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The main objective of this study was to estimate threshold values for severe combined immunodeficiency (SCID) incidence, above which BCG is associated with greater risk than benefit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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 \u2013 including early detection and treatment of infection \u2013 may be a safer, more effective alternative.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2431-6-5","type":"journal-article","created":{"date-parts":[[2006,3,10]],"date-time":"2006-03-10T19:16:35Z","timestamp":1142018195000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The benefits and risks of bacille Calmette-Gu\u00e9rin vaccination among infants at high risk for both tuberculosis and severe combined immunodeficiency: assessment by Markov model"],"prefix":"10.1186","volume":"6","author":[{"given":"Michael","family":"Clark","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D William","family":"Cameron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2006,3,3]]},"reference":[{"key":"107_CR1","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1093\/ije\/22.6.1154","volume":"22","author":"LC Rodrigues","year":"1993","unstructured":"Rodrigues LC, Diwan VK, Wheeler JG: Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: a meta-analysis. 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