Factors influencing scar formation following Bacille Calmette-Guérin (BCG) vaccination

The prevalence of scar formation following Bacille Calmette-Guérin (BCG) vaccination varies globally. The beneficial effects of BCG are stronger amongst children who develop a BCG scar. Within an international randomised trial (‘BCG vaccination to reduce the impact of coronavirus disease 2019 (COVID-19) in healthcare workers';BRACE Trial), this nested prospective cohort study assessed the prevalence of and factors influencing scar formation, as well as participant perception of BCG scarring 12 months following vaccination in healthcare workers. Amongst 3071 BCG-recipients, 2341 (76%) developed a BCG scar. Scar prevalence was lowest in Spain and highest in UK. Absence of post-injection wheal (OR 0.4, 95%CI 0.2–0.9), BCG revaccination (OR 1.7, 95%CI 1.3–2.0), female sex (OR 2.0, 95%CI 1.7–2.4), older age (OR 0.4, 95%CI 0.4–0.5) and study country (Brazil OR 1.6, 95%CI 1.3–2.0) influenced BCG scar prevalence. Of the 2341 participants with a BCG scar, 1806 (77%) did not mind having the scar. Participants more likely to not mind were those in Brazil, males and those with a prior BCG vaccination history. The majority (2242/2341, 96%) did not regret having the vaccine due to scar development. Both vaccination-related (amenable to optimisation) and individual-related factors affected BCG scar prevalence 12 months following BCG vaccination of adults, with implications for maximising the effectiveness of BCG vaccination.

Factors influencing scar formation following Bacille Calmette-Guérin (BCG) vaccination.

The prevalence of scar formation following Bacille Calmette-Guérin (BCG) vaccination varies globally. The beneficial off-target effects of BCG are proposed to be stronger amongst children who develop a BCG scar. Within an international randomised trial ('BCG vaccination to reduce the impact of coronavirus disease 2019 (COVID-19) in healthcare workers'; BRACE Trial), this nested prospective cohort study assessed the prevalence of and factors influencing scar formation, as well as participant perception of BCG scarring 12 months following vaccination . Amongst 3071 BCG-recipients, 2341 (76%) developed a BCG scar. Scar prevalence was lowest in Spain and highest in UK. Absence of post-injection wheal (OR 0.4, 95%CI 0.2-0.9), BCG revaccination (OR 1.7, 95%CI 1.3-2.0), female sex (OR 2.0, 95%CI 1.7-2.4), older age (OR 0.4, 95%CI 0.4-0.5) and study country (Brazil OR 1.6, 95%CI 1.3-2.0) influenced BCG scar prevalence. Of the 2341 participants with a BCG scar, 1806 (77%) did not mind having the scar. Participants more likely to not mind were those in Brazil, males and those with a prior BCG vaccination history. The majority (96%) did not regret having the vaccine. Both vaccination-related (amenable to optimisation) and individual-related factors affected BCG scar prevalence 12 months following BCG vaccination of adults, with implications for maximising the effectiveness of BCG vaccination.

Randomized Trial of BCG Vaccine to Protect against Covid-19 in Health Care Workers.

BACKGROUND: The bacille Calmette-Guérin (BCG) vaccine has immunomodulatory "off-target" effects that have been hypothesized to protect against coronavirus disease 2019 (Covid-19). METHODS: In this international, double-blind, placebo-controlled trial, we randomly assigned health care workers to receive the BCG-Denmark vaccine or saline placebo and followed them for 12 months. Symptomatic Covid-19 and severe Covid-19, the primary outcomes, were assessed at 6 months; the primary analyses involved the modified intention-to-treat population, which was restricted to participants with a negative test for severe acute respiratory syndrome coronavirus 2 at baseline. RESULTS: A total of 3988 participants underwent randomization; recruitment ceased before the planned sample size was reached owing to the availability of Covid-19 vaccines. The modified intention-to-treat population included 84.9% of the participants who underwent randomization: 1703 in the BCG group and 1683 in the placebo group. The estimated risk of symptomatic Covid-19 by 6 months was 14.7% in the BCG group and 12.3% in the placebo group (risk difference, 2.4 percentage points; 95% confidence interval [CI], -0.7 to 5.5; P = 0.13). The risk of severe Covid-19 by 6 months was 7.6% in the BCG group and 6.5% in the placebo group (risk difference, 1.1 percentage points; 95% CI, -1.2 to 3.5; P = 0.34); the majority of participants who met the trial definition of severe Covid-19 were not hospitalized but were unable to work for at least 3 consecutive days. In supplementary and sensitivity analyses that used less conservative censoring rules, the risk differences were similar but the confidence intervals were narrower. There were five hospitalizations due to Covid-19 in each group (including one death in the placebo group). The hazard ratio for any Covid-19 episode in the BCG group as compared with the placebo group was 1.23 (95% CI, 0.96 to 1.59). No safety concerns were identified. CONCLUSIONS: Vaccination with BCG-Denmark did not result in a lower risk of Covid-19 among health care workers than placebo. (Funded by the Bill and Melinda Gates Foundation and others; BRACE ClinicalTrials.gov number, NCT04327206.).

Comparison of Antimicrobial Stewardship and Infection Prevention and Control Activities and Resources Between Low-/Middle- and High-income Countries.

BACKGROUND: The growth of antimicrobial resistance worldwide has led to increased focus on antimicrobial stewardship (AMS) and infection prevention and control (IPC) measures, although primarily in high-income countries (HIC). We aimed to compare pediatric AMS and IPC resources/activities between low- and middle-income countries (LMIC) and HIC and to determine the barriers and priorities for AMS and IPC in LMIC as assessed by clinicians in those settings. METHODS: An online questionnaire was distributed to clinicians working in HIC and LMIC healthcare facilities in 2020. RESULTS: Participants were from 135 healthcare settings in 39 LMIC and 27 HIC. Formal AMS and IPC programs were less frequent in LMIC than HIC settings (AMS 42% versus 76% and IPC 58% versus 89%). Only 47% of LMIC facilities conducted audits of antibiotic use for pediatric patients, with less reliable availability of World Health Organization Access list antibiotics (29% of LMIC facilities). Hand hygiene promotion was the most common IPC intervention in both LMIC and HIC settings (82% versus 91%), although LMIC hospitals had more limited access to reliable water supply for handwashing and antiseptic hand rub. The greatest perceived barrier to pediatric AMS and IPC in both LMIC and HIC was lack of education: only 17% of LMIC settings had regular/required education on antimicrobial prescribing and only 25% on IPC. CONCLUSIONS: Marked differences exist in availability of AMS and IPC resources in LMIC as compared with HIC. A collaborative international approach is urgently needed to combat antimicrobial resistance, using targeted strategies that address the imbalance in global AMS and IPC resource availability and activities.

BCG vaccination to reduce the impact of COVID-19 in healthcare workers: Protocol for a randomised controlled trial (BRACE trial).

INTRODUCTION: BCG vaccination modulates immune responses to unrelated pathogens. This off-target effect could reduce the impact of emerging pathogens. As a readily available, inexpensive intervention that has a well-established safety profile, BCG is a good candidate for protecting healthcare workers (HCWs) and other vulnerable groups against COVID-19. METHODS AND ANALYSIS: This international multicentre phase III randomised controlled trial aims to determine if BCG vaccination reduces the incidence of symptomatic and severe COVID-19 at 6 months (co-primary outcomes) compared with no BCG vaccination. We plan to randomise 10 078 HCWs from Australia, The Netherlands, Spain, the UK and Brazil in a 1:1 ratio to BCG vaccination or no BCG (control group). The participants will be followed for 1 year with questionnaires and collection of blood samples. For any episode of illness, clinical details will be collected daily, and the participant will be tested for SARS-CoV-2 infection. The secondary objectives are to determine if BCG vaccination reduces the rate, incidence, and severity of any febrile or respiratory illness (including SARS-CoV-2), as well as work absenteeism. The safety of BCG vaccination in HCWs will also be evaluated. Immunological analyses will assess changes in the immune system following vaccination, and identify factors associated with susceptibility to or protection against SARS-CoV-2 and other infections. ETHICS AND DISSEMINATION: Ethical and governance approval will be obtained from participating sites. Results will be published in peer-reviewed open-access journals. The final cleaned and locked database will be deposited in a data sharing repository archiving system. TRIAL REGISTRATION: ClinicalTrials.gov NCT04327206.