BCG Revaccination With the Third Dose of Diphtheria-tetanus-pertussis Vaccine and Infant Mortality in Africa

Summary

Studies in low-income countries show that vaccines can have important non-specific effects on other infections. Live BCG vaccine can train the immune system and reduce susceptibility to unrelated infections. In contrast, non-live diphtheria-tetanus-pertussis-containing (DTP) vaccine enhances susceptibility in females: DTP vs no DTP is associated with 2-fold higher mortality, and in DTP-vaccinated children, females have higher mortality than males. These effects are seen as long as a vaccine is the most recent vaccine. WHO recommends BCG at birth followed by three DTP vaccines. A metaanalysis based on observational studies has shown that co-administration of BCG+DTP is associated with lower mortality than BCG followed by DTP. The investigators will implement a randomised trial in urban Guinea-Bissau, including 6000 children, to test the hypothesis that an extra dose of BCG given with DTP3 (BCG2+DTP3 vs. DTP3) can: * reduce death and hospital admissions by 25% * reduce the F/M severe morbidity hazard ratio

Timeline

Start

2025-05-09

Primary completion

2030-05

Completion

2030-07

Publications

• Background Aaby P, Ravn H, Benn CS. The WHO Review of the Possible Nonspecific Effects of Diphtheria-Tetanus-Pertussis Vaccine. Pediatr Infect Dis J. 2016 Nov;35(11):1247-1257. doi: 10.1097/INF.0000000000001269.
• Background Aaby P, Nielsen J, Benn CS, Trape JF. Sex-differential and non-specific effects of routine vaccinations in a rural area with low vaccination coverage: an observational study from Senegal. Trans R Soc Trop Med Hyg. 2015 Jan;109(1):77-84. doi: 10.1093/trstmh/tru186.
• Background Hirve S, Bavdekar A, Juvekar S, Benn CS, Nielsen J, Aaby P. Non-specific and sex-differential effects of vaccinations on child survival in rural western India. Vaccine. 2012 Nov 26;30(50):7300-8. doi: 10.1016/j.vaccine.2012.09.035. Epub 2012 Sep 26.
• Background Aaby P, Andersen A, Ravn H, Zaman K. Co-administration of BCG and Diphtheria-tetanus-pertussis (DTP) Vaccinations May Reduce Infant Mortality More Than the WHO-schedule of BCG First and Then DTP. A Re-analysis of Demographic Surveillance Data From Rural Bangladesh. EBioMedicine. 2017 Aug;22:173-180. doi: 10.1016/j.ebiom.2017.07.012. Epub 2017 Jul 14.
• 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 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.

Drugs

Indications

No indication recorded.