The burden of hand, foot, and mouth disease (HFMD) in children under five is substantial, with the greatest burden in China. Most cases are mild, although some are severe and even fatal. A vaccine against EV-A71, the pathogen most commonly associated with severe HFMD, was licensed in China in Dec 2015 but not introduced into the National Immunisation Programme (NIP). It was hence not covered by routine national vaccine surveillance and its coverage remained unknown for the years following its initial licensure. Here we report the results of a novel data collection and analysis approach to address this knowledge gap. Local public health entities were invited to report county-specific numbers of EV-A71 vaccine doses administered between 2016 and 2019 in mainland China. A cohort model was then used to estimate vaccine coverage. The association between county-level factors (epidemiological, socioeconomic, demographic, and environmental) and vaccine coverage was assessed using zero-inflated beta regression models. We received responses from 2,248 out of 3,252 counties in 23 of 31provinces in mainland China. The median county-level EV-A71 vaccine coverage was 10.17% [IQR: 3.50%, 19.39%] in 2018 and 16.70% [IQR: 8.78%, 27.45%] in 2019. However, the median absolute differences in coverage (i.e., max-min) within-prefecture were ~30%. Results from the regression model indicate that low vaccine coverage was associated with low socioeconomic status, small populations and high proportions of young children. Coverage of EV-A71 vaccines was low in China prior to the COVID-19 pandemic, with substantial geographical disparities over 4 years after the initial vaccine licensure. Our results illustrate the private market response to a new childhood vaccine that is licensed but not centrally funded. Despite economic growth, vaccine coverage among marginalised populations will likely be low without targeted policy and financial support.

BACKGROUND:Estimates of vaccine impact have typically been used to quantify the effects of, and inform, immunisation strategies. Given the growing resource constraints on health systems worldwide, robust estimates of vaccine impact that allow comparison across different vaccines are now more crucial for decision making than ever. Building on previous modelling studies, we aimed to estimate vaccine impact ratios for an expanded portfolio of Gavi, the Vaccine Alliance-supported vaccination programmes against 14 vaccine-preventable diseases across 117 low-income and middle-income countries using multiple models. METHODS:In this modelling study, we have presented Vaccine Impact Modelling Consortium estimates of vaccine impact ratios, defined as deaths or disability-adjusted life-years averted per 1000 vaccinations, for the Gavi portfolio of vaccines. Modelling groups used standardised inputs for demographic data and vaccination coverage assumptions, including a no-vaccination counterfactual, and accounted for structural, parameter, and stochastic uncertainty to produce burden estimates. These estimates were then compared to calculate vaccine impact ratios, disaggregated by immunisation activity type and geographical subregions for vaccinations given between 2000 and 2030 (or 2000 and 2040 for cholera). FINDINGS:Overall, we observed human papillomavirus (11·24 [95% uncertainty interval 10·88-11·64]) and measles (6·09 [4·90-7·07])vaccines averting a higher number of deaths per 1000 vaccinations than others. For other vaccines, the impact ratios varied across subregions and activity types. Due to parameter, structural, and stochastic uncertainty, the ranges of these ratios often overlap. INTERPRETATION:Decisions around which vaccines to use are increasingly important in the context of Gavi's country vaccine budgets. Robust metrics that allow comparison between vaccines are thus essential to inform discussions. The vaccine impact ratios presented in this study can be used to complement other evidence to support effective planning and prioritisation in national immunisation programmes. FUNDING:Gavi, the Vaccine Alliance, Gates Foundation, and Wellcome Trust.

The basic reproduction number, R0, is an epidemiological measure to describe the transmissibility of infectious diseases and evaluate the potential effect of interventions. Measles R0 has historically been considered to be between 12-18, with contextual factors contributing to its heterogeneity, but has rarely been estimated using data across multiple countries. Our study aims to estimate measles R0 in low- and middle-income countries using a standardised database of population-based serosurveys. We fitted an age-structured compartmental model of measles transmission dynamics and vaccination (DynaMICE) to the age-specific seroprevalence data extracted from a recent systematic review. Using Markov Chain Monte Carlo, we estimated setting-specific posterior distributions of R0 in 172 studies with unique survey years and locations from 57 countries. Bootstrapped samples of R0 estimates were pooled by study characteristics, including survey period, geography, and overall bias in sampling, measurement, and reporting results. Measles R0 estimates varied substantially across serostudies, ranging from 0.93 (95% credible interval (CrI): 0.70-1.00) to 147 (95% CrI: 76.5-208), with fewer than 13% of studies having median R0 values in the range of 12-18. Pooled R0 estimates showed smaller medians and variation in serostudies conducted after 2000 or including the adult population, while no distinguishable variation was identified across the World Health Organization regions. Our revised estimates demonstrated the wide range of measles R0 across low- and middle-income settings and highlighted the importance of considering the heterogeneity in measles transmissibility when modelling epidemics and planning interventions and vaccination strategies.

Background In China, many vaccines that are free in other countries have to be paid out of pocket. This makes them inaccessible to low-income and vulnerable people who often have the highest disease burden. China has been investigating whether to increase the range of central government-funded vaccines, but this will require considerable investment and manufacturing capacity. Objectives The National Institute for Health Research Group on Evidence to Policy Pathway to Immunisation in China brought together leading academic and public health institutions in the United Kingdom and China to conduct joint vaccine research to help decision-makers in China develop a vaccination programme that ensures reliable, affordable, equitable and uninterrupted supply of vaccines to the Chinese population. It was also able to address two events with vaccine-related implications in China: the Changchun Changsheng vaccine incident (where a company knowingly sold substandard vaccines) and the COVID-19 pandemic. Design and methods National Institute for Health Research Group on Evidence to Policy Pathway to Immunisation in China established 33 subprojects using different methods, including laboratory testing, qualitative and quantitative surveys of the public and patients, systematic reviews, database searches and modelling (including statistical, mechanistic, geospatial and economic modelling). Setting and participants National Institute for Health Research Group on Evidence to Policy Pathway to Immunisation in China was a United Kingdom–China collaboration involving reciprocal exchanges of research students, scientists and government experts. The four main partners were the London School of Hygiene & Tropical Medicine, Public Health England, Fudan University (one of China’s leading universities in public health) and the Chinese Center for Disease Control and Prevention. Interventions Immunisation against hand, foot and mouth disease, pneumococcal disease, seasonal influenza, respiratory syncytial virus and human papillomavirus. Main outcome measures National Institute for Health Research Group on Evidence to Policy Pathway to Immunisation in China focused on (1) collecting and analysing data about the health and economic consequences of vaccine-preventable diseases in China; (2) understanding vaccine supply, demand and decision-making and (3) projecting the health and economic impact that vaccine introduction could have, particularly among the worst off. Results Vaccine-preventable diseases have the potential to spread rapidly in China. New vaccines against diseases like hand, foot and mouth disease, respiratory syncytial virus and seasonal influenza could have large health benefits and be cost-effective. Public confidence in vaccines was high and recovered quickly after the Changchun Changsheng incident, but awareness and uptake of vaccines that were not centrally funded were low. Non-pharmaceutical interventions and vaccine prioritisation strategies contributed to COVID-19 control in China and elsewhere. Limitations Some subprojects and stakeholder engagement activities were curtailed during the COVID-19 pandemic. Conclusions Results provided evidence of the feasibility, acceptability, potential health benefits, equity impact, budget impact and value for money of funding new vaccines. Future work National Institute for Health Research Group on Evidence to Policy Pathway to Immunisation in China aims to inspire similar models of collaborative research to inform immunisation policy elsewhere in Asia and around the world. Funding This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Global Health Research programme as award number 16/137/109.

Combination vaccines combine several components in a single dose administration. They offer programmatic and public health advantages, particularly as vaccine schedules become increasingly crowded. They are often more expensive to develop and produce, which discourages manufacturer investment without clear market signals. Hence their benefits need to be captured with existing health economic evaluation reference cases used by decision-makers to guide vaccine investments. We propose that the value of combination vaccines can be captured through at least four domains: (1) reductions in tangible and intangible costs to caregivers, (2) operational efficiencies to the health system, (3) opportunity costs of vaccine schedule slots, and (4) more streamlined vaccine schedules. We demonstrate the practicality of our framework by comparing the value of introducing a hypothetical vaccine to a crowded schedule as a standalone formulation, a replacement for a vaccine already in the schedule, or a combination product. The framework could also be applied to estimate the value of reducing the number of separate administrations needed for a standalone vaccine. Applying it in real-world situations could be facilitated by further data collection, particularly on collating results on the value of existing vaccines in the schedule and estimating willingness-to-pay for fewer vaccine administrations.

BACKGROUND:2024 marked the 50th anniversary of the Expanded Programme on Immunization (EPI), launched by WHO. Despite its crucial role in preventing infectious diseases, EPI's 50-year economic impact has not been systematically evaluated. This study aims to estimate the benefit-cost ratios (BCRs) and incremental cost-effectiveness ratios (ICERs) of EPI at global, regional, and national levels. METHODS:We conducted an economic evaluation of EPI for 14 globally important pathogens with robust long-term data availability: Corynebacterium diphtheriae (diphtheria), Haemophilus influenzae type b, hepatitis B virus (hepatitis B), Japanese encephalitis virus (Japanese encephalitis), measles virus (measles), Neisseria meningitidis group A (meningitis A), Streptococcus pneumoniae, Bordetella pertussis (pertussis), poliovirus (polio), rotavirus, rubella virus (rubella), Clostridium tetani (tetanus), Mycobacterium tuberculosis (tuberculosis), and yellow fever virus (yellow fever) from Jan 1, 1974, to Dec 31, 2024, across 194 WHO member states. We compared costs (procurement, administration, and family additional costs from time spent synthesised from authoritative global databases and systematic literature reviews) and benefits (primarily averted mortality retrieved from published global burden estimates) between observed EPI implementation and a counterfactual scenario of no vaccination, from which BCRs and ICERs were derived. FINDINGS:From 1974 to 2024, the cost of EPI reached US$937 billion (95% CI 699-1187), offset by $15 050 billion (12 609-17 605) in averted productivity losses due to mortality (aggregate BCR 16·06 [95% CI 10·62-25·20]; ICER cost-saving). Immunisation against all 14 pathogens showed favourable economic outcomes. Measles vaccination produced the highest BCR (73·97 [45·78-124·06]), and the ICERs for all vaccines remained below conventional cost-effectiveness thresholds. EPI against 14 pathogens in aggregate achieved cost savings (BCR>1) in all 194 WHO member states. Economic returns varied across six WHO regions and four World Bank income groups, with the Eastern Mediterranean region (BCR 17·22 [11·22-28·67]) and low-income countries (BCR 23·63 [16·87-34·32]) showing the highest BCRs. INTERPRETATION:The 50-year EPI has proven highly cost-effective at global, regional, and national levels, and remains a worthwhile investment. The EPI delivered impactful life-saving benefits and favourable economic returns, especially in high-burden and low-income settings. FUNDING:The National Natural Science Foundation of China, the China Postdoctoral Science Foundation, the Vaccine Impact Modelling Consortium, and the Japan Agency for Medical Research and Development.

Public health and social measures (PHSMs) are key interventions during pandemics. This study quantifies temporal changes in daily interpersonal contacts associated with PHSM implementation and their potential impact on disease transmission across different phases of the COVID-19 pandemic in Hong Kong from 2021 to 2023. We recruited 7,053 individuals from the general population and 3,462 participants from selected high-contact groups between September 2021 and December 2023. The study period spanned the infection-naïve phase before 2022 through the city’s fifth wave of COVID-19 (January–April 2022) driven by the Omicron BA.2 variant. Reported cumulative incidence was < 0.2

Seasonal influenza remains a significant global public health challenge, causing substantial morbidity and mortality each year and there remains a need for more effective and durable influenza vaccines. To direct and accelerate research efforts, a full value of vaccine assessment (FVVA) was initiated to quantify the value of next-generation, improved influenza vaccines and identify key challenges that may limit their uptake once available. The FVVA utilized a mixed-methods approach with rapid assessment of literature, stakeholder interviews, and surveys, and quantitative data analysis to estimate the full value of influenza vaccines with improved characteristics. These analyses found that if improved influenza vaccines are broadly employed, depending on their characteristics, using our demand forecast they could avert 6.6-18 billion additional influenza cases, 2.3-6.2 million additional influenza deaths, and 21-57 million disability-adjusted life years (DALYs) between 2025 and 2050 beyond those averted by current seasonal influenza vaccines. Under this scenario, introducing improved influenza vaccines could be cost-effective in 9-48 % of countries at the lowest assumed price point. However, uncertainties about price and future vaccine coverage may impact the potential cost-effectiveness. Furthermore, from the producer perspective, the FVVA highlighted the robust financial value proposition to develop and commercialize improved influenza vaccines, in both established and emerging markets. Strongly tiered prices could make these vaccines cost-effective in more countries and boost impact further. To ensure that improved influenza vaccines achieve the greatest public health benefit, effective collaboration between vaccine developers, vaccine manufacturers, donors, financiers, multilateral organisations, and policy- and decision-makers will be essential.

Even though two widely used combination vaccines (measles-rubella- and diphtheria- tetanus-pertussis-containing vaccines) are universally acknowledged as the cornerstones of pediatric immunization programs, the development of new combination vaccines for children has not been a priority for manufacturers, policy bodies, or decision-makers. At the same time, economic evaluations have not assessed the full array of benefits and risks associated with combination vaccines. As part of an effort to identify and prioritize potential new combination vaccines, we aimed to enhance efforts to establish their value, a crucial step toward a more thorough, quantifiable, and realistic assessment of these vaccines.We reviewed the literature on economic evaluations of combination vaccines to more precisely identify and define current gaps in value assessment. We identified a set of (often unvalued) benefits and risks and created a list of value drivers and metrics for potential inclusion in future evaluations. Value drivers were then categorized based on how they resonate with decision-makers' priorities and their contribution to product value. Metrics were categorized based on their quantifiability and their fit within existing economic evaluation frameworks. We developed a prioritized checklist of value drivers and metrics to assess combination vaccines through a consultative process involving numerous immunization stakeholders (e.g., immunization specialists, regional immunization advisors, policy bodies). The checklist was further refined through a convening of health economics experts and ultimately endorsed by the World Health Organization's Immunization and Vaccines-related Implementation Research Advisory Committee.This checklist of prioritized value drivers and metrics is meant to serve as a tool for analysts to value combination vaccines and help ensure these vaccines are more comprehensively assessed by decision-makers to inform investment decisions or adoption.

BACKGROUND:The introduction of rotavirus vaccine (RVV), pneumococcal conjugate vaccine (PCV) and human papillomavirus vaccine (HPVV) has been slow in Pacific Island Countries, particularly among middle-income countries. To assist decision-making on the simultaneous introduction of these three vaccines, cost-effectiveness and budget impact evaluations were undertaken in Samoa, Tonga, Tuvalu and Vanuatu, using locally relevant data. METHODS AND FINDINGS:A proportionate outcomes model was used to evaluate vaccine introduction in each country from a health systems perspective, using country-specific data supplemented with regional and global estimates. A 10-year vaccination program was modelled from 2021, with costs and outcomes (disability-adjusted life years [DALYs]) summed over a life-time horizon and discounted at 3%. Vaccine dose costs were based on Pan American Health Organization (PAHO) Revolving Fund prices, with lower-priced products also explored. Introduction of all three vaccines in all countries could prevent over 1,000 deaths over the lifetimes of the vaccinated cohorts. The cost per DALY averted at PAHO Revolving Fund prices ranged from 42% to 73% of the per capita gross domestic product (GDP) in each country, and 15% to 58% for lower-priced vaccines. The budget impact ranged from 359% (Samoa) to 1,368% (Vanuatu) of the 2019 vaccine budgets, and 149% (Samoa) to 775% (Vanuatu) for lower-priced vaccines. Cost-effectiveness results were most sensitive to disease burden, discount rate, vaccine efficacy, and program costs. A limitation of our study is the reliance on data from Fiji to inform disease burden, as availability of country-specific data was limited. CONCLUSIONS:With development partner support, introduction of HPVV, PCV and RVV may represent good value for money in Samoa, Tonga, Tuvalu and Vanuatu, depending on willingness to pay thresholds. However, inclusion of these three vaccines will place considerable burden on immunisation budgets. Financial sustainability requires increases in immunisation budgets and negotiation of affordable vaccine prices. This analysis provides evidence of the benefit of introducing new vaccines, but shows the importance of affordable pricing to ensure sustainability for small Pacific Island countries.

Therapeutic HPV vaccines (TxVs) may complement existing cervical cancer prevention strategies, particularly for women already infected with HPV who derive limited benefit from prophylactic vaccination. As China advances toward the WHO 90–70–90 cervical cancer elimination targets, understanding the potential health impact of therapeutic vaccines under varying implementation scenarios is critical. We developed a two-stage hybrid model combining a dynamic HPV transmission model with a natural history model of HPV-related disease progression to project the long-term health impact of therapeutic HPV vaccines in China from 2025 to 2125. Two vaccine types aligned with WHO Preferred Product Characteristics were evaluated: one targeting HPV infection clearance (TxV1) and one targeting treatment of cervical intraepithelial neoplasia (CIN) grade 2 or 3 (TxV2). Vaccination was modelled under two use cases: population-based delivery and integration into existing national screening programmes. Outcomes included cervical cancer cases and deaths averted, relative reductions compared with no therapeutic vaccination, age-standardised incidence, and the projected year of elimination. One-way and probabilistic sensitivity analyses evaluate model uncertainty. In the base case, screening-integrated TxV1 (Use Case 2) could avert up to 834.0 thousand cervical cancer cases (12.7

Improved influenza vaccines, which may offer broader and longer-lasting protection than current seasonal vaccines, are under development and may play a critical role in reducing the global burden of seasonal influenza. Previous analyses have shown their potential health and economic benefits, but these depend on pricing structures and national-level adoption timelines. This analysis uses established epidemiological and economic influenza models, and demand and price projections outlined by the WHO Full Value of Improved Influenza Vaccines Assessment, to estimate the health impact and net monetary benefits of improved vaccines compared to current seasonal vaccines, under different programmatic scenarios. We employed varying assumptions about vaccine characteristics, age-specific uptake, and introduction years of improved influenza vaccines, and modelled influenza burden between 2025 and 2050 in 178 countries. Our findings suggest that improved vaccines, deployed under plausible programmatic scenarios, could avert up to 17.9 (95% CI: 16.5-19.7) billion additional influenza infections and 6.0 (95% CI: 4.8-7.9) million deaths globally between 2025 and 2050, with estimated global net monetary benefit of up to 440 billion (95% CI: 257-652 billion) USD at lower projected price points. However, estimated cost-effectiveness varies widely by country income level and assumptions about demand. Despite the projected benefits, demand scenarios - largely based on historical use - may not reflect the most impactful or efficient use of improved influenza vaccines. Strategies targeting children may be more cost-effective in low-income countries than those focused on older adults. Optimising delivery strategies could increase the value and accessibility of improved influenza vaccines globally. The global net monetary benefit of improved influenza vaccines is largely driven by high monetary benefits in Europe and the Americas, suggesting that economic surplus in these regions could support more strongly tiered vaccine pricing to establish more equitable global access to improved influenza vaccines.

BACKGROUND:Maternal respiratory syncytial virus (RSV) vaccine, RSV prefusion F protein vaccine (RSVpreF (Abrysvo)), was found to be safe and efficacious in the MATISSE trial. However, post-hoc stratified analyses identified an excess of preterm births in the intervention arm in two upper-middle-income countries, most prominently in South Africa. This study weighs the potential benefits and risks in mortality associated with maternal RSV vaccination in South Africa, assuming the increased risk of preterm births observed in the trial was caused by vaccination. METHODS AND FINDINGS:We compared the estimated RSV-associated infant deaths averted by vaccination (benefits) and neonatal mortality potentially associated with vaccine-associated risk in preterm birth (risks) in South Africa. The benefit model estimated the South African RSV disease burden in 2011-2016 and waning vaccine protection during infancy. The risk model estimated excess neonatal mortality using gestational age (GA)-specific mortality data from the Drakenstein Child Health Study and the GA-specific birth distribution in South Africa in the MATISSE trial, but did not incorporate the mortality risk found in the MATISSE vaccine trial in which no excess deaths occurred. The benefit model estimated that vaccination would reduce RSV-associated infant deaths by 31 (95% credible interval (Crl): 27, 35) per 100,000 live births born to vaccinated mothers in South Africa. Using the number of infants born to mothers vaccinated at 24-36 GA weeks in the MATISSE trial, if the association in South Africa between vaccination and preterm birth is actually causal, the risk model suggested that neonatal deaths would increase by 44 (95%CrI: -43, 210), totaling 1.4 (95%CrI: -1.4, 6.9) excess neonatal deaths for every infant RSV death prevented. When this was changed to the number of infants born to mothers vaccinated at 27-36 GA weeks in the MATISSE trial, the predicted risks dropped and in 97% of the simulations the benefits outweighed the risks. The outcome was sensitive to the GA window that we used to determine which infants to include in the analysis. The study was limited by only considering mortality associated with RSV disease and preterm birth. CONCLUSIONS:If RSVpreF increases preterm birth risk, and if this increases neonatal mortality, then the benefit-risk analysis failed to show that the direct benefits of vaccination in reducing RSV-associated infant mortality would substantially outweigh the risks of preterm birth-associated neonatal mortality in South Africa with vaccination from 24 GA to 36 GA weeks. There was large uncertainty in the analyses due to small numbers of preterm births. With vaccination from 27 GA weeks, the benefit-risk analysis favored vaccination. RSVpreF vaccination has the potential to be safe and effective when used from the third trimester.

INTRODUCTION:Human papillomavirus (HPV) is a leading cause of both cervical and non-cervical cancers, including anal, oropharyngeal, vaginal and vulvar cancers. While most HPV vaccination impact assessments have focused on preventing cervical cancer among women, the broader benefits of vaccination against other HPV-attributable cancers in low- and middle-income countries (LMICs) remain less explored. METHODS:We used a static cohort model to assess the potential health impact of bivalent HPV vaccination on HPV-attributable female non-cervical cancers in 117 LMICs from 2030 to 2100. The model incorporated country-specific data on cancer mortality, HPV type distribution, demographic projections and vaccine coverage. Sensitivity analyses were performed to account for uncertainties in cancer incidence, cancer mortality and HPV type distribution. RESULTS:Our projections suggest that HPV vaccination could contribute to prevention of approximately five 90 000 cases of anal, 880 000 cases of oropharyngeal, 1.27 million cases of vaginal and 2.18 million cases of vulvar cancers over the analytic period. In total, 3.02 million deaths from these non-cervical cancers among women could be averted by 2100. The African region is expected to see the largest relative reductions in both cases and deaths while the European region showed the smallest gains. By the end of the century, 58 countries are projected to reach at least a 25% reduction in anal cancer mortality compared with just 25 countries for oropharyngeal cancer. These findings reflect substantial regional disparities in both burden and vaccination impact. CONCLUSION:HPV vaccination holds considerable promise in reducing the burden of non-cervical cancers among women in LMICs, especially in regions with high incidence and limited access to care. Recognising and harnessing these broader benefits can strengthen the public health case for scaling up vaccine access, implementing region-specific strategies and investing in equitable healthcare systems to decrease global disparities.

Background:Since 2019, Hong Kong has implemented a routine nonavalent human papillomavirus (HPV) vaccination program for schoolgirls aged 10-12 years with two-dose uptake of over 85%. However, Hong Kong is one of the high-income populations in Asia that lacks an assessment of the impacts of gender-neutral vaccination (GNV) with a single-dose schedule. This study evaluates the cost-effectiveness of expanding the two-dose female-only vaccination (2dFOV) to GNV and reducing the schedule to one dose. Methods:We modeled the impacts of 2dFOV and GNV (a single- or two-dose schedule) on the burden of HPV-related cancers and genital warts in both genders. We estimated the associated costs and health outcomes over a time horizon of 100 years with a 3% annual discount rate. We compared the incremental cost-effectiveness ratio (ICER) of expanding 2dFOV to GNV to a threshold of one gross domestic product per capita (US$52,120). Findings:Assuming a base case vaccination cost of US$177 per dose and 85% uptake for both genders, two-dose GNV (2F2M) has an ICER of US$71,105 (90% prediction interval: (US$44,085, US$153,197)) compared to 2dFOV and is not cost-effective. Compared to 2dFOV, giving one dose to both genders (1F1M) is cost-effective or dominant in all simulations, if boys' uptake is more than 50% and if the single-dose schedule provides 30 years of protection. If the single-dose schedule gives only 20 years of protection, 1F1M is cost-effective or dominant in 92% and 73% of simulations if boys' uptake is 85% and 50%, respectively. Interpretation:Expanding the current 2dFOV to GNV with a one-dose schedule for males (1F1M or 2F1M) could be a cost-effective strategy if the uptake among boys is sufficiently high. Funding:Health and Medical Research Fund, AIR@InnoHK.

Meningitis is a serious disease and it brings challenges to the health system worldwide. The aim was to estimate the health-related quality of life (HRQOL) and economic burden of children with meningitis in China and to explore the associated factors. A longitudinal cohort study was conducted to track HRQOL measured with a proxy version of the proxy youth version of the 5-level EuroQol-five dimensions questionnaire (EQ-5D-Y) in children under six years of age before and after receiving medical treatment for meningitis, and to collect data on both direct and indirect costs associated with the disease in multiregions. A total of 323 subjects were included in the study. The mean EQ-5D-Y utility value was 0.701 (standard deviation (SD) 0.202) (EQ visual analogue scale (EQ-VAS) score: 55.5 (17.5)) at baseline, with the most reported problems occurring in two dimensions: having pain or discomfort (94.4%) and feeling worried, sad or unhappy (89.8%). At discharge, the mean utility value increased to 0.926 (0.104) (EQ-VAS score: 89.8 (10.3)). The average total cost and hospitalization cost was 12,260 Chinese Yuan (CNY) and 7723 CNY, respectively. Region and loss of the work time were the main factors both had impact on utility value and total cost in regression analyses. These findings indicate substantial regional variation in HRQOL outcomes and highlight the heavy economic burden meningitis imposes on affected families and society.

INTRODUCTION:Since September 2023, England's national immunisation programme has offered the recombinant zoster vaccine (RZV) to adults aged 65-79 as a preventative measure against shingles (herpes zoster) and its complications. However, adults aged 80 and over are currently not eligible for the vaccine. We aimed to evaluate the feasibility and cost-effectiveness of providing RZV to adults aged 80 and older in England. METHODS:This cost-utility analysis employs a static cohort model considering herpes zoster (HZ) cases and severe cases leading to post-herpetic neuralgia, HZ-related hospitalisation, and deaths from the perspective of the National Health Service. The long-term impacts of RZV are assessed using the model, accounting for changing population demographics and the previously-offered live zoster vaccine (ZVL). We consider different eligibility scenarios for RZV focusing on the older population (80+ years old) and provide comparisons to the pre-2023 programme. RESULTS:Expanding the current programme to offer a single dose of RZV to people aged 80 and up is likely to be cost-effective relative to the current programme. Offering two doses to this group would be less cost-effective but would offer greater protection against HZ. For preventing health-related quality of life loss, it is most efficient to vaccinate 60-69-year-olds, but for averting hospitalisation costs, it is most efficient to vaccinate 80-89-year-olds. CONCLUSION:Providing one or two doses of RZV for older adults can be cost-effective and would reduce the healthcare burden of shingles.

Background: The first human papillomavirus (HPV) vaccines were licensed in 2006. Global vaccine access and coverage have improved tremendously since then, but gaps between countries remain. To track progress over two decades of HPV vaccine rollout globally, this study aims to estimate how the magnitude and distribution of lifetime health impacts among vaccinated females have evolved from 2006 to 2024 at the global, regional, and national levels. Methods: We parameterised a previously validated static HPV vaccination model (the Papillomavirus Rapid Interface for Modelling and Economics, PRIME) with data on country-level HPV vaccine introductions, female HPV vaccination coverage, cervical cancer burden and demography to assess the lifetime vaccine-attributable reduction in cervical cancer cases, deaths, and disability-adjusted life years (DALYs) during 2006 - 2024. We explored the extent to which vaccines reached the countries with the highest disease burden at global and regional levels using concentration curves and concentration indices. Findings: Over 109 million girls were vaccinated with the HPV vaccine from 2006 to 2024. This is estimated to have already prevented 38,557 cervical cancer cases, 8,786 deaths, and 481,920 DALYs. Over the lifetime of the vaccinated cohorts, it is projected to prevent 5·92 million cases, 4·14 million deaths, and 87·76 DALYs. Initially, vaccines mainly reached countries with low disease burden, but these inequities have narrowed as more high-burden countries have included HPV vaccination in their national immunisation programme. Interpretation: The historical HPV vaccination programme over the past two decades has contributed to substantial health benefits. Inequities in vaccine coverage have narrowed but still remain. Sustained momentum is needed to broaden national HPV vaccination implementation and to ensure equitable access wherever needed.

BackgroundRecent shifts in the global health funding landscape-most notably the dismantling of the United States Agency for International Development (USAID) and possible reduced contributions to the Global Fund to Fight AIDS, TB, and Malaria (Global Fund)-threaten essential tuberculosis (TB) services in low- and middle-income countries (LMICs). We quantified the potential impact on the household economic burden of TB.Methods and findingsWe used linked epidemiological and economic models, calibrated to 79 LMICs, to estimate future TB patient costs under six scenarios: continuation of 2024 funding levels (baseline), termination of USAID, termination of USAID plus announced reductions in Global Fund contributions from the USA alone, termination of USAID plus complete termination of Global Fund contributions from the USA alone, termination of USAID plus announced reductions in Global Fund contributions from all donor countries contributing 1% or more to the budget, and full elimination of external funding for TB. Outcomes included total TB-attributable household costs and numbers of households experiencing catastrophic costs (disease-related costs >20% of annual income). USAID termination was projected to produce US$7.5 (95% uncertainty interval: $6.1-8.9) billion in additional patient-incurred costs and 3.9 (3.1-4.6) million additional households experiencing catastrophic costs over 2025-2050. The worst-case scenario (elimination of all external funding) resulted in $79.7 ($60.0-99.2) billion in additional patient-incurred costs and 40.5 (30.9-50.7) million additional households experiencing catastrophic costs-a 32% increase over baseline. Impacts were greatest for poorer households, with over 50% of additional catastrophic costs occurring in the poorest 20% of households. This analysis is limited by substantial uncertainty regarding costs faced by untreated patients and assumptions of constant patient costs and uniform treatment reductions over time.ConclusionsAbrupt reductions in international donor funding for TB may reverse recent progress toward financial risk protection and health equity in LMICs. Strategies to reduce the disruption caused by funding cuts and protect vulnerable populations are urgently needed.