Epstein–Barr virus central nervous system infections and mortality risk in patients presenting with suspected meningitis: results from the Botswana National Meningitis Survey and the Harare Meningitis Aetiology Study

Background Epstein-Barr virus (EBV) central nervous system (CNS) infection in immunocompromised hosts and amongst meningitis cohorts is well recognised. The clinical significance of EBV CNS infection however is poorly understood. Methods Data were collected as part of the Botswana National Meningitis Survey and the Harare Meningitis Aetiology Study. EBV CNS infection (EBV DNA detected in CSF by quantitative polymerase chain reaction) prevalence is described, alongside associations with baseline covariates, and in-hospital mortality. Results 581 participants with suspected meningitis were recruited: 54% male, median age 38 (IQR 29-46) years, 76% were persons living with HIV. Cryptococcal meningitis was the most common microbiologically-confirmed infectious meningitis (12.0%), and 6.4% had definite TB meningitis. EBV CNS infection was common (26%, 152/581) and was associated with older age, being HIV positive, and with CSF pleocytosis (p<0.001). EBV CNS infection was associated with increased in-hospital mortality (odds ratio (OR) 1.64, 95%CI 1.10–2.43, p=0.01); but following adjustment for sex, age, and HIV status, there was no longer evidence of an association (adjusted OR 1.29, 95%CI 0.84-1.98, p=0.25). In sub-group analyses, there was an indication that the association between EBV CNS infection and mortality may differ by meningitis sub-group. Conclusion EBV CNS infection was common amongst our cohort, and was strongly associated with CSF pleocytosis. Following multivariable analyses, overall having EBV CNS infection was not associated with in-hospital mortality. EBV CNS infection in the context of meningitis is most likely a “by-stander virus” which reflects heightened CSF inflammation.