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Background: There is increasing evidence that invasive fungal disease (IFD) is more likely to occur in non-neutropenic patients in critical care units. A number of randomised controlled trials (RCTs) have evaluated antifungal prophylaxis in non-neutropenic, critically ill patients, demonstrating a reduction in the risk of proven IFD and suggesting a reduction in mortality. It is necessary to establish a method to identify and target antifungal prophylaxis at those patients at highest risk of IFD, who stand to benefit most from any antifungal prophylaxis strategy. Objectives: To develop and validate risk models to identify non-neutropenic, critically ill adult patients at high risk of invasive Candida infection, who would benefit from antifungal prophylaxis, and to assess the cost-effectiveness of targeting antifungal prophylaxis to high-risk patients based on these models. Design: Systematic review, prospective data collection, statistical modelling, economic decision modelling and value of information analysis. Setting: Ninety-six UK adult general critical care units. Participants: Consecutive admissions to participating critical care units. Interventions: None. Main outcome measures: Invasive fungal disease, defined as a blood culture or sample from a normally sterile site showing yeast/mould cells in a microbiological or histopathological report. For statistical and economic modelling, the primary outcome was invasive Candida infection, defined as IFD-positive for Candida species. Results: Systematic review: Thirteen articles exploring risk factors, risk models or clinical decision rules for IFD in critically ill adult patients were identified. Risk factors reported to be significantly associated with IFD were included in the final data set for the prospective data collection. Data collection: Data were collected on 60,778 admissions between July 2009 and March 2011. Overall, 383 patients (0.6%) were admitted with or developed IFD. The majority of IFD patients (94%) were positive for Candida species. The most common site of infection was blood (55%). The incidence of IFD identified in unit was 4.7 cases per 1000 admissions, and for unit-acquired IFD was 3.2 cases per 1000 admissions. Statistical modelling: Risk models were developed at admission to the critical care unit, 24 hours and the end of calendar day 3. The risk model at admission had fair discrimination (c-index 0.705). Discrimination improved at 24 hours (c-index 0.823) and this was maintained at the end of calendar day 3 (c-index 0.835). There was a drop in model performance in the validation sample. Economic decision model: Irrespective of risk threshold, incremental quality-adjusted life-years of prophylaxis strategies compared with current practice were positive but small. Incremental costs of the prophylaxis strategies compared with current practice were positive for most strategies, although a few strategies were cost saving. Incremental net benefits of each prophylaxis strategy compared with current practice were positive for most, but not all, of the strategies. Cost-effectiveness acceptability curves showed that risk assessment and prophylaxis at the end of calendar day 3 was the strategy most likely to be cost-effective when the risk threshold was 1% or 2%. At a lower risk threshold (0.5%) it was most cost-effective to assess risk at each time point; this led to a relatively high proportion of patients receiving antifungal prophylaxis (30%), which may lead to additional burden from increased resistance. The estimates of cost-effectiveness were highly uncertain and the value of further research for the whole population of interest is high relative to the research costs. Conclusions: The results of the Fungal Infection Risk Evaluation (FIRE) Study, derived from a highly representative sample of adult general critical care units across the UK, indicated a low incidence of IFD among non-neutropenic, critically ill adult patients. IFD was associated with substantially higher mortality, more intensive organ support and longer length of stay. Risk modelling produced simple risk models that provided acceptable discrimination for identifying patients at ‘high risk’ of invasive Candida infection. Results of the economic model suggested that the current most cost-effective treatment strategy among non-neutropenic, critically ill adult patients admitted to NHS adult general critical care units is a strategy of risk assessment and antifungal prophylaxis at the end of calendar day 3, but this finding is highly uncertain and future studies should consider the potential impact of increased resistance. Funding: Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research.: A previous version of this report was published in February 2013. The report was subsequently modified to reflect a substantial reduction in the unit cost of fluconazole that took place between the original analysis being conducted and the publication of the report.

Abstract Background The COVID-19 pandemic has disrupted routine measles immunisation and supplementary immunisation activities (SIAs) in most countries including Kenya. We assessed the risk of measles outbreaks during the pandemic in Kenya as a case study for the African Region. Methods Combining measles serological data, local contact patterns, and vaccination coverage into a cohort model, we predicted the age-adjusted population immunity in Kenya and estimated the probability of outbreaks when contact-reducing COVID-19 interventions are lifted. We considered various scenarios for reduced measles vaccination coverage from April 2020. Results In February 2020, when a scheduled SIA was postponed, population immunity was close to the herd immunity threshold and the probability of a large outbreak was 34% (8–54). As the COVID-19 contact restrictions are nearly fully eased, from December 2020, the probability of a large measles outbreak will increase to 38% (19–54), 46% (30–59), and 54% (43–64) assuming a 15%, 50%, and 100% reduction in measles vaccination coverage. By December 2021, this risk increases further to 43% (25–56), 54% (43–63), and 67% (59–72) for the same coverage scenarios respectively. However, the increased risk of a measles outbreak following the lifting of all restrictions can be overcome by conducting a SIA with ≥ 95% coverage in under-fives. Conclusion While contact restrictions sufficient for SAR-CoV-2 control temporarily reduce measles transmissibility and the risk of an outbreak from a measles immunity gap, this risk rises rapidly once these restrictions are lifted. Implementing delayed SIAs will be critical for prevention of measles outbreaks given the roll-back of contact restrictions in Kenya.

A comparative study of the equatorial spread F occurrence was conducted at different longitudes during 2010 and 2013 representing the low (LSA) and moderate (MSA) solar activity periods respectively. The ionogram data were recorded at low-latitude stations including Jicamarca (JIC;75.76∘ W, 8.17∘ S), Fortaleza (FZA; 38.52∘ W, 3.73∘ S), Ilorin (ILR; 7.55∘ E, 9.93∘ N), Chumphon (CPN; 88.46∘ E, 11∘ N) and Kwajalein (KWA; 167.73∘ E, 8.72∘ N). The range type spread F (RSF) occurrence was manually recorded at an hourly interval between 18:00 and 06:00 LT, and a monthly average of the RSF occurrence was estimated for each season. The longitudinal distribution of the RSF occurrence features included the observed difference in the onset time, the duration and the seasonal occurrence peak. The seasonal asymmetry in the RSF occurrence distribution was analysed in relation to the zonal drift reversal’s effect on the plasma irregularity initiation. We believe that the inconsistent equinoctial asymmetry pattern in the RSF occurrence is modulated by the seasonal/longitudinal variation of the zonal drift reversal delay during both solar epochs. Likewise, the seeding effect and the background ionospheric condition were also considered as major factors influencing the frequency of irregularity generation in these regions.

Objective: Previous HPV models have only included genital transmission, when evidence suggests that transmission between several anatomical sites occurs. We compared model predictions of population-level HPV vaccination effectiveness against genital HPV16 infection in women, using a 1) uni-site (genital site), and a 2) multi-site model (genital and one extragenital site). Methods: We developed a uni-site and a multi-site deterministic HPV transmission model, assuming natural immunity was either site-specific or systemic. Both models were calibrated to genital HPV16 prevalence (5%–7.5%), whilst the multi-site model was calibrated to HPV16 prevalence representative of oral (0%–1%) and anal (1%–7.5%) sites. For each model, we identified 2500 parameter sets that fit endemic genital and extragenital prevalences within pre-specified target ranges. In the Base-case analysis, vaccination was girls-only with 40% coverage. Vaccine efficacy was 100% for all sites with lifetime protection. The outcome was the relative reduction in genital HPV16 prevalence among women at post-vaccination equilibrium (RRprev). RRprev was stratified by extragenital prevalence pre-vaccination. Results: Under assumptions of site-specific immunity, RRprev with the multi-site model was generally greater than with the uni-site model. Differences between the uni-site and multi-site models were greater when transmission from the extragenital site to the genital site was high. Under assumptions of systemic immunity, the multi-site and uni-site models yielded similar RRprev in the scenario without immunity after extragenital infection. In the scenario with systemic immunity after extragenital infection, the multi-site model yielded lower predictions of RRprev than the uni-site model. Conclusions: Modelling genital-site only transmission may overestimate vaccination impact if extragenital infections contribute to systemic natural immunity or underestimate vaccination impact if a high proportion of genital infections originate from extragenital infections. Under current understanding of heterosexual HPV transmission and immunity, a substantial bias from using uni-site models in predicting vaccination effectiveness against genital HPV infection is unlikely to occur.

Objectives: Disease transmission models are used in impact assessment and economic evaluations of infectious disease prevention and treatment strategies, prominently so in the COVID-19 response. These models rarely consider dimensions of equity relating to the differential health burden between individuals and groups. We describe concepts and approaches which are useful when considering equity in the priority setting process, and outline the technical choices concerning model structure, outputs, and data requirements needed to use transmission models in analyses of health equity. Methods: We reviewed the literature on equity concepts and approaches to their application in economic evaluation and undertook a technical consultation on how equity can be incorporated in priority setting for infectious disease control. The technical consultation brought together health economists with an interest in equity-informative economic evaluation, ethicists specialising in public health, mathematical modellers from various disease backgrounds, and representatives of global health funding and technical assistance organisations, to formulate key areas of consensus and recommendations. Results: We provide a series of recommendations for applying the Reference Case for Economic Evaluation in Global Health to infectious disease interventions, comprising guidance on 1) the specification of equity concepts; 2) choice of evaluation framework; 3) model structure; and 4) data needs. We present available conceptual and analytical choices, for example how correlation between different equity- and disease-relevant strata should be considered dependent on available data, and outline how assumptions and data limitations can be reported transparently by noting key factors for consideration. Conclusions: Current developments in economic evaluations in global health provide a wide range of methodologies to incorporate equity into economic evaluations. Those employing infectious disease models need to use these frameworks more in priority setting to accurately represent health inequities. We provide guidance on the technical approaches to support this goal and ultimately, to achieve more equitable health policies.

Introduction: Social contact patterns significantly influence the transmission dynamics of respiratory pathogens. Previous surveys have quantified human social contact patterns, yielding heterogeneous results across different locations. However, significant gaps remain in understanding social contact patterns in rural areas of China., Methods: We conducted a pioneering study to quantify social contact patterns in Anhua County, Hunan Province, China, from June to October 2021, when there were minimal coronavirus disease-related restrictions in the area. Additionally, we simulated the epidemics under different assumptions regarding the relative transmission risks of various contact types (e.g., indoor versus outdoor, and physical versus non-physical)., Results: Participants reported an average of 12.0 contacts per day (95% confidence interval: 11.3-12.6), with a significantly higher number of indoor contacts compared to outdoor contacts. The number of contacts was associated with various socio-demographic characteristics, including age, education level, income, household size, and travel patterns. Contact patterns were assortative by age and varied based on the type of contact (e.g., physical versus non-physical). The reproduction number, daily incidence, and infection attack rate of simulated epidemics were remarkably stable., Discussion: We found many intergenerational households and contacts that pose challenges in preventing and controlling infections among the elderly in rural China. Our study also underscores the importance of integrating various types of contact pattern data into epidemiological models and provides guidance to public health authorities and other major stakeholders in preparing and responding to infectious disease threats in rural China., Competing Interests: H.Y. has received research funding from Sanofi Pasteur, Shenzhen Sanofi Pasteur Biological Products Co., Ltd and SINOVAC Biotech Ltd. None of the research funding is related to this work., (© 2024 The Authors.)

Mathematical models are established tools to assist in outbreak response. They help characterise complex patterns in disease spread, simulate control options to assist public health authorities in decision-making, and longer-term operational and financial planning. In the context of vaccine-preventable diseases (VPDs), vaccines are one of the most-cost effective outbreak response interventions, with the potential to avert significant morbidity and mortality through timely delivery. Models can contribute to the design of vaccine response by investigating the importance of timeliness, identifying high-risk areas, prioritising the use of limited vaccine supply, highlighting surveillance gaps and reporting, and determining the short- and long-term benefits. In this review, we examine how models have been used to inform vaccine response for 10 VPDs, and provide additional insights into the challenges of outbreak response modelling, such as data gaps, key vaccine-specific considerations, and communication between modellers and stakeholders. We illustrate that while models are key to policy-oriented outbreak vaccine response, they can only be as good as the surveillance data that inform them., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: KAMG reports speaker fees from Sanofi Pasteur outside the submitted work. All other authors have no conflicts of interest to declare. MS, A-MH, EG, HK, J-HK, HF, MJ, AP , CLT, and KAMG received funding from Gavi, BMGF and/or the Wellcome Trust via VIMC during the course of the study., (© 2024. The Author(s).)

Background: Between 2020 and 2022, countries used a range of different public health and social measures (PHSMs) to reduce the transmission of SARS-CoV-2. The impact of these PHSMs varied as the pandemic progressed, variants of concern (VOCs) emerged, vaccines rolled out and acceptance/uptake rates evolved. In this study, we assessed the impact of PHSMs in the World Health Organization (WHO) European Region during VOC phases., Methods: We relied on time series data on genome sequencing, PHSMs, health outcomes and physical contacts. Panel regression models were used to assess the association between PHSMs and SARS-CoV-2 transmission (approximated using time-varying reproduction numbers). The interpretation of these regression models was assisted by hierarchical clustering, which was used to detect the temporal co-occurrence of PHSMs. Generalised linear models were used to check if PHSMs are associated with physical contacts., Results: We identified four phases based on the dominating VOC in the WHO European Region: wild type (before early 2021), Alpha (early to mid-2021), Delta (mid-to-late 2021) and Omicron (after late 2021). 'School closure', 'stay-at-home requirement' and 'testing policy' were consistently associated with lower transmission across VOC phases. The impact of most PHSMs varied by VOC phases without clear increasing or decreasing trends as the pandemic progressed. Several PHSMs associated with lower transmission were not associated with fewer physical contacts., Conclusions: The impact of PHSMs evolved as the pandemic progressed-although without clear trends. The specific mechanisms by which some PHSMs reduce SARS-CoV-2 transmission require further research., (© 2024 World Health Organization and The Author(s); licensed by John Wiley & Sons Ltd. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Introduction: Thailand was one of the first low- and middle-income countries to publicly fund seasonal influenza vaccines, but the lack of predictability in the timing of epidemics and difficulty in predicting the dominant influenza subtypes present a challenge for existing vaccines. Next-generation influenza vaccines (NGIVs) are being developed with the dual aims of broadening the strain coverage and conferring longer-lasting immunity. However, there are no economic evaluations of NGIVs in Thailand., Methods: We estimated the health impact and cost-effectiveness of NGIVs in Thailand between 2005 and 2009 using a combined epidemiological and economic model. We fitted the model to data on laboratory-confirmed influenza cases and then simulated the number of influenza infections, symptomatic cases, hospitalisations and deaths under different vaccination scenarios based on WHO-preferred product characteristics for NGIVs. We used previous estimates of costs and disability adjusted life years (DALYs) for influenza health outcomes to estimate incremental net monetary benefit, vaccine threshold prices and budget impact., Results: With the current vaccine programme, there were an estimated 61 million influenza infections. Increasing coverage to 50% using improved vaccines reduced infections to between 23 and 57 million, and with universal vaccines to between 21 and 49 million, depending on the age groups targeted. Depending on the comparator, threshold prices for NGIVs ranged from US$2.80 to US$12.90 per dose for minimally improved vaccines and US$24.60 to US$69.90 for universal vaccines., Conclusion: Influenza immunisation programmes using NGIVs are anticipated to provide considerable health benefits and be cost-effective in Thailand. However, although NGIVs might even be cost-saving in the long run, there could be significant budget implications for the Thai government even if the vaccines can be procured at a substantial discount to the maximum threshold price., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Recently, several novel RSV immunisation products that protect infants and older adults against RSV disease have been licensed in Europe. We estimated the effectiveness and efficiency of introducing these RSV immunisation strategies in Germany., Methods: We used a Bayesian framework to fit a deterministic age-structured dynamic transmission model of RSV to sentinel surveillance and RSV-specific hospitalisation data in Germany from 2015 to 2019. The calibrated model was used to evaluate different RSV intervention strategies over 5 years: long-acting, single-dose monoclonal antibodies (mAbs) in high-risk infants aged 1-5 months; long-acting mAbs in all infants aged 1-5 months; seasonal vaccination of pregnant women and one-time seasonal vaccination of older adults (75 + /65 + /55 + years). We performed sensitivity analysis on vaccine uptake, seasonal vs. year-round maternal vaccination, and the effect of under-ascertainment for older adults., Results: The model was able to match the various RSV datasets. Replacing the current short-acting mAB for high-risk infants with long-acting mAbs prevented 1.1% of RSV-specific hospitalisations in infants per year at the same uptake. Expanding the long-acting mAB programme to all infants prevented 39.3% of infant hospitalisations per year. Maternal vaccination required a larger number to be immunised to prevent one additional hospitalisation than a long-acting mAB for the same uptake. Vaccination of adults older than 75 years at an uptake of 40% in addition to Nirsevimab in all infants prevented an additional 4.5% of all RSV hospitalisations over 5 years, with substantial uncertainty in the correction for under-ascertainment of the RSV burden., Conclusions: Immunisation has the potential to reduce the RSV disease burden in Germany., (© 2024. The Author(s).)

Background: The high price of HPV vaccines remains a significant barrier to vaccine accessibility in China, hindering the country's efforts toward cervical cancer elimination and exacerbating health inequity. We aimed to inform HPV vaccine price negotiations by identifying threshold prices that ensure that a government-funded HPV vaccination programme is cost-effective or cost-saving., Methods: We used a previously validated transmission model to estimate the health and economic impact of HPV vaccination over a 100-year time horizon from a healthcare payer perspective. Threshold analysis was conducted considering different settings (national, rural, and urban), cervical cancer screening scenarios (cytology-based or HPV DNA-based, with different paces of scale-up), vaccine types (four types available in China), vaccine schedules (two-dose or one-dose), mode of vaccination (routine vaccination with or without later switching to high-valency vaccines), willingness-to-pay thresholds, and decision-making criteria (cost-effective or cost-saving). Furthermore, we examined the budget impact of introducing nationwide vaccination at the identified threshold prices., Findings: Using the current market price, national routine HPV vaccination with any currently available vaccine is unlikely cost-effective. Under a two-dose schedule, the prices of the four available HPV vaccine types cannot exceed $26-$36 per dose (44.1%-80.2% reduction from current market prices) depending on vaccine type to ensure the cost-effectiveness of the national programme. Adopting vaccination at threshold prices would require an annual increase of 72.18%-96.95% of the total annual National Immunization Programme (NIP) budget in China. A cost-saving routine vaccination programme requires vaccine prices of $5-$10 per dose (depending on vaccine type), producing a 21.38%-34.23% increase in the annual NIP budget. Adding the second dose is unlikely to be cost-effective compared to a one-dose schedule, with the threshold price approaching or even falling below zero. Rural pilot vaccination programmes require lower threshold prices compared with a national programme., Interpretation: Our study could inform vaccine price negotiation and thus facilitate nationwide scale-up of current HPV vaccination pilot programmes in China. The evidence may potentially be valuable to other countries facing HPV introduction barriers due to high costs. This approach may also be adapted for other contexts that involve the introduction of a pricy vaccine., Funding: CAMS Innovation Fund for Medical Sciences (CIFMS); Bill & Melinda Gates Foundation., Competing Interests: FZ reports receiving grants from GlaxoSmithKline Biologicals, Merck & Co., and Xiamen Innovax Biotech to her institution for conducting clinical trials on the HPV vaccines. YQ reports receiving grants from Merck & Co., and Xiamen Innovax Biotech to his institution for similar clinical trials. YL reports receiving grants from BMGF, WHO, and InnoHK to her institution. MJ reports receiving research grants from NIHR, RCUK, BMGF, WHO, Gavi, Wellcome Trust, European Commission, InnoHK, TFGH, and CDC to his institution. The other co-authors declare no competing interests., (© 2024 The Author(s).)

Measles and rubella micro-array patches (MR-MAPs) are a promising innovation to address limitations of the current needle and syringe (N&S) presentation due to their single-dose presentation, ease of use, and improved thermostability. To direct and accelerate further research and interventions, an initial full value vaccine assessment (iFVVA) was initiated prior to MR-MAPs entering phase I trials to quantify their value and identify key data gaps and challenges. The iFVVA utilized a mixed-methods approach with rapid assessment of literature, stakeholder interviews and surveys, and quantitative data analyses to (i) assess global need for improved MR vaccines and how MR-MAPs could address MR problem statements; (ii) estimate costs and benefits of MR-MAPs; (iii) identify the best pathway from development to delivery; and (iv) identify outstanding areas of need where stakeholder intervention can be helpful. These analyses found that if MR-MAPs are broadly deployed, they can potentially reach an additional 80 million children compared to the N&S presentation between 2030-2040. MR-MAPs can avert up to 37 million measles cases, 400,000 measles deaths, and 26 million disability-adjusted life years (DALYs). MR-MAPs with the most optimal product characteristics of low price, controlled temperature chain (CTC) properties, and small cold chain volumes were shown to be cost saving for routine immunization (RI) in low- and middle-income countries (LMICs) compared to N&S. Uncertainties about price and future vaccine coverage impact the potential cost-effectiveness of introducing MR-MAPs in LMICs, indicating that it could be cost-effective in 16-81% of LMICs. Furthermore, this iFVVA highlighted the importance of upfront donor investment in manufacturing set-up and clinical studies and the critical influence of an appropriate price to ensure country and manufacturer financial sustainability. To ensure that MR-MAPs achieve the greatest public health benefit, MAP developers, vaccine manufacturers, donors, financiers, and policy- and decision-makers will need close collaboration and open communications.

Estimates of the global health impact of immunisation are important for quantifying historical benefits as well as planning future investments and strategy. The Vaccine Impact Modelling Consortium (VIMC) was established in 2016 to provide reliable estimates of the health impact of immunisation. In this article we examine the consortium in its first five-year phase. We detail how vaccine impact was defined and the methods used to estimate it as well as the technical infrastructure required to underpin robust reproducibility of the outputs. We highlight some of the applications of estimates to date, how these were communicated and what their effect were. Finally, we explore some of the lessons learnt and remaining challenges for estimating the impact of vaccines and forming effective modelling consortia then discuss how this may be addressed in the second phase of VIMC. Modelled estimates are not a replacement for surveillance; however, they can examine theoretical counterfactuals and highlight data gaps to complement other activities. VIMC has implemented strategies to produce robust, standardised estimates of immunisation impact. But through the first phase of the consortium, critical lessons have been learnt both on the technical infrastructure and the effective engagement with modellers and stakeholders. To be successful, a productive dialogue with estimate consumers, producers and stakeholders needs to be underpinned by a rigorous and transparent analytical framework as well as an approach for building expertise in the short and long term., Competing Interests: Competing interests: KAMG, XL, HC, ED, RF, WH, DH, MJ, TM, TAP, AP, EV, KW, NMF, CLT, received funding from Gavi, BMGF and/or the Wellcome Trust via VIMC during the course of the study. The authors declare no other competing interests., (Copyright: © 2024 Gaythorpe KAM et al.)

Background: Respiratory syncytial virus (RSV) is one of the main causes of hospitalization for lower respiratory tract infection in children under five years of age globally. Maternal vaccines and monoclonal antibodies for RSV prevention among infants are approved for use in high income countries. However, data are limited on the economic burden of RSV disease from low- and middle-income countries (LMIC) to inform decision making on prioritization and introduction of such interventions. This study aimed to estimate household and health system costs associated with childhood RSV in Kenya., Methods: A structured questionnaire was administered to caregivers of children aged < 5 years admitted to referral hospitals in Kilifi (coastal Kenya) and Siaya (western Kenya) with symptoms of acute lower respiratory tract infection (LRTI) during the 2019-2021 RSV seasons. These children had been enrolled in ongoing in-patient surveillance for respiratory viruses. Household expenditures on direct and indirect medical costs were collected 10 days prior to, during, and two weeks post hospitalization. Aggregated health system costs were acquired from the hospital administration and were included to calculate the cost per episode of hospitalized RSV illness., Results: We enrolled a total of 241 and 184 participants from Kilifi and Siaya hospitals, respectively. Out of these, 79 (32.9%) in Kilifi and 21(11.4%) in Siaya, tested positive for RSV infection. The total (health system and household) mean costs per episode of severe RSV illness was USD 329 (95% confidence interval (95% CI): 251-408 ) in Kilifi and USD 527 (95% CI: 405- 649) in Siaya. Household costs were USD 67 (95% CI: 54-80) and USD 172 (95% CI: 131- 214) in Kilifi and Siaya, respectively. Mean direct medical costs to the household during hospitalization were USD 11 (95% CI: 10-12) and USD 67 (95% CI: 51-83) among Kilifi and Siaya participants, respectively. Observed costs were lower in Kilifi due to differences in healthcare administration., Conclusions: RSV-associated disease among young children leads to a substantial economic burden to both families and the health system in Kenya. This burden may differ between Counties in Kenya and similar multi-site studies are advised to support cost-effectiveness analyses., (© 2024. The Author(s).)

Background: Streptococcus pneumoniae has been estimated to cause 9·18 million cases of pneumococcal pneumonia, meningitis, and invasive non-pneumonia non-meningitis disease and 318 000 deaths among children younger than 5 years in 2015. We estimated the potential impact and cost-effectiveness of pneumococcal conjugate vaccine (PCV) introduction., Methods: We updated our existing pseudodynamic model to estimate the impact of 13-valent PCV (PCV13) in 112 low-income and middle-income countries by adapting our previously published pseudodynamic model with new country-specific evidence on vaccine coverage, burden, and post-introduction vaccine impact from WHO-UNICEF estimates of national immunisation coverage and a global burden study. Deaths, disability-adjusted life-years (DALYs), and cases averted were estimated for children younger than 5 years born between 2000 and 2030. We used specific PCV coverage in each country and a hypothetical scenario in which coverage increased to diphtheria-tetanus-pertussis (DTP) levels. We conducted probabilistic uncertainty analyses., Findings: Using specific vaccine coverage in countries, we estimated that PCV13 could prevent 697 000 (95% credibility interval 359 000-1 040 000) deaths, 46·0 (24·0-68·9) million DALYs, and 131 (89·0-172) million cases in 112 countries between 2000 and 2030. PCV was estimated to prevent 5·3% of pneumococcal deaths in children younger than 5 years during 2000-30. The incremental cost of vaccination would be I$851 (510-1530) per DALY averted. If PCV coverage were increased to DTP coverage in 2020, PCV13 could prevent an additional 146 000 (75 500-219 000) deaths., Interpretation: The inclusion of real-world evidence from lower-income settings revealed that delays in PCV roll-out globally and low PCV coverage have cost many lives. Countries with delays in vaccine introduction or low vaccine coverage have experienced many PCV-preventable deaths. These findings underscore the importance of rapidly scaling up PCV to achieve high coverage and maximise vaccine impact., Funding: Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance., Competing Interests: Declaration of interests MJ and CC received funding from the Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance (INV-009125/OPP1157270) for this study. MJ received research grants to his institution from UK National Institute for Health and Care Research (NIHR), Resuscitation Council UK, Bill & Melinda Gates Foundation, WHO, Gavi, Wellcome Trust, European Commission, InnoHK, Task Force for Global Health, and US Centers for Disease Control and Prevention. JAGS has received research grants from Gavi, the UK Medical Research Council, Wellcome Trust, NIHR, Bill & Melinda Gates Foundation, and Emory University to his institution. CC has received research grants to her institution from the Singapore Ministry of Health's National Medical Research Council (HCSAINV22jul-0005; PHRGOC22Jul-0020), the Ministry of Education (MOE2018-T2–2-070), Singapore Food Agency, Jurong Health Fund, Woodlands Health Campus, and the Thai Health Promotion Foundation. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Rapid diagnostic tests (RDTs) for coronavirus disease (COVID) are used in low- and middle-income countries (LMICs) to inform treatment decisions. However, to date, it is unclear when this use is cost-effective. Existing analyses are limited to a narrow set of countries and uses. The aim of this study is to assess the cost-effectiveness of COVID RDTs to inform the treatment of patients with severe illness in LMICs, considering real world practice., Methods and Findings: We assessed the cost-effectiveness of COVID testing across LMICs using a decision tree model, differentiating results by country income level, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) prevalence, and testing scenario (none, RDTs, polymerase chain reaction tests-PCRs and combinations). LMIC experts defined realistic care pathways and treatment options. Using a healthcare provider perspective and net monetary benefit approach, we assessed both intended (COVID symptom alleviation) and unintended (treatment side effects) health and economic impacts for each testing scenario. We included the side effects of corticosteroids, which are often the only available treatment for COVID. Because side effects depend both on the treatment and the patient's underlying illness (COVID or COVID-like illnesses, such as influenza), we considered the prevalence of COVID-like illnesses in our analyses. We found that SARS-CoV-2 testing of patients with severe COVID-like illness can be cost-effective in all LMICs, though only in some circumstances. High influenza prevalence among suspected COVID cases improves cost-effectiveness, since incorrectly provided corticosteroids may worsen influenza outcomes. In low- and some lower-middle-income countries, only patients with a high index of suspicion for COVID should be tested with RDTs, while other patients should be presumed to not have COVID. In some lower-middle-income and upper-middle-income countries, suspected severe COVID cases should almost always be tested. Further, in these settings, negative test results in patients with a high initial index of suspicion should be confirmed through PCR and, during influenza outbreaks, positive results in patients with a low initial index of suspicion should also be confirmed with a PCR. The use of interleukin-6 receptor blockers, when supported by testing, may also be cost-effective in higher-income LMICs. The cost at which they would be cost-effective in low-income countries ($162 to $406 per treatment course) is below current prices. The primary limitation of our analysis is substantial uncertainty around some of the parameters in our model due to limited data, most notably on current COVID mortality with standard of care, and insufficient evidence on the impact of corticosteroids on patients with severe influenza., Conclusions: COVID testing can be cost-effective to inform treatment of LMIC patients with severe COVID-like disease. The optimal algorithm is driven by country income level and health budgets, the level of suspicion that the patient may have COVID, and influenza prevalence. Further research to better characterize the unintended effects of corticosteroids, particularly on influenza cases, could improve decision making around the treatment of those with COVID-like symptoms in LMICs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bonnet et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Countries are recommended to immunise adolescent girls routinely with one or two doses of human papillomavirus (HPV) vaccines to eliminate cervical cancer as a public health problem. With most existing vaccine doses absorbed by countries (mostly high-income) with existing HPV vaccination programmes, limited supply has been left for new country introductions until 2022; many of those, low- and middle-income countries with higher mortality. Several vaccination strategies were considered by the Strategic Advisory Group of Experts on Immunization to allow more countries to introduce vaccination despite constrained supplies., Methods: We examined the impact of nine strategies for allocating limited vaccine doses to 100 pre-introduction countries from 2020 to 2030. Two algorithms were used to optimise the total number of cancer deaths that can be averted worldwide by a limited number of doses (knapsack and decreasing order of country-specific mortality rates), and an unoptimised algorithm (decreasing order of Human Development Index) were used., Findings: Routinely vaccinating 14-year-old girls with either one or two doses and switching to a routine 9-year-old programme when supply is no longer constrained could prevent the most cervical cancer deaths, regardless of allocation algorithm. The unoptimised allocation averts fewer deaths because it allocates first to higher-income countries, usually with lower cervical cancer mortality., Interpretation: To optimise the deaths averted through vaccination when supply is limited, it is important to prioritise high-burden countries and vaccinating older girls first., Funding: WHO, Bill & Melinda Gates Foundation., Competing Interests: All other authors involved in the research have confirmed that they had no commercial or financial interests that could potentially create a conflict of interest. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., (© 2024 The Authors.)

Many low- and middle-income countries have been slow to introduce the pneumococcal conjugate vaccine (PCV) into their routine childhood immunization schedules despite a high burden of disease. We estimated the global economic surplus of PCV, defined as the sum of the net value to 194 countries (i.e., monetized health benefits minus net costs) and to vaccine manufacturers (i.e., profits). We further explored the distribution of global economic surplus across country income groups and manufacturers and the effect of different pricing strategies based on cross-subsidization, pooled procurement, and various tiered pricing mechanisms. We found that current PCV pricing policies disproportionately benefit high-income countries and manufacturers. Based on the 2021 birth cohort, high-income countries and manufacturers combined received 76.5% of the net economic benefits generated by the vaccine. Over the two decades of PCV availability, low- and middle-income countries have not received the full economic benefits of PCV. Cross-subsidization of the vaccine price for low- and middle-income countries and pooled procurement policies that would relate the vaccine price to the value of economic benefits generated for each country could reduce these inequalities. This analysis offers important considerations that may improve the equitable introduction and use of new and under-utilized vaccines.

Background: Vaccination of infants with pneumococcal conjugate vaccines is recommended by the World Health Organization. Evidence is mixed regarding the differences in immunogenicity and efficacy of the different pneumococcal vaccines., Objectives: The primary objective was to compare the immunogenicity of pneumococcal conjugate vaccine-10 versus pneumococcal conjugate vaccine-13. The main secondary objective was to compare the seroefficacy of pneumococcal conjugate vaccine-10 versus pneumococcal conjugate vaccine-13., Methods: We searched the Cochrane Library, EMBASE, Global Health, MEDLINE, ClinicalTrials.gov and trialsearch.who.int up to July 2022. Studies were eligible if they directly compared either pneumococcal conjugate vaccine-7, pneumococcal conjugate vaccine-10 or pneumococcal conjugate vaccine-13 in randomised trials of children under 2 years of age, and provided immunogenicity data for at least one time point. Individual participant data were requested and aggregate data used otherwise. Outcomes included the geometric mean ratio of serotype-specific immunoglobulin G and the relative risk of seroinfection. Seroinfection was defined for each individual as a rise in antibody between the post-primary vaccination series time point and the booster dose, evidence of presumed subclinical infection. Each trial was analysed to obtain the log of the ratio of geometric means and its standard error. The relative risk of seroinfection ('seroefficacy') was estimated by comparing the proportion of participants with seroinfection between vaccine groups. The log-geometric mean ratios, log-relative risks and their standard errors constituted the input data for evidence synthesis. For serotypes contained in all three vaccines, evidence could be synthesised using a network meta-analysis. For other serotypes, meta-analysis was used. Results from seroefficacy analyses were incorporated into a mathematical model of pneumococcal transmission dynamics to compare the differential impact of pneumococcal conjugate vaccine-10 and pneumococcal conjugate vaccine-13 introduction on invasive pneumococcal disease cases. The model estimated the impact of vaccine introduction over a 25-year time period and an economic evaluation was conducted., Results: In total, 47 studies were eligible from 38 countries. Twenty-eight and 12 studies with data available were included in immunogenicity and seroefficacy analyses, respectively. Geometric mean ratios comparing pneumococcal conjugate vaccine-13 versus pneumococcal conjugate vaccine-10 favoured pneumococcal conjugate vaccine-13 for serotypes 4, 9V and 23F at 1 month after primary vaccination series, with 1.14- to 1.54-fold significantly higher immunoglobulin G responses with pneumococcal conjugate vaccine-13. Risk of seroinfection prior to the time of booster dose was lower for pneumococcal conjugate vaccine-13 for serotype 4, 6B, 9V, 18C and 23F than for pneumococcal conjugate vaccine-10. Significant heterogeneity and inconsistency were present for most serotypes and for both outcomes. Twofold higher antibody after primary vaccination was associated with a 54% decrease in risk of seroinfection (relative risk 0.46, 95% confidence interval 0.23 to 0.96). In modelled scenarios, pneumococcal conjugate vaccine-13 or pneumococcal conjugate vaccine-10 introduction in 2006 resulted in a reduction in cases that was less rapid for pneumococcal conjugate vaccine-10 than for pneumococcal conjugate vaccine-13. The pneumococcal conjugate vaccine-13 programme was predicted to avoid an additional 2808 (95% confidence interval 2690 to 2925) cases of invasive pneumococcal disease compared with pneumococcal conjugate vaccine-10 introduction between 2006 and 2030., Limitations: Analyses used data from infant vaccine studies with blood samples taken prior to a booster dose. The impact of extrapolating pre-booster efficacy to post-booster time points is unknown. Network meta-analysis models contained significant heterogeneity which may lead to bias., Conclusions: Serotype-specific differences were found in immunogenicity and seroefficacy between pneumococcal conjugate vaccine-13 and pneumococcal conjugate vaccine-10. Higher antibody response after vaccination was associated with a lower risk of subsequent infection. These methods can be used to compare the pneumococcal conjugate vaccines and optimise vaccination strategies. For future work, seroefficacy estimates can be determined for other pneumococcal vaccines, which could contribute to licensing or policy decisions for new pneumococcal vaccines., Study Registration: This study is registered as PROSPERO CRD42019124580., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/148/03) and is published in full in Health Technology Assessment ; Vol. 28, No. 34. See the NIHR Funding and Awards website for further award information.

Background: Nigeria commenced rollout of vaccination for coronavirus disease 2019 (COVID-19) in March 2021 as part of the national public health response to the pandemic. Findings from appropriately contextualized cost-effectiveness analyses (CEA) as part of a wider process involving health technology assessment (HTA) approaches have been important in informing decision-making in this area. In this paper we outline the processes that were followed to identify COVID-19 vaccine stakeholders involved in the selection, approval, funding, procurement and rollout of vaccines in Nigeria, and describe the process routes we identified to support uptake of HTA-related information for evidence-informed policy in Nigeria., Methods: Our approach to engaging with policy-makers and other stakeholders as part of an HTA of COVID vaccination in Nigeria consisted of three steps, namely: (i) informal discussions with key stakeholders; (ii) stakeholder mapping, analysis and engagement; and (iii) communication and dissemination strategies for the HTA-relevant evidence produced. The analysis of the stakeholder mapping uses the power/interest grid framework., Results: The informal discussion with key stakeholders generated six initial policy questions. Further discussions with policy-makers yielded three suitable policy questions for analysis: which COVID-19 vaccines should be bought; what is the optimal mode of delivery of these vaccines; and what are the cost and cost-effectiveness of vaccinating people highlighted in Nigeria's phase 2 vaccine rollout prioritized by the government, especially the inclusion of those aged between 18 and 49 years. The stakeholder mapping exercise highlighted the range of organizations and groups within Nigeria that could use the information from this HTA to guide decision-making. These stakeholders included both public/government, private and international organizations The dissemination plan developed included disseminating the full HTA results to key stakeholders; production of policy briefs; and presentation at different national and international conferences and peer-reviewed publications., Conclusions: HTA processes that involve stakeholder engagement will help ensure important policy questions are taken into account when designing any HTA including any underpinning evidence generation. Further guidance about stakeholder engagement throughout HTA is required, especially for those with low interest in vaccine procurement and use., (© 2024. The Author(s).)

Background: Long COVID potentially increases healthcare utilisation and costs. However, its impact on the NHS remains to be determined., Methods: This study aims to assess the healthcare utilisation of individuals with long COVID. With the approval of NHS England, we conducted a matched cohort study using primary and secondary care data via OpenSAFELY, a platform for analysing anonymous electronic health records. The long COVID exposure group, defined by diagnostic codes, was matched with five comparators without long COVID between Nov 2020 and Jan 2023. We compared their total healthcare utilisation from GP consultations, prescriptions, hospital admissions, A&E visits, and outpatient appointments. Healthcare utilisation and costs were evaluated using a two-part model adjusting for covariates. Using a difference-in-difference model, we also compared healthcare utilisation after long COVID with pre-pandemic records., Results: We identified 52,988 individuals with a long COVID diagnosis, matched to 264,867 comparators without a diagnosis. In the 12 months post-diagnosis, there was strong evidence that those with long COVID were more likely to use healthcare resources (OR: 8.29, 95% CI: 7.74-8.87), and have 49% more healthcare utilisation (RR: 1.49, 95% CI: 1.48-1.51). Our model estimated that the long COVID group had 30 healthcare visits per year (predicted mean: 29.23, 95% CI: 28.58-29.92), compared to 16 in the comparator group (predicted mean visits: 16.04, 95% CI: 15.73-16.36). Individuals with long COVID were more likely to have non-zero healthcare expenditures (OR = 7.66, 95% CI = 7.20-8.15), with costs being 44% higher than the comparator group (cost ratio = 1.44, 95% CI: 1.39-1.50). The long COVID group costs approximately £2500 per person per year (predicted mean cost: £2562.50, 95% CI: £2335.60-£2819.22), and the comparator group costs £1500 (predicted mean cost: £1527.43, 95% CI: £1404.33-1664.45). Historically, individuals with long COVID utilised healthcare resources more frequently, but their average healthcare utilisation increased more after being diagnosed with long COVID, compared to the comparator group., Conclusions: Long COVID increases healthcare utilisation and costs. Public health policies should allocate more resources towards preventing, treating, and supporting individuals with long COVID., (© 2024. The Author(s).)

Background: Measles seroprevalence data have potential to be a useful tool for understanding transmission dynamics and for decision making efforts to strengthen immunization programs. In this study, we conducted a systematized review and bias assessment of all primary data on measles seroprevalence in low- and middle-income countries (as defined by World Bank 2021 income classifications) published from 1962 to 2021., Methods: On 9 March 2022, we searched PubMed for all available data. We included studies containing primary data on measles seroprevalence and excluded studies if they were clinical trials or brief reports, from only health-care workers, suspected measles cases, or only vaccinated persons. We extracted all available information on measles seroprevalence, study design, and seroassay protocol. We conducted a bias assessment based on multiple categories and classified each study as having low, moderate, severe, or critical bias. This review was registered with PROSPERO (CRD42022326075)., Results: We identified 221 relevant studies across all World Health Organization regions, decades, and unique age ranges. The overall crude mean seroprevalence across all studies was 78.0% (SD: 19.3%), and the median seroprevalence was 84.0% (IQR: 72.8-91.7%). We classified 80 (36.2%) studies as having severe or critical overall bias. Studies from country-years with lower measles vaccine coverage or higher measles incidence had higher overall bias., Conclusions: While many studies have substantial underlying bias, many studies still provide some insights or data that could be used to inform modelling efforts to examine measles dynamics and programmatic decisions to reduce measles susceptibility.

Bacteria are becoming increasingly resistant to antibiotics, reducing our ability to treat infections and threatening to undermine modern health care. Optimising antibiotic use is a key element in tackling the problem. Traditional economic evaluation methods do not capture many of the benefits from improved antibiotic use and the potential impact on resistance. Not capturing these benefits is a major obstacle to optimising antibiotic use, as it fails to incentivise the development and use of interventions to optimise the use of antibiotics and preserve their effectiveness (stewardship interventions). Estimates of the benefits of improving antibiotic use involve considerable uncertainty as they depend on the evolution of resistance and associated health outcomes and costs. Here we discuss how economic evaluation methods might be adapted, in the face of such uncertainties. We propose a threshold-based approach that estimates the minimum resistance-related costs that would need to be averted by an intervention to make it cost-effective. If it is probable that without the intervention costs will exceed the threshold then the intervention should be deemed cost-effective., (© 2024. The Author(s).)

Introduction: There are no published data on the long-term impact of invasive group B Streptococcus disease (iGBS) on economic costs or health-related quality of life (HRQoL) in low-income and middle-income countries. We assessed the impact of iGBS on healthcare utilisation, costs and HRQoL in Argentina, India, Kenya, Mozambique and South Africa., Methods: Inpatient and outpatient visits, out-of-pocket (OOP) healthcare payments in the 12 months before study enrolment, and health-state utility of children and caregivers (using the EuroQol 5-Dimensions-3-Level) were collected from iGBS survivors and an unexposed cohort matched on site, age at recruitment and sex. We used logistic or Poisson regression for analysing healthcare utilisation and zero-inflated gamma regression models for family and health system costs. For HRQoL, we used a zero-inflated beta model of disutility pooled data., Results: 161 iGBS-exposed and 439 unexposed children and young adults (age 1-20) were included in the analysis. Compared with unexposed participants, iGBS was associated with increased odds of any healthcare utilisation in India (adjusted OR 11.2, 95% CI 2.9 to 43.1) and Mozambique (6.8, 95% CI 2.2 to 21.1) and more frequent healthcare visits (adjusted incidence rate ratio (IRR) for India 1.7 (95% CI 1.4 to 2.2) and for Mozambique 6.0 (95% CI 3.2 to 11.2)). iGBS was also associated with more frequent days in inpatient care in India (adjusted IRR 4.0 (95% CI 2.3 to 6.8) and Kenya 6.4 (95% CI 2.9 to 14.3)). OOP payments were higher in the iGBS cohort in India (adjusted mean: Int$682.22 (95% CI Int$364.28 to Int$1000.16) vs Int$133.95 (95% CI Int$72.83 to Int$195.06)) and Argentina (Int$244.86 (95% CI Int$47.38 to Int$442.33) vs Int$52.38 (95% CI Int$-1.39 to Int$106.1)). For all remaining sites, differences were in the same direction but not statistically significant for almost all outcomes. Health-state disutility was higher in iGBS survivors (0.08, 0.04-0.13 vs 0.06, 0.02-0.10)., Conclusion: The iGBS health and economic burden may persist for years after acute disease. Larger studies are needed for more robust estimates to inform the cost-effectiveness of iGBS prevention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

The term 'perspective' in the context of economic evaluations and costing studies in healthcare refers to the viewpoint that an analyst has adopted to define the types of costs and outcomes to consider in their studies. However, there are currently notable variations in terms of methodological recommendations, definitions, and applications of different perspectives, depending on the objective or intended user of the study. This can make it a complex area for stakeholders when interpreting these studies. Consequently, there is a need for a comprehensive overview regarding the different types of perspectives employed in such analyses, along with the corresponding implications of their use. This is particularly important, in the context of low-and-middle-income countries (LMICs), where practical guidelines may be less well-established and infrastructure for conducting economic evaluations may be more limited. This article addresses this gap by summarising the main types of perspectives commonly found in the literature to a broad audience (namely the patient, payer, health care providers, healthcare sector, health system, and societal perspectives), providing their most established definitions and outlining the corresponding implications of their uses in health economic studies, with examples particularly from LMIC settings. We then discuss important considerations when selecting the perspective and present key arguments to consider when deciding whether the societal perspective should be used. We conclude that there is no one-size-fits-all answer to what perspective should be used and the perspective chosen will be influenced by the context, policymakers'/stakeholders' viewpoints, resource/data availability, and intended use of the analysis. Moving forward, considering the ongoing issues regarding the variation in terminology and practice in this area, we urge that more standardised definitions of the different perspectives and the boundaries between them are further developed to support future studies and guidelines, as well as to improve the interpretation and comparison of health economic evidence., (© 2024. The Author(s).)

Background: Hand, foot, and mouth disease (HFMD) is an infectious disease with high morbidity and mortality rates among children under 5 years old. This study aimed to explore the health-related quality of life (HRQOL), economic burden, and related influencing factors among Chinese HFMD patients., Methods: From January to October 2019, a longitudinal cohort study of 296 hospitalized patients (≤ 5 years old) with HFMD and their guardians was conducted using the proxy version of the 5-level EQ-5D-Y (EQ-5D-Y-5L, Y-5L) in face-to-face interviews in Shanghai, Zhengzhou, and Kunming, representing three regions with different economic development levels. Multiple linear regression was used to explore the factors associated with HRQOL and costs., Results: The mean Y-5L health utility score (HUS) (standard deviation, SD), and visual analogue scale (VAS) score (SD) were 0.730 (0.140) and 60.33 (16.52) at admission and increased to 0.920 (0.120) and 89.95 (11.88) at discharge, respectively. The children from Shanghai had the lowest HUSs at admission and had the best health improvement. The mean hospitalization cost and total cost were 4037 CNY and 5157 CNY, respectively. The children from Shanghai had the highest hospitalization cost (4559 CNY) and total cost (5491 CNY). Multiple regression analysis suggested that medical insurance status, type of employment, residence type, and religious status were significantly associated with the baseline HUS and improvement in the HUS after treatment. Region, loss of work time, and length of stay had a significant impact on the hospitalization cost and total cost., Conclusion: Our findings demonstrate that HFMD could lead to poor HRQOL and the economic burden varies in different regions in China. Many pediatric patients still have physical or mental health problems shortly after treatment., (© 2023. The Author(s).)

Background: Long COVID is a major problem affecting patient health, the health service, and the workforce. To optimise the design of future interventions against COVID-19, and to better plan and allocate health resources, it is critical to quantify the health and economic burden of this novel condition. We aimed to evaluate and estimate the differences in health impacts of long COVID across sociodemographic categories and quantify this in Quality-Adjusted Life-Years (QALYs), widely used measures across health systems., Methods: With the approval of NHS England, we utilised OpenPROMPT, a UK cohort study measuring the impact of long COVID on health-related quality-of-life (HRQoL). OpenPROMPT invited responses to Patient Reported Outcome Measures (PROMs) using a smartphone application and recruited between November 2022 and October 2023. We used the validated EuroQol EQ-5D questionnaire with the UK Value Set to develop disutility scores (1-utility) for respondents with and without Long COVID using linear mixed models, and we calculated subsequent Quality-Adjusted Life-Months (QALMs) for long COVID., Findings: The total OpenPROMPT cohort consisted of 7575 individuals who consented to data collection, with which we used data from 6070 participants who completed a baseline research questionnaire where 24.6% self-reported long COVID. In multivariable regressions, long COVID had a consistent impact on HRQoL, showing a higher likelihood or odds of reporting loss in quality-of-life (Odds Ratio (OR): 4.7, 95% CI: 3.72-5.93) compared with people who did not report long COVID. Reporting a disability was the largest predictor of losses of HRQoL (OR: 17.7, 95% CI: 10.37-30.33) across survey responses. Self-reported long COVID was associated with an 0.37 QALM loss., Interpretation: We found substantial impacts on quality-of-life due to long COVID, representing a major burden on patients and the health service. We highlight the need for continued support and research for long COVID, as HRQoL scores compared unfavourably to patients with conditions such as multiple sclerosis, heart failure, and renal disease., Funding: This research was supported by the National Institute for Health and Care Research (NIHR) (OpenPROMPT: COV-LT2-0073)., Competing Interests: BG has received funding via the University of Oxford from a wide range of public and charitable funders: the NHS National Institute for Health Research (NIHR), NHS England, the NIHR School of Primary Care Research, the NIHR Oxford Biomedical Research Centre, the Peter Bennett Foundation, the Laura and John Arnold Foundation, the Mohn-Westlake Foundation, NIHR Applied Research Collaboration Oxford and Thames Valley, UKRI/MRC, the Wellcome Trust, the Good Thinking Foundation, Health Data Research UK, the Health Foundation, and the World Health Organisation; he also receives personal income from speaking and writing for lay audiences on the misuse of science. He led the Goldacre Review (“Better, broader, safer: using health data for research and analysis” March 2022) for Secretary Of State for Health and Social Care; I chaired the HealthTech Advisory Board for Sec of State; I was a Non-Executive Director at NHS Digital; I am on the UKHSA Data Science Advisory Board; I have sat on various other local and national committees in the public sector. BMK is also employed by NHS England working on medicines policy and clinical lead for primary care medicines data. AM is a senior clinical researcher at the University of Oxford in the Bennett Institute, which is funded by contracts and grants obtained from the Bennett Foundation, Wellcome Trust, NIHR Oxford Biomedical Research Centre, NIHR Applied Research Collaboration Oxford and Thames Valley, Mohn-Westlake Foundation, and NHS England, and has consulted for health care vendors, the last time in 2022; the companies consulted in the last 3 years have no relationship to OpenSAFELY; he has represented the RCGP in the health informatics group and the Profession Advisory Group that advises on access to GP Data for Pandemic Planning and Research (GDPPR); the latter was a paid role; and he is a former employee and interim Chief Medical Officer of NHS Digital. REC holds shares in AstraZeneca. AB has received consulting fees from AstraZeneca, Roche, Takeda, Daiichi-Sankyo, Eisai, Novartis, Idorsia and Rhythmn. LAT has received grants or contracts from MRC, Wellcome, NIHR and GSK for an epidemiological study of kidney disease (no personal payment received) and has consulted for Bayer in relation to an observational study of chronic kidney disease (no personal payment received); she has received support for attending the MHRA Expert advisory group on Women's health and is an unpaid member of 4 non-industry funded NIHR/MRC trial advisory committees. JP has acted as an expert witness for the GMC with all fees paid to the company, and is an employee of TPP who provide the SystmOne software. MJ received support from NIHR for the funding of this manuscript and has received research grants from BMGF, Gavi, RCUK, WHO, Wellcome Trust, European Commission, InnoHK, TFGH and CDC. All other authors declare no competing interests., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Most studies on the impact of the COVID-19 pandemic on depression burden focused on the earlier pandemic phase specific to lockdowns, but the longer-term impact of the pandemic is less well-studied. In this population-based cohort study, we examined the short-term and long-term impacts of COVID-19 on depression incidence and healthcare service use among patients with depression., Methods: Using the territory-wide electronic medical records in Hong Kong, we identified all patients aged ≥ 10 years with new diagnoses of depression from 2014 to 2022. We performed an interrupted time-series (ITS) analysis to examine changes in incidence of medically attended depression before and during the pandemic. We then divided all patients into nine cohorts based on year of depression incidence and studied their initial and ongoing service use patterns until the end of 2022. We applied generalized linear modeling to compare the rates of healthcare service use in the year of diagnosis between patients newly diagnosed before and during the pandemic. A separate ITS analysis explored the pandemic impact on the ongoing service use among prevalent patients with depression., Results: We found an immediate increase in depression incidence (RR = 1.21, 95% CI: 1.10-1.33, p < 0.001) in the population after the pandemic began with non-significant slope change, suggesting a sustained effect until the end of 2022. Subgroup analysis showed that the increases in incidence were significant among adults and the older population, but not adolescents. Depression patients newly diagnosed during the pandemic used 11% fewer resources than the pre-pandemic patients in the first diagnosis year. Pre-existing depression patients also had an immediate decrease of 16% in overall all-cause service use since the pandemic, with a positive slope change indicating a gradual rebound over a 3-year period., Conclusions: During the pandemic, service provision for depression was suboptimal in the face of increased demand generated by the increasing depression incidence during the COVID-19 pandemic. Our findings indicate the need to improve mental health resource planning preparedness for future public health crises., (© 2024. The Author(s).)

For vaccine development and adoption decisions, the 'Full Value of Vaccine Assessment' (FVVA) framework has been proposed by the WHO to expand the range of evidence available to support the prioritization of candidate vaccines for investment and eventual uptake by low- and middle-income countries. Recent applications of the FVVA framework have already shown benefits. Building on the success of these applications, we see important new opportunities to maximize the future utility of FVVAs to country and global stakeholders and provide a proof-of-concept for analyses in other areas of disease control and prevention. These opportunities include the following: (1) FVVA producers should aim to create evidence that explicitly meets the needs of multiple key FVVA consumers, (2) the WHO and other key stakeholders should develop standardized methodologies for FVVAs, as well as guidance for how different stakeholders can explicitly reflect their values within the FVVA framework, and (3) the WHO should convene experts to further develop and prioritize the research agenda for outcomes and benefits relevant to the FVVA and elucidate methodological approaches and opportunities for standardization not only for less well-established benefits, but also for any relevant research gaps. We encourage FVVA stakeholders to engage with these opportunities.

Objective: To quantify the association between reduction in child mortality and routine immunization across 204 countries and territories from 1990 to 2019., Methods: We used child mortality and vaccine coverage data from the Global Burden of Disease Study. We used a modified child survival framework and applied a mixed-effects regression model to estimate the reduction in deaths in children younger than 5 years associated with eight vaccines., Findings: Between 1990 and 2019, the diphtheria-tetanus-pertussis (DTP), measles, rotavirus and Haemophilus influenzae type b vaccines were significantly associated with an estimated 86.9 (95% confidence interval, CI: 57.2 to 132.4) million fewer deaths in children younger than 5 years worldwide. This decrease represented a 24.2% (95% CI: 19.8 to 28.9) reduction in deaths relative to a scenario without vaccines. The DTP and measles vaccines averted 46.7 (95% CI: 30.0 to 72.7) million and 37.9 (95% CI: 25.4 to 56.8) million deaths, respectively. Of the total reduction in child mortality associated with vaccines, 84.2% (95% CI: 83.0 to 85.1) occurred in 73 countries supported by Gavi, the Vaccine Alliance, with an estimated 45.4 (95% CI: 29.8 to 69.2) million fewer deaths from 2000 to 2019. The largest reductions in deaths associated with these four vaccines were in India, China, Ethiopia, Pakistan and Bangladesh (in order of the size of reduction)., Conclusion: Vaccines continue to reduce childhood mortality significantly, especially in Gavi-supported countries, emphasizing the need for increased investment in routine immunization programmes., ((c) 2024 The authors; licensee World Health Organization.)

Background: There have been declines in global immunisation coverage due to the COVID-19 pandemic. Recovery has begun but is geographically variable. This disruption has led to under-immunised cohorts and interrupted progress in reducing vaccine-preventable disease burden. There have, so far, been few studies of the effects of coverage disruption on vaccine effects. We aimed to quantify the effects of vaccine-coverage disruption on routine and campaign immunisation services, identify cohorts and regions that could particularly benefit from catch-up activities, and establish if losses in effect could be recovered., Methods: For this modelling study, we used modelling groups from the Vaccine Impact Modelling Consortium from 112 low-income and middle-income countries to estimate vaccine effect for 14 pathogens. One set of modelling estimates used vaccine-coverage data from 1937 to 2021 for a subset of vaccine-preventable, outbreak-prone or priority diseases (ie, measles, rubella, hepatitis B, human papillomavirus [HPV], meningitis A, and yellow fever) to examine mitigation measures, hereafter referred to as recovery runs. The second set of estimates were conducted with vaccine-coverage data from 1937 to 2020, used to calculate effect ratios (ie, the burden averted per dose) for all 14 included vaccines and diseases, hereafter referred to as full runs. Both runs were modelled from Jan 1, 2000, to Dec 31, 2100. Countries were included if they were in the Gavi, the Vaccine Alliance portfolio; had notable burden; or had notable strategic vaccination activities. These countries represented the majority of global vaccine-preventable disease burden. Vaccine coverage was informed by historical estimates from WHO-UNICEF Estimates of National Immunization Coverage and the immunisation repository of WHO for data up to and including 2021. From 2022 onwards, we estimated coverage on the basis of guidance about campaign frequency, non-linear assumptions about the recovery of routine immunisation to pre-disruption magnitude, and 2030 endpoints informed by the WHO Immunization Agenda 2030 aims and expert consultation. We examined three main scenarios: no disruption, baseline recovery, and baseline recovery and catch-up., Findings: We estimated that disruption to measles, rubella, HPV, hepatitis B, meningitis A, and yellow fever vaccination could lead to 49 119 additional deaths (95% credible interval [CrI] 17 248-134 941) during calendar years 2020-30, largely due to measles. For years of vaccination 2020-30 for all 14 pathogens, disruption could lead to a 2·66% (95% CrI 2·52-2·81) reduction in long-term effect from 37 378 194 deaths averted (34 450 249-40 241 202) to 36 410 559 deaths averted (33 515 397-39 241 799). We estimated that catch-up activities could avert 78·9% (40·4-151·4) of excess deaths between calendar years 2023 and 2030 (ie, 18 900 [7037-60 223] of 25 356 [9859-75 073])., Interpretation: Our results highlight the importance of the timing of catch-up activities, considering estimated burden to improve vaccine coverage in affected cohorts. We estimated that mitigation measures for measles and yellow fever were particularly effective at reducing excess burden in the short term. Additionally, the high long-term effect of HPV vaccine as an important cervical-cancer prevention tool warrants continued immunisation efforts after disruption., Funding: The Vaccine Impact Modelling Consortium, funded by Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation., Translations: For the Arabic, Chinese, French, Portguese and Spanish translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests A-MH, XL, SE-L, JR, KA, MA, MJdV, MJF, KF, HF, TH, MJ, AK, SMM, SN, TP, TAP, AP, QTM, EV, AKW, HB, CC, HEC, AD, SH, JH, KJ, CK, J-HK, JK, BAL, VEP, YT, KW, NMF, CLT, and KAMG received funding from Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation via the Vaccine Impact Modelling Consortium (VIMC) during the study. A-MH, JR, SE-L, XL, SN, MJdV, TH, WH, KW, NMF, CLT, and KAMG receive funding from the Medical Research Council Centre for Global Infectious Disease Analysis (reference MR/R015600/1), which is jointly funded by the UK Medical Research Council and the UK Foreign, Commonwealth, and Development Office under a concordant agreement, and is also part of the European and Developing Countries Clinical Trials Partnership programme supported by the EU. A-MH, JR, SE-L, XL, SN, MJdV, TH, WH, KW, NMF, CLT, and KAMG receive funding from Community Jameel. A-MH is supported by the German Federal Ministry of Education and Research (grant 01LN2210A) and declares stock options in BIONTECH. CLT received payment for advice from GlaxoSmithKline. KA is supported by the Japan Agency for Medical Research and Development (JP223fa627004). KAMG received a speaker fee from Sanofi Pasteur. SN receives consulting fees from WHO. VEP is a member of the WHO Immunization and Implementation Research Advisory Committee. BAL receives personal fees from Epidemiologic Research and Methods and Hillevax. SMM receives consultant fees from Emergent Biosolutions. NMF receives grant funding from Janssen Pharmaceuticals, UK Research and Innovation, and the UK National Institute for Health and Care Research; declares consulting fees from the World Bank, WHO, and Gavi; receives travel expenses for WHO meetings; was on an advisory board for Takeda; and is a senior editor for eLife. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: While human papillomavirus (HPV) vaccines have been available since 2006, the coverage has varied among countries. Our aim is to analyse the equity impact of HPV vaccination on the lifetime projections of cervical cancer burden among vaccinated cohorts of 2010-22 in 84 countries., Methods: We used WHO and UNICEF estimates of national immunisation coverage for HPV vaccination in 84 countries during 2010-22. We used PRIME (Papillomavirus Rapid Interface for Modelling and Economics) to estimate the lifetime health impact of HPV vaccination on cervical cancer burden in terms of deaths, cases, and disability-adjusted life years (DALYs) averted by vaccination in their respective countries. We generated concentration indices and curves to assess the equity impact of HPV vaccination across 84 countries., Findings: The health impact of HPV vaccination varied across the 84 countries and ranged from Switzerland to Tanzania at 2 to 34 deaths, 4 to 47 cases, and 40 to 735 DALYs averted per 1000 vaccinated adolescent girls over the lifetime of the vaccinated cohorts of 2010-22. The concentration index for the distribution of average coverage during 2010-22 among the 84 countries ranked by vaccine impact was 0.33 (95% CI: 0.27-0.40) and highlights the wide inequities in HPV vaccination coverage., Interpretation: Our findings suggested that countries with a relatively higher cervical cancer burden and thereby a relatively higher need for HPV vaccination had relatively lower coverage during 2010-22. Further, there were significant inequities in HPV vaccination coverage within the Americas, Europe, and Western Pacific regions, and in high- and low-income countries with a pro-advantaged and regressive distribution favouring countries with lower vaccine impact., Funding: Gavi, the Vaccine Alliance; Bill & Melinda Gates Foundation., Competing Interests: We declare no competing interests., (© 2024 The Author(s).)

Background: Adolescent girls in China have a low HPV vaccination rate. Although vaccination is recommended by the Chinese health authorities, the cost is not covered by the national immunisation programme. Vaccination delay, among other reasons such as supply shortage and poor affordability, may contribute to low uptake. This sequential mixed methods study aimed to identify potential factors of delayed HPV vaccination among Chinese adolescent girls., Methods: Quantitative data about the attitudes and perceptions of HPV vaccination were collected from 100 caregivers of 14-18-year-old girls using an online survey in Chengdu, China. The survey data informed a subsequent qualitative study using four focus group discussions. We conducted a descriptive analysis of the survey data and a thematic analysis of the qualitative data. The findings were interpreted using a health behaviour model adapted from the Health Belief Model and the Andersen's Behavioural Model for Health Services Use., Results: A total of 100 caregivers - 85 were mothers and 15 were fathers - participated in the survey; 21 caregivers joined focus group discussions. When asked about their intended course of action if the 9vHPV vaccine was out-of-stock, 74% chose to delay until the 9vHPV vaccine is available while 26% would consider 2vHPV or 4vHPV vaccines or seek alternative ways to procure the vaccine. Qualitative results confirmed that caregivers preferred delaying HPV vaccination for adolescent girls. The intent to delay was influenced by systemic barriers such as supply shortage and individual-level factors such as a preference for the 9vHPV vaccine, safety concerns, inadequate health communication, and the belief that adolescents were unlikely to be sexually active., Conclusion: In urban areas, Chinese caregivers' intent to delay vaccination in favour of 9vHPV vaccine over receiving the more accessible options was influenced by a mix of individual and contextual factors. Focussed health communication strategies are needed to accelerate HPV vaccination among adolescents., (© 2024. The Author(s).)

Background: Two new products for preventing Respiratory Syncytial Virus (RSV) in young children have been licensed: a single-dose long-acting monoclonal antibody (la-mAB) and a maternal vaccine (MV). To facilitate the selection of new RSV intervention programmes for large-scale implementation, this study provides an assessment to compare the costs of potential programmes with the health benefits accrued., Methods: Using an existing dynamic transmission model, we compared maternal vaccination to la-mAB therapy against RSV in England and Wales by calculating the impact and cost-effectiveness. We calibrated a statistical model to the efficacy trial data to accurately capture their immune waning and estimated the impact of seasonal and year-round programmes for la-mAB and MV programmes. Using these impact estimates, we identified the most cost-effective programme across pricing and delivery cost assumptions., Findings: For infants under six months old in England and Wales, a year-round MV programme with 60% coverage would avert 32% (95% CrI 22-41%) of RSV hospital admissions and a year-round la-mAB programme with 90% coverage would avert 57% (95% CrI 41-69%). The MV programme has additional health benefits for pregnant women, which account for 20% of the population-level health burden averted. A seasonal la-mAB programme could be cost-effective for up to £84 for purchasing and administration (CCPA) and a seasonal MV could be cost-effective for up to £80 CCPA., Interpretation: This modelling and cost-effectiveness analysis has shown that both the long-acting monoclonal antibodies and the maternal vaccine could substantially reduce the burden of RSV disease in the infant population. Our analysis has informed JCVI's recommendations for an RSV immunisation programme to protect newborns and infants., Funding: National Institute for Health Research., Competing Interests: All authors declare no conflict of interest., (© 2023 Published by Elsevier Ltd.)

Objective: To assess spatiotemporal trends in, and determinants of, the acceptance of coronavirus disease 2019 (COVID-19) vaccination globally, as expressed on the social media platform X (formerly Twitter)., Methods: We collected over 13 million posts on the platform regarding COVID-19 vaccination made between November 2020 and March 2022 in 90 languages. Multilingual deep learning XLM-RoBERTa models annotated all posts using an annotation framework after being fine-tuned on 8125 manually annotated, English-language posts. The annotation results were used to assess spatiotemporal trends in COVID-19 vaccine acceptance and confidence as expressed by platform users in 135 countries and territories. We identified associations between spatiotemporal trends in vaccine acceptance and country-level characteristics and public policies by using univariate and multivariate regression analysis., Findings: A greater proportion of platform users in the World Health Organization's South-East Asia, Eastern Mediterranean and Western Pacific Regions expressed vaccine acceptance than users in the rest of the world. Countries in which a greater proportion of platform users expressed vaccine acceptance had higher COVID-19 vaccine coverage rates. Trust in government was also associated with greater vaccine acceptance. Internationally, vaccine acceptance and confidence declined among platform users as: (i) vaccination eligibility was extended to adolescents; (ii) vaccine supplies became sufficient; (iii) nonpharmaceutical interventions were relaxed; and (iv) global reports on adverse events following vaccination appeared., Conclusion: Social media listening could provide an effective and expeditious means of informing public health policies during pandemics, and could supplement existing public health surveillance approaches in addressing global health issues., ((c) 2024 The authors; licensee World Health Organization.)

Objectives: The COVID-19 pandemic placed significant strain on many health systems and economies. Mitigation policies decreased health impacts but had major macroeconomic impact. This article reviews models combining epidemiological and macroeconomic projections to enable policy makers to consider both macroeconomic and health objectives., Methods: A scoping review of epidemiological-macroeconomic models of COVID-19 was conducted, covering preprints, working articles, and journal publications. We assessed model methodologies, scope, and application to empirical data., Results: We found 80 articles modeling both the epidemiological and macroeconomic outcomes of COVID-19. Model scope is often limited to the impact of lockdown on health and total gross domestic product or aggregate consumption and to high-income countries. Just 14% of models assess disparities or poverty. Most models fall under 4 categories: compartmental-utility-maximization models, epidemiological models with stylized macroeconomic projections, epidemiological models linked to computable general equilibrium or input-output models, and epidemiological-economic agent-based models. We propose a taxonomy comparing these approaches to guide future model development., Conclusions: The epidemiological-macroeconomic models of COVID-19 identified have varying complexity and meet different modeling needs. Priorities for future modeling include increasing developing country applications, assessing disparities and poverty, and estimating of long-run impacts. This may require better integration between epidemiologists and economists., Competing Interests: Author Disclosures Dr Bonnet reported receiving grants from Consultative Group for International Agricultural Research, UK Health Security Agency, and the European Union during the conduct of the study. Dr Pearson reported receiving grants from the Bill & Melinda Gates Foundation and United Kingdom Research and Innovation during the conduct of the study. Dr Ruiz reported receiving grants from the Bill and Melinda Gates Foundation during the conduct of the study. Dr Lines reported receiving grants from CGIAR during the conduct of the study and grants from the Wellcome Trust and Foreign, Commonwealth and Development Office UK Government outside of the submitted work. Dr Jit reported receiving grants from the National Institute for Health Research during the conduct of the study. No other disclosures were reported., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: We estimated the global impact of rotavirus vaccines on deaths among children under five years old by year., Methods: We used a proportionate outcomes model with a finely disaggregated age structure to estimate rotavirus deaths prevented by vaccination over the period 2006-2019 in 186 countries. We ran deterministic and probabilistic uncertainty analyses and compared our estimates to surveillance-based estimates in 20 countries., Results: We estimate that rotavirus vaccines prevented 139,000 under-five rotavirus deaths (95% uncertainty interval 98,000-201,000) in the period 2006-2019. In 2019 alone, rotavirus vaccines prevented 15% (95% uncertainty interval 11-21%) of under-five rotavirus deaths (0.5% of child mortality). Assuming global use of rotavirus vaccines and coverage equivalent to other co-administered vaccines could prevent 37% of under-five rotavirus deaths (1.2% of child mortality). Our estimates were sensitive to the choice of rotavirus mortality burden data and several vaccine impact modeling assumptions. The World Health Organization's recommendation to remove age restrictions in 2012 could have prevented up to 17,000 rotavirus deaths in the period 2013-2019. Our modeled estimates of rotavirus vaccine impact were broadly consistent with estimates from post-vaccination surveillance sites., Conclusion: Rotavirus vaccines have made a valuable contribution to global public health. Enhanced rotavirus mortality prevention strategies are needed in countries with high mortality in under-5-year-old children., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)