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It has been recognized since ancient times that malaria fever is highly periodic but the mechanism has been poorly understood. Malaria fever is related to the parasite growth cycle in erythrocytes. After a fixed period of replication, a mature parasite (schizont) causes the infected erythrocyte to rupture, releasing progeny that quickly invade other erythrocytes. Simultaneous rupture of a large number of schizonts stimulates a host fever response. Febrile temperatures are damaging to Plasmodium falciparum, particularly in the second half of its 48-hr replicative cycle. Using a mathematical model, we show that these interactions naturally tend to generate periodic fever. The model predicts chaotic parasite population dynamics at high multiplication rates, consistent with the classical observation that P. falciparum causes less regular fever than other species of parasite.

Original publication





Publication Date





5111 - 5113


Institute of Molecular Medicine, Oxford University, John Radcliffe Hospital, United Kingdom.


Animals, Humans, Plasmodium, Plasmodium falciparum, Plasmodium malariae, Plasmodium vivax, Malaria, Fever, Species Specificity, Host-Parasite Interactions