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Effect of revaccination with BCG in early childhood on mortality: randomised trial in Guinea-Bissau

BMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c671 (Published 15 March 2010) Cite this as: BMJ 2010;340:c671
  1. Adam Edvin Roth, clinician12,
  2. Christine Stabell Benn, senior researcher3,
  3. Henrik Ravn, senior statistician3,
  4. Amabelia Rodrigues, research director1,
  5. Ida Maria Lisse, senior registrar4,
  6. Maria Yazdanbakhsh, professor5,
  7. Hilton Whittle, professor6,
  8. Peter Aaby, professor13
  1. 1Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau
  2. 2Department of Medical Microbiology, Lund University, 205 02 Malmö, Sweden
  3. 3Bandim Health Project, Danish Epidemiology Science Centre, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark
  4. 4Department of Pathology, Herlev University Hospital, 2730 Herlev, Denmark
  5. 5Department of Parasitology, Leiden University, Netherlands
  6. 6MRC Laboratories, Fajara, POB 273, Gambia
  1. Correspondence to: P Aaby, Bandim Health Project, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark p.aaby{at}bandim.org
  • Accepted 11 December 2009

Abstract

Objective To determine whether BCG revaccination at 19 months of age reduces overall child mortality.

Design Randomised trial, with follow-up to age 5.

Setting A health project in Bissau, Guinea-Bissau, which maintains a health and demographic surveillance system in an urban area with 90 000 inhabitants.

Participants 2871 children aged 19 months to 5 years with low or no reactivity to tuberculin and who were not severely sick on the day of enrolment.

Intervention BCG vaccination or no vaccination (control).

Main outcome measure Hazard ratios for mortality.

Results 77 children died during follow-up. Compared with controls, the BCG revaccinated children had a hazard ratio of 1.20 (95% confidence interval 0.77 to 1.89). Two hundred and fifty children were admitted to hospital for the first time between enrolment and the end of the study, with an incidence rate ratio for BCG revaccinated children versus controls of 1.04 (0.81 to 1.33). The trial was stopped prematurely because of a cluster of deaths in the BCG arm of the study. This increase in mortality occurred at a time when many children had received missing vaccinations or vitamin A or iron supplementation; the hazard ratio for BCG revaccinated children compared with controls was 2.69 (1.05 to 6.88) in the period after these campaigns. Throughout the trial, the effect of BCG revaccination on mortality was significantly different (P=0.006) in children who had received diphtheria-tetanus-pertussis (DTP) booster vaccination before enrolment (hazard ratio 0.36, 0.13 to 0.99) and children who had not received the booster before enrolment (1.78, 1.04 to 3.04).

Conclusions There was no overall beneficial effect of being revaccinated with BCG. The effect of BCG revaccination on mortality might depend on other health interventions.

Trial registration Clinical Trials ICA4-CT-2002-10053-REVAC.

Footnotes

  • Contributors: AER and PA were the chief investigators and are guarantors. AER, CSB, MY, HW, IML, and PA designed the study. AER, CSB, and PA initiated the study. AER, AR, and IML were responsible for the recruitment and follow-up of participants. HR was responsible for statistical analysis. PA wrote the first draft of the paper. All authors contributed to and approved the final version of the paper.

  • Funding: The study was funded by the EU (ICA4-CT-2002-10053) and the Danish National Research Foundation. The Bandim Health Project received support from DANIDA. PA holds a research professorship grant from the Novo Nordisk Foundation. The funding agencies had no role in the study design, data collection, data analysis, data interpretation, or the writing of the report.

  • Competing interests: None declared.

  • Ethical approval: The protocol was approved by the Danish Central Ethical Committee and the Guinean Ministry of Health’s Research Coordination Committee and all participants gave informed consent. Participants had access to free consultations at local health centres and to essential drugs free of charge.

  • Data sharing: Data on number of children receiving vaccinations after enrolment available from corresponding author.

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