Fig. 2

Plasmodium life cycle. After a mosquito bite, malaria parasites are deposited into the host’s skin and within minutes are carried via the bloodstream into the liver, where through asexual proliferation within the hepatocytes tens of thousands of merozoites are produced. Following hepatocyte rupture, merozoites are released into the bloodstream where they can invade the host’s red blood cells (RBC), leading to the initiation of the intra-erythrocytic development cycle (IDC). During the IDC (lasting about 48–72 h in human and about 24 h in rodent malaria parasites), Plasmodium parasites multiply asexually through the completion of several morphologically distinct stages within the RBCs. After RBC invasion, malaria parasites develop via the ring and trophozoite stage into schizonts, each containing a species-specific number of merozoites (typically 10–30). Upon schizont rupture, merozoites are released into the bloodstream, where they can invade new RBCs and initiate a new IDC. However, a small fraction of ring-stage parasites sporadically differentiate into male or female gametocytes, which are responsible for initiating transmission back to the mosquito. Through another mosquito blood meal gametocytes are taken up into the mosquito midgut where they are activated and form male (eight per gametocyte) and female (one) gametes. Following fertilization, the zygote undergoes meiosis (and therefore true sexual recombination) and develops into a motile, tetraploid ookinete that traverses the midgut and forms an oocyst. Via another round of asexual proliferation inside the oocyst several thousands of new haploid sporozoites are generated that, upon their release, colonize the mosquito salivary glands, poised to initiate a new infection of another mammalian host