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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.

Received September 18, 2005. Accepted for publication November 20, 2005.

Acknowledgments: We thank Dan Anderegg for translating papers from French to English and Professor Klaus Dietz for helpful discussions. We also thank the members of the Technical Advisory Group (Michael Alpers, Paul Coleman, David Evans, Brian Greenwood, Carol Levin, Kevin Marsh, F. Ellis McKenzie, Mark Miller, and Brian Sharp), the Project Management Team at the Program for Appropriate Technology in Health (PATH) Vaccine Initiative, and Glaxo-SmithKline Biologicals S.A. for their assistance.

Financial support: The mathematical modeling study was supported by the PATH Malaria Vaccine Initiative and GlaxoSmithKline Biologicals S.A.

Disclaimer: Publication of this report and the contents hereof do not necessarily reflect the endorsement, opinion, or viewpoints of the PATH Malaria Vaccine Initiative or GlaxoSmithKline Biologicals S.A.

^* Address correspondence to Thomas Smith, Swiss Tropical Institute, Socinstrasse 57, Postfach, CH 4002 Basel, Switzerland. E-mail: Thomas-A.Smith{at}unibas.ch

Authors’ addresses: Amanda Ross, Nicolas Maire, and Thomas Smith, Swiss Tropical Institute, Socinstrasse 57, Postfach, CH 4002 Basel, Switzerland, Telephone: 41-61-284-8273, Fax: 41-61-284-8105, E-mails: amanda.ross{at}unibas.ch, nicolas.maire{at}unibas.ch, and Thomas-A.Smith{at}unibas.ch. Louis Molineaux, Peney-Dessus, CH-1242 Satigny, Geneva, Switzerland.

Reprint requests: Thomas Smith, Swiss Tropical Institute, Socinstrasse 57, Postfach, CH 4002, Basel, Switzerland.

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