Rickettsia
Professor Dr. Ihsan Edan Alsaimary
General Characteristics
 Small obligate intracellular coccobacilli
 Gram negative (poorly), better stained with
Giemsa (Blue)
 Have cell membrane, bigger than virus but
smaller than bacteria
 Have DNA and RNA
 Have an ATP transport system that allows them to
use host ATP
 Arthropod reservoirs and vectors ( e.g., ticks,
mites, lice or fleas).
 Sensitive to antibiotics
Structure:
Similar with Gram negative bacteria
Cell membrane: outer membrane
peptidoglycan
lipopolysaccharide (LPS)
Microcapsule and polysaccharide
Two antigenically distinct groups:
 LPS: heat-stable, cross-reactive with somatic antigens
of non-motile Proteus species (Weil-Felix test)
 Outer membrane protein: heat-unstable, species-specific
six genera in this class cause human
diseases:
Rickettsia
Bartonella
Coxiella (does NOT cause skin rash)
Ehrlichia
Orientia
Anaplasma
Diseases Caused by the Rickettsia
Pathogenic Mechanism
Materials:
Mechanism:
Local lymph or micro blood vessels
Endothelial cells, micro blood vessels
in whole body
Fever, rash, headache, etc
(1st bacteremia)
(2nd bacteremia)
Endothelial cells, micro blood vessels
Endotoxin and Phospholipase A
Bites or faeces of arthropod
Targets:
Replication
Pathogenesis
 Rickettsia (also Ehrlichia) is unstable and die
quickly outside host cells.
 Coxiella highly resistant to desiccation, remain
viable in environment for months to years.
 Rickettsia replicate in endothelial cells, cause cell
damage and blood leakage, skin rash, microthrombi,
hemorrhage.
 Hypovolemia, hypoproteinemia, reduced perfusion,
organ failure.
Immunity
 Cellular immunity is important, and humoral
immunity is helpful.
 Persons become immune to further infection
following recovery from the disease.
Diagnosis and Prevention
 Microscopy
 Serological Test (Weil-Felix reaction, ELISA, IF,
PCR)
 Breaking the infection chain ( controlling and
killing the intermediate hosts and reservoir
hosts)
 Inactivated vaccine has protective effect
 Chloromycetin, tetracycline are helpful for
therapy, sulphonamides are not administered
(increasing the penetrating of the vessel).
 Diagnosis/serological tests
 Direct detection of Rickettsia in tissues (Giemsa
stain or direct fluorescent antibody test) Weil-
Felix reaction – in certain rickettsial infections
(typhus group) antibodies are formed that will
agglutinate OX strains of Proteus vulgaris.
 This is used as a presumptive evidence of typhus
group infection, however, the test is not very
sensitive or specific and many false positives occur.
 Agglutination or complement fixation tests
using specific Rickettsial antigens are better
serological diagnostic tests.
Virulence factors
Rickettsial sp.
Induced phagocytosis
Recruitment of actin for intracellular
spread
Coxiella burnetti
Is resistant to lysosomal enzymes
Coxiella burnetii
 Biologically and genomically distinct from
Rickettsia; more closely related to Legionella
and Francisella.
 Obligate intracellular pathogen
 Multiply in phagolysosome
Coxiella Burnetii
 Q fever(query fever )
 Self-limiting flu-like syndrome with high
fever (40℃)
 Primary reservoirs are wild (cattle, sheep,
goat etc.)
 Non-cross reactive antigen with non-motile
Proteus (Weil-Felix reaction negative)
 Live in macrophages of vertebrate host
Q fever
 Most infections are mild or asymptomatic
 Acute disease:
 Pneumonia - high fever, severe headache, chill,
resemble “atypical pneumonia”
 Granulomatous hepatitis, hepatosplenomegaly,
 Chronic disease: subacute endocarditis with
long incubation period and poor prognosis
Pathogenesis
 Target tissue is the lung, proliferate in
phagolysosomes of infected cells, then disseminate
to other organs
 Undergo antigenic variation (cell wall LPS):
phase I antigen: LPS with a complex carbohydrate,
can block antibody binding; infectious form
phase II antigen: modified LPS, expose surface
proteins to antibody, less infectious form
 Formation of immune complex: cause of signs and
symptoms
Diagnosis
Serologic tests (IFA, ELISA, CF)
 Acute Q fever: IgM and IgG are
developed against phase II antigen.
 Chronic Q fever: antibodies against both
phase I and II antigens are elicited.
(phase I antigen: weak antigenic)
T/P/C:
 Doxycycline for prolonged period
 Vaccine is available (single dose
with no booster immunization for
uninfected people)
Spotted fever
 Have a restricted geographic distribution; Rocky
mountain spotted fever (RMSF) is the prototype of
the group, caused by R. rickettsii.
 Organisms are maintained in hard ticks (wood
tick and dog tick) by transovarian transmission.
 Transmitted to humans by ticks (need 24-48h to
establish infection).
 High fever, chills, headache, skin rash (>90%,
extremities to trunk)
 GI symptoms, respiratory failure, encephalitis,
renal failure.
 Diagnosis is urgent, because the prognosis
depends on the duration of illness. (identify
key clinical signs – rash)
 Culture: tissue culture or embryonated eggs
(danger for personals )
 Microscopy: Giemsa stain; FA for biopsy
tissue specimens (rapid and specific)
 Serology: migration inhibitory factor test
(MIF), measure MIF(monocyte/macrophage
inhibitory factor.
 Molecular diagnosis: PCR, not species-
specific
Prevention/Control:
 Tetracyclines (e.g., doxycycline)
 No vaccine
 Prevent tick bites (can survive for as
long as 4 years without feeding)
Brill-Zinsser Disease
A recrudescent form of
epidemic typhus arising years
after the initial attack.
Diagnosis:
MIF test
T/P/C:
Tetracyclines, Chloramphenicol
Louse-control
Formaldehyde-inactivated vaccine
Bartonella Henselae
 Cat scratch disease (CSD)
 Weil-Felix reaction negative
 Infection by cats or dogs
 “Parinaud” Eye-Lymph node syndrome
The eye looks red, irritated, and painful,
similar to conjunctivitis.
Ehrlichia and Anaplasma
 Intracellular bacteria that
lodge in phagosomes of
mononuclear and
granulocytic phagocytes, but
not RBC.
 multiply in phagosomes =
morulae
Grow cycle: three stages -
elementary body, initial body,
morula
Clinical disease
Human monocytic ehrlichiosis
 E. chaffeensis : infect blood monocytes and
mononuclear phagocytes in tissues and organs
 Vector - Lone Star tick
 Reservoir - white-tailed deer, domestic dogs
Ehrlichia inclusions (peripheral blood
smear, Wright-Giemsa)
T/P/C:
 Diagnosis is urgent. Prompt
treatment with doxycycline
 No vaccine
 Avoid tick-infested areas
Reckettsia dr.ihsan alsaimary

Reckettsia dr.ihsan alsaimary

  • 1.
  • 2.
    General Characteristics  Smallobligate intracellular coccobacilli  Gram negative (poorly), better stained with Giemsa (Blue)  Have cell membrane, bigger than virus but smaller than bacteria  Have DNA and RNA  Have an ATP transport system that allows them to use host ATP  Arthropod reservoirs and vectors ( e.g., ticks, mites, lice or fleas).  Sensitive to antibiotics
  • 3.
    Structure: Similar with Gramnegative bacteria Cell membrane: outer membrane peptidoglycan lipopolysaccharide (LPS) Microcapsule and polysaccharide Two antigenically distinct groups:  LPS: heat-stable, cross-reactive with somatic antigens of non-motile Proteus species (Weil-Felix test)  Outer membrane protein: heat-unstable, species-specific
  • 4.
    six genera inthis class cause human diseases: Rickettsia Bartonella Coxiella (does NOT cause skin rash) Ehrlichia Orientia Anaplasma
  • 5.
    Diseases Caused bythe Rickettsia
  • 6.
    Pathogenic Mechanism Materials: Mechanism: Local lymphor micro blood vessels Endothelial cells, micro blood vessels in whole body Fever, rash, headache, etc (1st bacteremia) (2nd bacteremia) Endothelial cells, micro blood vessels Endotoxin and Phospholipase A Bites or faeces of arthropod Targets:
  • 7.
  • 8.
    Pathogenesis  Rickettsia (alsoEhrlichia) is unstable and die quickly outside host cells.  Coxiella highly resistant to desiccation, remain viable in environment for months to years.  Rickettsia replicate in endothelial cells, cause cell damage and blood leakage, skin rash, microthrombi, hemorrhage.  Hypovolemia, hypoproteinemia, reduced perfusion, organ failure.
  • 9.
    Immunity  Cellular immunityis important, and humoral immunity is helpful.  Persons become immune to further infection following recovery from the disease.
  • 10.
    Diagnosis and Prevention Microscopy  Serological Test (Weil-Felix reaction, ELISA, IF, PCR)  Breaking the infection chain ( controlling and killing the intermediate hosts and reservoir hosts)  Inactivated vaccine has protective effect  Chloromycetin, tetracycline are helpful for therapy, sulphonamides are not administered (increasing the penetrating of the vessel).
  • 11.
     Diagnosis/serological tests Direct detection of Rickettsia in tissues (Giemsa stain or direct fluorescent antibody test) Weil- Felix reaction – in certain rickettsial infections (typhus group) antibodies are formed that will agglutinate OX strains of Proteus vulgaris.  This is used as a presumptive evidence of typhus group infection, however, the test is not very sensitive or specific and many false positives occur.  Agglutination or complement fixation tests using specific Rickettsial antigens are better serological diagnostic tests.
  • 12.
    Virulence factors Rickettsial sp. Inducedphagocytosis Recruitment of actin for intracellular spread Coxiella burnetti Is resistant to lysosomal enzymes
  • 13.
    Coxiella burnetii  Biologicallyand genomically distinct from Rickettsia; more closely related to Legionella and Francisella.  Obligate intracellular pathogen  Multiply in phagolysosome
  • 14.
    Coxiella Burnetii  Qfever(query fever )  Self-limiting flu-like syndrome with high fever (40℃)  Primary reservoirs are wild (cattle, sheep, goat etc.)  Non-cross reactive antigen with non-motile Proteus (Weil-Felix reaction negative)  Live in macrophages of vertebrate host
  • 15.
    Q fever  Mostinfections are mild or asymptomatic  Acute disease:  Pneumonia - high fever, severe headache, chill, resemble “atypical pneumonia”  Granulomatous hepatitis, hepatosplenomegaly,  Chronic disease: subacute endocarditis with long incubation period and poor prognosis
  • 16.
    Pathogenesis  Target tissueis the lung, proliferate in phagolysosomes of infected cells, then disseminate to other organs  Undergo antigenic variation (cell wall LPS): phase I antigen: LPS with a complex carbohydrate, can block antibody binding; infectious form phase II antigen: modified LPS, expose surface proteins to antibody, less infectious form  Formation of immune complex: cause of signs and symptoms
  • 17.
    Diagnosis Serologic tests (IFA,ELISA, CF)  Acute Q fever: IgM and IgG are developed against phase II antigen.  Chronic Q fever: antibodies against both phase I and II antigens are elicited. (phase I antigen: weak antigenic)
  • 18.
    T/P/C:  Doxycycline forprolonged period  Vaccine is available (single dose with no booster immunization for uninfected people)
  • 19.
    Spotted fever  Havea restricted geographic distribution; Rocky mountain spotted fever (RMSF) is the prototype of the group, caused by R. rickettsii.  Organisms are maintained in hard ticks (wood tick and dog tick) by transovarian transmission.  Transmitted to humans by ticks (need 24-48h to establish infection).  High fever, chills, headache, skin rash (>90%, extremities to trunk)  GI symptoms, respiratory failure, encephalitis, renal failure.
  • 20.
     Diagnosis isurgent, because the prognosis depends on the duration of illness. (identify key clinical signs – rash)  Culture: tissue culture or embryonated eggs (danger for personals )  Microscopy: Giemsa stain; FA for biopsy tissue specimens (rapid and specific)  Serology: migration inhibitory factor test (MIF), measure MIF(monocyte/macrophage inhibitory factor.  Molecular diagnosis: PCR, not species- specific
  • 21.
    Prevention/Control:  Tetracyclines (e.g.,doxycycline)  No vaccine  Prevent tick bites (can survive for as long as 4 years without feeding)
  • 22.
    Brill-Zinsser Disease A recrudescentform of epidemic typhus arising years after the initial attack.
  • 23.
  • 24.
    Bartonella Henselae  Catscratch disease (CSD)  Weil-Felix reaction negative  Infection by cats or dogs  “Parinaud” Eye-Lymph node syndrome The eye looks red, irritated, and painful, similar to conjunctivitis.
  • 25.
    Ehrlichia and Anaplasma Intracellular bacteria that lodge in phagosomes of mononuclear and granulocytic phagocytes, but not RBC.  multiply in phagosomes = morulae Grow cycle: three stages - elementary body, initial body, morula
  • 26.
    Clinical disease Human monocyticehrlichiosis  E. chaffeensis : infect blood monocytes and mononuclear phagocytes in tissues and organs  Vector - Lone Star tick  Reservoir - white-tailed deer, domestic dogs Ehrlichia inclusions (peripheral blood smear, Wright-Giemsa)
  • 27.
    T/P/C:  Diagnosis isurgent. Prompt treatment with doxycycline  No vaccine  Avoid tick-infested areas