Characterization of Mycobacterium orygis, Mycobacterium bovis, and Mycobacterium caprae Infections in Humans in Western Canada.

Epidemiologic research on zoonotic tuberculosis historically used Mycobacterium bovis as a surrogate measure, however, increased reports of human tuberculosis caused by other animal-associated Mycobacterium tuberculosis complex members like Mycobacterium orygis necessitates their inclusion. We performed a retrospective cohort study including persons infected with any animal-lineage M. tuberculosis complex species in Alberta, Canada, from January 1995 to July 2021, identifying 42 patients (20 M. bovis, 21 M. orygis, one M. caprae). Demographic, epidemiologic and clinical characteristics were compared against persons with culture-confirmed M. tuberculosis infection. The proportion of culture-positive infections caused by M. orygis increased continuously from 2016-2020. Significantly more females at a higher median age were impacted by M. orygis, with all patients originating from South Asia. M. bovis caused significantly more extra-pulmonary disease, and disproportionately impacted young females, particularly those pregnant or post-partum. All infections were acquired abroad. These findings can aid in developing targeted public health interventions.

The association between phylogenetic lineage and the subclinical phenotype of pulmonary tuberculosis: A retrospective 2-cohort study.

BACKGROUND: Subclinical pulmonary tuberculosis (PTB) is an asymptomatic disease state between established TB infection and symptomatic (clinical) TB disease. It is present in 20-25% of PTB patients in high-income countries. Mycobacterium tuberculosis complex (MTBC) genetic heterogeneity, and differential host immunological responses, have been implicated in its pathogenesis. METHODS: To determine the association between MTBC lineage and PTB disease phenotype, we used two retrospective cohorts of PTB patients in Canada and two independent lineage attribution methods (DNA fingerprinting and genome sequencing). The first cohort, Cohort 1, consisted of consecutively diagnosed PTB patients between 2014 and 2020. The second, Cohort 2, consisted of newly-arrived foreign-born PTB patients who either were or were not referred for post-landing medical surveillance between 2004 and 2017. Univariable and multivariable logistic regression models were sequentially fitted to both cohorts, adjusting for age, sex, disease type, drug resistance and HIV. Evolution of radiographic features was correlated to lineage in Cohort 2. FINDINGS: Cohort 1 and 2 included 874 (209 subclinical) and 111 (44 subclinical) patients, respectively. In both cohorts, subclinical patients were more likely than clinical patients to have relapse/retreatment disease, be smear-negative, have longer times-to-culture positivity and to harbor an ancestral MTBC lineage (Indo-Oceanic or Mycobacterium africanum). Relapse/retreatment disease and ancestral MTBC lineage were independent predictors of subclinical disease (ORs and 95% CIs in Cohort 1, 1.85 [1.07,3.28], p < 0.029 and 2.30 [1.66,3.18], p < 0.001, respectively, and Cohort 2, 5.74 [1.37-24.06], p < 0.017 and 3.21 (1.29,7.97], p < 0.012, respectively). The geographic distribution of Indo-Oceanic strains causing subclinical disease was uneven. Non-progressive lung disease was more common in patients infected with ancestral than modern lineages in Cohort 2, 56.0% vs 25.4%, p < 0.005. INTERPRETATION: MTBC lineage is a strong predictor of PTB disease phenotype. The genetic drivers of this association, and the relative contribution of other explanatory variables, are unknown.

The state of tuberculosis surveillance in Canada.

Tuberculosis incidence in Canada has remained essentially unchanged over the past decade. A strategic plan to reduce the burden of disease, underpinned by high-quality surveillance data, is sorely needed. However, tuberculosis surveillance data are lacking in Canada for multiple reasons. There is no single entity responsible for coordinating a tuberculosis response, including strategies for surveillance, thus inhibiting effective solutions. This in turn affects the timeliness and comprehensiveness of national tuberculosis surveillance reporting: between 2000 and 2020, there was an average 25-month delay to publication of annual surveillance data and the comprehensiveness of reports has precipitously fallen over time. Compounding these issues are case report forms for tuberculosis surveillance data which have not been updated since 2011, failing to keep up with the changing tuberculosis epidemiology and to provide information required for strategic planning. Common-sense steps can be taken to vastly improve the utility of collected tuberculosis surveillance data, and the development of a strategic plan for tuberculosis elimination. These include initiating a country-wide consultation on surveillance needs; allocating resources for data collection and analysis and data sharing; setting precise, measurable goals; and, importantly, establishing an oversight committee with representation from all provincial/territorial tuberculosis program leads who are held to account for performance.

RéSUMé: L'incidence de la tuberculose au Canada est demeurée essentiellement inchangée au cours de la dernière décennie. Un plan stratégique visant à réduire le fardeau de la maladie, étayé par des données de surveillance de haute qualité, est grandement nécessaire. Cependant, les données de surveillance de la tuberculose font défaut au Canada pour de multiples raisons. Il n'existe pas d'entité unique chargée de coordonner la réponse à la tuberculose, y compris les stratégies de surveillance, ce qui empêche de trouver des solutions efficaces. Cette situation a une incidence sur la rapidité et l'exhaustivité des rapports nationaux de surveillance de la tuberculose : entre 2000 et 2020, la publication des données annuelles de surveillance a été retardée de 25 mois en moyenne, et l'exhaustivité des rapports a chuté de façon vertigineuse au fil du temps. Ces problèmes sont aggravés par le fait que les formulaires de déclaration des cas pour les données de surveillance de la tuberculose n'ont pas été mis à jour depuis 2011, ce qui entrave leur capacité à suivre l'évolution de l'épidémiologie de la tuberculose et à fournir les informations nécessaires à la planification stratégique. Des mesures de bon sens peuvent être prises pour améliorer considérablement l'utilité des données de surveillance de la tuberculose collectées et le développement d'un plan stratégique pour l'élimination de la tuberculose. Il s'agit notamment de lancer une consultation à l'échelle du pays sur les besoins en matière de surveillance, d'allouer des ressources pour la collecte et l'analyse des données et leur partage, de fixer des objectifs précis et mesurables et, surtout, d'établir un comité de surveillance composé de représentants de tous les responsables provinciaux/territoriaux du programme de lutte contre la tuberculose qui sont tenus de rendre compte des performances.

Time to diagnosis and treatment of pulmonary tuberculosis in indigenous peoples: a systematic review.

BACKGROUND: Time to diagnosis and treatment is a major factor in determining the likelihood of tuberculosis (TB) transmission and is an important area of intervention to reduce the reservoir of TB infection and prevent disease and mortality. Although Indigenous peoples experience an elevated incidence of TB, prior systematic reviews have not focused on this group. We summarize and report findings related to time to diagnosis and treatment of pulmonary TB (PTB) among Indigenous peoples, globally. METHODS: A Systematic review was performed using Ovid and PubMed databases. Articles or abstracts estimating time to diagnosis, or treatment of PTB among Indigenous peoples were included with no restriction on sample size with publication dates restricted up to 2019. Studies that focused on outbreaks, solely extrapulmonary TB alone in non-Indigenous populations were excluded. Literature was assessed using the Hawker checklist. Registration Protocol (PROSPERO): CRD42018102463. RESULTS: Twenty-four studies were selected after initial assessment of 2021 records. These included Indigenous groups from five of six geographical regions outlined by the World Health Organization (all except the European Region). The range of time to treatment (24-240 days), and patient delay (20 days-2.5 years) were highly variable across studies and, in at least 60% of the studies, longer in Indigenous compared to non-Indigenous peoples. Risk factors associated with longer patient delays included poor awareness of TB, type of health provider first seen, and self-treatment. CONCLUSION: Time to diagnosis and treatment estimates for Indigenous peoples are generally within previously reported ranges from other systematic reviews focusing on the general population. However among literature examined in this systematic review that stratified by Indigenous and non-Indigenous peoples, patient delay and time to treatment were longer compared to non-Indigenous populations in over half of the studies. Studies included were sparse and highlight an overall gap in literature important to interrupting transmission and preventing new TB cases among Indigenous peoples. Although, risk factors unique to Indigenous populations were not identified, further investigation is needed as social determinants of health among studies conducted in medium and high incidence countries may be shared across both population groups. Trial registration N/a.

The prevalence, risk factors, and public health consequences of peripheral lymph node-associated clinical and subclinical pulmonary tuberculosis.

OBJECTIVES: Relatively little is known about the prevalence, risk factors, and public health consequences of peripheral lymph node (PLN)-associated pulmonary tuberculosis (PTB). METHODS: We developed a 10-year (2010-2019) population-based cohort of PLNTB patients in Canada. We used systematically collected primary source data and expert reader chest radiograph interpretations in a multivariable logistic regression to determine associations between sputum culture positivity and demographic, clinical, and radiographic features. Public health risks were estimated among contacts of PLNTB patients. RESULTS: There were 306 patients with PLNTB, among whom 283 (92.5%) were 15-64 years of age, 159 (52.0%) were female, and 293 (95.8%) were foreign-born. Respiratory symptoms were present in 21.6%, and abnormal chest radiograph in 23.2%. Sputum culture positivity ranged from 12.9% in patients with no symptoms and normal lung parenchyma to 66.7% in patients with both. Respiratory symptoms, abnormal lung parenchyma, and HIV-coinfection (borderline) were independent predictors of sputum culture positivity (odds ratio [OR] 2.24 [95% confidence interval [CI] 1.15-4.39], P = 0.01, OR 4.78 [95% CI 2.41-9.48], P < 0.001, and OR 2.54 [95% CI 0.99-6.52], P = 0.05), respectively. Among contacts of sputum culture-positive PLNTB patients, one secondary case and 16 new infections were identified. CONCLUSION: Isochronous PTB is common in PLNTB patients. Routine screening of PLNTB patients for PTB is strongly recommended.

Exploration of inter-jurisdictional TB programming and mobility in a Canadian First Nation community.

BACKGROUND: Colonially imposed jurisdictional boundaries that have little meaning to Indigenous peoples in Canada may confound tuberculosis (TB) prevention and care activities. This study explores how inter-jurisdictional mobility and the current accommodation of mobility through policies and programming sustain a regional TB epidemic in northwestern Saskatchewan, and northeastern Alberta. METHODS: A qualitative instrumental case study was performed using a community based participatory approach. Semi-structured interviews were conducted with First Nations peoples from a high-incidence community in Canada including community-based healthcare workers. These interview data are presented in the context of a multi-level document analysis of TB program guidelines. RESULTS: The location of the community, and related lack of access to employment, services and care, necessitates mobility across jurisdictional boundaries. There are currently no formal federal or provincial guidelines in place to accommodate highly mobile patients and clients within and across provincial TB prevention and care programs. As a result, locally developed community-based protocols, and related ad-hoc strategies ensure continuity of care. CONCLUSION: Indigenous peoples living in remote communities face unique push/pull factors that motivate mobility. When these motivations exist in communities with increased risk of contagion by communicable infectious diseases such as TB, public health risks extend into increasingly large areas with competing jurisdictional authority. Such mobility poses several threats to TB elimination. We have identified a gap in TB services to systematically accommodate mobility, with specific implications for Indigenous peoples and reconciliation. We recommend clearly defined communication paths and inter-jurisdictional coordination to ensure maintenance of care for mobile populations.

A comparison of the chest radiographic and computed tomographic features of subclinical pulmonary tuberculosis.

Subclinical pulmonary tuberculosis (PTB) is a recently described intermediate state of great interest, but about which little is known. This study sought to describe and compare the frequency of key radiologic features of subclinical PTB on chest radiograph (CXR) versus computed tomographic scan (CT), 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.

Developing Data Governance Agreements with Indigenous Communities in Canada: Toward Equitable Tuberculosis Programming, Research, and Reconciliation.

Indigenous rights to self-determination and data sovereignty support Indigenous-led data governance, which, when adequately resourced, can act as a catalyst for Indigenous-led strategic planning and decision-making in public health research and programming. Respecting Indigenous data sovereignty and governance requires time, resources, education, and planning. Here we share our experiences and lessons learned when developing and implementing data governance agreements with select First Nations and Métis partnering communities in Canada in the context of tuberculosis prevention and care. We define the process undertaken to create a decision space, supported by data governance agreements, where researchers, program (government) stakeholders, and Indigenous community partners are equally and equitably informed to co-develop public health interventions. The decision space has implications for tackling all manner of public health concerns and can inform policy for nation-to-nation public health relationships to advance public health goals.

The Radiographic and Mycobacteriologic Correlates of Subclinical Pulmonary TB in Canada: A Retrospective Cohort Study.

BACKGROUND: Very little is known about subclinical pulmonary TB (PTB), a recently described intermediate state, in high-income countries. RESEARCH QUESTION: 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? STUDY DESIGN AND METHODS: 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. RESULTS: 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. INTERPRETATION: 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.

How much do smear-negative patients really contribute to tuberculosis transmissions? Re-examining an old question with new tools.

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 to 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 diagnosed in the province of Alberta, Canada from 2003 to 2016 as potential transmitters. The primary data sources were the Alberta TB Registry and the Provincial Laboratory for Public Health. 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 molecular (DNA) fingerprint clustering. Then, using a prospectively collected registry of TB contacts, we defined transmission events as active TB amongst identified contacts who either had a 100% DNA fingerprint match to the source case or a clinical diagnosis. We supplemented our analysis with genome sequencing on temporally and geographically linked DNA fingerprint clusters of cases not identified as contacts. FINDINGS: There were 1176 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% (95% CI, 12-19%) and the relative transmission rate was 0.19 (95% CI, 0.14-0.26). With our combined approach, the proportion of transmission was 8% (95% CI, 3-14%) and the relative transmission rate became 0.10 (95% CI, 0.05-0.19). INTERPRETATION: When we examined the same outcomes as in previous studies but refined transmission ascertainment with the addition of conventional epidemiology and genomics, we found that smear-negative cases were ∼50% less infectious than previously thought. FUNDING: Alberta Innovates Health Solutions.

Engaging frontline providers: an important key to eliminating tuberculosis in Canada, and other high-income countries.

The greatest human cost of the rapidly moving pandemic of SARS-CoV-2 may be due to its impact on the response to other diseases. One such other disease is tuberculosis (TB). All indications suggest that COVID-19-related diversions of healthcare resources and disruptions to public health programming will exacerbate the slower moving pandemic of TB. This is expected to set back TB elimination efforts by years. This is a prediction that is especially relevant to Canada, which has repeatedly failed to meet pre-set targets for the elimination of TB even before the COVID-19 pandemic began. A collaborative approach to achieve TB elimination, one that engages all care providers, has recently been emphasized by the STOP-TB Partnership. Among TB elimination strategies, frontline providers (e.g., family physicians, emergency room physicians, and others) are well positioned to identify candidates for the treatment of latent TB infection, and make the diagnosis of infection-spreading cases of TB in a timely manner, thereby interrupting forward-moving chains of transmission. Electronic medical records offer the promise of automating these processes. In this commentary, we promote broader engagement of the workforce across multiple sectors of medicine to reduce TB associated morbidity and mortality, interrupt transmission, and shrink the reservoir of latent TB infection.

RéSUMé: Le plus grand coût humain de la pandémie de SRAS-CoV-2, une maladie à évolution rapide, pourrait être son impact sur la riposte aux autres maladies. L'une d'elles est la tuberculose. Selon tous les indicateurs, les ressources de soins de santé détournées et les programmes de santé publique perturbés pour lutter contre la COVID-19 vont exacerber la pandémie de tuberculose, dont l'évolution est plus lente. Il faut s'attendre à une régression de plusieurs années dans les efforts pour éliminer la tuberculose. C'est une prédiction qui concerne particulièrement le Canada, qui a à maintes reprises été incapable de respecter les objectifs préétablis d'élimination de la tuberculose, même avant la pandémie de COVID-19. Le Partenariat Halte à la tuberculose promulgue depuis peu une démarche concertée, impliquant tous les prestataires de soins, pour parvenir à éliminer la tuberculose. Entre autres stratégies d'élimination, on compte sur les prestataires de première ligne (médecins de famille, médecins d'urgence et autres), bien placés pour repérer les personnes candidates au traitement de la tuberculose-infection (latente) et pour diagnostiquer les cas de tuberculose-maladie (active) dans les meilleurs délais, ce qui interromprait les chaînes de transmission en mouvement. Le dossier médical électronique recèle la promesse d'automatiser ces processus. Dans notre commentaire, nous préconisons une plus grande mobilisation de la main-d'œuvre de plusieurs secteurs de la médecine afin de réduire la morbidité et la mortalité associées à la tuberculose, d'en interrompre la transmission et de réduire la taille du réservoir d'infection tuberculeuse latente.

Individual and public health consequences associated with a missed diagnosis of pulmonary tuberculosis in the emergency department: A retrospective cohort study.

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.

Local Transmission Plays No Important Role in the Occurrence of Multidrug-Resistant Tuberculosis in Immigrants to Canada: An In-depth Epidemiologic Analysis.

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.

Treating latent tuberculosis infection (LTBI) with isoniazid and rifapentine (3HP) in an inner-city population with psychosocial barriers to treatment adherence: A qualitative descriptive study.

In Canada, preventive therapy for latent tuberculosis infection (LTBI) has required multiple doses of medication over an extended period of time. Such regimens are associated with poor adherence and completion rates. A shortened treatment regimen of once weekly isoniazid plus rifapentine for 3 months (3HP), is now available, and holds promise in populations facing challenges to treatment adherence. Although many factors impact treatment adherence, a knowledge gap exists in describing these factors in the context of this regimen. We present findings from a qualitative descriptive study, involving semi-structured interviews with unstably housed or homeless individuals in Edmonton and Fort McMurray, Alberta, Canada who were offered directly-observed preventive therapy (DOPT) with 3HP, and their health care providers. Latent content analysis revealed incomplete understandings of LTBI and about the need for preventive therapy. Clients' motivation to be healthy, alongside education, health care outreach, relationships developed in the context of DOPT, ease of treatment regimen, incentives, and collaboration were all described as supporting treatment completion. Competing priorities, difficulty in reaching clients, undesirable aspects of the regimen and difficulties obtaining and initiating 3HP were identified as barriers. Perceptions of stigma related to LTBI and TB were described by clients in addition to feelings of shame related to their diagnosis. Our study provides insight into LTBI and indicates that multiple interacting psychosocial factors influence preventive therapy access, uptake, and adherence. Findings from this study of both client and provider perspectives can be used to inform and address inequities among individuals experiencing homelessness, and ultimately contribute to a diminished reservoir of LTBI.

Prompt recognition of infectious pulmonary tuberculosis is critical to achieving elimination goals: a retrospective cohort study.

INTRODUCTION: All pulmonary tuberculosis (PTB) cases are presumed to be infectious to some degree. This spectrum of infectiousness is independently described by both the acid-fast bacilli smear and radiographic findings. Smear-positive patients with chest radiographic findings that are typical for adult-type PTB are believed to be most infectious. HYPOTHESIS: Characterisation of the presumed most infectious PTB case is possible by reference to readily available clinical features and laboratory results. METHODS: Retrospective cohort study of adult, culture-positive PTB cases (151 smear-positive; 162 smear-negative) diagnosed between 1 January 2013 and 30 April 2017 in Canada. We describe cases according to demographic, clinical and laboratory features. We use multivariable multinomial logistic regression to estimate the relative risk ratio (RRR) with 95% CI of features associated with an outcome of smear-positive PTB, characterised by 'typical' chest radiograph findings. RESULTS: Being Canadian-born, symptomatic, having a subacute duration of symptoms and broad-spectrum antibiotic prescriptions were all more commonly associated with smear-positive than smear-negative disease (36% vs 20%; 95% vs 63%; 88% vs 54%; and 59% vs 28%, respectively). After combining smear status and radiographic features, we show that smear-positive patients with typical chest radiographs were younger, had a longer duration of symptoms (RRR 2.41; 95% CI 1.01 to 5.74 and 2.93; 95% CI 1.20 to 7.11, respectively) and were less likely to be foreign-born, or have a moderate to high-risk factor for reactivation (RRR 0.40; 95% CI 0.17 to 0.92 and 0.18; 95% CI 0.04 to 0.71, respectively) compared with smear-negative patients with atypical chest radiograph findings. CONCLUSION: A clear picture of the presumed most infectious PTB case emerges from available historical and laboratory information; vigilance for this presentation by front-line providers will support elimination strategies aimed at reducing transmission.

Two Row Wampum, Human Rights, and the Elimination of Tuberculosis from High-Incidence Indigenous Communities.

The Two Row Wampum belt is a symbolic record of the first agreement between Europeans and American Indians on Turtle Island (North America). The agreement outlined a commitment to friendship and peace between people living perpetually in parallel, with each party recognizing the other as an equal partner. Subsequent treaty relationships between the Indigenous peoples of the Canadian prairies and settler society, along with the colonially imposed structures they spawned, are widely regarded as having broken the Covenant Chain, the foundation of which is Two Row Wampum. For example, the universal right to health, especially public health, as protected by provincial and territorial legislation in Canada, is under threat in Indigenous communities with a high incidence of tuberculosis. The rights of Indigenous peoples have been asserted, and reasserted, in the United Nations Declaration on the Rights of Indigenous Peoples, the Truth and Reconciliation Commission of Canada, the International Patients' Charter for Tuberculosis Care, and Jordan's Principle. Herein we describe the implementation of a strategic plan that reinforces human rights and dignity in the spirit of Two Row Wampum in contemporary tuberculosis elimination efforts.

Is there a fundamental flaw in Canada's post-arrival immigrant surveillance system for tuberculosis?

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.