View an illustration about the life cycle of the malaria parasite.
Fidel P. Zavala, M.D., Johns Hopkins Bloomberg School of Public Health, and his research team at the Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Research Institute, have generated strains of transgenic mice for use in parasite antibody studies. The rodent models have excellent systems for studying the general principles of protective immunity against intracellular infections, as was proven in a study the team did on cerebral malaria.
Cerebral malaria results from a combination of blood vessel and immune system dysfunction. Dr. Zavala and colleagues discovered that platelets, cells that cause blood to clot, play an important early role in causing cerebral malaria. Working with their transgenic mouse model, the team found that when the malaria parasite infects red blood cells, 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. The scientists found that something as simple as aspirin, because of its effect on platelets, might be able to improve the outcomes of those with cerebral malaria.
The team infected three separate sets of live mice with malaria: one set lacked platelets, and the two others received aspirin or Plavix, platelet inhibitors that prevent the release of PF4. When the researchers treated mice with platelet inhibitors one day after infecting them, those mice survived more often than control mice. However, when researchers waited three days to treat infected mice with platelet inhibitors, those mice did not do better than the mice lacking platelets in terms of survival.
Platelets, by releasing PF4, play a role in the early phase of cerebral malaria. The mouse studies show that timing is critical; the team knew when the mice were infected and treated. The challenge in translating this to people is that the time of infection is not a known.
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Last Updated June 17, 2009