Neonatal BCG vaccination and child survival in TB-exposed and TB-unexposed children: a prospective cohort study

Abstract

ObjectivesTo assess the association between neonatal BCG vaccination and mortality between 28 days and 3 years of age among tuberculosis (TB)-exposed and TB-unexposed children.DesignProspective cohort study.SettingBandim Health Project runs an urban Health and Demographic Surveillance site in Guinea-Bissau with registration of mortality, vaccination status and TB cases.ParticipantsChildren entered the analysis when their vaccination card was inspected after 28 days of age and remained under surveillance to 3 years of age. Children residing in the same house as a TB case were classified as TB-exposed from 3 months prior to case registration to the end of follow-up.MethodsUsing Cox-proportional hazards models with age as underlying time scale, we compared mortality of children with and without neonatal BCG between October 2003 and September 2017.Main outcome measureHR for neonatal BCG compared with no neonatal BCG by TB-exposure status.ResultsAmong the 39 421 children who entered the analyses, 3022 (8%) had observation time as TB-exposed. In total, 84% of children received neonatal BCG. Children with neonatal BCG had lower mortality both in TB-exposed (adjusted HR: 0.57 (0.26 to 1.27)) and in TB-unexposed children (HR: 0.57 (95% CI 0.47 to 0.69)) than children without neonatal BCG. Children exposed to TB had higher mortality than TB-unexposed children if they had not received neonatal BCG.ConclusionNeonatal BCG vaccination was associated with lower mortality among both TB-exposed and TB-unexposed children, consistent with neonatal BCG vaccination having beneficial non-specific effects. Interventions to increase timely BCG vaccination are urgently warranted.

On the relationship between BCG coverage and national COVID‐19 outcome: could ‘heterologous’ herd immunity explain why some countries are better off?

“…Most of the effect could not be explained by reduction of tuberculosis (TB), against which the vaccine was intended. This finding has been confirmed in several recent international studies [21–23], and other live vaccines such as measles and yellow fever vaccines have been demonstrated to have similar effects [24]. This heterologous immunity induced through BCG can be viewed as targeted priming of immunological responses, so that a second microbial challenge will result in a more powerful and tailored counterstrike by the immune system [10, 11, 25].…”

Postneonatal under-5 mortality in peri-urban and rural Eastern Uganda, 2005–2015

“…In addition, increasing evidence suggests BCG vaccine has non-specific effects on child survival, protecting vaccinated children from infections beyond tuberculosis (TB). 26 Our study did not attempt to clarify to what extent vaccinated children had a reduced mortality from TB or other causes. But based on existing evidence and a very small proportion of under-5 deaths from TB in Uganda, it is likely that those who received BCG vaccine were protected against non-TB infectious diseases.…”

COVID-19: A model correlating BCG vaccination to protection from mortality implicates trained immunity

“…Neonatal BCG vaccination has been shown to be associated with lower mortality rates among both TB-exposed and TB-unexposed children. 12 Three randomized controlled trials of early BCG vaccination in Guinea-Bissau found a 38% reduction in all-cause neonatal mortality. 13 These effects do not only benefit infants, as a recent clinical trial revealed that revaccinating at-risk teenagers with the BCG vaccine they first got as infants, could significantly reduce the threat of these patients becoming carriers of TB infection.…”

“…Numerous studies have investigated whether BCG vaccination reduces TB disease burden and associated mortality. Neonatal BCG vaccination has been shown to be associated with lower mortality rates among both TB-exposed and TB-unexposed children (Thysen et al, 2020). Three randomized controlled trials of early BCG vaccination in Guinea-Bissau found a 38% reduction in all-cause neonatal mortality (Jensen et al, 2020).…”