Estimated global and regional incidence and prevalence of herpes simplex virus infections and genital ulcer disease in 2020: Mathematical modeling analyses

Abstract Background Genital herpes simplex virus (HSV) type 1 and 2 infections are lifelong and can cause symptomatic genital ulcer disease (GUD). HSV-2 almost always causes sexually transmitted genital infection, while HSV-1 mainly causes oral infection but can be sexually transmitted to cause genital infection. This study estimated genital infection with both HSV types and associated GUD globally in 2020, breaking down the data by World Health Organization (WHO) region and sex for females and males. Methods A calibrated mathematical model was employed to generate estimates for the incidence and prevalence of HSV-2 infection, genital HSV-1 infection, and GUD caused by both HSV types. Estimates for non-genital infections caused by HSV-1 were also generated. Model input was derived from a comprehensive systematic review and meta-analyses of HSV prevalence data for all WHO regions. Results Globally in 2020 there were 25.6 million (95% uncertainty interval (UI): 23.1-29.4 million) people aged 15 to 49 years with new HSV-2 infections and 519.5 million (95% UI: 464.3-611.3 million), or 13.3% (95% UI: 11.9-15.6%), with existing (prevalent) HSV-2 infections. In addition, there were 16.8 million (95% UI: 10.6-22.4 million) people aged 15-49 years with new genital HSV-1 infections and 376.2 million (95% UI: 235.6-483.5 million), or 10.2% (95% UI: 6.4-13.1%), with prevalent genital HSV-1 infections. The estimated number of people aged 15 to 49 years with at least one episode of HSV-attributable genital ulcer disease in 2020 was 187.9 million (95% UI: 116.0-291.8 million) for HSV-2 and 16.7 million (95% UI: 9.3-25.2 million) for HSV-1, totaling 204.6 million (95% UI: 132.3-306.5). Conclusion Genital HSV infections have a high incidence and prevalence worldwide, contributing to a significant GUD disease burden. New prevention and treatment measures, such as prophylactic and therapeutic HSV vaccines, are critically needed to control HSV infections and reduce the associated disease burden.