Abstract
The investigation of factors associated with susceptibility to severe malaria is best achieved using case-control studies. The presence of a history of severe malaria in controls could affect the quality of their phenotype and study findings and hence should be rigorously determined. Here, we assessed the performance of a qualitative questionnaire to identify a history of cerebral malaria in controls in a case-control study of severe malaria in Mali. We evaluated the archived medical records of 220 children diagnosed with severe diseases at health care centers in rural and urban settings in Mali from 2018 to 2019. Parents of enrolled children were then identified and interviewed using a structured questionnaire by an investigator blinded to the diagnosis. The diagnosis derived from the interview was then compared with the diagnosis from the medical records as the reference diagnosis. The sensitivity and specificity of the questionnaire to detect cerebral malaria in history were, respectively, 84% and 76%. The questionnaire was concordant with the medical record diagnosis in 60% (95% CI: 50-71%) of cases. For other clinical phenotypes of malaria (severe malaria anemia, uncomplicated malaria, and severe malaria anemia concurrent with cerebral malaria), sensitivity and specificity ranged from 42% to 85% and 88% to 96%, respectively. Positive and negative predictive values were, respectively, 75% and 85%. The questionnaire demonstrated suitable sensitivity and specificity to identify cerebral malaria in a participant's history. In sub-Saharan Africa, a region with suboptimal medical record archives, such a tool could be used in case-control studies of severe malaria to select controls.