
may be present.  Video capsule endoscopy: Can visualize the small
 The abdominal pain can be colicky, or felt as dis- bowel when regular endoscopy or colonoscopy
comfort. cannot reach these areas.
 Diarrhea may be associated with blood, making it diffi-  Colonic biopsy: Can be used to confirm the diagnosis
cult to differentiate from ulcerative colitis. Steatorrhea of IBD and exclude other diagnoses. The biopsy


may be present due to small intestinal involvement. characteristically reveals crypt abscesses, branching

4  It can present as an emergency with acute right iliac

fossa pain mimicking appendicitis.
of crypts, atrophy of glands, and loss of mucin in
goblet cells in ulcerative colitis.

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Treatment Nutritional Therapies 281
 The aim of management is to induce and then  Patients with active CD respond to bowel rest,
maintain a remission. along with total enteral or total parenteral nutrition
(TPN). Bowel rest and TPN are as effective as gluco-
General Measures corticoids at inducing remission of active CD but
 Cigarette smoking should be stopped. are not effective as maintenance therapy. However,
 Diarrhea can be controlled with loperamide or UC does not respond to dietary measures.
codeine phosphate. Diarrhea in long standing Surgical Management
inactive disease may be due to bile acid malabsorp-
 In Crohn’s disease surgery is indicated in stricture
tion and responds to cholestyramine.
and obstruction unresponsive to medical therapy,
 Anemia may be due to B12/folic acid or iron massive hemorrhage and refractory fistula.
deficiency, which should be replaced.
Q. Describe the etiology, pathology, clinical features,
5-ASA (Amino Salicylic Acid) Agents investigations and treatment of ulcerative colitis.
 The mainstay of therapy for IBD is 5-ASA agents.
These agents are effective at inducing remission in  Ulcerative colitis is an idiopathic inflammatory
both UC and CD and in maintaining remission in condition of the colon which results in diffuse friabi-
UC. It is unclear whether they can maintain lity and superficial erosions on the colonic wall.
remission in CD also. Example is sulfasalazine.  It is the most common form of inflammatory bowel
disease worldwide. There is an increased prevalence
 Sulfasalazine is not broken down in small intestine
of ulcerative colitis in nonsmokers or those who
and the intact molecule reaches colon where it is
recently quit smoking.
broken down by colonic bacteria into sulfa and 5-ASA
moieties. 5-ASA acts as local anti-inflammatory Etiology
agent in the colon.
 Refer to previous question on IBD.
 There are many side effects of sulfasalazine includ-
ing folate malabsorption. These side effects are due Pathology
to sulfa moiety. Patients on sulfasalazine should be Macroscopic Changes
given folic acid supplements.
 UC usually involves only colon and spares small
 Newer sulfa-free agents such as mesalamine,
intestine except in a few patients where terminal
olsalazine and balsalazide have less of side
ileum can also be involved (backwash ileitis).
effects.
 Mucosa is erythematous and has a fine granular
 Topical mesalamine enemas are effective in mild-
surface that looks like sandpaper. Mucosal involve-
to-moderate distal CD. Mesalamine suppositories
ment is continuous without skip lesions.
are effective in treating proctitis.
 Rectum is also involved in 95% of cases.
Glucocorticoids  Inflammatory swollen mucosa gives the appearance
of pseudopolyps.
 These are effective in patients with moderate to
 In severe inflammation, toxic dilatation can occur.
severe UC and CD. Prednisone 40 to 60 mg/d is
 On healing, the mucosa can return to normal,
given if there is poor response to 5-ASA therapy.
although there is usually some residual glandular
 Glucocorticoids play no role in maintenance therapy distortion.
of either UC or CD. Once clinical remission has been
induced, they should be tapered slowly. Microscopic Changes
 Mucosa shows a chronic inflammatory cell infiltrate
Immunosuppressive Agents in the lamina propria. Crypt abscesses and goblet
 Azathioprine, 6-mercaptopurine, methotrexate and cell depletion are also seen.


cyclosporine are mainly employed as steroid spar-  Inflammation is restricted to the mucosa and
Gastrointestinal System

ing agents in the management of glucocorticoid- submucosa of the colon.

dependent IBD. Tacrolimus and mycophenolate
mofetil are newer immunosuppressive agents.

Biologics
 Infliximab is a monoclonal antibody against TNF
that is extremely effective in CD. Two other anti-
TNF agents, adalimumab and golimumab may be
less immunogenic than infliximab and have shown
efficacy in the treatment of Crohn’s disease. Figure 4.7 Ulcerative colitis 4
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282 Clinical Features Flexible Sigmoidoscopy and Colonoscopy
 The disease can be mild, moderate or severe, and  Sigmoidoscopy is enough initially since total
in most patients runs a course of remissions and colonoscopy may precipitate toxic megacolon or
exacerbations. perforation in severe disease. Colonoscopy can be
 The major symptom in ulcerative colitis is diarrhea done in mild cases.
with blood and mucus, sometimes accompanied by  Mucosa is erythematous. In addition, petechiae,
lower abdominal discomfort. Diarrhea is often exudates, touch friability, and frank hemorrhage
nocturnal and/or postprandial. may be present.
 General features include malaise, lethargy and  Severe cases may have ulcers, profuse bleeding, and
anorexia. copious exudates. Colonic involvement is continuous
 Aphthous ulceration in the mouth is seen. in ulcerative colitis (skip lesions in Crohn’s disease).
 When there is proctitis (rectal inflammation) blood  Pseudopolyps may be present.
mixed with the stool, urgency and tenesmus are seen.
 Extraintestinal manifestations can be seen in some Barium Enema
patients and include episcleritis, scleritis, uveitis,  Rarely used in the diagnosis of ulcerative colitis. It
peripheral arthropathies, sacroiliitis, ankylosing may be normal in mild forms of disease.
spondylitis, primary sclerosing cholangitis,  It shows ulcers, shortening of the colon, loss of
erythema nodosum, and pyoderma gangrenosum. haustrae, narrowing of the lumen, and pseudo-
polyps. It should be avoided in severely ill patients
Investigations as it may precipitate ileus with toxic megacolon.
Blood Tests
Colonic Biopsy
 Anemia is common due to blood loss. ESR, CRP and
white cell counts are raised indicating inflamma-  Can be used to confirm the diagnosis. It reveals
tion. Hypoalbuminemia is present in severe disease crypt abscesses and chronic changes including
due to protein loss from intestine. pANCA may be branching of crypts, atrophy of glands, and loss of
positive in ulcerative colitis. mucin in goblet cells.

Stool Examination Treatment

 This should be done to exclude infective causes of  Treatment is same as that of Crohn’s disease.
colitis.  Surgery (total proctocolectomy with ileostomy) is
indicated in severe ulcerative colitis associated with
Plain X-ray Abdomen toxic megacolon, colonic perforation and massive
 To exclude toxic dilatation of colon. colonic hemorrhage.

Q. Comparison of ulcerative colitis and Crohn’s disease.

TABLE 4.21: Comparison of ulcerative colitis and Crohn’s disease

Ulcerative colitis Crohn’s Disease
Male:female ratio Equal Slightly more common in males
Smoking May prevent disease May cause disease
Oral contraceptives No increased risk Increased risk
Appendectomy Protective Not protective
Manipal Prep Manual of Medicine

Gross blood and mucus in stool Frequent Occasional

Systemic symptoms Occasional Frequent
Pain abdomen Occasional Frequent
Abdominal mass Rare Yes
Perineal disease Rare Frequent
Small intestinal involvement No (only backwash ileitis) Yes
Stricture of intestine Occasional Frequent
Intestinal obstruction Rare Frequent
Response to antibiotics No Yes
Recurrence after surgery No Yes
pANCA-positive Frequently Rarely
Presence of anti-Saccharomyces cerevisiae antibodies No Yes


Rectal sparing Rarely Frequently

4
Skip leisons No Yes
Cobblestone appearance No Yes

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Q. Toxic megacolon.  Physical examination reveals a toxic appearing 283
patient with altered sensorium, tachycardia, fever,
 Toxic megacolon is total or segmental nonobstruc- postural hypotension, lower abdominal distension
tive colonic dilatation associated with systemic and tenderness.
toxicity. It is a potentially lethal complication of
 Peritonitis symptoms indicate bowel perforation.
inflammatory bowel disease (IBD) or infectious
 Large doses of steroids and analgesics may mask
colitis.
the signs or symptoms of toxic megacolon.
 Colonic dilatation without systemic toxicity is not
considered toxic megacolon (e.g. Hirschsprung’s Investigations
disease, chronic constipation, intestinal pseudo-
obstruction, diffuse gastrointestinal dysmotility).  Anemia related to blood loss.
 Leukocytosis.
Etiology  Electrolyte disturbances.
 Hypoalbuminemia.
TABLE 4.22: Causes of toxic megacolon  ESR and CRP are usually increased.
Inflammatory bowel disease  Plain X-ray abdomen: Transverse or right colon is
• Ulcerative colitis commonly affected, multiple air-fluid levels in the
• Crohn’s disease colon are seen. Normal colonic haustral pattern is
Infectious either absent or severely disturbed.
• Clostridium difficile pseudomembranous colitis  Stool specimens should be sent for culture, micro-
• Salmonella—typhoid and non-typhoid scopic analysis, and C. difficile toxin.
• Shigella  Ultrasonography and computed tomography (CT).
• Campylobacter
 Limited endoscopy without bowel preparation is
• Yersinia
useful to diagnose the cause. Only minimal air
• Entamoeba histolytica
should be introduced into the colon to avoid
• CMV colitis (common in HIV patients)
worsening ileus or distention and perforation. Full
Ischemia colonoscopy is risky in toxic megacolon. It can lead
to perforation.
Pathogenesis
 Mucosal inflammation leads to the release of Treatment
inflammatory mediators and bacterial products,  Initial therapy is medical. However, a surgical
increased inducible nitric oxide synthase, which in consultation should be obtained upon admission,
turn increases nitric oxide. Nitric acid relaxes and the patient should be evaluated daily by both
smooth muscle in colon leading to dilatation. the medical and surgical team.
 Extension of the mucosal inflammation to the
smooth muscle layer paralyzes the colonic smooth Medical Therapy
muscle, leading to dilatation.  Patients with IBD should be kept nil per oral and a
 Precipitating factors of toxic megacolon include nasogastric tube is inserted to decompress the
hypokalemia, antimotility agents, opiates, anti- gastrointestinal tract. Enteral feeding is begun as
cholinergics, antidepressants, barium enema, and soon as the patient shows signs of improvement.
colonoscopy. Discontinuing or rapid tapering of  Anemia, dehydration, and electrolyte imbalances
corticosteroids, sulfasalazine, or 5-ASA compounds should be treated aggressively.
in IBD may contribute to the development of
 All antimotility agents, opiates, and anticholinergics
megacolon.
should be discontinued as they aggravate ileus.
 Intravenous H2 blockers or proton pump inhibitors
Pathology
should be given to prevent gastric stress ulcers.


 Marked dilatation of the colon, thinning of the  Broad spectrum antibiotics are given to reduce
Gastrointestinal System

bowel wall, and deep ulcers. septic complications and to prevent possible
 Acute inflammation in all layers of the colon. peritonitis in case of perforation (third-generation
cephalosporin plus metronidazole).
Clinical Features
 Intravenous corticosteroids (hydrocortisone 100 mg
 Toxic megacolon affects all ages and both sexes. or equivalent every six to eight hours or by conti-
 Signs and symptoms of acute colitis may precede nuous infusion) should be given to all patients for
the onset of acute dilatation. the treatment of underlying ulcerative colitis or
 Patients usually present with abdominal pain and Crohn’s disease. Steroids do not increase the risk
distention, nausea, vomiting, diarrhea (may or may
not be bloody), and altered sensorium.
of perforation. Steroids are not used in toxic mega-
colon due to C. difficile colitis or infective colitis. 4
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284  If toxic megacolon is due to severe C. difficile colitis  There is edema and hyperemia of the full thickness
(antibiotic induced), the first step is to stop the of the bowel wall.
offending antibiotic, followed by oral vancomycin
via a nasogastric tube. Intravenous vancomycin has Clinical Features
no effect on C. difficile colitis since the antibiotic is  Symptoms usually begin during or shortly after anti-
not excreted into the colon. If there is response to biotic therapy but may be delayed for up to 2 months.
vancomycin, intravenous metronidazole may be  Most patients report mild to moderate greenish,
added at a dose of 500 mg every eight hours. foul-smelling watery diarrhea with lower abdo-
Surgical Therapy minal cramps. With more serious illness, there is
abdominal pain and profuse watery diarrhea with
 Perforation, massive hemorrhage, increasing trans- up to 30 stools per day. The stools may have mucus
fusion requirements, worsening signs of toxicity, but seldom gross blood.
and progression of colonic dilatation are absolute
 Physical examination is normal or reveals left lower
indications for surgery.
quadrant tenderness. There may be fever up to 40°C.
 Subtotal colectomy with end-ileostomy is the proce-
 Rarely fulminant colitis with serious complications,
dure of choice for urgent or emergent surgery.
such as perforation, prolonged ileus, toxic mega-
colon, and death can occur.
Q. Discuss the etiology, clinical features, investigations,
and management of pseudomembranous colitis. Investigations
Etiology Stool studies
 Demonstration of C. difficile toxins in the stool by
 Pseudomembranous colitis is severe inflammation
of the inner lining of the colon. It is most often cytotoxicity assay (toxin B) or rapid enzyme
caused by overgrowth of Clostridioides (formerly immunoassays (EIA) for toxins A and B.
 Culture for C. difficile is sensitive, but slower (2–3
Clostridium) difficile after prolonged broad spectrum
antibiotic therapy. days), more costly, and less specific than toxin
 Commonly implicated antibiotics are: assays, and not used in most clinical settings.
 Fecal leukocytes are present in only 50% of patients
– Ampicillin
with colitis.
– Clindamycin
– Tetracycline Flexible sigmoidoscopy
– Third-generation cephalosporins  Reveals typical pseudomembranes.

– Fluoroquinolones Plain X-ray abdomen

 To look for evidence of toxic dilation or megacolon
Pathogenesis
but are of no value in mild disease.
 C. difficile is an anaerobic bacterium which colonizes
the colon of 3% of healthy adults. It is acquired by Abdominal CT scan
fecal-oral transmission. It is readily transmitted from  Useful in detecting colonic edema, and evaluation

patient to patient by hospital personnel. of possible complications.

 Antibiotics disrupt the normal bowel flora and
allow C. difficile to flourish. Treatment
 After multiplication, it produces two toxins; toxin A  Offending antibiotic should be discontinued. This
and toxin B. Both toxins possess cytotoxic activity alone may lead to resolution of symptoms in mild
and can damage the colon. Both toxins adhere to cases.
Manipal Prep Manual of Medicine

receptors on the human colonocyte brush border,  If diarrhea is severe, the drug of choice is oral vanco-
and cause necrosis and shedding of these cells into mycin, 125 mg orally four times daily due to faster
the lumen. Both the toxins cause an acute inflamma- symptom resolution and fewer treatment failures
tory diarrhea with massive infiltration of the than metronidazole. Vancomycin is not absorbed
intestinal mucosa with neutrophils and monocytes. and acts directly at the infection site. Intravenous
 Shedding of colonic epithelial cells produces shallow vancomycin should be not be used as it is not effec-
ulcers. Serum proteins, mucus, and inflammatory tive. Oral or intravenous metronidazole 500 mg three
cells flow outward from the ulcer, creating a pseudo- times daily is an alternative. In fulminant cases, both
membrane. vancomycin and metronidazole can be combined.
 Fidaxomicin is a new macrolide approved for the
Pathology treatment of C. difficile-associated diarrhea. This


 Rectum and colon show a yellow or off-white mem- agent has a narrower antimicrobial spectrum and

4 brane adherent to the eroded mucosa (pseudomem-

brane). Pseudomembranes are patchily distributed.
alters the gut microflora less than do metronidazole
and vancomycin.

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 Probiotics such as Saccharomyces boulardii, and lacto-  Sudden onset of cramping, left-sided lower abdo- 285
bacillus may help in controlling the disease and also minal pain, and rectal bleeding.
prevent relapses.  Symptoms usually resolve over 24–48 hours and
 Frequent recurrences despite therapy with oral healing occurs within 2 weeks.
vancomycin, can be treated with fecal microbiota  Some have a residual fibrous stricture or segmental
transplantation. colitis.
 Total colectomy may be required in patients with  A minority develop gangrene and peritonitis.
toxic megacolon, perforation, sepsis, or hemorr-
hage. Investigations
 Leukocytosis, metabolic acidosis, and high amylase
Q. Discuss the etiology, clinical features, investigations levels.
and management of mesenteric ischemia.  Plain X-ray abdomen may show ‘thumb-printing’
due to mucosal edema.
Or
 Ultrasound abdomen.
Q. Discuss the etiology, clinical features, investigations  CT abdomen.
and management of ischemic colitis.  Mesenteric or CT angiography shows occluded or
 Mesenteric ischemia is caused by a reduction in narrowed mesenteric artery.
intestinal blood flow. It can be acute or chronic,  Investigations for underlying prothrombotic dis-
involve small or large bowel. orders.
 It is a serious condition and can lead to sepsis, bowel  Colonoscopy and barium enema in ischemic colitis.
infarction, and death.
Treatment
 Ischemic colitis is the most frequent form of mesen-
teric ischemia, affecting mostly the elderly.  Patient is kept nil by mouth (NBM).
 IV fluids and electrolytes.
Etiology of Mesenteric Ischemia  Intravenous antibiotic therapy (ciprofloxacin and
metronidazole).
 Embolic occlusion (emboli arise from heart or
 Embolectomy and vascular reconstruction if possible.
aorta).
 Thrombolysis may sometimes be effective in
 Thrombotic occlusion (due to atherosclerosis).
patients at high surgical risk.
 Hypotension (myocardial infarction, heart failure,
 Anticoagulation in mesenteric vein thrombosis.
arrhythmias or sudden blood loss).
 Laparotomy and resection of the involved segment
 Vasculitis.
with end-to-end anastomosis is required in patients
 Venous occlusion. with bowel gangrene and signs of peritonitis.
 Strangulated hernia.  Small bowel transplantation can be considered in
 Colon volvulus. selected patients.

Clinical Features Q. Discuss the etiology, clinical features, investigations

Small Bowel Ischemia and management of irritable bowel syndrome (IBS).
 It is due to occlusion of superior mesenteric artery.  Irritable bowel syndrome (IBS) is a functional
 Pathological changes may range from mild gastrointestinal disorder characterized by chronic
ischemia to transmural hemorrhagic necrosis and abdominal pain and altered bowel habits in the
gangrene. absence of any organic cause.
 Sudden onset abdominal pain with minimal  Organic causes should be ruled out before making
physical signs. a diagnosis of IBS.
 Abdomen may be distended with diminished


bowel sounds. Etiology

Gastrointestinal System

 Signs of peritonitis may be present.  Hereditary and environmental factors.

 Patients may have evidence of cardiac disease and  Abnormal gastrointestinal motility in the form of
arrhythmia responsible for emboli. exaggerated gastrocolic reflex, altered gastric
emptying, increased small bowel contractions and
Large Bowel Ischemia (Ischemic Colitis) increased small intestinal transit.
 The splenic flexure and descending colon are prone  Visceral hypersensitivity.
for ischemic injury since they have little collateral  Neurotransmitters such as serotonin may be an
circulation. Ischemic injury can range from transient important factor. It stimulates intestinal secretion


colitis to gangrene and fulminant pancolitis.
Patient is usually elderly.
and peristalsis in addition to visceral pain receptors
via 5-HT3 and 5-HT4 pathways. 4
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286  Microscopic inflammation: Detailed immunohistologic  Malabsorption syndromes (such as celiac sprue).
investigation has revealed mucosal immune system  Gastroenteritis.
activation in a subset of patients with irritable bowel  Giardiasis.
syndrome (mostly those with the diarrhea predomi-  Hypercalcemia.
nant type).  Hyperthyroidism.
 Role of infection (post-infectious IBS): Gastroenteritis  Inflammatory bowel disease.
is a common trigger for IBS. The IBS symptoms can
 Colon cancer.
be triggered by an enteric infection and can persist
for weeks, months and years. Investigations
 Psychologic disturbances: Many patients with IBS
have increased anxiety, depression, phobias, and  Since IBS is a diagnosis of exclusion, following
somatization. investigations should be done routinely to exclude
other diseases with similar presentation.
 Certain foods may precipitate an attack, e.g. excess
coffee.  Complete blood count.
 Stool examination—to look for ova, cysts and occult
Clinical Features blood.
 IBS is common in young people. It is 3 times more  Colonoscopy—in those older than 50 years to rule
common in women. out carcinoma colon.
 Hydrogen breath test—if the main symptoms are
Rome IV Criteria for the Diagnosis of IBS diarrhea and increased gas to rule out malabsorp-
tion.
Recurrent abdominal pain on average at least 1 day per week during
the previous 3 months associated with two or more of the following:  Upper GI scopy—if the patient has prominent dys-
• Related to defecation (may be increased or unchanged by pepsia.
defecation)  Ultrasound abdomen.
• Associated with a change in stool frequency
• Associated with a change in stool form or appearance Treatment
Patient Counseling and Dietary Alterations
 Four subtypes of IBS have been recognized:
(1) Constipation predominant, (2) Diarrhea pre-  Patients should be reassured and functional nature
dominant, (3) Mixed, (4) Alternating diarrhea and of the disorder explained. Foods which aggravate
constipation. The usefulness of this classification is symptoms (such as coffee, disaccharides, legumes,
debatable because the symptoms can change from and cabbage) should be avoided. Such diet is called
one type to another in a given patient. low FODMAP diet. (FODMAP stands for ferment-
 Abdominal pain in IBS is highly variable in intensity able oligo-, di-, mono-saccharides and polyols).
and location. It is frequently episodic and crampy, Stool-Bulking Agents
but may be dull aching also. Pain may be mild or it
may interfere with daily activities. Abdominal pain  High-fiber diets and bulking agents, such as bran
is mainly present during daytime, hence sleep or hydrophilic colloid, are helpful in treating IBS.
disturbance is rare. Pain is often exacerbated by Dietary fiber has multiple effects on colonic
eating or emotional stress and relieved by passage physiology. Because of their hydrophilic properties,
of flatus or stools. stool-bulking agents bind water and thus prevent
 Alteration in bowel habits usually begins in adult both excessive hydration and dehydration of stool.
life. The most common pattern is constipation Hence these agents can reduce both diarrhea and
alternating with diarrhea, usually with one of these constipation in IBS patients.
Manipal Prep Manual of Medicine

symptoms predominating. Diarrhea in IBS usually

consists of small volumes of loose stools. Nocturnal Antispasmodics
diarrhea does not occur in IBS. Bleeding, mal-  Anticholinergic drugs (e.g. hyoscyamine) may
absorption and weight loss does not occur in IBS. provide temporary relief for symptoms such as
 Patients with IBS also complain of increased painful cramps related to intestinal spasm.
belching or flatulence. Many patients also complain
of dyspepsia, heartburn, nausea, and vomiting. Antidiarrheal Agents
 Physical examination is usually normal, but  Peripherally acting opiate-based agents are the
palpation of the abdomen may reveal tenderness, initial therapy of choice for diarrhea-predominant
particularly in the left lower quadrant. IBS.
 Diphenoxylate (Lomotil), 2.5 to 5 mg every 4 to 6 h,


Differential Diagnosis can be prescribed. Codeine is also helpful. These

4 


Anxiety disorders.
Bacterial overgrowth syndrome.
agents should be used only temporarily and should
be replaced gradually with high-fiber diet.

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Antidepressant Drugs Clinical Features of Acute Abdomen 287
 Tricyclic antidepressants (amitryptyline, imipramine, History
desipramine) slow jejunal migrating motor complex  Complaints: Acute abdomen usually presents with
transit propagation and delay orocecal and whole-gut pain abdomen. Find out the exact location and
transit. They improve diarrhea, pain, and depression. nature of pain. In general, the pain of an acute abdo-
 The selective serotonin reuptake inhibitor (SSRI) men can either be constant (due to inflammation)
paroxetine accelerates orocecal transit, and may be or colicky because of a blocked hollow organ.
useful in constipation-predominant patients.  A sudden onset of pain suggests a perforation (e.g.
 The SSRI citalopram blunts perception of rectal of a duodenal ulcer), a rupture (e.g. of an aneurysm
distention and reduces abdominal pain. or ectopic pregnancy), torsion (e.g. of an ovarian
5HT 3-receptor Antagonists cyst), or acute pancreatitis.
 Vomiting is usually present in any acute abdomen
 A 5HT 3-receptor antagonists such as alosetron, but, if persistent, suggests intestinal obstruction.
cilansetron, and ramosetron are useful in diarrhea The character of the vomitus should be asked—does
predominant IBS. They reduce abdominal discom- it contain blood, bile or small bowel contents.
fort and improve stool frequency, consistency, and
 Absolute constipation and abdominal distension
urgency. However, a major side effect ischemic
may be present in intestinal obstruction.
colitis has been observed with alosetron and this
 Past history: Enquire about any previous operations,
drug is not commonly used now. Cilansetron was
gynecological problems and any concurrent medical
not marketed. Ramosetron is now widely available
condition.
and commonly used. Ischemic colitis has not been
observed with ramosetron. General Examination
5HT 4-receptor Agonist  The general condition of the patient should be
 Tegaserod is a 5HT4-receptor agonist which has been assessed.
approved for use in constipation predominant IBS.  Most acute abdomen patients look acutely ill.
 Fever suggests an acute infectious process.
Lubiprostone  Note pulse rate, respiratory rate, blood pressure
 This agent activates chloride channels in the small and state of hydration. Large volumes of fluid may
intestine. As a result, chloride ions are secreted and be lost from the vascular compartment into the
sodium and water passively diffuse into the lumen peritoneal cavity or into the lumen of the bowel,
to maintain isotonicity. It is useful in constipation giving rise to hypovolemia, i.e. a pale cold skin, a
predominant IBS. weak rapid pulse and hypotension.

Q. Enumerate the causes of acute abdomen. What are The Abdomen

the clinical features of acute abdomen? How do you  Inspection: Note the presence of scars, distension or
investigate and manage a case of acute abdomen? mass.
 Palpation: Tenderness, rebound tenderness, presence
TABLE 4.23: Causes of acute abdomen or absence of guarding should be noted. Guarding
Surgical causes indicates peritonitis. Guarding can be localized or
• Acute appendicitis generalized.
• Renal colic  Bowel sounds: Increased bowel sounds indicate
• Gynecological disorders (torsion of ovarian cyst) intestinal obstruction. Absent bowel sounds suggest
• Intestinal obstruction peritonitis.
• Urinary tract infection  Other systems should be examined to rule out any
• Gallbladder disease
concurrent disease.
• Perforated ulcer

Gastrointestinal System

• Diverticular disease Investigations

Medical causes
 Blood count: White cell count is raised in inflamma-
• Acute pyelonephritis
• Diabetic ketoacidosis tory conditions.
• Acute intermittent porphyria  Serum amylase and lipase: High levels (more than five
• Lead poisoning times normal) indicate acute pancreatitis.
• Haemophilia and other bleeding disorders  Urine pregnancy test: Should be done in women of
• Henoch-Schönlein purpura child bearing age to rule out ectopic pregnancy and
• Sickle cell crisis its rupture.

4
• Polycythemia vera
 X-ray erect abdomen: Air under the diaphragm may
• Embolic phenomenon
be seen in abdominal viscus perforation. Multiple

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288 air fluid levels are seen in peritonitis and intestinal Localized Peritonitis
obstruction.  This is seen with acute inflammatory conditions of
 Ultrasound: This is useful in the diagnosis of acute the gastrointestinal tract (e.g. acute appendicitis,
cholangitis, cholecystitis and aortic aneurysm, acute acute cholecystitis). There is local pain and tender-
pancreatitis and acute appendicitis. It can detect renal ness. The treatment is for the underlying disease.
and ureteric stones and ruptured ectopic gestation.
 CT scan: It is more accurate than ultrasound in most Generalized Peritonitis
acute emergencies.  This is a surgical emergency and is usually due to
 Laparoscopy: This has gained increasing importance perforation of a hollow viscus (e.g. perforated
as a diagnostic tool prior to proceeding with appendix, perforated peptic ulcer).
surgery. In addition, therapeutic maneuvers, such  In case of perforated peptic ulcer, acid contents leak
as appendicectomy, can be performed. into peritoneal cavity and cause chemical peritonitis
which gets infected later with bacteria.
Treatment of Acute Abdomen
 E. coli and Bacteroides are the most common
 Acute abdomen is a medical emergency. organisms responsible for peritonitis since these are
 Initial treatment involves keeping the patient nil present in the intestine.
per oral and continuous nasogastric aspiration of  The peritoneal cavity becomes acutely inflamed,
stomach contents through a Ryle’s tube. with production of an inflammatory exudate that
 Hydration should be maintained by intravenous spreads throughout the peritoneum, leading to
fluids. intestinal dilatation and paralytic ileus.
 Empirical antibiotis (cephalosporins plus metro-
nidazole or tinidazole intravenously) should be Clinical Features
started pending the identification of cause.  The cardinal manifestations of peritonitis are acute
 Once the cause is identified, treatment should be abdominal pain and tenderness, usually with fever.
directed towards that.  The location of the pain depends on the underlying
 Most cases of acute abdomen require surgery for cause and whether the inflammation is localized or
the underlying cause (e.g. acute appendicitis, generalized. In case of localized peritonitis, physical
perforation of peptic ulcer, etc.). findings are limited to the area of inflammation.
Generalized peritonitis is associated with diffuse
Q. Describe the etiology, clinical features and manage- abdominal tenderness and rebound tenderness.
ment of acute peritonitis.  Rigidity of the abdominal wall is common in both
 Peritonitis is an inflammation of the peritoneum. localized and generalized peritonitis.
 It may be acute or chronic, localized or diffuse,  Bowel sounds are usually absent due to paralytic
infectious or due to aseptic inflammation. ileus.
 Acute peritonitis is most often infectious and is  Tachycardia, hypotension, and signs of dehydration
usually related to a perforated viscus. are common.

Etiology Investigations
 Leukocytosis and acidosis.
TABLE 4.24: Causes of acute peritonitis
 Elevated serum amylase and lipase levels may
Perforation of bowel detect pancreatitis.
• Penetrating trauma
 Plain abdominal X-ray: Shows dilated and edematous
Manipal Prep Manual of Medicine

• Appendicitis
bowel loops with air fluid levels. Gas under the
• Diverticulitis
• Peptic ulcer
diaphragm may be seen in perforated viscus.
• Inflammatory bowel disease  CT and/or ultrasonography can identify the cause
• Endoscopic perforation of acute abdomen and the presence of free fluid or
• Ischemia an abscess.
• Strangulated hernias  If ascites is present, fluid should be aspirated and
Perforations or leaking of other organs sent for cell count cell type, protein, lactate dehydro-
• Pancreatitis genase levels, Gram’s stain and culture (>250
• Cholecystitis neutrophils/μL is usual in peritonitis).
• Salphingitis
Iatrogenic Treatment


• Peritoneal dialysis  Patient should be hydrated well with IV fluids.

4
• After ascitic fluid tapping
 Continuous nasogastric aspiration should be done
• Postoperative
in view of paralytic ileus.

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 Empirical antibiotis (cephalosporins plus metroni-  Examination of the abdomen reveals distension 289
dazole or tinidazole intravenously) should be with increased bowel sounds.
started.  Pulse is rapid and there may be dehydration and
 Treatment of peritonitis is always surgical. Usually signs of shock.
laparotomy is required.  Tenderness of abdomen suggests strangulation or
 Surgery has a two fold objective; peritoneal lavage peritonitis, and urgent surgery is necessary.
of the abdominal cavity and specific treatment of  Examination of the hernial orifices and rectum must
the underlying condition. be performed.

Q. Discuss the causes, clinical features, investigations Investigations

and management of intestinal obstruction.  Plain X-ray of the abdomen (erect view) shows
distended bowel loops with air fluid levels.
 Intestinal obstruction may be mechanical or non-
 Ultrasound abdomen and CT can identify the cause
mechanical (e.g. paralytic ileus).
of obstruction.
Causes of Obstruction Management
TABLE 4.25: Causes of intestinal obstruction  Initial management is by resuscitation with intra-
Mechanical obstruction
venous fluids (mainly isotonic saline with
• Adhesive bands potassium) and continuous nasogastric aspiration
• Obstructed hernia through a Ryle’s tube. Many cases will settle on
• Diverticulitis conservative management.
• Intestinal neoplasms  Exploratory laparotomy may be required in serious
• Regional enteritis cases not responding to conservative therapy. If the
• Gallstone obstruction bowel is gangrenous, that segment has to be
• Intussusception resected and end-to-end anastomosis done.
• Volvulus
Non-mechanical (pseudoobstruction) Q. Ileus (paralytic ileus, functional ileus).
• Adynamic ileus—peritonitis, retroperitoneal, lower-lobe
pneumonia, electrolyte disturbances (hypokalemia)  Ileus, also known as paralytic ileus or functional
• Spastic ileus, or dynamic ileus—results from prolonged ileus, occurs when there is temporary arrest of
contraction of the intestine. Seen in heavy metal poisoning, peristalsis. Clinical presentation of ileus is similar
uremia, porphyria, and extensive intestinal ulcerations. to mechanical bowel obstruction.

Pathophysiology Causes of Ileus

 Distention of the intestine is caused by the accumu-  Postoperative (especially abdominal surgery, most
lation of gas and fluid proximal to and within the common cause).
obstructed segment.  Intra-abdominal infection/inflammation (sepsis/
 Most of the air consists of swallowed air. Fluid peritonitis).
accumulation is due to ingested fluid, swallowed  Retroperitoneal or intra-abdominal hematomas
saliva, gastric juice, and biliary and pancreatic (e.g. from ruptured abdominal aortic aneurysm,
secretions. Fluid from the body may also move into blunt abdominal trauma).
the lumen causing further accumulation of fluid.  Metabolic disturbances (e.g. hypokalemia).
This may lead to sequestration of large volumes of  Drugs (e.g. opioids, anticholinergics).
fluid in the lumen leading to dehydration, hypo-
tension, shock and renal failure. Clinical Features
 Blood supply to the obstructed segment of intestine  Abdominal distension which is of slow onset as


may get compromised (e.g. in obstructive hernia) compared to the sudden onset seen with mechanical
Gastrointestinal System

and lead to gangrene of intestine and blood loss intestinal obstruction.

into the lumen.  Pain abdomen which is usually diffuse without
 Bacteria may get into the peritoneum through the peritoneal signs.
gangrenous segment leading to peritonitis.  Nausea and vomiting
 Massive abdominal distension may compromise  Decreased or inability to pass flatus.
breathing and cause inferior vena cava compression.  Examination shows distended and tympanic
abdomen with mild diffuse tenderness. Bowel
Clinical Features sounds are usually sparse or absent as opposed to
 Patient presents with colicky abdominal pain,
vomiting and constipation.
a mechanical obstruction where there is increased
bowel sounds in the early phase. 4
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290 Investigations Q. Prebiotics.
 Plain X-ray abdomen usually shows multiple air  Prebiotics are dietary substances that induce the
fluid levels. growth and/or activity of beneficial micro-
 CT abdomen. organisms (e.g., bacteria and fungi) that contribute
 RFT and LFT. to the well-being of their host.
 Serum amylase and lipase to rule out pancreatitis.  In diet, prebiotics are typically non-digestible fiber
 Serum electrolytes to rule out hypokalemia. compounds that pass undigested through the upper
 Complete blood count—anemia is seen in intra- part of the gastrointestinal tract and stimulate the
abdominal bleeding, raised WBC count is seen in growth and/or activity of advantageous bacteria
intra-abdominal infection, abscess, or intestinal that colonize the large bowel by acting as substrate
ischemia. for them.
 Commonly known prebiotics are: Oligofructose,
Treatment inulin, galacto-oligosaccharides, lactulose, breast
 Bowel rest is given by keeping the patient nil by milk oligosaccharides.
mouth and giving intravenous (IV) fluids. Total
parenteral nutrition (TPN) is recommended if the Sources of Prebiotics
patient is unable to tolerate adequate oral intake  Chicory root is the richest natural source. Other
after seven days. dietary sources are beans, raw oats, unrefined wheat,
 Nasogastric aspiration of stomach contents is done unrefined barley, onion, garlic and raw banana.
if required.
Effects of Prebiotics
 Chewing gum has been shown to be a cheap, well-
tolerated way to potentially help with ileus as it  Reduce exogenous and endogenous intestinal
stimulates the cephalocaudal reflex, which promotes infection.
peristalsis and inhibits inflammation.  Improved bowel habit.
 Treatment of the underlying condition is very  Suppress IBD inflammation.
important. Treating the infection, electrolyte abnor-  Immunomodulation (anti-inflammatory).
malities, decreasing opiate use, can all potentially  Controlled serum lipids and cholesterol.
decrease the durability of an ileus.
 Incidence of ileus can be decreased by using Q. Carcinoid syndrome.
regional anesthesia rather than general anesthesia,
 Carcinoid syndrome results from vasoactive sub-
using laparoscopic surgery wherever possible, and
stances (including serotonin, bradykinin, histamine,
decreasing the use of opiate analgesics.
prostaglandins, polypeptide hormones) secreted by
carcinoid tumor (neuroendocrine tumor). Serotonin
Q. Probiotics.
acts on smooth muscle to cause diarrhea, colic, and
 Probiotics are microorganisms that have beneficial malabsorption. Histamine and bradykinin cause
properties for the host. Examples are Lactobacillus, flushing through their vasodilator effects.
Bifidobacterium, Clostridium butyricum, Strepto-  Carcinoid tumors are neoplastic proliferation of
coccus salivarius, and Saccharmomyces boulardii. enterochromaffin cells.
 Carcinoid tumors can be found in GIT, bronchi,
Mechanisms of Benefit thyroid, ovary and testes.
 Suppression of growth or invasion by pathogenic  In GIT, the most common site is ileum and
appendix.
Manipal Prep Manual of Medicine

bacteria.
 These tumors are less aggressive than carcinomas
 Improvement of intestinal barrier function.
and their growth is usually slow. They can spread
 Modulation of the immune system.
locally and also metastasize to other organs
especially liver.
Potential Uses
 Carcinoid syndrome refers to the systemic symp-
 Ulcerative colitis toms produced by secretory products of carcinoid
 Crohn’s disease tumors. The secretory products produced by the
 Antibiotic associated diarrhea primary tumor are metabolized in the liver and
 Infectious diarrhea hence, do not reach the systemic circulation.
However, when there are liver metastases, secretory
 Irritable bowel syndrome
products from these metastases reach systemic
Lactose intolerance



circulation and produce symptoms. Therefore,

4 


Hepatic encephalopathy
Allergy.
carcinoid syndrome is seen only when there are
liver metastases.

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 These tumors follow the so-called rule of one-third, Treatment 291
which is as follows:  The treatment of a carcinoid tumor without liver
– One-third of these tumors are multiple metastases is surgical resection.
– One-third of those in the gastrointestinal (GI)  The treatment of carcinoid tumor with liver meta-
tract are located in the small bowel stases (carcinoid syndrome) is palliative. However,
– One-third of patients have a second malignancy primary tumor and hepatic metastases can be
– One-third of these tumors metastasize. excised as it decreases the tumor burden and
improves the symptoms. Hepatic artery embolisa-
Clinical Features tion can decrease the size of hepatic metastases.
 Carcinoids occur most frequently in patients aged Octreotide 200 μg 8-hourly by subcutaneous
50–70 years. injection is used to reduce release of secretory
 Episodic cutaneous flushing is the clinical hallmark products by tumor. Cytotoxic chemotherapy has
of the carcinoid syndrome, and occurs in most of only a limited role.
patients. It occurs in the face, neck, upper chest and  Symptomatic treatment: Bronchodilators for wheeze,
lasts from 30 seconds to 30 minutes. There may be loperamide and serotonin-receptor antagonists
associated lacrimation, periorbital edema, tachy- (cyproheptadine, ondansetron) to control diarrhea.
cardia and hypotension.  Avoidance of conditions and diets precipitating
 Venous telangiectasias are purplish vascular lesions flushing and diarrhea.
seen on the face, and occur due to prolonged vaso-  Supplementation of food with niacin to prevent
dilatation. pellagra.
 Secretory diarrhea occurs in most patients. Stools
are watery and non-bloody, and may be accom- Q. Zollinger-Ellison syndrome (gastrinoma).
panied by abdominal cramping.
 Wheezing and dyspnea due to bronchospasm often  Zollinger-Ellison syndrome is caused by gastrin-
during flushing episodes. secreting gut neuroendocrine tumors (gastrinomas),
 Cardiac valvular lesions: Right sided valves (tricuspid which result in hypergastrinemia and increased
regurgitation and pulmonary stenosis) are most acid secretion.
often affected, because inactivation of humoral  Gastrinomas are usually located in the pancreas or
substances by the lung protects the left heart. the duodenal wall.
 Diversion of tryptophan for synthesis of serotonin  Most gastrinomas are solitary or multifocal nodules
can result in the development of pellagra. Normally that are potentially resectable. Over two-thirds of
niacin is produced from tryptophan. gastrinomas are malignant, and one-third would
 Hepatomegaly due to hepatic metastases, intestinal have already metastasized to the liver at initial
obstruction and bleeding from intestinal tumors. presentation. Multifocal gastrinomas are associated
 Other features include increased incidence of peptic with MEN 1 syndrome.
ulcer, muscle wasting due to poor protein synthesis
and ureteral obstruction due to retroperitoneal Clinical Features
fibrosis.  Abdominal pain occurs due to peptic ulcers. Over
Investigations 90% of patients with Zollinger-Ellison syndrome
develop peptic ulcers. Ulcer is usually single and
 Increased urinary excretion of 5-hydroxyindole found in the duodenum, but there can be multiple
acetic acid (5-HIAA) in 24-hour collection (more ulcers. These ulcers may be refractory to standard
than 9 mg). 5-HIAA is the end product of serotonin treatment, big (>2 cm), and may recur.
metabolism.
 Symptoms of gastroesophageal reflux.
 Serotonin level in blood and platelets is high.
 Diarrhea and weight loss occur in one-third of
 Chest X-ray, CT scan, barium and endoscopic
patients due to direct intestinal mucosal injury and


studies are used to localize the tumor.

Gastrointestinal System

pancreatic enzyme inactivation by acid, leading to

 Somatostatin receptor imaging with positron
maldigestion, and malabsorption.
emission tomography (PET)/CT is a very useful
investigation to localize carcinoid tumors since
Investigations
somatostatin receptors are present on the cell
surface of neuroendocrine cells. For this purpose  Upper GI endoscopy: To look for duodenal ulcera-
scan various somatostatin analogues can be labeled tions and hypertrophy of gastric folds.
with radioisotopes and injected intravenously and  Increased fasting serum gastrin concentration (>150 pg/
then scan is done. mL): H2-blocker should be withheld for 24 hours
 Laparotomy and biopsy of the lesion can be
attempted in selected cases.
and proton pump inhibitors for 6 days before
measuring gastrin levels. 4
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292  Measurement of gastric pH: Most patients have very Investigations
low pH due to high acid output. A gastric pH of Colonoscopy and genetic testing
>3.0 excludes gastrinoma.  All first-degree relatives of the affected patients
 Secretin stimulation test: Useful to distinguish should also undergo testing. In families with known
Zollinger-Ellison syndrome from other causes of FAP, at-risk family members should undergo direct
hypergastrinemia. Intravenous secretin produces a mutation testing at 13–14 years of age.
rise in serum gastrin within minutes in patients
Treatment
with gastrinoma.
 High serum calcium level suggests hyperpara-  Affected individuals should undergo colectomy
(total proctocolectomy with ileal pouch-anal
thyroidism and MEN 1 syndrome.
anastomosis). This will prevent the transformation
 Serum parathyroid hormone (PTH), prolactin, of polyps into adenocarcinoma.
luteinizing hormone (LH), follicle-stimulating  Sulindac is a NSAID that has been shown to reduce
hormone (FSH), and growth hormone (GH) level the number and size of adenomas if given for a long
should be obtained to exclude MEN 1. time.
 Imaging studies are used to locate the site of primary  The selective COX-2 inhibitor celecoxib has also
tumor and to identify metastases. Gastrinomas been shown to reduce the adenoma burden.
express somatostatin receptors that bind radio-
labeled octreotide. Somatostatin receptor imaging Q. Peutz-Jeghers syndrome.
with single photon emission computed tomography  This is characterized by multiple hamartomatous
(SPECT) can identify the site of gastrinomas. polyps in the small intestine and colon, as well as
Endoscopic ultrasonography (EUS) may be useful melanin pigmentation of the lips, mouth and digits.
to detect small gastrinomas in the duodenal wall,  The disorder is caused by a mutation on chromo-
pancreas, or peripancreatic lymph nodes. CT and some 19p.
MRI scans may be helpful to identify liver meta-  Most cases are asymptomatic. However, chronic
stases and primary lesions, but less sensitive than bleeding, anemia or intussusception may be seen.
SPECT. Malignant potential of polyps is low though there
is a small risk of adenocarcinoma.
Treatment  Management involves surveillance of polyps with
 Localized disease is treated with surgical resection. colonoscopy and biopsy every 1 to 3 years.
 In patients with liver metastases, initial therapy Q. Discuss the etiology, clinical features, investigations
should be directed at controlling hypersecretion. and management of acute pancreatitis. What are
Oral proton pump inhibitors (omeprazole, the complications of acute pancreatitis?
esomeprazole, rabeprazole, pantoprazole, or
lansoprazole) are used to decrease the acid  Acute pancreatitis is an inflammatory condition of
secretion. Surgical resection or cryoablation can be the pancreas characterized by abdominal pain and
tried for single metastases. Other options for liver elevated levels of pancreatic enzymes in the blood.
metastases include somatostatin analogues,
Etiology
interferon alpha, cytotoxic chemotherapy, and
hepatic arterial chemoembolization. TABLE 4.26: Causes of acute pancreatitis
Common causes
Q. Gardner’s syndrome (familial adenomatous • Gallstones
polyposis). • Alcohol
Manipal Prep Manual of Medicine

• Post-ERCP
 This is an uncommon autosomal dominant disorder • Idiopathic
characterized by multiple adenomatous polyps Rare causes
throughout the colon. Hundreds to thousands of • Postsurgical (abdominal, cardiopulmonary bypass)
adenomatous colonic polyps will develop by age • Trauma (blunt or penetrating abdominal injury)
15. Most will develop colorectal cancer by the age • Drugs (azathioprine, thiazides, sulphasalazine, valproate)
of 50 years. • Metabolic (hypercalcemia, hypertriglyceridemia)
• Pancreas divisum
 It results from germline mutation of the APC gene • Vascular (ischemia, atheroembolism, vasculitis)
on the long arm of chromosome 5 followed by • Infections (mumps, Coxsackievirus, HIV, leptospira, ascaris)
acquired mutation of the remaining allele. • Cystic fibrosis
 Many extra-intestinal features are also seen in FAP • Toxins (methanol, scorpion venom, organophosphates)


which include subcutaneous epidermoid cysts, • Renal failure

4
• Organ transplantation (kidney, liver)
osteomas, dental abnormalities, retinal abnormali-
• Severe hypothermia
ties, desmoid tumors, and lipomas.

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Pathophysiology levels are also found in pancreatic ascites and 293
 Damage to pancreas by any of the above causes pleural effusion. Serum amylase concentration has
leads to premature activation of zymogen granules, no prognostic value.
releasing proteases which digest the pancreas and  Elevated amylase is not specific to pancreatitis. High
surrounding tissue. serum amylase levels can also occur in mesenteric
 Pancreas becomes swollen. In severe cases there ischemia, perforated peptic ulcer, ruptured ovarian
may be necrosis and hemorrhage. cyst, renal failure, DKA, and parotitis.
 Pancreas has a poorly developed capsule, and Serum Lipase
adjacent structures, including the common bile
duct, duodenum, splenic vein and transverse colon,  This is more specific than that of amylase in
are commonly involved. diagnosing pancreatitis.
 Both the endocrine and exocrine function of the  Lipase takes longer time to clear from the blood.
pancreas is altered during an attack of acute Hence, it is helpful to make a diagnosis of pancrea-
pancreatitis which will return to normal if the attack titis even if the patient presents late.
is mild. However, permanent exocrine and
Ultrasound Abdomen
endocrine insufficiency may develop in severe
pancreatitis (necrotizing pancreatitis).  Shows swollen pancreas. It is also useful to pick up
gallstones, biliary obstruction or pseudocyst forma-
Clinical Features tion.
Symptoms CT Scan Abdomen
 Abdominal pain: Severe, constant upper abdominal  This is the most important imaging test for the
pain which radiates to the back. Pain is sudden in diagnosis of acute pancreatitis and its local
onset and gradually increases in severity. Pain complications. Patients who do not improve with
decreases if patient sits up and leans forward and initial conservative therapy or who are suspected
increases on lying down. of having complications should undergo CT scan
 Nausea and vomiting. of the abdomen.
 Anorexia.  MRI is an alternative to CT especially if contrast
cannot be used due to renal failure.
Signs
 Fever (low-grade). Plain X-ray Abdomen and Chest
 Tachycardia.  To exclude other causes of acute abdominal pain
 Tachypnea (due to pleural effusion, inflammation (e.g. gas under diaphragm in perforation).
of lungs, or atelectasis).  Calcification in pancreas in chronic pancreatitis.
 Jaundice due to compression of common bile duct.  Multiple air fluid levels due to paralytic ileus.
 Epigastric tenderness.  Chest X-ray may show pleural effusion and signs
 Guarding and rebound tenderness in severe cases. of ARDS.
 Bluish discoloration of the flanks (Grey Turner’s
sign) or the periumbilical region (Cullen’s sign) are Other Blood Investigations
features of severe pancreatitis with hemorrhage.  Blood glucose, total leukocyte count, platelet count,
 Absent bowel sounds due to paralytic ileus. ESR, CRP, blood urea, creatinine, calcium and other
 Hypotension and shock in severe cases. electrolytes, triglycerides, arterial blood gases.
 Erythematous skin nodules due to focal subcuta-
neous fat necrosis. Assessment of Severity of Acute Pancreatitis
 Ischemic injury to retina seen on fundus examina-  There are two scoring systems to predict the
tion (Purtscher retinopathy).


severity and mortality in acute pancreatitis. These

Gastrointestinal System

are Ranson criteria and Bedside Index Severity in

Investigations Acute Pancreatitis (BISAP) score. BISAP score is
Serum Amylase easy to calculate and immediate assessment can be
 This is elevated in acute pancreatitis for three to done about the severity of pancreatitis. In addition,
five days. It is rapidly cleared by kidneys. Hence, BISAP score has good predictive performance for
levels may be normal if measured after 3–5 days. both severe acute pancreatitis and mortality.
In this situation the diagnosis can be made by
BISAP Score
elevated urinary amylase–creatinine ratio. A
persistently elevated serum amylase concentration
suggests pseudocyst formation. High amylase



Each of the following parameter carries 1 point.
0 to 2 points: Lower mortality (<2 percent). 4
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294  3 to 5 points: Higher mortality (>15 percent). Differential Diagnosis
 Perforated peptic ulcer
• BUN >25 mg/dL (8.9 mmol/L)
 Perforation of any other hollow viscus
• Abnormal mental status with a Glasgow Coma Scale score <15
• Evidence of SIRS (systemic inflammatory response syndrome)  Acute cholecystitis
• Patient age >60 years old (1 point)  Acute intestinal obstruction
• Imaging study reveals pleural effusion  Leaking aortic aneurysm
 Renal colic
Ranson criteria to predict severity of acute pancreatitis  Acute mesenteric ischemia or thrombosis.
TABLE 4.27: Ranson criteria
Management
On admission
• Age >55
 Nothing by mouth.
• White blood cell count >16,000/mm3  Intravenous fluids to maintain intravascular
• Blood glucose >200 mg/dL volume. This is the most important step and Ringer
• Lactate dehydrogenase >350 U/L lactate is the preferred fluid.
• Aspartate aminotransferase (AST) >250 U/L  Nasogastric aspiration: Not routinely necessary.
First 48 hours Required if the patient has persistent abdominal
• Hematocrit fall by >10 percent pain in spite of analgesics, paralytic ileus, protracted
• Blood urea increase by 5 mg/dL despite fluids vomiting or intestinal obstruction.
• Serum calcium <8 mg/dL  Analgesics for abdominal pain. Adequate pain control
• pO2 <60 mmHg requires opiates such as meperidine or tramadol.
• Base deficit >4 mEq/L  Admit severe cases in intensive care unit. Monitor
• Fluid sequestration >6 liters pulse, BP, abdominal girth, urine output, blood
glucose and calcium levels.
 Each of the above parameters counts for 1 point  Prophylactic systemic antibiotics (imipenem or
toward the score. A Ranson score of 0–2 has a meropenem or ceftazidime) should be given in
minimal mortality. A Ranson score of 3–5 has a severe cases to prevent pancreatic infection.
10–20% mortality rate, and the patient should be  Proton-pump inhibitors are used to decrease the
admitted to the intensive care unit (ICU). A Ranson acid output.
score higher than 5 after 48 hours has a mortality
 The role of somatostatin or octreotide infusion is
of more than 50% and is associated with more
controversial.
systemic complications.
 ERCP with endoscopic sphincterotomy and stone
Complications of Acute Pancreatitis extraction is indicated if pancreatitis results from
gallstone particularly if jaundice (serum total
TABLE 4.28: Complications of acute pancreatitis bilirubin >5 mg/dL) or cholangitis is present.
Local  Surgery is indicated for complications such as
• Pancreatic necrosis infected pancreatic necrosis, pancreatic abscess,
• Abscess formation intestinal obstruction, perforation, etc.
• Pseudocyst formation
• Pancreatic ascites or pleural effusion Q. Chronic pancreatitis
• Upper gastrointestinal bleeding
• Splenic or portal vein thrombosis  Chronic pancreatitis is persistent inflammation of
• Erosion into colon the pancreas that results in permanent structural
Manipal Prep Manual of Medicine

• Duodenal obstruction (compression by pancreatic mass) damage with fibrosis and ductal strictures, followed
• Obstructive jaundice (due to compression of common bile by a decline in exocrine and endocrine function
duct) (pancreatic insufficiency).
Systemic
• Systemic inflammatory response syndrome (SIRS) and multi- TABLE 4.29: Causes of chronic pancreatitis
organ failure • Chronic alcoholism
• DIC • Smoking
• Renal failure • Tropical pancreatitis (India)
• Hypoxia • Stenosis of the ampulla of Vater
• Acute respiratory distress syndrome (ARDS) • Pancreas divisum
• Hyperglycemia • Cystic fibrosis
• Fat necrosis • Familial


• Hypocalcemia (due to sequestration of calcium in fat • Autoimmune diseases (Sjögren’s syndrome, primary biliary
necrosis)
4
cirrhosis)
• Hypoalbuminemia (due to increased capillary permeability) • Idiopathic

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Clinical Features Q. Discuss the causes and differential diagnosis of 295
 Middle-aged alcoholic men are predominantly acute upper abdominal pain.
affected.
TABLE 4.30: Causes of acute upper abdominal pain
 Pain in the upper abdomen is the most common
symptom. It may be constant or intermittent. It may • Peptic ulcer perforation
• Acute cholecystitis
radiate to back. Pain may be relieved by leaning
• Biliary colic
forward and worsened by food intake.
• Acute pancreatitis
 Features of malabsorption: Diarrhea, steatorrhea, and • Lower lobe pneumonia
weight loss. • Myocardial infarction
 Diabetes develops in advanced cases. • Aortic dissection or rupture
 Physical examination reveals a thin, malnourished • Splenic abscess and infarct
patient with epigastric tenderness. Skin pigmenta-
tion over the abdomen and back is common due to Peptic Ulcer Perforation
chronic use of a hot water bottle to relieve the
abdominal pain.  Previous history of recurrent epigastric pain with
relation to food and periodicity.
Investigations  After perforation, pain becomes severe and pene-
trating type. Initially it is felt in the epigastrium,
 Serum amylase and lipase usually normal. but later spreads to whole abdomen due to
 Ultrasound abdomen. generalized peritonitis.
 CT (may show atrophy, calcification, ductal stricture  Tachycardia and hypotension are usually present.
or dilatation).  Abdominal examination shows board like rigidity,
 Abdominal X-ray (may show calcification). guarding and absent bowel sounds due to
 ERCP accurately demonstrates the anatomy of peritonitis. Liver dullness may be absent or reduced
pancreatic ducts. Magnetic resonance. cholangio- due to gas collection below the diaphragm.
pancreatography (MRCP) is a non-invasive  Plain X-ray abdomen in the erect posture may show
alternative to ERCP. gas under the diaphragm and multiple air fluid
 Endoscopic ultrasound. levels.
 Tests of pancreatic function: Seceretin/cholecysto-
kinin (CCK) stimulation test, 24-hour faecal fat Acute Cholecystitis
estimation, oral glucose tolerance test.  Pain is mainly in the right hypochondrium. Pain is
constant and may also be felt in the right shoulder
Complications of Chronic Pancreatitis tip.
 Pseudocyst.  Associated fever, jaundice, nausea and vomiting.
 Pancreatic ascites.  Tenderness in the right hypochondrium and rigidity.
 Obstructive jaundice due to stricture of the common Murphy’s sign present (sudden inspiratory arrest
bile duct as it passes through the diseased pancreas. due to pain while palpating right hypochondrium).
 Duodenal stenosis.  Gallbladder may be palpable.
 Portal or splenic vein thrombosis.  Blood tests show leukocytosis, raised bilirubin, and
 Peptic ulcer. liver enzymes.
 Plain X-ray abdomen may show gallstones.
Management  Ultrasound abdomen may show gallstones, gall-
 Stop alcohol intake. bladder wall thickening and pericholic fluid collection.
 Pain relief: NSAIDs, opiates, celiac ganglion  Cholescintigraphy shows cystic duct obstruction.
blockade.


 Oral pancreatic enzyme supplements to improve Biliary Colic

Gastrointestinal System

the digestion and absorption of food.  Biliary colic is usually due to gallbladder contract-
 Patients with severe chronic pain resistant to ing and pressing a stone against the gallbladder
conservative measures are considered for surgical outlet or cystic duct opening, leading to increased
or endoscopic pancreatic therapy. gallbladder pressure and pain.
 Endoscopic therapy involves dilatation or stenting  Biliary colic is a misnomer, since the pain is not
of pancreatic duct strictures and removal of calculi typically colicky.
(mechanical or shock-wave lithotripsy).  Pain is deep and gnawing type and is occasionally
 Surgical interventions are partial pancreatic resec- sharp and severe.
tion preserving the duodenum, total pancreatectomy
and pancreaticojejunostomy.
 Pain is localized in the right upper quadrant or
epigastrium. 4
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296  As the gallbladder relaxes, stones often fall back from  Chest X-ray shows mediastinal and/or aortic
the cystic duct. As a result, the attack reaches a widening.
crescendo over many hours and resolves completely.  CT, MRI or aortogram can confirm the diagnosis.
 Pain may recur multiple times.
Splenic Abscess and Infarct
Acute Pancreatitis  Splenic abscesses are associated with fever and
 History of precipitating factors like alcohol binge, tenderness in the left upper quadrant.
and gallstones.  Similar findings may be present in splenic infarction.
 Pain is steady and usually felt in the mid-epigastrium,  Risk factors for splenic infarction such as atrial
radiates to back between scapulae. Its onset is rapid, fibrillation, hypercoagulable state, sickle cell anemia,
but not as abrupt as that with a perforated viscus. etc. may be present.
 Pain of pancreatitis lasts for many days. Pain is  Leukocytosis, high ESR in case of abscess.
accompanied by nausea and vomiting.  Ultrasound abdomen can confirm the presence of
 Pain decreases on sitting and leaning forward. splenic abscess.
 Cullen’s sign and Grey Turner’s sign rarely.
 Amylase and lipase are elevated. Q. Discuss the causes and differential diagnosis of
 Ultrasound abdomen and CT scan shows swollen acute lower abdominal pain.
pancreas.
Causes of Acute Lower Abdominal Pain
Lower Lobe Pneumonia  Appendicitis.
 Lower lobe pneumonia causes referred pain to  Acute diverticulitis.
upper abdomen probably due to diaphragmatic  Ureteric colic.
irritation.  Torsion of ovarian cyst.
 Pleuritic chest pain may be present in the lower  Rupture of ectopic pregnancy.
chest.
 Fever, dyspnea and cough with expectoration are Appendicitis
usually present.  Common in young individuals.
 Chest examination reveals crepitations and bronchial  Pain is initially periumbilical. Later it shifts to right
breath sounds over the affected area. lower quadrant due to development of local
 Chest X-ray shows pneumonic patch. peritonitis.
 Abdominal pain is occasionally the sole presenting  Associated nausea and vomiting present.
complaint in a patient with lower lobe pneumonia.  Tenderness and rebound tenderness positive in
right iliac fossa.
Myocardial Infarction  Ultrasound abdomen reveals swollen appendix or
 Risk factors such as old age, hypertension, diabetes, appendicular mass.
and smoking may be present.
 Pain is felt more in the left side of chest and restro- Acute Diverticulitis
sternal area. It may radiate to left shoulder and left  Usually occurs in older individuals.
arm.  Pain is often present for several days prior to
 There may be associated symptoms such as dypnea, presentation.
sweating.  Pain occurs in the right or left lower quadrant.
Manipal Prep Manual of Medicine

 Examination may show bilateral basal crepitations  Abdominal tenderness.

over the lungs, third and fourth heart sound.  CT scan and contrast enema are helpful in diagnosis.
 ECG shows evidence of MI such as ST segment
elevation and pathological Q waves. Ureteric Colic
 CK-MB and troponins are elevated.  Past history of kidney stones may be present.
 Echocardiogram shows akinesia or hypokinesia of  Pain is severe and radiates from loin to groin. Pain
the involved myocardium. comes on and off and paroxysms of severe pain last
20 to 60 minutes. Pain may radiate to the ipsilateral
Aortic Dissection testicle, tip of the penis, or labia.
 Sudden, severe, tearing pain radiating to the back.  Hematuria may be present.
 Predisposing factors may be present such as  Nausea, vomiting, dysuria, and urgency may be


hypertension, previous aortic aneurysm, Marfan’s present.

4 
syndrome, etc.
Asymmetric pulses may be present.
 Ultrasound abdomen and CT scan can confirm the
diagnosis.

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Ovarian Cyst Ruptured Aneurysm 297
 Sudden onset lower abdominal pain often associa-  Patients present with abdominal or back pain.
ted with waves of nausea and vomiting. However,  Physical examination shows pallor, hypotension
this can occur in other conditions also and hence, and a pulsatile abdominal mass.
nonspecific.
 Ultrasound abdomen, CT or MRI can confirm the
 Previous history of ovarian cyst/mass.
diagnosis.
 History of recent vigorous activity.
 Ultrasound and CT-abdomen can confirm the Peritonitis
diagnosis.
 Pain is diffuse and constant. It is aggravated by
Rupture of Ectopic Pregnancy movement, coughing and deep breathing. Hence,
patients with peritonitis lie down still, in supine
 Women in reproductive age group.
position with the knees flexed.
 History of amenorrhea present.
 Sudden onset lower abdominal pain with vaginal  Patient appears sick.
hemorrhage.  Fever, tachycardia and hypotension.
 Signs of hypovolemic shock may be present such  Abdominal tenderness, rebound tenderness and
as hypotension, tachycardia, and pallor. guarding present.
 Pregnancy test positive. Hemoglobin low.  Bowel sounds are absent.
 Ultrasound abdomen confirms the diagnosis.  Plain X-ray abdomen shows multiple air fluid levels
and gas under diaphragm in case of visceral
Q. Discuss the causes and differential diagnosis of perforation causing peritonitis.
diffuse abdominal pain.
Intestinal Obstruction
Causes
 Pain is colicky and intermittent. Paroxysms of pain
 Mesenteric infarction
occur every four or five minutes.
 Ruptured abdominal aortic aneurysm
 Associated vomiting, constipation and abdominal
 Diffuse peritonitis.
distention.
 Intestinal obstruction
 Hypotension, oliguria, and dry mucous membranes
Mesenteric Infarction indicate dehydration.
 Acute and severe onset of diffuse and persistent  Tenderness may be present.
abdominal pain.  Tympanic note on percussion due to air filled bowel
 Pain is out of proportion to physical findings. loops.
 Patients have evidence of cardiovascular, ischemic,  Bowel sounds increase initially but later decrease.
or atheriosclerotic disease.  Plain X-ray abdomen shows multiple air fluid
 Stool occult blood may be positive. levels.
 Angiography or MRI angiography of the celiac artery  Ultrasound abdomen, and CT abdomen can confirm
or mesenteric arteries can confirm the diagnosis. the diagnosis and reveal the cause of obstruction.


Gastrointestinal System

4
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