An epidemiologic model of severe morbidity and mortality caused by Plasmodium falciparum

The intensity of Plasmodium falciparum transmission has multifarious and sometimes counter-intuitive effects on age-specific rates of severe morbidity and mortality in endemic areas. This has led to conflicting speculations about the likely impact of malaria control interventions. We propose a quantitative framework to reconcile the various apparently contradictory observations relating morbidity and mortality rates to malaria transmission. Our model considers two sub-categories of severe malaria episodes. These comprise episodes with extremely high parasite densities in hosts with little previous exposure, and acute malaria episodes accompanied by co-morbidity or other risk factors enhancing susceptibility. In addition to direct malaria mortality from severe malaria episodes, the model also considers the enhanced risk of indirect mortality following acute episodes accompanied by co-morbidity after the parasites have been cleared. We fit this model to summaries of field data from endemic areas of Africa, and show that it can account for the observed age- and exposure-specific patterns of pediatric severe malaria and malaria-associated mortality in children. This model will allow us to make predictions of the long-term impact of potential malaria interventions. Predictions for children will be more reliable than those for older people because there is a paucity of epidemiologic studies of adults and adolescents.