Courtney Heffernan

A 10-Year Population Based Study of ‘Opt-Out’ HIV Testing of Tuberculosis Patients in Alberta, Canada: National Implications

Introduction Compliance with the recommendation that all tuberculosis (TB) patients be tested for human immunodeficiency virus (HIV) has not yet been achieved in Canada or globally. Methods The experience of “opt-out” HIV testing of TB patients in the Province of Alberta, Canada is described over a 10-year period, 2003–2012. Testing rates are reported before and after the introduction of the “opt-out” approach. Risk factors for HIV seropositivity are described and demographic, clinical and laboratory characteristics of TB patients who were newly diagnosed versus previously diagnosed with HIV are compared. Genotypic clusters, defined as groups of two or more cases whose isolates of Mycobacterium tuberculosis had identical DNA fingerprints over the 10-year period or within 2 years of one another, were analyzed for their ability to predict HIV co-infection. Results HIV testing rates were 26% before and 90% after the introduction of “opt-out” testing. During the “opt-out” testing years those <15 or >64 years of age at diagnosis were less likely to have been tested. In those tested the prevalence of HIV was 5.6%. In the age group 15–64 years, risk factors for HIV were: age (35–64 years), Canadian-born Aboriginal or foreign-born sub-Saharan African origin, and combined respiratory and non-respiratory disease. Compared to TB patients previously known to be HIV positive, TB patients newly discovered to be HIV positive had more advanced HIV disease (lower CD4 counts; higher viral loads) at diagnosis. Large cluster size was associated with Aboriginal ancestry. Cluster size predicted HIV co-infection in Aboriginal peoples when clusters included all cases reported over 10 years but not when clusters included cases reported within 2 years of one another. Conclusion “Opt-out” HIV testing of TB patients is effective and well received. Universal HIV testing of TB patients (>80% of patients tested) has immediate (patients) and longer-term (TB/HIV program planning) benefits.

Is Early Tuberculosis Death Associated with Increased Tuberculosis Transmission

Introduction Tuberculosis (TB) is now a relatively uncommon disease in high income countries. As such, its diagnosis may be missed or delayed resulting in death before or shortly after the introduction of treatment. Whether early TB death is associated with increased TB transmission is unknown. To determine the transmission risk attributable to early TB death we undertook a case-control study. Methods All adults who were: (1) diagnosed with culture-positive pulmonary TB in the Province of Alberta, Canada between 1996 and 2012, and (2) died a TB-related death before or within the first 60 days of treatment, were identified. For each of these “cases” two sets of “controls” were randomly selected from among culture-positive pulmonary TB cases that survived beyond 60 days of treatment. “Controls” were matched by age, sex, population group, +/- smear status. Secondary cases of “cases” and “controls” were identified using conventional and molecular epidemiologic tools and compared. In addition, new infections were identified and compared in contacts of “cases” that died before treatment and contacts of their smear-matched “controls”. Conditional logistic regression was used to find associations in both univariate and multivariate analysis. Results “Cases” were as, but not more, likely than “controls” to transmit. This was so whether transmission was measured in terms of the number of “cases” and smear-unmatched or -matched “controls” that had a secondary case, the number of secondary cases that they had or the number of new infections found in contacts of “cases” that died before treatment and their smear-matched “controls”. Conclusion In a low TB incidence/low HIV prevalence country, pulmonary TB patients that die a TB-related death before or in the initial phase of treatment and pulmonary TB patients that survive beyond the initial phase of treatment are equally likely to transmit.

Do “Virtual” and “Outpatient” Public Health Tuberculosis Clinics Perform Equally Well? A Program-Wide Evaluation in Alberta, Canada

Background Meeting the challenge of tuberculosis (TB) elimination will require adopting new models of delivering patient-centered care customized to diverse settings and contexts. In areas of low incidence with cases spread out across jurisdictions and large geographic areas, a “virtual” model is attractive. However, whether “virtual” clinics and telemedicine deliver the same outcomes as face-to-face encounters in general and within the sphere of public health in particular, is unknown. This evidence is generated here by analyzing outcomes between the “virtual” and “outpatient” public health TB clinics in Alberta, a province of Western Canada with a large geographic area and relatively small population. Methods In response to the challenge of delivering equitable TB services over long distances and to hard to reach communities, Alberta established three public health clinics for the delivery of its program: two outpatient serving major metropolitan areas, and one virtual serving mainly rural areas. The virtual clinic receives paper-based or electronic referrals and generates directives which are acted upon by local providers. Clinics are staffed by dedicated public health nurses and university-based TB physicians. Performance of the two types of clinics is compared between the years 2008 and 2012 using 16 case management and treatment outcome indicators and 12 contact management indicators. Findings In the outpatient and virtual clinics, respectively, 691 and 150 cases and their contacts were managed. Individually and together both types of clinics met most performance targets. Compared to outpatient clinics, virtual clinic performance was comparable, superior and inferior in 22, 3, and 3 indicators, respectively. Conclusions Outpatient and virtual public health TB clinics perform equally well. In low incidence settings a combination of the two clinic types has the potential to address issues around equitable service delivery and declining expertise.

Effectiveness of Canada's tuberculosis surveillance strategy in identifying immigrants at risk of developing and transmitting tuberculosis: a population-based retrospective cohort study

BACKGROUND In Canada, tuberculosis disproportionately affects the foreign-born population. The national tuberculosis medical surveillance programme aims to prevent these cases. Individuals referred for further in-country surveillance (referrals) have a history of active tuberculosis or have features of old, healed tuberculosis on chest radiograph; those not referred (non-referrals) do not undergo surveillance. We aimed to examine the risk of transmission arising from referrals versus non-referrals. METHODS We did this population-based retrospective cohort study of foreign-born migrants (aged 15-64 years) to Alberta, Canada, between Jan 1, 2002, and Dec 31, 2013. We obtained information about year of arrival and country of citizenship from Immigration, Refugees and Citizenship Canada, and data for tuberculosis cases and their contacts from the Alberta Tuberculosis Registry. The outcome of interest was culture-positive pulmonary tuberculosis. We compared the incidence of pulmonary tuberculosis and the odds of transmission among referrals versus non-referrals. By use of conventional and molecular epidemiological techniques, we defined transmission as either a secondary case or a tuberculin skin-test (TST) conversion among close contacts. We used multivariate logistic regression to determine the independent association between referral for tuberculosis surveillance and transmission. FINDINGS Between 2002 and 2013, there were 223 225 foreign-born migrants to Alberta, of whom 5500 (2%) were referrals and 217 657 (98%) were non-referrals. 3805 (69%) referrals and 115 226 (53%) non-referrals were from countries with a tuberculosis incidence of more than 150 per 100 000 populations, or sub-Saharan Africa. 234 foreign-born individuals were diagnosed with culture-positive pulmonary tuberculosis between Jan 1, 2004, and Dec 31, 2013. The incidence of culture-positive pulmonary disease was nine times higher in referrals (n=50) than all non-referrals (n=184; incidence rate ratio 9·1, 95% CI 6·7-12·5) and five times higher in referrals than non-referrals from high-risk countries (n=167; 5·0, 3·6-6·8). 71 total transmission events arose from the individuals with culture-positive pulmonary tuberculosis-three (4%) from referrals and 68 (96%) from non-referrals. No secondary cases were attributable to a referral source case, whereas 18 secondary cases were attributable to 11 different non-referral source cases. Three TST conversions were attributable to three different referral source cases compared with 50 conversions from 31 different non-referral source cases. That is, three (6%) referrals transmitted tuberculosis compared with 42 (22%) non-referrals (adjusted odds ratio of 0·19, 95% CI 0·054-0·66; p=0·009). INTERPRETATION Despite a much higher incidence of pulmonary tuberculosis in referrals than non-referrals, referrals were 80% less likely to transmit tuberculosis. Rather than a focus on referrals, Canada could consider screening and treatment of latent tuberculosis in all migrants from high-risk countries-a group that accounted for 100% of secondary cases. FUNDING Canadian Institutes of Health Research.

A population-based study of tuberculosis case fatality in Canada: do Aboriginal peoples fare less well?

SETTING The Province of Alberta, Canada. OBJECTIVES To explore trends in tuberculosis (TB) case fatality, compare TB case-fatality rates by population group and determine prognostic factors associated with TB-related death in Alberta from 1996 to 2012. DESIGN Retrospective cohort analysis. RESULTS During the study years, all-cause TB case fatality fell from 10.7% to 6.3%; the fall was attributable to a change in population structure, as there were more foreign-born and fewer older cases with time. A stable 2% of TB cases died without treatment. Compared to other population groups, Canadian-born Aboriginal case patients were more likely to die without treatment and to die younger. Of TB deaths that were TB-related, 68.9% occurred before or during the initial phase of treatment; of these, TB was a contributory cause of death in 77.5%, i.e., another medical condition was the primary cause of death. In multivariate analysis, age >64 years, aboriginality and miliary/disseminated or central nervous system disease were independent predictors for TB-related death. CONCLUSION Preventive therapy for those with latent tuberculous infection and a high-risk medical condition, early diagnosis of disease, and special support of older, Aboriginal or comorbid cases, once diagnosed, are necessary to further minimise TB case fatality in Alberta, Canada.

Contact investigation outcomes of Canadian-born adults with tuberculosis in Indigenous and non-Indigenous populations in Alberta

OBJECTIVES: Contact investigations are a critical component of tuberculosis control in high-income countries. However, the relative success of conventional methods by population group and place of residence is unknown. This study compares outcomes of contact investigations of Canadian-born Indigenous tuberculosis cases living on- and off-reserve with other Canadian-born cases.METHODS: In a retrospective analysis, Canadian-born adult culture-positive pulmonary TB cases (2001–2010) were identified. Characteristics of source cases and their contacts were compared by population group. Outcomes of contact investigations, including completion of recommended investigations and preventive therapy, were compared in multivariable analysis.RESULTS: Of 171 cases of tuberculosis identified, 49 (29%) were Indigenous on-reserve, 62 (36%) Indigenous off-reserve, and 60 (35%) non-Indigenous or Canadian-born, “other”. Indigenous people had more contacts identified per case compared to non-Indigenous patients. Case population group and smear status were the main predictors of the success of contact investigations. Of those recommended preventive therapy, close contacts of Indigenous cases onreserve had the highest rate of completion, at 54%, vs. 41% and 37% for close contacts of Indigenous living off-reserve and Canadian-born “other” respectively (p = 0.02). Contacts of Indigenous cases living off-reserve had the greatest delay in assessment and the lowest rates of completion of assessment and preventive therapy. In multivariable analysis, population group, smear status of source case and proximity of contact were predictors of preventive therapy acceptance and/or completion.CONCLUSIONS: Significant differences in outcomes of contact investigations were observed between population groups. The higher priority of contacts of smear-positive cases appears to influence efficiency of service delivery, regardless of population group. Jurisdictional differences in program delivery, resource availability and perceived risk of transmission likely influence outcomes of contact investigations.RésuméOBJECTIFS: Le traçage des contacts est un élément essentiel de la lutte contre la tuberculose dans les pays à revenu élevé. On ignore cependant quel est le succès relatif des méthodes classiques selon le segment démographique et le lieu de résidence. Notre étude compare les effets du traçage des contacts de cas de tuberculose autochtones nés au Canada (vivant dans des réserves et hors des réserves) avec d’autres cas nés au Canada.MÉTHODE: Une analyse rétrospective a permis d’identifier les cas de tuberculose pulmonaire positifs par culture chez les adultes nés au Canada (2001–2010). Nous avons comparé les caractéristiques des cas sources et de leurs contacts selon le segment démographique. Les résultats du traçage des contacts, dont l’exécution des traçages recommandés et l’achèvement du traitement préventif, ont été comparés par analyse multivariée.RÉSULTATS: Sur les 171 cas de tuberculose identifiés, 49 (29 %) étaient des Autochtones dans les réserves, 62 (36 %) étaient des Autochtones hors des réserves, et 60 (35 %) étaient des personnes non autochtones ou « autres » nées au Canada. Il y avait davantage de contacts identifiés par cas pour les patients autochtones que pour les patients non autochtones. Le segment démographique et la positivité ou non des frottis d’expectoration des cas étaient les principaux prédicteurs de succès du traçage des contacts. Parmi les contacts pour lesquels un traitement préventif était recommandé, les contacts étroits des cas autochtones dans les réserves présentaient le taux d’achèvement le plus élevé, soit 54 %, contre 41 % et 37 % pour les contacts étroits des Autochtones vivant hors des réserves et des « autres » personnes nées au Canada, respectivement (p = 0,02). Les contacts des cas autochtones vivant hors des réserves présentaient le plus long délai d’évaluation et les plus faibles taux d’exécution de l’évaluation et d’achèvement du traitement préventif. Selon l’analyse multivariée, le segment démographique, la positivité ou non des frottis d’expectoration des cas sources et la proximité du contact étaient des prédicteurs de l’acceptation et/ou de l’achèvement du traitement préventif.CONCLUSIONS: Des écarts significatifs dans les résultats du traçage des contacts ont été observés entre les segments démographiques. La priorité plus élevée accordée aux contacts des cas dont les frottis sont positifs semble influencer l’efficience de la prestation des services, peu importe le segment démographique. Les écarts dans la prestation des programmes et la disponibilité des ressources selon la province ou le territoire et les écarts dans le risque de transmission perçu influencent probablement les résultats du traçage des contacts.

Predicting pulmonary tuberculosis in immigrants: a retrospective cohort study

Our objective was to investigate whether pulmonary tuberculosis (PTB) can be predicted from features of a targeted medical history and basic laboratory investigations in immigrants. A retrospective cohort of 391 foreign-born adults referred to the Edmonton Tuberculosis Clinic (Edmonton, AB, Canada) was studied using multiple logistic regression analysis to predict PTB. Seven characteristics of disease were used as explanatory variables. Cross-validation assessed performance. Each predictor was tested on two outcomes: “culture-positive” and “smear-positive”. Receiver operating characteristic (ROC) curves were generated and the area under the ROC curve (AUC) was quantified. Symptoms, subacute duration of symptoms, risk factors for reactivation of latent TB infection and anaemia were all associated with a positive culture (adjusted OR 1.79, 2.24, 1.72 and 2.28, respectively; p<0.05). Symptoms, inappropriate prescription of broad-spectrum antibiotics and a “typical” chest radiograph were associated with smear-positive PTB (adjusted OR 2.91, 1.55 and 12.34, respectively; p<0.05). ROC curve analysis was used to test each model, yielding AUC=0.91 for the outcome “culture-positive” disease and AUC=0.94 for the outcome “smear-positive” disease. PTB among the foreign-born can be predicted from a targeted medical history and basic laboratory investigations, raising the threshold of suspicion in settings where the disease is relatively rare. In high-income, low tuberculosis incidence countries, certain clinical characteristics should raise the threshold of suspicion to confirm a timely diagnosis http://ow.ly/bRDZ30iPurz

Would program performance indicators and a nationally coordinated response accelerate the elimination of tuberculosis in Canada

Twenty years ago, a National Consensus Conference on Tuberculosis (TB) recommended that the provinces and territories of Canada jointly declare a commitment to TB elimination with national coordination and assured funding, executed by a committee of federal and provincial/territorial representatives. Canada has committed to the global TB elimination targets set forth by the World Health Organization but lacks a coordinated response. In particular, with the exception of one published and implemented by Indigenous Services Canada, there has been no national monitoring and performance framework. Herein, we provide a commentary on the importance, to TB elimination in Canada, of developing such a framework. We invite a debate about whether more can and should be done to monitor and report for action at every jurisdictional level. Of utmost importance will be the need to achieve consensus from stakeholders about what is measured, among whom, how often, who collects and processes data, and how to respond to the successes and failures those data indicate. Insofar, as performance targets are well defined and implemented, national progress towards tuberculosis elimination should accelerate.RésuméIl y a 20 ans, la Conférence nationale de concertation sur la tuberculose recommandait aux provinces et aux territoires du Canada de s’engager conjointement à mettre en œuvre un programme d’élimination de la tuberculose coordonné à l’échelle nationale et jouissant d’un financement garanti, exécuté par un comité de représentants des autorités fédérales, provinciales et territoriales. Le Canada souscrit aux cibles mondiales d’élimination de la tuberculose établies par l’Organisation mondiale de la santé, mais manque une réponse coordonnée. En particulier, sauf pour celui publié et mis en œuvre par Services aux Autochtones Canada, il n’y a aucun cadre national de suivi des résultats. Notre commentaire porte sur l’importance d’un tel cadre pour l’élimination de la tuberculose au Canada. Nous cherchons à engager un débat pour déterminer s’il est possible et souhaitable d’en faire plus pour assurer le suivi et le compte rendu des mesures prises à tout ordre de gouvernement. Il sera de la plus haute importance de parvenir à un consensus des acteurs sur ce qui est mesuré, par qui, à quelle fréquence, qui recueille et traite les données, et comment réagir aux réussites et aux échecs que ces données indiquent. Dans la mesure où les cibles de résultats sont bien définies et mises en œuvre, les progrès réalisés à l’échelle nationale en vue d’éliminer la tuberculose devraient s’accélérer.

Epidemiological and genomic determinants of tuberculosis outbreaks in First Nations communities in Canada

BackgroundIn Canada, tuberculosis disproportionately affects foreign-born and First Nations populations. Within First Nations’ peoples, a high proportion of cases occur in association with outbreaks. Tuberculosis transmission in the context of outbreaks is thought to result from the convergence of several factors including characteristics of the cases, contacts, the environment, and the pathogen.MethodsWe examined the epidemiological and genomic determinants of two well-characterized tuberculosis outbreaks attributed to two super-spreaders among First Nations in the province of Alberta. These outbreaks were associated with two distinct DNA fingerprints (restriction fragment-length polymorphisms or RFLPs 0.0142 and 0.0728). We compared outbreak isolates with endemic isolates not spatio-temporarily linked to outbreak cases. We extracted epidemiological variables pertaining to tuberculosis cases and contacts from individual public health records and the provincial tuberculosis registry. We conducted group analyses using parametric and non-parametric statistical tests. We carried out whole-genome sequencing and bioinformatic analysis using validated protocols.ResultsWe observed differences between outbreak and endemic groups in the mean number of total and child-aged contacts and the number of contacts with new positive and converted tuberculin skin tests in all group comparisons (p < 0.05). Differences were also detected in the proportion of cases with cavitation on a chest radiograph and the mean number of close contacts in selected group comparisons (p < 0.02). A phylogenetic network analysis of whole-genome sequencing data indicated that most outbreak and endemic strains were closely related to the source case for the 0.0142 fingerprint. For the 0.0728 fingerprint, the source case haplotype was circulating among endemic cases prior to the outbreak. Genetic and temporal distances were not correlated for either RFLP 0.0142 (r2 = − 0.05) or RFLP 0.0728 (r2 = 0.09) when all isolates were analyzed.ConclusionsWe found no evidence that endemic strains acquired mutations resulting in their emergence in outbreak form. We conclude that the propagation of these outbreaks was likely driven by the combination of characteristics of the source cases, contacts, and the environment. The role of whole-genome sequencing in understanding mycobacterial evolution and in assisting public health authorities in conducting contact investigations and managing outbreaks is important and expected to grow in the future.

Tuberculosis transmission in the Indigenous peoples of the Canadian prairies

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.