Malaria Life Cycle Life Cycle

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Adrian Craig
5 years ago
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1 Malaria

2 Malaria Life Cycle Life Cycle Oocyst Zygote Sporogony Sporozoites Mosquito Salivary Gland Gametocytes Exoerythrocytic (hepatic) cycle Hypnozoites (for P. vivax and P. ovale) Erythrocytic Cycle Schizogony

3 Plasmodium spp. 1. Plasmodium vivax : Benign Tertian, Tertian Malaria 2. Plasmodium ovale : Ovale tertian Malaria 3. Plasmodium malariae : Quartan malaria 4. Plasmodium falciparum : Malignant Tertian malaria.

4 Affinity of Parasite to Erythrocytes P.vivax P.malariae P.ovale Infectes only young or Old Erythocytes P.falciparum Infects all age groups

5 Alteration of Host Cells A variety of structural changes, which alter its function, appearance or antigenicity. These alterations are a consequence of parasite growth Advantage to the parasite (e.g. increased membrane permeability, increased selective intake of nutrients, or escape from immunity by sequestration). The nature of the alterations induced are variable from one species to another.

The presence of electron- dense protrusions or 'knobs 3.

6 The alterations identified include : 1. A visible change of shape and reduced deformability 2. The presence of electron- dense protrusions or 'knobs 3. The presence of small depressions, or "caveolae", at the surface of the red cell, connected by a network of small vesicles and clefts in P. vivax and P. ovale

7 The alterations identified include : 4. The cytoadherence to endothelial cells 5. The adherence to normal erythrocytes ("rosetting") or to other infected erythrocytes ("auto- agglutination or clumping) 6. The presence of new metabolic channels; evidence of new parasite- specific antigens associated with the red cell membrane

8 Pathogenesis Related to erythrocytic infection by the asexual stages, Gametocytes not involve in pathogenesis Pathology is associated with: Haemolysis - Direct invasion & rupture of RBC during erythrocytic cycle - Increased osmotic fragility of RBC Increased adhesiveness of infected RBC - Increases with the maturity of the parasite (schizont > trophozoite) - Knob theory Release of pyrogens, toxin and cytokines Capillary permeability Tissue hypoxia Immunological responses

9 Pathogenesis Rosetting Sequestration Sludging

stickier Cytokines can induce (mimic) many of symptoms and signs of malaria (shivering, headache, chills, spiking

10 Pathogenesis Cytoadherence seems to be the main culprit for pathogenesis Infected RBCs will adhere to the endothelium as well as to each other High cytokine levels induce expression of endothelial adhesins -- inflammation makes the endothelia stickier Cytokines can induce (mimic) many of symptoms and signs of malaria (shivering, headache, chills, spiking fever,sweating, vasodilation, hypoglycemia) Adherence and inflammation reinforce each other in an unholy circle causing pathology

11 Immunity Influenced by Genetics Age Health condition Pregnancy status Intensity of transmission in region Length of exposure Maintenance of exposure

12 Immunity Innate Red cell polymorphisms associated with some protection Hemoglobin S sickle cell trait or disease Hemoglobin C and hemoglobin E Thalessemia α α and β Glucose 6 phosphate dehydrogenase deficiency (G6PD) Red cell membrane changes Absence of certain Duffy coat antigens improves resistance to P.v.

13 Immunity Acquired Transferred from mother to child 3-6 months protection Then children have increased susceptibility Increased susceptibility during early childhood Hyper- and holoendemic areas By age 5 attacks usually < frequent and severe Can have > parasite densities with fewer symptoms Meso- or hypoendemic areas Less transmission and repeated attacks May acquire partial immunity and be at higher risk for symptomatic disease as adults

14 Immunity Acquired No complete immunity Can be parasitemic without clinical disease Need long period of exposure for induction May need continued exposure for maintenance Immunity can be unstable Can wane as one spends time outside endemic area Can change with movement to area with different endemicity Decreases during pregnancy, risk improves with increasing gravidity

15 Immune Mechanisms Stage specific : Anti sporozoite antibodies in adults in endemic areas- blocks liver invasion Anti sporozoite/merozoite antibodies - block rbc invasion Cytokines : TNF blocks merozoite development; IL1 ; IL10 Erythrocyte clearance - liver and spleen Block cyto-adherence Enhance clearance through opsonisation ADCC likely NK activity 15

17 Thank You

Malaria. An Overview of Life-cycle, Morphology and Clinical Picture

Malaria. An Overview of Life-cycle, Morphology and Clinical Picture Malaria An Overview of Life-cycle, Morphology and Clinical Picture Malaria Malaria is the most important of all tropical parasitic disease,causes death and debility and is endemic throughout the tropics