Twenty years of herpes simplex virus type 2 (HSV-2) research in low-income and middle-income countries: systematic evaluation of progress made in addressing WHO prioritiesfor research in HSV-2 epidemiology and diagnostics.

Introduction: Low-income and middle-income countries (LMICs) have a high burden of herpes simplex virus type 2 (HSV-2) infection, which has been strongly associated with HIV. In 2001, the WHO hosted a workshop to set research priorities for HSV-2 in LMICs. Periodic re-evaluation of research priorities is essential to ensure effective allocation of resources. This study describes the progress made between 2000 and 2020 in addressing the priorities identified in two of the five thematic areas that were the workshop's focus: HSV-2 epidemiology and diagnostics. The remaining areas are addressed in a companion paper.

Methods: A systematic search of MEDLINE, CINAHL, Global Health and Cochrane databases was carried out. Relevant primary and secondary research studies conducted in LMICs, written in English and published from 2000-2020 were included. Two independent researchers screened, identified papers and extracted preidentified variables from study texts. Data were organised into an Excel spreadsheet and analysed using IBM SPSS V.26.

Results: Overall, 4445 discrete papers were identified, of which 165 publications were eligible for inclusion. The highest general population HSV-2 prevalence was reported in South and West Africa. Prevalence was higher among women than men and increased with age. HSV-2 prevalence studies among key populations were few, and the majority were in East and South Asia. Cohort studies of HSV-2 incidence among younger populations (mean age=25 years) and HSV-2 infection prevalence in North Africa and the Middle East were few. The most researched topic in HSV-2 diagnostics addressed serological techniques and direct molecular biology. Studies of point-of-care testing were also few.

Conclusion: HSV-2 research identified in LMICs has mainly addressed the epidemiology and diagnostics priorities identified by the 2001 WHO workshop. Unaddressed priorities include point-of-care testing, antiviral resistance and exploration of HSV-2 epidemiology in neglected geographical settings and population subgroups.