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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.

Stigma and discrimination ontinue to undermine the effectiveness of the HIV response. Despite a growing body of evidence of the negative relationship between stigma and HIV outcomes, there is a paucity of data available on the prevalence of stigma and its impact. We present a probabilistic cascade model to estimate the magnitude of impact stigma has on mother-to-child-transmission (MTCT). The model was parameterized using 2010 data from Johannesburg, South Africa, from which loss-to-care at each stage of the antenatal cascade were available. Three scenarios were compared to assess the individual contributions of stigma, non-stigma related barriers, and drug ineffectiveness on the overall number of infant infections. Uncertainty analysis was used to estimate plausible ranges. The model follows the guidelines in place in 2010 when the data were extracted (WHO Option A), and compares this with model results had Option B+ been implemented at the time. The model estimated under Option A, 35% of infant infections being attributed to stigma. This compares to 51% of total infections had Option B+ been implemented in 2010. Under Option B+, the model estimated fewer infections than Option A, due to the availability of more effective drugs. Only 8% (Option A) and 9% (Option B+) of infant infections were attributed to drug ineffectiveness, with the trade-off in the proportion of infections being between stigma and non-stigma-related barriers. The model demonstrates that while the effect of stigma on retention of women at any given stage along the cascade can be relatively small, the cumulative effect can be large. Reducing stigma may be critical in reaching MTCT elimination targets, because as countries improve supply-side factors, the relative impact of stigma becomes greater. The cumulative nature of the PMTCT cascade results in stigma having a large effect, this feature may be harnessed for efficiency in investment by prioritizing interventions that can affect multiple stages of the cascade simultaneously.

Population HIV prevalence across West Africa varies substantially. We assess the national epidemiological and behavioural factors associated with this. National, urban and rural data on HIV prevalence, the percentage of younger (15-24) and older (25-49) women and men reporting multiple (2+) partners in the past year, HIV prevalence among female sex workers (FSWs), men who have bought sex in the past year (clients), and ART coverage, were compiled for 13 countries. An Ecological analysis using linear regression assessed which factors are associated with national variations in population female and male HIV prevalence, and with each other. National population HIV prevalence varies between 0 4-2 9% for men and 0 4-5.6% for women. ART coverage ranges from 6-23%. National variations in HIV prevalence are not shown to be associated with variations in HIV prevalence among FSWs or clients. Instead they are associated with variations in the percentage of younger and older males and females reporting multiple partners. HIV prevalence is weakly negatively associated with ART coverage, implying it is not increased survival that is the cause of variations in HIV prevalence. FSWs and younger female HIV prevalence are associated with client population sizes, especially older men. Younger female HIV prevalence is strongly associated with older male and female HIV prevalence. In West Africa, population HIV prevalence is not significantly higher in countries with high FSW HIV prevalence. Our analysis suggests, higher prevalence occurs where more men buy sex, and where a higher percentage of younger women, and older men and women have multiple partnerships. If a sexual network between clients and young females exists, clients may potentially bridge infection to younger females. HIV prevention should focus both on commercial sex and transmission between clients and younger females with multiple partners.

The Avahan programme has provided HIV prevention activities, including condom promotion, to female sex workers (FSWs) in southern India since 2004. Evidence suggests Avahan averted 202,000 HIV infections over 4 years. For replicating this intervention elsewhere, it is essential to understand how the intervention's impact could have been optimised for different budget levels. Behavioural data were used to determine how condom use varied for FSWs with different levels of intervention intensity. Cost data from 64 Avahan districts quantified how district-level costs related to intervention scale and intensity. A deterministic model for HIV transmission amongst FSWs and clients projected the impact and cost of intervention strategies for different scale and intensity, and identified the optimal strategies that maximise impact for different budget levels. As budget levels increase, the optimal intervention strategy is to first increase intervention intensity which achieves little impact, then scale-up coverage to high levels for large increases in impact, and lastly increase intensity further for small additional gains. The cost-effectiveness of these optimal strategies generally improves with increasing resources, while straying from these strategies can triple costs for the same impact. Projections suggest Avahan was close to being optimal, and moderate budget reductions (≥ 20%) would have reduced impact considerably (>40%). Our analysis suggests that tailoring the design of HIV prevention programmes for FSWs can improve impact, and that a certain level of resources are required to achieve demonstrable impact. These insights are critical for optimising the use of limited resources for preventing HIV.

Introduction In Bangalore, new HIV infections of female sex workers and men who have sex with men continue to occur, despite high condom use. Pre‐exposure prophylaxis (PrEP) has high anti‐HIV efficacy for men who have sex with men. PrEP demonstration projects are underway amongst Indian female sex workers. We estimated the impact and efficiency of prioritizing PrEP to female sex workers and/or men who have sex with men in Bangalore. Methods A mathematical model of HIV transmission and treatment for female sex workers, clients, men who have sex with men and low‐risk groups was parameterized and fitted to Bangalore data. The proportion of transmission attributable (population attributable fraction) to commercial sex and sex between men was calculated. PrEP impact (infections averted, life‐years gained) and efficiency (life‐years gained/infections averted per 100 person‐years on PrEP) were estimated for different levels of PrEP adherence, coverage and prioritization strategies (female sex workers, high‐risk men who have sex with men, both female sex workers and high‐risk men who have sex with men, or female sex workers with lower condom use), under current conditions and in a scenario with lower baseline condom use amongst key populations. Results Population attributable fractions for commercial sex and sex between men have declined over time, and they are predicted to account for 19% of all new infections between 2016 and 2025. PrEP could prevent a substantial proportion of infections amongst female sex workers and men who have sex with men in this setting (23%/27% over 5/10 years, with 60% coverage and 50% adherence), which could avert 2.9%/4.3% of infections over 5/10 years in the whole Bangalore population. Impact and efficiency in the whole population was greater if female sex workers were prioritized. Efficiency increased, but impact decreased, if only female sex workers with lower condom use were given PrEP. Greater impact and efficiency was predicted for the scenario with lower condom use. Conclusions PrEP could be beneficial for female sex workers and men who have sex with men in Bangalore, and give some benefits in the general population, especially in similar settings with lower condom use levels.

Diarrhoeal infections are one of the leading causes of child’s mortality and morbidity. Vaccines against Shigella, enterotoxigenic E. coli (ETEC), norovirus and invasive non-typhoidal Salmonella are in clinical development, however, their full value in terms of short and long-term health and socio-economic burden needs to be evaluated and communicated, to rationalise investment in vaccine development, and deployment. While estimates of mortality of enteric infections exist, the long-term morbidity estimates are scarce and have not been systematically collected. The World Health Organization (WHO) has convened a Burden of Enteric Diseases Morbidity Working Group (BoED MWG) who identified key workstreams needed to characterise the morbidity burden of enteric infections. The group also identified four criteria for the prioritisation of pathogens of which impact on long-term morbidity needs to be assessed. The BoED MWG suggested to identify and analyse the individual level data from historical datasets to estimate the impact of enteric infections and confounders on long-term morbidity, including growth faltering and cognitive impairment in children (workstream 1); to conduct a systematic review of evidence on the association of aetiology specific diarrhoea with short- and long- term impact on growth, including stunting, and possibly cognitive impairment in children, while accounting for potential confounders (workstream 2); and to conduct a systematic review of evidence on the association of aetiology specific diarrhoea with short- and long- term impact on health outcomes in adults. The experts prioritised four pathogens for this work: Campylobacter jejuni, ETEC (LT or ST), norovirus (G1 or G2), and Shigella (dysenteriae, flexneri, sonnei). The proposed work will contribute to improving the understanding of the impact of enteric pathogens on long-term morbidity. The timing of this work is critical as all four pathogens have vaccine candidates in the clinical pipeline and decisions about investments in development, manufacturing or vaccine procurement and use are expected to be made soon.

Multiple factors contribute to variation in disease burden, including the type and quality of data, and inherent properties of the models used. Understanding how these factors affect mortality estimates is crucial, especially in the context of public health decision making. We examine how the quality of the studies selected to provide mortality data, influence estimates of burden and provide recommendations about the inclusion of studies and datasets to calculate mortality estimates. To determine how mortality estimates are affected by the data used to generate model outputs, we compared the studies used by The Institute of Health Metrics and Evaluation (IHME) and Maternal and Child Epidemiology Estimation (MCEE) modelling groups to generate enterotoxigenic Escherichia coli (ETEC) and Shigella-associated mortality estimates for 2016. Guided by an expert WHO Working Group, we applied a modified Newcastle-Ottawa Scale (NOS) to evaluate the quality of studies used by both modelling groups. IHME and MCEE used different sets of ETEC and Shigella studies in their models and the majority of studies were high quality. The distribution of the NOS scores was similar between the two modelling groups. We observed an overrepresentation of studies from some countries in SEAR, AFR and WPR compared to other WHO regions. We identified key differences in study inclusion and exclusion criteria used by IHME and MCEE and discuss their impact on datasets used to generate diarrhoea-associated mortality estimates. Based on these observations, we provide a set of recommendations for future estimates of mortality associated with enteric diseases.

Background The Avahan intervention promotes consistent (100%) condom use amongst men who have sex with men in southern India. We assessed how condom use varies with intervention exposure for men who have sex with men in Bangalore. Methods Self-reported condom use and intervention exposure data were derived from a cross-sectional survey. Consistent condom use and condom use at last sex act with all, main, and casual male sex partners were assessed. Binary and continuous variables reflecting intervention exposure (including contact(s) with intervention staff, receiving condoms and seeing condom demonstrations) were used. Multivariable logistic regression was employed to assess the relationship between condom use with each type of partner and each exposure variable independently, controlling for socio-demographic and behavioural factors associated with condom use or intervention exposure. Results Condom use with all partners was higher among those who had ever been contacted by, received condoms from, or seen a condom demonstration by intervention staff (adjusted odds ratio >2, p < 0.02 for all). Consistent condom use with all types of partner increased with the number of condom demonstrations seen in the last month (adjusted odds ratio = 2.1 per demonstration, p < 0.025), while condom use at last sex act with a casual (but not main) partner increased with the number of condoms received from the intervention (adjusted odds ratio = 1.4 per condom, p = 0.04). Conclusions Direct contact with Avahan program staff is associated with increased reported condom use among men who have sex with men in Bangalore. Reported consistent condom use and condom use at last sex act are associated with contacts involving demonstrations of correct condom use, and with receiving condoms, respectively.

In Bangalore, new HIV infections of female sex workers and men who have sex with men continue to occur, despite high condom use. Pre?exposure prophylaxis (PrEP) has high anti?HIV efficacy for men who have sex with men. PrEP demonstration projects are underway amongst Indian female sex workers. We estimated the impact and efficiency of prioritizing PrEP to female sex workers and/or men who have sex with men in Bangalore. A mathematical model of HIV transmission and treatment for female sex workers, clients, men who have sex with men and low?risk groups was parameterized and fitted to Bangalore data. The proportion of transmission attributable (population attributable fraction) to commercial sex and sex between men was calculated. PrEP impact (infections averted, life?years gained) and efficiency (life?years gained/infections averted per 100 person?years on PrEP) were estimated for different levels of PrEP adherence, coverage and prioritization strategies (female sex workers, high?risk men who have sex with men, both female sex workers and high?risk men who have sex with men, or female sex workers with lower condom use), under current conditions and in a scenario with lower baseline condom use amongst key populations. PrEP could be beneficial for female sex workers and men who have sex with men in Bangalore, and give some benefits in the general population, especially in similar settings with lower condom use levels.