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.
BACKGROUND
Bacille Calmette-Guérin (BCG) vaccine is given to Canadian Aboriginal neonates in selected communities. Severe reactions and deaths associated with BCG have been reported among infants born with immunodeficiency syndromes. 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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Clark
Michael
M
Division of Infectious Diseases, Department of Medicine, University of Ottawa, Ottawa, Ontario, K1H 8L6, Canada. mclar018@uottawa.ca
Cameron
D William
DW
D001500:BCG Vaccine / Q000009:adverse effects; D001766:Blindness / Q000209:etiology / Q000523:psychology; D001925:Brain Damage, Chronic / Q000209:etiology / Q000523:psychology; D002170:Canada / Q000453:epidemiology; D002755:Choice Behavior; D015331:Cohort Studies; D003258:Consumer Behavior / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D007198:Indians, North American; D007231:Infant, Newborn; D008390:Markov Chains; D008962:Models, Theoretical; D009010:Monte Carlo Method; D019057:Quality-Adjusted Life Years; D012306:Risk; D018570:Risk Assessment; D016511:Severe Combined Immunodeficiency / Q000453:epidemiology*; D014376:Tuberculosis / Q000453:epidemiology / Q000517:prevention & control*; D014390:Tuberculosis, Meningeal / Q000150:complications / Q000523:psychology; D014611:Vaccination / Q000009:adverse effects / Q000401:mortality / Q000523:psychology; D015349:Vision, Monocular
D001500:BCG Vaccine