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Background: Plasmodium falciparum malaria accounts for >1 million deaths annually, mostly among young children in sub-Saharan Africa. Identifying those individuals who are likely to die is crucial. Several factors have been independently associated with death. Because malaria is a systemic disease, a quantitative score combining such risk factors may be superior., Methods: We used both forward and backward stepwise logistic regression to select the best predictors of death, as evaluated for 23,890 African children with severe P. falciparum malaria. The study was conducted from December 2000 through May 2005 in 6 hospital-based research units (in Banjul in the Gambia, Blantyre in Malawi, Kilifi in Kenya, Kumasi in Ghana, and Lambaréné and Libreville in Gabon) in a network established to study severe malaria in African children (ie, the SMAC Network)., Results: The Lambaréné Organ Dysfunction Score (LODS) combines 3 variables: coma, prostration, and deep breathing. A LODS >0 (odd ratio, 9.6; 95% confidence interval, 8.0-11.4) has 85% sensitivity to predict death, and a LODS <3 is highly (98%) specific for survival., Conclusions: The LODS is a simple clinical predictor of fatal malaria in African children. This score provides accurate and rapid identification of children needing either referral or increased attention.