Malaria

Malaria Life Sporogony

Cycle Oocyst

Life Cycle Sporozoites

Mosquito Salivary
Zygote Gland

Hypnozoites
Exo- (for P. vivax
and P. ovale)
erythrocytic
(hepatic) cycle
Gametocytes

Erythrocytic
Cycle

Schizogony
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.
 Affinity of Parasite to Erythrocytes

• P.vivax
• P.malariae Infectes only young or
• P.ovale Old Erythocytes

• P.falciparum Infects all age groups

 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 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
 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
 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
 Pathogenesis

Rosetting

Sequestration

Sludging
 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
 Immunity
Influenced by
– Genetics
– Age
– Health condition
– Pregnancy status
– Intensity of transmission in region
– Length of exposure
– Maintenance of exposure
 Immunity
Innate
– Red cell polymorphisms associated with some
protection
• Hemoglobin S sickle cell trait or disease
• Hemoglobin C and hemoglobin E
• Thalessemia – α and β
• Glucose – 6 – phosphate dehydrogenase deficiency
(G6PD)
– Red cell membrane changes
• Absence of certain Duffy coat antigens improves
resistance to P.v.
 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
 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
 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
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