MECHANISMS OF ERYTHROCYTIC INFECTIONS AND ANEMIA: NHP MODEL MALARIAL ANEMIA

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall objective of this program project has been to develop an understanding of the molecular and cellular mechanisms by which malaria parasites infect erythrocytes and induce anemia in their mammalian hosts. The main objective of this project is to establish non-human primate models of anemia. To achieve these objectives a group of investigators with expertise in hematology, parasitology, cell biology, biochemistry, molecular biology, immunology, parasite genetics, functional genomics, rodent and non-human primate models came together to mount a concerted effort. This program has been expected to lead to the development of therapeutic strategies against malarial infection and anemia. To date, we have established and refined an animal model to study the physiology of P. falciparum malarial anemia using the rhesus monkey / P. coatneyi model system; an ideal model to examine infected blood and bone marrow samples. This past year, consecutive P. coatneyi infections were completed in a group of rhesus monkeys with refined protocols, to establish the course of anemia and mechanisms of disease and recovery in both na¿ve and subsequently semi-immune animals. Follow-up immunological and histopathological analyses will be required. A manuscript relating to these infections has been in preparation and planning has been underway to similarly establish the P. cynomolgi - rhesus model to study P. vivax malaria anemia. This in vivo model, which is far preferable to a mouse model, has been providing critical and unique insights relevant to understanding the multi-factorial causes of severe malaria disease in humans. Several other basic blood-stage studies have also been facilitated by the funding support of this project, and a series of manuscripts are in preparation. A review has also been published which highlights P. vivax and the importance of the P. cynomolgi simian malaria model for studying the biology and pathogenesis of this widespread human malaria parasite.