Progression to tuberculosis disease increases with multiple exposures

During a single year, a Canadian village had 34 individuals with microbiologically confirmed tuberculosis (TB) among 169 people with a new infection (20%). A contact investigation revealed multiple exposures for each person. We investigated whether the intensity of exposure might contribute to this extraordinary risk of disease. We carried out a case-control study using a public health database. Among those with a new infection, 34 had culture-confirmed TB (cases) and 118 did not progress to disease (controls). 17 patients with probable disease were excluded. Contact investigation data were utilised to tabulate the number of potential sources (total exposures). Generalised estimating equations with a logit link were used to identify associations between exposures and progression, and to investigate other potential risk factors. The median (interquartile range) number of total exposures was 15 (3-23) for cases and 3 (2-12) for controls (p=0.001). The adjusted OR for disease was 1.11 (95% CI 1.06-1.16) per additional exposure, corresponding to an OR of 3.4 for disease when comparing the medians of 15 versus 3 total exposures. This association increased when restricting to tuberculin skin test conversions. Increased exposure could be a marker of greater risk of progression to TB disease. Therefore, this risk may not be transportable across epidemiologic settings with variable exposure intensities.