Using malarial retinopathy to improve the diagnosis of pediatric cerebral malaria

Abstract

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 (PfHRP2). 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 (AUROC: 0.89 vs. 0.75, p-value < 0.001). We conclude that malarial retinopathy is highly predictive of malaria-caused vs. non-malaria-caused coma and recommend an ocular funduscopic examination to determine malarial retinopathy status be included in the assessment of parasitemic comatose African children.

Bo Zhang

Assistant Professor of Biostatistics

My research interests include design of observational studies, instrumental variables, application of causal inference in medicine and applied statistics in general.