A Primate Model for Severe Human Malaria with Cerebral Involvement: Plasmodium coatneyi-Infected Macaca fuscata

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  • Department of Parasitology, Gunma University School of Medicine, Institute of Pathology, Case Western Reserve University, Maebashi, Japan

To develop an animal model for severe human malaria, we carried out clinical and pathologic observations of Japanese monkeys (Macaca fuscata) infected with Plasmodium coatneyi. Two monkeys, eight and nine months of age, were used in this experiment. After inoculation with the parasite, both monkeys developed a fulminating acute infection with high parasitemia (20–28.2%) and became moribund with typical signs of severe malaria. In the splenectomized Japanese monkey, sequestered infected erythrocytes blocked brain capillaries. Electron microscopic studies on brain tissues revealed electron-dense knobs protruding from the membrane of infected erythrocytes that formed focal junctions with the cerebral capillary endothelial cells. These findings were remarkably similar to those seen in human cases. Prominent sequestration of the infected erythrocytes was uniformly distributed in capillaries of the lungs and heart. The non-splenectomized Japanese monkey developed acute anemia with a packed cell volume of 6%, but blockage of brain capillaries was minimal. However, sequestered, infected erythrocytes were evident in capillaries of the heart and lungs of this animal. Our study showed that the Japanese monkey is highly susceptible to P. coatneyi infection and that this system provides a model for the study of severe human malaria.

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