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Abstract
Introduction Herpes 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.
Methods We 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.
Results We 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.
Conclusion Our 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.
- epidemiology
- infections, diseases, disorders, injuries
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Footnotes
Handling editor Sanni Yaya
Contributors KJL did the literature review and data extraction, generated the estimates, and produced the drafts of the manuscript. SLG oversaw the study, advised on the broader concepts and relevance of different measures of burden, and helped redraft the manuscript. CJo checked the data extraction, gave input on the natural history parameters and advised on the broader concepts. NW provided detailed statistical advice. CJa produced the map figure and provided code for the uncertainty analysis. PV and KMET provided supervision to KJL. M-CB gave input on the broader concepts and methods. All authors contributed to the direction of the work, provided technical expertise and gave detailed edits on the drafts.
Funding This work was funded by the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction. WHO commissioned the study, advised as required, helped with redrafts and approved manuscript submission. SLG received support from the US National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (U01 AI108543). KJL had full access to all data in the study and had final responsibility for the decision to submit for publication. The authors alone are responsible for the views expressed in this article, and they do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated, WHO, NHS, NIHR, Department of Health and Social Care, or Public Health England.
Map disclaimer The depiction of boundaries on the map(s) in this article do not imply the expression of any opinion whatsoever on the part of BMJ (or any member of its group) concerning the legal status of any country, territory, jurisdiction or area or of its authorities. The map(s) are provided without any warranty of any kind, either express or implied.
Competing interests KJL reports grants from WHO during the conduct of the study and outside the submitted work. CJo reports grants from Sanofi Pasteur, the US National Institutes of Health, and the US Centers for Disease Control and Prevention, consultancy fees from Novavax, and royalties from UpToDate, outside the submitted work. In addition, CJo has a patent 'Epitopes cross-reactive between HSV-1, HSV-2 and VZV' issued. NW reports grants from the National Institute for Health Research during the conduct of the study and grants from Pfizer outside the submitted work. M-CB reports grants and other from WHO outside the submitted work. SLG reports grants from the National Institute of Allergy and Infectious Diseases during the conduct of the study.
Patient consent for publication Not required.
Ethics approval This study used collated data from published studies and sources and did not collect any new data; therefore, ethics approval and consent to participate were not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement The pooled parameter data generated during this study are included in this published article and its supplementary information files. The individual study data which were used to generate these pooled parameter data are available from the corresponding author on reasonable request.