Malaria

MALARIAMALARIADepartment of PathologyDepartment of Pathology

MosquitoMosquito

Plasmodium MalariaePlasmodium Malariae

MalariaMalaria Malaria affects 270 million people each Malaria affects 270 million people each

year and has mortality rate of 1%year and has mortality rate of 1% Malaria is primarily a disease of hot, Malaria is primarily a disease of hot,

humid countries.humid countries. In humans, malaria is caused by four In humans, malaria is caused by four

species of species of plasmodium, p. ovale, p. plasmodium, p. ovale, p. falciparum, p. vivax, p. marlariaefalciparum, p. vivax, p. marlariae

P. ovale has been reported P. ovale has been reported predominantly from east and west predominantly from east and west AfricaAfrica

Geographical Geographical DistributionDistribution

MalariaMalaria P. vivax is the major species in temperate P. vivax is the major species in temperate

zone whereas in tropics all forms of zone whereas in tropics all forms of malaria are seenmalaria are seen

Humans, the intermediate hosts, are Humans, the intermediate hosts, are infected following the bite of an infected infected following the bite of an infected female anopheles mosquito, the definitive female anopheles mosquito, the definitive hosthost

The parasite can be transmitted by blood The parasite can be transmitted by blood transfusion, transplacentally and transfusion, transplacentally and increasingly between drug addicts who increasingly between drug addicts who use improperly cleaned syringes. use improperly cleaned syringes.

MalariaMalaria The introduction of sporozoites, the The introduction of sporozoites, the

infective form of parasite, through the infective form of parasite, through the skin by anopheles mosquito heralds skin by anopheles mosquito heralds the commencement of human cycle. the commencement of human cycle. The following stages occurThe following stages occur Pre-erythrocytic shizogonyPre-erythrocytic shizogony Erythrocytic shizognyErythrocytic shizogny GametogonyGametogony Exoerythrocytic shizognyExoerythrocytic shizogny

Life CycleLife Cycle

Life CycleLife Cycle

MalariaMalaria When an anopheles mosquito When an anopheles mosquito

ingest human blood containing ingest human blood containing gametocytes it marks the gametocytes it marks the commencement of sexual cycle commencement of sexual cycle in mosquitoin mosquito

The external incubation period The external incubation period varies from 7-20 daysvaries from 7-20 days

ImmunityImmunity May be natural or acquired The presence of Hb S, glucose-6-phosphate

dehydrogenase deficiency, thalasaemia, and pyruvate kinase deficiency offer resistance against P. falciparum.

Splenectomized individuals are highly susceptible to the malarial parasite

Infants are protected by transfer of maternal IgG antibodies across the placenta

Clinical FeaturesClinical Features Malarial febrile paroxysms typically have Malarial febrile paroxysms typically have

three stagesthree stages The The “cold stage” “cold stage” is characterized by marked is characterized by marked

vasoconstriction and lasts from 30 minute 1 hour. vasoconstriction and lasts from 30 minute 1 hour. The patient feels intensely cold and The patient feels intensely cold and uncomfortable. There is marked shivering. The uncomfortable. There is marked shivering. The temperature rises rapidly often to as high as 41temperature rises rapidly often to as high as 41ooCC

The The “hot stage” “hot stage” abruptly follows and lasts for 2-6 abruptly follows and lasts for 2-6 hours. Patient feels intensely hothours. Patient feels intensely hot

The The “sweating stage” “sweating stage” then occurs, during which then occurs, during which the bed clothes are drenched. The patient feels the bed clothes are drenched. The patient feels fatigued and exhausted but otherwise well.fatigued and exhausted but otherwise well.

P. Vivax and P. ovaleP. Vivax and P. ovale The fever occurs every other The fever occurs every other

day when establishedday when established Usually mild infectionUsually mild infection There are frequent relapses There are frequent relapses

and eradication of organism and eradication of organism is difficultis difficult

P. MalariaeP. Malariae Usually mild disease but Usually mild disease but

tends to run a more chronic tends to run a more chronic coursecourse

Nephrotic syndrome is seen Nephrotic syndrome is seen between the age of 4 and 5 between the age of 4 and 5 yearsyears

P. FalciparumP. Falciparum Is the most severe form of malaria Is the most severe form of malaria

(pernicious malaria)(pernicious malaria) The prodrome tends to be severeThe prodrome tends to be severe The fever follows no particular pattern The fever follows no particular pattern

and the characteristic cold, hot and and the characteristic cold, hot and sweating stages are not prominentsweating stages are not prominent

There is severe organ damage, chiefly There is severe organ damage, chiefly in the kidneys, liver, brain and in the kidneys, liver, brain and gastrointestinal tractgastrointestinal tract

Cerebral MalariaCerebral Malaria It is likely to occur when It is likely to occur when

more than 2% of RBC are more than 2% of RBC are parasitizedparasitized

There is high grade fever, There is high grade fever, deterioration in concious deterioration in concious level, convulsion coma and level, convulsion coma and deathdeath

Black Water FeverBlack Water Fever This rapidly progressive illness This rapidly progressive illness

characterized by abrupt onset of fever, characterized by abrupt onset of fever, marked haemolysis, haemoglobinuria, marked haemolysis, haemoglobinuria, hyperbilirubinemia, vomiting circulatory hyperbilirubinemia, vomiting circulatory collapse and acute renal failurecollapse and acute renal failure

Malarial parasite can not be detected in Malarial parasite can not be detected in peripheral blood smear after the onset of peripheral blood smear after the onset of intravascular haemolysisintravascular haemolysis

Severe anaemiaSevere anaemia DICDIC

Black Water FeverBlack Water Fever Respiratory complications

Adult respiratory distress syndrome Metabolic

Hypoglycemia, Metabolic acidosis Gastrointestinal/ liver

Diarrhea, Jaundice, Splenetic rupture Shock secondary to septicaemia In pregnancy

Maternal death, Abortion, Still birth, low birth weight

Tropical Splenomegaly Tropical Splenomegaly SyndromeSyndrome

Seen in areas where malaria is Seen in areas where malaria is hyperendemichyperendemic

There is massive splenomegalyThere is massive splenomegaly Marked elevation of serum IgM levelMarked elevation of serum IgM level IgM aggregates in kupffer cells in the liver IgM aggregates in kupffer cells in the liver

detected by immunofluorescencedetected by immunofluorescence Splenomegaly and anaemia resolves over Splenomegaly and anaemia resolves over

periods of months of continuous treatment periods of months of continuous treatment with proguanil 100mg/day along with folic with proguanil 100mg/day along with folic acid.acid.

DiagnosisDiagnosis Thick and thin blood film will Thick and thin blood film will

demonstrate malarial parasite 2-3 demonstrate malarial parasite 2-3 smear taken each day for 3-4 day and smear taken each day for 3-4 day and found to be negative are necessaryfound to be negative are necessary

Serological test includeSerological test includei)i) Indirect immunoflorescence, Indirect immunoflorescence, ii)ii)Indirect haemagglutination Indirect haemagglutination iii)iii)Gel diffusion techniquesGel diffusion techniques

TreatmentTreatmentChemotherapy of acute attackChemotherapy of acute attackChloroquine is the drug of Chloroquine is the drug of

choicechoice600 mg of the effective base 600 mg of the effective base followed by 300 mg base in 6 followed by 300 mg base in 6 hrs and then 150 mg base hrs and then 150 mg base twice daily for two daystwice daily for two days

TreatmentTreatment Infections with P. falciparum from Infections with P. falciparum from

chloroquine-resistant area should be chloroquine-resistant area should be treated with quinine dihydrochloride or treated with quinine dihydrochloride or sulphatesulphate 600 mg salt (10 mg/kg) 8 hourly until better 600 mg salt (10 mg/kg) 8 hourly until better

and the blood is free of parasite (usually 3-5 and the blood is free of parasite (usually 3-5 days)days)

This regimen should be followed by a single This regimen should be followed by a single dose of sulphadoxin 1.5 gram conutined with dose of sulphadoxin 1.5 gram conutined with pyramethamine 15 mg i.e. 3 tab of fansidarpyramethamine 15 mg i.e. 3 tab of fansidar

TreatmentTreatment Alternative to quinine and fansidar are Alternative to quinine and fansidar are

melfoquine 20 mg/kg up to max of 1.5 g melfoquine 20 mg/kg up to max of 1.5 g in two divided dose 8 hours apart. It may in two divided dose 8 hours apart. It may cause neuropsychiatric symptomscause neuropsychiatric symptoms

Halofantrine (Halfan) 500 mg every 6 Halofantrine (Halfan) 500 mg every 6 hours for 3 doses prolonged GT, cardiac hours for 3 doses prolonged GT, cardiac arrythmia in susceptible individualarrythmia in susceptible individual

Artemesinin and derivatives (artemetter, Artemesinin and derivatives (artemetter, artesunate) they are effective but have artesunate) they are effective but have no action on liver stageno action on liver stage

Management of Management of complicatedcomplicated

P. falciparum malaria P. falciparum malaria Patient with cerebral malaria, or Patient with cerebral malaria, or

other severe manifestations are other severe manifestations are medical emergenciesmedical emergencies

Quinine is given as an intravenous Quinine is given as an intravenous infusion over 4 hours. Dose is 10 infusion over 4 hours. Dose is 10 mg/kg of quinine salt up to max of mg/kg of quinine salt up to max of 700 mg-8 hourly until the patient 700 mg-8 hourly until the patient is able to take the drug orallyis able to take the drug orally

ChemoprophylaxisChemoprophylaxis Choloroquine resistant patientsCholoroquine resistant patients

Chloroquine plusChloroquine plus Proguanil orProguanil or mafloquinemafloquine

Chloroquine resistance absent Chloroquine resistance absent Chloroquine orChloroquine or ProguanilProguanil

P. Vivax TrophozitesP. Vivax Trophozites

P.Falciparum P.Falciparum TrophozitesTrophozites

P.Malariae trophozitesP.Malariae trophozites

P.Ovale SchizontP.Ovale Schizont

P.Ovale SchizontP.Ovale Schizont

MerozitesMerozites

P.Falciparum P.Falciparum GametocytesGametocytes

Vivax GametocytesVivax Gametocytes

Peripheral Smear Preparation

Peripheral smear examination for Peripheral smear examination for malarial parasite is the gold-malarial parasite is the gold-standard in confirming the diagnosis standard in confirming the diagnosis of malaria. Thick and thin smears of malaria. Thick and thin smears prepared from the peripheral blood prepared from the peripheral blood are used for the purpose.are used for the purpose.

STEP 1STEP 1

Hold the third finger of the left hand and clean it with swab dipped in Savlon or dettol

Step 2Step 2

Prick the finger with needle or lancet and allow the blood to ooze out.

Step 3Step 3

Take a clean glass slide. Take 3 drops of blood 1 cm from the edge of the slide, take another drop of blood one cm from the first drop of blood

Step 4Step 4

Take another clean slide with smooth edges and use it as a spreader...

Step 5Step 5

...and make thick and thin smears. Allow it to dry

Prepared SmearPrepared Smear

Thick FilmThick Film The thick smear of correct thickness is the one The thick smear of correct thickness is the one

through which newsprint is barely visible. through which newsprint is barely visible. It is dried for 30 minutes and not fixed with It is dried for 30 minutes and not fixed with

methanol. methanol. This allows the red blood cells to be hemolyzed and This allows the red blood cells to be hemolyzed and

leukocytes and any malaria parasites present will be leukocytes and any malaria parasites present will be the only detectable elements.the only detectable elements.

However, due to the hemolysis and slow drying, the However, due to the hemolysis and slow drying, the plasmodia morphology can get distorted, making plasmodia morphology can get distorted, making differentiation of species difficult. differentiation of species difficult.

Thick smears are therefore used to detect infection, Thick smears are therefore used to detect infection, and to estimate parasite concentration.and to estimate parasite concentration.

Thin FilmThin Film Air dry the thin smear for 10 minutes.Air dry the thin smear for 10 minutes. After drying, the thin smear should be After drying, the thin smear should be

fixed in methanol. This can be done by fixed in methanol. This can be done by either dipping the thin smear into either dipping the thin smear into methanol for 5 seconds or by dabbing methanol for 5 seconds or by dabbing the thin smear with a methanol-soaked the thin smear with a methanol-soaked cotton ball.cotton ball.

While fixing the thin smear, all care While fixing the thin smear, all care should be taken to avoid exposure of should be taken to avoid exposure of the thick smear to methanol.the thick smear to methanol.

EXERCISEEXERCISE

P. Vivax TrophozitesP. Vivax Trophozites

P.Falciparum P.Falciparum TrophozitesTrophozites

P.Malariae trophozitesP.Malariae trophozites

P.Ovale SchizontP.Ovale Schizont

P.Ovale SchizontP.Ovale Schizont

MerozitesMerozites

P.Falciparum P.Falciparum GametocytesGametocytes

Vivax GametocytesVivax Gametocytes