• Accelerated vaccine rollout is imperative to mitigate highly transmissible COVID-19 variants

      Sah, Pratha; Vilches, Thomas N; Moghadas, Seyed M; Fitzpatrick, Meagan C; Singer, Burton H; Hotez, Peter J; Galvani, Alison P (Elsevier Inc., 2021-04-25)
      Background: More contagious variants of SARS-CoV-2 have emerged around the world, sparking concerns about impending surge in cases and severe outcomes. Despite the development of effective vaccines, rollout has been slow. We evaluated the impact of accelerated vaccine distribution on curbing the disease burden of novel SARS-CoV-2 variants. Methods: We used an agent-based model of SARS-CoV-2 transmission and vaccination to simulate the spread of novel variants with S-Gene Target Failure (SGTF) in addition to the original strain. We incorporated age-specific risk and contact patterns and implemented a two-dose vaccination campaign in accord with CDC-recommended prioritization. As a base case, we projected hospitalizations and deaths at a daily vaccination rate of 1 million doses in the United States (US) and compared with accelerated campaigns in which daily doses were expanded to 1.5, 2, 2.5, or 3 million. Findings: We found that at a vaccination rate of 1 million doses per day, an emergent SGTF variant that is 20–70% more transmissible than the original variant would become dominant within 2 to 9 weeks, accounting for as much as 99% of cases at the outbreak peak. Our results show that accelerating vaccine delivery would substantially reduce severe health outcomes. For a SGTF with 30% higher transmissibility, increasing vaccine doses from 1 to 3 million per day would avert 152,048 (95% CrI: 134,772–168,696) hospitalizations and 48,448 (95% CrI: 42,042–54,285) deaths over 300 days. Accelerated vaccination would also prevent additional COVID-19 waves that would otherwise be fuelled by waning adherence to non-pharmaceutical interventions (NPIs). Interpretation: We found that the current pace of vaccine rollout is insufficient to prevent the exacerbation of the pandemic that will be attributable to the novel, more contagious SARS-CoV-2 variants. Accelerating the vaccination rate should be a public health priority for averting the expected surge in COVID-19 hospitalizations and deaths that would be associated with widespread dissemination of the SGTF variants. Our results underscore the need to bolster the production and distribution of COVID-19 vaccines, to rapidly expand vaccination priority groups and distribution sites. © 2021 The Authors
    • Addressing COVID-19 Vaccine Hesitancy in Patients with IBD

      Hudhud, Dania; Caldera, Freddy; Cross, Raymond K (Oxford University Press, 2021-09-24)
      It is recommended that all patients with IBD undergo vaccination against COVID-19. In this commentary, we encourage IBD providers to serve as vaccine advocates and suggest implementing different methods for battling misinformation, paying careful attention to minority population.
    • Equination (inoculation of horsepox): An early alternative to vaccination (inoculation of cowpox) and the potential role of horsepox virus in the origin of the smallpox vaccine

      Esparza, J.; Schrick, L.; Damaso, C.R.; Nitsche, A. (Elsevier Ltd, 2017)
      For almost 150 years after Edward Jenner had published the "Inquiry" in 1798, it was generally assumed that the cowpox virus was the vaccine against smallpox. It was not until 1939 when it was shown that vaccinia, the smallpox vaccine virus, was serologically related but different from the cowpox virus. In the absence of a known natural host, vaccinia has been considered to be a laboratory virus that may have originated from mutational or recombinational events involving cowpox virus, variola viruses or some unknown ancestral Orthopoxvirus. A favorite candidate for a vaccinia ancestor has been the horsepox virus. Edward Jenner himself suspected that cowpox derived from horsepox and he also believed that "matter" obtained from either disease could be used as preventative of smallpox. During the 19th century, inoculation with cowpox (vaccination) was used in Europe alongside with inoculation with horsepox (equination) to prevent smallpox. Vaccine-manufacturing practices during the 19th century may have resulted in the use of virus mixtures, leading to different genetic modifications that resulted in present-day vaccinia strains. Horsepox, a disease previously reported only in Europe, has been disappearing on that continent since the beginning of the 20th century and now seems to have become extinct, although the virus perhaps remains circulating in an unknown reservoir. Genomic sequencing of a horsepox virus isolated in Mongolia in 1976 indicated that, while closely related to vaccinia, this horsepox virus contained additional, potentially ancestral sequences absent in vaccinia. Recent genetic analyses of extant vaccinia viruses have revealed that some strains contain ancestral horsepox virus genes or are phylogenetically related to horsepox virus. We have recently reported that a commercially produced smallpox vaccine, manufactured in the United States in 1902, is genetically highly similar to horsepox virus, providing a missing link in this 200-year-old mystery.
    • Evaluation of post-introduction COVID-19 vaccine effectiveness: Summary of interim guidance of the World Health Organization

      Patel, Minal K; Bergeri, Isabel; Bresee, Joseph S; Cowling, Benjamin J; Crowcroft, Natasha S; Fahmy, Kamal; Hirve, Siddhivinayak; Kang, Gagandeep; Katz, Mark A; Lanata, Claudio F; et al. (Elsevier Ltd., 2021-06-01)
      Phase 3 randomized-controlled trials have provided promising results of COVID-19 vaccine efficacy, ranging from 50 to 95% against symptomatic disease as the primary endpoints, resulting in emergency use authorization/listing for several vaccines. However, given the short duration of follow-up during the clinical trials, strict eligibility criteria, emerging variants of concern, and the changing epidemiology of the pandemic, many questions still remain unanswered regarding vaccine performance. Post-introduction vaccine effectiveness evaluations can help us to understand the vaccine's effect on reducing infection and disease when used in real-world conditions. They can also address important questions that were either not studied or were incompletely studied in the trials and that will inform evolving vaccine policy, including assessment of the duration of effectiveness; effectiveness in key subpopulations, such as the very old or immunocompromised; against severe disease and death due to COVID-19; against emerging SARS-CoV-2 variants of concern; and with different vaccination schedules, such as number of doses and varying dosing intervals. WHO convened an expert panel to develop interim best practice guidance for COVID-19 vaccine effectiveness evaluations. We present a summary of the interim guidance, including discussion of different study designs, priority outcomes to evaluate, potential biases, existing surveillance platforms that can be used, and recommendations for reporting results.
    • Identification of Helicobacter pylori and the evolution of an efficacious childhood vaccine to protect against gastritis and peptic ulcer disease

      Blanchard, T.G.; Czinn, S.J. (Nature Publishing Group, 2017)
      Establishment of Helicobacter pylori infection as an etiologic agent of peptic ulcer disease and other gastric pathologies marked a revolution in gastroenterology which spurred an enormous interest in gastric physiology and immunology research. The association was soon also demonstrated in children as well. Application of antimicrobial therapies have proven remarkably efficacious in eradicating H. pylori and curing pediatric patients of duodenal ulcers as well as gastritis, negating a lifetime of ineffective therapy and life-threatening disease. Countries with high H. pylori prevalence and where H. pylori associated gastric cancer remains a primary cause of death due to cancer however would benefit from childhood vaccination. Studies in rodents and humans utilizing oral vaccination with bacterial exotoxin adjuvants demonstrated potential for limiting H. pylori colonization in the stomach. Almost 25 y of vaccine research recently culminated in a phase III clinical trial of over 4,000 children aged 6-15 y old to test an oral vaccine consisting of the H. pylori urease B subunit genetically fused to the E. coli heat labile toxin. Vaccination was demonstrated to have an efficacy of over 70%. Vaccination may now serve as an effective strategy to significantly reduce H. pylori associated disease in children throughout the world.
    • Linked vaccination coverage surveys plus serosurveys among Ethiopian toddlers undertaken three years apart to compare coverage and serologic evidence of protection in districts implementing the RED-QI approach

      Campbell, James D; Pasetti, Marcela F; Oot, Lisa; Adam, Zenaw; Tefera, Mesfin; Beyane, Berhane; Mulholland, Nigisti; Steinglass, Robert; Krey, Rebecca; Chen, Wilbur H; et al. (Elsevier Ltd., 2021-08-28)
      In low and middle-income countries, estimating the proportion of vaccinated toddlers in a population is important for controlling vaccine-preventable diseases by identifying districts where immunization services need strengthening. Estimates measured before and several years after specific interventions can assess program performance. However, employing different methods to derive vaccination coverage estimates often yield differing results. Methods: Linked vaccination coverage surveys and seroprotection surveys performed among ~300 toddlers 12-23 months of age in districts (woredas), one per region, of Ethiopia (total, ~900 toddlers) in 2013 to estimate the proportion vaccinated with tetanus toxoid (a proxy for pentavalent vaccine) and measles vaccine. The surveys were followed by implementation of the Reaching Every District using Quality Improvement (RED-QI) approach to strengthen the immunization system. Linked coverage/serosurveys were repeated in 2016 to assess effects of the interventions on vaccination coverage. Indicators included "documented coverage" (vaccination card and/or health facility register records) and "crude coverage" (documented plus parent/caretaker recall for children without cards). Seroprotection thresholds were IgG-ELISA tetanus antitoxin ≥0.05 IU/ml and plaque reduction neutralization (PRN) measles titers ≥120 mIU/ml. Findings: Improved markers in 2016 over 2013 include coverage of pentavalent vaccination, vaccination timeliness, and fewer missed opportunities to vaccinate. In parallel, tetanus seroprotection increased in the 3 woredas from 59.6% to 79.1%, 72.9% to 83.7%, and 94.3 to 99.3%. In 2015, the Ethiopian government conducted supplemental measles mass vaccination campaigns in several regions including one that involved a project woreda and the campaign overlapped with the RED-QI intervention timeframe; protective measles PRN titers there rose from 31.0% to 50.0%. Interpretation: The prevalence of seroprotective titers of tetanus antitoxin (stimulated by tetanus toxoid components within pentavalent vaccine) provides a reliable biomarker to identify children who received pentavalent vaccine. In the three study woredas, the RED-QI intervention appeared to improve immunization service delivery, as documented by enhanced pentavalent vaccine coverage, vaccination timeliness, and fewer missed vaccination opportunities. A measles mass vaccination campaign was followed by a markedly increased prevalence of measles PRN antibodies. Collectively, these observations suggest that wider implementation of RED-QI can strengthen immunization, and periodic linked vaccination surveys/serosurveys can monitor changes.
    • Optimizing age-specific vaccination

      Fitzpatrick, Meagan C; Galvani, Alison P (American Association for the Advancement of Science, 2021-02-26)
    • Optimizing the impact of low-efficacy influenza vaccines

      Sah, Pratha; Medlock, Jan; Fitzpatrick, Meagan C. (National Academy of Sciences, 2018-05-15)
      The efficacy of influenza vaccines varies from one year to the next, with efficacy during the 2017–2018 season anticipated to be lower than usual. However, the impact of low-efficacy vaccines at the population level and their optimal age-specific distribution have yet to be ascertained. Applying an optimization algorithm to a mathematical model of influenza transmission and vaccination in the United States, we determined the optimal age-specific uptake of low-efficacy vaccine that would minimize incidence, hospitalization, mortality, and disability-adjusted life-years (DALYs), respectively. We found that even relatively low-efficacy influenza vaccines can be highly impactful, particularly when vaccine uptake is optimally distributed across age groups. As vaccine efficacy declines, the optimal distribution of vaccine uptake shifts toward the elderly to minimize mortality and DALYs. Health practitioner encouragement and concerted recruitment efforts are required to achieve optimal coverage among target age groups, thereby minimizing influenza morbidity and mortality for the population overall.
    • The Rapid Evaluation of COVID-19 Vaccination in Emergency Departments for Underserved Patients Study

      Rodriguez, Robert M; Torres, Jesus R; Chang, Anna Marie; Haggins, Adrianne N; Eucker, Stephanie A; O'Laughlin, Kelli N; Anderson, Erik; Miller, Daniel G; Wilkerson, R Gentry; Caldwell, Martina; et al. (Elsevier Inc., 2021-05-31)
      Study objective: Emergency departments (EDs) often serve vulnerable populations who may lack primary care and have suffered disproportionate COVID-19 pandemic effects. Comparing patients having and lacking a regular source of medical care and other ED patient characteristics, we assessed COVID-19 vaccine hesitancy, reasons for not wanting the vaccine, perceived access to vaccine sites, and willingness to get the vaccine as part of ED care. Methods: This was a cross-sectional survey conducted from December 10, 2020, to March 7, 2021, at 15 safety net US EDs. Primary outcomes were COVID-19 vaccine hesitancy, reasons for vaccine hesitancy, and sites (including EDs) for potential COVID-19 vaccine receipt. Results: Of 2,575 patients approached, 2,301 (89.4%) participated. Of the 18.4% of respondents who lacked a regular source of medical care, 65% used the ED as their usual source of health care. The overall rate of vaccine hesitancy was 39%; the range among the 15 sites was 28% to 58%. Respondents who lacked a regular source of medical care were more commonly vaccine hesitant than those who had a regular source of medical care (47% versus 38%, 9% difference, 95% confidence interval 4% to 14%). Other characteristics associated with greater vaccine hesitancy were younger age, female sex, Black race, Latinx ethnicity, and not having received an influenza vaccine in the past 5 years. Of the 61% who would accept a COVID-19 vaccine, 21% stated that they lacked a primary physician or clinic at which to receive it; the vast majority (95%) of these respondents would accept the COVID-19 vaccine as part of their care in the ED. Conclusion: ED patients who lack a regular source of medical care are particularly hesitant regarding COVID-19 vaccination. Most COVID-19 vaccine acceptors would accept it as part of their care in the ED. EDs may play pivotal roles in COVID-19 vaccine messaging and delivery to highly vulnerable populations.
    • The Role American Thoracic Society Healthcare Providers Have in Immunization

      Ortiz, Justin R; Hartert, Tina V (American Thoracic Society, 2021-02-19)