Herpes simplex virus: global infection prevalence and incidence estimates, 2016.

OBJECTIVE: To generate global and regional estimates for the prevalence and incidence of herpes simplex virus (HSV) type 1 and type 2 infection for 2016. METHODS: To obtain data, we undertook a systematic review to identify studies up to August 2018. Adjustments were made to account for HSV test sensitivity and specificity. For each World Health Organization (WHO) region, we applied a constant incidence model to pooled prevalence by age and sex to estimate the prevalence and incidence of HSV types 1 and 2 infections. For HSV type 1, we apportioned infection by anatomical site using pooled estimates of the proportions that were oral and genital. FINDINGS: In 2016, an estimated 491.5 million people (95% uncertainty interval, UI: 430.4 million-610.6 million) were living with HSV type 2 infection, equivalent to 13.2% of the world's population aged 15-49 years. An estimated 3752.0 million people (95% UI: 3555.5 million-3854.6 million) had HSV type 1 infection at any site, equivalent to a global prevalence of 66.6% in 0-49-year-olds. Differing patterns were observed by age, sex and geographical region, with HSV type 2 prevalence being highest among women and in the WHO African Region. CONCLUSION: An estimated half a billion people had genital infection with HSV type 2 or type 1, and several billion had oral HSV type 1 infection. Millions of people may also be at higher risk of acquiring human immunodeficiency virus (HIV), particularly women in the WHO African Region who have the highest HSV type 2 prevalence and exposure to HIV.

Advancing vaccine development for gonorrhoea and the Global STI Vaccine Roadmap.

Efforts to develop vaccines against Neisseria gonorrhoeae have become increasingly important, given the rising threat of gonococcal antimicrobial resistance (AMR). Recent data suggest vaccines for gonorrhoea are biologically feasible; in particular, epidemiological evidence shows that vaccines against a closely related pathogen, serogroup B Neisseria meningitidis outer membrane vesicle (OMV) vaccines, may reduce gonorrhoea incidence. Vaccine candidates using several approaches are currently in preclinical development, including meningococcal and gonococcal OMV vaccines, a lipooligosaccharide epitope and purified protein subunit vaccines. The Global STI Vaccine Roadmap provides action steps to build on this technical momentum and advance gonococcal vaccine development. Better quantifying the magnitude of gonorrhoea-associated disease burden, for outcomes like infertility, and modelling the predicted role of gonococcal vaccines in addressing AMR will be essential for building a full public health value proposition, which can justify investment and help with decision making about future vaccine policy and programs. Efforts are underway to gain consensus on gonorrhoea vaccine target populations, implementation strategies and other preferred product characteristics that would make these vaccines suitable for use in low- and middle-income, as well as high-income, contexts. Addressing these epidemiological, programmatic and policy considerations in parallel to advancing research and development, including direct assessment of the ability of meningococcal B OMV vaccines to prevent gonorrhoea, can help bring about the development of viable gonococcal vaccines.

Correction: Prevalence of sexually transmitted infections and bacterial vaginosis among women in sub-Saharan Africa: An individual participant data meta-analysis of 18 HIV prevention studies.

[This corrects the article DOI: 10.1371/journal.pmed.1002511.].

Prevalence of sexually transmitted infections and bacterial vaginosis among women in sub-Saharan Africa: An individual participant data meta-analysis of 18 HIV prevention studies.

BACKGROUND: Estimates of sexually transmitted infection (STI) prevalence are essential for efforts to prevent and control STIs. Few large STI prevalence studies exist, especially for low- and middle-income countries (LMICs). Our primary objective was to estimate the prevalence of chlamydia, gonorrhea, trichomoniasis, syphilis, herpes simplex virus type 2 (HSV-2), and bacterial vaginosis (BV) among women in sub-Saharan Africa by age, region, and population type. METHODS AND FINDINGS: We analyzed individual-level data from 18 HIV prevention studies (cohort studies and randomized controlled trials; conducted during 1993-2011), representing >37,000 women, that tested participants for ≥1 selected STIs or BV at baseline. We used a 2-stage meta-analysis to combine data. After calculating the proportion of participants with each infection and standard error by study, we used a random-effects model to obtain a summary mean prevalence of each infection and 95% confidence interval (CI) across ages, regions, and population types. Despite substantial study heterogeneity for some STIs/populations, several patterns emerged. Across the three primary region/population groups (South Africa community-based, Southern/Eastern Africa community-based, and Eastern Africa higher-risk), prevalence was higher among 15-24-year-old than 25-49-year-old women for all STIs except HSV-2. In general, higher-risk populations had greater prevalence of gonorrhea and syphilis than clinic/community-based populations. For chlamydia, prevalence among 15-24-year-olds was 10.3% (95% CI: 7.4%, 14.1%; I2 = 75.7%) among women specifically recruited from higher-risk settings for HIV in Eastern Africa and was 15.1% (95% CI: 12.7%, 17.8%; I2 = 82.3%) in South African clinic/community-based populations. Among clinic/community-based populations, prevalence was generally greater in South Africa than in Southern/Eastern Africa for most STIs; for gonorrhea, prevalence among 15-24-year-olds was 4.6% (95% CI: 3.3%, 6.4%; I2 = 82.8%) in South Africa and was 1.7% (95% CI: 1.2%, 2.6%; I2 = 55.2%) in Southern/Eastern Africa. Across the three primary region/population groups, HSV-2 and BV prevalence was high among 25-49-year-olds (ranging from 70% to 83% and 33% to 44%, respectively). The main study limitation is that the data are not from random samples of the target populations. CONCLUSIONS: Combining data from 18 HIV prevention studies, our findings highlight important features of STI/BV epidemiology among sub-Saharan African women. This methodology can be used where routine STI surveillance is limited and offers a new approach to obtaining critical information on STI and BV prevalence in LMICs.

Future prospects for new vaccines against sexually transmitted infections.

PURPOSE OF REVIEW: This review provides an update on the need, development status, and important next steps for advancing development of vaccines against sexually transmitted infections (STIs), including herpes simplex virus (HSV), Neisseria gonorrhoeae (gonorrhea), Chlamydia trachomatis (chlamydia), and Treponema pallidum (syphilis). RECENT FINDINGS: Global estimates suggest that more than a million STIs are acquired every day, and many new and emerging challenges to STI control highlight the critical need for development of new STI vaccines. Several therapeutic HSV-2 vaccine candidates are in Phase I/II clinical trials, and one subunit vaccine has shown sustained reductions in genital lesions and viral shedding, providing hope that an effective HSV vaccine is on the horizon. The first vaccine candidate for genital chlamydia infection has entered Phase I trials, and several more are in the pipeline. Use of novel technological approaches will likely see viable vaccine candidates for gonorrhea and syphilis in the future. The global STI vaccine roadmap outlines key activities to further advance STI vaccine development. SUMMARY: Major progress is being made in addressing the large global unmet need for STI vaccines. With continued collaboration and support, these critically important vaccines for global sexual and reproductive health can become a reality.

Trends and patterns of sexual behaviors among adolescents and adults aged 14 to 59 years, United States.

BACKGROUND: Evaluation of sexual behaviors is essential to better understand the epidemiology of sexually transmitted infections and their sequelae. METHODS: The National Health and Nutrition Examination Surveys (NHANES) is an ongoing probability sample survey of the US population. Using NHANES sexual behavior data from 1999 to 2012, we performed the following: (1) trend analyses among adults aged 25 to 59 years by 10-year birth cohorts and (2) descriptive analyses among participants aged 14 to 24 years. Sex was defined as vaginal, anal, or oral sex. RESULTS: Among adults aged 25 to 59 years, median age at sexual initiation decreased between the 1940-1949 and 1980-1989 cohorts from 17.9 to 16.2 among females (P trend < 0.001) and from 17.1 to 16.1 among males (P trend < 0.001). Median lifetime partners increased between the 1940-1949 and 1970-1979 cohorts, from 2.6 to 5.3 among females (P trend < 0.001) and from 6.7 to 8.8 among males (P trend < 0.001). The percentage of females reporting ever having a same-sex partner increased from 5.2% to 9.3% between the 1940-1949 and 1970-1979 cohorts (P trend < 0.001). Among participants aged 14 to 24 years, the percentage having had sex increased with age, from 12.5% among females and 13.1% among males at age 14 years to more than 75% at age 19 years for both sexes. Among sexually experienced 14- to 19-year-olds, 45.2% of females and 55.0% of males had at least 3 lifetime partners; 39.4% of females and 48.6% of males had at least 2 partners in the past year. The proportion of females aged 20 to 24 years who reported ever having a same-sex partner was 14.9%. The proportion of participants aged 14-19 or 20-24 years reporting ever having sex did not differ by survey year from 1999 to 2012 for either males or females. CONCLUSIONS: Sexual behaviors changed with successive birth cohorts, with more pronounced changes among females. A substantial proportion of adolescents are sexually active and have multiple partners. These data reinforce existing recommendations for sexual health education and sexually transmitted infection prevention targeting adolescents before sexual debut.

Vaccine value profile for Neisseria gonorrhoeae.

Neisseria gonorrhoeae infection (gonorrhoea) is a global public health challenge, causing substantial sexual and reproductive health consequences, such as infertility, pregnancy complications and increased acquisition or transmission of HIV. There is an urgency to controlling gonorrhoea because of increasing antimicrobial resistance to ceftriaxone, the last remaining treatment option, and the potential for gonorrhoea to become untreatable. No licensed gonococcal vaccine is available. Mounting observational evidence suggests that N. meningitidis serogroup B outer membrane vesicle-based vaccines may induce cross-protection against N. gonorrhoeae (estimated 30%-40% effectiveness using the 4CMenB vaccine). Clinical trials to determine the efficacy of the 4CMenB vaccine against N. gonorrhoeae are underway, as are Phase 1/2 studies of a new gonococcal-specific vaccine candidate. Ultimately, a gonococcal vaccine must be accessible, affordable and equitably dispensed, given that those most affected by gonorrhoea are also those who may be most disadvantaged in our societies, and most cases are in less-resourced settings. This vaccine value profile (VVP) provides a high level, holistic assessment of the current data to inform the potential public health, economic and societal value of pipeline vaccines. This was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations. All contributors have extensive expertise on various elements of the N. gonorrhoeae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using published data obtained from peer-reviewed journals or reports.

Meeting report: Considerations for trial design and endpoints in licensing therapeutic HPV16/18 vaccines to prevent cervical cancer.

Cervical cancer is a major cause of morbidity and mortality globally with a disproportionate impact on women in low- and middle-income countries. In 2021, the World Health Organization (WHO) called for increased vaccination, screening, and treatment to eliminate cervical cancer. However, even with widespread rollout of human papillomavirus (HPV) prophylactic vaccines, millions of women who previously acquired HPV infections will remain at risk for progression to cancer for decades to come. The development and licensing of an affordable, accessible therapeutic HPV vaccine, designed to clear or control carcinogenic HPV and/or to induce regression precancer could significantly contribute to the elimination efforts, particularly benefiting those who missed out on the prophylactic vaccine. One barrier to development of such vaccines is clarity around the regulatory pathway for licensure. In Washington, D.C. on September 12-13, 2023, a meeting was convened to provide input and guidance on trial design with associated ethical and regulatory considerations. This report summarizes the discussion and conclusions from the meeting. Expert presentation topics included the current state of research, potential regulatory challenges, WHO preferred product characteristics, modeling results of impact of vaccine implementation, epidemiology and natural history of HPV infection, immune responses related to viral clearance and/or precancer regression including potential biomarkers, and ethical considerations. Panel discussions were held to explore specific trial design recommendations to support the licensure process for two vaccine indications: (1) treatment of prevalent HPV infection or (2) treatment of cervical precancers. Discussion covered inclusion/exclusion criteria, study endpoints, sample size and power, safety, study length, and additional data needed, which are reported here. Further research of HPV natural history is needed to address identified gaps in regulatory guidance, especially for therapeutic vaccines intended to treat existing HPV infections.

WHO global research priorities for sexually transmitted infections.

Sexually transmitted infections (STIs) are widespread worldwide and negatively affect sexual and reproductive health. Gaps in evidence and in available tools have long hindered STI programmes and policies, particularly in resource-limited settings. In 2022, WHO initiated a research prioritisation process to identify the most important STI research areas to address the global public health need. Using an adapted Child Health and Nutrition Research Initiative methodology including two global stakeholder surveys, the process identified 40 priority STI research needs. The top priorities centred on developing and implementing affordable, feasible, rapid point-of-care STI diagnostic tests and new treatments, especially for gonorrhoea, chlamydia, and syphilis; designing new multipurpose prevention technologies and vaccines for STIs; and collecting improved STI epidemiologic data on both infection and disease outcomes. The priorities also included innovative programmatic approaches, such as new STI communication and partner management strategies. An additional six research areas related to mpox (formerly known as monkeypox) reflect the need for STI-related research during disease outbreaks where sexual transmission can have a key role. These STI research priorities provide a call to action for focus, investment, and innovation to address existing roadblocks in STI prevention, control, and management to advance sexual and reproductive health and wellbeing for all.

Effectiveness and safety of COVID-19 vaccines on maternal and perinatal outcomes: a systematic review and meta-analysis.

OBJECTIVE: To assess the effects of COVID-19 vaccines in women before or during pregnancy on SARS-CoV-2 infection-related, pregnancy, offspring and reactogenicity outcomes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Major databases between December 2019 and January 2023. STUDY SELECTION: Nine pairs of reviewers contributed to study selection. We included test-negative designs, comparative cohorts and randomised trials on effects of COVID-19 vaccines on infection-related and pregnancy outcomes. Non-comparative cohort studies reporting reactogenicity outcomes were also included. QUALITY ASSESSMENT, DATA EXTRACTION AND ANALYSIS: Two reviewers independently assessed study quality and extracted data. We undertook random-effects meta-analysis and reported findings as HRs, risk ratios (RRs), ORs or rates with 95% CIs. RESULTS: Sixty-seven studies (1 813 947 women) were included. Overall, in test-negative design studies, pregnant women fully vaccinated with any COVID-19 vaccine had 61% reduced odds of SARS-CoV-2 infection during pregnancy (OR 0.39, 95% CI 0.21 to 0.75; 4 studies, 23 927 women; I2=87.2%) and 94% reduced odds of hospital admission (OR 0.06, 95% CI 0.01 to 0.71; 2 studies, 868 women; I2=92%). In adjusted cohort studies, the risk of hypertensive disorders in pregnancy was reduced by 12% (RR 0.88, 95% CI 0.82 to 0.92; 2 studies; 115 085 women), while caesarean section was reduced by 9% (OR 0.91, 95% CI 0.85 to 0.98; 6 studies; 30 192 women). We observed an 8% reduction in the risk of neonatal intensive care unit admission (RR 0.92, 95% CI 0.87 to 0.97; 2 studies; 54 569 women) in babies born to vaccinated versus not vaccinated women. In general, vaccination during pregnancy was not associated with increased risk of adverse pregnancy or perinatal outcomes. Pain at the injection site was the most common side effect reported (77%, 95% CI 52% to 94%; 11 studies; 27 195 women). CONCLUSION: COVID-19 vaccines are effective in preventing SARS-CoV-2 infection and related complications in pregnant women. PROSPERO REGISTRATION NUMBER: CRD42020178076.

Screening and treating Chlamydia trachomatis genital infection to prevent pelvic inflammatory disease: interpretation of findings from randomized controlled trials.

We critically reviewed randomized controlled trials evaluating chlamydia screening to prevent pelvic inflammatory disease (PID) and explored factors affecting interpretation and translation of trial data into public health prevention. Taken together, data from these trials offer evidence that chlamydia screening and treatment is an important and useful intervention to reduce the risk of PID among young women. However, the magnitude of benefit to be expected from screening may have been overestimated based on the earliest trials. It is likely that chlamydia screening programs have contributed to declines in PID incidence through shortening prevalent infections, although the magnitude of their contribution remains unclear. Program factors such as screening coverage as well as natural history factors such as risk of PID after repeat chlamydia infection can be important in determining the impact of chlamydia screening on PID incidence in a population. Uptake of chlamydia screening is currently suboptimal, and expansion of screening among young, sexually active women remains a priority. To reduce transmission and repeat infections, implementation of efficient strategies to treat partners of infected women is also essential. Results of ongoing randomized evaluations of the effect of screening on community-wide chlamydia prevalence and PID will also be valuable.

Missed opportunities for HIV testing among those who accessed sexually transmitted infection (STI) services, tested for STIs and diagnosed with STIs: a systematic review and meta-analysis.

INTRODUCTION: Of 37.7 million people living with HIV in 2020, 6.1 million still do not know their HIV status. We synthesize evidence on concurrent HIV testing among people who tested for other sexually transmitted infections (STIs). METHODS: We conducted a systematic review using five databases, HIV conferences and clinical trial registries. We included publications between 2010 and May 2021 that reported primary data on concurrent HIV/STI testing. We conducted a random-effects meta-analysis and meta-regression of the pooled proportion for concurrent HIV/STI testing. RESULTS: We identified 96 eligible studies. Among those, 49 studies had relevant data for a meta-analysis. The remaining studies provided data on the acceptability, feasibility, barriers, facilitators, economic evaluation and social harms of concurrent HIV/STI testing. The pooled proportion of people tested for HIV among those attending an STI service (n = 18 studies) was 71.0% (95% confidence intervals: 61.0-80.1, I2 = 99.9%), people tested for HIV among those who were tested for STIs (n = 15) was 61.3% (53.9-68.4, I2 = 99.9%), people tested for HIV among those who were diagnosed with an STI (n = 13) was 35.3% (27.1-43.9, I2 = 99.9%) and people tested for HIV among those presenting with STI symptoms (n = 3) was 27.1% (20.5-34.3, I2 = 92.0%). The meta-regression analysis found that heterogeneity was driven mainly by identity as a sexual and gender minority, the latest year of study, country-income level and region of the world. DISCUSSION: This review found poor concurrent HIV/STI testing among those already diagnosed with an STI (35.3%) or who had symptoms with STIs (27.1%). Additionally, concurrent HIV/STI testing among those tested for STIs varied significantly according to the testing location, country income level and region of the world. A few potential reasons for these observations include differences in national STI-related policies, lack of standard operation procedures, clinician-level factors, poor awareness and adherence to HIV indicator condition-guided HIV testing and stigma associated with HIV compared to other curable STIs. CONCLUSIONS: Not testing for HIV among people using STI services presents a significant missed opportunity, particularly among those diagnosed with an STI. Stronger integration of HIV and STI services is urgently needed to improve prevention, early diagnosis and linkage to care services.

Safety, immunogenicity, and effectiveness of COVID-19 vaccines for pregnant persons: A protocol for systematic review and meta analysis.

INTRODUCTION: Numerous vaccines have been evaluated and approved for coronavirus disease 2019 (COVID-19). Since pregnant persons have been excluded from most clinical trials of COVID-19 vaccines, sufficient data regarding the safety of these vaccines for the pregnant person and their fetus have rarely been available at the time of product licensure. However, as COVID-19 vaccines have been deployed, data on the safety, reactogenicity, immunogenicity, and efficacy of COVID-19 vaccines for pregnant persons and neonates are becoming increasingly available. A living systematic review and meta-analysis of the safety and effectiveness of COVID-19 vaccines for pregnant persons and newborns could provide the information necessary to help guide vaccine policy decisions. METHODS AND ANALYSIS: We aim to conduct a living systematic review and meta-analysis based on biweekly searches of medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries to systematically identify relevant studies of COVID-19 vaccines for pregnant persons. Pairs of reviewers will independently select, extract data, and conduct risk of bias assessments. We will include randomized clinical trials, quasi-experimental studies, cohort, case-control, cross-sectional studies, and case reports. Primary outcomes will be the safety, efficacy, and effectiveness of COVID-19 vaccines in pregnant persons, including neonatal outcomes. Secondary outcomes will be immunogenicity and reactogenicity. We will conduct paired meta-analyses, including prespecified subgroup and sensitivity analyses. We will use the grading of recommendations assessment, development, and evaluation approach to evaluate the certainty of evidence.

Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis.

INTRODUCTION: Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies. METHODS: We screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale. RESULTS: We screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection-as compared with uninfected pregnant women-were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias. CONCLUSIONS: This analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.

Case-crossover analysis of condom use and herpes simplex virus type 2 acquisition.

BACKGROUND: Although growing evidence suggests that condoms offer moderate protection against herpes simplex virus type 2 (HSV-2), inability to control for unknown or unmeasured confounders associated with sexual activity may reduce the accuracy of the estimates. The case-crossover design offers increased control of individual-level confounders, and was thus used with the aim of producing a more accurate estimate of the effect of condom use on HSV-2 acquisition. METHODS: Data were pooled from 6 prospective studies that measured HSV-2 status at enrollment and over follow-up, and included periodic self-reported condom use and sexual activity. Sexual activity contemporaneous with acquisition was assigned to a case period; earlier sexual activity was assigned to a control period. Conditional logistic regression was used to assess differences in behavior during the case and control periods. RESULTS: One hundred ninety-one eligible participants acquired HSV-2 during follow-up. This approach detected a 3.6% increase in the odds of HSV-2 acquisition with each unprotected act (odds ratio = 1.036; 95% confidence interval: 1.021-1.052), but no increase in the odds of acquisition associated with protected acts (odds ratio = 1.008; 95% confidence interval: 0.987-1.030). CONCLUSIONS: This analysis suggests that condoms offer significant protection against HSV-2 transmission.

Human papillomavirus vaccine discussions: an opportunity for mothers to talk with their daughters about sexual health.

PURPOSE: Mother-daughter communication about sex is associated with healthier behavior during adolescence. We sought to characterize mothers' communication with their daughters about human papillomavirus (HPV) vaccine and the potential for these discussions to provide an opportunity for talking about sexual health. METHODS: During December 2009, we conducted an online survey with a nationally representative sample of US mothers of girls aged 11 to 14 years (n = 900; response rate = 66%). We used 3 complimentary approaches to assess HPV vaccine as an opportunity for mother-daughter communication about sex. Estimates are weighted. RESULTS: Sixty-five percent of mothers reported talking with their daughters about HPV vaccine, of whom 41% said that doing so led to a conversation about sex. Mothers who had talked with their daughters about HPV vaccine were more likely than those who had not to have also talked with their daughters about sex (92% vs. 74%, OR = 3.25, CI = 1.57-6.68, P < 0.05), in multivariate analyses. Among mothers who talked about sex when they talked about HPV vaccine, many felt that HPV vaccine provided a good reason to do so (64%) or that it made it easier to start a conversation (33%). CONCLUSIONS: HPV vaccine discussions provide a cue to mother-daughter communication about sex that is as important as some more widely recognized cues. Discussions about HPV vaccine are an acceptable opportunity for mothers to talk with their daughters at an age when communication about sex is most influential. It may be possible for parents to capitalize on HPV vaccine discussions already happening in many families to promote sexual health.

Healthcare resource utilisation pattern and costs associated with herpes simplex virus diagnosis and management: a systematic review.

OBJECTIVES: Little is known about the economic burden of herpes simplex virus (HSV) across countries. This article aims to summarise existing evidence on estimates of costs and healthcare resource utilisation associated with genital and neonatal HSV infection. DESIGN: Systematic literature review. DATA SOURCES: Seven databases were searched from inception to 31 August 2020. A focused search was performed to supplement the results. ELIGIBILITY CRITERIA: Studies which reported either healthcare resource utilisation or costs associated with HSV-related healthcare, including screening, diagnosis and treatment of genital HSV infection and neonatal herpes prevention and treatment. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed the risk of bias using the Larg and Moss's checklist. All data were summarised narratively. RESULTS: Out of 11 443 articles, 38 were included. Most studies (35/38, 94.6%) were conducted in high-income countries, primarily the United States, and were more often related to the prevention or management of neonatal herpes (n=21) than HSV genital ulcer disease (n=17). Most analyses were conducted before 2010. There was substantial heterogeneity in the reporting of HSV-related healthcare resource utilisation, with 74%-93% individuals who sought care for HSV, 11.6%-68.4% individuals who received care, while neonates with herpes required a median of 6-34 hospitalisation days. The costs reported were similarly heterogeneous, with wide variation in methodology, assumptions and outcome measures between studies. Cost for screening ranged from US$7-100, treatment ranged from US$0.53-35 for an episodic therapy, US$240-2580 yearly for suppressive therapy, while hospitalisation for neonatal care ranged from US$5321-32 683. CONCLUSIONS: A paucity of evidence exists on healthcare resource utilisation and costs associated with HSV infection, especially among low-income and middle-income countries. Future research is needed on costs and healthcare utilisation patterns to improve overall understanding of the global economic burden of HSV.

INCIDENCE OF HERPES SIMPLEX VIRUS KERATITIS AND OTHER OCULAR DISEASE: GLOBAL REVIEW AND ESTIMATES.

PURPOSE: We aimed to review available data on the incidence of herpes simplex virus (HSV) keratitis and other HSV ocular disease and to estimate the global burden of HSV ocular disease. METHODS: We searched Medline and Embase databases to October 2020 for studies reporting on the incidence of HSV ocular disease. Study quality was evaluated using a four-point checklist. Pooled estimates were applied to 2016 population data to estimate global HSV ocular disease burden. Numbers with uniocular vision impairment (any visual acuity <6/12) were estimated by applying published risks to case numbers. RESULTS: Fourteen studies had incidence data; seven met our quality criteria. In 2016, an estimated 1.7 (95% confidence interval, 95% CI 1.0-3.0) million people had HSV keratitis, based on a pooled incidence of 24.0 (95% CI 14.0-41.0; N = 2; I2 = 97.7%) per 100,000 person-years. The majority had epithelial keratitis (pooled incidence 16.1 per 100,000; 95% CI 11.6-22.3; N = 3; I2 = 92.6%). Available studies were few and limited to the USA and Europe. Data were even more limited for HSV uveitis and retinitis, although these conditions may collectively contribute a further >0.1 million cases. Based on global incidence, some 230,000 people may have newly acquired uniocular vision impairment associated with HSV keratitis in 2016. CONCLUSION: Over 1.8 million people may have herpetic eye disease annually. Preventing HSV infection could therefore have an important impact on eye health. Herpetic eye disease burden is likely to have been underestimated, as many settings outside of the USA and Europe have higher HSV-1 prevalence and poorer access to treatment.

Understanding the public health value and defining preferred product characteristics for therapeutic human papillomavirus (HPV) vaccines: World Health Organization consultations, October 2021-March 2022.

The World Health Organization (WHO) global strategy to eliminate cervical cancer (CxCa) could result in >62 million lives saved by 2120 if strategy targets are reached and maintained: 90% of adolescent girls receiving prophylactic human papillomavirus (HPV) vaccine, 70% of women receiving twice-lifetime cervical cancer screening, and 90% of cervical pre-cancer lesions and invasive CxCa treated. However, the cost and complexity of CxCa screening and treatment approaches has hampered scale-up, particularly in low- and middle-income countries (LMICs), and new approaches are needed. Therapeutic HPV vaccines (TxV), which could clear persistent high-risk HPV infection and/or cause regression of pre-cancerous lesions, are in early clinical development and might offer one such approach. During October 2021 to March 2022, WHO, in collaboration with the Bill and Melinda Gates Foundation, convened a series of global expert consultations to lay the groundwork for understanding the potential value of TxV in the context of current CxCa prevention efforts and for defining WHO preferred product characteristics (PPCs) for TxV. WHO PPCs describe preferences for vaccine attributes that would help optimize vaccine value and use in meeting the global public health need. This paper reports on the main discussion points and findings from the expert consultations. Experts identified several ways in which TxV might address challenges in current CxCa prevention programmes, but emphasized that the potential value of TxV will depend on their degree of efficacy and how quickly they can be developed and implemented relative to ongoing scale-up of existing interventions. Consultation participants also discussed potential use-cases for TxV, important PPC considerations (e.g., vaccine indications, target populations, and delivery strategies), and critical modelling needs for predicting TxV impact and cost-effectiveness.