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.

A review of authorship in herpes simplex virus type-2 (HSV-2) research conducted in low-income and middle-income countries between 2000 and 2020.

INTRODUCTION: Equitable inclusion of low-income and middle-income country (LMIC) researchers and women in research authorship is a priority. A review of progress in addressing WHO-identified priorities provided an opportunity to examine the geographical and gender distribution of authorship in herpes simplex virus type-2 (HSV-2) research. METHODS: Publications addressing five areas prioritised in a WHO workshop and published between 2000 and 2020 were identified. Data on author country, gender, authorship position and research funding source were collected by manuscript review and internet searches and analysed using IBM SPSS V.26. RESULTS: Of, 297 eligible papers identified, (n=294) had multiple authors. Of these, 241 (82%) included at least one LMIC author and 143 (49%) and 122 (41%) had LMIC first and last authors, respectively. LMICs funded studies were more than twice as likely to include an LMIC first or last author as high-income country-funded studies (relative risk 2.36, 95% CI 1.93 to 2.89). Respectively, 129 (46%) and 106 (36%) studies had female first and last authors. LMIC first and last authorship varied widely by HSV-2 research area and increased over time to 65% and 59% by 2015-2020. CONCLUSION: Despite location of the research itself in LMIC settings, over the 20-year period, LMIC researchers held only a minority of first and last authorship positions. While LMIC representation in these positions improved over time, important inequities remain in key research areas and for women. Addressing current and historical power disparities in global health research, research infrastructure and how it is funded may be key addressing to addressing these issues.

20 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 priorities for research in HSV-2/HIV interactions, HSV-2 control and mathematical modelling.

INTRODUCTION: Reviewing and updating research priorities is essential to assess progress and to ensure optimal allocation of financial and human resources in research. In 2001, WHO held a research priority setting workshop for herpes simplex virus type 2 (HSV-2) research in low-income and middle-income countries (LMICs). This study aimed to describe progress between 2000 and 2020 in three of the five key research priority areas outlined in the workshop: HSV-2/HIV interactions, HSV-2 control measures and HSV-2 mathematical modelling. The remaining priorities are addressed in a companion paper. METHOD: A systematic literature search of MEDLINE, CINAHL, Global Health and Cochrane databases was carried out. Relevant primary research studies based in LMICs, written in English and published on 2000-2020 were included. Papers were screened by two independent reviewers, and suitable variables were selected for manual extraction from study texts. Data were organised into an Excel spreadsheet and analysed using IBM SPSS. RESULTS: In total, 3214 discrete papers were identified, of which 180 were eligible for inclusion (HSV-2/HIV interactions, 98; control measures, 58; mathematical modelling, 24). Most studies were conducted in East Africa. The majority of the 2001 WHO HSV-2 research priorities were addressed at least in part. Overall, despite several studies describing a strong relationship between HSV-2 and the acquisition and transmission of HIV, HSV-2 control repeatedly demonstrated little effect on HIV shedding or transmission. Further, although mathematical modelling predicted that vaccines could significantly impact HSV-2 indicators, HSV-2 vaccine studies were few. Studies of antiviral resistance were also few. CONCLUSION: Since 2000, LMIC HSV-2 research addressing its control, HIV interactions and mathematical modelling has largely addressed the priorities set in the 2001 WHO HSV-2 workshop. However, key knowledge gaps remain in vaccine research, antiviral cost-effectiveness, antiviral resistance and specific geographical areas.