The benefits and risks of bacille Calmette-Guérin vaccination among infants at high risk for both tuberculosis and severe combined immunodeficiency: assessment by Markov model

A Markov model was developed to simulate the natural histories of tuberculosis (TB) and SCID in children from birth to 14 years. The annual risk of tuberculous infection (ARI) and SCID incidence were varied in analyses. The model compared a scenario of no vaccination to intervention with BCG. Appropriate variability and uncertainty analyses were conducted. Outcomes included TB incidence and quality-adjusted life years (QALYs).In sensitivity analyses, QALYs were lower among vaccinated infants if the ARI was 0.1% and the rate of SCID was higher than 4.2 per 100,000. Assuming an ARI of 1%, this threshold increased to 41 per 100,000. In uncertainty analyses (Monte Carlo simulations) which assumed an ARI of 0.1%, QALYs were not significantly increased by BCG unless SCID incidence is 0. With this ARI, QALYs were significantly decreased among vaccinated children if SCID incidence exceeds 23 per 100,000. BCG is associated with a significant increase in QALYs if the ARI is 1%, and SCID incidence is below 5 per 100,000.The possibility that Canadian Aboriginal children are at increased risk for SCID has serious implications for continued BCG use in this population. In this context, enhanced TB Control – including early detection and treatment of infection – may be a safer, more effective alternative.Bacille Calmette-Guerin (BCG) is a live, attenuated vaccine derived from Mycobacterium bovis. The vaccine provides 65–95% protection against miliary and meningeal tuberculosis (TB) in children vaccinated as neonates [1]. Local and systemic adverse reactions to BCG have been summarized [2,3]. The most severe of these – and fortunately the rarest – is disseminated BCG infection. This complication usually occurs among children with underlying congenital or acquired immunodeficiency disorders [4,5].BCG use in Canada is confined to high-risk groups, and routine neonatal vaccination programs exist only in TB-endemic Aboriginal (First Nations and Inuit) communities. Since 1982, eight case