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Neonatal BCG vaccination and child survival in TB-exposed and TB-unexposed children: a prospective cohort study
  1. Sanne M Thysen1,2,3,4,
  2. Christine Stabell Benn1,2,3,
  3. Victor Francisco Gomes2,
  4. Frauke Rudolf2,5,
  5. Christian Wejse2,4,5,
  6. Adam Roth6,7,
  7. Per Kallestrup4,
  8. Peter Aaby2,3,
  9. Ane Fisker2,3
  1. 1Bandim Health Project, OPEN, University of Southern Denmark, Odense, Syddanmark, Denmark
  2. 2Bandim Health Project, Bissau, Guinea-Bissau
  3. 3Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark
  4. 4Center for Global Health (GloHAU), Department of Public Health, Aarhus University, Aarhus, Denmark
  5. 5Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
  6. 6Department of Communicable Disease Control and Health Protection, Public Health Agency of Sweden, Solna, Stockholm, Sweden
  7. 7Department of Translational Medicine, Lund University, Lund, Sweden
  1. Correspondence to Dr Sanne M Thysen; s.thysen{at}bandim.org

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.

  • epidemiology
  • public health
  • tuberculosis
  • paediatric infectious disease & immunisation
  • public health
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Twitter @PerKallestrup

  • Contributors SMT and AF conceived the idea for the study and planned the analyses. CSB, AR, PA and AF supervised the demographic surveillance data collection. AR and AF supervised and cleaned the PPD data. VFG, FR and CW supervised the data registration of patients with TB. SMT analysed the data and wrote the first manuscript draft with input from PK, PA and AF. All authors received and approved the final manuscript.

  • Funding This work was supported by Augustinus Foundation. The Bandim Health Project received support from the Novo Nordisk Foundation, DANIDA; EU (ICA 4-CT-2002–10053), the Danish National Research Foundation via Research Centre for Vitamins and Vaccines (DNRF108) and Karen Elise Jensen Foundation.

  • Disclaimer The sponsors had no role in designing the study, the data collection, data analysis, data interpretation or writing the paper.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. Data are available on a collaborative basis; please see http://www.bandim.org for further information.

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