The patterns of malaria illness vary significantly across sub-Saharan Africa; case management practices vary' considerably between the SMAC sites. Documenting our diverse experiences, in a prospective, standardized fashion, is an important function of this network. A """"""""core database"""""""" will allow us to develop and test rational case definitions, to identify new prognostic features and beneficial management practices, and it will permit better sample size estimates for future intervention studies. Therefore, a component of this project is the development of a core database to (a) document patterns of severe disease (cerebral malaria, acidosis, anemia), moderate disease and uncomplicated malaria (b) note outcomes associated with severe, moderate and uncomplicated malaria and (c) reveal risk factors associated with poor outcomes. In conjunction with the database, we propose to assess intraleukocytic malaria pigment as a marker of severe falciparum malaria and as an indicator of a poor prognosis. Quantifying pigment in circulating white cells can be accomplished quickly and easily, along with assessing peripheral parasitemia. Our hypothesis rests on the assumptions that pigment-laden white cells might be a more accurate measure of the parasite biomass and/or pigment-laden white cells may reflect the total body load of pigment, and that pigment itself is toxic. Intraleukocytic pigment has been associated with a poor outcome in Vietnamese adults, and with severity of disease (but not outcome) in children from Gabon and Nigeria. The results from these sites are widely discrepant and cannot be extrapolated. in vitro data suggest that malaria pigment can compromise macrophage function, enhance cytokine production and upregulate endothelial receptors. Any of these may contribute to malaria pathogenesis. All parasitemic children admitted to all five SMAC sites will be eligible for inclusion in the pigment study. Intraleukocytic pigment will be assessed on admission, along with other known predictors of malaria disease severity and outcome. Patients will be followed through to discharge; their clinical diagnosis and outcome will-then be related to pigment (presence/absence and quantified in terms of percentage of monocytes and neutrophils containing pigment). We anticipate admitting 10,000 patients annually; these sample sizes will be large enough to permit sub-analyses and inter- site comparisons. Whether leukocytic malaria pigment is a useful predictor of severe disease and/or a poor outcome in African children will be determined as a core database is being established for this nascent network. That such a question can be addressed quickly and easily in the process of maintaining the database is itself an indication of its utility
