Central nervous system virus infection in African children with cerebral malaria

Douglas Postels, George Washington University, District of Columbia;
Lawrence Osei-Tutu, Kwame Nkrumah University of Science and Technology, Ghana
Karl Seydel, Michigan State University, Michigan
Qian Xu, Michigan State University, Michigan
Chenxi Li, Michigan State University, Michigan
Terrie Taylor, Michigan State University, Michigan
Chandy John, Indiana University, Indiana
Macpherson Mallewa, University of Malawi College of Medicine, Malawi
Tom Solomon, University of Liverpool, United Kingdom
Robert Opoka, Aga Khan University

This work was published before the author joined Aga Khan University.


We aimed to identify the contribution of central nervous system (CNS) viral coinfection to illness in African children with retinopathy-negative or retinopathy-positive cerebral malaria (CM). We collected cerebrospinal fluid (CSF) from 272 children with retinopathy-negative or retinopathy-positive CM and selected CSF from 111 of these children (38 retinopathy positive, 71 retinopathy negative, 2 retinopathy unknown) for analysis by metagenomic next-generation sequencing. We found CSF viral coinfections in 7/38 (18.4%) retinopathy-positive children and in 18/71 (25.4%) retinopathy-negative children. Excluding HIV-1, human herpesviruses (HHV) represented 61% of viruses identified. Excluding HIV-1, CNS viral coinfection was equally likely in children who were retinopathy positive and retinopathy negative (P = 0.1431). Neither mortality nor neurological morbidity was associated with the presence of virus (odds ratio [OR] = 0.276, 95% CI: 0.056–1.363). Retinopathy-negative children with a higher temperature, lower white blood cell count, or being dehydrated were more likely to have viral coinfection. Level of consciousness at admission was not associated with CNS viral coinfection in retinopathy-negative children. Viral CNS coinfection is unlikely to contribute to coma in children with CM. The herpesviruses other than herpes simplex virus may represent incidental bystanders in CM, reactivating during acute malaria infection.