Malaria

MALARIAMALARIA
Department of PathologyDepartment of Pathology

Plasmodium MalariaePlasmodium Malariae

MalariaMalaria
 Malaria affects 270 million people eachMalaria 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, humidMalaria is primarily a disease of hot, humid
countries.countries.
 In humans, malaria is caused by fourIn humans, malaria is caused by four
species ofspecies of plasmodium, p. ovale, p. falciparum,plasmodium, p. ovale, p. falciparum,
p. vivax, p. marlariaep. vivax, p. marlariae
 P. ovale has been reported predominantlyP. ovale has been reported predominantly
from east and west Africafrom east and west Africa

Geographical DistributionGeographical Distribution

MalariaMalaria
 P. vivax is the major species in temperate zoneP. vivax is the major species in temperate zone
whereas in tropics all forms of malaria are seenwhereas in tropics all forms of malaria are seen
 Humans, the intermediate hosts, are infectedHumans, the intermediate hosts, are infected
following the bite of an infected femalefollowing the bite of an infected female
anopheles mosquito, the definitive hostanopheles mosquito, the definitive host
 The parasite can be transmitted by bloodThe parasite can be transmitted by blood
transfusion, transplacentally and increasinglytransfusion, transplacentally and increasingly
between drug addicts who use improperlybetween drug addicts who use improperly
cleaned syringes.cleaned syringes.

MalariaMalaria
 The introduction of sporozoites, theThe introduction of sporozoites, the
infective form of parasite, through the skininfective form of parasite, through the skin
by anopheles mosquito heralds theby anopheles mosquito heralds the
commencement of human cycle. Thecommencement of human cycle. The
following stages occurfollowing stages occur
 Pre-erythrocytic shizogonyPre-erythrocytic shizogony
 Erythrocytic shizognyErythrocytic shizogny
 GametogonyGametogony
 Exoerythrocytic shizognyExoerythrocytic shizogny

MalariaMalaria
 When an anopheles mosquito ingestWhen an anopheles mosquito ingest
human blood containing gametocytes ithuman blood containing gametocytes it
marks the commencement of sexual cyclemarks the commencement of sexual cycle
in mosquitoin mosquito
 The external incubation period varies fromThe external incubation period varies from
7-20 days7-20 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 threeMalarial febrile paroxysms typically have three
stagesstages
 TheThe “cold stage”“cold stage” is characterized by markedis 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 uncomfortable.The patient feels intensely cold and uncomfortable.
There is marked shivering. The temperature risesThere is marked shivering. The temperature rises
rapidly often to as high as 41rapidly often to as high as 41oo
CC
 TheThe “hot stage”“hot stage” abruptly follows and lasts for 2-6abruptly follows and lasts for 2-6
hours. Patient feels intensely hothours. Patient feels intensely hot
 TheThe “sweating stage”“sweating stage” then occurs, during which thethen occurs, during which the
bed clothes are drenched. The patient feels fatiguedbed clothes are drenched. The patient feels fatigued
and exhausted but otherwise well.and exhausted but otherwise well.

P. Vivax and P. ovaleP. Vivax and P. ovale
 The fever occurs every other day whenThe fever occurs every other day when
establishedestablished
 Usually mild infectionUsually mild infection
 There are frequent relapses andThere are frequent relapses and
eradication of organism is difficulteradication of organism is difficult

P. MalariaeP. Malariae
 Usually mild disease but tends to run aUsually mild disease but tends to run a
more chronic coursemore chronic course
 Nephrotic syndrome is seen betweenNephrotic syndrome is seen between
the age of 4 and 5 yearsthe age of 4 and 5 years

P. FalciparumP. Falciparum
 Is the most severe form of malariaIs 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 andThe fever follows no particular pattern and
the characteristic cold, hot and sweatingthe characteristic cold, hot and sweating
stages are not prominentstages are not prominent
 There is severe organ damage, chiefly inThere is severe organ damage, chiefly in
the kidneys, liver, brain and gastrointestinalthe kidneys, liver, brain and gastrointestinal
tracttract

Cerebral MalariaCerebral Malaria
 It is likely to occur when more thanIt is likely to occur when more than
2% of RBC are parasitized2% of RBC are parasitized
 There is high grade fever, deteriorationThere is high grade fever, deterioration
in concious level, convulsion coma andin concious level, convulsion coma and
deathdeath

Black Water FeverBlack Water Fever
 This rapidly progressive illness characterized byThis rapidly progressive illness characterized by
abrupt onset of fever, marked haemolysis,abrupt onset of fever, marked haemolysis,
haemoglobinuria, hyperbilirubinemia, vomitinghaemoglobinuria, hyperbilirubinemia, vomiting
circulatory collapse and acute renal failurecirculatory collapse and acute renal failure
 Malarial parasite can not be detected inMalarial parasite can not be detected in
peripheral blood smear after the onset ofperipheral 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 SyndromeTropical Splenomegaly Syndrome
 Seen in areas where malaria is hyperendemicSeen in areas where malaria is hyperendemic
 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 liverIgM aggregates in kupffer cells in the liver
detected by immunofluorescencedetected by immunofluorescence
 Splenomegaly and anaemia resolves over periodsSplenomegaly and anaemia resolves over periods
of months of continuous treatment withof months of continuous treatment with
proguanil 100mg/day along with folic acid.proguanil 100mg/day along with folic acid.

DiagnosisDiagnosis
 Thick and thin blood film will demonstrateThick and thin blood film will demonstrate
malarial parasite 2-3 smear taken each daymalarial parasite 2-3 smear taken each day
for 3-4 day and found to be negative arefor 3-4 day and found to be negative are
necessarynecessary
 Serological test includeSerological test include
i)i) Indirect immunoflorescence,Indirect immunoflorescence,
ii)ii) Indirect haemagglutinationIndirect haemagglutination
iii)iii) Gel diffusion techniquesGel diffusion techniques

TreatmentTreatment
 Chemotherapy of acute attackChemotherapy of acute attack
 Chloroquine is the drug of choiceChloroquine is the drug of choice
600 mg of the effective base600 mg of the effective base
followed by 300 mg base in 6 hrsfollowed by 300 mg base in 6 hrs
and then 150 mg base twice daily forand then 150 mg base twice daily for
two daystwo days

TreatmentTreatment
 Infections with P. falciparum fromInfections with P. falciparum from
chloroquine-resistant area should bechloroquine-resistant area should be
treated with quinine dihydrochloride ortreated with quinine dihydrochloride or
sulphatesulphate
 600 mg salt (10 mg/kg) 8 hourly until better600 mg salt (10 mg/kg) 8 hourly until better
and the blood is free of parasite (usually 3-5and the blood is free of parasite (usually 3-5
days)days)
 This regimen should be followed by a singleThis regimen should be followed by a single
dose of sulphadoxin 1.5 gram conutined withdose 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 areAlternative to quinine and fansidar are
melfoquine 20 mg/kg up to max of 1.5 g inmelfoquine 20 mg/kg up to max of 1.5 g in
two divided dose 8 hours apart. It maytwo divided dose 8 hours apart. It may
cause neuropsychiatric symptomscause neuropsychiatric symptoms
 Halofantrine (Halfan) 500 mg every 6Halofantrine (Halfan) 500 mg every 6
hours for 3 doses prolonged GT, cardiachours 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 noartesunate) they are effective but have no
action on liver stageaction on liver stage

Management of complicatedManagement of complicated
P. falciparum malariaP. falciparum malaria
 Patient with cerebral malaria, or otherPatient with cerebral malaria, or other
severe manifestations are medicalsevere manifestations are medical
emergenciesemergencies
 Quinine is given as an intravenousQuinine is given as an intravenous
infusion over 4 hours. Dose is 10infusion over 4 hours. Dose is 10
mg/kg of quinine salt up to max ofmg/kg of quinine salt up to max of
700 mg-8 hourly until the patient is700 mg-8 hourly until the patient is
able to take the drug orallyable to take the drug orally

ChemoprophylaxisChemoprophylaxis
 Choloroquine resistant patientsCholoroquine resistant patients
 Chloroquine plusChloroquine plus
 Proguanil orProguanil or
 mafloquinemafloquine
 Chloroquine resistance absentChloroquine resistance absent
 Chloroquine orChloroquine or
 ProguanilProguanil

P. Vivax TrophozitesP. Vivax Trophozites

P.Falciparum TrophozitesP.Falciparum Trophozites

P.Malariae trophozitesP.Malariae trophozites

P.Ovale SchizontP.Ovale Schizont

P.Falciparum GametocytesP.Falciparum Gametocytes

Vivax GametocytesVivax Gametocytes

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

Thick FilmThick Film
 The thick smear of correct thickness is the one through whichThe thick smear of correct thickness is the one through which
newsprint is barely visible.newsprint is barely visible.
 It is dried for 30 minutes and not fixed with methanol.It is dried for 30 minutes and not fixed with methanol.
 This allows the red blood cells to be hemolyzed and leukocytesThis allows the red blood cells to be hemolyzed and leukocytes
and any malaria parasites present will be the only detectableand any malaria parasites present will be the only detectable
elements.elements.
 However, due to the hemolysis and slow drying, the plasmodiaHowever, due to the hemolysis and slow drying, the plasmodia
morphology can get distorted, making differentiation of speciesmorphology can get distorted, making differentiation of species
difficult.difficult.
 Thick smears are therefore used to detect infection, and toThick smears are therefore used to detect infection, and to
estimate parasite concentration.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 fixed inAfter drying, the thin smear should be fixed in
methanol. This can be done by either dippingmethanol. This can be done by either dipping
the thin smear into methanol for 5 seconds orthe thin smear into methanol for 5 seconds or
by dabbing the thin smear with a methanol-by dabbing the thin smear with a methanol-
soaked cotton ball.soaked cotton ball.
 While fixing the thin smear, all care should beWhile fixing the thin smear, all care should be
taken to avoid exposure of the thick smear totaken to avoid exposure of the thick smear to
methanol.methanol.

Malaria

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Malaria