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Johns Hopkins scientists discover what drives the development of a fatal form of malaria
Date:8/18/2008

Platelets those tiny, unassuming cells that cause blood to clot and scabs to form when you cut yourself play an important early role in promoting cerebral malaria, an often lethal complication that occurs mostly in children. Affecting as many as half a billion people in tropical and subtropical regions, malaria is one of the oldest recorded diseases and the parasite responsible for it, Plasmodium, among the most studied pathogens of all time. Still, cerebral malaria, which results from a combination of blood vessel and immune system dysfunction, is not well understood.

In a study described in the August 14 issue of Cell Host and Microbe, Johns Hopkins researchers reveal that when red blood cells are infected with the malaria parasite, they activate platelets to secrete the PF4 protein, which triggers the immune system to inflame blood vessels and obstruct capillaries in the brain; both are hallmarks of cerebral malaria.

In their experiments, the Hopkins team first infected human red blood cells in culture with the malaria parasite and found that this did, indeed, induce platelet activation.

The researchers then infected separate sets of live mice with the malaria parasite: one set treated so that it lacked platelets altogether and two others treated with aspirin or Plavix, platelet inhibitors that prevent the release of PF4.

The survival rate of mice without platelets as well as those treated with inhibitors was improved over that of the mice left alone, but only when the treatment began very soon after infection. When researchers started treating mice with platelet inhibitors one day after infecting them, those mice survived more often than control mice. However, when researchers waited until after three days to treat infected mice with platelet inhibitors, that group did no better in terms of survival.

"Cerebral malaria is lethal 20 percent of the time in the best of hands, and here we've shown that
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Contact: Beth Simpkins
bsimpkins@jhmi.edu
Johns Hopkins Medical Institutions
Source:Eurekalert

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