Related Experiment Video
Updated: Jun 30, 2025
Protective Efficacy and Pulmonary Immune Response Following Subcutaneous and Intranasal BCG Administration in Mice
Published on: September 19, 2016
Effects of Neonatal BCG-Japan Versus BCG-Russia Vaccination on Overall Mortality and Morbidity: Randomized Controlled
Frederik Schaltz-Buchholzer1,2, Sebastian Nielsen1,2, Marcus Kjær Sørensen1
1Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau.
Insights
Bacille Calmette-Guérin (BCG) vaccine strains BCG-Japan and BCG-Russia showed similar effects on infant mortality and hospital admissions. However, BCG-Japan induced more pronounced skin reactions, an indicator of reduced mortality risk.
Area of Science:
- Immunology
- Global Health
- Pediatrics
Background:
- Bacille Calmette-Guérin (BCG) vaccination, particularly the Danish strain, is linked to reduced neonatal mortality.
- Post-vaccination skin reactions correlate with lower mortality risk.
- The impact of different BCG strains on these nonspecific benefits is not well understood.
Purpose of the Study:
- To compare the efficacy of BCG-Japan versus BCG-Russia in preventing infant hospital admissions and mortality.
- To investigate the association between BCG strains and the prevalence and intensity of skin reactions.
Main Methods:
- An open-label randomized controlled trial in Guinea-Bissau involving 17,506 infants.
- Comparison of BCG-Japan and BCG-Russia for all-cause hospital admission risk up to 6 months.
- Assessment of case-fatality risk, mortality, and BCG skin reactions as secondary outcomes.
Main Results:
- No significant difference in hospital admission risk between BCG-Japan and BCG-Russia up to 6 months.
- BCG-Japan was associated with significantly fewer infants lacking skin reactions (1% vs. 2%) and larger reactions compared to BCG-Russia.
- BCG-Japan showed a risk ratio of 0.36 for no skin reaction by 6 months.
Conclusions:
- Both BCG-Japan and BCG-Russia demonstrate comparable effects on infant morbidity and mortality.
- BCG-Japan's association with more pronounced skin reactions suggests a potentially stronger protective effect, despite similar overall outcomes.
- Further research may clarify the clinical significance of strain-specific variations in BCG immunogenicity.
Background:
Vaccination with the Danish strain of bacille Calmette-Guérin (BCG) has been associated with pronounced reductions in all-cause neonatal mortality and morbidity. Developing a skin reaction postvaccination is associated with markedly reduced mortality risk. It is unknown whether the beneficial nonspecific effects are maintained across different BCG strains.
Methods:
This was an open-label randomized controlled trial in Guinea-Bissau, comparing BCG-Japan (n = 8754) versus BCG-Russia (n = 8752) for all-cause hospital admission risk by 6 weeks of age (primary outcome) and 6 months of age. Additional secondary outcomes were in-hospital case-fatality risk (CFR), all-cause mortality, and BCG skin reaction prevalence. Participants were followed through telephone calls at 6 weeks and 6 months, with a subgroup also visited at home. We assessed admission and mortality risk in Cox models providing incidence rate ratios (IRRs) and mortality rate ratios. CFR and skin reactions were assessed by binomial regression providing risk ratios. Analyses were done overall and stratified by sex.
Results:
BCG strain was not associated with admission risk, the BCG-Japan/BCG-Russia IRR being 0.92 (95% confidence interval [CI], .81-1.05) by 6 weeks and 0.92 (95% CI, .82-1.02) by 6 months. By 6 months of age, there were significantly fewer BCG-Japan infants with no skin reaction (1%) than for BCG-Russia (2%), the risk ratio being 0.36 (95% CI, .16-.81). BCG-Japan skin reactions were also larger.
Conclusions:
Both vaccines induced a skin reaction in almost all participants. The BCG strains had comparable effects on morbidity and mortality, but BCG-Japan was associated with more and larger skin reactions that are indicators of lower mortality risk.
Clinical Trials Registration:
NCT03400878.
