Vaccination for healthy aging.

As the world's population grows older, vaccination is becoming a key strategy for promoting healthy aging. Despite scientific progress in adult vaccine development, obstacles such as immunosenescence and vaccine hesitancy remain. To unlock the potential of adult vaccines fully, we must enhance immunization programs, dispel misinformation, and invest in research that deepens our understanding of aging and immunity.

Strep A: challenges, opportunities, vaccine-based solutions, and economics.

This collection of articles focuses on Streptococcus pyogenes (Strep A) vaccine research and innovation, with a focus on emerging efforts to understand and estimate the full societal value of Strep A vaccination.

Health and Economic Growth: Reconciling the Micro and Macro Evidence.

Economists use micro-based and macro-based approaches to assess the macroeconomic return to population health. The macro-based approach tends to yield estimates that are either negative and close to zero or positive and an order of magnitude larger than the range of estimates derived from the micro-based approach. This presents a micro-macro puzzle regarding the macroeconomic return to health. We reconcile the two approaches by controlling for the indirect effects of health on income per capita, which macro-based approaches usually include but micro-based approaches deliberately omit when isolating the direct income effects of health. Our results show that the macroeconomic return to health lies in the range of plausible microeconomic estimates, demonstrating that both approaches are in fact consistent with one another.

Cost of care for Alzheimer's disease and related dementias in the United States: 2016 to 2060.

Medical and long-term care for Alzheimer's disease and related dementias (ADRDs) can impose a large economic burden on individuals and societies. We estimated the per capita cost of ADRDs care in the in the United States in 2016 and projected future aggregate care costs during 2020-2060. Based on a previously published methodology, we used U.S. Health and Retirement Survey (2010-2016) longitudinal data to estimate formal and informal care costs. In 2016, the estimated per patient cost of formal care was $28,078 (95% confidence interval [CI]: $25,893-$30,433), and informal care cost valued in terms of replacement cost and forgone wages was $36,667 ($34,025-$39,473) and $15,792 ($12,980-$18,713), respectively. Aggregate formal care cost and formal plus informal care cost using replacement cost and forgone wage methods were $196 billion (95% uncertainty range [UR]: $179-$213 billion), $450 billion ($424-$478 billion), and $305 billion ($278-$333 billion), respectively, in 2020. These were projected to increase to $1.4 trillion ($837 billion-$2.2 trillion), $3.3 trillion ($1.9-$5.1 trillion), and $2.2 trillion ($1.3-$3.5 trillion), respectively, in 2060.

Lifecycle model-based evaluation of infant 4CMenB vaccination in the UK.

OBJECTIVES: Invasive meningococcal disease, an uncommon but severe disease, imposes catastrophic health and economic burdens. Cost-utility analysis (CUA) assumes separability in lifetime health and economic variables and cannot capture the full value of preventing such burdens. We overcome these limitations with a retrospective societal perspective cost-benefit analysis (CBA) of meningococcal serogroup B vaccination (4CMenB) of one infant cohort in the United Kingdom using a health-augmented lifecycle model (HALM) incorporating health's interactions with consumption, earnings, non-market time and financial risk. METHODS: We used a static Markov model of vaccination's health impact and an HALM to estimate the private willingness to pay (PWTP) for the intrinsic and instrumental value of health under perfect capital markets, financial risk protection in the absence of insurance against permanent disability, parental spillovers, and acute phase disability. We estimated social WTP (SWTP) incorporating social severity preferences. We estimated rates of return that inform health payer reimbursement decisions, finance ministry budgeting decisions, and legislature taxation decisions. An expert Advisory Board investigated the validity of applying the HALM to infant 4CMenB. RESULTS: The PWTP for a 2 + 1 vaccination schedule is £395, comprising £166 of disability insurance value, £79 of positive parental spillover value, £28 in the value of averting acute phase disability, and £122 in residual intrinsic and instrumental value of health. SWTP is £969. CONCLUSIONS: HALM-based CBA provides an empirically richer, more utility-theoretically grounded approach to vaccine evaluation than CUA, demonstrating good value for money for legislatures (based on private values) and for all decision-makers (based on social values).

Trajectories and correlates of poor mental health in India over the course of the COVID-19 pandemic: a nationwide survey.

INTRODUCTION: The COVID-19 pandemic had large impacts on mental health; however, most existing evidence is focused on the initial lockdown period and high-income contexts. By assessing trajectories of mental health symptoms in India over 2 years, we aim to understand the effect of later time periods and pandemic characteristics on mental health in a lower-middle income context. METHODS: We used data from the Real-Time Insights of COVID-19 in India cohort study (N=3709). We used covariate-adjusted linear regression models with generalised estimating equations to assess associations between mental health (Patient Health Questionnaire (PHQ-4) score; range 0-12) and pandemic periods as well as pandemic characteristics (COVID-19 cases and deaths, government stringency, self-reported financial impact, COVID-19 infection in the household) and explored effect modification by age, gender and rural/urban residence. RESULTS: Mental health symptoms dropped immediately following the lockdown period but rose again during the delta and omicron waves. Associations between mental health and later pandemic stages were stronger for adults 45 years of age and older (p<0.001). PHQ-4 scores were significantly associated with all pandemic characteristics considered, including estimated COVID-19 deaths (PHQ-4 difference of 0.10 units; 95% CI 0.06 to 0.13), government stringency index (0.14 units; 95% CI 0.11 to 0.18), self-reported major financial impacts (1.20 units; 95% CI 1.09 to 1.32) and COVID-19 infection in the household (0.36 units; 95% CI 0.23 to 0.50). CONCLUSION: While the lockdown period and associated financial stress had the largest mental health impacts on Indian adults, the effects of the pandemic on mental health persisted over time, especially among middle-aged and older adults. Results highlight the importance of investments in mental health supports and services to address the consequences of cyclical waves of infections and disease burden due to COVID-19 or other emerging pandemics.

Meningococcal Disease in the Post-COVID-19 Era: A Time to Prepare.

The global invasive meningococcal disease (IMD) landscape changed considerably during the COVID-19 pandemic, as evidenced by decreased incidence rates due to COVID-19 mitigation measures, such as limited social contact, physical distancing, mask wearing, and hand washing. Vaccination rates were also lower during the pandemic relative to pre-pandemic levels. Although policymakers may have shifted their focus away from IMD vaccination programs to COVID-19 vaccination programs, strong arguments support implementation and prioritization of IMD vaccination programs; IMD cases have increased in some countries and IMD rates may even have exceeded pre-pandemic levels. Additional concerns include increased susceptibility due to vaccination coverage gaps, increased incidence of other respiratory pathogens, immunity debt from lockdown restrictions, and increased IMD epidemiologic variability. The full range of benefits of widely available and effective meningococcal vaccines needs to be considered, especially in health technology assessments, where the broad benefits of these vaccines are neither accurately quantified nor captured in implementation policy decisions. Importantly, implementation of meningococcal vaccination programs in the current IMD climate also appeals to broader healthcare principles, including preparedness rather than reactive approaches, generally accepted benefit-risk approaches to vaccination, historical precedent, and the World Health Organization's goal of defeating meningitis by 2030. Countries should therefore act swiftly to bolster existing meningococcal vaccination strategies to provide broad coverage across age groups and serogroups given the recent increases in IMD incidence.

Antibiotic consumption for sore throat and the potential effect of a vaccine against group A Streptococcus: a systematic review and modelling study.

BACKGROUND: Antibiotic consumption can lead to antimicrobial resistance and microbiome imbalance. We sought to estimate global antibiotic consumption for sore throat, and the potential reduction in consumption due to effective vaccination against group A Streptococcus (Strep A). METHODS: We reviewed and analysed articles published between January 2000 and February 2022, identified though Clarivate Analytics' Web of Science search platform, with reference to antibiotic prescribing or consumption, sore throat, pharyngitis, or tonsillitis. We then used those analyses, combined with assumptions for the effectiveness, duration of protection, and coverage of a vaccine, to calculate the estimated reduction in antibiotic prescribing due to the introduction of Strep A vaccines. FINDINGS: We identified 101 studies covering 38 countries. The mean prescribing rate for sore throat was approximately 5 courses per 100 population per year, accounting for approximately 5% of all antibiotic consumption. Based on 2020 population estimates for countries with empiric prescribing rates, antibiotic consumption for sore throat was estimated to exceed 37 million courses annually, of which half could be attributable to treatment for Strep A. A vaccine that reduces rates of Strep A infection by 80%, with 80% coverage and 10 year's duration of protection, could avert 2.8 million courses of antibiotics prescribed for sore throat treatment among 5-14 year-olds in countries with observed prescribing rates, increasing to an estimated 7.5 million averted if an effective vaccination program also reduced precautionary prescribing. INTERPRETATION: A vaccine that prevents Strep A throat infections in children may reduce antibiotic prescribing for sore throat by 32-87% depending on changes to prescribing and consumption behaviours. FUNDING: The Wellcome Trust, grant agreement number 215490/Z/19/Z.

The macroeconomic burden of noncommunicable diseases and mental health conditions in South America.

Noncommunicable diseases and mental health conditions (referred to collectively as NMHs) are the greatest cause of preventable death, illness, and disability in South America and negatively affect countries' economic performance through their detrimental impacts on labor supply and capital investments. Sound, evidence-based policy-making requires a deep understanding of the macroeconomic costs of NMHs and of their distribution across countries and diseases. The paper estimates and projects the macroeconomic burden of NMHs over the period 2020-2050 in 10 South American countries. We estimate the impact of NMHs on gross domestic product (GDP) through a human capital-augmented production function approach, accounting for mortality and morbidity effects of NMHs on labor supply, for the impact of treatment costs on physical capital accumulation, and for variations in human capital by age. Our central estimates suggest that the overall burden of NMHs in these countries amounts to $7.3 trillion (2022 international $, 3% discount rate, 95% confidence interval: $6.8-$7.8 trillion). Overall, the macroeconomic burden of NMHs is around 4% of total GDP over 2020-2050, with little variation across countries (from 3.2% in Peru to 4.5% in Brazil). In other words, without NMHs, annual GDP over 2020-2050 would be about 4% larger. In most countries, the largest macroeconomic burden is associated with cancers. Results from the paper point to a significant macroeconomic burden of NMHs in South America and provide a strong justification for investment in NMH prevention, early detection, treatment, and formal and informal care.

The full health, economic, and social benefits of prospective Strep A vaccination.

Recent research has documented a wide range of health, economic, and social benefits conferred by vaccination, beyond the direct reductions in morbidity, mortality, and future healthcare costs traditionally captured in economic evaluations. In this paper, we describe the societal benefits that would likely stem from widespread administration of safe and effective vaccines against Streptococcus pyogenes (Strep A), which was estimated to be the fifth-leading cause of infectious disease deaths globally prior to the COVID-19 pandemic. We then estimate the global societal gains from prospective Strep A vaccination through a value-per-statistical-life approach. Estimated aggregate lifetime benefits for 30 global birth cohorts range from $1.7 to $5.1 trillion, depending on the age at which vaccination is administered and other factors. These results suggest that the benefits of Strep A vaccination would be large and justify substantial investment in the vaccines' development, manufacture, and delivery.

Public economic gains from tax-financed investments in childhood immunization in the United States.

The emergence of COVID-19 has displayed the importance of immunization and the need for continued public investment in vaccination programs. Globally, national vaccination programs rely heavily on tax-financed expenditure, requiring upfront investments and ongoing financial commitments. To evaluate annual public investments, we conducted a fiscal analysis that quantifies the public economic consequences to government in the United States attributable to childhood vaccination. To estimate the change in net government revenue, we developed a decision-analytic model that quantifies lifetime tax revenues and transfers based on changes in morbidity and mortality arising from vaccination of the 2017 U.S. birth cohort. Reductions in deaths and comorbid conditions attributed to pediatric vaccines were used to derive gross lifetime earnings gains, tax revenue gains attributed to averted morbidity and mortality avoided, disability transfer cost savings, and averted special education costs associated with each vaccine. Our analysis indicates a fiscal dividend of $41.7 billion from vaccinating this cohort. The bulk of this gain for government reflects avoiding the loss of $30.6 billion in present-value tax revenues. All pediatric vaccines raise tax revenues by reducing vaccine-preventable morbidity and mortality in amounts ranging from $7.3 million (hepatitis A) to $20.3 billion (diphtheria) over the life course. Based on public investments in pediatric vaccines, a benefit-cost ratio of 17.8 was calculated for each dollar invested in childhood immunization. The public economic yield attributed to childhood vaccination in the U.S. is significant from a government perspective, providing fiscal justification for ongoing investment.

Trajectories and correlates of poor mental health in India over the course of the COVID-19 pandemic: a nation-wide survey.

Introduction: The COVID-19 pandemic had large impacts on mental health; however, most existing evidence is focused on the initial lockdown period and high-income contexts. By assessing trajectories of mental health symptoms in India over two years, we aim to understand the effect of later time periods and pandemic characteristics on mental health in a lower-middle income context. Methods: We used data from the Real-Time Insights of COVID-19 in India (RTI COVID-India) cohort study (N=3,662). We used covariate-adjusted linear regression models with generalized estimating equations to assess associations between mental health (PHQ-4 score) and pandemic periods as well as pandemic characteristics (COVID-19 cases and deaths, government stringency, self-reported financial impact, COVID-19 infection in the household) and explored effect modification by age, gender, and rural/urban residence. Results: Mental health symptoms dropped immediately following the lockdown period but rose again during the delta and omicron waves. Associations between mental health and later pandemic stages were stronger for adults 45 years of age and older (p<0.001). PHQ-4 scores were significantly and independently associated with all pandemic characteristics considered, including estimated COVID-19 deaths (PHQ-4 difference of 0.041 SD units; 95% Confidence Interval 0.030 - 0.053), government stringency index (0.060 SD units; 0.048 - 0.072), self-reported major financial impacts (0.45 SD units; 0.41-0.49), and COVID-19 infection in the household (0.11 SD units; 0.07-0.16). Conclusion: While the lockdown period and associated financial stress had the largest mental health impacts on Indian adults, the effects of the pandemic on mental health persisted over time, especially among middle-age and older adults. Results highlight the importance of investments in mental health supports and services to address the consequences of cyclical waves of infections and disease burden due to COVID-19 or other emerging pandemics.

Rule of Prevention: a potential framework to evaluate preventive interventions for rare diseases.

Background: The benefits of preventive interventions lack comprehensive evaluation in standard health technology assessments (HTA), particularly for rare and transmissible diseases. Objective: To identify possible considerations for future HTA using analogies between the treatment and prevention of rare diseases. Study design: An Expert panel meeting assessed whether one HTA assessment framework can be applied to assess both rare disease treatments and preventive interventions. Experts also evaluated the range of value elements currently included in HTAs and their applicability to rare, transmissible, and/or preventable diseases. Results: A broad range of value should be considered when assessing rare, transmissible disease prevention. Although standard HTA can be applied to transmissible diseases, the risk of local outbreaks and the need for large-scale prevention programs suggest a modified assessment framework, capable of incorporating prevention-specific value elements in HTAs. A 'Rule of Prevention' framework was proposed to allow broader value considerations anchored to severity, equity, and prevention benefits in decision-making for preventive interventions for rare transmissible diseases. Conclusion: The proposed prevention framework introduces an explicit initial approach to consistently assess rare transmissible diseases, and to incorporate the broader value of preventive interventions compared with treatment.

The global economic burden of chronic obstructive pulmonary disease for 204 countries and territories in 2020-50: a health-augmented macroeconomic modelling study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and imposes a substantial economic burden. Gaining a thorough understanding of the economic implications of COPD is an important prerequisite for sound, evidence-based policy making. We aimed to estimate the macroeconomic burden of COPD for each country and establish its distribution across world regions. METHODS: In this health-augmented macroeconomic modelling study we estimated the macroeconomic burden of COPD for 204 countries and territories over the period 2020-50. The model accounted for (1) the effect of COPD mortality and morbidity on labour supply, (2) age and sex specific differences in education and work experience among those affected by COPD, and (3) the impact of COPD treatment costs on physical capital accumulation. We obtained data from various public sources including the Global Burden of Disease Study 2019, the World Bank database, and the literature. The macroeconomic burden of COPD was assessed by comparing gross domestic product (GDP) between a scenario projecting disease prevalence based on current estimates and a counterfactual scenario with zero COPD prevalence from 2020 to 2050. FINDINGS: Our findings suggest that COPD will cost the world economy INT$4·326 trillion (uncertainty interval 3·327-5·516; at constant 2017 prices) in 2020-50. This economic effect is equivalent to a yearly tax of 0·111% (0·085-0·141) on global GDP. China and the USA face the largest economic burdens from COPD, accounting for INT$1·363 trillion (uncertainty interval 1·034-1·801) and INT$1·037 trillion (0·868-1·175), respectively. INTERPRETATION: The macroeconomic burden of COPD is large and unequally distributed across countries, world regions, and income levels. Our study stresses the urgent need to invest in global efforts to curb the health and economic burdens of COPD. Investments in effective interventions against COPD do not represent a burden but could instead provide substantial economic returns in the foreseeable future. FUNDING: Alexander von Humboldt Foundation, National Natural Science Foundation of China, CAMS Innovation Fund for Medical Science, Chinese Academy of Engineering project, Chinese Academy of Medical Sciences and Peking Union Medical College project, and Horizon Europe. TRANSLATIONS: For the Chinese and German translations of the abstract see Supplementary Materials section.

Modeling the potential health impact of prospective Strep A vaccines.

The World Health Organization published the preferred product characteristics for a Group A Streptococcus (Strep A) vaccine in 2018. Based on these parameters for the age of vaccination, vaccine efficacy, duration of protection from vaccine-derived immunity, and vaccination coverage, we developed a static cohort model to estimate the projected health impact of Strep A vaccination at the global, regional, and national levels and by country-income category. We used the model to analyse six strategic scenarios. Based on Strep A vaccine introduction between 2022 and 2034 for the primary scenario, we estimated vaccination at birth for 30 vaccinated cohorts could avert 2.5 billion episodes of pharyngitis, 354 million episodes of impetigo, 1.4 million episodes of invasive disease, 24 million episodes of cellulitis, and 6 million cases of rheumatic heart disease globally. Vaccination impact in terms of burden averted per fully vaccinated individual is highest in North America for cellulitis and in Sub-Saharan Africa for rheumatic heart disease.

Optimal global spending for group A Streptococcus vaccine research and development.

Group A Streptococcus (Strep A) leads to 600,000 deaths and 600 million cases of pharyngitis annually. Although long a promising target for vaccine development, how much funding should be allocated to develop a Strep A vaccine is unclear. We aim to calculate the optimal amount of global spending for Strep A vaccine development, the resulting benefits, and the social rate of return on this spending. We develop a model of optimal spending, from a global societal perspective, on research and development (R&D) for vaccines and treatments. The model takes as inputs total harm from the disease, the probability an R&D project succeeds, the cost of a project, and the fraction of total harm a success alleviates. Based on these inputs the model outputs an optimal amount of spending and a rate of return. We calibrate the model for Strep A. Optimal spending is estimated to be 2020 USD33 billion. This spending leads to 2020 USD1.63 trillion in benefits and a real return of 22.3% per year for thirty years. Sensitivity shows an optimal spending range of 15.9 billion to 58.5 billion, a benefits range of 1.6 trillion to 37.9 trillion, and a return range of 18.0-48.2%. Investment in a Strep A vaccine could create enormous benefits for comparatively little cost. It represents one of the highest return uses of public spending. Policy can promote Strep A vaccine development through direct funding of projects and by promoting financial mechanisms that allow the private sector to diversify its R&D investment.

Vaccines for a sustainable planet.

The health of the planet is one objective of the United Nations' Sustainable Development Goals. Vaccines can affect not only human health but also planet health by reducing poverty, preserving microbial diversity, reducing antimicrobial resistance, and preventing an increase in pandemics that is fueled partly by climate change.