Overview of Plasmodium spp. and Animal Models in Malaria Research

Abstract

Malaria is a parasitic disease caused by protozoan species of the genus Plasmodium and transmitted by female mosquitos of the genus Anopheles and other Culicidae. Most of the parasites of the genus Plasmodium are highly species specific with more than 200 species described affecting different species of mammals, birds, and reptiles. Plasmodium species strictly affecting humans are P. falciparum, P. vivax, P. ovale, and P. malariae. More recently, P. knowlesi and other nonhuman primate plasmodia were found to naturally infect humans. Currently, malaria occurs mostly in poor tropical and subtropical areas of the world, and in many of these countries it is the leading cause of illness and death. For more than 100 y, animal models, have played a major role in our understanding of malaria biology. Avian Plasmodium species were the first to be used as models to study human malaria. Malaria parasite biology and immunity were first studied using mainly P. gallinaceum and P. relictum. Rodent malarias, particularly P. berghei and P. yoelii, have been used extensively as models to study malaria in mammals. Several species of Plasmodium from nonhuman primates have been used as surrogate models to study human malaria immunology, pathogenesis, candidate vaccines, and treatments. Plasmodium cynomolgi, P. simiovale, and P. fieldi are important models for studying malaria produced by P. vivax and P. ovale, while P. coatneyi is used as a model for study- ing severe malaria. Other nonhuman primate malarias used in research are P. fragile, P. inui, P. knowlesi, P. simium, and P. brasilianum. Very few nonhuman primate species can develop an infection with human malarias. Macaques in general are resistant to infection with P. falciparum, P. vivax, P. malariae, and P. ovale. Only apes and a few species of New World monkeys can support infection with human malarias. Herein we review the most common, and some less common, avian, reptile, and mammal plasmodia species used as models to study human malaria.

Figure 1.

Plasmodium life cycle. 1) Malaria infection begins when an infected female Anopheles mosquito bites a person, injecting Plasmodium parasites, in the form of sporozoites, into the bloodstream. 2) The sporozoites pass quickly into the human liver. 3) The sporozoites multiply asexually in the liver cells during the next 7 to 10 d, causing no symptoms. 4) In animal models, and probably in humans, the parasites, in the form of merozoites, are released from the liver cells in vesicles, journey through the heart, and arrive in the lungs, where they settle within lung capillaries. The vesicles eventually disintegrate, freeing the merozoites to enter the blood phase of their development. 5) In the bloodstream, the merozoites invade erythrocytes and multiply again until the cells burst. Then, they invade more erythrocytes. This cycle is repeated, causing fever each time parasites break free and invade red blood cells. 6) Some of the infected red blood cells leave the cycle of asexual multiplication. Instead of replicating, the merozoites in these cells develop into sexual forms of the parasite, called gametocytes, that circulate in the blood stream. 7) When a mosquito bites an infected human, it ingests the gametocytes, which develop further into mature sex cells called gametes. 8) The fertilized female gametes develop into actively moving ookinetes that burrow through the mosquito’s midgut wall and form oocysts on the exterior surface. 9) Inside the oocyst, thousands of active sporozoites develop. The oocyst eventually bursts, releasing sporozoites into the body cavity that travel to the mosquito’s salivary glands. 10) The cycle of human infection begins again when the mosquito bites another person. This figure was reproduced/adapted with permission from the Malaria Vaccine Initiative Web site at https://www.malariavaccine.org, 2015.