Study Implicates Immune System in Fatal Cerebral Malaria

by Rajashri on Aug 20 2008 4:49 PM

Platelets, the cells that cause blood clots, play an important early role in promoting cerebral malaria, an often fatal form of malaria that occurs mostly in children, according to Johns Hopkins scientists.

The team revealed 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 traits of cerebral malaria.

During the study, human red blood cells were infected in culture with the malaria parasite, which indeed, stimulated platelet activation.

For further analysis, three separate sets of live mice were infected with the malaria parasite. One set treated so that it lacked platelets altogether and two others were treated with aspirin or Plavix, platelet inhibitors that prevent the release of PF4.

The results showed that 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.

"Cerebral malaria is lethal 20 percent of the time in the best of hands, and here we've shown that something as simple as aspirin, because of its affect on platelets, might be able to improve the outcomes of those who contract this deadly form of the disease," said Dr David Sullivan, an associate professor of molecular microbiology and immunology in the Johns Hopkins University Bloomberg School of Public Health.

"Our mouse studies show that timing is critical; with the mice, we know when we infected them and controlled when we treated them. A big challenge in translating this to humans is that people don't know when they get infected," said Craig Morrell, DVM, Ph.D., an assistant professor of molecular and comparative pathobiology at the Johns Hopkins University School of Medicine

"By taking what we know about platelets and their activation and applying it to malaria, we have found a driver of cerebral malaria," he added.