Malaria (marsh fever, periodic fever) is a parasitic disease involving infection of the red blood cells (RBCs). It is transmitted to people by a type of mosquito called Anopheles, which is found mainly in tropical and subtropical areas. An infected Anopheles mosquito bites a person and injects the malaria parasites, known as plasmodium, into the blood. These parasites travel through the bloodstream into the liver and eventually infect the RBCs, destroying them and releasing more parasites to attack more RBCs. The parasites can lie dormant in the liver with some forms of the disease, causing relapses of malaria.
Studies being conducted at Johns Hopkins, Yale, and other institutions uncovered at least one important contributor to the anemia that accompanies malaria and is responsible for killing almost half of the two million people worldwide who succumb to the disease each year. The guilty party is migration inhibitory factor (MIF), a protein that cells make in response to inflammation. MIF appears to suppress RBC production in people whose RBCs are already infected by the malaria parasites, decreasing the total number of RBCs, and causing anemia. There have been cases where patients have been cured of the malaria but still develop severe anemia.
The study, published online April 24th in the Journal of Experimental Medicine, provides evidence that an individual's unique genetic makeup can affect the prevalence and outcome of diseases. A simple genetic test to identify those children who may be most susceptible to the lethal complication of malarial infection is of great importance in places where malaria is endemic and drug treatment resources are scarce. "There are many difficulties with blood transfusion safety and access in Africa, especially in rural areas where most of the malaria-related deaths occur," says Michael A. McDevit, MD, PhD, an assistant professor of medicine and hematology at the Johns Hopkins School of Medicine and the primary author of the study. "That led us to search for a better way to identify those most at risk and a better way to treat the disease," he says.
The researchers, utilizing mice that were genetically engineered to lack the MIF protein and infected with plasmodium, found that the mice experienced less severe anemia and were more likely to survive. It was found that without the MIF in the body to prevent blood cells from maturing, the mice appear to maintain their oxygen-carrying capacity in a better manner and do not lose as much hemoglobin, the protein found in RBCs responsible for binding to oxygen molecules. "Demonstrating that MIF clearly contributes to severe anemia suggests new ideas for therapies that can block MIF in malaria patients," says the senior author of the study, Richard Bucala, MD, PhD, a professor of medicine at Yale University School of Medicine.
The researchers were funded by the National Institutes of Health, the Office of Research on Minority Health, a Howard University General Clinical Research Center grant, and the Department of Medicine at Johns Hopkins.
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