Malaria Mechanism of infection Parasitology Departement Medical Faculty of USU
Introduction Malaria parasites Phylum Order Suborder Family Genus Species : : Apicomplexa : Eucoccidiida : Haemosporida : Plasmodiida : Plasmodium Plasmodium vivax Plasmodium falciparum Plasmodium ovale Plasmodium malariae 11/4/2009 Dewi M.Darlan 2
Introduction Malaria distribution 11/4/2009 Dewi M.Darlan 3
Introduction Malaria vectors Malaria is transmitted exclusively by Anopheles mosquitoes 422 species of Anopheles 70 species can transmit malaria Major significance only 40 Vectors in Indonesia: Anopheles aconitus, An. sundaicus, An. letifer, An. maculatus, An. nigerrimus, An. subpictus, An. balabacensis, An. sinensis, An. umbrosus, An. barbirostris, An. flavirostris, An. minimus, An. ludlowae, An. farautu, An. punctulatus, An. kochi, An. vagus and An. koliensis Found in tropical and subtropical regions 11/4/2009 Dewi M.Darlan 4
Introduction Malaria vectors Prerequisites for an efficient vector: Susceptibility Longevity Host preference Density 11/4/2009 Dewi M.Darlan 5
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Pre-erythrocytic erythrocytic cycle How many parasites injected at one time in the field is not known but laboratory studies showed that number of parasites injected during a blood meal is 15 to 25 (Ponnudurai et al., 1991, Rosenberg et al., 1990) 2 2 to 10 sporozoites enough to initiate an infection (Khusmith et al., 1988; Ungureanu et al., 1976) 11/4/2009 Dewi M.Darlan 7
Pre-erythrocytic erythrocytic cycle Sporozoite surface is covered by circumsporozoite protein bearing a ligand that binds to receptors on the hepatocyte cell membrane (receptor mediated mechanism) Entrance into the hepatocytes initiates pre-erythrocytic erythrocytic cycle 11/4/2009 Dewi M.Darlan 8
Pre-erythrocytic erythrocytic cycle In the life cycle of P. vivax and P. ovale, some sporozoites become dormant for an indefinite time after entering liver cells (Bignami, 1913), called hipnozoites (Krotoski et al., 1982) Those are the sporozoites enter liver cells but do not undergo nuclear division to form tissue schizonts 11/4/2009 Dewi M.Darlan 9
Erythrocytic cycle Merozoites can invade erythrocytes of host specific: P. vivax: prefers old erythrocytes P. malariae: prefers young erythrocytes P. falciparum: any age of erythrocytes, including reticulocytes 11/4/2009 Dewi M.Darlan 10
Erythrocytic cycle How does merozoite enter erythrocyte? (Mark Wiser, 2001) 1. Initial interaction 2. Reorientation 3. Attachment & binding formation 4. Invasion Initial attachment RBC deformation orientation and apical attachment Invagination 11/4/2009 Dewi M.Darlan 11
Erythrocytic cycle 1. Initial interaction: random collision between merozoite and RBC markers Merozoite marker: merozoite surface protein (MSP-1) RBC marker: glycophorin A and glycophorin B 2. Reorientation: the merozoite reorients itself so that the apical ends to the erythrocyte membrane 11/4/2009 Dewi M.Darlan 12
Erythrocytic cycle 3. Binding formation: merozoite releases secretion, changes nature of RBC surface, then expands inward as merozoite pushes itself into it, form parasitophorous vacuoles 4. Invasion: once inside the RBC, merozoite turns into ring form 11/4/2009 Dewi M.Darlan 13
Erythrocytic cycle Once inside the erythrocyte, the parasite matures and undergoes a replicative phase During this erythrocytic period, parasite modifies the host to make it a more suitable habitat. Erythrocyte membrane become more permeable to small molecules metabolites for the growth of the parasite 11/4/2009 Dewi M.Darlan 14
Erythrocytic cycle The parasites feed on red cell (haemoglobin) producing insoluble haemozoin as waste products contents pigment End of 2 days, schizont rupture releasing merozoites, parasite metabolic wastes and residual body, including haemozoin Merozoites enter fresh RBC, cycle may continue 11/4/2009 Dewi M.Darlan 15
Erythrocytic cycle Theories on gametogenesis: Clinical manifestation of malaria (Miller, 1958) Drug treatment (Shute & Morgan, 1951) Host antibody respond (Smalley, Brown & Bassett, 1981) 11/4/2009 Dewi M.Darlan 16