Epidemiology of herpes simplex virus type 2 in Europe: systematic review, meta-analyses, and meta-regressions

BACKGROUND: Herpes simplex virus type 2 (HSV-2) infection is a globally prevalent, life-long, sexually transmitted infection. This study characterized HSV-2 seroprevalence in Europe for various at-risk populations and proportions of HSV-2 detection in genital ulcer disease (GUD) and in genital herpes. Data on neonatal herpes and HSV-2's contribution to HIV transmission were also reviewed. METHODS: Cochrane and PRISMA guidelines were followed to systematically review, synthesize, and report HSV-2 related findings. The search was conducted in PubMed and Embase databases up to February 20, 2022. Any publication reporting data on the outcome measures was included. Meta-analyses and meta-regressions were conducted. FINDINGS: 211 relevant reports were identified, including 12 overall incidence measures, 294 overall (813 stratified by factors such as age and sex) seroprevalence measures, 13 overall (15 stratified by sex) proportions of HSV-2 detection in clinically diagnosed GUD, and 70 overall (183 stratified by factors such as age and sex) proportions of HSV-2 detection in laboratory-confirmed genital herpes. Pooled mean seroprevalence was 12.4% (95% CI: 11.5–13.3%) among general populations, 27.8% (95% CI: 17.5–39.4%) among men who have sex with men, 46.0% (95% CI: 40.1–51.8%) among people living with HIV and people in HIV discordant couples, and 63.2% (95% CI: 55.5–70.6%) among female sex workers. Most measures showed heterogeneity in HSV-2 seroprevalence. The pooled mean seroprevalence among general populations increased with age and was 0.65-fold (95% CI: 0.58–0.74) lower in men than women. Seroprevalence decreased by 1% per calendar year. Pooled mean proportions of HSV-2 detection in GUD and in genital herpes were 22.0% (95% CI: 15.3–29.6%) and 66.0% (95% CI: 62.9–69.1%), respectively. HSV-2 detection in genital herpes cases was 1.21-fold (95% CI: 1.10–1.32) higher in men compared to women and decreased by 1% per calendar year. Incidence of neonatal herpes indicated an increasing trend. INTERPRETATION: Although seroprevalence is declining, a significant proportion of Europe's population is infected with HSV-2. HSV-2 accounts for approximately one-fifth of GUD cases and two-thirds of genital herpes cases. Findings support the need to invest in HSV-2 vaccine development, and sexual and reproductive health services. FUNDING: 10.13039/100008982Qatar National Research Fund [NPRP 9-040-3-008] and pilot funding from the Biomedical Research Program at 10.13039/100019460Weill Cornell Medicine in Qatar supported this study.