Snapshot A 25-year-old woman presents to the clinic with a one-week history of continuous high-grade fevers, myalgia, chills, and night sweats. She recently returned to the United States after volunteering with the Peace Corps in Nigeria. Her temperature is 103.2°F (39.6°C) and physical reveals a palpable spleen. A peripheral blood smear is shown. Introduction Epidemiology geography endemic throughout most of the tropics disproportionately high burden of malaria in Sub-Saharan Africa prevalence WHO estimated 216 million cases of malaria in 91 countries in 2016 risk factors exposure to Anopheles mosquitos, particularly at dusk and dawn Pathogenesis transmission through bites of female Anopheles mosquitos Plasmodium life cycle involves two hosts: human and Anopheles mosquito human host sporozoite stage the Plasmodium-infected Anopheles mosquito inoculates sporozoites into the human host during a blood meal sporozoites infect hepatocytes and mature into schizonts, which rupture and release merozoites hypnozoite stage for Plasmodium vivax and Plasmodium ovale, a dormant stage (hypnozoites) can persist in the liver and cause relapses merozoite and trophozoite stage merozoites undergo asexual multiplication in erythrocytes merozoites reform to become trophozoites, which are ring-shaped schizont stage trophozoites undergo division to form large multi-nucleated schizonts the schizont ruptures releasing merozoites rupture of erythrocytes correlates with fever spikes gametocyte stage some parasites differentiate into sexual gametocytes, which are the form of the parasite that is ingested by an Anopheles mosquito Anopheles mosquito host oocyst stage male and female gametocytes fuse in the stomach of the mosquito to form an oocyst sporozoite stage the oocyst divides into many sporozoites, which are then inoculated into the human host to begin the cycle anew 4 main speces of Plasmodium cause malaria Plasmodium falciparum irregular fever patterns Plasmodium vivax 48-hour fever cycle Plasmodium ovale 48-hour fever cycle Plasmodium malariae 72-hour fever cycle Associated conditions occlusion of capillaries in the brain (cerebral malaria), kidneys, and lungs (Plasmodium falciparum) Presentation Symptoms fever headache anemia splenomegaly Physical exam palpable spleen conjunctival pallor Studies Labs Peripheral blood smear shows trophozoites and schizonts within erythrocytes trophozoite ring form within erythrocyte schizont containing merozoites red granules throughout cytoplasm in erythrocytes seen with Plasmodium vivax and Plasmodium ovale Making the diagnosis most cases are clinically diagnosed Differential Babesiosis differentiating factor predominantly in northeastern United States Trypanosomiasis differentiating factors lymphadenopathy, somnolence, coma Borrelia recurrentis differentiating factor history of tick exposure Treatment Medical chloroquine used in areas with low drug resistance mefloquine used in areas with high rates of chloroquine resistance atovaquone/proguanil or artemether-lumefantrine used in areas with high rates of chloroquine resistance first-line treatment for P. falciparum resistant to chloroquine primaquine used to kill latent hypnozoites in Plasmodium vivax and Plasmodium ovale infection intravenous quinidine or artesunate used in life-threatening situations Complications Cerebral malaria complication of Plasmodium falciparum infection parasitized erythrocytes occlude capillaries in the brain Renal failure complication of Plasmodium falciparum infection parasitized erythrocytes occlude capillaries in the kidney