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 among meningitis cohorts is well recognized. 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. The prevalence of EBV CNS infection (EBV DNA detected in cerebrospinal fluid [CSF] by means of quantitative polymerase chain reaction) was determined, alongside associations with baseline covariates and the in-hospital mortality rate.

RESULTS: A total of 581 participants with suspected meningitis were recruited. Of these, 54% were male, the median age (interquartile range) was 38 (29-46) years, and 76% were persons living with human immunodeficiency virus (HIV). Cryptococcal meningitis was the most common microbiologically confirmed infectious meningitis (12.0%), and 6.4% of participants had definite tuberculous meningitis. EBV CNS infection was common (26% [152 of 581]) and was associated with older age, being HIV positive, and CSF pleocytosis (< .001). It was also associated with increased in-hospital mortality rate (odds ratio, 1.64, [95% confidence interval, 1.10-2.43];= .01), but after adjustment for sex, age, and HIV status, there was no longer evidence of an association (adjusted odds ratio, 1.29 [.84-1.98];= .25). In subgroup analyses, there was an indication that the association between EBV CNS infection and mortality rate may differ by meningitis subgroup.

CONCLUSIONS: EBV CNS infection was common among our cohort, and it was strongly associated with CSF pleocytosis. Following multivariable analyses, EBV CNS infection overall was not associated with in-hospital mortality rate. EBV CNS infection in the context of meningitis is most likely a "bystander" virus that reflects heightened CSF inflammation.