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Background Multidrug-resistant (MDR) tuberculosis has increased among migrants in Canada. The cause(s) of this increase is unknown. Methods We performed a retrospective cohort study in a Canadian province with substantially increased immigration between 1982–2001 and 2002–2019. The proportion of MDR tuberculosis among migrants arriving from high MDR (HMDR) tuberculosis burden countries during these 2 periods was used to estimate the proportion of cases due to immigration versus change in proportion in the country of birth. Epidemiologic, spatiotemporal, and drug resistance pattern data were used to confirm local transmission. Results Fifty-two of 3514 (1.48%) foreign-born culture-positive tuberculosis patients had MDR tuberculosis: 8 (0.6%) in 1982–2001 and 44 (2.0%) in 2002–2019. Between time periods, the proportion of MDR tuberculosis among migrants with tuberculosis from HMDR tuberculosis countries increased from 1.11% to 3.62%, P = .003; 31.6% attributable to recent immigration and 68.4% to a higher proportion of MDR tuberculosis in cases arrived from HMDR tuberculosis countries. No cases of MDR tuberculosis were attributable to local transmission. Conclusions In stark contrast to HMDR tuberculosis countries, local transmission plays no important role in the occurrence of MDR tuberculosis in Canada. Improved tuberculosis programming in HMDR tuberculosis countries is urgently needed.

Subclinical pulmonary tuberculosis (PTB) is a recently described intermediate state of great interest, but about which little is known. This study sought to estimate the extent to which chest radiographs (CXRs), as compared to computed tomographic (CT) scans, under-detect key radiologic features in subclinical PTB, and to interpret the clinical and public health relevance of the differences. Diagnostic CXRs and CT scans of the thorax and neck in a 16-year cohort of subclinical PTB patients in Canada were re-acquired and read by two independent readers and arbitrated by a third reader. Logistic regression models were fit to determine how likely CXR features can be detected by CT scan versus CXR after adjustment for age and sex. Among 296 subclinical patients, CXRs were available in 286 (96.6%) and CT scans in 94 (32.9%). CXR features in patients with and without CT scans were comparable. Lung cavitation was 4.77 times (95% CI, 1.95–11.66), endobronchial spread 19.36 times (95% CI, 8.05–46.52), and moderate/far-advanced parenchymal disease 3.23 times (95% CI, 1.66–6.30), more common on CT scan than CXR. We conclude that the extent to which CXRs under-detect key radiologic features in subclinical PTB is substantial. This may have public health and treatment implications.

Very little is known about subclinical pulmonary TB (PTB), a recently described intermediate state, in high-income countries.What is the prevalence of subclinical PTB in Canada? What are its diagnostic chest radiography features? What is the relationship between those features and time to culture positivity, and what is the association between DNA fingerprint clustering, a measure of local transmission, and radiographic or other features in the foreign-born?We used primary source data to identify a 16-year retrospective cohort of patients with PTB. Demographic and mycobacteriologic features in patients with subclinical and clinical disease were compared, and the reason for assessment of patients with subclinical disease was described. Diagnostic chest radiographs in patients with subclinical disease were read by two independent readers and were arbitrated by a third reader. Linear regression was used to compute time to culture positivity (in days) in relationship to the change in chest radiograph findings from normal or minimally abnormal to moderately or far advanced, adjusted for age and sex and stratified by reason for assessment. Multivariate logistic regression was used in foreign-born patients with subclinical disease to determine associations between DNA fingerprint clustering of Mycobacterium TB isolates and age, sex, chest radiograph features, and time since arrival.We identified 1,656 patients with PTB, 347 of whom (21%) were subclinical. Compared with patients with clinical disease, patients with subclinical disease were more likely to be foreign-born (90.2% vs 79.6%) and to demonstrate negative smear results (88.2% vs 43.5%). The median time to culture-positivity was 18 days (interquartile range [IQR], 14-25 days) vs 12 days (IQR, 7-17 days). Most patients with PTB (75.2%) were identified during active case finding. Parenchymal disease was absent or minimal on chest radiography in 86.4% of patients. More advanced disease on chest radiography was associated with shorter times to culture positivity in nonstratified (by 3.3 days) and stratified (by 4.5-5.8 days) analysis (active case-finding groups). DNA fingerprint clustering was associated with male sex and a longer time between arrival and diagnosis.Subclinical patients with PTB constitute a substantial and heterogeneous minority of patients with PTB in high-income countries. DNA fingerprint clustering is consistent with some, albeit limited, local transmission.

Objectives To determine: i) the emergency department (ED) utilization history of pulmonary tuberculosis (PTB) patients, and ii) the potential individual and public health consequences of a missed diagnosis of PTB in this setting. Design Retrospective observational cohort study. Participants Patients with PTB aged >16 years diagnosed between April 1, 2010 and December 31, 2016 in the Province of Alberta, Canada. Methods We identified valid new cases of PTB from a provincial registry and linked them to ED attendees in administrative databases. Visits are considered ‘PTB’, pulmonary ‘other’, and non-pulmonary based on the most responsible discharge diagnosis. Individual consequences of a missed diagnosis included health system delay and PTB-related death; public health consequences included nosocomial ED exposure time and secondary cases. Results Of 711 PTB patients, 378 (53%) made 845 ED visits in the six months immediately preceding the date of diagnosis. The most responsible ED discharge diagnosis was PTB in 92 (10.9%), pulmonary ‘other’ in 273 (32%) and non-pulmonary in 480 (56.8%). ED attendees had a median (IQR) health system delay of 27 (7,180) days and, compared to non-ED attendees were more likely to die a TB-related death 5.9% vs 1.2%, p = 0.001. Emergency attendees generated 3812 hours of ED nosocomial exposure time, and 31 secondary cases (60.8% of all secondary cases reported). Mycobacterium tuberculosis isolates from ED-attendees were more likely than non-attendees to be clustered–i.e., have an identical DNA fingerprint with another isolate (27% vs. 21%, p = 0.037). Conclusions ED utilization by PTB patients, and related consequences, are substantial. EDs are a potential resource for earlier PTB diagnosis.

Background The End TB Strategy calls for global scale-up of preventive treatment for latent tuberculosis infection (LTBI), but little information is available about the associated human resource requirements. Our study aimed to quantify the healthcare worker (HCW) time needed to perform the tasks associated with each step along the LTBI cascade of care for household contacts of TB patients. Methods We conducted a time and motion (TAM) study between January 2018 and March 2019, in which consenting HCWs were observed throughout a typical workday. The precise time spent was recorded in pre-specified categories of work activities for each step along the cascade. A linear mixed model was fit to estimate the time at each step. Results A total of 173 HCWs in Benin, Canada, Ghana, Indonesia, and Vietnam participated. The greatest amount of time was spent for the medical evaluation (median: 11 min; IQR: 6–16), while the least time was spent on reading a tuberculin skin test (TST) (median: 4 min; IQR: 2–9). The greatest variability was seen in the time spent for each medical evaluation, while TST placement and reading showed the least variability. The total time required to complete all steps along the LTBI cascade, from identification of household contacts (HHC) through to treatment initiation ranged from 1.8 h per index TB patient in Vietnam to 5.2 h in Ghana. Conclusions Our findings suggest that the time requirements are very modest to perform each step in the latent TB cascade of care, but to achieve full identification and management of all household contacts will require additional human resources in many settings.

Background: Sputum smear microscopy is a common surrogate for tuberculosis infectiousness. Previous estimates that smear-negative patients contribute 13-20% of transmissions and are, on average, 20-25% as infectious as smear-positive cases are understood to be high. Herein, we use an ideal real-world setting, a comprehensive dataset, and new high-resolution techniques to more accurately estimate the true transmission risk of smear-negative cases. Methods: We treated all adult culture-positive pulmonary TB patients as potential transmitters. Over a 15.5-year period we measured, as primary outcomes, the proportion of transmissions attributable to smear-negative sources and the relative transmission rate. First, we replicated previous studies by using only molecular (DNA) fingerprint clustering. Then, using a prospectively collected registry of TB contacts, we defined transmission events as active TB among identified contacts who either had a 100% DNA fingerprint match to the source case or a clinical diagnosis. To minimize omission of secondary cases who had not been identified as contacts, we undertook genome sequencing on temporally and geographically linked DNA fingerprint clusters. Findings: There were 1,176 cases, 563 smear-negative and 613 smear-positive, and 23,131 contacts. Replicating previous studies, the proportion of transmissions attributable to smear-negative source cases was 16% and the relative transmission rate was 0.19. With our combined approach, the proportion of transmission was 8% and the relative transmission rate became 0.10. Interpretation: After enhancing molecular data with conventional epidemiologic, spatial/temporal and genomic data, we found that smear-negative cases were approximately 50% less infectious than previously thought. The public health implications of this are substantial. Funding: Alberta Innovates Health Solutions Declaration of Interest: We declare no competing interests. Ethical Approval: The University of Alberta Health Research Ethics Board (HREB) Biomedical Panel for review of non-invasive studies involving humans provided approval for this study, protocol ID Pro00088408.

Purpose Treatment for oral cancer can result in speech impairments that can have varying impacts on patient quality of life. This study explored the relationship between clinical measures of speech impairment and the perception that patients had of this change in the early stage of recovery. Method This was a quasi-experimental 1-group pre–post study design carried out on 10 patients with surgical intervention for oral cancer. Two clinical measures (word intelligibility and consonant phoneme error) and 2 patient-perception measures (Speech Handicap Index total score and Speech Handicap Index patient criteria score) were collected at preoperative and 1-month postoperative appointments. Results Qualitative analysis revealed discordance between clinical and patient-perceived measures in 4 of 10 patients. Change in consonant phoneme error and change in word intelligibility were significantly correlated ( r = .827). Furthermore, on average, statistically significant relationships were not found between clinical and patient-perceived measures or between the 2 patient-perception measures. Conclusions Discordance between clinical and patient-perceived measures was observed in almost half of the sample, indicating that clinical tests did not fully explain the extent of impairment perceived by patients. Speech outcomes should focus on both types of measures, and patient perception outcomes should be carefully considered when recommending speech therapy.

Setting The prairie provinces of Canada. Objective To characterize tuberculosis (TB) transmission among the Indigenous and non-Indigenous Canadian-born peoples of the prairie provinces of Canada. Design A prospective epidemiologic study of consecutively diagnosed adult (age ≥ 14 years) Canadian-born culture-positive pulmonary TB cases on the prairies, hereafter termed "potential transmitters," and the transmission events generated by them. "Transmission events" included new positive tuberculin skin tests (TSTs), TST conversions, and secondary cases among contacts. Results In the years 2007 and 2008, 222 potential transmitters were diagnosed on the prairies. Of these, the vast majority (198; 89.2%) were Indigenous peoples who resided in either an Indigenous community (135; 68.2%) or a major metropolitan area (44; 22.2%). Over the 4.5-year period between July 1st, 2006 and December 31st 2010, 1085 transmission events occurred in connection with these potential transmitters. Most of these transmission events were attributable to potential transmitters who identified as Indigenous (94.5%). With a few notable exceptions most transmitters and their infected contacts resided in the same community type. In multivariate models positive smear status and a higher number of close contacts were associated with increased transmission; adjusted odds ratios (ORs) and 95% confidence intervals (CIs), 4.30 [1.88, 9.84] and 2.88 [1.31, 6.34], respectively. Among infected contacts, being Indigenous was associated with disease progression; OR and 95% CI, 3.59 [1.27, 10.14] and 6.89 [2.04, 23.25] depending upon Indigenous group, while being an infected casual contact was less likely than being a close contact to be associated with disease progression, 0.66 [0.44, 1.00]. Conclusion In the prairie provinces of Canada and among Canadian-born persons, Indigenous peoples account for the vast majority of cases with the potential to transmit as well as the vast majority of infected contacts. Active case finding and preventative therapy measures need to focus on high-incidence Indigenous communities.

BackgroundNew 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.MethodsTo 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.ResultsThere 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.ConclusionsPhenotypically 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.

Summary Sensorimotor impairment of the tongue has the potential to affect speech and swallowing. The purpose of this study was to critically examine the effects of nerve preservation and reinnervation after reconstruction of the base of tongue on patient-perceived outcomes of quality of life (QoL) related to speech and swallowing through completion of the EORTC QLQ-H&N35 stan-dardised questionnaire. Thirty participants with a diagnosis of base of tongue cancer underwent primary resection and reconstruction with a radial forearm free flap, which may or may not have included nerve repair to the lingual nerve, hypoglossal nerve or both. Eight QoL domains sensitive to changes in motor and sensory nerve function were included in the analysis. Transected lingual and hypoglossal nerves were associated with difficulty in swallowing, social eating, dry mouth and social contact. There were fewer problems reported when these nerves were either repaired or left intact. There were no significant differences between patient nerve status and QoL outcomes for speech, sticky saliva and use of feeding tubes. This study was the first to examine the impact of sensory or motor nerve transection and reconstruction on health-related QoL outcomes.