Acute Lower Respiratory Infection Among Bacille Calmette-Guérin (BCG)–Vaccinated Children

Abstract

WHAT'S KNOWN ON THIS SUBJECT: Bacille Calmette-Guerin (BCG) vaccination may provide benefits beyond protecting against pediatric tuberculosis. Evidence suggests links between cellmediated immunity from tuberculosis and bacterial/viral-related pneumonia but the impact of BCG on acute lower respiratory infection is not fully known.WHAT THIS STUDY ADDS: BCG-vaccinated children had a lower risk of suspected acute lower respiratory infection. Protection was amplified when children were vaccinated against diphtheriatetanus-pertussis (DTP). Number of DTP doses did not modify this effect, but order in which vaccines were received did. abstract OBJECTIVE: To determine whether Bacille Calmette-Guerin (BCG) vaccination is linked to the risk of acute lower respiratory infection (ALRI) among children ,5 years of age. METHODS: Data from Macro International Demographic and HealthSurveys and United Nations Children' s Fund Multiple Indicator Cluster Surveys were used to identify a primary cohort of 58 021 children in 19 countries (2005)(2006)(2007)(2008)(2009)(2010) and a secondary cohort of 93 301 children in 18 countries (2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007). Information was collected by trained interviewers during home visits using standardized questionnaires, review of vaccination health cards, and measurement of health indicators.RESULTS: BCG vaccination was associated with a 17% to 37% risk reduction for suspected ALRI in both cohorts. The only vaccine or vitamin supplement to modify the effect of BCG was diphtheria-tetanuspertussis (DTP; P , .001). The order in which the vaccines were first received was central to this phenomena (BCG before DTP, adjusted/propensity score-weighted relative risk [apRR]: 0.79, 95% confidence interval [CI]: 0.70-0.89; BCG with DTP, apRR: 0.82, 95% CI: 0.71-0.94; and BCG after DTP, apRR: 1.00, 95% CI: 0.87-1.13) but not number of DTP doses received. Other modifiers included vaccine strain used in immunization programs, chlorinating drinking water, using wood-burning fuel cook stoves, and owning livestock.CONCLUSIONS: Children vaccinated with BCG had a significantly lower risk of suspected ALRI. Clarification is needed as to whether this is due to reductions in the underlying risk of tuberculosis or ALRI per se.

Increased Lytic Efficiency of Bovine Macrophages Trained with Killed Mycobacteria

“…Most importantly, our results indicate that this effect remains active in young adults for at least six months after exposure. Intriguingly, lower doses of killed-mycobacteria might be more efficient at inducing trained immune responses than higher doses, in agreement with field observations [3, 13, 14]. …”

Could BCG be used to protect against COVID-19?

“…Second, what is the optimal time to vaccinate? Studies on the effect of BCG vaccination on respiratory infections in childhood and mortality demonstrate an advantage of vaccinating early in life (before 9 months of age versus later in childhood) 4 . However, whether age at vaccination will also influence the effect of BCG on COVID-19 is unknown.…”

“…In addition to its expected effect on prevention of severe disease caused by tuberculosis, BCG vaccination of children has been shown to have a number of heterologous protective effects. Most notably, BCG vaccination of neonates might decrease overall childhood mortality, including mortality unrelated to tuberculosis 3 , which is mainly driven by a decrease in sepsis and respiratory infections in childhood 4 .…”

Non-specific effects of vaccines: plausible and potentially important, but implications uncertain

“…Other recent studies have suggested a beneficial effect of BCG vaccination on reducing (non-tuberculosis) respiratory infections. A population-based analysis from 33 countries over 25 years showed that BCG-vaccinated children had a 17%–37% lower risk of acute lower respiratory tract infections 8. Similarly, a large retrospective observational study from Spain found that there was a 40% lower rate of hospitalisation for respiratory infections and a 36% decrease in sepsis admissions among BCG-vaccinated children, but the vaccinated and control groups were from different regions and it was not possible to control for confounding 9…”