Malaria

Question 0

Describe the exoerythrocytic life cycle

Answer 0

Sporozoites in blood stream -> Enter hepatocytes -> schizogony -> schizont ruptures, merozoites released -> invade erythrocyte

Exoerythrocytic life cycle begins after sporozoites have been inoculated into the blood stream. They circulate to the liver where they penetrate hepatocytes. Once inside, they undergo schizogony, creating thousands of merozoites. This forms a cyst known as schizont that eventually ruptures to release all the merozoites that are prepared to invade erythrocytes due to protein surface expression, such as MSP1

Question 1

What are the 4 species that cause malaria in humans?

Name their vector

Answer 1

Plasmodium falciparum (most mortality), Plasmodium vivax, Plasmodium ovale & Plasmodium malarie.
The vector for the disease is the mosquito Anopheles

Question 2

Describe the intraerythrocytic cycle

Answer 2

Merozoite enters -> 12-18h ‘ring’ phase -> trophozoite -> schizogony -> schizont forms, ruptures cell -> merozoites enter circulation ALT -> ‘ring’ phase -> gametocytogenesis

Once a merozoite has bound to a receptor on an erythrocytes and gained entry, it can then begin the next phase. First it enters the ‘ring’ stage and between 12-18h move onto the trophozoite form. Multiplication by schizogony leads to the formation of a schizont, containing merozoites. Eventually the cell ruptures, releasing parasites into the bloodstream to start the cycle again OR, some may undergo gametocytogenesis

Question 3

Describe the process of gametocytogenesis and explain how this completes the life cycle

Answer 3

Gametocytogenesis -> gametocytes ingested -> transform to gametes in midgut -> gametes fuse, zygote forms -> zygote transforms to ookinete -> ookinete leaves and penetrates gut -> schizogony -> rupture of schizont to release sporozoites -> migrate to salivary gland -> differentiate to infective

After the intraerythrocyctic cycle, some merozoites mature into male and female gametocytes (micro- and macro- respectively). These are ingested by a feeding Anopheles and end up in the peritrophic membrane, contained within the midgut. The acidic conditions and drop in temperature in the midgut cause the release of the gametocytes from the erythrocytes. These then transform into gametes that fuse, forming a zygote. The zygotes then differentiate into a motile ookinete that invades the gut lining of the mosquito and forms an oocyst. Schizogony follows, creating multiple sporozoites until the oocyst ruptures. The sporozoites then migrate toward the salivary glands, where a final stage of differentiation turns them into infective sporozoites that wait for inoculation

Question 4

Uncomplicated malaria: phases and causes

Answer 4

Uncomplicated: cold phase - shivering, head aches, nausea, vomiting, rise in BT
Hot phase - rise in BT to 39.5-40°C
Sweating phase - fall in BT accompanied by fatigue and weakness
Other symptoms: fever, chills, general malaise, splenomegaly, hepatomegaly
Cause: waste substances (hemozoin, glucose phosphate isomerase) and erythrocyte debris cause activation of mø, prompting severe immune response and cytokine release

Question 5

Complicated malaria: symptoms and causes (give a least five symptoms)

Answer 5

Caused by Plasmodium falciparum.
Severe anaemia due to RBC destruction
Ischemia due to less O2 transportation
PfEMP1 expression causes ‘knob’ formation on RBC. These adhere to epithelial cells (cytoadherence) and can cause non-infected RBC to bind (rosetting). Both these factors slow blood flow and can cause occlusions, resulting in acidosis and decreased O2
Depending on occlusion, patients can suffer from organ failure, pulmonary oedema, and haemorrhaging.
Parasites present in brain can also cause swelling, inducing coma, paralysis and death.
Haemoglobinuria (black water fever) due to increased haemoglobin in the blood
Hepatomegaly/splenomegaly due to resident mø in the organs phagocytosing all the cellular debris