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Potential effect of age of BCG vaccination on global paediatric tuberculosis mortality: a modelling study
Partho Roy1, Johan Vekemans2, Andrew Clark3
1TB Modelling Group, TB Centre and Centre for the Mathematical Modelling of Infectious Diseases, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
Insights
Timely Bacillus Calmette-Guérin (BCG) vaccination at birth significantly reduces global childhood tuberculosis deaths. Delayed BCG vaccination increases mortality, underscoring the importance of adhering to the birth dose recommendation.
Area of Science:
- Immunology
- Public Health
- Epidemiology
Background:
- Bacillus Calmette-Guérin (BCG) vaccination is recommended at birth in high tuberculosis (TB) burden countries.
- Delayed BCG vaccination is a widespread issue, impacting its effectiveness.
- This study supports a World Health Organization (WHO) guidance review on BCG vaccination timing.
Purpose of the Study:
- To estimate the global TB mortality benefit of timely BCG administration at birth.
- To assess the consequences of delayed BCG vaccination on TB mortality.
- To inform WHO guidance on optimal BCG vaccination strategies.
Main Methods:
- Utilized age-specific BCG coverage data from household surveys in 152 high-burden countries.
- Employed a static mathematical model calibrated to global childhood TB deaths in 2016.
- Simulated 12 scenarios exploring BCG delivery at birth, 6 weeks, 6 months, and 9-12 months, including DTP1 and MCV1 timings.
Main Results:
- Estimated 2016 BCG coverage was 37% at 1 week, 67% at 6 weeks, and 92% by 3 years.
- Achieving 92% BCG coverage at birth could reduce TB deaths by 2.8% (5449 deaths) by age 15.
- 100% BCG coverage at birth could reduce TB deaths by 16.5%; later vaccination increased deaths.
Conclusions:
- Reducing BCG vaccination delays and increasing birth coverage substantially lowers global pediatric TB mortality.
- Later BCG administration, even with increased coverage, is projected to increase TB deaths.
- The WHO recommendation for BCG at birth should be maintained and emphasized.
Background:
BCG has been recommended at birth in countries with a high tuberculosis burden for decades, yet delayed vaccination is widespread. To support a WHO guidance review, we estimated the potential global tuberculosis mortality benefit of administering BCG on time and consequences of later administration.
Methods:
We estimated age-specific BCG coverage in 152 high-burden countries using data from large, nationally representative household surveys, to parameterise a static mathematical model, calibrated to global childhood tuberculosis deaths in 2016. 12 hypothetical scenarios explored the effect of BCG delivery at birth, 6 weeks, 6 months, or 9-12 months, on tuberculosis deaths per global birth cohort by age 15 years, including delivery at the time of the first diphtheria-tetanus-pertussis vaccine (DTP1) or the first measles-containing vaccine (MCV1). We assumed constant vaccine efficacy by age, but varied coverage and degree of vaccination delay, including no delay.
Findings:
In 152 high-burden countries, we estimated that BCG coverage in 2016 was 37% at 1 week of age, 67% at 6 weeks, and 92% at 3 years. Modelled scenarios in which 92% BCG coverage was achieved at birth reduced tuberculosis deaths in the global birth cohort by 5449 (95% uncertainty range 218-15 071) or 2·8% (0·1-7·0) by age 15 years. 100% coverage at birth reduced tuberculosis deaths by 16·5% (0·7-41·9). Later administration increased tuberculosis deaths-eg, BCG vaccination at 6 weeks, the recommended age of DTP1, increased tuberculosis deaths by 0·2% (0-0·4), even if BCG reached DTP1 coverage levels (94% at 3 years).
Interpretation:
Reducing delays and increasing coverage at birth would substantially reduce global paediatric tuberculosis mortality. Modelled scenarios whereby BCG was administered later in the infant schedule were all estimated to increase tuberculosis deaths, even with increased coverage. The WHO recommendation for BCG at birth should be maintained and emphasised.
Funding:
WHO.
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