Clinical features of severe malaria associated with death: a 13-year observational study in the Gambia

Abstract

Background: Severe malaria (SM) is a major cause of death in sub-Saharan Africa. Identification of both specific and sensitive clinical features to predict death is needed to improve clinical management.

Methods: A 13-year observational study was conducted from 1997 through 2009 of 2,901 children with SM enrolled at the Royal Victoria Teaching Hospital in The Gambia to identify sensitive and specific predictors of poor outcome in Gambian children with severe malaria between the ages 4 months to 14 years. We have measured the sensitivity and specificity of clinical features that predict death or development of neurological sequelae.

Findings: Impaired consciousness (odds ratio {OR} 4.4 [95% confidence interval {CI}, 2.7-7.3]), respiratory distress (OR 2.4 [95%CI, 1.7-3.2]), hypoglycemia (OR 1.7 [95%CI, 1.2-2.3]), jaundice (OR 1.9 [95%CI, 1.2-2.9]) and renal failure (OR 11.1 [95%CI, 3.3-36.5]) were independently associated with death in children with SM. The clinical features that showed the highest sensitivity and specificity to predict death were respiratory distress (area under the curve 0.63 [95%CI, 0.60-0.65]) and impaired consciousness (AUC 0.61[95%CI, 0.59-0.63]), which were comparable to the ability of hyperlactatemia (blood lactate>5 mM) to predict death (AUC 0.64 [95%CI, 0.55-0.72]). A Blantyre coma score (BCS) of 2 or less had a sensitivity of 74% and specificity of 67% to predict death (AUC 0.70 [95% C.I. 0.68-0.72]), and sensitivity and specificity of 74% and 69%, respectively to predict development of neurological sequelae (AUC 0.72 [95% CI, 0.67-0.76]).The specificity of this BCS threshold to identify children at risk of dying improved in children less than 3 years of age (AUC 0.74, [95% C.I 0.71-0.76]).

Conclusion: The BCS is a quantitative predictor of death. A BCS of 2 or less is the most sensitive and specific clinical feature to predict death or development of neurological sequelae in children with SM.

Figure 1. Clinical features associated with death in children with SM.

Odds of death and blood lactate concentration in children with SM. Data show the odds ratio (95%CI) of death in relation to increasing concentrations of blood lactate in 467 children with SM (a). Odds of death and Blantyre coma score. OR and P values are relative to BCS = 5 (b). Specificity and sensitivity of different blood lactate concentration cut-off values (c) and coma scores measured by BCS (d) to predict death. AUC =  area under the curve,* P<0.05, ***P<0.001.

Figure 2. Age distribution of severe malaria syndromes and mortality in Gambian children from 1997 to 2009.

Data show the cumulative percentage of children with severe malaria (a), the cumulative percentage of death per age group (b), and absolute number of cases of these SM syndromes (c) and death per age group (d). Age groups indicate year of life: age group 1 includes children up to 12 months of age.