Mystery of Malarias Fatal Form Unraveled

August 18, 2008






"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," says David Sullivan MD, an associate professor of molecular microbiology and immunology in the Johns Hopkins University Bloomberg School of Public Health.

To make the specific connection between PF4 and malaria, the scientists compared the responses to malaria infection by so-called "wild type" normal mice and mice genetically engineered to lack pF4. They found that the amount of parasite in the blood was the same in both sets of mice. The notable difference was in the animals' immune responses to that same parasite burden. More than 60 percent of the mice lacking PF4 were still alive after day 10, while only 30 percent of the mice with PF4 survived that long.

"The take-home lesson is that platelets, by releasing PF4, are playing an early role in the wind-up phase of cerebral malaria," says Craig Morrell, DVM, PhD, an assistant professor of molecular and comparative pathobiology at the Johns Hopkins University School of Medicine. "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. Platelets don't get any respect, but they're the second most abundant cell in the blood after red blood cells and packed full of factors that rally the immune system to action. By taking what we know about platelets and their activation and applying it to malaria, we have found a driver of cerebral malaria."

