The answer is c. Recurrent fever of malaria is caused by successive waves of merozoite release from red blood cells.
Malaria is caused by Plasmodium species of protozoan parasites, transmitted from person to person by the bites of female Anopheles mosquitos.
When a malaria carrying, mosquito bites a human, Plasmodium sporozoites enter the bloodstream with the mosquito saliva (fig 1). The sporozoites migrate to the liver, invade hepatocytes where they rapidly grow and multiply to form thousands of merozoites. After around 5-7 days the hepatocyte ruptures releasing merozoites into the circulation. Sporozoites of vivax and ovale malaria can enter a dormant stage within the liver – where they are known as hypnozoites – with reactivation and hepatocyte rupture up to 5 years later (recurrent bouts of illness years apart therefore sometimes characterise these types of malaria).
Circulating merozoites invade red blood cells where they become trophozoites. The trophozoites initially enlarge through feeding on erythrocyte haemoglobin to form a multinuclear schizont. The schizont then asexually multiplies by several fold division to form new infective particles (more merozoites) in a process known as schizogeny.
After 2 – 3 days, red cell rupture releases even more merozoites into circulation (Figure 1), which go on to infect further red cells and the erythrocytic cycle repeats. The cyclical fever of malaria coincides with the synchronised release of merozoites into the blood stream. The proportion of red cells infected with malaria parasites is called the parasitaemia.
Some trophozoites, instead of undergoing schizogeny, can transform into sausage-shaped structures known as gametocytes. These are infective to any mosquito that might bite the patient, and exist in male and female forms. Gametocytes undergo sexual reproduction within the mosquito gut to produce more sporozoites which migrate to the mosquito salivary glands and infect further humans during subsequent mosquito feeds.
P. falciparum is the most dangerous of the malaria parasites because the merozoites infect young red cells, and with each schizogeny the parasite count can rise higher and higher. The life-threatening complications of falciparum malaria – cerebral malaria, pulmonary oedema and renal failure (blackwater fever) – relate to schizogeny, during which infected red cells adhere to capillary walls, obstructing the microvasculature of the brain, lungs and kidney. Other serious complications include severe haemolytic anaemia (considered <5g/dL) and shock (algid malaria).
- Figure 1. Plasmodium life cycle