Malaria

malaria
Dr. Yuva Sri Sai Anumula
Assistant Professor
Department of Pharmacy Practice
Nirmala College of Pharmacy

CONTENTS
• DEFINITION
• HISTORY
• EPIDEMIOLOGY
• ETIOLOGY
• RISKFACTORS
• VECTOR
• MODE OF TRANSMISSION
• LIFECYCLE AND PATHOGENESIS
• SYMPTOMS
• LABORATORY INVESTIGATIONS
• DIAGNOSIS
• COMPLICATIONS
• TREATMENT
• PREVENTION

DEFINITION
• The term “malaria” originates from the Italian mala aria, meaning
“bad air” in 18th century. When the term was coined, it was commonly
believed that malaria was caused by breathing in bad air.
• Formerly called ague or marsh fever due to its association with swamps
and marshland.
• Malaria is a life threatening vector borne-disease disease caused by
plasmodium protozoa which is transmitted via bites of an infected female
anopheles mosquito.
• Uncomplicated malaria: symptomatic malaria without signs of vital organ
dysfunction.

HISTORY
• One of the oldest known diseases.
• King Tut died of malaria.
• Malaria has been infecting humans for over 50,000 years.
• References to malaria have been recorded for nearly 6000 years, starting
in China.
• Used to be common in Europe and North America.
• First advances in malaria were made in 1880 by a French army doctor

It was discovered
more than 100 years ago
•A French army doctor working in the
military hospital of Constantine in
Algeria—observed parasites inside red
blood cells of malaria patients and
proposed for the first time that a
protozoan caused disease.
•For this and later discoveries, he was
awarded the 1907 Nobel Prize for
Physiology or Medicine.
Charles Louis Alphonse Laveran
4

RONALD ROSS DISCOVERS THE ROLE OF
MOSQUITOS AND TRANSMISSION
Scottish Physician Sir Ronald Ross
discovered that Mosquito was the
vector for malaria in 1898.
First effective medicine was
discovered by Pierre Pelletier and
Joseph Caventou. This medicine is
called quinine, which comes from the
bark of cinchona trees in Peru.
No effective vaccine: only immunity
is a result of multiple infections.

Epidemiology

 Around 300-500 million clinical cases of malaria are
reported every year, of which more than a million die of
severe and complicated cases of malaria.
 Malaria is known to kill one child every 30 sec, 3000
children per day under the age of 5 years.
 Malaria ranks third among the major infectious diseases
in causing deaths after pneumococcal acute respiratory
infections and tuberculosis, and accounts for
approximately 2.6% of the total disease burden of the
world.

Epidemiology (cont.)

 It mainly occurs throughout tropical regions
 515 million clinical cases per year
 An estimated 655,000 people died from malaria in
2010
 with two-thirds of these occurring in sub-Saharan
Africa
 especially amongst children and pregnant women
 the incidence of malaria was greatly reduced
between 1950 and 1960
 but since 1970 there has been resurgence.

INDIA
• 95 % malaria prone area
• 1.5 – 2 million cases annually.
• The incidence of malaria in India accounted for 58% of cases in the South
East Asia Region of WHO.
• In 2014, there were 1.07 cases of malaria in million, 0.70 cases of
plasmodium falciparum in million and 535 deaths due to malaria.
• 21.98% - high transmission areas.
(High transmission >1 case/ 1000 popln)
• 92% of cases & 97% of death – north-eastern states, Chhattisgarh,
Jharkhand, M.P, Gujarat, Orissa,A.P, W.P, Karnatka.
• API has declined from 3.29 (1995) to 0.85 (2012)

ETIOLOGY
• Malaria is caused by a parasite called Plasmodium, which is transmitted via the
bites of infected mosquitoes
• The genus Plasmodium contains over 200 species of that at least 11 species
infect humans.
• Most important are:
Plasmodium falciparum
Plasmodium malariae
Plasmodium ovale
Plasmodium vivax
Plasmodium knowlesi
• Among those infected, P. falciparum is the most common species identified
(~75%) followed by P. vivax (~20%).
• Transmission of Malaria do not occur <16 c and >33 c
• Do not occur > 2000 meters altitude.

SPECIES CHARACTERISTICS
PV PO PM
72
PF
Periodicity(hrs.)
Parasites/Ml
RBC Age
48 50 48
20-50 9-30 6-20
Old
No
50-2000
AnyYoung Young
Hyponozoite
Duration (yrs.)
Yes Yes No
1.5-5 1.5-5 3->50 1-2

Who is at Risk?

 Most people who get
malaria are travelers or
people who live in an
area with malaria
transmission.
 Young children and
pregnant women.
 Poor people that live in
rural areas who lack
knowledge, money and
the access to health care.

Vector

 Female mosquitos of genus Anopheles are primary
hosts and transmission vectors.
 There are approximately 460 recognized species
 Over 100 can transmit human malaria
 Only 30–40 commonly transmit parasites of the
genus Plasmodium
 Anopheles gambiae is one of the best known which
transmits Plasmodium falciparum

Vector (cont.)

Only female mosquitoes feed on blood while
the males feed on plant nectar and do not
transmit the disease.
The females of Anopheles genus prefer to
feed at night
They start searching for a meal at dusk and
continue throughout the night until they take
a meal

MODE OF TRANSMISSION
• Malaria is caused by a type of
microscopic parasite that's
transmitted most commonly
by mosquito bites.
• Other transmission:
• From mother to unborn child
• Through blood transfusions
• By sharing needles used to
inject drugs

LIFE CYCLE AND PATHOGENESIS
1 Pre erythrocytic
schizogony
2 Erythrocytic
Schizogony
3 Gametogony
4 Exoerythrocytic
schizogony

Pre erythrocytic cycle
Sprozoites undergo developemtnal phase in the
liver cell
Sprozoites are elongated and spindle shaped
become rounded inside the liver parenchyma
Multiple nuclear divisions develop to Schozonts
A Schizont contains 20,000 – 50,000
merozoites.

Period of Pre erythrocytic cycle
1 P.vivax 8 days
2 P.falciparum – 6 days
3 P.malariae - 13 – 16 days,
4 P.ovale 9 days
On maturation Liver cells ruputure
Liberate Merozoites into blood stream

Affinity of Parasite to
Erythrocytes
P.vivax
P.malariae
P.ovale
Infectes only young or
Old Erythocytes
P.falciparum Infects all age groups
Also adhere to the endothelial lining of
Blood vessesl
Causes the obstruction, Thrombosis and
Local Ischemias

Erythrocytic Schizogony
Liberated Merozoites
penetrate RBC
Three stages occur
1 Trophozoites
2 Schizont
3 Merozoite

Erythrocytic cycle
Ruptured red cells release
Merozoites which attack
new red cells
Continue with Schizogony
Repeated cycles will
continue
In P.falciparum - infected
erythrocytes with
Schizonts aggregate in
the capillaries of brain and
other internal organs
Only ring forms are seen
in the blood smears

Trophozoites
After invasion grow
and feed on
hemoglobin
Blue cytoplasm and
red nucleus, Called
as Signet ring
appearance
Hence called ring
form

Schizont
When the Trophozoite is fully developed
becomes compact.
Malarial pigments are scattered through
the cytoplasm
The Nucleus is large and lies at the
periphery starts dividing.
Becomes Schizont

Exo Erythrocytic Schizogony
Some Sprozoites do not undergo
sporogony in the first instance
But go into resting stage called as
Hypnozoites,( hibernation )
Within 2 years reactivate to form
Schizonts release Merozoites and attack
red cell and produce relapses
Absent in P falciparum

Gametogony
Merozoites differentiate into Male and female
gametocytes
Macrogametocytes also called female
gametocytes
Microgametocyte also called as male
gametocytes
They develop in the red cells
Found in the peripheral blood smears
Microgametocyte of all species are similar in
size
Macro gametocytes are larger in size.

Mosquito cycle
A definitive Host – Mosquito

Mosquito cycle
Sexual cycle
Sexual cycle will be initiated in the Humans by
the formation of Gametocytes
female AnophelesDevelop further in the
Mosquito
Only mature sexual forms are capable of further
development in Mosquito
In midgut one Microgametocyte develops into 4-
8 thread like filamentous structures named Micro
gametes
From one macrogametocyte only one
macrogamete is formed

Events in Mosquitos
Fertilization occurs when a
Microgametocyte penetrate into
Macrogametocyte
Fertilized macrogametocyte is known as
ZYGOTE
ZYGOTE matures into OOKINETE
OOKINETE to OOCYST

Formation of Sporozoites in
Mosquitos.
OOCYST matures with large number of
Sporozoites ( A few hundred to thousands.)
OOCYST ruptures and release SPOROZOITES
in the body cavity of Mosquito
There is a specific predilection for salivary
glands
Now capable to transmit the infection to new
Host

Incubation Period
 It is usually 7 to 30 days.
 Reduced in p. falciparum
 Increased in p. malariae

Signs & symptoms:
The pathology and clinical manifestations
associated with malaria are almost
exclusively due to the asexual erythrocytic
stage parasites.
Tissue schizonts and gametocytes cause
little, if any, pathology..

Plasmodium infection causes an acute
febrile illness which is most notable for
its periodic fever paroxysms occuring at
either 48 or 72 hour intervals.
The severity of the attack depends on
the Plasmodium species as well as
other circumstances

Sometimes the incubation periods can be
prolonged for several months in P. vivax, P. ovale,
and P. malariae.
All four species can exhibit non-specific
prodromal symptoms a few days before the first
febrile attack.
These prodromal symptoms are generally
described as 'flu-like' and include: headache, slight
fever, muscle pain, anorexia and nausea.
The symptoms tend to correlate with increasing
numbers of parasites.

In contrast to the other three species, P.
falciparum can produce serious disease with mortal
consequences.
This increased morbidity and mortality is due in
part to the high parasitemias associated with P.
falciparum infections.
These potentially high parasitemias are due in
part to the large number of merozoites produced
and the ability of P. falciparum to invade all
erythrocytes.

Disease Severity and Duration
vivax ovale malariae falciparum
Initial Paraoxysm moderate to moderate to
severe
mild severe
Severity severe
Average
Parasitemia
(mm3)
50,000-
500,000
20,000 9,000 6,000
Symptom
Duration
(untreated)
3-8weeks 2-3 weeks 3-24 weeks 2-3 weeks
Maximum
Infection
Duration
(untreated)
12-20
months
5-8 years
++
20-50 years 6-17 months
Anemia + ++ ++++
Complications renal cerebral

Clinical Features

 P. falciparum (malignant tertian):
 It is the most dangerous of the malarias
 Onset is insidious, with malaise, headache and
vomiting… commonly mistaken for influenza
 The fever has no particular pattern.
 Jaundice is common due to hemolysis & hepatic
dysfunction
 There is hepatosplenomegaly
 Anemia develops rapidly

Clinical Features

 P. vivax & P. ovale (benign tertian):
 In many cases the illness starts with several days of
continued fever before the development of classical
bouts of fever on alternate days. Fever starts with a
rigor. The patient feels cold and the temperature
rises to about 40 C. After an hour hot or flush phase
begins. It lasts several hours and gives way to
profuse perspiration and a gradual fall in
temperature. The cycle is repeated 48 hours later.
 Anemia develops slowly

How Malaria present Clinically
 Stage 1(cold stage)
 Chills for 15 mt to 1 hour
 Caused due to rupture from the host red cells
escape into Blood
 Preset with nausea, vomitting,headache
 Stage 2(hotstage)
 Fever may reach upto 400c may last for
several hours starts invading newer red cells.

Clinical Malaria
 Stage 3(sweating stage)
Patent starts sweating, concludes the episode
Cycles are frequentlyAsynchronous
Paroxysms occur every 48 – 72 hours
In P.malariae pyrexia may last for 8 hours or
more and temperature my exceed 410c

Clinical Features

P. malariae infection (quartan):
 This is usually associated with mild symptoms and
bouts of fever every third day. Parasitemia may
persist for many years with the occasional recurrence
of fever, or without producing any symptoms.

Malaria
Paroxysm
• paroxysms associated with
synchrony of merozoite
release
• between paroxysms temper-
ature is normal and patient
feels well
• falciparum may not exhibit
classic paroxysms
(continuous fever)
tertian malaria
quartan malaria
DR.T.V.RAO MD 40

Laboratory Investigations
of Malaria

Diagnostic Tools
for Human Infections with Malaria
 Blood film examination(Microscopy)
 QBC system
 Rapid Diagnostic Tests" (RDTs)
 PCR (determine the species of
plasmodium)

Blood collected with sterile
technique

Microscopy
Malaria parasites can be identified by
examining under the microscope a drop of
the patient's blood, spread out as a "blood
smear" on a microscope slide. Prior to
examination, the specimen is stained
(most often with the Giemsa stain) to give
to the parasites a distinctive appearance.
This technique remains the gold standard
for laboratory confirmation of malaria

Microscopic demonstration still
the Gold standard in Diagnosis
Blood smear
stained with
Giemsa’s stain

QBC system has evolved as
rapid and precise method in
Diagnosis
The QBC Malaria method is the simplest and
most sensitive method for diagnosing the
following diseases.
Malaria
Babesiosis
Trypanosomiasis (Chagas disease, Sleeping Sickness)
Filariasis (Elephantiasis, Loa-Loa)
Relapsing Fever (Borreliosis)

Appearance of Malarial parasite
in QBC system

 Detects circulating
malaria antigens in
whole blood.
 Most often use a
dipstick or cassette format,
and provide results in 2-15
minutes.
 The only FDA cleared
rapid malaria test.
These "Rapid Diagnostic Tests" (RDTs)
offer a useful alternative to microscopy in
situations where reliable microscopic
diagnosis is not available
Antigen Detection Methods are Rapid
and Precise

How the test works?

 The test targets the histidine-rich protein II (HRPII)
antigen specific to P. falciparum and a pan-malarial
antigen (aldolase), common to all four malaria
species capable of infecting humans - P. falciparum,
P. vivax, P. ovale, and P. malariae.
 It is intended to aid in the rapid diagnosis of human
malaria infections and to aid in the differential
diagnosis of Plasmodium falciparum infections from
other less virulent malarial infections. Negative
results must be confirmed by thin / thick smear
microscopy.

Serology
Serology detects antibodies against
malaria parasites, using either indirect
immunofluorescence (IFA) or enzyme-
linked immunosorbent assay (ELISA).
Serology does not detect current infection
but rather measures past experience.

Newer Diagnostic methods
Molecular Diagnosis
Parasite nucleic acids are detected using
polymerase chain reaction (PCR). This
technique is more accurate than
microscopy. However, it is expensive, and
requires a specialized laboratory (even
though technical advances will likely result
in field-operated PCR machines).

Other Laboratory Findings
Normocytic anemia of variable severity.
Liver function tests may be abnormal
Presence of protein and casts in the Urine
of children with P.malariae is suggestive of
Quartan nephrosis.
In severe Falciparum malaria with renal
damage may cause oliguria and
appearance of casts, protein, and red cells
in the Urine

chest x-ray: helpful if respiratory
symptoms are present
CT scan: to evaluate evidence of
cerebral edema or hemorrhage

Diagnosis
 Clinical
 Fever, sweat, chills, headache and muscle pain
 Serology
 PCR
 ELISA
 Blood Film (gold standard)
 Banana-shaped intraerythrocytic gametocytes identify P.
falciparum
 Enlarged erythrocytes with Schuffner’s dots are
characteristics of P. vivax
 Schuffner’s dots in ovale-shaped red blood cells are
characteristic of P. ovale
 Band-form trophozoites are seen in P. malariae

Periodicity can be clue in Diagnosis
and species relation
 Malaria tertiana:
48h between fevers
(P. vivax and ovale)
 Malaria quartana:
72h between fevers
(P. malariae)
 Malaria tropica:
irregular high fever
(P. falciparum)

Malaria is probably the only infection that can be
treated in just three days, yet that kills millions every
year .
Malaria may become a medical emergency by rapidly
progressing to complications and death.
Early diagnosis & proper management can prevent
serious complication.
Most complications have similar pathogenesis .

Predisposing factors for complications
(1.) Extremes of age.
(2.) Pregnancy, especially in primigravidae and in 2nd
half of pregnancy.
(3.) Immunosuppressed - patients on steroids, anti-
cancer drugs, immunosuppressant drugs.
(4.) Immunocompromised - patients with advanced
tuberculosis and cancers.
(5.) Splenectomy.
(6.) Lack of previous exposure to malaria (non-immune)
or lapsed immunity
(7.) Pre-existing organ failure.

Complications of P. falciparum Complications of P. vivax / P.
malaria malariae
◦ Cerebral malaria ( coma )
◦ Convulsions
◦Rupture of spleen
◦Hepatic dysfunction
◦Thrombocytopenia
◦Severe anemia
◦ Hyperpyrexia
◦ Severe anemia
◦ Metabolic (Lactic) Acidosis
◦ jaundice ◦ nephropathymalarial
◦ renal failure (Black water fever)
◦ Pulmonary odema & ARDS
◦ hypoglycemia
◦ Hypotention & shock
◦ Bleeding & clotting disorder
◦ haemoglobinuria
◦ hyperparasitemia
◦ Associated infection

Why Falciparum Infections are
Dangerous
 Can produce fatal complications,
1.Cerebral malaria
2.Malarial hyperpyrexia
3.Gastrointestinal disorders.
4.Algid malaria(SHOCK)
5 Black water fever can lead to death

Pernicious Malaria
 Is a life threatening complication in acute
falciparum malaria
 It is due to heavy parasitization
 Manifest with
1 Cerebral malaria – it presents with
hyperpyrexia, coma and paralysis. Brain is
congested
2 Algid malaria – presents with clammy skin
leading to peripheral circulatory failure.

Cerebral malaria
For a diagnosis of cerebral malaria, the
following criteria should be met:
(i.) Deep, unarousable coma: Motor
response to noxious stimuli is non-localising
or absent.
(ii.) Exclusion of other encephalopathies.
(iii.) Confirmation of P. falciparum infection
all patients with P. falciparum malaria with
neurological manifestations of any degree
should be treated as cases of cerebral
malaria.

HAS HH
Causes of neurological manifestations in malaria:
◦High-grade fever
◦Antimalarial drugs
◦Hypoglycemia
◦Hyponatremia
◦Severe anaemia

Pathogenesis of
Cerebral malaria
 High cytokine levels could be toxic on their own
 High levels of cytokine also enhance the second process
thought to be responsible for cerebral malaria: sequestration
of infected RBCs

Cerebral Malaria
 Present with Hyperpyrexia
•It is characterized by changes
in the level of consciousness,
Convulsions.
Paralysis and other
complications
•Can lead to coma
•Brain appears congested

Management of cerebral
malaria :
manage airway
Phenobarbitone IM, 10-15 mg/kg body
weight should be given y to prevent
convulsions
Antimalarial treatment: (see the dose)

Shock :
Hypotension in malaria could be due to
many reasons:
◦ Dehydration due to high-grade fever,
excessive sweating and inadequate fluid
intake.
◦ Dehydration due to vomiting and/or
diarrhoea.
◦
◦
◦
◦
Pulmonary oedema.
Metabolic acidosis.
Associated Gram negative septicemia.
Massive gastrointestinal haemorrhage

Metabolic (Lactic)
Acidosis
Increased production of lactic acid by parasites
Decreased clearance by the liver
Most importantly the combined effects of several
factors that reduce oxygen delivery to tissues
.
.
.
Marked reductions in the deformability of uninfected RBCs may
compromise blood flow through tissues
Dehydrated and hypovolemia can exacerbates microvascular
obstruction by reducing perfusion pressure
Destruction of RBCs and anemia further compromises oxygen
delivery

Acute Pulmonary Odema:
It is a fatal complication of severe falciparum
malaria with more than 50% mortality .
In a few patients it could be due to fluid
overload
increased permeability of pulmonary
capillaries.
Sequestration of red cells and clogging of
pulmonary microcirculation and disseminated
intravascular coagulation DIC
more common in patients with
hyperparasitemia, renal failure and pregnancy .

Black water fever
Massive intravascular hemolysis
Due to P. falciprum
Severe acute hemolytic anemia
RBC=1-2*106 /ml
Hemoglobinuruia
Increase bilirubin
Acute tubcular necrosis & Hb casts

Black Water Fever
 In malignant malaria a large
number of the red blood
corpuscles are destroyed.
Haemoglobin from the blood
corpuscles is excreted in the
urine, which therefore is dark
and almost the colour of cola

Renal Failure :
Renal dysfunction in falciparum
malaria can be due to many factors:
◦Renal failure in malaria is caused by
renal cortical vasoconstriction and
resultant hypoperfusion, sequestration
and resultant acute tubular necrosis due
to microvascular obstruction and due to
massive intravascular hemolysis in
blackwater fever .

Anemia :
In falciparum malaria, anemia can develop
rapidly due to profound hemolysis
The degree of anemia correlates with
parasitemia and schizontemia
More serious in children and pregnant .
Bleeding disorder :
◦Thrombocytopenia
◦Disseminated intravascular coagulation DIC

Hypoglycemia:
Hypoglycemia in malaria may be asymptomatic
Therefore, hypoglycemia, which is easily
treatable, may be missed
Causes:
◦1. Increased consumption of glucose by the host and
the growing parasites.
◦2. Failure of hepatic gluconeogenesis and
glycogenolysis as a result of impaired liver function
and acidemia and hyperinsulinemia
◦3. Stimulation of pancreatic insulin secretion by drugs
like quinine. More than one of these factors may be
at play in a given patient

Rupture of spleen:
.It is more common in vivax malaria than falciparum
malaria
.occur in up to 0.7% of the patients
.Rupture occurs in acute, rapid, hyperplastic enlargement of
spleen
.Patients present with abdominal pain, fever, tachycardia,
prostration and rapidly developing anemia and
hypotension.
.Ultra sound evaluation of abdomen and paracentesis of the
abdomen can confirm the diagnosis
.Treatment includes replacement of fluid and blood,
laparotomy and splenectomy

Complication due to
medication
Vomiting
Dizziness
Itching ( chloroquine )
Abdominal pain
Convulsion ( chloroquine , quinine, meflequine )
Coma ( chloroquine , quinine)
Hypoglycemia ( quinine)
Anemia , jaudice ,Haemoglobinuria ( primaquine in pt
with G6PD deficiency )
Fever HAJ by

Sequestration & cytoadherence
 Rosetting (adhesion of
infected RBCs to other
RBCs) and clumping
(adhesion between
infected cells) was first
observed in in vitro culture

How long Malaria infection can lost in
Man
 Without treatment P.falciparum will terminate in
less than 1 year.
 But in P.vivax and P.ovale persist as
hypnozoites after the parasites have disppeared
from blood.
 Can prodce periodic relapses upto 5 years
 In P.malariae may last for 40 years
( Called as recrudescence X relapse )
Parasites survive in erythrocytes Liver ?

Malaria Relapses
 In P. vivax and P. ovale infections, patients
having recovered from the first episode of illness
may suffer several additional attacks
("relapses") after months or even years without
symptoms. Relapses occur because P. vivax
and P. ovale have dormant liver stage parasites
("hypnozoites") that may reactivate.

Where Microscopy Result Is Not Available Within 24 Hours And
Monovalent RDT Is Used

THE PHARMACOLOGY OF ANTIMALARIALS
Class Class Definition Examples Class Definition Examples
Definition
Examples
Blood
schizonticidal
drugs
Act on (erythrocytic) stage of Quinine, artemisinins,
the parasite thereby amodiaquine, chloroquine,
terminating clinical illness lumefantrine, tetracyclinea ,
atovaquone, sulphadoxine,
clindamycina , proguanila
Tissue Act on primary tissue forms of Primaquine, pyrimethamine,
schizonticidal
drugs
plasmodia which initiate the
erythrocytic stage. They block
further
proguanil, tetracycline
development of the
infection
Gametocytocid Destroy sexual forms of the Primaquine, artemisinins,
quininebal drugs parasite thereby preventing
transmission of infection to
mosquitoes
a Slow acting, cannot be used alone to avert clinical symptoms
b Weakly gametocytocidal

THE PHARMACOLOGY OF ANTIMALARIALS (cont.)
Class Definition
Examples
Class Definition
Examples
Class Definition
Examples
Hypnozoitocidal
drugs
These act on persistent Primaquine,
liver stages of P.ovale
and P.vivax which cause
recurrent illness
tafenoquine
Sporozontocidal
drugs
These act by affecting
further development of chlorguanil
gametocytes into
Primaquine, proguanil,
oocytes
within the mosquito thus
abating transmission

1. Treatment of severe falciparum malaria
Preferred regime Alternative regime
IV Artesunate (60mg): 2.4mg/kg on
admission, followed by 2.4mg/kg at 12h &
24h, then once daily for 7 days.
IV Quinine loading 7mg salt /kg over 1hr
followed by infusion quinine 10mg salt/kg over
4 hrs, then 10mg salt/kg Q8H or IV Quinine
20mg/kg over 4 hrs, then 10mg/kg Q8H.
Plus
Adult & child >8yrs old: Doxycycline
(3.5mg/kg once daily)
or
Once the patient can tolerate oral therapy,
treatment should be switched to a complete
dosage of Riamet (artemether/lumefantrine)
for 3 day.
Pregnant women & child < 8yrs old:
Clindamycin (10mg/kg twice daily). Both drug
can be given for 7 days.
Reconstitute with 5% Sodium Bicarbonate & Dilute injection quinine in 250ml od D5%
shake 2-3min until clear solution obtained.
Then add 5ml of D5% or 0.9%NaCl to create
total volume of 6ml.
and infused over 4hrs.
Infusion rate should not exceed 5 mg salt/kg
Slow IV injection with rate of 3-4ml/min or
IM injection to the anterior thigh.
per hour.
The solution should be prepared freshly for
each administration & should not be stored.

2. Treatment of uncomplicated p.falciparum
Preferred regime Alternative regime
Artemether plus lumefantrine(Riamet) Quinine sulphate (300mg/tab)
(1 tab: 20mg artemether/120mg lumefantrine)
Weight Day 1
Group
Day 2 Day3 Day 1-7: Quinine 10mg salt/kg PO
Q8H
5-14kg 1 tab stat
then 8hr
1 tab
Q12H
1 tab
Q12H Plus
*Doxycycline (3.5mg/kg once a
day)
later
15-24kg 2 tab stat
then 8hr
2 tab
Q12H
2 tab
Q12H OR
later
25-34kg 3 tab stat
then 8hr
3 tab
Q12H
3 tab
Q12H
*Clindamycin (10mg/kg twice a
day)
later
*Any of these combinations should
be given for 7 days.
Doxycycline: Children>8yr
Clindamycin: Children<8yr
>34kg 4 tab stat
then 8hr
later
4 tab
Q12H
4 tab
Q12H
Take immediately after a meal or drink
containing at least 1.2g fat to enhance

Treating Drug Resistance in
P.falciparum
Should be treated with
Quinine sulphate plus single dose of
Combination Drug Pyramethamine and
Sulphodoxine ( Fansidar )
Other Alternatives
1 Quinine plus Doxycycline or Tetracycline
2 Quinine plus Clindamycin
Newer alternatives
1 Mefloquine and Halofantril.

Children under 5 kg or below 4 months should not be given Riamet
instead treat with the following regimen (see table).
Dosage and administration Plasmodium falciparum for young infant
Weight
group
Age Group Artesunate or *Quinine
Oral
** IM first dose Quinine 10
mg/kgTDS
for 4 days
then 15-20
mg/kg TDS
for 4 days
***Oral
Artesunate 1.2
mg/kg or IM
Arthemeter 1.6
mg/kg)
0 - 4
months
Artesunate
2mg/kg/day
day 2 to day 7
<5 kg
Source: Malaria in Children, Department of tropical Pediatrics, Faculty of Tropical Medicine,
Mahidol University.
** Preferably Artesunate/Artemether IM on day 1 if available
*** When Artesunate/Artemether IM is unavailable, give oral Artesunate from day 1 to day 7
* Treat the young infant with Quinine when oral Artesunate is not available

3. Treatment of malaria caused by p.knowlesi
& mixed infection (p. falciparum + p. vivax)
Treat as p. falciparum

4. Treatment of malaria caused by p.vivax, p. ovale or p.
malariae.
CHLOROQUINE
PRIMAQUINE
(150 mg base/tab) 25 mg
(7.5 mg base/tab)
base/kg divided over 3 days
Start concurrently withDay 1 Day 2 Day 3
CHLOROQUINE 0.5 mg base/kg Q24H
for 2 weeks
Take with food
Check G6PD status before start
primaquine
In mild-to-moderate G6PD deficiency,
primaquine 0.75 mg base/kg body weight
given once a week for 8 weeks.
In severe G6PD deficiency, primaquine
is contraindicated and should not be
used.
10mg
base/kg
stat,
then
5mg
base/kg
5mg 5mg
base/kg base/kg
Q24H Q24H
1 tab of chloroquine phosphate 250mg equivalent to 150mg base. Calculation of
dose for chloroquine is based on BASE, not SALT form. 1 tab of primaquine
phosphate contains 7.5mg base.

Treatment in specific population & situations
Specific Preferred regime Alternative regime
populations
Pregnancy Quinine plus clindamycin to be given for Artesunate plus Clindamycin
7 day for 7 days is indicated if first
line treatment fails
Lactating
women
Should receive standard antimalarial treatment (includingACTs) except for
dapsone, primaquine and tetracyclines, which should be withheld during
lactation
Hepatic
impairment
Chloroquine: 30-50% is modified by liver, appropriate dosage adjustment
is needed, monitor closely.
Quinine : Mild to moderate hepatic impairment-no dosage adjustment,
monitor closely.
Artemisinins : No dosage adjustment
Renal Chloroquine : ClCr<10ml/min-50% of normal dose.
Impairment Hemodialysis, peritoneal dialysis: 50% of normal dose.
Continuous Renal Replacement Therapy(CRRT) :100% of normal dose.
Quinine : .ClCr 10-50ml/min : Administer Q8-12H, CLCr<10ml/min :
administer Q24H,Severe chronic renal failure not on dialysis : initial dose:
600mg followed by 300mg Q12H, Hemo- or peritoneal dialysis: administer
Q24H ,Continuous arteriovenous or hemodialysis: Administer Q8-12H.
Artemisinin : no dosage adjustment.

Treatment of complications of malaria
 Severe & complicated falciparum or
knowlesi malaria is a medical emergency
that requires intervention and intensive care
as rapidly as possible.
 Fluid, electolyte glucose & acid-base balance
must be monitored.Intake & output should be
carefully recorded.

Immediate clinical management of severe manifestations and
complications of P. falciparum malaria
Definitive clinical
features
Immediate management/treatment
Come (Cerebral malaria) Monitor & record level of consciousness using Glaslow
coma scale, temperature, respiratory, and depth, BP and
vital signs.
Hyperpyrexia (rectal
body temperature
>40°C)
Treated by sponging, fanning &with an antipyretic drug.
Rectal paracetamol is preferred over more nephrotoxic
drugs (e.g. NSAIDs)
Convulsions A slow IV injection of diazepam(0.15mg/kg, maximum
20mg for adults).
Hypoglycaemia (glucose Correct with 50% dextrose (as infusion fluids). Check
conc. <2.8mmol/L) blood glucose Q4-6H in the first 48hrs.
Severe anaemia (hb <
7g/dl)
Transfuse with packed cells. Monitor carefully to avoid
fluid overload. Give small IV dose of frusemide, 20mg,
as necessary during blood transfusion to avoid
circulatory overload.
Acute pulmonary
oedema
Prop patient upright (45°), give oxygen, give IV diuretic
(but most patient response poorly to diuretics), stop
intravenous fluids. Early mechanical ventilation should

Immediate clinical management of severe manifestations and
complications of P. falciparum malaria (cont.)
Definitive clinical
features
Immediate management/treatment
Acute renal failure (urine Exclude pre-renal causes by assessing hydration status.
output <400ml in 24hrs Rule out urinary tract obstruction by abdominal
in adults or 0.5ml/kg/hr, examination or ultrasound.
failing to improve after
rehydration & a serum
creatinine of
Give intravenous normal saline
If in established renal failure add haemofiltration or
haemodialysis, or if unavailable, peritoneal dialysis.
>265μmol/L)
Disseminated
intravascular
Coagulopathy (DIVC)
Transfuse with packed cell, clotting factors or platelet.
Usual regime: Cryoprecipitate 10units,platelets 4-8units,
fresh frozen plasma(10-15ml/kg).
For prolonged PT, give vitamin K, 10mg by slow IV
injection.
metabolic acidosis Infuse sodium bicarbonate 8.4% 1mg/kg over 30min
and repeat if needed.
if severe, add haemodialysis.
Shock (hypotension with Suspect septicaemia, take blood for cultures; give
systolic blood pressure parenteral broad-spectrum antimicrobials, correct

Monitoring & follow-up
 Blood smear should be repeated daily
(twice daily in severe infection). Within 48-
72 hr after start of treatment, patients
usually become afebrile and improve
clinically except in complicated cases.
 All patients should be investigated with
repeated blood film of malarial parasite
one month upon recovery of malarial
infection, to ensure no recrudescence.

CHEMOPROPHYLAXIS
• Indicated for travellers travel to endemic areas
•Short term chemoprophylaxis (up to 6 weeks) Doxycycline : 100
mg once daily for adults and 1.5 mg/kg once daily for
children(contraindicated in children below 8 years). The drug
should be started 2 days before travel and continued for 4 weeks
after leaving the malarious area.
• Chemoprophylaxis for longer stay (more than 6 weeks)
Mefloqiune: 250 mg weekly for adults and should be
administered two weeks before, during and four weeks after
exposure.

Dosing schedule for mefloquine
Weight Age No of tablets
per
week
< 5 kg < 3 months Not
recommended
5 - 12 kg 3 - 23 months 1/4
1/2
3/4
1
13 - 24 kg
25 - 35 kg
2 - 7 yrs
8 - 10 yrs
36 and above 11 yrs and
above

Dosing schedule for doxycycline
Weight in Age in No of tablets
kg years
< 25 < 8 Contraindicated
½25 - 35 8 - 10
36 - 50 11 - 13 ¾
50+ 14+ 1

PREVENTION

 Medications (will be mentioned in treatment)
 Vector control
 Mosquito nets and bedclothes
 Immunity (natural & vaccines)
 Education

Vector Control

 Efforts to eradicate malaria by eliminating
mosquitoes have been successful in some areas.
Malaria was once common in the United States and
southern Europe, but vector control programs, in
conjunction with the monitoring and treatment of
infected humans, eliminated it from those regions.
 Malaria was eliminated from most parts of the USA
in the early 20th century by use of the pesticide DDT.

Mosquito nets

 Mosquito nets help keep mosquitoes away from people
and greatly reduce the infection and transmission of
malaria. The nets are not a perfect barrier and they are
often treated with an insecticide designed to kill the
mosquito before it has time to search for a way past the
net. Insecticide-treated nets (ITNs) are estimated to be
twice as effective as untreated nets and offer greater than
70% protection compared with no net. Since the
Anopheles mosquitoes feed at night, the preferred
method is to hang a large "bed net" above the center of a
bed such that it drapes down and covers the bed
completely.

Immunity

 Natural immunity occurs, but only in response to
repeated infection with multiple strains of malaria.
 A completely effective vaccine is not yet available for
malaria, although several vaccines are under
development.
 SPf66 was tested extensively in endemic areas in the
1990s, but clinical trials showed it to be insufficiently
effective.
 Other vaccine candidates, targeting the blood-stage of the
parasite's life cycle, have also been insufficient on their
own.
 Several potential vaccines targeting the pre-erythrocytic
stage are being developed.

Vaccines

First proposed in 1960s, still nothing fully effective
Difficulties include :
 Intracellular parasites
 Polymorphism and clonal variation
 Parasite induced immunosuppression
 Antigenic variation
 Evaluation and trials difficult to interpret
 High level of parasite mutation

Education
 Education in recognizing the symptoms of malaria
has reduced the number of cases in some areas of the
developing world by as much as 20%.
 Recognizing the disease in the early stages can also
stop the disease from becoming a killer.
 Education can also inform people to cover over areas
of stagnant, still water which are ideal breeding
grounds for the parasite and mosquito, thus cutting
down the risk of the transmission between people.
 This is most put in practice in urban areas where
there are large centers of population in a confined
space and transmission would be most likely in these
areas.

WHAT ARE WAYS TO PREVENT
MOSQUITO BITES?
• Use mosquito
repellants.
• Wear long pants and
long sleeves.
• Wear light-colored
clothes.
• Use window screens
• Use bed nets.
DR.T.V.RAO MD 54

INSECTICIDE-TREATED NETS (ITNS)
• What is happening here?
• What needs to happen within six months?
• Can you think of any practical challenges?
Source: HEPFDC, 2009.
DR.T.V.RAO MD 55

ORIGINAL ERADICATION PLANS
• Interruption of
transmission of main
species infecting
humans by DDT
spraying
• Malaria disappears
spontaneously in under
3 years
Source: Gabaldon
DR.T.V.RAO MD
56

OTHER WAYS TO PREVENT MALARIA
Who is at the highest risk of malaria?
• Travelers to an area high in malaria
• Travelers often take prophylactic (preventive)
medicines to prevent malaria.
• Pregnant women (especially those with HIV)
• Pregnant women are given intermittent preventive
treatment. They are given at least 2 doses of a
malaria drug during their pregnancy.
• Young children
• How can you protect young children?
DR.T.V.RAO MD 57

MILESTONES
. Sir Bhore Committee Report 1946
1953
1958
1971
1977
1995
1977
1999
2002
. National Malaria Control Program
. National Malaria Eradication Program
. Urban Malaria Scheme
. Modified Plan Of Operation
. Malaria Action Program
. Enhanced Malaria Control Program
. National Anti Malaria Program
. National Health Policy
. National Vector Borne Disease Cont Program 2004
. Intensified Malaria Control Project
. National Rural Health Mission
2005
2005

NATIONAL MALARIA CONTROL
PROGRAMME 1953
OBJECTIVES
• To bring down malaria transmission
• To hold down malaria transmission at low level
ACHIEVEMENT
•Decline in incidence from 75 million to only 2 million in 1958

NATIONAL MALARIA ERADICATION
PROGRAMM 1958
OBJECTIVE
To eradicate malaria from India in 7 to 9 years
ACTIVITIES
Spraying operation
Fortnightly active case detection
Radical treatment
Investigation of positive cases and remedial measures
ACHIEVEMENTS
Lowest ever incidence of 0.1 million in 1965
No reported deaths due to malaria

URBAN MALARIA SCHEME 1971
In 139 towns in 19 states and union territories.
OBJECTIVES
a) To prevent deaths due to malaria.
b) Reduction in transmission and morbidity.
NORMS
The towns should have a minimum population of 50,000.
The API should be 2 or above.
The towns should strictly implement the civic by-laws to
prevent/eliminate domestic and peri-domestic breeding places.

Control Strategies under Urban Malaria Scheme:
-Parasite control
-Vector control
Parasite control: Treatment is done through passive agencies viz. hospitals, dispensaries both in
private & public sectors and private practitioners. In mega cities malaria clinics are established
by each health sector/ malaria control agencies viz. Municipal Corporations, Railways, Defence
services
Vector control comprises of the following components
Source reduction
Use of larvicides
Use of larvivorous fish
Space spray
Minor engineering
Legislative measure
Aerosol Space Spray
Space spraying of pyrethrum extract (2%) in 50 houses in and around every malaria and
dengue positive cases to kill the infective mosquitoes is recommended.
Town –biologist
State-additional director (malaria/filaria)
Central level-director NVBDCP

MODIFIED PLAN OF OPERATION 1977
OBJECTIVES
•Prevention Of Death Due To Malaria
•Reduction Of Morbidity Due To Malaria
•Retention Of Achievements Gained So Far
•Re-classification Of Endemic Areas
•Based On
• API Less T
Pa idence
ater Than 2
•Areas With API > 2
•Spraying
•Entomological Assessment
•Surveillance
•Treatment Of Cases
•Decentralization Of Laboratory Services At-phc
•Establishment Of Ddcs And Ftds

•Areas With Api < 2
•Focal Spraying
•Surveillance And Treatment
•Follow Up
•Epidemiological Investigation

MALARIA ACTION PROGRAMME
1995
RESURGENCE OF MALARIA
(RAJASTHAN/MANIPUR/NAGALAND/ASSAM/WB/MAHARASHTRA)
EXPERT COMMITTEE 1994
HIGH RISK AREAS IDENTIFIED
FTD MICROSCOPY FACILITY
30,000 POPULATION1,000 POPULATION

ELEMENTS
Early diagnosis and prompt treatment
Sustainable preventive measures including vector control
Prevention of epidemics
Regular assessment
HIGH RISK AREAS
High API
High proportion of pf cases
Reported death due to malaria
SPR doubled
SPR >5%

ENHANCED MALARIA CONTROL PROJEC 1997
•With World Bank Assistance
•1997-2003, Extn To 2005
Objectives
.Effective control of malaria
.Bring down malaria morbidity
.Prevention of death due to malaria
.Consolidation of gain achieved so far
Selection Of Phc-criteria
.API>2 for last 3 yrs
.P. Falciparum >30% of cases
.25% tribal population
.Death due to malaria

MAIN COMPONENTS
•Early case detection and treatment
•Selective vector control and personal protection
•Health education and community participation
PLAN OF ACTION
•Synthetic pyrethroids
•Bed nets
•Rapid diagnostic kits
•Arteether injections
•Blister packs
•Funds for training

NATIONAL AN MALARIA PROGRAMME 1999
OBJECTIVES
•Reduce malaria morbidity and mortality by 50%
TARGETS AND INDICATORS
•ABER>10%
•API 1.3 or less
•25% reduction in morbidity and mortality by 2010
•50% reduction in morbidity and mortality by 2012

NATIONAL VECTOR BORNE DISEASE CONTROL
PROGRAMME
•Launched in year 2003-04
•Major vector borne diseases-
•Malaria
•Filaria
•Kala-azar
•Japanese Encephalitis
•Dengue / Dengue Hemorrhagic fevers
•Chikungunya
Integrated accelerated action towards
•Reducing mortality on account of Malaria, Dengue and JE by half

INTENSIFIED MALARIA CONTROL PROJECT
Launched in July 2005 with assistance of global fund for AIDS,TB and
malaria in NE states,Odisha,Jharkhand and WB.
OBJECTIVES:
1-Increase access rapid diagnosis and treatment through community
participation
2-Reduce transmission by used of insecticide treated bednets and
larvivorous fish
3-Enhance awareness about malaria control
4-To promote community,NGO,private sector participation

• Indoor residual spraying or IRS is the process of spraying the inside of
dwellings with an insecticide to kill mosquitoes that spread malaria.
• The main purpose of IRS is to reduce transmission by reducing the
survival of malaria vectors entering houses or sleeping units.
Effectiveness of IRS depends on:
• Target area
• Selection of Insecticides
• Change of Insecticide
• Insecticide formulations used under NVBDCP
1. DDT( Dichloro-diphenyl-trichloroethane)
2. Organophosphorus (OP) compounds
3. Synthetic Pyrethroids

• An insecticide-treated net is a mosquito net that repels,
disables and/or kills mosquitoes coming into contact with
insecticide on the netting material. There are two
categories of ITNs:
• • A conventionally treated net is a mosquito net that
has been treated by dipping in a WHO-recommended
insecticide.
• • A long-lasting insecticidal net is a factory-treated
mosquito net made with netting material that has
insecticide incorporated within or bound around the
fibres.

• Specific Objectives: Reduce human contact, reduce morbidity,
prevent deaths, promote community participation, modalities for
social marketing through public-private partnership.
• Synthetic Pyrethroids mainly two Deltamethrin(2.5%) at a
dosage of 25mg/m2 and cyfluthrin (5%) at 50mg/m2.

• Environmental control: Good water management practices are
best. Could be Temporary and Permanent.
• Biological control: Fishes, Insects, Protozoans, Arthropods,
Bacteria, Fungi & viruses.
• Genetic control: Genetic Engineering like Transgenic Mosquito.
• Chemical control: Given high priority in Operational Measures.

:
Bacillus thuringiensis and
B. sphaericus
- Predatory mosquito larvae
(Toxorhynchites)
- Copepods (Macrocyclops
albidus)

INTEGRATION UNDER NRHM
At Village Level
Monthly meetings of Village Health & Sanitation Committee serve
as a platform for health education and counseling of community.
Involvement of ASHA as-
Surveillance worker to inform any increase in fever cases including
Dengue/ Chikungunya and J.E.
FTD for early detection of suspected malaria cases and treatment.
Linkage between ANC services and prevention & treatment of
malaria.
Organizer, motivator and trainer in village level meetings/training
workshops.

MDG 6 COMBAT HIV/AIDS, MALARIA AND
OTHER DISEASES
Target 6c: Halt and begin to reverse the incidence of
malaria and other major diseases
6.6 Incidence and death rates associated with malaria
6.7 Proportion of children under 5 sleeping under
insecticide-treated bed nets
6.8 Proportion of children under 5 with fever who are
treated with appropriate anti-malarial drugs

• Integrated Disease Surveillance Project(IDSP) - The
Project with weekly fever alerts is increasingly providing
early warning signals on malaria outbreaks.
• Other Vector borne diseases - Dengue & malaria control
activities overlap in many Urban areas, Malaria & kala-azar
in few districts of Jharkhand.
• Reproductive and Child Health - ANC services utilized in
distribution of LLINs to pregnant women.

• Global Fund for AIDS, TB & Malaria(GFATM) supported
Intensified Malaria Control Project(IMCP):
• It was for a period of 5years from July 2005 to June 2010.
Implemented in 106 districts in 10 states.
• It helped to achieve 23.4% decline in Malaria Incidence.
• IMCP-II has been initiated for a period of five years (2010-
2015).

• Approved for 5years(March 2009-Dec 2012). Total
financial outlay Rs.1000 Crore.
• Being implemented in 93 malarious districts of eight
states including Andhra Pradesh.
• Provides additional Support for procuring ACT, LLIN’s,
Provision of additional manpower.

ROLL BACK MALARIA
• RBM is a global partnership founded in 1998 by (WHO), (UNDP),
(UNICEF) and the World Bank with the goal of halving the
world's malaria burden by 2010.
• It forges consensus among key actors in malaria control,
harmonises action and mobilises resources to fight malaria in
endemic countries and to improve and support capacity to scale
up action against malaria.

• RBM's four pillars of action
ROLL BACK MALARIA is promoting four main strategies
to pursue its goal of halving the world's burden of
malaria by 2010. The strategies are evidence-based
• Prompt access to treatment
• Insecticide-treated mosquito nets (ITNs)
• Prevention and control of malaria in pregnant women
• Malaria epidemic and emergency response

Vaccines developed are basically of three types:
• Pre-erythrocytic stage vaccine
• Blood stage vaccine and
• Transmission blocking vaccine
• SPf-66—1st malaria vaccine that was tried in clinical trials in 1990s.
• RTS,S - Most successful vaccine candidate.
• On July 25th 2015 World's first malaria vaccine got a green light from
European drugs regulators who recommended it should be licensed for
use in babies in Africa at risk of the mosquito-borne disease.
• The shot, called RTS,S or Mosquirix developed by British drugmaker
GlaxoSmithKline in partnership with the PATH Malaria Vaccine Initiative,
would be the first licensed human vaccine against a parasitic disease.

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