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.

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.

The benefits and costs of U.S. employer COVID-19 vaccine mandates.

In 2021, the Biden Administration issued mandates requiring COVID-19 vaccinations for U.S. federal employees and contractors and for some healthcare and private sector workers. These mandates have been challenged in court; some have been halted or delayed. However, their costs and benefits have not been rigorously appraised. This study helps fill that gap. We estimate the direct costs and health-related benefits that would have accrued if these vaccination requirements had been implemented as intended. Compared with the January 2022 vaccination rates, we find that the mandates could have led to 15 million additional vaccinated individuals, increasing the overall proportion of the fully vaccinated U.S. population from 64% to 68%. The associated net benefits depend on the subsequent evolution of the pandemic-information unavailable ex ante to analysts or policymakers. In scenarios involving the emergence of a novel, more transmissible variant, against which vaccination and previous infection offer moderate protection, the estimated net benefits are potentially large. They reach almost $20,000 per additional vaccinated individual, with more than 20,000 total deaths averted over the 6-month period assessed. In scenarios involving a fading pandemic, existing vaccination-acquired or infection-acquired immunity provides sufficient protection, and the mandates' benefits are unlikely to exceed their costs. Thus, mandates may be most useful when the consequences of inaction are catastrophic. However, we do not compare the effects of mandates with alternative policies for increasing vaccination rates or for promoting other protective measures, which may receive stronger public support and be less likely to be overturned by litigation.

The global burden of sore throat and group A Streptococcus pharyngitis: A systematic review and meta-analysis.

Background: Contemporary data for the global burden of sore throat and group A Streptococcus (Strep A) pharyngitis are required to understand the frequency of disease and develop value propositions for Strep A vaccines. Methods: We used Clarivate Analytics' Web of Science platform to search WoS core collection, PubMed, Medline, data citation index, KCI-Korean Journal Database, Russian Science Citation Index, and the SciELO Citation Index for articles published between Jan 1, 2000, and Feb 15, 2021, from any country and in any language. The risk of bias was assessed using the JBI critical appraisal checklist. We used random-effects meta-analyses to pool sore throat and Strep A sore throat incidence rates from community-based studies. Our study was registered with PROSPERO (CRD42020181103). Findings: Of 5,529 articles identified by the search strategy, 26 studies met the inclusion criteria, but only two included data to determine incidence among adults. The pooled incidence rate, calculated for children only, was 82.2 episodes per 100 child-years (95% CI 25.2-286.3, I2 = 100%) for sore throat (7 studies; 7,964 person years) and 22.1 episodes per 100 child-years (95% CI 14.7-33.1, I2 = 98%) for Strep A sore throat (9 studies; 15,696 person years). The pooled cumulative incidence rate of sore throat from five studies was 31.9 per 100 children. There was significant methodological and statistical heterogeneity among studies, and five of 26 studies had a risk of bias score less than five (range: nine [maximum score] to one). Interpretation: Strep A sore throat has a considerable global burden. However, methodologically standardised studies are required to quantify that burden, analyse differences in rates between populations, and evaluate the likely impact of future Strep A vaccines. Funding: This study was funded by Wellcome Trust 215,490/Z/19/Z.

COVID-19 Vaccine Allocation: Modeling Health Outcomes and Equity Implications of Alternative Strategies.

Given the scarcity of safe and effective COVID-19 vaccines, a chief policy question is how to allocate them among different sociodemographic groups. This paper evaluates COVID-19 vaccine prioritization strategies proposed to date, focusing on their stated goals; the mechanisms through which the selected allocations affect the course and burden of the pandemic; and the main epidemiological, economic, logistical, and political issues that arise when setting the prioritization strategy. The paper uses a simple, age-stratified susceptible-exposed-infectious-recovered model applied to the United States to quantitatively assess the performance of alternative prioritization strategies with respect to avoided deaths, avoided infections, and life-years gained. We demonstrate that prioritizing essential workers is a viable strategy for reducing the number of cases and years of life lost, while the largest reduction in deaths is achieved by prioritizing older adults in most scenarios, even if the vaccine is effective at blocking viral transmission. Uncertainty regarding this property and potential delays in dose delivery reinforce the call for prioritizing older adults. Additionally, we investigate the strength of the equity motive that would support an allocation strategy attaching absolute priority to essential workers for a vaccine that reduces infection-fatality risk.

The Societal Value of Vaccination in the Age of COVID-19.

In recent years, academics and policymakers have increasingly recognized that the full societal value of vaccination encompasses broad health, economic, and social benefits beyond avoided morbidity and mortality due to infection by the targeted pathogen and limited health care costs. Nevertheless, standard economic evaluations of vaccines continue to focus on a relatively narrow set of health-centric benefits, with consequences for vaccination policies and public investments.The COVID-19 pandemic illustrates in stark terms the multiplicity and magnitude of harms that infectious diseases may inflict on society. COVID-19 has overtaxed health systems, disrupted routine immunization programs, forced school and workplace closures, impeded the operation of international supply chains, suppressed aggregate demand, and exacerbated existing social inequities.The obvious nature of the pandemic's broad effects could conceivably convince more policymakers to identify and account for the full societal impacts of infectious disease when evaluating the potential benefits of vaccination. Such a shift could make a big difference in how we allocate societal resources in the service of population health and in how much we stand to gain from that spending.

How New Models Of Vaccine Development For COVID-19 Have Helped Address An Epic Public Health Crisis.

Coronavirus disease 2019 (COVID-19) vaccine development and manufacturing have proceeded at a historically unprecedented pace. This speed may be accounted for by the unprecedented scale of resources being devoted to addressing COVID-19; an unusual intensity of cooperation, encompassing the public and private sectors and occurring both within and across national borders; and innovation with respect to both technologies (for example, new vaccine platforms) and processes (for example, vaccine clinical trials). In this article we describe and analyze how resources, cooperation, and innovation have contributed to the accelerated development of COVID-19 vaccines. Similar levels and types of public investment, models of cooperation, and harnessing of innovative processes and technologies could be applied to future epidemics and other global health challenges.

Infectious Disease Threats in the Twenty-First Century: Strengthening the Global Response.

The world has developed an elaborate global health system as a bulwark against known and unknown infectious disease threats. The system consists of various formal and informal networks of organizations that serve different stakeholders; have varying goals, modalities, resources, and accountability; operate at different regional levels (i.e., local, national, regional, or global); and cut across the public, private-for-profit, and private-not-for-profit sectors. The evolving global health system has done much to protect and promote human health. However, the world continues to be confronted by longstanding, emerging, and reemerging infectious disease threats. These threats differ widely in terms of severity and probability. They also have varying consequences for morbidity and mortality, as well as for a complex set of social and economic outcomes. To various degrees, they are also amenable to alternative responses, ranging from clean water provision to regulation to biomedical countermeasures. Whether the global health system as currently constituted can provide effective protection against a dynamic array of infectious disease threats has been called into question by recent outbreaks of Ebola, Zika, dengue, Middle East respiratory syndrome, severe acute respiratory syndrome, and influenza and by the looming threat of rising antimicrobial resistance. The concern is magnified by rapid population growth in areas with weak health systems, urbanization, globalization, climate change, civil conflict, and the changing nature of pathogen transmission between human and animal populations. There is also potential for human-originated outbreaks emanating from laboratory accidents or intentional biological attacks. This paper discusses these issues, along with the need for a (possibly self-standing) multi-disciplinary Global Technical Council on Infectious Disease Threats to address emerging global challenges with regard to infectious disease and associated social and economic risks. This Council would strengthen the global health system by improving collaboration and coordination across organizations (e.g., the WHO, Gavi, CEPI, national centers for disease control, pharmaceutical manufacturers, etc.); filling in knowledge gaps with respect to (for example) infectious disease surveillance, research and development needs, financing models, supply chain logistics, and the social and economic impacts of potential threats; and making high-level, evidence-based recommendations for managing global risks associated with infectious disease.

Toward economic evaluation of the value of vaccines and other health technologies in addressing AMR.

We discuss the need to make economic evaluations of vaccines antimicrobial resistance (AMR)-sensitive and ways to do so. Such AMR-sensitive evaluations can play a role in value-for-money comparisons of different vaccines within a national immunization program, or in comparisons of vaccine-centric and non-vaccine-centric technologies within an anti-AMR program. In general terms, incremental cost-effectiveness ratios and rates of return and their associated decision rules are unaltered by consideration of AMR-related value. The decision metrics need to have their various health, cost, and socioeconomic terms disaggregated into resistance-related subcategories, which in turn have to be measured carefully before they are reaggregated. The fundamental scientific challenges lie primarily in quantifying the causal impact of health technologies on resistance-related health outcomes, and secondarily in ascertaining the economic value of those outcomes. We emphasize the importance of evaluating vaccines in the context of other potentially complementary and substitutable nonvaccine technologies. Complementarity implies that optimal spending on each set of interventions is positive, and substitutability implies that the ratio of spending will depend on relative value for money. We exemplify this general point through a qualitative discussion of the complementarities and (especially the) substitutability between pneumococcal conjugate vaccines and antimicrobial stewardship and between research and development (R&D) of a gonorrhea vaccine versus R&D of a gonorrhea antibiotic. We propose a roadmap for future work, which includes quantifying the causal effects of vaccination and other health technologies on short-term and long-term resistance-related outcomes, measuring the health-sector costs and broader socioeconomic consequences of resistance-related mortality and morbidity, and evaluating vaccines in the context of nonvaccine complements and substitutes.

Moving beyond traditional valuation of vaccination: Needs and opportunities.

Economic evaluations of vaccination traditionally focus on a relatively narrow set of vaccine benefits, such as averted medical care costs among those who are immunized. In recent years, researchers have identified additional vaccination benefits that should be incorporated into economic evaluations in order to reflect vaccination's full value. Early efforts to estimate the magnitude of these broader benefits suggest that vaccination has been substantially undervalued, which has important implications for public and private vaccine policy and human health and welfare. More and better data will be required to advance this emerging line of research on the value of vaccination. The article discusses promising data sources and methods and research questions needing to be addressed.