Box 15.1. Life cycle of Plasmodium
The malarial cycle, shown here modified after Kettle (1984) and Katz et al. (1989), commences with an infected female Anopheles mosquito taking a blood meal from a human host (H). Saliva contaminated with the sporozoite stage of the Plasmodium is injected (a). The sporozoite circulates in the blood until reaching the liver, where a pre- (or exo-) erythrocytic schizogonous cycle (b, c) takes place in the parenchyma cells of the liver. This leads to the formation of a large schizont, containing from 2000 to 40,000 merozoites, according to Plasmodium species. The prepatent period of infection, which started with an infective bite, ends when the merozoites are released (c) to either infect more liver cells or enter the bloodstream and invade the erythrocytes. Invasion occurs by the erythrocyte invaginating to engulf the merozoite, which subsequently feeds as a trophozoite (e) within a vacuole.
The first and several subsequent erythrocyte schizogonous (d—f) cycles produce a trophozoite that becomes a schizont, which releases from 6 to 16 merozoites (f), which commence the repetition of the erythrocytic cycle. Synchronous release of merozoites from the erythrocytes liberates parasite products that stimulate the host’s cells to release cytokines (a class of immunological mediators) and these provoke the fever and illness of a malaria attack. Thus, the duration of the erythrocyte schizogonous cycle is the duration of the interval between attacks (i.e. 48 h for tertian, 72 h for quartan).
After several erythrocyte cycles, some trophozoites mature to gametocytes (g,h), a process that takes eight days for P. falciparum but only four days for P. vivax. If a female Anopheles (M) feeds on an infected human host at this stage in the cycle, she ingests blood containing erythrocytes, some of which contain both types of gametocytes. Within a susceptible mosquito the erythrocyte is disposed of and both types of gametocytes (i) develop further: half are female gametocytes, which remain large and are termed macrogametes; the other half are males, which divide into eight flagellate microgametes ( j), which rapidly deflagellate (k), and seek and fuse with a macrogamete to form a zygote (l). All this sexual activity has taken place in a matter of 15 min or so while within the female mosquito the blood meal passes towards the midgut. Here the initially inactive zygote becomes an active ookinete (m) which burrows into the epithelial lining of the midgut to form a mature oocyst (n—p).
Asexual reproduction (sporogony) now takes place within the expanding oocyst. In a temperature- dependent process, numerous nuclear divisions give rise to sporozoites. Sporogony does not occur below 16°C or above 33°C, thus explaining the temperature limitations for Plasmodium development noted in section 15.5.1. The mature oocyst may contain 10,000 sporozoites, which are shed into the hemocoel (q), from whence they migrate into the mosquito’s salivary glands ®. This sporogonic cycle takes a minimum of 8–9 days and produces sporozoites that are active for up to 12 weeks, which is several times the complete life expectancy of the mosquito. At each subsequent feeding, the infective female Anopheles injects sporozoites into the next host along with the saliva containing an anticoagulant, and the cycle recommences.