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

Sanne M Thysen, Christine Stabell Benn, Victor Francisco Gomes, Frauke Rudolf, Christian Wejse, Adam Roth, Per Kallestrup, Peter Aaby, Ane Fisker, Sanne M Thysen, Christine Stabell Benn, Victor Francisco Gomes, Frauke Rudolf, Christian Wejse, Adam Roth, Per Kallestrup, Peter Aaby, Ane Fisker

Abstract

Objectives: To 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.

Design: Prospective cohort study.

Setting: Bandim Health Project runs an urban Health and Demographic Surveillance site in Guinea-Bissau with registration of mortality, vaccination status and TB cases.

Participants: Children 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.

Methods: Using 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 measure: HR for neonatal BCG compared with no neonatal BCG by TB-exposure status.

Results: Among 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.

Conclusion: Neonatal 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.

Keywords: epidemiology; paediatric infectious disease & immunisation; public health; tuberculosis.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Timeline of study period. TB, tuberculosis.

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