Malaria exoantigens induce T-independent antibody that blocks ...
Malaria Pp t
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MALARIAMALARIA
Safana Mushtaq, MDSafana Mushtaq, MD
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OBJECTIVESOBJECTIVES
Geographical distributionGeographical distribution
Malaria in US & World wideMalaria in US & World wide
Life Cycle of Malarial parasiteLife Cycle of Malarial parasite
Types of plasmodiumTypes of plasmodium
DiagnosisDiagnosis
Clinical featureClinical feature
Treatment & preventionTreatment & prevention
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Geographical DistributionGeographical Distribution
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Malaria WorldwideMalaria Worldwide
41% of worlds population live in areas where41% of worlds population live in areas where
malaria is transmittedmalaria is transmitted There are 300There are 300--500 million new cases of malaria500 million new cases of malaria
every year.every year.
An estimated 700,000An estimated 700,000--2.7 million persons die of2.7 million persons die ofMalaria every year, 75% of them are African childrenMalaria every year, 75% of them are African children
In areas of Africa with high transmission there areIn areas of Africa with high transmission there are
about 2700 deaths per day, 2 deaths per minute.about 2700 deaths per day, 2 deaths per minute. Malaria is fourth leading cause of death.Malaria is fourth leading cause of death.
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Mortality andMortality and ChloroquineChloroquine resistanceresistance
0
5
10
15
20
25
1900 1920 1940 1960 1980 1997
Sub-Saharan Africa Outside Sub-Saharan Africa
resistance enters Africa
Chloroquine introduced
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100.010,596Total
101,022Other causes
3305Injuries7
3321HIV/AIDS6
4395Measles5
8853Malaria4
171,762Diarrheal diseases3
192,027Acute respiratory infections2
373,910Neonatal causes1
% of alldeaths
Numbers(x1000/year)
CauseRank
Leading Causes of Death in Children UnderFive, for 2000-03 (WHO)
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Malaria in the United StatesMalaria in the United States
Malaria eradicated from USMalaria eradicated from US
Over 1300 cases of malaria were reported in USOver 1300 cases of malaria were reported in USevery yearevery year
Out of these case, nearly all are imported , InOut of these case, nearly all are imported , In
2002 out 13370 cases expect 5 cases all were2002 out 13370 cases expect 5 cases all wereimportedimported
Constant risk of reintroduction of malaria in USConstant risk of reintroduction of malaria in US
Transfusion related malariaTransfusion related malaria
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PlasmodiumPlasmodium -- life cyclelife cycle
Malaria transmitted by female Anopheles. OverMalaria transmitted by female Anopheles. Over
60 types60 types Apicomplexa group of protozoa, haveApicomplexa group of protozoa, have
specialized complex of apical organellesspecialized complex of apical organelles
involved in host cell invasion.involved in host cell invasion. Four Plasmodium species cause humanFour Plasmodium species cause human
Malaria:Malaria: P.vivaxP.vivax,, P.ovaleP.ovale,, P.malariaeP.malariae,,
P.falciparumP.falciparum
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Life Cycle..contLife Cycle..cont
Schizogony, occurs in human, intermediate host,Schizogony, occurs in human, intermediate host,
haploid replication.haploid replication.exoexo--erythrocytic stageerythrocytic stage
erythrocytic stageerythrocytic stage
Sporogony, occurs in mosquito gut, diploidSporogony, occurs in mosquito gut, diploid
zygoteszygotes
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Life cycleLife cycle
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Life cycle contLife cycle cont
ExoExo--erythrocytic Stage (liver)erythrocytic Stage (liver)
Sporozites invades and replicatesSporozites invades and replicates
All P.falciparum and P.malariae complete in 1All P.falciparum and P.malariae complete in 1--22
weeks.weeks.
P.Vivax and P.ovale may persist in liver, relapseP.Vivax and P.ovale may persist in liver, relapse
Erythrocytic Stage (RBC)Erythrocytic Stage (RBC)
Gametocyte FormationGametocyte Formation
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Clinical featuresClinical features
The classical attack lasts 6The classical attack lasts 6--10 hours.10 hours.
a cold stage (sensation of cold, shivering)a cold stage (sensation of cold, shivering)
a hot stage (fever, headaches, vomiting;a hot stage (fever, headaches, vomiting;
seizures in young children) , fever up to 104 Fseizures in young children) , fever up to 104 F
and finally a sweating stage (sweats, return toand finally a sweating stage (sweats, return to
normal temperature, tiredness)normal temperature, tiredness)
Paroxysms coincideParoxysms coincide synchronussynchronus rupturerupture
schizontschizont
Elevated TNFElevated TNF--alphaalpha
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Clinical featurescontClinical featurescont
Tertian Malaria , where paroxysms of malaria isTertian Malaria , where paroxysms of malaria is
repeated after 48 hrs or fever occurs every thirdrepeated after 48 hrs or fever occurs every thirdday. It is feature of P.falciparum, P.ovale andday. It is feature of P.falciparum, P.ovale and
P.vivaxP.vivax
Quartan Malaria , where paroxysms occurs afterQuartan Malaria , where paroxysms occurs afterevery 72 hour or fever occurs every fourth day. Itevery 72 hour or fever occurs every fourth day. It
is seen in P.malariaeis seen in P.malariae
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Severe MalariaSevere Malaria Pathogenesis : ability of parasite to sequester inPathogenesis : ability of parasite to sequester in
deep venous microvasculature through processdeep venous microvasculature through process
of cytoadherence.of cytoadherence.
Cerebral malariaCerebral malaria
Severe AnemiaSevere Anemia HemoglobinuriaHemoglobinuria
Pulmonary Edema/ARDSPulmonary Edema/ARDS
Coagulation Abnormalities andCoagulation Abnormalities andThrombocytopeniaThrombocytopenia
Cardiovascular collapse and shockCardiovascular collapse and shock
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Severe MalariacontSevere Malariacont
Nephrotic syndrome , seen inNephrotic syndrome , seen in P.malariaeP.malariae, young, young
children pronechildren prone Hyperparasitemia :>5% RBC infectedHyperparasitemia :>5% RBC infected
Metabolic acidosisMetabolic acidosis
Hypoglycemia : esp. in pregnant females even inHypoglycemia : esp. in pregnant females even in
uncomplicated malaria , after treatment withuncomplicated malaria , after treatment with
QuinineQuinine
Hyperactive malarial spleenomegalyHyperactive malarial spleenomegaly
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DiagnosisDiagnosis
Malaria must be recognized promptly in order toMalaria must be recognized promptly in order to
treat the patient in time and to prevent furthertreat the patient in time and to prevent furtherspread of infection in the communityspread of infection in the community
Malaria considered a potential medicalMalaria considered a potential medical
emergency. Delay in diagnosis and treatment isemergency. Delay in diagnosis and treatment isa leading cause of death in malaria patients ina leading cause of death in malaria patients in
the United States.the United States.
Suspect clinically, confirm with labsSuspect clinically, confirm with labs
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DiagnosiscontDiagnosiscont
History and Physical examHistory and Physical exam
Microscopic, Thin and Thick Blood filmsMicroscopic, Thin and Thick Blood films
Serology, rapid diagnostic tests( antigenSerology, rapid diagnostic tests( antigen
detection)detection)
ParsSight F, and OptiMalParsSight F, and OptiMal
Serology, antibody detection, indirect fluorescentSerology, antibody detection, indirect fluorescent
antibody, enzyme immunoassayantibody, enzyme immunoassay
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DiagnosisDiagnosisThick and Thin Blood SmearsThick and Thin Blood Smears
Light microscopy of Giemsa stained blood filmsLight microscopy of Giemsa stained blood films
Should be prepared and read immediately byShould be prepared and read immediately byexperienced personnelexperienced personnel
Thick smears , detect parasiteThick smears , detect parasite
Thin smears , for speciesThin smears , for species
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Diagnosis.contDiagnosis.contRapid Diagnostic testRapid Diagnostic test
ParaSight F and ICT Malaria PFParaSight F and ICT Malaria PF
Helpful , no expert microscopyHelpful , no expert microscopy
It depends on detection of P.falciparum histidineIt depends on detection of P.falciparum histidine--
rich protein 2 (HRPrich protein 2 (HRP--2)2)
Sensitivity is 77% to 100%Sensitivity is 77% to 100%
Specificity 83% to 100%Specificity 83% to 100%
LimitationsLimitations
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DiagnosisDiagnosisRapid Diagnostic TestRapid Diagnostic Test
OptiMal testOptiMal test
Detects plasmodium lactate dehydrogenaseDetects plasmodium lactate dehydrogenase(pLDH)(pLDH)
Sensitivity similar to ParaSight FSensitivity similar to ParaSight F
Advantage for all speciesAdvantage for all species
Therapeutic responseTherapeutic response
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Plasmodium FalciparumPlasmodium Falciparum
P. falciparum:P. falciparum:
trophozoites are smalltrophozoites are small
rings with single orrings with single or
double smalldouble small
chromatin dots, andchromatin dots, and
regular cytoplasm.regular cytoplasm.
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Plasmodium FalciparumPlasmodium Falciparum
Thin Smear, GiemsaThin Smear, Giemsa
MatureMature trophozoitetrophozoite
Thin Smear,Thin Smear, GiemsaGiemsa
TrophozoiteTrophozoite
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Plasmodium FalciparumPlasmodium Falciparum Thin Smear, GiemsaThin Smear, Giemsa
P.falciparum:P.falciparum:micromicro-- andand
macrogametocytesmacrogametocytes
crescenticcrescentic, cigar, cigar-- or bananaor banana--
like shape.like shape.
GametocyteGametocyte
QuantitaveQuantitave buffybuffy coatcoat
techniquetechnique
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Plasmodium MalariaePlasmodium Malariae
P.P. malariaemalariae,,
trophozoitestrophozoites Band shapeBand shape
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Plasmodium MalariaePlasmodium Malariae Thin Smear, Giemsa stain
Schizont Rosettes
Central pigment
Thin Smear,Thin Smear, GiemsaGiemsa
P.P. ovaleovale, ring, ring fornforn
Presence of dots or clefts onPresence of dots or clefts on
infected RBC are diagnostic oninfected RBC are diagnostic on
OvaleOvale speciesspecies
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Plasmodium ovalePlasmodium ovale
P.ovale, Giemsa StainP.ovale, Giemsa Stain
TrophozoiteTrophozoite All stages are seen inAll stages are seen in
blood filmsblood films
Prominent ShuffnersProminent Shuffners
dotsdots
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Plasmodium ovalePlasmodium ovale
SchizontSchizont
Enlarged RBCEnlarged RBC
OvalisedOvalised RBCRBC
P.ovaleP.ovale
GametocyteGametocyte
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Prevention and TreatmentPrevention and Treatment Prevention is based on followingPrevention is based on following
Evaluating risk of exposure to infectionEvaluating risk of exposure to infection
Preventing mosquito bitesPreventing mosquito bites ChemoprophylaxisChemoprophylaxis
Advice to seek medical care if malaria likeAdvice to seek medical care if malaria like
symptoms occursymptoms occur Presumptive treatment of malariaPresumptive treatment of malaria
Risk of ExposureRisk of Exposure
may be difficult to determine since it varies bymay be difficult to determine since it varies byclimate, rainy season, altitude, degree of mosquitoclimate, rainy season, altitude, degree of mosquitocontrol in rural versus urban areas, nature of visitcontrol in rural versus urban areas, nature of visit
adventure vs. business tripadventure vs. business trip
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Prevention..contPrevention..cont
Preventing mosquito bites is importantPreventing mosquito bites is important
Preventive measures when out door betweenPreventive measures when out door betweendusk and dawndusk and dawn
Clothing should cover most of bodyClothing should cover most of body
Mosquito repellents: deet ( N,NMosquito repellents: deet ( N,N--diethyldiethyl--33--methylmethylbenzamide) should be applied to exposed areasbenzamide) should be applied to exposed areasq 3q 3--4 hours,4 hours,
Living quarters be air conditioned or wellLiving quarters be air conditioned or wellscreenedscreened
Mosquito nets ,Mosquito nets , premethrinpremethrin
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Chemoprophylaxis
Less 8 yrs
pregnancy
100 mg q dayDoxycycline
Pregnancycategory C
250/100 mg q day
1-2 days before and continue 7
days after leaving area
Atovaquoneplus proguanil
Cardiacconduction
Psychiatric dis
250 q week1-2 wks before travel
4 wks after leaving area
Mefloquine
retinopathy500 mg q weekly
1-2 weeks before travel,
continue 4 weeks after leavingmalarious area
Chloroquine
Phosphate
precautionAdult doseDrug
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TreatmentTreatment
QuinidineQuinidine gluconategluconate IV,IV,
exchange transfusion if >15%exchange transfusion if >15%Complicated/Severe P.Complicated/Severe P.
FalciparumFalciparum
Quinine Sulfate +Quinine Sulfate + doxycyclinedoxycycline
oror atovaquoneatovaquone ++ proguanilproguanilUncomplicated P.Uncomplicated P. FalciparumFalciparum,,
chloroquinechloroquine resistantresistant
Chloroquine + PRIMAQUINE
G6PD screen
P. Ovale and P. Vivax
ChloroquineUncomplicated, P. Falciparumchloroquine sensitive
DrugType of Malaria
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Final CommentFinal Comment Malaria is mainly a disease of tropical and subtropicalMalaria is mainly a disease of tropical and subtropical
areas.areas.
There is constant risk of reintroduction of malaria inThere is constant risk of reintroduction of malaria inUnited States because of presence of AnophelesUnited States because of presence of Anopheles
Travelers should be given preTravelers should be given pre--travel advice andtravel advice and
chemoprophylaxis before departure tochemoprophylaxis before departure to malariousmalarious areaarea Since Chemoprophylaxis is not 100% effective measureSince Chemoprophylaxis is not 100% effective measure
should be taken to prevent mosquito bitesshould be taken to prevent mosquito bites
Detailed travel history and immigration history whenDetailed travel history and immigration history when
evaluating unexplained fever and considering malaria asevaluating unexplained fever and considering malaria asaa differntialdifferntial..
Fever before 8 days after reaching a endemic area isFever before 8 days after reaching a endemic area isunlikely to be malariaunlikely to be malaria
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Final CommentcontFinal Commentcont
Efforts should be made on part of WHO withEfforts should be made on part of WHO with
malaria endemic countries to eradicate malaria,malaria endemic countries to eradicate malaria,which is not just a killer but holds back humanwhich is not just a killer but holds back human
and economic developmentand economic development
DDT : second chanceDDT : second chance
Malarial Vaccine, more funding and researchMalarial Vaccine, more funding and research