MALARIADr. DWI HANDAYANI

MALARIAReferenceParasitology Protozoology and Helmintology Basic Clinical Parsitology: Brown & BeldingK.D. ChatterjeeClinical Parasitology: Paul Chester Beaver c.s.The immunology of Parasitic infection omar o. BarrigaFaundation of ParasitologyGerald D. Schmidt & L.S. ROBERTAtlas of Medical Helmintology & Parasitology: Jeffrey & leachModern Parasitology : Edited by F.E.G. CoxMedical Parasitology, Apractical ApproachEdited by S. H. Gillespie and P. M. HawkeyPerubahan Radidkal dalam Pengobatan Malaria di IndonesiaP.N. Harijanto. Cermin Dunia Kedokteran, 20069. Internet

Classification of malarial parasitePhylumProtozoa

SubphylumSporozoaClassTelosporidea

SubclassHaemosporidiaFamilyPlasmodiidaeGenesPlasmodium

SpeciesP. vivax P. malariae P. falciparum P. ovale

Monkey plasmodium

P. cynomolgi

P. knowlesi

Morphology:- Chromatin- Cytoplasm- Pigment- Granula

Plasmodium vivax

Plasmodium falciparum

Plasmodium malariae

Ring form; band form; schizont

Plasmodium ovale

PhysiologyLatent period in the body :-P. falciparum: shortestP. malariae: longest

Plasmodium: Hb Iron porphyrin hematin + GlobinHematin= ferrihemic acid=pigment malaria

For survival the malarial parasitesneed: CHO; PROTEIN; FATBesides they also need:MethioninRiboflavinPara-aminobenzoic acidPanthotenic acidVit C

Life cycle-Intrinsic phase:in the vertebrate host,asexual schizogony

Extrinsic phase:in the female anopheles mosquito,sexual sporogony

Life cycle of malarial parasites

Life cycle of P. vivax or P.ovaleMIKROGAMETOCYTE

Epidemiology of malaria

2,770 m above sea levelCochabamba 400 m bellow Dead sea basinEquator

Impact of malariaMalaria causes about 350-500 million infections in humans and approximately one to three million deaths annually.The vast majority of cases occur in children under the age of 5.Pregnant women are also especially vulnerable.

(Epidemiology) anopheles mosquitoesVectors in indonesia:Anopheles annularisAnopheles vagusAnopheles barbirostrisAnopheles aconitusAnopheles sundaicusAnopheles maculatusAnopheles balabacensisAnopheles punctularisAnopheles subpictus Ano;heles indefinitus

(Epidemiology)Endemic: connotes natural transmission in an area so that there are autochthonous, locally contracted cases

Imported malaria: is acquired outside the area Introduced malaria : cases derived from Imported malariaSporadic : cases are few and scattered

Malaria endemicity:The prevailing frequency and intensity of endemic malaria.

Classification of endemicity:Based on spleen index (%) of children in age group 2-9, and the spleen rate of adult

(Epidemiology)Classification of endemicity:

Hypoendemic malaria: spleen rate in age group 2-9 10%Mesoendemic malaria: 2-9: 11-50%Hyperendemic malaria: 2- 9 > 50% andadult spleen rate Holoendemic malaria: spleen rate in age group 2-9 > 75% but adult tolerance high andadult spleen rate

Mode of infections:1. Bitten by female anopheles2. Congenital3. Transfusion4. Organ transplantationPathologyVascular blockade of vascular by parasistized rbc.Anoxia (organ)Deposition of pigments

Incubation period:P malariae: 12-14 daysP. falciparum: 10-12 daysP. ovale: 10-12 daysP. vivax: 14-17 days

SymptomatologyThe febrile paroxysm may be divided into 3 clinical stages: - cold stage (15-16 minutes)- host stage (about 2 hours: 39-40o C)- sweating stage (about 1 hour)

Secondary anemia3.splenomegaly

The attack of paroxysmP. vivax and P. ovale : 48 hoursP. falciparum : 24-48 (36-48) hoursP. malariaae : 72 hours

Diagnosis Thick film (DDRThin filmQ.B.C. (Quantitative Buffy Coat)I.R.M.A. (Immunoradiometric assay)Elisa for Ag p. falcliparum(HRP-2 = histidine Rich Protlein-2)RNA probeDNA HybridizationRapid Manuel test (P.falciparum)HRP-IIalso available for vivax

(Diagnosis of malaria) 9. Indirect fluorescence Assay (IFA)

10. Polymerase Chain Reaction (PCR)

Pernicious manifestationWarning signs:asexual parasitemia 5%, 10 % with multiple rings in red cells and schizonts in peripheral blood

Pernicious manifestation:Cerebral malariaMalaria with jaundiceDiarrhoea, dysenteryRenal failurePulmonary edemaBlack water feverAlgid malaria, shock Hyperpyrexia

Algic malariaA condition analogous to cerebral malaria, except that the gut and other abdominal viscera are involved.

The skin is cold and clammy, but internal temperature is high.

(Algic malaria)Two types:

Gastric: with persistent vomiting Dysenteric: with bloody, diarrheic stools containing enormous numbers of parasites.

Definition of severe malaria (WH0)One or more of the following criteria + the presence of asexual parasitaemia defines severe malaria

Cerebral malaria/unarousable comaSevere anaemiaRenal failurePulmonary oedema/adult respiratory distress syndrome (ARDS)

[Definition of severe malaria (WH0)]HypoglycaemiaHypotension/shockBleeding/disseminated intravascular coagulation (DIC)Convulsion Acidosis/ Acidaemia Macroscopic haemoglobinuria

Pathophysiology of Cerebral malaria:It is exactly not knownProposed hypotheses:Permeability hypothesis (Maegraith and fletcher)Toxic/cytokine hypothesisMechanical hypothesis

Black water feverHaemoglobinuriafeverNausia & vomitusIcterus Pamaquinequinine(qinghousu)Death due to Renal failure

Treatment 1. Non-specific treatment:symptomatic and supportive measures according to the clinical manifestation2. Specific treatment:Blood schizontocide:- Chloroquine- sulfadoxine & pyrimethamine (SP)- quinine; Mefloquine- Artemisinin/Qinghausu (artesunate; artemeter; dihidroartemisinin)- Artemisinin based combination therapy (ACT):e.g.: Artesdiaquine (Artesunate 50 mg + amodiaquine 200 mg).- Non Artemisinin based bcombination therapy (NON-ACT):e.g. Quinine + SP Chloroquine + teteracycline /doxicycline

Gametocytocide : Primaquine

ChemoprophylaxisChloroquine: 300 mg base weeklySulfadoxine 1 g + Pyrimethamine 50 mgevery two weeksSulfadoxine .1.5 g + Pyrimethamine 70 mgevery four weeksMefloquine: 5 mg/kg BB/weekly(250 mg/tablet base)

Suppressive treatment:Chloroquine: 0.5 g weekly

Early treatment failure: One or two condition occur as bellow within the first 3 days of treatmentParasitemia with complication of severe malaria on day 1, 2 and 3.Parasitemia on day 2 > that on day 0Parasit count on day 3 > 25% of day 0Or the axial temperature: > 37.5

Late treatment failure:if the following conditions occur on day 4 28, divided into 2 sub group:

Late Clinical (and parasitological) Failure (LCF)- Parasitemia (the same species with that of day 0) complicated with severe malaria after day 3.- The axial temperature > 37 C with parasitemia between day 4 - 28.

Late treatment failureLate Parasitological Failure (LPF)Parasitemia (the same species with day 0)on day 7, 14 or 28 without rising of the axial temperature (< 37 C)

Resistance of asexual parasites (P. falciparum) to schizontocidal drugs (4-aminoquinolines)Resistance:The ability of a parasite strain to survive and /or to multiply despite the administration and absorption of a drug given in doses equal to or higher than those usually recommended but within the limits of tolerance of the subject.

Immunologi of malaria innatePlasmodium: host specificP. vivax

P. berghei In the liver of man:In liver of chimpanse:sporozoiteWell developedNot developThe liver of mouse: 1%In the liver of a tree rodent: 50%sporozoite

The immunity of malariaThe combination of those mechanisms which:Prevent infectionPrevent reinfectionPrevent super infectionWith the outcome of:Destruction of the malarial parasitesHindrance of their multiplication,Modification of their effects andHelping specifically for the repairing of tissues.

(Immunity)P. falciparum : infection disappears within a year

P. vivax : 1-1 years.P. Malariae : infection persists until 20-30 years

(Immunity of malaria)innate:Such as: - G6PD deficiency- Duffy factor negative- Sickle cell anemia- Thallasemia Hb & Hb E- Hb foetus of human- ATP deficiency

(immunity of malaria)Acquired

- Passive- Active: 1. concomitant2. residual

(Immunity of malaria):Non specificRESSpecific: Gamma globulinlysinAgglutininPrecipitinOpsoninAblastinComplement-fixingCytoplasm-modifying

In high endemic area of malaria:

Receptor : glycoprotein

Duffy factorGenotype:

Fy, Fy

RBC

Premunision: a specific immune response clinical recovery & resistant to super infection.

Tolerant

Immunities: - species specific- strain specific

P. falciparum TNFPatologiHigh levelLow levelProtection Inhibition of parasites in:The liver &RBCDyserythropoisis-Erythro phagocytosis

AnemiaCytoadherenceAdherence of parasitized rbc to vascular endotheliumClinical manfestations:Such as: Headache Fever Chill etc.

Macrophage