Public Health Impact of Paxlovid as Treatment for COVID-19, United States.

We evaluated the population-level benefits of expanding treatment with the antiviral drug Paxlovid (nirmatrelvir/ritonavir) in the United States for SARS-CoV-2 Omicron variant infections. Using a multiscale mathematical model, we found that treating 20% of symptomatic case-patients with Paxlovid over a period of 300 days beginning in January 2022 resulted in life and cost savings. In a low-transmission scenario (effective reproduction number of 1.2), this approach could avert 0.28 million (95% CI 0.03-0.59 million) hospitalizations and save US $56.95 billion (95% CI US $2.62-$122.63 billion). In a higher transmission scenario (effective reproduction number of 3), the benefits increase, potentially preventing 0.85 million (95% CI 0.36-1.38 million) hospitalizations and saving US $170.17 billion (95% CI US $60.49-$286.14 billion). Our findings suggest that timely and widespread use of Paxlovid could be an effective and economical approach to mitigate the effects of COVID-19.

Quantitative Measurement of the Direct Public Health Impact of Medicines Withdrawals in Europe: Development of a Modelling Method and Proof-of-Concept Study to Estimate the Morbidity and Mortality Prevented by Regulatory Action.

PURPOSE: Removing medicines from market may benefit public health by preventing adverse drug reactions (ADRs), which should be quantified. This study's aim was to identify a model to quantify the impact of medicines' marketing authorisation (MA) withdrawal and revocation in terms of preventing morbidity and mortality. METHODS: MA withdrawals and revocations for safety reasons in France, Germany and/or the United Kingdom between July 2012 and December 2016 were identified for prescription medicines. Annual exposure was estimated for each medicine, using IQVIA Medical Research Data (IMRD)-France, IMRD-Germany and IMRD-UK primary care electronic health record databases. European Medicines Agency records provided reasons for regulatory action for each medicine. Absolute risks of ADRs which led to MA withdrawal were estimated for patients exposed to each medicine by systematic review of quantitative research. Public health impact, expressed as annual number of ADRs avoided, was estimated by modelling exposure and ADR risk. RESULTS: Four MA withdrawals and two revocations met study inclusion criteria. Each product's usage decreased following MA withdrawal or revocation. Absolute risk for ADRs was 0.1%-41.25%. To estimate impact of each withdrawal or revocation, its average annual exposure within each IMRD population was multiplied by the absolute risk to give the crude number of ADRs prevented annually due to regulatory action. CONCLUSIONS: This model quantifies the public health impact of MA withdrawal and revocation in terms of serious morbidity, resulting from eliminated or reduced usage of medicines. This method can be applied to products in other settings to quantify the impact of other pharmacovigilance actions.

Thinking flexibly about who digital mental health interventions are for and how they should be evaluated and used: Commentary on McClure et al. (2023).

Less than 20% of individuals with eating disorders (EDs) ever receive treatment. Digital interventions offer one solution to this problem and have demonstrated promise, but there is a need to understand predictors, moderators, and mediators of response, which McClure and colleagues aimed to do in their systematic review. Yet their review also raised key definitional and measurement issues pertinent to conducting research on digital interventions for EDs and other mental health problems, which may have impacted the conclusions drawn and which may stem from applying what has "always been done" in research on more traditional psychological interventions to research on digital interventions. This commentary suggests that digital interventions for EDs and other mental health problems should not be conceived as a 1:1 replacement for individual psychotherapy, and rather, these interventions should be viewed as one option in a wide-ranging menu of services that should be available, as the reality is that not all individuals want or can access the same type of care. If we accept that digital interventions need not be viewed as a 1:1 replacement for psychotherapy, then it logically follows that we should not evaluate or use these two approaches in the exact same manner.

Nurturing innovation, catalyzing change: Honoring the legacy of Dr. C. Barr Taylor in the eating disorders field.

This Virtual Issue of the International Journal of Eating Disorders honors the legacy of the late Dr. C. Barr Taylor in the eating disorders (EDs) field. For decades, Dr. Taylor led the way in not only conducting the research needed to achieve the ultimate goal of making affordable, accessible, and evidence-based care for EDs available to all, but also nurturing the next generation of scientific leaders and innovators. Articles included in this Virtual Issue are a selection of Dr. Taylor's published works in the Journal in the past decade, spanning original research, ideas worth researching, commentaries, and a systematic review. We hope this Virtual Issue will inspire the next generation of research in EDs, and equally, if not more importantly, the next generation of young investigators in the field. We urge the field to continue and build upon Dr. Taylor's vision-to increase access to targeted prevention and intervention for EDs in innovative and forward-thinking ways-while embracing his unique and powerful mentorship style to lift up early career investigators and create a community of leaders to address and solve our field's biggest challenges.

Modeling the population health impact of accurate and inaccurate perceptions of harm from nicotine.

BACKGROUND: Scientific evidence clearly demonstrates that inhaling the smoke from the combustion of cigarettes is responsible for most of the harm caused by smoking, and not the nicotine. However, a majority of U.S. adults who smoke inaccurately believe that nicotine causes cancer which may be a significant barrier, preventing switching to potentially reduced risk, non-combustible products like electronic nicotine delivery systems (ENDS) and smokeless tobacco (ST). We assessed the population health impact associated with nicotine perceptions. METHODS: Using a previously validated agent-based model to the U.S. population, we analyzed nationally representative data from the Population Assessment of Tobacco and Health (PATH) study to estimate base case rates of sustained (maintained over four waves) cessation and switching to non-combustible product use, by sex. Nicotine perception scenarios were determined from PATH data. The overall switch rate from smoking in Wave 4 to non-combustible product use in Wave 5 (3.94%) was stratified based on responses to the nicotine perception question "Do you believe nicotine is the chemical that causes most of the cancer caused by smoking cigarettes?", (four-item scale from "Definitely not" to "Definitely yes"). The relative percent change between the overall and stratified rates, corresponding to each item, was used to adjust the base case rates of switching, to determine the impact, if all adults who smoke exhibited switching behaviors based on responses to the nicotine perceptions question. The public health impact of nicotine perceptions was estimated as the difference in all-cause mortality between the base case and the four nicotine perception scenarios. RESULTS: Switch rates associated with those who responded, "Definitely not" (8.39%) resulted in a net benefit of preventing nearly 800,000 premature deaths over an 85-year period. Conversely switch rates reflective of those who responded, "Definitely yes" (2.59%) resulted in a net harm of nearly 300,000 additional premature deaths over the same period. CONCLUSIONS: Accurate knowledge regarding the role of nicotine is associated with higher switch rates and prevention of premature deaths. Our findings suggest that promoting public education to correct perceptions of harm from nicotine has the potential to benefit public health.

Decreasing the public health burden of eating disorders: Commentary Schleider et al. (2023).

Eating disorders (EDs) are common, disabling, and costly; yet, less than 20% of those with EDs receive treatment. EDs have also skyrocketed in the COVID-19 pandemic, with access to care worse than ever, further solidifying the need to not only make EDs a priority but also embrace new approaches to address this major public health problem. Schleider et al. argue for the single-session intervention (SSI) as one such option and outline an agenda that would aid in building the evidence base and realizing the promise of SSIs for EDs. This commentary details three additional key issues that need to be addressed in order to realize the full potential of SSIs and related approaches and ultimately decrease the public health burden of EDs. These include conducting work to optimize interventions for greatest effectiveness, recognizing the value and working to massively increase reach of interventions like SSIs that can scale and meet diverse needs, and engaging in the work needed to address structural barriers to widespread dissemination of these approaches. Through this agenda, we will do more than embrace a single-session "mindset" and will catalyze the work needed to disseminate SSIs and related approaches at massive scale and maximize their impact.

The imported infections among foreign travelers in China: an observational study.

BACKGROUND: In the past few decades, globalization has rendered more frequent and intensive population movement between countries, which has changed the original disease spectrum and brought a huge health impact on the global population including China. This study aims to describe the spectrum and epidemiological characteristics of imported infections among foreign travelers travelling to China. METHODS: The data on imported infections among foreign travelers were obtained from Custom Inbound Screening System (CISS) and the National Notifiable Infectious Disease Reporting System (NNIDRS). All the infections were classified into respiratory, gastrointestinal, vector-borne, blood/sex-transmitted and mucocutaneous diseases, of which case numbers and incidences were calculated and the proportions were compared among subgroups. RESULTS: In total, 17,189 travelers diagnosed with 58 imported infectious diseases were reported from 2014 to 2018, with an overall incidence of 122.59 per million. Respiratory infection (7,351 cases, mainly influenza) and blood/sex-transmitted diseases (6,114 cases mainly Hepatitis B and HIV infection) were the most frequently diagnosed diseases, followed by vector-borne infections (3,128 cases, mainly dengue fever and malaria). The highest case number was from Asia and Europe, while the highest incidence rate was from Africa (296.00 per million). When specific diagnosis was compared, both the highest absolute case number and incidence were observed for influenza. An obvious seasonal pattern was observed for vector-borne diseases, with the annual epidemic spanning from July to November. The origin-destination matrices disclosed the movement of imported infection followed specific routes. CONCLUSIONS: Our study provided a profile of infectious diseases among foreign travelers travelling to China and pinpointed the target regions, seasons and populations for prevention and control, to attain an informed control of imported infections in China.

Estimating the reduction in US mortality if cigarettes were largely replaced by e-cigarettes.

BACKGROUND: Recent estimates indicated substantially replacing cigarettes by e-cigarettes would, during 2016-2100, reduce US deaths and life-years lost (millions) by 6.6 and 86.7 (Optimistic Scenario) and 1.6 and 20.8 (Pessimistic). To provide additional insight we use alternative modelling based on a shorter period (1991-2040), four main smoking-associated diseases, deaths aged 30-79 years, and a full product history. We consider variations in: assumed effective dose of e-cigarettes versus cigarettes (F); their relative quitting rate (Q); proportions smoking after 10 years (X); and initiation rate (I) of vaping, relative to smoking. METHODS: We set F = 0.05, X = 5%, Q = 1.0 and I = 1.0 (Main Scenario) and F = 0.4, X = 10%, Q = 0.5 and I = 1.5 (Pessimistic Scenario). Sensitivity Analyses varied Main Scenario parameters singly; F from 0 to 0.4, X 0.01% to 15%, and Q and I 0.5 to 1.5. To allow comparison with prior work, individuals cannot be dual users, re-initiate, or switch except from cigarettes to e-cigarettes. RESULTS: Main Scenario reductions were 2.52 and 26.23 million deaths and life-years lost; Pessimistic Scenario reductions were 0.76 and 8.31 million. These were less than previously, due to the more limited age-range and follow-up, and restriction to four diseases. Reductions in deaths (millions) varied most for X, from 3.22 (X = 0.01%) to 1.31 (X = 15%), and F, 2.74 (F = 0) to 1.35 (F = 0.4). Varying Q or I had little effect. CONCLUSIONS: Substantial reductions in deaths and life-years lost were observed even under pessimistic assumptions. Estimates varied most for X and F. These findings supplement literature indicating e-cigarettes can importantly impact health challenges from smoking.

Public health potential of guidelines-based dietary scores for non-communicable diseases mortality prevention: simulation study using the Preventable Risk Integrated ModEl (PRIME) model.

OBJECTIVE: Dietary indexes measure the adherence of individuals to a set of nutritional recommendations. However, the health gains associated with adherence to various dietary indexes may vary. Our objective was to compare the magnitude of estimated avoided deaths by chronic diseases obtained by improving diet quality in the French population, measured by a variety of dietary indexes. DESIGN: Simulation study based on observational data. SETTING: Weighted data from a French population-based cohort study. PARTICIPANTS: In participants from the NutriNet-Santé cohort, we computed dietary scores reflecting the adherence to various recommendations (Medi-Lite, Healthy Diet Indicator (HDI), Programme National Nutrition Santé/National Nutrition and Health Program - Guidelines Score, Diet Quality Index (DQI), Alternative Healthy Eating Index (AHEI) and the modified Food Standards Agency nutrient profiling system dietary index (FSAm-NPS DI)). Quintiles of the food groups' consumption and dietary intakes were used as input in a simulation model (Preventable Risk Integrated ModEl (PRIME)), yielding the number of delayed or avoided deaths in nutrition-related non-communicable diseases, comparing between very high or very low nutritional quality of the diet and medium nutritional quality. RESULTS: A modification of dietary intakes from medium quality to very low quality (i.e. from the middle quintile to the quintile with the lowest nutritional quality) was associated with an increased number of deaths ranging from 3485 (95 % uncertainty interval (CI) 4002, 2987) for HDI and 3379 (95 % CI 3881, 2894) for FSAm-NPS DI to 838 (95 % CI 1163, 523) for Medi-Lite. Conversely, a modification of dietary intakes from medium quality to very high quality was associated with a decrease in the number of deaths ranging from 1995 (95 % CI 1676, 2299) for Probability of Adequate Nutrient intake diet, 1986 (95 % CI 1565, 2361) for DQI-International, 1931 (95 % CI 1499, 2316) for FSAm-NPS DI and 858 (95 % CI 499, 1205) for HDI. CONCLUSIONS: Our results provide some insights as the potential impact of following various dietary guidelines to reduce mortality from nutrition-related diseases.

Qualitative Analysis of Administrator, Provider, and Stakeholder Views on the Costs and Benefits of a Treatment for Problematic Sexual Behavior of Youth.

Evidence-based treatment for youth with problematic sexual behavior (PSB) has the potential for a broad range of costs and benefits, raising the importance of querying its public health impact. This qualitative study examined the impact of treatment for youth with PSB through content analysis of interviews (N = 57) with service agency administrators, treatment providers, and professional stakeholders in communities where recent implementation of interventions for youth with PSB had occurred. Interviewees emphasized multi-level impacts of the program on families (e.g., knowledge, well-being), communities (e.g., public safety, education), and public agencies (e.g., caseloads, stress). Implications for comprehensively evaluating the impact of PSB interventions are discussed.

Managing nicotine without smoke to save lives now: Evidence for harm minimization.

Tobacco control has made strides in prevention and cessation, but deaths will not decline rapidly without massive behavior change. Currently, inhaled smoke from combusting tobacco is chiefly responsible for prematurely killing 7.2 million people worldwide and 530,000 in the United States annually. An array of noncombustible nicotine products (NNPs) has emerged and has disrupted the marketplace. Saving lives more speedily will require societal acceptance of locating a "sweet spot" within a three-dimensional framework where NNPs are simultaneously: 1. Less toxic, 2. Appealing (can reach smokers at scale), and 3. Satisfying (adequate nicotine delivery) to displace smoking. For this harm minimization framework to eliminate smoking, a laser focus on "smoking control" (not general tobacco control) is needed. By adopting these economically viable NNPs as part of the solution, NNPs can be smoking control's valued ally. Synthesis of the science indicates that policy and regulation can sufficiently protect youth while speeding the switch away from smoking. Despite some risks of nicotine dependence that can be mitigated but not eliminated, no credible evidence counters the assertion that NNPs will save lives if they displace smoking. But scientific evidence and advocacy has selectively exaggerated NNP harms over benefits. Accurate communication is crucial to dispel the misperception of NNPs harms and reassure smokers they can successfully replace smoking cigarettes with NNPs. Saving more lives now is an attainable and pragmatic way to call for alignment of all stakeholders and factions within traditional tobacco control rather than perpetuate the unrealized and unrealizable perfection of nicotine prohibition.

Peer support to improve diabetes care: an implementation evaluation of the Australasian Peers for Progress Diabetes Program.

BACKGROUND: Several studies have now demonstrated the benefits of peer support in promoting diabetes control. The aim of this study is to evaluate the implementation of a cluster randomised controlled trial of a group-based, peer support program to improve diabetes self-management and thereby, diabetes control in people with Type 2 Diabetes in Victoria, Australia. METHODS: The intervention program was designed to address four key peer support functions i.e. 1) assistance in daily management, 2) social and emotional support, 3) regular linkage to clinical care, and 4) ongoing and sustained support to assist with the lifelong needs of diabetes self-care management. The intervention participants attended monthly group meetings facilitated by a trained peer leader for 12 months. Data was collected on the intervention's reach, participation, implementation fidelity, groups' effectiveness and participants' perceived support and satisfaction with the intervention. The RE-AIM and PIPE frameworks were used to guide this evaluation. RESULTS: The trial reached a high proportion (79%) of its target population through mailed invitations. Out of a total of 441 eligible individuals, 273 (61.9%) were willing to participate. The intervention fidelity was high (92.7%). The proportion of successful participants who demonstrated a reduction in 5 years cardiovascular disease risk score was 65.1 and 44.8% in the intervention and control arm respectively. Ninety-four percent (94%) of the intervention participants stated that the program helped them manage their diabetes on a day to day basis. Overall, attending monthly group meetings provided 'a lot of support' to 57% and 'moderate' support to 34% of the participants. CONCLUSION: Peer support programs are feasible, acceptable and can be used to supplement treatment for patients motivated to improve behaviours related to diabetes. However, program planners need to focus on the participation component in designing future programs. The use of two evaluation frameworks allowed a comprehensive evaluation of the trial from the provider-, participant- and public health perspective. The learnings gained from this evaluation will guide and improve future implementation by improving program feasibility for adoption and acceptability among participants, and will ultimately increase the likelihood of program effectiveness for the participants. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12609000469213 . Registered 16 June 2009.

The public health value of vaccines beyond efficacy: methods, measures and outcomes.

BACKGROUND: Assessments of vaccine efficacy and safety capture only the minimum information needed for regulatory approval, rather than the full public health value of vaccines. Vaccine efficacy provides a measure of proportionate disease reduction, is usually limited to etiologically confirmed disease, and focuses on the direct protection of the vaccinated individual. Herein, we propose a broader scope of methods, measures and outcomes to evaluate the effectiveness and public health impact to be considered for evidence-informed policymaking in both pre- and post-licensure stages. DISCUSSION: Pre-licensure: Regulatory concerns dictate an individually randomised clinical trial. However, some circumstances (such as the West African Ebola epidemic) may require novel designs that could be considered valid for licensure by regulatory agencies. In addition, protocol-defined analytic plans for these studies should include clinical as well as etiologically confirmed endpoints (e.g. all cause hospitalisations, pneumonias, acute gastroenteritis and others as appropriate to the vaccine target), and should include vaccine-preventable disease incidence and 'number needed to vaccinate' as outcomes. Post-licensure: There is a central role for phase IV cluster randomised clinical trials that allows for estimation of population-level vaccine impact, including indirect, total and overall effects. Dynamic models should be prioritised over static models as the constant force of infection assumed in static models will usually underestimate the effectiveness and cost-effectiveness of the immunisation programme by underestimating indirect effects. The economic impact of vaccinations should incorporate health and non-health benefits of vaccination in both the vaccinated and unvaccinated populations, thus allowing for estimation of the net social value of vaccination. CONCLUSIONS: The full benefits of vaccination reach beyond direct prevention of etiologically confirmed disease and often extend across the life course of a vaccinated person, prevent outcomes in the wider community, stabilise health systems, promote health equity, and benefit local and national economies. The degree to which vaccinations provide broad public health benefits is stronger than for other preventive and curative interventions.

The Evolution of the Meningitis Vaccine Project.

BACKGROUND: In 2001, the Meningitis Vaccine Project (MVP) was tasked to develop, test, license, and introduce a group A meningococcal (MenA) conjugate vaccine for sub-Saharan Africa. African public health officials emphasized that a vaccine price of less than US$0.50 per dose was necessary to ensure introduction and sustained use of this new vaccine. METHODS: Initially, MVP envisioned partnering with a multinational vaccine manufacturer, but the target price and opportunity costs were problematic and formal negotiations ended in 2002. MVP chose to become a "virtual vaccine company," and over the next decade managed a network of public-private and public-public partnerships for pharmaceutical development, clinical development, and regulatory submission. MVP supported the transfer of key know-how for the production of group A polysaccharide and a new conjugation method to the Serum Institute of India, Ltd, based in Pune, India. A robust staff structure supported by technical consultants and overseen by advisory groups in Europe and Africa ensured that the MenA conjugate vaccine would meet all international standards. RESULTS: A robust project structure including a team of technical consultants and 3 advisory groups in Europe and Africa ensured that the MenA conjugate vaccine (PsA-TT, MenAfriVac) was licensed by the Drug Controller General of India and prequalified by the World Health Organization in June 2010. The vaccine was introduced in Burkina Faso, Mali, and Niger in December 2010. CONCLUSIONS: The development, through a public-private partnership, of a safe, effective, and affordable vaccine for sub-Saharan Africa, PsA-TT, offers a new paradigm for the development of vaccines specifically targeting populations in resource-poor countries.

Efficacy thresholds and target populations for antiviral COVID-19 treatments to save lives and costs: a modelling study.

Background: In 2023 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared endemic, yet hospital admissions have persisted and risen within populations at high and moderate risk of developing severe disease, which include those of older age, and those with co-morbidities. Antiviral treatments, currently only available for high-risk individuals, play an important role in preventing severe disease and hospitalisation within this subpopulation. Here, we further explore the public health and economic benefits of extending target populations for treatment, and assess efficacy thresholds for a treatment strategy to be cost-saving. Methods: We adapted an individual-based transmission model of SARS-CoV-2, OpenCOVID, which was calibrated and validated to 2020-2023 Swiss, European, and Northern Hemisphere epidemiological data. We used the model to estimate hospitalisations and overall costs for preventatively treating three risk groups for a full range of treatment efficacies and coverages with, besides vaccination and hospital treatments, no other interventions in place. We further calculated efficacy thresholds for strategies to be cost-saving. A global sensitivity analysis was conducted to test the sensitivity of all outcomes for a wide range of treatment properties, emerging variant properties, and vaccination coverages. Findings: In a high vaccination coverage setting, we found that a high efficacy antiviral treatment given to all those at high-risk could reduce hospitalisations by up to 40%. When expanding treatment coverage to also include all those at moderate-risk, an additional 50% of hospitalisations could be averted. Targeting both high-risk and moderate-risk groups was found to be cost-saving for a treatment efficacy greater than ∼40%. This threshold was found to be robust regardless of vaccination coverage and emerging variant properties, but highly sensitive to treatment costs. Interpretation: For a sufficiently efficacious antiviral treatment, expanding the target population to include both high-risk and moderate-risk groups should be considered. Equitable treatment costs are found crucial in achieving the best possible public health and health economic outcomes. Funding: Botnar Research Centre for Child Health (DZX2165 to MAP), the Swiss National Science Foundation Professorship of MAP (P00P3_203450) and Swiss National Science Foundation NFP 78 Covid-19 2020 (4079P0_198428 to MAP).

How the French national authority for health assesses medicines for use in pediatrics.

Children deserve to be treated with appropriate medicines based on robust assessments. Despite the introduction of new regulations, the availability of medicines for children is suboptimal because of the frequent lack of relevant clinical trials due to the difficulty of conducting such trials. Thus, the Transparency Committee (TC) of the French National Authority for Health, who oversees the assessment of medicinal products in France, set up a pediatric working group with two aims: (1) The first aim was to review all opinions on medicines for pediatric use. Out of 536 opinions delivered between 2020 and 2022, 181 (34 %) concerned medicines for pediatric use. Whereas oncology largely dominated the medicines for adults, medicines for infectious diseases, endocrinology/metabolism, neurology, and hematology mostly prevailed for children. (2) The second aim was to clarify the evaluation criteria assessed by the TC, namely, the clinical benefit (CB), the clinical added value (CAV), and the public health impact (PHI) for pediatric medicinal products. An important CB was given to 113 out of 161 (71 %) opinions on medicines for pediatric use when it concerned pathologies with a severe prognosis. The quality of the demonstration (e.g., double-blind randomized trial vs. placebo or another active medicine) played a major role in the CB level. Clinical pediatric studies were also consistently associated with higher CAV levels: levels I (major) to III (moderate) in 26 out of 42 (62 %) opinions, level IV (minor) and level V (no therapeutic progress) in 43 out of 84 (51 %) and 30 out of 43 (70 %) opinions granting a sufficient CB, respectively. Conversely, 22 out of 30 (73 %) dossiers based only on literature reviews were given a level V. The main criteria leading to the qualification of a medicine for pediatric use as providing a PHI included a significant change in the morbidity and mortality of the disease and an improvement in the care pathway. Assessments were mostly aligned on the adults in the case of subsequent extensions of indications to children. Lastly, new measures were taken aimed at shortening median delays in the assessment process in order to reduce off-label use of medicines in France.

A Narrative Review on the Pandemic Zoonotic RNA Virus Infections Occurred During the Last 25 Years.

BACKGROUND: Pandemic zoonotic RNA virus infections have continued to threaten humans and animals worldwide. The objective of this review was to highlight the epidemiology and socioeconomic impacts of pandemic zoonotic RNA virus infections that occurred between 1997 and 2021. METHODS: Literature search was done from Web of Science, PubMed, Google Scholar and Scopus databases, cumulative case fatalities of individual viral infection calculated, and geographic coverage of the pandemics were shown by maps. RESULTS: Seven major pandemic zoonotic RNA virus infections occurred from 1997 to 2021 and were presented in three groups: The first group consists of highly pathogenic avian influenza (HPAI-H5N1) and swine-origin influenza (H1N1) viruses with cumulative fatality rates of 53.5% and 0.5% in humans, respectively. Moreover, HPAI-H5N1 infection caused 90-100% death in poultry and economic losses of >$10 billion worldwide. Similarly, H1N1 caused a serious infection in swine and economic losses of 0.5-1.5% of the Gross Domestic Product (GDP) of the affected countries. The second group consists of severe acute respiratory syndrome-associated coronavirus infection (SARS-CoV), Middle East Respiratory Syndrome (MERS-CoV) and Coronavirus disease 2019 (COVID-19) with case fatalities of 9.6%, 34.3% and 2.0%, respectively in humans; but this group only caused mild infections in animals. The third group consists of Ebola and Zika virus infections with case fatalities of 39.5% and 0.02%, respectively in humans but causing only mild infections in animals. CONCLUSION: Similar infections are expected in the near future, and hence strict implementation of conventional biosecurity-based measures and development of efficacious vaccines would help minimize the impacts of the next pandemic infection.

An Application of an Initial Full Value of Vaccine Assessment Methodology to Measles-Rubella MAPs for Use in Low- and Middle-Income Countries.

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.

Pneumococcal serotypes missing prespecified efficacy threshold in immunogenicity trials: real-world evidence from national immunization programs.

OBJECTIVES: The 13-valent (PCV13) and 10-valent (PCV10) pneumococcal conjugate vaccines missed non-inferiority for certain 7-valent (PCV7) serotypes in immunogenicity trials. This study examines the population-level IPD case trends for these serotypes. METHODS: We identified six countries with national IPD surveillance data that introduced PCV13 (Canada, Germany, Israel, Italy, South Africa, and the United States) and three with PCV10 (Finland, Brazil, and the Netherlands). We extracted country-specific annual IPD case counts for PCV7 serotypes that missed non-inferiority and met non-inferiority (6B + 23F and PCV7 minus [6B + 23F] serotypes for PCV10 countries; 6B +9V + 23F, and PCV7 minus [6B +9V + 23F] serotypes for PCV13 countries) in clinical trials. Case count data for each country were plotted for observed serotype trends in different age groups (<5 and ≥5 years) for 8 years following PCV13/PCV10 introduction. RESULTS: For all ages and countries, IPD cases due to PCV7 serotypes that missed non-inferiority either decreased or remained suppressed following PCV13/PCV10 introduction. Similar trends were found for PCV7 serotypes that met non-inferiority in those <5 years. Paradoxically, cases increased in those ≥5 years in Canada, Italy, and the US, primarily driven by increases in serotypes 4 and 19F disease. CONCLUSIONS: Despite missing non-inferiority of serotypes in immunogenicity trials, higher-valent PCVs effectively suppressed these serotypes across all ages. Non-inferiority criteria from immunogenicity trials may not fully predict real-world disease impact after PCV implementation.

The public health impact of recombinant herpes zoster vaccination in adults over 50 years in Spain.

The recombinant zoster vaccine (RZV) is included in the Spanish National Immunisation Programme for adults 65 years of age (years), with a potential progressive catch-up program for adults 66-80 years, starting with 80 years. However, the risk of herpes zoster (HZ) increases significantly from 50 years. We estimated the public health impact (PHI) of vaccinating adults ≥50 years in Spain versus no vaccination, using a Markov model adapted to the Spanish setting. The model simulated a hypothetical ≥50 years cohort over a lifetime, with inputs from Spanish publications, databases, or publications from other countries where Spanish data were unavailable. Base case inputs included 67.7% RZV coverage and 61.1% second dose compliance. Outputs included clinical outcomes avoided, healthcare resource use avoided, and number-needed-to-vaccinate (NNV) to prevent one HZ case. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were also conducted. The model estimated that, compared with no vaccination, vaccinating adults ≥50 years in Spain (N = 19,850,213) with RZV could prevent 1,533,353 HZ cases, 261,610 postherpetic neuralgia episodes, 274,159 other complications, and 138 deaths through the cohorts' remaining lifetime, mostly in the 50-59 years cohort. Furthermore, 3,500,492 primary care visits and 71,156 hospitalizations could be avoided, with NNV = 9 to prevent one HZ case. DSA predicted NNV = 7 to prevent one HZ case when second dose compliance was increased to 100%. PSA demonstrated ≥200,000 and ≥1,400,000 cases could be prevented in 86.9% and 18.4% of simulations, respectively. Starting RZV from 50 years could therefore prevent a substantial number of HZ cases and complications. Increasing RZV coverage and second dose compliance could further alleviate PHI of HZ.