Malaria Malaria Malaria translates Latin as bad air reflects ancient belief disease was caused by fetid air emanating from swamps which can be habitats for Anopheles mosquitoes Disease is caused by several species of the apicomplexan protozoan parasite Plasmodium vectored by certain species of Anopheles mosquitoes WHO estimate of global number of cases 1976 365 million cases 1 000 000 deaths 2010 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 years Complicating 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 mortality Note differences in erythrocytic cycle i e in red blood cells sequestration and relapses more on each of these in a couple of slides Incubation period refers to the intrinsic incubation period 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 species can 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 emerge months to years later to initiate blood erythrocytic stages These 2 are temperate zone species and this strategy allows the parasites to persist through seasons when mosquito vectors are absent In some cases some parasites go directly to the erythrocytic stages causing disease and others become dormant and emerge later causing relapse Plasmodium Life Cycle Symptoms cycle repeats For all species extreme fever alternating with extreme chills brief period without either then Related to the erythrocytic red blood cell cycle merozoites emerge from infected red blood cells 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 in chills Duration of fever chills cycle is different for different malaria species see slide 3 Each cycle 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 spontaneous abortion low birth weight babies correlated with poor survivorship increased likelihood of impaired mental development Symptoms Falciparum malaria Plasmodium falciparum but not the other species produces VAR proteins that are exported to the 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 is referred to as sequestration as in the table in slide 3 or sometimes rosetting as the cells may clump together forming rosettes Infected erythrocytes accumulating in capillaries can block blood flow starving downstream tissues 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 In areas with constant endemic malaria transmission two main groups of people are most at Falciparum malaria continued risk 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 na ve and are prone to develop severe infections and cerebral malaria After about five years in areas with endemic malaria transmission most individuals have had exposure to a large fraction of the parasite strains genotypes in their area and develop a partial immunity that does not prevent infection but that does lead to less severe disease without mortality