Department of Statistics, The Wharton School, University of Pennsylvania, Philadelphia, United States
Terrie E Taylor
Department of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University, East Lansing, United States; Blantyre Malaria Project, Blantyre, Malawi
Douglas G Postels
Department of Neurology and Ophthalmology, College of Osteopathic Medicine, Michigan State University, East Lansing, United States
Nicholas AV Beare
Department of Eye and Vision Science, University of Liverpool, Liverpool, United Kingdom; St. Paul’s Eye Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom
Jing Cheng
Department of Preventive and Restorative Dental Sciences, University of California, San Francisco, San Francisco, United States
Ian JC MacCormick
Department of Eye and Vision Science, University of Liverpool, Liverpool, United Kingdom; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi
Karl B Seydel
Department of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University, East Lansing, United States; Blantyre Malaria Project, Blantyre, Malawi
Cerebral malaria (CM) can be classified as retinopathy-positive or retinopathy-negative, based on the presence or absence of characteristic retinal features. While malaria parasites are considered central to the pathogenesis of retinopathy-positive CM, their contribution to retinopathy-negative CM is largely unknown. One theory is that malaria parasites are innocent bystanders in retinopathy-negative CM and the etiology of the coma is entirely non-malarial. Because hospitals in malaria-endemic areas often lack diagnostic facilities to identify non-malarial causes of coma, it has not been possible to evaluate the contribution of malaria infection to retinopathy-negative CM. To overcome this barrier, we studied a natural experiment involving genetically inherited traits, and find evidence that malaria parasitemia does contribute to the pathogenesis of retinopathy-negative CM. A lower bound for the fraction of retinopathy-negative CM that would be prevented if malaria parasitemia were to be eliminated is estimated to be 0.93 (95% confidence interval: 0.68, 1).
