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In malaria endemic areas, a high proportion of children have detectable parasitemia but show no clinical symptoms. When comatose from a cause other than malaria, this group confounds the cerebral malaria (CM) definition, making accurate diagnosis challenging. One important biomarker of CM is malarial retinopathy, a set of specific features visible in the ocular fundus. In this study, we quantified the contribution of malarial retinopathy in discriminating malaria-caused coma from non–malaria-caused coma. We estimated that 10% of our study cohort of N = 1,192 patients who met the WHO clinical definition of CM in Malawi had non-malarial coma based on a Gaussian mixture model using the parasite protein Plasmodium falciparum histidine-rich protein-2. A classification based on platelets, white blood cells, and retinopathy significantly improved the discriminative power of a previously established model including only platelets plus white blood cells (area under the receiver operating characteristic curve: 0.89 versus 0.75, P value < 0.001). We conclude that malarial retinopathy is highly predictive of malaria-caused versus non–malaria-caused coma and recommend that an ocular funduscopic examination to determine malarial retinopathy status be included in the assessment of parasitemic comatose African children.
Disclosure: T. T. sits on the Strategic Advisory Board for the Novartis Institute for Tropical Diseases and the Malaria Advisory Board for Novartis Pharma AG. Other authors declare no conflicts of interest.
Authors’ addresses: Yuzhou Lin, Department of Statistics, Harvard University, Cambridge, MA, E-mail: email@example.com. Andrew Tebulo, Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi, E-mail: firstname.lastname@example.org. Dylan Small, Department of Statistics and Data Science, The Wharton School, University of Pennsylvania, Philadelphia, PA, E-mail: email@example.com. Karl Seydel and Terrie Taylor, Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi, and Department of Osteopathic Medical Specialties, Michigan State University, East Lansing, MI, E-mails: firstname.lastname@example.org and email@example.com. Bo Zhang, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, E-mail: firstname.lastname@example.org.