The global and regional burden of genital ulcer disease due to herpes simplex virus: a natural history modelling study

Abstract

IntroductionHerpes simplex virus (HSV) infection can cause painful, recurrent genital ulcer disease (GUD), which can have a substantial impact on sexual and reproductive health. HSV-related GUD is most often due to HSV type 2 (HSV-2), but may also be due to genital HSV type 1 (HSV-1), which has less frequent recurrent episodes than HSV-2. The global burden of GUD has never been quantified. Here we present the first global and regional estimates of GUD due to HSV-1 and HSV-2 among women and men aged 15–49 years old.MethodsWe developed a natural history model reflecting the clinical course of GUD following HSV-2 and genital HSV-1 infection, informed by a literature search for data on model parameters. We considered both diagnosed and undiagnosed symptomatic infection. This model was then applied to existing infection estimates and population sizes for 2016. A sensitivity analysis was carried out varying the assumptions made.ResultsWe estimated that 187 million people aged 15–49 years had at least one episode of HSV-related GUD globally in 2016: 5.0% of the world’s population. Of these, 178 million (95% of those with HSV-related GUD) had HSV-2 compared with 9 million (5%) with HSV-1. GUD burden was highest in Africa, and approximately double in women compared with men. Altogether there were an estimated 8 billion person-days spent with HSV-related GUD globally in 2016, with 99% of days due to HSV-2. Taking into account parameter uncertainty, the percentage with at least one episode of HSV-related GUD ranged from 3.2% to 7.9% (120–296 million). However, the estimates were sensitive to the model assumptions.ConclusionOur study represents a first attempt to quantify the global burden of HSV-related GUD, which is large. New interventions such as HSV vaccines, antivirals or microbicides have the potential to improve the quality of life of millions of people worldwide.

The epidemiology of herpes simplex virus type 2 in sub-Saharan Africa: systematic review, meta-analyses, and meta-regressions

“…Another finding of this study is that HSV-2 infection is the cause of half of GUD cases in SSA (Table 5), confirming that this infection is the main cause of this disease in this part of the world where nearly 60 million individuals are estimated to be affected with HSV-related GUD. (79)…”

An HSV-2 nucleoside-modified mRNA genital herpes vaccine containing glycoproteins gC, gD, and gE protects mice against HSV-1 genital lesions and latent infection

“…However, DRG infection was rare, suggesting potent protection when using DRG as a marker for vaccine efficacy. Fourth, HSV-1 comprises only 5% of the global burden of genital herpes [3]. HSV-1 genital infections reactivate at a lower frequency than HSV-2 [5].…”

“…Herpes simplex virus type 2 (HSV-2) genital infection affects a half-billion people worldwide [1]. Herpes simplex virus type 1 (HSV-1) genital infection affects an additional 190 million people [2,3]. Fifty percent of first-time genital herpes infections in resource-rich countries are caused by HSV-1.…”

“…Although HSV-1 is an important cause of first-time genital infections, HSV-1 is much less likely to cause recurrent genital infections than HSV-2 [5]. As a result, HSV-2 accounts for 95% of genital herpes disease worldwide [3]. This epidemiology suggests that HSV-2 is the dominant genital pathogen but ideally a prophylactic genital herpes vaccine will protect against both HSV-1 and HSV-2.…”

Genital HSV-1 DNA detection is associated with a low inflammatory profile in HIV-uninfected South African women

“…Genital herpes is predominantly attributed to HSV-2 infection, while HSV-1 primarily infects the oral cavity, but can also affect the genital tract. 1 Several studies have reported an increasing prevalence of genital HSV-1 infection. 2 3 Genital inflammation is associated with increased risk of HIV infection in young women.…”