Evidence from a natural experiment that malaria parasitemia is pathogenic in retinopathy-negative cerebral malaria

DS Small, TE Taylor, DG Postels, NAV Beare, J Cheng… - Elife, 2017 - elifesciences.org
Elife, 2017elifesciences.org
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 …
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).
DOI: http://dx.doi.org/10.7554/eLife.23699.001
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