Can BCG Vaccination at First Health-facility Contact Reduce Early Infant Mortality?

Summary

Bacillus Calmette-Guérin (BCG) vaccination is recommended at birth to protect against tuberculosis (TB) in countries with high TB burden. BCG is supplied in multidose vials with limited durability after reconstitution. In Guinea-Bissau, this has led to a practice of only opening a BCG vial at specific days, and only if sufficient children are present. Therefore, BCG vaccination is frequently delayed. Accumulating evidence indicates that BCG has beneficial effects on survival beyond the specific protection against tuberculosis, so called non-specific effects (NSEs). The hypothesis of this study is that increasing the availability of BCG and vaccinating children at the first health-facility contact can reduce early infant non-accidental mortality by 25%. In a cluster-randomised crossover trial, 23 health facilities (HFs) in three rural regions in Guinea-Bissau will be randomised to either continue with current practice (typically BCG vaccination once a week if a sufficient number of children are present for vaccination); or to offer additional BCG vaccines to make BCG available every day and open a vial of BCG if there is just one eligible child present. All children born in the three regions and registered during the study period, will be eligible for inclusion into the trial 1 day after birth. If consent is given by the mother, the child will be followed until day 42 after birth, when other vaccines are scheduled to be given. The primary outcome will be non-accidental mortality, secondary outcomes are non-accidental hospital admissions, non-accidental neonatal mortality and cost-effectiveness of making BCG available at the first health-facility contact.

Timeline

Start

2021-02-25

Primary completion

2026-03

Completion

2026-07

Publications

• Background World Health Organization. BCG vaccine: WHO position paper, February 2018 - Recommendations. Vaccine. 2018 Jun 7;36(24):3408-3410. doi: 10.1016/j.vaccine.2018.03.009. Epub 2018 Mar 30.
• Background Thysen SM, Byberg S, Pedersen M, Rodrigues A, Ravn H, Martins C, Benn CS, Aaby P, Fisker AB. BCG coverage and barriers to BCG vaccination in Guinea-Bissau: an observational study. BMC Public Health. 2014 Oct 4;14:1037. doi: 10.1186/1471-2458-14-1037.
• Background Kagone M, Ye M, Nebie E, Sie A, Schoeps A, Becher H, Muller O, Fisker AB. Vaccination coverage and factors associated with adherence to the vaccination schedule in young children of a rural area in Burkina Faso. Glob Health Action. 2017;10(1):1399749. doi: 10.1080/16549716.2017.1399749.
• Background Wallace AS, Willis F, Nwaze E, Dieng B, Sipilanyambe N, Daniels D, Abanida E, Gasasira A, Mahmud M, Ryman TK. Vaccine wastage in Nigeria: An assessment of wastage rates and related vaccinator knowledge, attitudes and practices. Vaccine. 2017 Dec 4;35(48 Pt B):6751-6758. doi: 10.1016/j.vaccine.2017.09.082. Epub 2017 Oct 21.
• Background Mutua, M.K., et al. Analysis of Fully Immunized Child (FIC), Associated Factors, Outcomes, and Impact Using Routinely Population Cohort Data 2001-2014. Report by the INDEPTH Network as a collaboration with GAVI 2015 18th April 2020 ]; Available from: http://www.indepth-network.org/sites/default/files/content/project_pages/files/Fully%20Immunized%20Child%20Report%20and%20Appendices.pdf.
• Background Lawn JE, Blencowe H, Oza S, You D, Lee AC, Waiswa P, Lalli M, Bhutta Z, Barros AJ, Christian P, Mathers C, Cousens SN; Lancet Every Newborn Study Group. Every Newborn: progress, priorities, and potential beyond survival. Lancet. 2014 Jul 12;384(9938):189-205. doi: 10.1016/S0140-6736(14)60496-7. Epub 2014 May 19.
• Background Higgins JP, Soares-Weiser K, Lopez-Lopez JA, Kakourou A, Chaplin K, Christensen H, Martin NK, Sterne JA, Reingold AL. Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review. BMJ. 2016 Oct 13;355:i5170. doi: 10.1136/bmj.i5170.
• Background Roth A, Jensen H, Garly ML, Djana Q, Martins CL, Sodemann M, Rodrigues A, Aaby P. Low birth weight infants and Calmette-Guerin bacillus vaccination at birth: community study from Guinea-Bissau. Pediatr Infect Dis J. 2004 Jun;23(6):544-50. doi: 10.1097/01.inf.0000129693.81082.a0.
• Background Biering-Sorensen S, Aaby P, Lund N, Monteiro I, Jensen KJ, Eriksen HB, Schaltz-Buchholzer F, Jorgensen ASP, Rodrigues A, Fisker AB, Benn CS. Early BCG-Denmark and Neonatal Mortality Among Infants Weighing <2500 g: A Randomized Controlled Trial. Clin Infect Dis. 2017 Oct 1;65(7):1183-1190. doi: 10.1093/cid/cix525.
• Background Schaltz-Buchholzer F, Biering-Sorensen S, Lund N, Monteiro I, Umbasse P, Fisker AB, Andersen A, Rodrigues A, Aaby P, Benn CS. Early BCG Vaccination, Hospitalizations, and Hospital Deaths: Analysis of a Secondary Outcome in 3 Randomized Trials from Guinea-Bissau. J Infect Dis. 2019 Jan 29;219(4):624-632. doi: 10.1093/infdis/jiy544.
• Background Jayaraman K, Adhisivam B, Nallasivan S, Krishnan RG, Kamalarathnam C, Bharathi M, McSharry B, Namachivayam SP, Shann F, Boopalan SI, David P, Bhat BV. Two Randomized Trials of the Effect of the Russian Strain of Bacillus Calmette-Guerin Alone or With Oral Polio Vaccine on Neonatal Mortality in Infants Weighing <2000 g in India. Pediatr Infect Dis J. 2019 Feb;38(2):198-202. doi: 10.1097/INF.0000000000002198.
• Background Curtis N. BCG Vaccination and All-Cause Neonatal Mortality. Pediatr Infect Dis J. 2019 Feb;38(2):195-197. doi: 10.1097/INF.0000000000002230. No abstract available.
• Background Thysen SM, Benn CS, Gomes VF, Rudolf F, Wejse C, Roth A, Kallestrup P, Aaby P, Fisker A. Neonatal BCG vaccination and child survival in TB-exposed and TB-unexposed children: a prospective cohort study. BMJ Open. 2020 Feb 28;10(2):e035595. doi: 10.1136/bmjopen-2019-035595.
• Thysen SM, Moller Jensen A, Vedel JO, da Silva Borges I, Aaby P, Jensen AKG, Benn CS, Fisker AB. Can BCG vaccination at first health-facility contact reduce early infant mortality? Study protocol for a cluster-randomised trial (CS-BCG). BMJ Open. 2022 Nov 21;12(11):e063872. doi: 10.1136/bmjopen-2022-063872.

Drugs

Indications

No indication recorded.