Life cycle of malaria parasites

There are over 170 described species of Plasmodium, which infect mammals, birds and a wide variety of reptiles. The life-cycle of malaria parasites (in the genus Plasmodium) includes several rounds of asexual replication in a vertebrate host and sexual reproduction in a dipteran vector (often mosquitoes). Different types of parasite life-history stages accomplish these tasks; asexually replicating stages cannot survive when taken up by a vector and sexually reproducing stages only replicate in their vector.

When an infected vector bites a host, it injects infective stages that travel into the new host's tissues (the liver in mammals) and each infective stage starts to replicate asexually. After several rounds of replication, red blood cell invading stages are released into the circulation. These blood-stage parasites replicate asexually and disease symptoms develop (anaemia, weight loss and cerebral malaria in some cases).

For every parasite replication cycle a small proportion of these asexually produced parasites develop into male or female sexual stages (gametocytes). When a vector takes an infected blood meal the gametocytes rapidly differentiate into gametes and fertilization occurs within about twenty minutes.

The resulting zygotes undergo a series of morphological transformations to establish infections in their vector, leading to the formation of thousands of parasites that migrate to the salivary glands ready for transmission to new hosts.

Mating in malaria parasites

When taken up in a vector's blood meal, gametocytes must leave the relative safety of their red blood cells and rapidly differentiate into gametes. Each male gametocyte can differentiate into up to eight gametes whereas each female gametocyte can only differentiate into a single gamete.

To make their gametes male gametocytes must leave their red blood cells, replicate their DNA in 3 rounds of mitosis, synthesise 8 flagella, and attach each genome to a flagellum. Conversely, female gametocytes become gametes once they have left their red blood cells and are subsequently located and fertilised by male gametes.

Blood meals are a challenging mating environment because blood is rapidly cooling and possibly starting to clot. Red blood cells are packed in tightly and moving around the midgut. Furthermore, when gametocytes leave the relatively protective environment of their red blood cells they become exposed to host derived transmission-blocking immune factors.

These pressures mean that fertilisation must occur within a very brief (20min) time window and this, coupled with the low fecundity of male gametocytes, makes the mating system of malaria parasites quite unusual.

Why we use rodent malaria parasites

To disentangle variation due to parasite phenotypic plasticity from less interesting constraints imposed on parasites by different types of in-host environment, it is ideal to study parasites in common environments. The rodent malarias are amenable in this regard as infections can be initiated in the same host genotype and replicate infections can be initiated for each parasite genotype under investigation. A bank of genotypes (clonal isolates) exist for these species and during their acute infections they vary in traits such as maximum parasite and gametocyte density, and the degree of harm caused to their hosts in terms of weight loss, anaemia and mortality risk.