Malaria

Malaria Life
Cycle
Life Cycle

Sporogony
Oocyst
Sporozoites

Mosquito Salivary
Gland

Zygote

Exoerythrocytic
(hepatic) cycle

Gametocytes

Erythrocytic
Cycle

Schizogony

Hypnozoites
(for P. vivax
and P. ovale)

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
P.ovale

Infectes only young or

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 electrondense 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 :

The cytoadherence to endothelial cells
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 parasitespecific antigens associated with the red
cell membrane
4.
5.

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 and
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 areasblocks 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

Thank You