CONSORTIUM FOR ANTIMALARIAL DEVELOPMENT

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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. We developed a rhesus monkey model to examine the effects of malaria (Plasmodium coatneyi) during pregnancy. This project, supported by an NIH R01, explores maternal immunologic responses, the effects of gravidity, and preexisting immunity on the severity of clinical malaria and fetal outcome. The FACS analysis and per diem for the infants is supported by a subcontract through Mississippi state university and the CDC. The terms ¿low birth weight¿ (LBW) and ¿small for gestational age¿ (SGA) describe infants born prematurely and/or with intrauterine growth retardation (IUGR), but do not define the nature of the problem. The monkey model shows that there are complex indicators of poor infant outcome and weight alone is not sufficient as the sole determinant. Human studies show that malaria, not prematurity, leads to IUGR but this has been based on birth weight with clinical assessment of gestational age, not on ultrasonography. Utilizing ultrasonography, we demonstrated skeletal abnormalities (dysregulated osteogenesis) including small head measurments and femur length indicative of symmetric IUGR (SIUGR), as well as abnormal elliptical shaped heads with increased head length :head width ratios. Asymmetric IUGR (AIUGR) or reduced body fat deposition was also identified. After birth the infants continued to be measured and monthly FACs analysis was performed. Malaria was associated not only with impaired fetal growth but impaired infant growth and persistent immunologic alterations. Infants displayed malaria-induced modulation of their immune systems, whereby both humoral (B-lymphocytes) and cellular (T-lymphocyte) development was affected. In utero exposure to malaria or malaria antigens are likely responsible. Infants displayed increased susceptibility to a variety of microbial agents. Our findings indicate that the model is relevant for the examination ¿fetal programming¿ a hypothesis which states that the origins of adult disease are related to the fetal environment in utero.