- Malaria, an intracellular parasite, is of widespread importance in the world
- When an infected Anopheles mosquito bites a human, it injects sporozoites into the small blood vessels.
- Sporozoites migrate to the liver where they infect hepatocytes, after which the parasite develops into a multinucleate liver stage (schizont) that contains merozoites (Figure 1).
- This stage is referred to as exoerythrocytic schizogony and may occur with a single infecting parasite (e.g., P. falciparum) or with multiple organisms (e.g., P. vivax, Povale).
- The mature schizonts eventually rupture, releasing thousands of uninucleate merozoites into the bloodstream, each of which can infect a red blood cell.
- Within the red blood cell, the merozoite develops to form either an erythrocytic stage (blood stage) schizont or a spherical or banana-shaped uninucleate gametocyte.
- The gametocyte, which is the sexual stage of the parasite, is infectious for mosquitoes that ingest it while feeding.
- Within the mosquito, gametocytes develop into female and male gametes (macrogametes and microgametes, respectively), which undergo fertilization and then develop into sporozoites that can infect humans.
- Symptoms of malaria include fever, chills, arthralgia, vomiting, anemia caused by hemolysis, hemoglobinuria, and convulsions.
- There may be the feeling of tingling in the skin, particularly with malaria caused by P falciparum.
- The classical symptom of malaria is a cyclical fever pattern occurring every two days in P. falciparum, P. vivax, and P. ovale infections (tertian fever).
- Severe malaria is almost exclusively caused by P. falciparum infection and is associated with coma and death if untreated.
- Splenomegaly, severe headache, cerebral ischemia, hepatomegaly, and hemoglobinuria with renal failure, i.e., black water fever, may also be seen in severe malaria.
- Young children and pregnant women are especially vulnerable.
- Chronic malaria is seen in both P. vivax and P. ovale infections, but not in P. falciparum, where only the acute fulminating form is usually observed.
- In the chronic form of malaria, the disease can relapse months or years after initial infection, with recurrent waves of parasitemia emanating from the persistence of latent parasites in the liver.
- Hosts can mount a level of protective immunity, which can occur following initial infection and render the host shielded against subsequent disease.
- Individuals who are repeatedly exposed to malaria develop antibodies against the sporozoite, liver-stage, blood-stage, and/or sexual-stage malaria antigens.
- It is thought that antibodies acting directly against these antigens are responsible for the decreased susceptibility to malaria infection and disease seen in adults in malaria-infested areas.
- Antibodies directed against the sexual stages of plasmodia may also reduce malaria transmission.
- Additional components of naturally acquired immunity include the release of cytokines that act against all stages of the parasite and also a cytotoxic T cell response directed at liver stages of the parasite.
- Below are some of the presumed mechanisms of adaptive immunity to malaria.
- Antibodies block invasion of sporozoites into liver cells.
- IFN-y and CD8 T cells inhibit parasite development in hepatocytes.
- Antibodies block invasion of merozoites into erythrocytes.
- Antibodies prevent sequestration of infected erythrocytes by preventing binding to adhesion molecules on the vascular endothelium.
- IFN-y and CD4+ T cells activate macrophages to phago-cytose intra-erythrocytic parasites and free merozoites.
- Antibodies neutralize parasite glycosylphosphatidylinositol and inhibit induction of the inflammatory cytokine cascade.
- Antibodies mediate complement-mediated cytolysis of extracellular gametes and prevent fertilization of gametes and the development of zygotes. (From Stevenson MM, Riley EM. Innate immunity to malaria. Nat Rev Immunol. 2004;4:169-80)
Jeff Dorfman, University of Cape Town – The Immune Mechanisms of Fighting a Malaria Infection
Immunopaedia case study
Test your knowledge for this section – Online Quiz