k23. kuliah malaria blok tropmed.ppt

8/10/2019 K23. Kuliah Malaria Blok Tropmed.ppt

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Malaria


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Exo-erythrocytic(hepatic) cycle

Sporozoites

Mosquito SalivaryGland

Malaria LifeCycleLife Cycle

Gametocytes

Oocyst

ErythrocyticCycle

Zygote

Schizogony

Sporogony

Hypnozoites(for P. vivaxand P. ovale)


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Plasmodium spp.1. Plasmodium vivax : Benign Tertian, Tertian

Malaria

2. Plasmodium ovale : Ovale tertian Malaria3. Plasmodium malariae : Quartan malaria

4. Plasmodium falciparum : Malignant Tertian

malaria.


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Affinity of Parasite to Erythrocytes

P.vivax

P.malariae Infectes only young or

P.ovale Old Erythocytes

P.falciparum Infects all age groups


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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.


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1. A visible change of shape andreduced deformability

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

3. The presence of smalldepressions, or "caveolae", atthe surface of the red cell,connected by a network of

small vesicles and clefts in P.vivaxand P. ovale

The alterations identified include :


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4. The cytoadherence to endothelial cells

5. The adherence to normal erythrocytes

("rosetting") or to other infected

erythrocytes ("auto-agglutinationor

clumping)

6. The presence of new metabolic

channels; evidence of new parasite-

specific antigens associated with the redcell membrane

The alterations identified include :


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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 Immunological responses

Capillary permeability

Tissue hypoxia


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Rosetting

Sludging

Sequestration

Pathogenesis


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Pathogenesis

Cytokines can induce (mimic) many of symptoms and signs ofmalaria (shivering, headache, chills, spiking fever,sweating,vasodilation, hypoglycemia)

Adherence and inflammation reinforce each other in an unholy

circle causing pathology

Cytoadherence seems to be the main culprit forpathogenesis

Infected RBCs will adhere to the endothelium aswell as to each other

High cytokine levels induce

expression of endothelialadhesins -- inflammationmakes the endotheliastickier


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Immunity

Influenced by

Genetics

Age

Health condition Pregnancy status

Intensity of transmission in region

Length of exposure Maintenance of exposure


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Immunity

Innate Red cell polymorphisms associated with some

protection

Hemoglobin S sickle cell trait or disease

Hemoglobin C and hemoglobin E Thalessemia and

Glucose6phosphate dehydrogenase deficiency(G6PD)

Red cell membrane changes Absence of certain Duffy coat antigens improves

resistance to P.v.


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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 riskfor symptomatic disease as adults


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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


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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


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Thank You

k23. kuliah malaria blok tropmed.ppt

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