Brachytherapy for rhabdomyosarcoma: Survey of international clinical practice and development of guidelines.

BACKGROUND AND PURPOSE: The purpose of this study was to address the lack of published data on the use of brachytherapy in pediatric rhabdomyosarcoma by describing current practice as starting point to develop consensus guidelines. MATERIALS AND METHODS: An international expert panel on the treatment of pediatric rhabdomyosarcoma comprising 24 (pediatric) radiation oncologists, brachytherapists and pediatric surgeons met for a Brachytherapy Workshop hosted by the European paediatric Soft tissue Sarcoma Study Group (EpSSG). The panel's clinical experience, the results of a previously distributed questionnaire, and a review of the literature were presented. RESULTS: The survey indicated the most common use of brachytherapy to be in combination with tumor resection, followed by brachytherapy as sole local therapy modality. HDR was increasingly deployed in pediatric practice, especially for genitourinary sites. Brachytherapy planning was mostly by 3D imaging based on CT. Recommendations for patient selection, treatment requirements, implant technique, delineation, dose prescription, dose reporting and clinical management were defined. CONCLUSIONS: Consensus guidelines for the use of brachytherapy in pediatric rhabdomyosarcoma have been developed through multicenter collaboration establishing the basis for future work. These have been adopted for the open EpSSG overarching study for children and adults with Frontline and Relapsed RhabdoMyoSarcoma (FaR-RMS).

Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-vaccinated participants.

We report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4% showing evidence of previous SARS-CoV-2 infection. A total of 286 adults (with or without HIV) were enrolled >4 months after an Ad26.COV2.S prime and randomized 1:1:1:1 to receive either a full or half-dose booster of Ad26.COV2.S or BNT162b2 vaccine. B cell responses (binding, neutralization and antibody dependent cellular cytotoxicity-ADCC), and spike-specific T-cell responses were evaluated at baseline, 2, 12 and 24 weeks post-boost. Antibody and T-cell immunity targeting the Ad26 vector was also evaluated. No vaccine-associated serious adverse events were recorded. The full- and half-dose BNT162b2 boosted anti-SARS-CoV-2 binding antibody levels (3.9- and 4.5-fold, respectively) and neutralizing antibody levels (4.4- and 10-fold). Binding and neutralizing antibodies following half-dose Ad26.COV2.S were not significantly boosted. Full-dose Ad26.COV2.S did not boost binding antibodies but slightly enhanced neutralizing antibodies (2.1-fold). ADCC was marginally increased only after a full-dose BNT162b2. T-cell responses followed a similar pattern to neutralizing antibodies. Six months post-boost, antibody and T-cell responses had waned to baseline levels. While we detected strong anti-vector immunity, there was no correlation between anti-vector immunity in Ad26.COV2.S recipients and spike-specific neutralizing antibody or T-cell responses post-Ad26.COV2.S boosting. Overall, in the context of hybrid immunity, boosting with heterologous full- or half-dose BNT162b2 mRNA vaccine demonstrated superior immunogenicity 2 weeks post-vaccination compared to homologous Ad26.COV2.S, though rapid waning occurred by 12 weeks post-boost. Trial Registration: The study has been registered to the South African National Clinical Trial Registry (SANCTR): DOH-27-012022-7841. The approval letter from SANCTR has been provided in the up-loaded documents.

Frontline and Relapsed Rhabdomyosarcoma (FAR-RMS) Clinical Trial: A Report from the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG).

The Frontline and Relapsed Rhabdomyosarcoma (FaR-RMS) clinical trial is an overarching, multinational study for children and adults with rhabdomyosarcoma (RMS). The trial, developed by the European Soft Tissue Sarcoma Study Group (EpSSG), incorporates multiple different research questions within a multistage design with a focus on (i) novel regimens for poor prognostic subgroups, (ii) optimal duration of maintenance chemotherapy, and (iii) optimal use of radiotherapy for local control and widespread metastatic disease. Additional sub-studies focusing on biological risk stratification, use of imaging modalities, including [18F]FDG PET-CT and diffusion-weighted MRI imaging (DWI) as prognostic markers, and impact of therapy on quality of life are described. This paper forms part of a Special Issue on rhabdomyosarcoma and outlines the study background, rationale for randomisations and sub-studies, design, and plans for utilisation and dissemination of results.

Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-vaccinated participants.

Background: We report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4% showing evidence of previous SARS-CoV-2 infection. Methods: A total of 286 adults (with or without HIV) were enrolled >4 months after an Ad26.COV2.S prime and randomized 1:1:1:1 to receive either a full or half-dose booster of Ad26.COV2.S or BNT162b2 vaccine. B cell responses (binding, neutralization and antibody dependent cellular cytotoxicity-ADCC), and spike-specific T-cell responses were evaluated at baseline, 2, 12 and 24 weeks post-boost. Antibody and T-cell immunity targeting the Ad26 vector was also evaluated. Results: No vaccine-associated serious adverse events were recorded. The full- and half-dose BNT162b2 boosted anti-SARS-CoV-2 binding antibody levels (3.9- and 4.5-fold, respectively) and neutralizing antibody levels (4.4- and 10-fold). Binding and neutralizing antibodies following half-dose Ad26.COV2.S were not significantly boosted. Full-dose Ad26.COV2.S did not boost binding antibodies but slightly enhanced neutralizing antibodies (2.1-fold). ADCC was marginally increased only after a full-dose BNT162b2. T-cell responses followed a similar pattern to neutralizing antibodies. Six months post-boost, antibody and T-cell responses had waned to baseline levels. While we detected strong anti-vector immunity, there was no correlation between anti-vector immunity in Ad26.COV2.S recipients and spike-specific neutralizing antibody or T-cell responses post-Ad26.COV2.S boosting. Conclusion: In the context of hybrid immunity, boosting with heterologous full- or half-dose BNT162b2 mRNA vaccine demonstrated superior immunogenicity 2 weeks post-vaccination compared to homologous Ad26.COV2.S, though rapid waning occurred by 12 weeks post-boost. Trial Registration: South African National Clinical Trial Registry (SANCR): DOH-27-012022-7841. Funding: South African Medical Research Council (SAMRC) and South African Department of Health (SA DoH).

A qPCR assay for the rapid and specific detection of Shining ram's-horn snail (Segmentina nitida) eDNA from Stodmarsh National Nature Reserve, UK.

Segmentina nitida Müller 1774 is a freshwater snail which was formerly widespread throughout England and south Wales. Since the 1840s it has seen a rapid decline in its range which has been attributed to deteriorating water quality due to nutrient enrichment, lowering of water tables and over-management of the ditches in which it resides. S. nitida has therefore been identified as a UK Biodiversity Action Plan (UKBAP) priority species which recommends further research for its conservation. Here we have developed a Taqman based qPCR eDNA assay for the detection of S. nitida at the Stodmarsh National Nature Reserve and compared the results with a manual survey of the ditches at this location. 32 ditches were surveyed in November 2020 (22 at Stodmarsh) and February 2021 (10 outside the known range of S.nitida). Our eDNA analysis exhibited an observed percentage agreement of 84% with a kappa coefficient of agreement between manual and eDNA surveys of 0.56 (95% CI 0.22 to 0.92). Three ditches determined to be negative for S. nitida by eDNA analysis were manual survey positive, and a further two ditches that were negative by manual survey were positive by eDNA analysis revealing the potential for improved overall detection rates using a combination of manual and eDNA methodologies. eDNA analysis could therefore augment manual survey techniques for S. nitida as a relatively quick and inexpensive tool for collecting presence and distribution data that could be used to inform manual surveys and management of ditches.

Reducing the risk of suicide among healthcare staff.

Reducing the number of deaths by suicide is an important area in public health. Several factors, including excessive workload demands and burnout, mean that healthcare staff such as nurses are at higher risk of death by suicide compared with people working in other occupations. This article explores the contributory factors involved in suicide among healthcare professionals and outlines some of the methods that nurses can use to enquire about suicide risk with their colleagues. It also details appropriate interventions that nurses can use to reduce the risk of suicide among their colleagues. The authors aim to increase nurses' understanding of their role in suicide prevention in the healthcare workforce.

Quantitative PCR (qPCR) assay for the specific detection of the Chinese mystery snail (Cipangopaludina chinensis) in the UK.

Cipangopaludina chinensis Gray 1833 is an East Asian freshwater snail and invasive species in many parts of the world (Global Invasive Species Database, 2022). Within the UK, it was first found at the Pevensey Levels, Sussex, and has since been reported at a second site at Southampton Common, Hampshire. Both sites are designated as Sites of Special Scientific Interest (SSSI) for their wildlife importance. Although the impacts of this species within the UK have not yet been investigated several exotic parasites of the snail have been reported and research suggests that its presence can negatively impact native snail species. This is especially important at the Pevensey Levels due to the presence of the rare freshwater mollusc Anisus vorticulus (Little Whirlpool Rams's-horn snail). Here, we have developed a qPCR-based eDNA assay for the detection of C. chinensis and compared water samples tested for eDNA with results from manual survey of the ditches at the Pevensey Levels. Our eDNA analysis exhibited an overall observed percentage agreement of 80% with a kappa coefficient of agreement between manual and eDNA surveys of 0.59 (95% CI 0.31 to 0.88). Some samples which were qPCR negative for C. chinensis were positive by manual survey, and vice versa revealing the potential for improved overall detection rates when using a combination of manual and eDNA methodologies. eDNA analysis can therefore augment manual survey techniques for C. chinensis as a relatively quick and inexpensive tool for collecting presence and distribution data that could be used to inform further manual surveys and control measures within the ditches.

State-of-the-Science of human papillomavirus vaccination in women with human immunodeficiency Virus: Summary of a scientific workshop.

The burden of cervical cancer is disproportionately distributed globally, with the vast majority of cases occurring in low- and middle-income countries. Women with human immunodeficiency virus (HIV) (WWH) are at increased risk of human papillomavirus (HPV) infection and cervical cancer as compared to HIV-negative individuals. HPV vaccination remains a priority in regions with a high burden of cervical cancer and high HIV prevalence. With HPV vaccines becoming more accessible, optimal use beyond the initial World Health Organization-recommended target population of 9 to 14-year-old girls is an important question. In March 2022, a group of experts in epidemiology, immunology, and vaccinology convened to discuss the state-of-the-science of HPV vaccination in WWH. This report summarizes the proceedings: review of HIV epidemiology and its intersection with cervical cancer burden, immunology, HPV vaccination including reduced-dose schedules and experience with other vaccines in people with HIV (PWH), HPV vaccination strategies and knowledge gaps, and outstanding research questions. Studies of HPV vaccine effectiveness among WWH, including duration of protection, are limited. Until data from ongoing research is available, the current recommendation for WWH remains for a multi-dose HPV vaccination regimen. A focus of the discussion included the potential impact of HIV acquisition following HPV vaccination. With no data currently existing for HPV vaccines and limited information from non-HPV vaccines, this question requires further research. Implementation research on optimal HPV vaccine delivery approaches for WWH and other priority populations is also urgently needed.

Counterfactual estimation of efficacy against placebo for novel PrEP agents using external trial data: example of injectable cabotegravir and oral PrEP in women.

INTRODUCTION: Multiple antiretroviral agents have demonstrated efficacy for human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP). As a result, clinical trials of novel agents have transitioned from placebo- to active-controlled designs; however, active-controlled trials do not provide an estimate of efficacy versus no use of PrEP. Counterfactual placebo comparisons using other data sources could be employed to provide this information. METHODS: We compared the active-controlled study (HPTN 084) of injectable cabotegravir (CAB-LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) among women from seven countries in Africa to three external, contemporaneous randomized HIV prevention trials from which we constructed counterfactual placebo estimates. We used direct standardization via analysis weights to achieve the same distribution of person-years between the external study and HPTN 084, across strata predictive of HIV risk (country and selected risk covariates). We estimated prevention efficacy against a counterfactual placebo to provide information on the use of CAB-LA and FTC/TDF compared to no intervention. We compared the counterfactual placebo findings for FTC/TDF to previous placebo-controlled trials, adjusted for observed adherence to daily pills. RESULTS: Distribution of age and baseline prevalence of gonorrhoea and chlamydia were similar among matched counterfactual placebo and observed HPTN 084 arms after standardization. Counterfactual estimates of CAB-LA versus placebo in all three settings showed a consistent risk reduction of 93%-94%, with lower bounds of the confidence intervals above 72%. Observed adherence (quantifiable tenofovir in plasma) in HPTN 084 was 54%-56%, and estimated efficacy of daily oral FTC/TDF against a counterfactual placebo was consistent with a predicted risk reduction of 39%-40% for this level of daily pill use. CONCLUSIONS: Counterfactual placebo rates of HIV acquisition derived from external trial data in similar locations and time can be used to support estimates of placebo-based efficacy of a novel HIV prevention agent. External trial data must be standardized to be representative of the clinical trial cohort testing the novel HIV prevention agent, accounting for confounders.

No woman left behind: achieving cervical cancer elimination among women living with HIV.

Cervical cancer is the fourth most common malignancy in women of reproductive age globally. The burden of this disease is highest in low-income and middle-income countries, especially among women living with HIV. In 2018, WHO launched a global strategy to accelerate cervical cancer elimination through rapid scale-up of prophylactic vaccination, cervical screening, and treatment of precancers and cancers. This initiative was key in raising a call for action to address the stark global disparities in cervical cancer burden. However, achieving elimination of cervical cancer among women with HIV requires consideration of biological and social issues affecting this population. This Position Paper shows specific challenges and uncertainties on the way to cervical cancer elimination for women living with HIV and highlights the scarcity of evidence for the effect of interventions in this population. We argue that reaching equity of outcomes for women with HIV will require substantial advances in approaches to HPV vaccination and improved understanding of the long-term effectiveness of HPV vaccines in settings with high HIV burden cervical cancer, just as HIV, is affected by social and structural factors such as poverty, stigma, and gender discrimination, that place the elimination strategy at risk. Global efforts must, therefore, be galvanised to ensure women living with HIV have optimised interventions, given their substantial risk of this preventable malignancy.

The Future of Epidemic and Pandemic Vaccines to Serve Global Public Health Needs.

This Review initiates a wide-ranging discussion over 2023 by selecting and exploring core themes to be investigated more deeply in papers submitted to the Vaccines Special Issue on the "Future of Epidemic and Pandemic Vaccines to Serve Global Public Health Needs". To tackle the SARS-CoV-2 pandemic, an acceleration of vaccine development across different technology platforms resulted in the emergency use authorization of multiple vaccines in less than a year. Despite this record speed, many limitations surfaced including unequal access to products and technologies, regulatory hurdles, restrictions on the flow of intellectual property needed to develop and manufacture vaccines, clinical trials challenges, development of vaccines that did not curtail or prevent transmission, unsustainable strategies for dealing with variants, and the distorted allocation of funding to favour dominant companies in affluent countries. Key to future epidemic and pandemic responses will be sustainable, global-public-health-driven vaccine development and manufacturing based on equitable access to platform technologies, decentralised and localised innovation, and multiple developers and manufacturers, especially in low- and middle-income countries (LMICs). There is talk of flexible, modular pandemic preparedness, of technology access pools based on non-exclusive global licensing agreements in exchange for fair compensation, of WHO-supported vaccine technology transfer hubs and spokes, and of the creation of vaccine prototypes ready for phase I/II trials, etc. However, all these concepts face extraordinary challenges shaped by current commercial incentives, the unwillingness of pharmaceutical companies and governments to share intellectual property and know-how, the precariousness of building capacity based solely on COVID-19 vaccines, the focus on large-scale manufacturing capacity rather than small-scale rapid-response innovation to stop outbreaks when and where they occur, and the inability of many resource-limited countries to afford next-generation vaccines for their national vaccine programmes. Once the current high subsidies are gone and interest has waned, sustaining vaccine innovation and manufacturing capability in interpandemic periods will require equitable access to vaccine innovation and manufacturing capabilities in all regions of the world based on many vaccines, not just "pandemic vaccines". Public and philanthropic investments will need to leverage enforceable commitments to share vaccines and critical technology so that countries everywhere can establish and scale up vaccine development and manufacturing capability. This will only happen if we question all prior assumptions and learn the lessons offered by the current pandemic. We invite submissions to the special issue, which we hope will help guide the world towards a global vaccine research, development, and manufacturing ecosystem that better balances and integrates scientific, clinical trial, regulatory, and commercial interests and puts global public health needs first.

A research and development (R&D) roadmap for broadly protective coronavirus vaccines: A pandemic preparedness strategy.

Broadly protective coronavirus vaccines are an important tool for protecting against future SARS-CoV-2 variants and could play a critical role in mitigating the impact of future outbreaks or pandemics caused by novel coronaviruses. The Coronavirus Vaccines Research and Development (R&D) Roadmap (CVR) is aimed at promoting the development of such vaccines. The CVR, funded by the Bill & Melinda Gates Foundation and The Rockefeller Foundation, was generated through a collaborative and iterative process, which was led by the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota and involved 50 international subject matter experts and recognized leaders in the field. This report summarizes the major issues and areas of research outlined in the CVR and identifies high-priority milestones. The CVR covers a 6-year timeframe and is organized into five topic areas: virology, immunology, vaccinology, animal and human infection models, and policy and finance. Included in each topic area are key barriers, gaps, strategic goals, milestones, and additional R&D priorities. The roadmap includes 20 goals and 86 R&D milestones, 26 of which are ranked as high priority. By identifying key issues, and milestones for addressing them, the CVR provides a framework to guide funding and research campaigns that promote the development of broadly protective coronavirus vaccines.

Impact and cost-effectiveness of the national scale-up of HIV pre-exposure prophylaxis among female sex workers in South Africa: a modelling analysis.

INTRODUCTION: In 2016, South Africa (SA) initiated a national programme to scale-up pre-exposure prophylaxis (PrEP) among female sex workers (FSWs), with ∼20,000 PrEP initiations among FSWs (∼14% of FSW) by 2020. We evaluated the impact and cost-effectiveness of this programme, including future scale-up scenarios and the potential detrimental impact of the COVID-19 pandemic. METHODS: A compartmental HIV transmission model for SA was adapted to include PrEP. Using estimates on self-reported PrEP adherence from a national study of FSW (67.7%) and the Treatment and Prevention for FSWs (TAPS) PrEP demonstration study in SA (80.8%), we down-adjusted TAPS estimates for the proportion of FSWs with detectable drug levels (adjusted range: 38.0-70.4%). The model stratified FSW by low (undetectable drug; 0% efficacy) and high adherence (detectable drug; 79.9%; 95% CI: 67.2-87.6% efficacy). FSWs can transition between adherence levels, with lower loss-to-follow-up among highly adherent FSWs (aHR: 0.58; 95% CI: 0.40-0.85; TAPS data). The model was calibrated to monthly data on the national scale-up of PrEP among FSWs over 2016-2020, including reductions in PrEP initiations during 2020. The model projected the impact of the current programme (2016-2020) and the future impact (2021-2040) at current coverage or if initiation and/or retention are doubled. Using published cost data, we assessed the cost-effectiveness (healthcare provider perspective; 3% discount rate; time horizon 2016-2040) of the current PrEP provision. RESULTS: Calibrated to national data, model projections suggest that 2.1% of HIV-negative FSWs were currently on PrEP in 2020, with PrEP preventing 0.45% (95% credibility interval, 0.35-0.57%) of HIV infections among FSWs over 2016-2020 or 605 (444-840) infections overall. Reductions in PrEP initiations in 2020 possibly reduced infections averted by 18.57% (13.99-23.29). PrEP is cost-saving, with $1.42 (1.03-1.99) of ART costs saved per dollar spent on PrEP. Going forward, existing coverage of PrEP will avert 5,635 (3,572-9,036) infections by 2040. However, if PrEP initiation and retention doubles, then PrEP coverage increases to 9.9% (8.7-11.6%) and impact increases 4.3 times with 24,114 (15,308-38,107) infections averted by 2040. CONCLUSIONS: Our findings advocate for the expansion of PrEP to FSWs throughout SA to maximize its impact. This should include strategies to optimize retention and should target women in contact with FSW services.

The Practical Role of Induced Resistance for Crop Protection.

Plants have evolved a highly sophisticated immune system to resist pathogen attack comprising both preformed and inducible mechanisms. Over the last 50 years, various biological and chemical inducers have been used to artificially trigger the defense response in plants, thereby promoting an induced resistance (IR) to subsequent pathogen attack. IR has proven effective for disease control in laboratory and glasshouse conditions but has seldom equalled the level of protection offered by synthetic pesticides in the field. However, renewed interest in IR for crop protection is being driven by legislation to reduce the use of synthetic chemicals in agriculture. Inducers can contribute to integrated crop management strategies when used in combination with fungicides, bactericides, and with other biological control options. Integrating inducers in this way can reduce chemical inputs without loss of efficacy. Moreover, advances in our understanding of plant defense are informing the development of new inducers and guiding new strategies for their implementation in sustainable crop protection. This review will discuss the use of IR in selected cropping systems and describe opportunities for optimizing its potential, including the development of more effective inducers and their integration with conventional and cultural control options.

Public health opportunities resulting from sufficient HPV vaccine supply and a single-dose vaccination schedule.

Many countries with the highest burdens of cervical cancer have not yet offered human papillomavirus (HPV) vaccines to most of their age-eligible girls, who as adults also have limited or no access to effective cervical cancer screening or treatment. There are now 2 complementary developments that could make HPV vaccines more accessible and affordable: 1) the current and projected increases in HPV vaccine supply; and 2) the permissive recommendation for single-dose HPV vaccination schedules. This change in policy paired with the healthier HPV vaccine supply is an incredible opportunity to facilitate rapid access and expansion of HPV vaccination. Female adolescent vaccination including multiage cohorts must be prioritized. In the coming decades, this is the most cost-effective approach to avert millions of projected cervical cancer cases, which account for most HPV-related cancers globally.

National advisory panels for childhood cancer in the United Kingdom: An evaluation of current practice and a best practice statement for the future.

BACKGROUND: National advisory panels (NAPs) have been established for the care of children and young people (CYP) with cancer in the United Kingdom since 2011, with an increase in panel number in recent years. Their practice has not previously been reviewed; therefore, we sought to evaluate the role, practice and impact of six selected NAPs offering expertise in ependymoma, histiocytosis, leukaemia, neuroblastoma, renal tumours and sarcoma. PROCEDURE: This service evaluation used mixed methodology, including review of NAP documentation, semi-structured interviews with the NAP chairs and an analysis of the cases referred for discussion. RESULTS: Total 1110 referrals were analysed. Results demonstrated the significant scope and amount of work undertaken by the NAPs, largely testament to the commitment of the panel members. Specific roles fulfilled have been highlighted, and NAP recommendations have been shown to influence clinical decision-making and be implemented in the majority of cases. Despite widespread good practice, areas to address have been identified; these include clarity regarding NAP membership, consistency in recommendations, the consideration of holistic information to promote personalised management and the exploration of wider multidisciplinary team roles. CONCLUSIONS: In the context of increasing demand and the escalating number of NAPs, it is timely to consider how service improvement can be facilitated. Best practice guidelines have been formulated as a product of this study, to promote a sustainable and effective model for NAPs. Review and benchmarking national panel performance against these guidelines will drive high standards of care going forward and they should be embedded as standard practice.

The Global Demand and Supply Balance of the Human Papillomavirus Vaccine: Implications for the Global Strategy for the Elimination of Cervical Cancer.

As of November 2023, 140 World Health Organization (WHO) member states had introduced human papillomavirus (HPV) vaccination in their routine immunization schedules. Despite a continuously increasing demand from countries across all income groups, supply constraints, COVID-19 pandemic disruptions, and other factors have slowed the pace of introduction, particularly in low-resource settings. Using a population-based forecasting methodology and leveraging the WHO's yearly vaccine supply data collection, we updated global demand and supply projections for the HPV vaccine for the period of 2022-2031. The analysis aimed at clarifying the magnitude of the challenges to bringing in equitable access to HPV vaccines, which can hinder the achievement of the Global Strategy for the Elimination of Cervical Cancer. The results of this analysis show that the risk of HPV shortages has significantly decreased, and global supply is now, under normal circumstances, sufficient to meet global demand. In the long term, HPV supply will be more than sufficient to meet the Global Strategy's goal of 90% of girls fully vaccinated with the HPV vaccine by the age of 15 years. Nonetheless, paying attention to the formulation of policies and carefully managing demand and supply will be required to ensure the long-term sustainability of the HPV vaccine program.

High prevalence of SARS-CoV-2 antibodies in pregnant women after the second wave of infections in the inner-city of Johannesburg, Gauteng Province, South Africa.

OBJECTIVES: After South Africa's second wave of COVID-19, this study estimated the SARS-CoV-2 seroprevalence among pregnant women in inner-city Johannesburg, South Africa. METHODS: In this cross-sectional survey, 500 pregnant women who were non-COVID-19-vaccinated (aged ≥12 years) were enrolled, and demographic and clinical data were collected. Serum samples were tested using the Wantai SARS-CoV-2 spike antibody enzyme-linked immunosorbent assay and Roche Elecsys® anti-SARS-CoV-2 nucleocapsid antibody assays. Seropositivity was defined as SARS-CoV-2 antibodies on either (primary) or both (secondary) assays. Univariate Poisson regression assessed risk factors associated with seropositivity. RESULTS: The median age was 27.4 years, and HIV prevalence was 26.7%. SARS-CoV-2 seroprevalence was 64.0% (95% confidence interval [CI]: 59.6-68.2%) on the primary and 54% (95% CI: 49.5-58.4%) on the secondary measure. Most (96.6%) women who were SARS-CoV-2-seropositive reported no symptoms. On the Roche assay, we detected lower seroprevalence among women living with HIV than women without HIV (48.9% vs 61.7%, P-value = 0.018), and especially low levels among women living with HIV with a clusters of differentiation 4 <350 cells/ml compared with women without immune suppression (22.2% vs 56.4%, prevalence rate ratio = 0.4; 95% CI: 0.2-0.9; P-value = 0.046). CONCLUSION: Pregnant women attending routine antenatal care had a high SARS-CoV-2 seroprevalence after the second wave in South Africa, and most had asymptomatic infections. Seroprevalence surveys in pregnant women present a feasible method of monitoring the course of the pandemic over time.