Health-Economic Value of Vaccination Against Group A Streptococcus in the United States.

BACKGROUND: Vaccines are needed to reduce the burden of group A Streptococcus (GAS). We assessed the potential health-economic value of GAS vaccines achievable through prevention of invasive disease and acute upper respiratory infections in the United States. METHODS: We estimated annual incidence of invasive GAS disease and associated costs incurred from hospitalization and management of long-term sequelae, as well as productivity losses resulting from acute illness, long-term disability, and mortality. We also estimated healthcare and productivity costs associated with GAS pharyngitis, sinusitis, and acute otitis media. We estimated costs averted by prevention of invasive disease and acute upper respiratory infections for vaccines with differing efficacy profiles; our base case considered vaccines meeting the World Health Organization Preferred Product Profile (WHO-PPP) with a 6-year average duration of protection. RESULTS: Costs of invasive GAS disease and acute upper respiratory infections totaled $6.08 (95% confidence interval [CI], $5.33-$6.86) billion annually. Direct effects of vaccines meeting WHO-PPP characteristics and administered at ages 12 and 18 months would avert $609 (95% CI, $558-$663) million in costs annually, primarily by preventing noninvasive disease; with an additional dose at age 5 years, averted costs would total $869 (95% CI, $798-$945) million annually. Adult vaccination at age 65 years would avert $326 (95% CI, $271-$387) million in annual costs associated with invasive GAS disease. Indirect effects of vaccination programs reducing incidence of GAS diseases across all ages by 20% would avert roughly $1 billion in costs each year. CONCLUSIONS: The economic burden of GAS is substantial. Our findings should inform prioritization of GAS vaccine development and evaluation.

Health inequities in SARS-CoV-2 infection, seroprevalence, and COVID-19 vaccination: Results from the East Bay COVID-19 study.

Comprehensive data on transmission mitigation behaviors and both SARS-CoV-2 infection and serostatus are needed from large, community-based cohorts to identify COVID-19 risk factors and the impact of public health measures. We conducted a longitudinal, population-based study in the East Bay Area of Northern California. From July 2020-March 2021, approximately 5,500 adults were recruited and followed over three data collection rounds to investigate the association between geographic and demographic characteristics and transmission mitigation behavior with SARS-CoV-2 prevalence. We estimated the populated-adjusted prevalence of antibodies from SARS-CoV-2 infection and COVID-19 vaccination, and self-reported COVID-19 test positivity. Population-adjusted SARS-CoV-2 seroprevalence was low, increasing from 1.03% (95% CI: 0.50-1.96) in Round 1 (July-September 2020), to 1.37% (95% CI: 0.75-2.39) in Round 2 (October-December 2020), to 2.18% (95% CI: 1.48-3.17) in Round 3 (February-March 2021). Population-adjusted seroprevalence of COVID-19 vaccination was 21.64% (95% CI: 19.20-24.34) in Round 3, with White individuals having 4.35% (95% CI: 0.35-8.32) higher COVID-19 vaccine seroprevalence than individuals identifying as African American or Black, American Indian or Alaskan Native, Asian, Hispanic, two or more races, or other. No evidence for an association between transmission mitigation behavior and seroprevalence was observed. Despite >99% of participants reporting wearing masks individuals identifying as African American or Black, American Indian or Alaskan Native, Asian, Hispanic, two or more races, or other, as well as those in lower-income households, and lower-educated individuals had the highest SARS-CoV-2 seroprevalence and lowest vaccination seroprevalence. Results demonstrate that more effective policies are needed to address these disparities and inequities.

Modelling the global burden of drug-resistant tuberculosis avertable by a post-exposure vaccine.

There have been notable advances in the development of vaccines against active tuberculosis (TB) disease for adults and adolescents. Using mathematical models, we seek to estimate the potential impact of a post-exposure TB vaccine, having 50% efficacy in reducing active disease, on global rifampicin-resistant (RR-) TB burden. In 30 countries that together accounted for 90% of global RR-TB incidence in 2018, a future TB vaccine could avert 10% (95% credible interval: 9.7-11%) of RR-TB cases and 7.3% (6.6-8.1%) of deaths over 2020-2035, with India, China, Indonesia, Pakistan, and the Russian Federation having the greatest contribution. This impact would increase to 14% (12-16%) and 31% (29-33%) respectively, when combined with improvements in RR-TB diagnosis and treatment relative to a scenario of no vaccine and no such improvements. A future TB vaccine could have important implications for the global control of RR-TB, especially if implemented alongside enhancements in management of drug resistance.

Childhood vaccines and antibiotic use in low- and middle-income countries.

Vaccines may reduce the burden of antimicrobial resistance, in part by preventing infections for which treatment often includes the use of antibiotics1-4. However, the effects of vaccination on antibiotic consumption remain poorly understood-especially in low- and middle-income countries (LMICs), where the burden of antimicrobial resistance is greatest5. Here we show that vaccines that have recently been implemented in the World Health Organization's Expanded Programme on Immunization reduce antibiotic consumption substantially among children under five years of age in LMICs. By analysing data from large-scale studies of households, we estimate that pneumococcal conjugate vaccines and live attenuated rotavirus vaccines confer 19.7% (95% confidence interval, 3.4-43.4%) and 11.4% (4.0-18.6%) protection against antibiotic-treated episodes of acute respiratory infection and diarrhoea, respectively, in age groups that experience the greatest disease burden attributable to the vaccine-targeted pathogens6,7. Under current coverage levels, pneumococcal and rotavirus vaccines prevent 23.8 million and 13.6 million episodes of antibiotic-treated illness, respectively, among children under five years of age in LMICs each year. Direct protection resulting from the achievement of universal coverage targets for these vaccines could prevent an additional 40.0 million episodes of antibiotic-treated illness. This evidence supports the prioritization of vaccines within the global strategy to combat antimicrobial resistance8.

Emerging Challenges and Opportunities in Infectious Disease Epidemiology.

Much of the intellectual tradition of modern epidemiology stems from efforts to understand and combat chronic diseases persisting through the 20th century epidemiologic transition of countries such as the United States and United Kingdom. After decades of relative obscurity, infectious disease epidemiology has undergone an intellectual rebirth in recent years amid increasing recognition of the threat posed by both new and familiar pathogens. Here, we review the emerging coalescence of infectious disease epidemiology around a core set of study designs and statistical methods bearing little resemblance to the chronic disease epidemiology toolkit. We offer our outlook on challenges and opportunities facing the field, including the integration of novel molecular and digital information sources into disease surveillance, the assimilation of such data into models of pathogen spread, and the increasing contribution of models to public health practice. We next consider emerging paradigms in causal inference for infectious diseases, ranging from approaches to evaluating vaccines and antimicrobial therapies to the task of ascribing clinical syndromes to etiologic microorganisms, an age-old problem transformed by our increasing ability to characterize human-associated microbiota. These areas represent an increasingly important component of epidemiology training programs for future generations of researchers and practitioners.

Measurement of Vaccine Direct Effects Under the Test-Negative Design.

Test-negative designs are commonplace in assessments of influenza vaccination effectiveness, estimating this value from the exposure odds ratio of vaccination among individuals treated for acute respiratory illness who test positive for influenza virus infection. This approach is widely believed to recover the vaccine direct effect by correcting for differential health-care-seeking behavior among vaccinated and unvaccinated persons. However, the relationship of the measured odds ratio to true vaccine effectiveness is poorly understood. We derived the odds ratio under circumstances of real-world test-negative studies. The odds ratio recovers the vaccine direct effect when 2 conditions are met: 1) Individuals' vaccination decisions are uncorrelated with exposure or susceptibility to the test-positive or test-negative conditions, and 2) vaccination confers "all-or-nothing" protection (whereby certain individuals have no protection while others are perfectly protected). Biased effect-size estimates arise if either condition is unmet. Such bias might suggest misleading associations of vaccine effectiveness with time since vaccination or the force of infection of influenza. The test-negative design could also fail to correct for differential health-care-seeking behavior among vaccinated and unvaccinated persons without stringent criteria for enrollment and testing. Our findings demonstrate a need to reassess how data from test-negative studies can inform policy decisions.