Date Published: March 8, 2019
Publisher: Public Library of Science
Author(s): Richard Long, Leyla Asadi, Courtney Heffernan, James Barrie, Christopher Winter, Mary Lou Egedahl, Catherine Paulsen, Brenden Kunimoto, Dick Menzies, Fawziah Marra.
New immigrants to Canada with a history of tuberculosis or evidence of old healed tuberculosis on chest radiograph are referred to public health authorities for medical surveillance. This ostensible public health protection measure identifies a subgroup of patients (referrals) who are at very low risk (compared to non-referrals) of transmission.
To assess whether earlier diagnosis or a different phenotypic expression of disease explains this difference, we systematically reconstructed the immigration and transmission histories from a well-defined cohort of recently-arrived referral and non-referral pulmonary tuberculosis cases in Canada. Incident case chest radiographs in all cases and sequential past radiographs in referrals were re-read by three experts. Change in disease severity from pre-immigration radiograph to incident radiograph was the primary, and transmission of tuberculosis, the secondary, outcome.
There were 174 cohort cases; 61 (35.1%) referrals and 113 (64.9%) non-referrals. Compared to non-referrals, referrals were less likely to be symptomatic (26% vs. 80%), smear-positive (15% vs. 50%), or to have cavitation (0% vs. 35%) or extensive disease (15% vs. 59%) on chest radiograph. After adjustment for referral status, time between films, country-of-birth, age and co-morbidities, referrals were less likely to have substantial changes on chest radiograph; OR 0.058 (95% CI 0.018–0.199). All secondary cases and 82% of tuberculin skin test conversions occurred in contacts of non-referrals.
Phenotypically different disease, and not earlier diagnosis, explains the difference in transmission risk between referrals and non-referrals. Screening, and treating high-risk non-referrals for latent tuberculosis is necessary to eliminate tuberculosis in Canada.
To mitigate the risk of importing tuberculosis (TB) and to protect the public’s health, many countries screen new immigrants for TB. After the Second World War, chest radiography became the standard screening practice [1–4]. However, with increasing calls for TB elimination and more widely available alternate screening methods (i.e. interferon-gamma release assays), this time-honoured radiograph-based screening strategy may at best be insufficient or at worst, creating a false sense of assurance [1, 5–8].
Between January 1, 2004 and April 30, 2017, 174 foreign-born persons ≥ 12 years of age were diagnosed with culture-positive pulmonary TB within 24 months of arrival. Of these, 61 (35.1%) were referrals and 113 (64.9%) were non-referrals. Of the referrals, 6 (9.8%) were diagnosed at an in-Canada IME and had past abnormal in-Canada chest radiographs; of the non-referrals, 15 (13.3%) were diagnosed at an in-Canada IME and had no past chest radiographs (see Fig 2). Most referrals (93.4%) were diagnosed at an initial or one-year follow-up visit; of those that were overseas IME referrals, most (90.6%) were documented to have negative sputum mycobacteriology at their IME. On average, referrals were diagnosed sooner after arrival than non-referrals (mean ± SD 21.6 ± 19.1 vs 47.0 ± 28.5 weeks; median 12.0 vs 41.9 weeks).
The disease manifested by referrals is relatively benign from an individual and public health perspective [12–14]. Referrals were more likely to be asymptomatic, smear-negative, and to have minimal or no disease on chest radiograph. At the time of diagnosis, the chest radiographic abnormalities in most (78.3%) referrals had been stable for an average of 62.2 weeks and even in referrals whose chest radiographic abnormalities worsened over time (21.7%), the changes were usually subtle or minimal. By contrast, over an average of ~77 weeks, non-referrals progressed from no disease to disease that was often both a threat to themselves and others. Adjusted for relevant demographic and clinical features, non-referrals were much more likely to have substantial changes on their chest radiographs over a similar period. Further, almost all transmission events occurred among contacts of non-referrals.