1

INTRODUCTION
Malaria is an infectious disease caused by a protozoan
parasite Plasmodium, acquired by the bite of female Anopheles
mosquito.
It is the most important of the parasitic diseases of the
humans. Malaria has now been eliminated from the United States ,
Canada, Europe, Russia but despite enormous control efforts has
resurged in many parts of the tropics
1
.
Malaria affects more than 2400 million people, over 40% of the
world' s population, in more than 100 countries in the tropics from
South America to the Indian peninsula
2
.
The tropics provide ideal breeding and living conditions for the
anopheles mosquito, and hence this distribution.
Every year 300 million to 500 million people suffer from this
disease (90% of them in sub-Saharan Africa, two thirds of the
remaining cases occur in six countries- India, Brazil, Sri Lanka,
Vietnam, Colombia and Solomon Islands). WHO forecasts a 16%
growth in malaria cases annually
2,3
. About 1.5 million to 3 million
people die of malaria every year (85% of these occur in Africa),
accounting for about 4-5% of all fatalities in the world.
One child dies of malaria somewhere in Africa every 20 sec.,
and there is one malarial death every 12 sec somewhere in the
2
world.
1 HIV/ AIDS death is equal to 50 malaria deaths
3
.
Malaria ranks third among the major infectious diseases in
causing deaths- after Pneumococcal acute respiratory infections and
Tuberculosis.
It is expected that by the turn of the century malaria would be
the number one infectious killer disease in the world.
It accounts for 2.6 percent of the total disease burden of the
world.
It is responsible for the loss of more than 35 million disability-
adjusted life-years each year.
Every year about 30000 visitors to endemic areas develop
malaria and 1% of them may die.
Estimated global annual cost (in 1995) for malaria: US$ 2
billion (direct and indirect costs, including loss of labour).
Estimated worldwide expenditure on malaria research: US$ 58
million, one thousandth of the US$ 56 billion spent globally on
health research annually.
Estimated annual expenditure on malaria research, prevention
and treatment: $ 84 million.
Estimated worldwide expenditure per malaria fatality: $ 65; as
3
compared to $ 3274 for HIV/ AIDS and $ 789 for asthma.
There is an increase in the incidence of drug resistance of the
parasite and insecticide resistance of the vector.
Malaria remains today, as it has been for centuries, a heavy
burden on tropical communities, a threat to non endemic countries,
and a danger to travellers.

4
AIMS AND OBJECTIVES
1. To study the incidence of thrombocytopenia in Malaria.
2. To correlate with the type and severity of Malaria.













5
REVIEW OF LITERATURE
HISTORY:
Malaria is an infectious disease caused by
protozoan parasite Plasmodium 1.
It is the most important of the parasitic diseases of humans1. Malaria is
known from antiquity. Malaria in Italian means bad air. Hippocrates in his
Aphorisms described the regular aroxysms of intermittent fever4.
Charaka and Susrutha described tertian and quartan fevers.
In 1880 Charles Alphonse Louis Laveran,a French surgeon,
first observed the erythrocytic stages of the parasite
4
.
Transmissibility of the infection in blood was proved by Gerhardt
4
.
Sir Ronald Ross, a Scottish physician working in Indian
army, in 1897 established the transmission of disease from mosquito.
Julius Wagner in 1917 inoculated blood from a soldier with
tertian malaria into patients GPI
4
(General Paralysis of Insane).
Both Ronald Ross (1902) and Laveran (1907) won the Nobel
prize for their discoveries in malaria
4
.
LIFE CYCLE:
The life cycle of all human malarial species consists of two
phases. A sexual phase (sporogony) with development and
multiplication in female anopheline mosquitoes and an asexual phase
6
with multiplication in man. The asexual phase in man has two parts,
schizogony in the cells of liver (prerythrocytic schizogony a tissue
phase) and schizogony in the red blood cells (erythrocytic
schizogony)
ASEXUAL PHASE IN HUMAN HOST:
EXOERYTHROCYTIC SCHIZOGONY: Sporozoites are inoculated
by the mosquito in to the host and disappear from the circulation in
half an hour. Some enter the parenchymal cells of liver where they
undergo development and multiplication known as Exoerythrocytic or
Preerythrocytic schizogony. The tissue schizont which develops from
the sporozoite enlarges and the nucleus and cytoplasm divide to form
many thousands of merozoites which after 6-16 days, rupture the
liver cells and invade the circulation, where they enter red cells by
process of invagination. The prepatent period is the time from
injection until the appearance of parasites in the blood and varies
with species of parasite. P.vivax
6-8 days, P. Malaria 12-16 days, P. Ovale 9 days, and P.falciparum
6-7 days.
7
Figure1:Life cycle of plasmodium
In P.vivax and P. Ovale malaria some of the exoerythrocytic
schizonts lie dormant and are known as hypnozoites. After periods of
upto 250 days they become active and mature allowing merozoites to
infect red cells and give rise to an erythrocytic phase. This is the
mechanism responsible for delayed prepatent period and relapses in
vivax and ovale malaria.
ERYTHROCYTIC SCHIZOGONY:
The merozoites liberated in to the blood stream closely
resembles sporozoites. They are motile ovoid forms which rapidly
8
invade red cells. The process of invasion involves attachment to the
erythrocyte surface and then interiorization takes place by a wriggling
and boring motion inside a vacuole composed of the invaginated
erythrocytic membrane. The attachment of the merozoite to the red
cell is mediated by specific erythrocytic surface receptor. In P.vivax
this is related to Duffy blood group antigens Fya or Fyb. The
receptors for P.falciparum have not been identified. The glycophorins,
a family of membrane receptors are probably involved as red cells
from subjects with some abnormal glycophorins resisting infection.
The young developing parasites look like a signet ring as in
the case of Plasmodium falciparum like a pair of stereo headphones.
Parasites are freely motile within the erythrocyte. As they grow they
consume the erythrocytic contents. Proteolysis of Hb within the
digestive vacuole releases amino acids and are taken up and utilized
by the growing parasite for protein synthesis but the liberated
haeme poses a problem. When haeme is freed from protein scaffold,
it oxidizes to toxic ferric form. Toxicity is avoided by spontaneous
polymerization
to an inert crystalline substance, haemozoin. The digested products,
mainly the brown or black insoluble pigment haemozoin can be
seen within the digestive vacuole of growing parasite. The injected
erythrocyte becomes progressively less elastic and deformable and
more spherical as the parasite grows.
At approximately 24-26 hrs of development of P.falciparum
9
parasites begin to exhibit a high molecular weight strain specific
variant antigen on the surface of the injected red cells, which
mediates attachment to vascular endothelium. There is also knob like
projection from the erythrocyte membrane. These red cells then
disappear from the circulation by attachment or cytoadherence to
the walls of venules and capillaries in the vital organs. This process
is called sequestration. The other three benign malaria do not
cytoadhere and all stages of development are seen in the peripheral
blood.
Eventually, the growing parasite occupies the entire red cell,
which becomes circular, rigid, depleted in hemoglobin and full of
merozoites. These then rupture and between 6 36 hrs ,
merozoites are released destroying the remnants of red cell. These
rapidly invade other red cells and start a new asexual cycle. Asexual
life cycle is 48 hrs for P.falciparum, P.vivax, P.ovale and 72 hrs for
P.malariae.
SEXUAL STAGES & DEVELOPMENT IN THE MOSQUITOES:
GAMETOGONY:
After a series of asexual life cycle, a sub population of parasites
develop in to sexual forms (gametocytes) which are long lived and
motile. This process
takes about 4 days in P.vivax infection, and more than 10 days in
P.falciparum. The male female genotypic sex ratio of P.falciparum is
10
1:4.

SPOROGONY:
Following ingestion in the blood meal of a biting female
anopheline mosquito, the male and female gametocytes become
activated. The male gametes undergo rapid nuclear division and each
of the eight nuclei formed associate with a flagellum. The motile
microgametes then separate and seek the female microgametes.
Fusion and meiosis takes place to form a zygote.
Within 24 hrs the enlarging zygote becomes motile and this form
(the ookinete) penetrates the wall of the mosquito mid gut where it
encysts. This spherical bag of parasites expands by asexual division
to reach a diameter of approximately 500 .
The oocyst finally bursts to liberate myriads of sporoziotes in to
the coelomic cavity of mosquito. The sporozoites then migrate to the
salivary glands to await inoculation in to the next human host during
feeding.
PATHOPHYSIOLOGY
5
:
The pathophysiology of malaria results from destruction of
erythrocytes, the liberation of parasite and erythrocyte material into
the circulation, and the host reaction to these events. P.falciparum
malaria infected erythrocytes also sequester in the microcirculation of
11
vital organs, interfering with microcirculatory flow and host tissue
metabolism.
1.1 TOXICITY OF CYTOKINES
Malaria parasite induces release of cytokines in the same way
as bacterial endotoxin. A glycolipid material with many of the
properties of bacterial endotoxin is released on meront rupture. This
material appears to be associated with glycosyl phosphatidylinositol
anchor which covalently links proteins including the malarial parasite
surface antigens to the cell membrane lipid bilayer. Cells of the
macrophage monocyte series, and possibly endothelium, are
stimulated to release cytokines. Initially, tumor necrosis factor (TNF)
and interleukin (IL-1) are produced and these in turn induce release
of other proinflammatory cytokines including 1L-6 and IL-8.
Cytokines may up-regulate the endothelial expressions of
vascular ligands for P.falciparum infected erythrocytes and thus
promote cytoadherence. They may also be important mediators of
parasites kil l i n g by activating leukocytes, and possibly other cells, to
release toxic oxygen species, nitric oxide by generating paracidal
lipid peroxides and by causing fever. Thus, high concentrations of
cytokines appear to be harmful. Lower levels probably benefit the
host.
1. SEQUESTRATION
The process whereby erythrocytes containing mature forms of
12
P.falciparum adhere to microvascular endothelium (Cytoadherence)
and disappears from the circulation, is known as sequestration.
Sequestration is thought to be central to the pathophysiology of
falciparum malaria. Sequestration occurs predominantly in the
venules of vital organs. It is not distributed uniformly throughout the
body, being greatest in the brain, particularly the white matter,
prominent in heart, liver, kidneys, intestines and adipose tissue and least
in the skin.
3. CYTOADHERENCE
Cytoadherence is mediated by a family of strain specific high
molecular weight parasite derived proteins termed P.falciparum
erythrocyte membrane protein l (Pf EMP1). This protein is exported to
the surface of the infecting erythrocyte where it is anchored through
the membrane to a sub-membranous accretion of parasite derived
histidine rich protein. These accretions cause humps or knobs on
the surface of the red cells, and these are the points of attachment to
vascular endothelium.
The adhesive protein, PfEMPl, is present in relatively low
amounts on the red cell surface. It is the only parasite protein
unequivocally present on the outside of the erythrocyte. It is a
trypsin sensitive antigen, and has been shown to undergo antigenic
variation within cloned parasite line.
There are two other antidotes for the ' glu e' which binds
parasitized red cells to endothelium. The protein MESA may also be
13
partially expressed on the
surface of the red cell. The other possibility is that a modified form of
the red cell cytoskeleton protein band 3 (the major erythrocyte anion
transporter) is the adhesion.
4. VASCULAR ENDOTHELIAL LIGANDS
Several different sticky proteins present on the surface of
vascular endothelium have been shown to bind parasitized red cells.
Most important of these proteins is the leukocyte differentiation
antigen CD36; nearly all freshly obtained parasites bind to CD 36. The
In ter cellular adhesion molecule ( ICAM1), also bind parasitized
erythrocytes. Expression of lCAMl, can be upregulated by cytokines
(notably TNF) and would provide a plausible pathological scenario
whereby cytokine release enhances ' Cytoadherence' .
Thrombospondin (a natural ligand to CD36) will also bind to some
parasitized red cells and recently the ubiquitous proteins VCAM and
ELAM have also been shown to bind.
ICAM1, appears to be the major vascular ligand in the brain
involved in cerebral sequestration and CD36 is probably the major
ligand in other organs. Chondroitin sulphate A is the major ligand in
the placenta.
5. ROSETTING
Erythrocytes containing mature parasites also adhere to
uninfected erythrocytes. This process leads to the formation of '
14
rosettes' . Rosetting shares some characteristics of cytoadherence. It
occurs mainly at the middle of asexual life cycle and it is trypsin
sensitive. Rosetting in P.falciparum infections is also seen in cerebral
malaria and increased cytoadherence with other vital organ
dysfunction.
Cytoadherence and related phenomenon of rosetting lead to
micro circulatory obstruction. The consequences are reduced oxygen
and substrate supply, leading to anaerobic glycolysis and lactic
acidosis.
AGGLUTINATION:
P. falciparum infected RBCs may also adhere to other
parasitized erythrocytes.
The process of sequestration, cytoadherence, rosetting and
agglutination are central to pathogenesis of falciparum malaria. They
interfere with micro circulatory flow and metabolism.
CLINICAL FEATURES:
The first symptoms of malaria are nonspecific that include lack
of sense of well being, headache, fatigue, myalgia, nausea and
vomiting. Malaria is characterised by acute febrile attacks in which
fever spikes, chills and rigors occur at regular intervals. They are
associated with synchrony of merozoite release. In falciparum malaria
paroxysms may occur at intervals of less than expected 48 hrs as
cycles are often poorly synchronised. The typical attack comprises
15
three stages i.e., cold stage, hot stage and sweating stage.
Physical examination may reveal pallor, icterus and
hepatosplenomegaly.
SEVERE FALCIPARUM MALARIA
5
:
In a patient with P.falciparum asexual parasitemia and no
other obvious cause of other symptoms, the presence of one or more
of the following clinical or laboratory features classifies the patients as
suffering from severe malaria.
CEREBRAL MALARIA:
May be defined strictly as unarousable coma. In cerebral
malaria the onset of coma may be sudden, often following a
generalized seizure, or gradual with drowsiness, confusion,
disoreintation, delirium followed by unconsciousness. It is associated
with death rates of 20% among adults and 15% among children. It
manifests as diffuse symmetric encephalopathy, focal neurological
signs are unusual, mild neck stiffness is present. Eyes may be
divergent and pout reflex is common. Abdominal and cremastric
reflexes are absent. Decorticate or decerebrate rigidity may occur.
Hepatosplenomegaly is common. About 15-40% patients have retinal
hemorrhages. Other fundoscopic abnormalities include discrete spots
of retinal opacification (30-60% ), papilloedema, cotton wool spots (<
5% ) and decolouration of retinal vessel. Adults rarely suffer
neurological sequelae.
16

HYPOGLYCEMIA:
It is defined as blood glucose level < 40mg/ dl. It results from
failure of hepatic gluconeogenesis and increase in consumption of
glucose by host and to a lesser extent by the malarial parasite. It is
associated with poor prognosis and particularly problematic in
children and pregnant women.
NONCARDIOGENIC PULMONARY EDEMA:
Often fatal acute noncardiogenic pulmonary edema can develop
rapidly and is associated with excessive intravenous therapy. Fast
laboured respiration with non productive cough and physical findings
of moist rales and rhonchi are usually present. The mortality rate is
about 80% .
RENAL FAILURE:
It is defined as urine output of < 400ml urine in 24 hrs in
adults and serum creatinine > 3mg/ dl. May be due to erythrocyte
sequestration interfering with renal microcirculatory flow and
metabolism. Clinically and pathologically manifests as acute tabular
necrosis. It may occur simultaneously with other vital organ
dysfunction or may progress as other manifestations resolve. Early
dialysis or hemofiltration enhances the likehood of a patient survival.

17











Figure2: Mechanism of renal failure in malaria
BLACK WATER FEVER: ( HAEMOGLOBINURIA)
Massive intravascular haemolysis results in haemoglobinuria
and black coloured urine formation. It results in acute renal failure.
Mortality is about 20- 30% .
LIVER DYSFUNCTION:
Severe jaundice associated with falciparum malaria is more
common among adults than children and results from haemolysis,
18
hepatocyte injury and cholestasis. Hepatic dysfunction contributes to
hypogycemia, lactic acidosis and impaired drug metabolism. It carries
poor prognosis when accompanied by other vital organ dysfunction.
CIRCULATORY COLLAPSE ( ALGID MALARIA)
It is a rare form of falciparum malaria presenting with
hypotension, cold clammy extremities, rapid feeble pulse, shallow
breathing, pallor and vascular collapse. The clinical picture is often
associated with gram negative septicemia.
LACTIC ACIDOSIS:
It is caused by the combination of anaerobic glycolysis in
tissues where sequestered parasites interfere with microcirculatory
flow, hypovolemia, lactate production by the parasites and a failure of
hepatic and renal lactate clearance.
HEMATOLOGICAL COMPLICATIONS IN MALARIA
Hematological changes are very common in malaria. These include :
Anaemia, one of the most common complication
particularly due to P.falciparum infection.
Leucopenia or Leucocytosis
Thrombocytopenia
DIC
19
Hematological complication while seen both in P.Falciparum
and P.Vivax malaria, can become serious and life threatening in
Falciparum malaria. The reason for this being high level of
parasitemia associated with P.falciparum .The severity of infection
and the hematological complication is modulated by immune status
of the host, nutritional factors, and inter current infection and genetic
as well as time to presentation and duration of the illness.
Pathophysiological mechanisms contributing to hematological
changes are both complex and multifactorial which include :-
Activation of immune complex system by antigens
released by the pa rasites and damage to the
hematological cells
Rupture of red cells due to multiplying parasites inside the
blood cells
Reversible bone marrow suppression, hypersplenism and
hyperplasia of the reticulo endothelial systems
6
.
DIAGNOSIS:
MICROSCOPY:
The diagnosis of malaria rests on the demonstration of the
parasite in stained peripheral blood smears. Both thick and thin blood
smears should be ex amined.
Thick smear - for rapid diagnosis
20
Thin smear - for identification of species




21
Figure3: Microscopic appearance of Species of malaria
ANTIGEN CAPTURE TESTS:
Dipstick antigen capture assays employ a monoclonal antibody
detecting pf. HRP 2 antigen (histidine rich protein 2) in the blood. Eg:
pf. ICI test ( immunochromatographic test).
22
Parasight f/ malachek, pf LDH dipstick test These test are rapid,
simple and sensitive.
ANTIBODY DETECTION TEST:
Antibodies persists for a long time so not helpful in acute infection
eg: radio immunoassay (RIA).
Enzyme linked im munosor bent assay ( ELISA)
QBC TEST: Quantitative Buffy Coat Test
Blood is collected in a specialized tube containing acridine
orange, anticoagulant and float. After centrifugation which
concentrates the parasitized red cells around the float,
florescence microscopy is performed.
PCR TEST: It can identify different species. It takes 48-72 hrs. It
is expensive.
DNA PROBE.
TREATMENT:
Uncomplicated falciparum malaria
41
: W.H.O GUIDELINES:-
Objective to cure the infection, prevent the emergence
and spread of resistance to antimalarials.
WHO recommends combining antimalarials with
different modes of action.
Artemisinin based combinati on therapy: ( ACT)
23
Artemisnin and its derivatives like Artesunate,
Artemether, Artemotil, Dihydroartemisinin produce rapid
clearance of parasitemia and resolution of symptoms.
The following ACT are currently recom mended.
Artimether + Lumefantrine (twice a day for three days
each tablet contains 20 mg of Artmether + 120mg of Lumifantrine.
Artesunate + Amodiaquine (4mg/ kg of Artesunate + 10mg
base/ kg of Amodiaquine once a day for 3 days).
Artesunate + Mefloquine ( 4mg/ kg of Artesunate once a day for
3 days + 25mg base/ kg of Mefloquine split over 2 or 3 days.
Artesunate + Sulfadoxine Pyrimethmine ( 4mg/ kg of
Artesunate one a day for 3 days + single dose 25/ 1.25mg/ kg of SP
on day 1)
In areas of multi drug resistance (South East Asia region)
Artesunate + Mefloquine
Artesunate + Lumefantrine
Non Artemesinin based combination th erapy:
It includes
Sulfadoxine Pyrimethamine with Chloroquine
Sulfadoxine Pyrimethamine with Amodiaquine.
24
Uncomplicated falciparum malaria in Pregnancy:
In first trimester Quinine + Clindamycin to be given for 7
days.
In second and third trimester ACT known to be
effective in the region or Artesunate + Clindamycin for 7
days.
SEVERE MALARIA
42
:
The main objective is to prevent the death, secondary
objectives are prevention of recrudescence, emergence of resistance
and prevention of disabilities.
Two classes of drugs are currently available for the parenteral
use.
Cinchona alkaloids Quinine and Quinidine.
Artemisinin derivatives Artesunate, Artemether,
Arteether and Artemotil.

QUININE :
I.V infusion of 20mg salt / kg of Quinine on admission as
a loading dose in 5% dextrose over 4 hours followed by
10mg / kg every 8 hours.
25
Patient can be shifted to oral Quinine after resuming oral
feeding.
ARTEMISININ DERIVATIVES:
Artesunate 2.4mg/ kg I.V or I.M given on admission then
at 12 hrs and 24 hrs followed by once daily.
Artemether 3.2mg/ kg given on admission than 1.6mg/ kg /
day.
Arteether 150 mg IM OD for 3 days.
FOLLOW ON TREATMENT
43
:
Once the patient can tolerate oral therapy complete the
treatment with an effective oral antimalarial to complete
full 7 days of treatment.
Doxycycline should be given for 7 days at 100mg/ day
(alternative is Clindamycin)
DOSAGE ADJUSTMENTS
44
:
In renal failure and hepatic dysfunction, Artemisinin
derivatives does not need adjustment as they are
eliminated very rapidly.
If the patient remains seriously or in acute renal failure
for more than 2 days the maintenance doses of Quinine
and Quinidine should be reduced by 30 50% to
26
prevent toxic accumulation of the drugs, the initial doses
should never be reduced.
TABLE 9- ANTIMALARIAL CHEMOPROPHYLAXIS

Weight adjusted dose for children Adult dose

Chloroquine sensitive

Chloroquine 5mg base/kg weekly or 300mg base
100mg base

Proguanil 3.5mg/kg daily 200mg base

Chloroquine resistant

Mefloquine 5mg base/kg/weekly 250mg base

Doxycycline 1.5mg/kg daily 100mg

Primaquine 0.5mg base/kg daily with food 30mg base

Atovaquone-Proguanil 4/1.6 mg/kg daily 250 / 100 mg


WHO recommendations for antimalarial prophylaxis
14
It is essential that
prophylaxis is taken 1 week prior to traveling and continue for 4 weeks
after leaving the trasmissionarea.

SEVERE MALARIA IN PREGNANCY
45
:
In the first trimester both Artesunate and Quinine
may be considered until more evidence becomes available.
In the second and third trimester, Artesunate is the first option
27
and Artemether is the second option.
II VECTOR CONTROL STRATEGIES:
The method used comprise
a) Anti adult measure :
i) Residual spraying: The spraying of the indoor surfaces of houses with
residual insecticides ( eg DDT, Malathion, fenitrothion ) is still the most
effective measure to kill the adult mosquito.
ii) Space application : This is a major anti epidemic measure in mosquito
borne diseases. It involves the application of pesticides in the form of fog or
mist using special equipment. The ultra low volume method of pesticide
dispersion by air or by ground equipment has proved to be effective and
economical.
iii) Individual protection: Man - vector contact can be reduced by other
preventive measures such as the use of repellents, protective clothing, bed
nets (preferably impregnated with safe long acting repellent insecticides)
mosquito coils, mosquito mats , screening of houses etc. The methods of
personal protection are of great value when properly employed.
The WHO recommends soaking of mosquito nets in insecticides as the most
cost effective method of personal prophylaxis.
b) Anti larval measures:
i) Larvicides: Modern larvicides such as temephos which confer long
28
effect with low toxicity are widely used. However larviciding must be
repeated at frequent intervals and hence it is a comparatively costly
operation. Also biological control can be done by using fishes ( Gambusia &
Guppies ) and biolarvicides.
ii) Source reduction: Techniques to reduce mosquito breeding sites
which include drainage or filling deepening or flushing, management of water
level, changing the salt content of water and intermittent irrigation are among
the classical methods of malaria control .
iii) Integrated control: In order to reduce dependence on residual
insecticides, bioenvironmental and personal protection measures are also
integrated.
PROGRESS TOWARDS A MALARIA VACCINE :
Despite considerable effort and expense, a generally available and
highly effective malaria vaccine is unlikely in the near future. Research has
concentrated on all stages of the parasite life cycle: the sporozoite, the liver
stage, the asexual blood stage, and the gametocyte.
14
The most effective
vaccine produced to date was produced over a quarter of a century ago and
consisted of irradiated sporozoites.
TYPE OF VACCINE
There are three major stages in the life cycle of the parasite that
are targets for vaccine development.
1 Sporozoite - A vaccine based on sporozoite is designed to prevent
29
infection.
2 A sexual blood stage- Vaccine based on these while not preventing
infection is expected to reduce or eliminate parasites in the blood which
are responsible for most of the pathology of malaria.
3 Sexual blood stage This vaccine is aimed to interfere with the ability of
the parasite to infect mosquitoes and there by prevent the transmission of
the disease.
Antigens currently under study as vaccine candidates include
1. Sporozoite antigens - circum sporozoite protein (CSP)
2. Merozoite antigen - (Merozoite surface protein) (MSP 1 )
3. Erythrocyte binding antigen 175 ( EBA 175 )
4. Rhoptry associated protein 1 ( RAP 1 )
5. Apical merozoite antigen AMA 1.
6. Gamatocyte antigens ( pfs 25 )
Spf 66
The so called patarroyo vaccine is a synthetic vaccine for
p.falciparum. the monomeric forms consists of antigens from 3 asexual
blood stage antigens and from CSP of P.falciparum. The vaccine has been
given to many thousands of people and its acute safety is established. The
result from south America are relatively modest level of protection. Presently
undergoing phase 3 trials.
30
MATERIAL AND METH ODS


A total of 60 patients diagnosed to have Malaria over a period
of one year (August 2012 to August 2014) admitted or treated on OP
basis at Prathima Instituteof Medical Sciences, Karimnagar are
included in the study. This is a prospective study. All study subjects
were identified positive for Malaria parasite on peripheral smear
examination with conventional microscopy. Platelet count was done
on a fully automated, quantitative analyzer. Platelet count is the
number of thrombocytes derived from directly measured platelet
pulses, multiplied by a calibration constant and expressed in
thousands of thrombocytes per microliter of whole blood. Repeat
platelet count was done in subjects with marked thrombocytopenia
until normal or near normal values are reached. P.falciparum antigen
test (PfHrp antigen test-Parascreen) was performed in all subjects
with malaria parasite positive on peripheral smear.P.vivax Malaria on
the peripheral smear with a platelet count less than 20,000cells/ cmm
for more emphatic exclusion of associated P.falciparum infection.
P.falciparum antigen test was also performed in subjects with high
index of clinical suspicion or multi organ involvement.
Other investigations include CBC, LFT, RFT, Chest X- Ray,
Ultrasound Abdomen, if necessary Blood Culture, Urine Culture,
Dengue serology.
P.falciparum was treated with either chloroquine or artesunate
depending upon the clinical severity. P.vivax malaria was treated
31
with chloroquine followed by two weeks course of primaquine.
Data was expressed on an excel spreadsheet and statistical
analysis was performed.
INCLUSION CRITERIA :
All patients 12 years of age and above whose blood smear is
positive for malaria by conventional microscopy are included in the
study.
Platelet count < 1, 50,000 / cmm is taken as
cut off for Thrombocytopenia is graded as
Mild, if < 1,50,000 /
cmm
Moderate, if < 1,00,000 /
cmm
Severe, if < 50,000 / cmm

EXCLUSION CRITERIA :
History of Congenital & Hereditary Thrombocytopenia Immune
induced thrombocytopenia Drug induced thrombocytopenia.
40
OBSERVATIONS & RESULTS

The mean age of patients was 36.28 years, youngest being 12
years and oldest being 75 years of age. 34 (56.67 % )patients
were males and 26 (43.33 % )were females. 22 (36.67 % ) subjects
had P. vivax malaria, 36(60 % ) subjects had P. falciparum malaria,
and 02(03.33 % ) had mixed parasitemia of P. vivax and P. falciparum
malaria. 43 (71.67 % )subjects had uncomplicated malaria where
as17 (28.33 % )had complicated malaria. Platelet count less than
1,50,000/ cmm was noted in 49(81.67 % ) cases. The mean platelet
count in P.vivax malaria was 1,81,454/ cmm(68,742) with a range
of 76,000 - 4,98,000/ cmm, as against P.falciparum malaria where
the mean platelet count was 1,13,111/ cmm (71,762) with a range
of 15,000-4,10,000/ cu.mm. 72.72 % of the subjects with vivax
malaria had thrombocytopenia as against 86.11 % of the subjects
with falciparum malaria. Mild thrombocytopenia was noted in 25 (41
.67 % )cases, moderate in 19 (31.67 % ) and severe
thrombocytopenia in 05 (08.33 % )cases.
72.72% of the subjects with vivax malaria had
thrombocytopenia as against 86.11 % of the subjects with falciparum
malaria. 74.1 % of the subjects with uncomplicated malaria had
thrombocytopenia against 100 % in subjects with complicated
malaria.
Platelet count < 20,000/ cmm was found in 01 (01.67 % )
patient. None of the subjects with P. vivax malaria and low platelet
41
counts had clinical manifestations of thrombocytopenia or bleeding
from any site.


42
TABLE 1
AGE DISTRIBUTION
Age group Number
11-20 11
21-30 14
31-40 16
41-50 11
51-60 04
61-70 02
71-80 02
Total 60





0
2
4
6
8
10
12
14
16
20-Nov 21-30 31-40 41-50 51-60 61-70 71-80
11
14
16
11
4
2 2
Age
Age
43
TABLE 2
SEX DISTRIBUTION
Sex Number Percent
Male 34 56.67 %
Female 26 43.33 %
Total 60 100 %
















0
5
10
15
20
25
30
35
Male Female
34
26
Sex Distribution
44
TABLE 3
TYPE OF SPECIES
Species Number Percent
Falciparum 36 60 .00 %
Vivax 22 36.67 %
Mixed 02 03.33 %
Total 60 100 %








0
5
10
15
20
25
30
35
40
Falciparum Vivax Mixed
36
22
2
TYPE OF SPECIES
TYPE OF SPECIES
45
TABLE 4
SEVERITY OF MALARIA
Type Number Percent
Uncomplicated 43 71.67 %
Complicated 17 28.33 %
Total 60 100 %








43
17
SEVERITY OF MALARIA
Uncomplicated
Complicated
46
TABLE 5
SEVERITY OF MALARIA WITH SPECIES

Falciparum Vivax Mixed Total
Uncomplicated 22 21 00 43
Complicated 14 01 02 17
Total 36 22 02 60








0
5
10
15
20
25
Falciparum Vivax Mixed
22
21
0
14
1
2
SEVERITY OF MALARIA WITH SPECIES
Uncomplicated
Complicated
47
TABLE 6
INCIDENCE OF COMPLICATIONS
COMPLICATIONS Number Percent
Jaundice 14 82.35%
Anaemia 10 58.82%
Coma 09 52.94%
Convulsions 07 41.18%
Haemoglobinuria 07 41.18%
Hypoglycemia 06 35.2%
Renal Failure 03 17.65%
Bleeding 03 17.65%
Pulmonary Edema 02 11.77%





0
5
10
15
14
10
9
7 7
6
3 3
2
COMPLICATIONS
48
TABLE 7
INCIDENCE OF THROMBOCYTOPENIA

Number Percent
Normal platelet count 11 18.33 %
Mild Thrombocytopenia 25 41.67 %
Moderate
Thrombocytopenia
19 31.67 %
Severe
Thrombocytopenia
05 08.33 %






11
25
19
5
5
INCIDENCE OF THROMBOCYTOPENIA
Normal platelet count
Mild Thrombocytopenia
Moderate
Thrombocytopenia
Severe Thrombocytopenia
Severe Thrombocytopenia
49
TABLE 8
ASSOCIATION OF THROMBOCYTOPENIA WITH SPECIES
Thrombocytopenia Falciparum Vivax Mixed Total
Mild 13 12 00 25
Moderate 13 04 02 19
Severe 05 00 00 05
Total 31 16 02 49







0
2
4
6
8
10
12
14
Falciparum Vivax Mixed
13
12
0
13
4
2
5
0 0
ASSOCIATION OF THROMBOCYTOPENIA WITH SPECIES
Mild
Moderate
Severe
50
TABLE 9
ASSOCIATION OF THROMBOCYTOPENIA WITH SEVERITY OF MALARIA

Number Percent
Uncomplicated 32 25.9%
Complicated 17 74.1 %
Total 49
100 %








0
5
10
15
20
25
30
35
Uncomplicated Complicated
32
17
ASSOCIATION OF THROMBOCYTOPENIA WITH SEVERITY OF MALARIA
51
TABLE 10
ASSOCIATION OF THROMBOCYTOPENIA WITH SEVERITY OF MALARIA
Thrombocytopeni
a
Uncomplicated
malaria
Complicated
Malaria
Total
Mild 24 01 25
Moderate 04 15 19
Severe 00 05 05
Total 28 21 49










0
5
10
15
20
25
Mild Moderate Severe
24
4
0
1
15
5
ASSOCIATION OF THROMBOCYTOPENIA WITH SEVERITY OF MALARIA
Uncomplicated malaria
Complicated Malaria
52
DISCUSSION
Thrombocytopenia is a common feature of acute malaria and occurs in both
P. falciparum and P. vivax infections regardless of the severity of infection.
The absence of the normal quantity of platelets on a peripheral smear in a
case of fever is often a clue to the presence of malaria as seen in this study
also. Thrombocytopenia is rarely accompanied by clinical bleeding or
biochemical evidence of DIC. Platelet counts can fall to below 25,000/cu.mm
but this is uncommon46. Platelet counts rise rapidly with recovery. The
prevalence of thrombocytopenia was 81.67 % of the cases studied in our
series and highlights the fact that a persistent normal platelet count is unlikely
in the laboratory findings of malaria. Thrombocytopenia was seen in 40%-90%
percent of patients infected with with falciparum infection in India47,48. The
mechanism of thrombocytopenia in malaria could be due to peripheral
destruction and consumption by DIC.50,51 Profound thrombocytopenia with
platelet count as low as 5000/cmm has been reported in the Indian literature
in a 43-year old female patient with vivax malaria52. Very low platelet counts
can be transient in the course of malaria illness and may not necessarily have
prognostic implications or merit platelet infusions. Most severe malaria
patients have thrombocytopenia; however, platelet concentrate transfusion is
indicated only in patients with systemic bleeding. Clinical bleeding in severe
malaria is not a common feature and occurs in less than 5-10% of individuals
with severe disease. Platelet and fibrin deposition are rarely seen in the
capillaries of patients at postmortem and despite numerous studies indicating
elevated levels of fibrin degradation
53
products, clinical DIC is rare. A host of other indicators of intravascular
coagulation may be found to be outside the normal range, but this appears to
be only a reflection of the severity of the disease.
Table 25: Comparision of Sex distribution :

G.Lalitha V.H.Talib et al MK Mohapatra Present study
murthy et al
Male 69.6 66.7 65.7 34.0
Female 31.4 33.3 34.3 26.0
Male: Female 2.3:1 2:1 1.9:1 1.3:1

The number of males out numbered the females in our study. This is
very closely correlated to study conducted by MK Mohapatra
5
V.H. Talib et
al
1114
and G. Lalitha Murthy et al
113
.The reason for this distribution
predominantly among males is due to the increased outdoor activities of
males and the chances of getting exposure to the risk of malaria is more in
males.
13
Table 28:Comparison of platelet count between present study and that
of G.
Lalitha Murthy et al.
113


Platelet count (cells/ cumm)
G. Lalitha Murthy et
al,

113 Present Study
Mild (1,00,000 -50,000) 21.51% 41.67%
Moderate (50,000 - 20,000) 17.72% 31.67%
Severe (<20,000) 1.26% 8.33%


54
Thrombocytopenia was present in 40.5% of cases. Majority of the
patient with thrombocytopenia were of mild degree i.e., 41.67%. Our study
resembels closely to that of G. Lalitha Murthy et al,
113
where the incidence of
thrombocytopenia 40.50%.
Table 29 :Comparison of complications of Falciparum malaria with the
study of
G. Lalitha Murthy et al
113
and Kochar et al.
7


Complication
G. Lalitha
Murthy et al
90

Kochar
DK Present study
Anaemia 74.68% 26.04% 58.82%
Thrombocytopenia 40.50% 19% 40.50%
Cerebral malaria 48.1% 10.94%
Jaundice 40.50% 58.85% 82.35%
Acute renal failure 24.68% 6.25% 17.65%
Hypoglycemia 8.22% 1.56% 35.2%
Hypotension/shock - 10.94% 52.94%
DIC 16.45% 25.52%
Pulmonary edema 11.39% 2.08% 11.77%
Hemoglobinuria 4.27% - 41.18%

In our study, the most common complication was jaundice (82.35%)
followed by , anaemia (58.82%), ARF (17.65%), ARDS(11.77%).
In a study by G. Lalitha Murthy et al
113,
anaemia (74.6%) and cerebral
malaria (48.1%) were the common manifestations followed by jaundice
(40.5%) and ARF.(24.6%).In a study by Kochar et al,
7
Bikaner Rajastan.
Jaundice and anaemia were most common manifestations followed by DIC
55
and cerebral malaria. This shows that the spectrum of common
manifestations and complications of malaria vary in different geographical
regions depending upon parasitic factor, epidemiological factors and host
defence factors.
A study conducted by Lathia TB et al on hematological
parameters discriminate malaria from nonmalarious acute febrile
illnesses in the tropics from Mahatma Gandhi Institute of Medical
Sciences, Maharashtra suggested that low hemoglobin and low
platelet count are the two hematological variables that increase the
probability of malaria, by a factor of 1.95 and 5.04 respectively. These
two variables also emerge useful when used in combination
(likelihood ratio 2.77). The 95% confidence interval for RDW however
crosses one, which implies measurement of this parameter to be less
precise.
The pathogenesis of anemia in malaria is multifactorial. A
complex chain of pathogenetic processes involving mechanical
destruction of parasitized RBC' s, marrow suppression,ineffective
erythropoiesis and accelerated immune destruction of nonparasitized
RBC' s have been implicated
7
. Thrombocytopenia is a common
observation in falciparum malaria with spontaneous recovery on
treatment. Both leukopenia
2
and leukocytosis
8
have been described
in malaria. Increased red cell population dispersions or red cell
distribution width (RDW) has been observed in malaria, and has
been attributed to the red cell response to malarial parasite, and
correlated with the degree of macrocytosis.
56
A study conducted by Jain M.et al in 2005 on Comparative
study of Microscopic detection methods and haematological changes
in malaria, observed that anaemia was present in 66 (94.28% )
samples, of which 37 (56.06% ) were Plasmodium falciparum,
21(31.81% ) were Plasmodium vivax and 8 (12.12% ) had mixed
infection (Plasmodium falciparum and Plasmodium vivax). 35 (50% )
cases showed normocytic normochromic anaemia. Majority of the
samples showed normal total and differential leukocyte count
9
.
Thrombocytopenia was found in 49 (70% ) samples, of which 33
(67.34% ) were Plasmodium falciparum. Thrombocytopenia is seen
in both complicated and uncomplicated malaria.
In the study by Sharma. K. et al thrombocytopenia was present
in as high as 90% of patients.Horstman et al found thrombocytopenia
in 85% of P.Falciparum and 72% of P.Vivax patients respectively
10
.
A Hospital based study in Saudi Arabia showed that
thrombocytopenia is more commonly found than anaemia in malaria.
Thrombocytopenia is generally unrelated to clinical severity but the
degree of thrombocytopenia co-related with the size of the spleen.
Thrombocytopenia usually resolves spontaneously once the infection
subsides. The pathogenesis of thrombocytopenia is thought to be
similar to that of anaemia and they often co-exsist.
Various studies have shown that anaemia and
thrombocytopenia occur simultaneously and subside gradually with
therapy and clearance of parasitemia. The factors involved in
57
pathogenesis of thrombocytopenia include :
1) Hypersplenism and splenic pooling of parasites.
2) Hyperplasia of reticulo endothelial cells and increased
phagocyte destruction.
3) Destruction of platelets bound by immune complexes by
the reticulo endothelial system and rarely
4) Disseminated intravascular coagulation
11
.
IMMUNOLOGICAL BASIS FOR THROMBOCYTOPENIA
12, 13

The low platelet count emerged as the strongest predictor of
malaria. In a study on over two thousand patients with fever, Erhart et
al21 reported that platelet count of less than 1,50,000 increases the
likelihood of malaria by 12-15 times. Various other studies have also
found thrombocytopenia to be commonly associated with
malaria
14,15
which resolves after therapy
16
. The suggested
mechanisms for thrombocytopenia include disseminated intravascular
coagulation, or excessive removal of platelets by reticulo-endothelial
system
17
. Anti-Platelet IgG has also been implicated in the
pathogenesis of thrombocytopenia
18
. Thrombocytopenic malaria, in
contrast to the non- thrombocytopenic variety correlates with a higher
degree of parasitemia and increased cytokine production
19
.


56
A Study was conducted by Koltas et al in 2007 on supportive
presumptive diagnosis of Plasmodium vivax malaria.
Thrombocytopenia and red cell distribution width suggested that
routinely used laboratory findings such as low hemoglobin, leukocyte
or platelet counts and especially high red cell distribution width values
could present a more supportive clue in the diagnosis of vivid malaria
in endemic areas
20
. Platelets are thought to be passively absorbed
by the malarial antigen which then bind to Immunoglobulin
molecules. These antibody coated platelets are then cleared by
phagocytosis in the spleen.
Towze et al in their series of patients infected with malaria
showed that there was an inverse relationship between the platelet
counts and the platelet antibody level
21
. This was supposed to be
the cause for thrombocytopenia however Loreesuwan et al showed
that there was no relationship between platelet count and the
platelet antibody level
22
It is possible that platelet bound
immunoglobulin is a qualitative recognition trigger for splenic removal
of platelet that the threshold is lowered in patients with malaria.
A study was conducted by Jadhav U.M et al
23
on
Thrombocytopenia in Malaria-Correlation with type and severity A
total of 1565 subjects, either hospitalized or treated on an out patient
basis over a period of three years . 590 subjects had P. falciparum
malaria and two subjects had mixed parasitemia of vivax and P.
falciparum malaria. Platelet count less than 1,50, 000/ cu.mm was

57
noted in 79.4% cases. Falciparum malaria presents with protean
manifestations and is associatedwith a variety of complications and
has a high
mortality. Thrombocytopenia is a common feature of acute malaria
and occurs in both P. falciparum and P.vivax infections regardless of
the severity of infection. The absence of the normal quantity of
platelets on a peripheral smear in a case of fever is often a clue to
the presence of malaria.Thrombocytopenia is rarely accompanied by
clinical bleeding or biochemical evidence of DIC. Platelet counts can
fall to below 25,000/ cmm but this is uncommon. Platelet counts rise
rapidly with recovery. The prevalence of thrombocytopenia was 78.4%
of the cases studied in this series and highlights the fact that a
persistent normal platelet count is unlikely in the laboratory findings
of malaria
24
. Maximum thrombocytopenia occurred on the fifth or
sixth day of infection, and gradually returned to normal within 5-7
days after parasitemia
25
ceased
26,27
.The mechanism of
thrombocytopenia in malaria could be due to peripheral destruction
and consumption by DIC. This must be considered inthe context
that very low platelet counts can be transient in the course of
malaria illness. Clinical bleeding in severe malaria is not a common
feature and occurs in less than 5-10% of individuals with severe
disease
28,29
. Platelet and fibrin deposition are rarely seen in the
capillaries of patients at postmortem and despite numerous studies
indicating elevated levels of fibrin degradation products, clinical DIC is

58
rare. Also, thrombocytopenia per se cannot be a distinguishing feature
in a particular case of malaria, although there is a statistical
significant difference in the prevalence and severity of
thrombocytopenia between the two types of malaria. The mechanism
of thrombocytopenia in malaria is uncertain. Immune- mediated lysis,
sequestration in the spleen and a dyspoietic process in the marrow
with diminished platelet production have all been
postulated. Abnormalities in platelet structure andfunction have been
described as a consequence of malaria, and in rare instances
platelets can be invaded by malarial parasites themselves.
A study conducted by John G Kelton et al Immune-mediated
Thrombocytopenia of Malaria from J. Clin. Invest, The American
Society for Clinical Investigation, suggested that thrombocytopenia is
a common finding in malaria, but the mechanism of the
thrombocytopenia unknown. Initially it was suggested that DIC was
responsible
30,31
.
Consistent with these observations are Thrombocytopenic
patients had elevated levels of PAIgG during the thrombocytopenic
episode. The PAIgG returned to normal as the thrombocytopenia
resolved, and while the patient continued on the same antimalarial
drugs, indicating that the thrombocytopenia was not drug
induced
32,33
. Thrombopoietin (TPO) is the key growth factor for
platelet production and is elevated in states of platelet depletion. TPO
serum levels have been shown to be significantly higher in subjects

59
with severe malaria normalizing within 14-21 days of therapy. Two
types of changes in platelet dysfunction are seen in malaria. Initially
there is platelet hyperactivity, followed by platelet hypoactivity.
Platelet hyperactivity results from various aggregating agents like
immune complexes, surface contact of platelet membrane to malarial
red cells and damage to endothelial cells. The injured platelets undergo
lysis intravascularly. The release of platelet contents can activte the
coagulation cascade and contributes to DIC. Transient platelet
hypoactivity is seen following this phase and returns to normal
in 1 to 2 weeks
34,35
. In many studies undertaken, the significance
of haemostatic abnormalities as a consequence of malaria has
been difficult to assess as a result of the presence of various
associated complications such as liver dysfunction, uraemia and
treatment with low molecular weight dextran, dexamethasone and
heparin. Absence of thrombocytopenia is uncommon in the
laboratory diagnosis of malaria. Presence of thrombocytopenia isnot a
distinguishing feature between the two types of malaria.
Thrombocytopenia less than 20,000/ cmm can occur in P. vivax
malaria although statistically more significant with P.falciparum
malaria
36
.
A case report by Kaur D et.al in 2007 on Unusual
Presentation of Plasmodium vivax Malaria with Severe
Thrombocytopenia and Acute Renal Failure was seen in 18 year old
boy
37
. A study conducted by Kumar A et.al in 2006 on

60
Thrombocytopenia-an indicator of acute vivax malaria suggested that
thrombocytopenia as an early indicator for acute malaria; a finding
that is frequent and present even before anemia and splenomegaly
set in. The possible mechanisms leading to thrombocytopenia in
malaria include immune mechanisms, oxidative stress, alterations in
splenic functions and a direct interaction between plasmodium and
platelets
38
.
A case report from the Department of Internal Medicine, Tokyo
Medical College, found that the thrombocytopenia complicating some
malarial infections is caused by immune mechanisms. A case of
malaria associated with thrombocytopenia and increased platelet
associated IgG (PAIgG).In this case, anti-malarial therapy reduced the
level of PAIgG to normal levels in association
with normalization of the platelet count. This case suggests the
immunological mechanisms of thrombocytopenia in malaria
12
.
Department of Internal Medicine, Fukaya Red Cross Hospital,
Saitama, Japan, showed that severe thrombocytopenia in P.vivax
malaria secondary to antibody mediated
13
.
A study conducted by Casals-Pascual C et.al in 2006 on
Thrombocytopenia in falciparum malaria is associated with high
concentrations of IL-10, suggested that
39
platelets may play a role in
the pathophysiology of severe malaria. However, somewhat
paradoxically, thrombocytopenia is not associated clearly with

61
outcome. When studied the relationship between thrombocytopenia
and cytokines in Kenyan children with severe malaria, showed that
thrombocytopenia (platelet count < 150 x 10(9)/ L) strongly correlates
with high levels of interleukin (IL)-10. Several studies have shown
that high levels of IL-10 are associated with a favorable outcome in
severe malaria. Taken together, these data suggest why
thrombocytopenia has a complex relationship with severe disease
and suggest one mechanism whereby IL-10 may modify the outcome
of severe disease
40
.
In Gupta et
66
al study group of 230 patients: 130 (56.51%) were positive for P.
vivax, 90 (39.13%) were positive for P. falciparum and 10 (4.34%) had mixed
infection with both P. vivax and falciparum. Out of 130 cases detected with
vivax malaria, 100 cases had thrombocytopenia,30 (13.04%) cases had
normal platelet count. 45 (19.5%)cases had mild thrombocytopenia, , 40
(17.39%) cases had moderate thrombocytopenia and 15 (6.51%) cases had
severe thrombocytopenia. Out of 90 cases detected with falciparum malaria,
70 cases had thrombocytopenia,In our study 36 out of 60 cases detected with
falciparum malaria had thrombocytopenia.
In Qurban HussainSeikh et al
67
Forty six (46%) patients with
thrombocytopenia had Plasmodium falciparum and 56 (56%) had Plasmodium
vivax (p=0.001). In our study 31outof60 patients with thrombocytopenia had
plasmodium falciparum and 16 out of 60 patients had vivax malaria.


62
CONCLUSIONS
In conclusion
1) Absence of thrombocytopenia is uncommon in the laboratory diagnosis of
malaria.
2) Presence of thrombocytopenia is not a distinguishing feature between the
two types of malaria although there is a statistical significant difference in the
prevalence and severity of thrombocytopenia between the two types of
malaria.
3) Thrombocytopenia less than 20,000/cmm can occur in P. vivax malaria
although statistically more significant with P. falciparum malaria.
4) The parachek should be ideally done on all cases with P. vivax malaria to
look for mixed infection.
5) Thrombocytopenia on a peripheral smear in a case of fever is often a clue
to the presence of malaria.
6) Thrombocytopenia is rarely accompanied by clinical bleeding or
biochemical evidence of DIC.
7) Platelet counts can fall to below 25,000/cu.mm but this is uncommon.
Platelet counts rise rapidly with recovery.
8) Platelet concentrate transfusion is indicated only in patients with systemic
bleeding.

63
9) The above findings can have therapeutic implications in context of avoiding
unnecessary platelet infusions with the relatively more benign course in P.
vivax malaria.


64
SUMMARY
Malaria is a major public health problem of the world.It affects more than 2400
million people, over 40% of the worlds population,in more than 100 countries
in the tropics from South America to Indian peninsula.In India, the incidence is
2-3 million cases per year, constituting 40% of all cases outside Africa53.
About 1.5 3 million people die of Malaria every year,accounting for 45% of
all fatalities in the world. Of the four species causing Malaria in
humans,,Plasmodium falciparum is associated with significant mortality and
morbidity.There is a change in trend in the spectrum of falciparum
malaria,worldwide, including India. There is an increase in the incidence of
renal and hepatic failure and multiorgan dysfunction54. The emergence of
resistance of parasite to antimalarial drugs and of the vector to insecticides is
also a major concern. Thrombocytopenia is a common feature of acute
malaria and occurs in both P. falciparum and P. vivax infections regardless of
the severity of infection. The absence of the normal quantity of platelets on a
peripheral smear in a case of fever is often a clue to the presence of malaria
as seen in this study also. Thrombocytopenia is rarely accompanied by
clinical bleeding or biochemical evidence of DIC. Platelet counts can fall to
below 25,000/cmm but this is uncommon. Platelet counts rise rapidly with
recovery. Clinical bleeding in severe malaria is not a common feature and
occurs in less than 5-10% of individuals with severe disease.


65
The objectives of malaria control on a priority basis include :
Reduction of mortality by prompt diagnosis and effective treatment
Reduction of morbidity and to rely on the use of effective drugs
To reduce transmission in the most appropriate and cost effective way
To anticipate and prevent the development of epidemics
Finally, in a carefully planned and multifaceted programme, work to
eliminate the disease55.


66
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R66ing stag





74
PROFORMA
S No:

Name :

Age: Sex:
IP No DOA: DOD:

Presentin g Com plain ts : Yes No
Fever

Chills & rigors

Altered sensorium

a. Delirium
b. Coma Seizures
Jaundice
Abdominal pain
Oliguria/ Anuria
Black coloured Urine
Bleeding manifestations
Shortness of breath,Others
Past History :
DM, HTN, CVA, CAD, COPD, Chronic liver
disease Others
Person al History:
Family History:

75
GENERAL EXAMINATION:
Appearance
e Febrile
Pallor
Icterus
Clubbing
Cyanosis
Lymphadenopathy
Bleeding manifestations
Puffiness of face
Pedal edema
VITAL DATA
Temperature
Pulse rate
Respiratory rate
Blood pressure
SYSTEMIC EXAMINATION:
CARDIO VASCULAR SYSTEM
RESPIRATORY SYSTEM
ABDOMINAL EXAMINATION
CENTRAL NERVOUS SYSTEM



76


LABORATORY DATA
Hem atological Param eters:
i. Hemogram
HB TLC
Platelets
ii. Peripheral Smear
iii. Biochemical parameters
RBS/ FBS
Serum Bilirubin
Blood urea
Serum creatinine
ABGA(Arterial blood Gas Analysis)
Prothrombin time.


77
MASTER CHART
Sl.
No.
Name I.P. No. Age Sex Type of Malaria Smear Platelet Count Outcome
1. S RAJAIAH 3039 35 M UNCOMPLICATED P v R 140,000 Recovered
2. K VENKATAMMA 3059 45 F UNCOMPLICATED P v R 1,12,000 Recovered
3. N RAMESH 3069 18 M COMPLICATED P f R 80,000 Recovered
4. N SWAPNA 3073 25 F UNCOMPLICATED P v R 76,000 Recovered
5. G SRISAILAM 3177 16 M UNCOMPLICATED P v T 1,35,000 Recovered
6. M LAXMI 3178 40 F UNCOMPLICATED P f G 1,12,000 Recovered
7. K VIMALA 3182 32 F COMPLICATED P f R 55,000 Recovered
8. D MARAMMA 3189 50 F UNCOMPLICATED P v T 1,10,000 Recovered
9. G BABU 3056 40 M UNCOMPLICATED P f R 1,09,000 Recovered
10. L VASU 3440 30 M UNCOMPLICATED P v T 3,90,000 Recovered
11. S SAMBAIAH 3443 40 M COMPLICATED P f R 76,000 Recovered
12. K VENKAT LAXMI 3443 35 F UNCOMPLICATED P v T 98,000 Recovered
13. B CHERALU 3573 45 M COMPLICATED P f R 82,000 Recovered
14. M RAJAIAH 3537 60 M COMPLICATED P f R 75,000 Recovered
15. B TIRUPATHI 3470 24 M UNCOMPLICATED P v R 1,20,000 Recovered
16. B PADMA 3487 23 F COMPLICATED P f G 42,000 Recovered
17. G LAXMAMMA 3769 55 F UNCOMPLICATED P v G 1,40,000 Recovered
18. G BLECY 3689 40 F UNCOMPLICATED P v R 1,11,000 Recovered
19. M VENKATESH 3782 52 M UNCOMPLICATED P v R 1,40,000 Recovered
20. G RAMU 3857 45 M UNCOMPLICATED P v R 1,14,000 Recovered


78
Sl.
No.
Name I.P. No. Age Sex Type of Malaria Smear Platelet Count Outcome
21. R POCHAMMA 3770 65 F UNCOMPLICATED P f R 1,16,000 Recovered
22. D SWAROOPA 3800 40 F COMPLICATED P f R 65,000 Recovered
23. M NARENDAR 3800 29 M UNCOMPLICATED P v R 2,60,000 Recovered
24. CH RAJITHA 4014 20 F UNCOMPLICATED P v T 2,00,000 Recovered
25. M VENKATESWARLU 4110 35 M UNCOMPLICATED P v R 3,82,000 Recovered
26. V MALLESHAM 4163 45 M UNCOMPLICATED P f R 1,10,000 Recovered
27. D BABU 4301 30 M COMPLICATED P f R 90,000 Recovered
28. B YADAGIRI 4175 40 M UNCOMPLICATED P f R 1,16,000 Recovered
29. G RAMASWAMY 4179 48 M UNCOMPLICATED P f R 1,40,000 Recovered
30. B VINOD OP 20 M UNCOMPLICATED P v R 4,98,000 Recovered
31. G YASHODA OP 40 F UNCOMPLICATED P v R 1,38,000 Recovered
32. K N IRMALA 4213 35 F UNCOMPLICATED P f R 1,40,000 Recovered
33. V SAMMAIAH 4340 55 F UNCOMPLICATED P f R 1,10,000 Recovered
34. N RAMADEVI 168 22 F UNCOMPLICATED P f R 96,000 Recovered
35. S KATTAIAH 173 30 M UNCOMPLICATED P f R 2,60,000 Recovered
36. P LATHA OP 35 F UNCOMPLICATED P f R 1,14,000 Recovered
37. K MUTHAIAH 1757 75 M UNCOMPLICATED P v R 3,11,000 Recovered
38. K SADANANDAM 4897 30 M COMPLICATED P f R 15,000 Recovered
39. P SRINIVAS 5136 50 M UNCOMPLICATED P f R 1,45,000 Recovered
40. S BHADRAMMA 5936 75 F COMPLICATED P f R + P v R 98,000 Recovered

79
Sl.
No.
Name I.P. No. Age Sex Type of Malaria Smear Platelet Count Outcome
41. VENKAT 5649 19 M UNCOMPLICATED P f R 4,10,000 Recovered
42. VASANTHA.K 5634 22 F COMPLICATED P f R 76,000 Recovered
43. G LATHA OP 24 F COMPLICATED P f R 82,000 Recovered
44. R RAJANI 6313 35 F UNCOMPLICATED P f R 1,12,000 Recovered
45. G YAKUBKHAN 8303 24 M COMPLICATED P f R 45,000 Recovered
46. J PAVANI 8422 23 F UNCOMPLICATED P f R 2,40,000 Recovered
47. CH PRASANNA 9016 18 M UNCOMPLICATED P f R 95,000 Recovered
48. E ANJALI 9268 20 F UNCOMPLICATED P f R 1,10,000 Recovered
49. G MANIKANTH 9360 35 M COMPLICATED P f R 74,000 Recovered
50. V TIRUPATAMMA 9591 45 F UNCOMPLICATED P f R 1,30,000 Recovered
51. K SIRISHA 10820 12 F COMPLICATED P f R + P v T 72,000 Recovered
52. K YADAGIRI 10327 42 M COMPLICATED P f R 35,000 Expired
53. M ADILAXMI 11128 28 F UNCOMPLICATED P f R 1,14,000 Recovered
54. MD MAHAMOOD OP 50 M UNCOMPLICATED P f R 2,50,000 Recovered
55. J KOMURAIAH 14078 50 M COMPLICATED P f R 84,000 Recovered
56. V PALLAVI 14554 12 F COMPLICATED P v T 78,000 Recovered
57. V VEERASWAMY 17344 35 M UNCOMPLICATED P v T 2,40,000 Recovered
58. P PRASAD 28623 17 M UNCOMPLICATED P f R 96,000 Recovered
59. K ALIVELU 37307 35 F UNCOMPLICATED P v T 95,000 Recovered
60. E MANAMMA 37851 62 F UNCOMPLICATED P v T 1,12,000 Recovered


80
e
66777
67ametocyte