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A nonhuman primate model for human cerebral malaria: rhesus monkeys experimentally infected with Plasmodium fragile
1Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106.
Abstract:
We studied the brains of rhesus monkeys infected with the primate malaria parasite Plasmodium fragile. Electron microscopy showed that, in these animals, erythrocytes infected with P. fragile undergo sequestration and that parasitized red blood cells adhere to endothelial cells in the cerebral microvessels by means of knobs. Cerebral microvessels with sequestered parasitized red blood cells were shown by immunohistochemical analysis to possess the platelet glycoprotein CD36, thrombospondin, and intracellular adhesion molecule-1. The formation of rosettes also was observed in the cerebral microvessels. In a fashion similar to human cerebral malaria, P. fragile produced neurological symptoms in the animals. Thus, rhesus monkeys infected with P. fragile, like those monkeys infected with Plasmodium coatneyi, can be used as a primate model to study human cerebral malaria.
Insights
Rhesus monkeys infected with Plasmodium fragile exhibit cerebral malaria symptoms. This primate model, showing sequestered infected red blood cells in brain microvessels, aids research into human cerebral malaria.
Area of Science:
- Neuroscience
- Infectious Diseases
- Primatology
Background:
- Cerebral malaria is a severe complication of Plasmodium falciparum infection in humans.
- Primate models are crucial for understanding the pathogenesis of human cerebral malaria.
- Plasmodium fragile is a primate malaria parasite that can infect rhesus monkeys.
Purpose of the Study:
- To investigate the pathological mechanisms of cerebral malaria in rhesus monkeys infected with Plasmodium fragile.
- To evaluate the utility of Plasmodium fragile-infected rhesus monkeys as a model for human cerebral malaria.
Main Methods:
- Electron microscopy to examine brain microvessels.
- Immunohistochemical analysis to identify adhesion molecules.
- Observation of neurological symptoms in infected animals.
Main Results:
- Plasmodium fragile-infected erythrocytes sequestered in cerebral microvessels.
- Parasitized red blood cells adhered to endothelial cells via knobs.
- Cerebral microvessels expressed CD36, thrombospondin, and ICAM-1.
- Rosette formation was observed in cerebral microvessels.
- Neurological symptoms consistent with human cerebral malaria were present.
Conclusions:
- Plasmodium fragile infection in rhesus monkeys mimics key pathological features of human cerebral malaria.
- Rhesus monkeys infected with Plasmodium fragile serve as a valuable primate model for studying human cerebral malaria.
- This model can advance research into the mechanisms and potential treatments for cerebral malaria.