Senior Scholar Award in Global Infectious Disease
Ronald P. Taylor, Ph.D.
University of Virginia
John Waitumbi, D.V.M., Ph.D

Investigation of Mechanisms Leading to Anemia at Low Parasite Burden in Children with Malaria

This research is being conducted by Dr. Taylor in collaboration with Dr. Waitumbe from the Kenyan Medical Research Institute.

One of the most confounding and important problems in understanding malaria concerns the mechanisms by which red blood cells are destroyed. Although it is common knowledge that the malaria parasite, Plasmodium falciparum (Pf), invades red blood cells and causes anemia and severe illness, the percentage of red cells that are infected is often far lower than the fraction that are destroyed. That is, a young child might have a parasitemia burden of 1 % (1 out of every 100 red cells is infected by Pf) yet, during a crisis 30-50 % or more of his/her red cells can be destroyed. We believe that when the body of a young child reacts to the malaria infection and attempts to rid itself of the Pf, many of the child’s red blood cells are destroyed in an “innocent bystander” reaction. That is, the body’s immunological defenses initiate destruction of the infecting Pf organism, but during this process large amounts of debris (destroyed and non-infectious PF) are generated. We suspect that much of this debris then binds to the outside of normal red blood cells, and therefore the red blood cells are mistakenly recognized as foreign by the immune system. The net result is that large numbers of the child’s red blood cells suffer attack by the immune system, even though there might be no detectable live Pf in the bloodstream.

We will investigate this hypothesis in an international collaboration between two laboratories: The Taylor lab at the University of Virginia, and the Waitumbi lab at the Kenyan Medical Research Institute. The Taylor lab has expertise in immunochemical model systems that are relevant to the postulated red cell destruction mechanism. The Waitumbi lab is involved in several clinical investigations of malaria and has recently focused on childhood anemia. Moreover, the Waitumbi lab has available the patient samples necessary to carry out the experiments. We established this collaboration more than one year ago, and Dr. Waitumbi and his students have already made two visits to our lab at UVA. We have provided reagents and training to the Waitumbi lab, and we anticipate initiating experiments on blood products provided to us from patients being treated in Dr. Waitumbi’s institution. If we can prove the hypothesis under investigation, then we will test several straight-forward and rational approaches for blocking the “innocent bystander” destruction of red blood cells. These tests have the potential to lead to simple and effective treatments to prevent red blood cell destruction. One other important aspect of this collaboration is the training of Kenyan scientists in the necessary immunochemical techniques through visits of two weeks or more to the Taylor laboratory.

Contact Dr. Taylor.