Immune Recognition of Plasmodium-Infected Erythrocytes

Over 40% of the worlds population is currently at risk of exposure to malaria with children being at greatest risk of developing severe disease1 and it is estimated that between 1.5 and 3 millions deaths per year are due to malaria.2 Infection can result in asymptomatic parasitemia or clinical syndromes ranging from a mild febrile illness to severe malaria characterised by acidosis, severe anaemia or cerebral complications.3 Approximately 10% of infections result in severe disease with a high fatality rate especially in nonimmune children and adults. Malaria is caused by the parasitic protozoa from the genus Plasmodium and is transmitted by the bite of infected female Anopheles mosquitoes. There are four species of Plasmodium that infect humans; of these, Plasmodium falciparum is responsible for the greatest morbidity and mortality. During the bite of an infected mosquito, sporozoites are injected into the bloodstream of the human host. They then rapidly migrate to the liver and invade hepatocytes. In the subsequent 5 to 10 days, parasites differentiate and multiply within the hepatocytes and finally 20,000 to 40,000 merozoites are released into the bloodstream that invade erythrocytes. During the intraerythrocytic phase of infection, parasites develop and multiply over 48 hours in the erythrocyte. When the infected red blood cell (iRBC) bursts 15–32 merozoites per erythrocyte are released, which invade erythrocytes to begin a new cycle. Parasite multiplication continues until it is controlled by the immune response or drug treatment and it is during this repeated intraerythrocytic cycle that symptoms of disease develop. A small proportion of iRBCs undergo differentiation into either male or female gametocytes, which are subsequently taken up in a mosquito blood meal. In the mosquito mid-gut, the male and female gametes are released and fuse to form a zygote, which then undergoes a series of complicated differentiation, and growth stages that results in the production of infective sporozoites in the salivary glands of the mosquito.