ABSTRACT
The organism causing malaria is Plasmodium, a protozoan with a complex life cycle. There are five species of Plasmodium able to infect humans: P. ovale; P. vivax, P. malariae, P. knowlesi and P. falciparum which is the most virulent species. The female Anopheles mosquito is the vector for malaria. The lifecycle of Plasmodium spp. includes a liver stage and erythrocyte stage. Gametocytes are produced that are released into the blood. When another mosquito feeds, it ingests the gametocytes and, in the stomach, they fuse to form a zygote, which becomes an oocyte. The oocytes mature into sporozoites which migrate to the salivary gland of the mosquito and are inoculated into another human when the mosquito feeds. And so the cycle starts again. In 2020, there were an estimated 241 million malaria cases. Children under 5 are still the most vulnerable to infection. Pregnancy increases the risk of malaria. Asia, Latin America, the Middle East, and parts of Europe are also affected by malaria. Absence of the Duffy blood group antigen in West Africans, sickle cell trait, and glucose 6 phosphate dehydrogenase (G6PD) deficiency are examples of genetic factors associated with reduced infection rates for malaria. The parasite uses a number of “escape mechanisms” at both the liver stage and erythrocyte stages to avoid the immune response. These include different life cycle forms and direct immunosuppression by the parasite. Immune mechanisms differ against the various stages of the life cycle and include antibodies (and complement), phagocytosis, NK cells, γδ T cells and cytotoxic T cells. Pathogenesis occurs due to: (a) cytokine release leading to spikes of fever at regular intervals, (b) destruction of erythrocytes leading to anemia, and (c) obstruction of capillaries due to binding of erythrocytes, through parasite encoded surface molecules, to endothelium. In uncomplicated malaria, the first symptoms are fever, headache, chills, vomiting, muscle pains and diarrhea that appear 10–15 days after a person is infected. Cyclical temperature fluctuations coincide with the rupture of erythrocytes and the release of merozoites into the bloodstream which, during the erythrocytic stage, occurs every 48 hours for P. falciparum, P. ovale, and P. vivax, and every 72 hours for P. malariae. This gives rise to fevers of differing periodicity. Complications include cerebral malaria, where thrombosis may occur (with P. falciparum, severe anemia and blackwater fever). Co-infection by HIV with malaria increases the risk of both uncomplicated and severe disease. Three diagnostic tests are used, namely microscopic diagnosis on a blood film which is the gold standard, the rapid detection test (RDT) which detects malaria antigens in a person’s blood and molecular diagnosis using PCR. The two main approaches to malaria control are: drug treatment of infected patients and prevention and control of the vector. Most drug treatments target the erythrocytic stage of the infection. Following increased resistance of P. falciparum to chloroquine, the WHO recommends artemisinin-based combination therapies (ACTs). ACTs act not only on the asexual blood stages to alleviate symptoms but also on the gametes, therefore reducing the spread of the disease. Personal prevention measures include the use of indoor residual spraying (IRS), repellents (such as DEET) and wearing of light-colored clothes, long pants, and long-sleeved shirts and insecticide-treated bed nets (ITNs). Mosquito larval control uses oils applied to the water surface, toxins from Bacillus thuringiensis and insect growth regulators such as methpropene. Prophylactic drugs for international travelers depend on drug resistance in the endemic areas to be visited and include atovaquone-proguanil, doxycycline, mefloquine, tafenoquine and primaquine.
