Post-tuberculosis airway disease: A population-based cohort study of people immigrating to British Columbia, Canada, 1985-2015.

BACKGROUND: Current epidemiological evidence of post-TB airway disease is largely cross-sectional and derived from high-TB-incidence settings. We present the first cohort study of post-TB airway disease in a low-TB-incidence setting. AIMS: (1) analyze the risk of airway disease by respiratory TB, (2) assess potential unmeasured confounding between TB and airway disease, and (3) investigate TB effect measure modification. METHODS: A population-based cohort study using healthcare claims data for immigrants to British Columbia (BC), Canada, 1985-2015. Airway disease included chronic airway obstruction, asthma, bronchitis, bronchiolitis, and emphysema. Respiratory TB was defined from TB registry data. Cox proportional hazards (PH) regressions were used to analyze time-to-airway disease by respiratory TB. Sensitivity analyses included varying definitions of TB and airway disease. Potential unmeasured confounding by smoking was evaluated by E-value and hybrid least absolute shrinkage and selection operator (LASSO)-high-dimensional propensity score (hdPS). FINDINGS: In our cohort (N = 1 005 328; nTB=1141) there were 116 840 incident cases of airway disease during our 30-year study period (10.43 per 1,000 person-years of follow-up), with cumulative incidence of 42·5% among respiratory TB patients compared with 11·6% among non-TB controls. The covariate-adjusted hazard ratio (aHR) for airway disease by respiratory TB was 2·08 (95% CI: 1·91-2·28) with E-value=3·58. The LASSO-hdPS analysis produced aHR=2·26 (95% CI: 2·07-2·47). INTERPRETATION: A twofold higher risk of airway disease was observed among immigrants diagnosed with respiratory TB, compared with non-TB controls, in a low-TB-incidence setting. Unmeasured confounding is unlikely to explain this relationship. Models of post-TB care are needed. FUNDING: Canadian Institutes of Health Research.

Risk of active tuberculosis in migrants diagnosed with cancer: a retrospective cohort study in British Columbia, Canada.

OBJECTIVES: To describe the association between types of cancer and active tuberculosis (TB) risk in migrants. Additionally, in order to better inform latent TB infection (LTBI) screening protocols, we assessed proportion of active TB cases potentially preventable through LTBI screening and treatment in migrants with cancer. DESIGN: Population-based, retrospective cohort study. SETTING: British Columbia (BC), Canada. PARTICIPANTS: 1 000 764 individuals who immigrated to Canada from 1985 to 2012 and established residency in BC at any point up to 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: Using linked health administrative databases and disease registries, data on demographics, comorbidities, cancer type, TB exposure and active TB diagnosis were extracted. Primary outcomes included: time to first active TB diagnoses, and risks of active TB following cancer diagnoses which were estimated using Cox extended hazard regression models. Potentially preventable TB was defined as active TB diagnosed >6 months postcancer diagnoses. RESULTS: Active TB risk was increased in migrants with cancer ((HR (95% CI)) 2.5 (2.0 to 3.1)), after adjustment for age, sex, TB incidence in country of origin, immigration classification, contact status and comorbidities. Highest risk was observed with lung cancer (HR 11.2 (7.4 to 16.9)) and sarcoma (HR 8.1 (3.3 to 19.5)), followed by leukaemia (HR 5.6 (3.1 to 10.2)), lymphoma (HR 4.9 (2.7 to 8.7)) and gastrointestinal cancers (HR 2.7 (1.7 to 4.4)). The majority (65.9%) of active TB cases were diagnosed >6 months postcancer diagnosis. CONCLUSION: Specific cancers increase active TB risk to varying degrees in the migrant population of BC, with approximately two-thirds of active TB cases identified as potentially preventable.

Latent Tuberculosis Therapy Outcomes in Dialysis Patients: A Retrospective Cohort.

RATIONALE & OBJECTIVES: Maintenance dialysis patients are at an increased risk for active tuberculosis (TB). In 2012, British Columbia, Canada, began systematically screening maintenance dialysis patients for latent TB infection (LTBI) and treating people with evidence of LTBI when appropriate. We examined LTBI treatment outcomes and compared treatment outcomes before and after rollout of the systematic screening program. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: The study comprised 365 people in British Columbia, Canada, initiating at least 90 days of dialysis from January 1, 2001, to May 31, 2017, and starting LTBI therapy: 290 (79.5%) people in the recent cohort and 75 (20.5%) in the historical cohort. People starting LTBI therapy from January 1, 2012, onward were classified as the recent cohort, whereas people starting LTBI therapy before January 1, 2012, were classified as the historical cohort. EXPOSURE: Systematic LTBI screening and therapy. OUTCOMES: Proportion of people who experience grade 3 to 5 adverse events (AEs) or any grade rash and end-of-treatment outcomes. ANALYTICAL APPROACH: Outcomes were reported using descriptive statistics. 2-sample test of proportions using χ2 distribution was used to test for statistical significance between the recent and historical cohorts. RESULTS: 298 (81.6%) people successfully completed LTBI therapy. The proportion of people experiencing a grade 3 to 4 AE or any grade rash was 21.1%. Most AEs were related to gastrointestinal events, general malaise, or pruritus that resulted in regimen changes. 2 (0.5%) people were hospitalized for AEs related to LTBI therapy. No significant difference was found between the recent and historical cohorts in all outcomes of interest. No grade 5 AEs (deaths) were attributed to LTBI therapy. LIMITATIONS: Retrospective data and generalizability outside low-TB-burden settings. CONCLUSIONS: Our findings suggest that a high proportion of people receiving maintenance dialysis can complete LTBI therapy. The rate of grade 3 to 4 AEs was high and associated with frequent medication changes during therapy. LTBI therapy in maintenance dialysis may be safe but requires close monitoring.

Safety and Efficacy of Rifampin or Isoniazid Among People With Mycobacterium tuberculosis Infection and Living With Human Immunodeficiency Virus or Other Health Conditions: Post Hoc Analysis of 2 Randomized Trials.

BACKGROUND: The safety and efficacy of rifampin among people living with human immunodeficiency virus (PLHIV) or other health conditions is uncertain. We assessed completion, safety, and efficacy of 4 months of rifampin vs 9 months of isoniazid among PLHIV or other health conditions. METHODS: We conducted post hoc analysis of 2 randomized trials that included 6859 adult participants with Mycobacterium tuberculosis infection. Participants were randomized 1:1 to 10 mg/kg/d rifampin or 5 mg/kg/d isoniazid. We report completion, drug-related adverse events (AE), and active tuberculosis incidence among people living with HIV; with renal failure or receiving immunosuppressants; using drugs or with hepatitis; with diabetes mellitus; consuming >1 alcoholic drink per week or current/former smokers; and with no health condition. RESULTS: Overall, 270 (3.9%) people were living with HIV (135 receiving antiretroviral therapy), 2012 (29.3%) had another health condition, and 4577 (66.8%) had no condition. Rifampin was more often or similarly completed to isoniazid in all populations. AEs were less common with rifampin than isoniazid among PLHIV (risk difference, -2.1%; 95% confidence interval [CI], -5.9 to 1.6). This was consistent for others except people with renal failure or on immunosuppressants (2.1%; 95% CI, -7.2 to 11.3). Tuberculosis incidence was similar among people receiving rifampin or isoniazid. Among participants receiving rifampin living with HIV, incidence was comparable to those with no health condition (rate difference, 4.1 per 1000 person-years; 95% CI, -6.4 to 14.7). CONCLUSIONS: Rifampin appears to be safe and as effective as isoniazid across many populations with health conditions, including HIV. CLINICAL TRIALS REGISTRATION: NCT00170209; NCT00931736.

Post-tuberculosis mortality risk among immigrants to British Columbia, Canada, 1985-2015: a time-dependent Cox regression analysis of linked immigration, public health, and vital statistics data.

OBJECTIVE: To compare non-tuberculosis (non-TB)-cause mortality risk overall and cause-specific mortality risks within the immigrant population of British Columbia (BC) with and without TB diagnosis through time-dependent Cox regressions. METHODS: All people immigrating to BC during 1985-2015 (N = 1,030,873) were included with n = 2435 TB patients, and the remaining as non-TB controls. Outcomes were time-to-mortality for all non-TB causes, respiratory diseases, cardiovascular diseases, cancers, and injuries/poisonings, and were ascertained using ICD-coded vital statistics data. Cox regressions were used, with a time-varying exposure variable for TB diagnosis. RESULTS: The non-TB-cause mortality hazard ratio (HR) was 4.01 (95% CI 3.57-4.51) with covariate-adjusted HR of 1.69 (95% CI 1.50-1.91). Cause-specific covariate-adjusted mortality risk was elevated for respiratory diseases (aHR = 2.96; 95% CI 2.18-4.00), cardiovascular diseases (aHR = 1.63; 95% CI 1.32-2.02), cancers (aHR = 1.40; 95% CI 1.13-1.75), and injuries/poisonings (aHR = 1.85; 95% CI 1.25-2.72). CONCLUSIONS: In any given year, if an immigrant to BC was diagnosed with TB, their risk of non-TB mortality was 69% higher than if they were not diagnosed with TB. Healthcare providers should consider multiple potential threats to the long-term health of TB patients during and after TB treatment. TB guidelines in high-income settings should address TB survivor health.

RéSUMé: OBJECTIF: Au moyen de régressions de Cox avec une covariable temporalisée, comparer le risque global de mortalité non due à la tuberculose et les risques de mortalité par cause au sein de la population immigrante de la Colombie-Britannique (C.-B.) avec et sans diagnostic de tuberculose. MéTHODE: Toutes les personnes ayant immigré en C.-B. entre 1985 et 2015 (N = 1 030 873) ont été incluses, dont n = 2 435 patients tuberculeux, le reste étant des témoins non tuberculeux. Nos résultats incluaient le temps jusqu'à la mortalité de toute cause autre que la tuberculose, soit les maladies respiratoires, les maladies cardiovasculaires, les cancers et les blessures/empoisonnements, déterminé à l'aide des statistiques de l'état civil codées selon la CIM. Nous avons utilisé des régressions de Cox avec une variable d'exposition temporalisée pour le diagnostic de tuberculose. RéSULTATS: Le coefficient de danger (CD) de mortalité non due à la tuberculose était de 4,01 (IC de 95 % : 3,57-4,51) avec un CD ajusté selon la covariable de 1,69 (IC de 95 % : 1,50-1,91). Le risque de mortalité par cause ajusté selon la covariable était élevé pour : les maladies respiratoires (CDa = 2,96; IC de 95 % : 2,18-4,00), les maladies cardiovasculaires (CDa = 1,63; IC de 95 % : 1,32-2,02), les cancers (CDa = 1,40; IC de 95 % : 1,13-1,75) et les blessures/empoisonnements (CDa = 1,85; IC de 95 % : 1,25-2,72). CONCLUSIONS: Chaque année, si une personne ayant immigré en C.-B. avait un diagnostic de tuberculose, son risque de mortalité non due à la tuberculose était supérieur de 69 % à celui d'une personne sans diagnostic de tuberculose. Les professionnels de santé devraient tenir compte des multiples menaces possibles à la santé à long terme de leurs patients tuberculeux pendant et après le traitement de la tuberculose. Les lignes directrices sur la tuberculose dans les milieux à revenu élevé devraient tenir compte de la santé des survivants de la tuberculose.

Estimated Impact of World Health Organization Latent Tuberculosis Screening Guidelines in a Region With a Low Tuberculosis Incidence: Retrospective Cohort Study.

BACKGROUND: Latent tuberculosis infection (LTBI) screening and treatment is a key component of the World Health Organization (WHO) EndTB Strategy, but the impact of LTBI screening and treatment at a population level is unclear. We aimed to estimate the impact of LTBI screening and treatment in a population of migrants to British Columbia (BC), Canada. METHODS: This retrospective cohort included all individuals (N = 1 080 908) who immigrated to Canada as permanent residents between 1985 and 2012 and were residents in BC at any time up to 2013. Multiple administrative databases were linked to identify people with risk factors who met the WHO strong recommendations for screening: people with tuberculosis (TB) contact, with human immunodeficiency virus, on dialysis, with tumor necrosis factor-alpha inhibitors, who had an organ/haematological transplant, or with silicosis. Additional TB risk factors included immunosuppressive medications, cancer, diabetes, and migration from a country with a high TB burden. We defined active TB as preventable if diagnosed ≥6 months after a risk factor diagnosis. We estimated the number of preventable TB cases, given optimal LTBI screening and treatment, based on these risk factors. RESULTS: There were 16 085 people (1.5%) identified with WHO strong risk factors. Of the 2814 people with active TB, 118 (4.2%) were considered preventable through screening with WHO risk factors. Less than half (49.4%) were considered preventable with expanded screening to include people migrating from countries with high TB burdens, people who had been prescribed immunosuppressive medications, or people with diabetes or cancer. CONCLUSIONS: The application of WHO LTBI strong recommendations for screening would have minimally impacted the TB incidence in this population. Further high-risk groups must be identified to develop an effective LTBI screening and treatment strategy for low-incidence regions.

Cost-effectiveness of Latent Tuberculosis Infection Screening before Immigration to Low-Incidence Countries.

Prospective migrants to countries where the incidence of tuberculosis (TB) is low (low-incidence countries) receive TB screening; however, screening for latent TB infection (LTBI) before immigration is rare. We evaluated the cost-effectiveness of mandated and sponsored preimmigration LTBI screening for migrants to low-incidence countries. We used discrete event simulation to model preimmigration LTBI screening coupled with postarrival follow-up and treatment for those who test positive. Preimmigration interferon-gamma release assay screening and postarrival rifampin treatment was preferred in deterministic analysis. We calculated cost per quality-adjusted life-year gained for migrants from countries with different TB incidences. Our analysis provides evidence of the cost-effectiveness of preimmigration LTBI screening for migrants to low-incidence countries. Coupled with research on sustainability, acceptability, and program implementation, these results can inform policy decisions.

Screening for Latent Tuberculosis Infection in Migrants With CKD: A Cost-effectiveness Analysis.

RATIONALE & OBJECTIVE: In countries with a low tuberculosis (TB) incidence, TB disproportionately affects populations born abroad. TB persists in these populations through reactivation of latent TB infection (LTBI) acquired before immigration. Those with chronic kidney disease (CKD) are at increased risk for reactivation and may benefit from LTBI screening and treatment. STUDY DESIGN: Health administrative data from British Columbia, Canada, were used to inform a cost-effectiveness analysis evaluating LTBI screening in those diagnosed with stage 4 or 5 CKD not requiring dialysis (late-stage CKD) and those who began dialysis therapy. SETTING & POPULATION: Permanent residents establishing residency in British Columbia, Canada, between 1985 and 2012 who had late-stage CKD diagnosed or began dialysis therapy. INTERVENTIONS: Screening with the tuberculin skin test or interferon-gamma release assay (IGRA) compared to no LTBI screening at the time of late-stage CKD diagnosis and time of dialysis therapy initiation. Treatment for those who tested positive was isoniazid for 9 months. OUTCOMES: Costs (2016 Can $), TB cases, and quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio for QALYs gained was calculated. MODEL, PERSPECTIVE, & TIMEFRAME: Discrete event simulation model using a health care system perspective, 1.5% discount rate, and 5-year time horizon. RESULTS: Screening with IGRA was superior to the tuberculin skin test in all situations. Screening with IGRA was less expensive and resulted in better outcomes compared to no screening in those initiating dialysis therapy from countries with an elevated TB incidence. In individuals with late-stage CKD, screening with IGRA was only cost-effective in those 60 years or older (cost per QALY gained, <$48,000) from countries with an elevated TB incidence. LIMITATIONS: This study has limitations in generalizability to different epidemiologic settings and in modeling complicated clinical decisions. CONCLUSIONS: LTBI screening should be considered in non-Canadian-born residents initiating dialysis therapy and those with late stage CKD who are older.

Demographic predictors of active tuberculosis in people migrating to British Columbia, Canada: a retrospective cohort study.

BACKGROUND: Canadian tuberculosis (TB) guidelines recommend targeting postlanding screening for and treatment of latent tuberculosis infection (LTBI) in people migrating to Canada who are at increased risk for TB reactivation. Our objectives were to calculate robust longitudinal estimates of TB incidence in a cohort of people migrating to British Columbia, Canada, over a 29-year period, and to identify groups at highest risk of developing TB based on demographic characteristics at time of landing. METHODS: We included all individuals (n = 1 080 908) who became permanent residents of Canada between Jan. 1, 1985, and Dec. 31, 2012, and were resident in BC at any time between 1985 and 2013. Multiple administrative databases were linked to the provincial TB registry. We used recursive partitioning models to identify populations with high TB yield. RESULTS: Active TB was diagnosed in 2814 individuals (incidence rate 24.2/100 000 person-years). Demographic factors (live-in caregiver, family, refugee immigration classes; higher TB incidence in country of birth; and older age) were strong predictors of TB incidence in BC, with elevated rates continuing many years after entry into the cohort. Recursive partitioning identified refugees 18-64 years of age from countries with a TB incidence greater than 224/100 000 population as a high-yield group, with 1% developing TB within the first 10 years. INTERPRETATION: These findings support recommendations in Canadian guidelines to target postlanding screening for and treatment of LTBI in adult refugees from high-incidence countries. Because high-yield populations can be identified at entry via demographic data, screening at this point may be practical and high-impact, particularly if the LTBI care cascade can be optimized.

Preventing Tuberculosis in a Low Incidence Setting: Evaluation of a Multi-lingual, Online, Educational Video on Latent Tuberculosis.

Treating latent tuberculosis infection (LTBI) in those at risk is an important yet challenging cornerstone of TB elimination. We evaluated a culturally-tailored, multi-lingual, 4.5-min, health promotional video on LTBI. Mixed methods study assessed use of the video with web-analytics, acceptability of content through interviews and survey questions, and compared knowledge scores in viewers and non-viewers using a survey. The video was viewed 6999 times in six languages over 1 year. Of 1598 survey respondents, 193 viewers had a mean knowledge score of 59%, compared to 38% in non-viewers. Eighty-four percent of viewers rated the video as helpful. When controlling for other factors, viewing the video was associated with a 1.04 (95% CI 0.85-1.26) or a 21% increase in a knowledge score. Qualitative data suggested the video was acceptable and may facilitate behavior change. This online, educational video shows promise as a tool to supplement clinical care.

Predicting tuberculosis risk in the foreign-born population of British Columbia, Canada: study protocol for a retrospective population-based cohort study.

INTRODUCTION: Improved understanding of risk factors for developing active tuberculosis (TB) will better inform decisions about diagnostic testing and treatment for latent TB infection (LTBI) in migrant populations in low-incidence regions. We aim to examine TB risk factors among the foreign-born population in British Columbia (BC), Canada, and to create and validate a clinically relevant multivariate risk score to predict active TB. METHODS AND ANALYSIS: This retrospective population-based cohort study will include all foreign-born individuals who acquired permanent resident status in Canada between 1 January 1985 and 31 December 2013 and acquired healthcare coverage in BC at any point during this period. Multiple administrative databases and disease registries will be linked, including a National Immigration Database, BC Provincial Health Insurance Registration, physician billings, hospitalisations, drugs dispensed from community pharmacies, vital statistics, HIV testing and notifications, cancer, chronic kidney disease and dialysis treatment, and all TB and LTBI testing and treatment data in BC. Extended proportional hazards regression will be used to estimate risk factors for TB and to create a prognostic TB risk score. ETHICS AND DISSEMINATION: Ethical approval for this study has been obtained from the University of British Columbia Clinical Ethics Review Board. Once completed, study findings will be presented at conferences and published in peer-reviewed journals. An online TB risk score calculator will also be created.

Tuberculosis and chronic kidney disease: an emerging global syndemic.

The link between chronic kidney disease (CKD) and tuberculosis (TB) has been known for more than 40 years, but the interaction between these 2 diseases is still poorly understood. Dialysis and renal transplant patients appear to be at a higher risk of TB, in part related to immunosuppression along with socioeconomic, demographic, and comorbid factors. Meanwhile, TB screening and diagnostic test performance is suboptimal in the CKD population, and there is limited evidence to guide protocols. Given the increasing prevalence of CKD in TB endemic areas, a merging of CKD and TB epidemics could have significant public health implications, especially in low- to middle-income countries such as India and China, that are experiencing rapid increases in CKD prevalence and account for more than one-third of global TB prevalence. To begin addressing TB-CKD, a clear understanding of the relationship between these 2 conditions needs to be established, and consistent, evidence-based screening and treatment guidelines need to be developed.

Longitudinal clinical findings and outcome among patients with Cryptococcus gattii infection in British Columbia.

BACKGROUND: Cryptococcus gattii (Cg) infection emerged in British Columbia in 1999. A longitudinal, clinical description of patients has not been reported. METHODS: Medical records were reviewed for Cg patients identified through surveillance (1999-2007). Risk factors for Cg mortality were explored using multivariate Cox regression; longitudinal patterns in serum cryptococcal antigen (SCrAg) titers and the probability of chest cryptococcomas over time were estimated using cubic B-splines in mixed-effects regression models. RESULTS: Among 152 patients, 111 (73.0%) were culture confirmed. Isolated lung infection was present in 105 (69.1%) patients; 47 (30.9%) had central nervous system infection, with or without lung involvement. Malignancy was the provisional diagnosis in 64 (42.1%) patients. Underlying diseases were present in 91 (59.9%) patients; 23 (15.1%) were immunocompromised, and 23 (15.1%) had asymptomatic disease. There were only 2 (1.8%) culture positive relapses, both within 12 months of follow-up. The estimated median time to resolution of lung cryptococcomas and decline in SCrAg titer to <1:8 was 2.8 and 2.9 years, respectively. Cg-related and all-cause mortality among culture-confirmed cases at 12 months' follow-up was 23.3% and 27.2%, respectively. Cg-related mortality was associated with age >50 years (hazard ratio [HR], 15.6; 95% confidence interval [CI], 1.9-130.5) and immunocompromise (HR, 5.8; CI, 1.5-21.6). All Cg-related mortality occurred among culture-positive cases within 1 year of diagnosis. CONCLUSIONS: Cryptococcomas and serum antigenemia were slow to resolve. However, late onset of failed therapy or relapse was uncommon, suggesting that delayed resolution of these findings does not require prolongation of treatment beyond that recommended by guidelines.

Genetic variations of NAT2 and CYP2E1 and isoniazid hepatotoxicity in a diverse population.

AIMS: TB is a serious global public health problem. Isoniazid, a key drug used to treat latent TB, can cause hepatotoxicity in some patients. This pilot study investigated the effects of genetic variation in NAT2 and CYP2E1 on isoniazid-induced hepatotoxicity in TB contacts in British Columbia, Canada. MATERIALS & METHODS: DNA re-sequencing was used to establish the spectrum of genetic variation in the exons, promoter and conserved regions of NAT2 in all subjects. For CYP2E1, the CYP2E1*1C polymorphism was genotyped by PCR-RFLP. Association tests of NAT2 variants and haplotypes, as well acetylator types were performed. RESULTS: We enrolled 170 subjects on isoniazid treatment (23 cases and 147 controls). Systematic re-sequencing of NAT2 revealed 18 known and 10 novel variants. CONCLUSION: No single genetic variant of NAT2 and CYP2E1 showed a significant association with isoniazid-induced hepatotoxicity in this highly heterogeneous population. There was evidence of a trend for increasing hepatotoxicity risk across the rapid, intermediate and slow acetylator groups (p = 0.08).

A Case of Acquired Rifampin Resistance in Mycobacterium Bovis Bacillus Calmette-Guérin-induced Cystitis: Necessity for Treatment Guidelines.

A case of presumed bacillus Calmette-Guérin (BCG) cystitis in an elderly female patient following direct intravesical BCG instillation treatment for papillary transitional cell carcinoma is reported. The organism cultured from urine samples was eventually identified as a rifampin-resistant Mycobacterium bovis BCG isolate. Because the patient had received rifampin monotherapy during the course of treatment for presumed BCG disease, the clinical picture favoured acquired rifampin resistance. Sequencing of the target gene for rifampin (rpoB) confirmed a known mutation responsible for conferring high levels of resistance to both rifampin and rifabutin (Ser531Tyr). To the authors' knowledge, this is the first reported case of M bovis BCG disease in a non-HIV patient where the organism had acquired drug resistance to rifampin, and the second reported case of M bovis BCG that had acquired drug resistance. The present case demonstrates the necessity to re-evaluate appropriate guidelines for the effective treatment of BCG disease.

Tuberculous lymphadenitis in Manitoba: incidence, clinical characteristics and treatment.

BACKGROUND: Tuberculous lymphadenitis (TBL) is an important form of extrapulmonary tuberculosis (TB). Recent studies have shown an increase in TBL in Canada. OBJECTIVES: To determine the incidence of TBL in Manitoba and to identify the characteristics associated with its presentation, diagnosis and treatment METHODS: Population data from the Manitoba Health Population Registry, the First Nations and Inuit Health Branch of Health Canada, and Statistics Canada were used to calculate incidence. Case characteristics and outcomes were determined by a systematic, retrospective review of all cases between January 1, 1990 and December 31, 2000. RESULTS: One-hundred forty seven cases of TBL were identified during the study period; 77% confirmed by culture; 68% women. TBL was found in Canadian-born/nonstatus Aboriginal (12%), status Aboriginal (29%) and foreign-born (59%) populations. Incidence of TBL was 1.17 per 100,000 person years (95% CI 0.98 to 1.36). The highest incidence was in status Aboriginals over 65 years (16.85 per 100,000 person years; 95% CI 3.37 to 30.33). TBL is seen most often in Western Pacific women. The most common presentation was a single, enlarged cervical node (80%). No atypical mycobacterium was found. Drug resistance occurred in 13% of cases and only in the foreign-born. Cure rates (81%) were influenced by comorbidity and burden of TB disease. Relapse occurred in 8.1 per 1000 person years of follow-up (95% CI 1.7 to 23.7). CONCLUSIONS: Respiratory physicians, who manage the majority of TB disease in Canada, need to remain aware that TB is an important and treatable cause of enlarged lymph nodes.