Herpes simplex virus 2 meningitis in adults: A prospective, nationwide, population-based cohort study

Abstract

Abstract Background Data on the clinical presentation are scarce and prognostic factors of Herpes simplex virus type 2 (HSV-2) meningitis remain unknown. Methods Prospective, nationwide, population-based database identifying all adults treated for HSV-2 meningitis at departments of infectious diseases in Denmark from 2015-2020. Unfavorable outcome was defined as Glasgow Outcome Scale (GOS) score of 1-4 and extended GOS score of 1-6. Modified Poisson regression was used to compute relative risks with 95% confidence intervals (RR, 95% CI) for unfavorable outcome. Results HSV-2 meningitis was diagnosed in 205 cases (76% female, median age 35 [IQR 27-49]) yielding an incidence of 0.7/100,000/year. Common symptoms were headache 195/204 (95%), photo/phonophobia 143/188 (76%), and neck stiffness 106/196 (54%). Median time to lumbar puncture was 2.0 hours (IQR 1-4.8) and cerebrospinal fluid (CSF) leukocyte count was 360x10 6/L (IQR 166-670) with a mononuclear predominance of 97% (IQR 91-99). Lumbar puncture was preceded by brain imaging in 61/205 (30%). Acyclovir/valaciclovir was administered in 197/205 (96%) cases for a median of 10 days (IQR 7-14). Unfavorable outcome was observed in 64/205 (31%) at discharge and 19/181 (11%) after six months and was not associated with female sex (RR 1.08, 95% CI 0.65-1.79), age ≥35 years (1.28, 0.83-1.97), immuno-compromise (1.07, 0.57-2.03), or CSF leukocyte count >1,000x10 6/L (0.78, 0.33-1.84). Conclusions HSV-2 meningitis often presented as meningeal symptoms in younger females. Unfavorable outcome at discharge was common and was not associated with sex, age, immune-compromise, or CSF leukocyte count. Sequelae persisted beyond six months in one tenth of patients.