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Malaria*Malaria“Malaria” translates (Latin) as “bad air”; reflects ancient belief disease was caused by fetid airemanating from swamps (which can be habitats for Anopheles mosquitoes!)Disease is caused by several species of the apicomplexanprotozoan parasite Plasmodium, vectored by certain species ofAnopheles mosquitoesWHO estimate of global number of cases:1976: 365 million cases, ~1,000,000 deaths2010: 239 million (“Roll Back Malaria” program)2015: 212 million (21% decrease since 2010)2018: 228 million (405,000 deaths)2020: 241 million (627,000 deaths)Progress towards malaria control has reversed in recent yearsComplicating factors: drug & insecticide resistance, Covid disruptions*Four species of Plasmodium cause malaria in humans:All 4 species are specific to humans (anthroponoses).*Only P. falciparum causes significant mortalityNote differences in erythrocytic cycle (i.e. in red blood cells), sequestration, and relapses (moreon each of these in a couple of slides). “Incubation period” refers to the intrinsic incubationperiod (from infection to disease in humans).Historically, malaria occurred throughout the tropics and much of the temperate zones as well.The vector: the mosquito genus Anopheles*Mainly A. gambiae species complex in Africa, A. stephensi in SE Asia, but many other speciescan have a role such as A. quadrimaculatus in North America.P. vivax and P. ovale: parasites can enter a dormant stage (hypnozoite) in the liver; emergemonths to years later to initiate blood (erythrocytic) stages.These 2 are temperate zone species and this strategy allows the parasites to persist throughseasons when mosquito vectors are absent. In some cases some parasites go directly to theerythrocytic stages (causing disease) and others become dormant and emerge later (causingrelapse).Plasmodium Life Cycle*Symptoms:For all species: extreme fever alternating with extreme chills, brief period without either, thencycle repeats.Related to the erythrocytic (red blood cell) cycle: merozoites emerge from infected red bloodcells in a coordinated manner (i.e. all at the same time), then invade new erythrocytes.Emergence (and release of contents from lysed erythrocytes) stimulates release of pyrogenic(fever-causing) factors in the body, including TNF-a.Clearance of extracellular parasites from the blood (as they enter new erythrocytes) results inchills.Duration of fever/chills cycle is different for different malaria species (see slide 3). Eachcycle leaves the patient progressively more exhausted.Each cycle destroys more red blood cells, leading to anemia.Anemia (and maybe other effects in the placenta) lead to increased rate of spontaneousabortion, low birth weight babies (correlated with poor survivorship, increased likelihood ofimpaired mental development).*Symptoms: Falciparum malariaPlasmodium falciparum (but not the other species) produces VAR proteins that are exported tothe erythrocyte (red blood cell) membrane.These proteins allow the infected erythrocytes to stick to the endothelial cells lining capillaries.Presumably this functions to prevent infected erythrocytes from circulating through the spleen,where they may be recognized as abnormal and destroyed (along with the parasites). This isreferred to as sequestration (as in the table in slide #3), or sometimes “rosetting” (as the cellsmay clump together, forming “rosettes”).Infected erythrocytes accumulating in capillaries can block blood flow, starving downstreamtissues of blood. Capillaries are especially abundant in brain tissue, so this effect can lead to*cerebral malaria, a major cause of death, especially in children.Falciparum malaria continuedIn areas with constant (endemic) malaria transmission, two main groups of people are most atrisk of dying of falciparum malaria:Children under the age of five*.Young children have had limited time to build up immunological tolerance to the parasite(i.e. they are immunologically naïve), and are prone to develop severe infections and cerebral*malaria. After about five years (in areas with endemic malaria transmission) most individualshave had exposure to a large fraction of the parasite strains (genotypes) in their area, and developa partial immunity that does not prevent infection, but that does lead to less severe diseasewithout

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GSU ECE 6660 - Malaria

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