anization and conclusion about your project.

8/10/2019 anization and conclusion about your project.

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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 tropics1.

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 peninsula2.

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 annually2,3. 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


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world.

1 HIV/ AIDS death is equal to 50 malaria deaths3.

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


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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.


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AIMS AND OBJECTIVES

1. To study the incidence of thrombocytopenia in Malaria.

2. To correlate with the type and severity of Malaria.


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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 parasite4.

Transmissibility of the infection in blood was proved by Gerhardt4.

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 GPI4 (General Paralysis of Insane).

Both Ronald Ross (1902) and Laveran (1907) won the Nobel

prize for their discoveries in malaria4.

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


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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.


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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


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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


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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


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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.

PATHOPHYSIOLOGY5

:

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


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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 ki ll in 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


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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


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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 cel lular 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 '


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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


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three stages i.e., cold stage, hot stage and sweating stage.

Physical examination may reveal pallor, icterus and

hepatosplenomegaly.

SEVERE FALCIPARUM MALARIA5

:

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 ( 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.


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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,


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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


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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 systems6.

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


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Thin smear - for identification of species


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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).


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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 m u n osorb en t 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 malaria41:

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 combin ation therapy: ( ACT)


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Artemisnin and its derivatives like Artesunate,

Artemether, Artemoti l, Dihydroartemisinin produce rapid

clearance of parasitemia and resolution of symptoms.

The following ACT are currently recom mend ed.

Artimether + Lumefan tr ine (twice a day for three days

each tablet contains 20 mg of Artmether + 120mg of Lum ifantrine.

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 + Lumefan tr ine

Non Artemesinin based combination th erapy:

It includes

Sulfadoxine Pyrimethamine with Chloroquine

Sulfadoxine Pyrimethamine with Amodiaquine.


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Uncomplicated falciparum malaria in Pregna ncy:

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 MALARIA42:

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 Artemoti l.

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.


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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 TREATMENT43:

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 ADJUSTMENTS44:

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


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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 prophylaxis14

It is essential that

prophylaxis is taken 1 week prior to traveling and continue for 4 weeks

after leaving the trasmissionarea.

SEVERE MALARIA IN PREGNANCY45:

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


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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 beeffective 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


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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


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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) (MSP1 )

3. Erythrocyte binding antigen 175 ( EBA175 )

4. Rhoptry associated protein 1 ( RAP1 )

5. Apical merozoite antigen AMA1.

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.


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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


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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 /

Moderate, if < 1,00,000 /

Severe, if < 50,000 / cmm

EXCLUSION CRITERIA :

History of Congenital & Hereditary Thrombocytopenia Immune

induced thrombocytopenia Drug induced thrombocytopenia.


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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


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41

counts had clinical manifestations of thrombocytopenia or bleeding

from any site.


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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


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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


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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


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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


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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


2221

0

14

12

SEVERITY OF MALARIA WITH SPECIES

Uncomplicated

Complicated


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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

1514

109

7 76

3 32

COMPLICATIONS


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TABLE 7

INCIDENCE OF THROMBOCYTOPENIA

Number Percent

Normal platelet count 11 18.33 %

Mild Thrombocytopenia 25 41.67 %

ModerateThrombocytopenia

19 31.67 %

SevereThrombocytopenia

05 08.33 %

11

25

19

5

5

INCIDENCE OF THROMBOCYTOPENIA

Normal platelet count

Mild Thrombocytopenia

Moderate

Thrombocytopenia

Severe Thrombocytopenia

Severe Thrombocytopenia


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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


1312

0

13

4

2

5

0 0

ASSOCIATION OF THROMBOCYTOPENIA WITH SPECIES

Mild

Moderate

Severe


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50

TABLE 9

ASSOCIATION OF THROMBOCYTOPENIA WITH SEVERITY OFMALARIA

Number Percent

Uncomplicated 32 25.9%

Complicated 17 74.1 %

Total 49100 %

0

5

10

15

20

25

30

35

Uncomplicated Complicated

32

17

ASSOCIATION OF THROMBOCYTOPENIA WITH SEVERITY OF MALARIA


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TABLE 10


Thrombocytopenia

Uncomplicatedmalaria

ComplicatedMalaria

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

01

15

5


Uncomplicated malaria

Complicated Malaria


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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


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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: Female2.3:1 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 Mohapatra5V.H. Talib et

al1114 and G. Lalitha Murthy et al113.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 thatof 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 (


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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, 113where the incidence of

thrombocytopenia 40.50%.

Table 29 :Comparison of complications of Falciparum malaria with thestudy of

G. Lalitha Murthy et al113and 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 al113,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


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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 leukopenia2 and leukocytosis8 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.


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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 count9.

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 respectively10.

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


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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 coagulation11.

IMMUNOLOGICAL BASIS FOR THROMBOCYTOPENIA12, 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

malaria14,15 which resolves after therapy16. 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 thrombocytopenia18. Thrombocytopenic malaria, in

contrast to the non- thrombocytopenic variety correlates with a higher

degree of parasitemia and increased cytokine production 19.


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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 level21. 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 level22 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 al23 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


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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 malaria24. Maximum thrombocytopenia occurred on the fifth or

sixth day of infection, and gradually returned to normal within 5-7

days after parasitemia25 ceased26,27 .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

disease28,29. 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


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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

responsible30,31.

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

induced32,33. 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


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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 weeks34,35. 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

malaria36.

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

boy37. A study conducted by Kumar A et.al in 2006 on


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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

platelets38.

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 malaria12.

Department of Internal Medicine, Fukaya Red Cross Hospital,

Saitama, Japan, showed that severe thrombocytopenia in P.vivax

malaria secondary to antibody mediated13.

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 that39 platelets may play a role in

the pathophysiology of severe malaria. However, somewhat

paradoxically, thrombocytopenia is not associated clearly with


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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 disease40.

In Gupta et66al 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 al67 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.


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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.


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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.


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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 than100 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 1.53 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.


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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.


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R66ing stag


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PROFORMA

S No:

Name :

Age: Sex:

IP No DOA: DOD:

Present in 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:


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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


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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.


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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 Recovered6. 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


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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 Recovered27. 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


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Sl.Name I.P. No. A e Sex T e 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 Recovered48. 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


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