Sustainability and impact of an intervention to improve initiation of tuberculosis preventive treatment: results from a follow-up study of the ACT4 randomized trial.

Background: In a cluster randomized trial (clinicaltrials.gov: NCT02810678) a flexible but comprehensive health system intervention significantly increased the number of household contacts (HHC) identified and started on tuberculosis preventive treatment (TPT). A follow-up study was conducted one year later to test the hypotheses that these effects were sustained, and were reproducible with a simplified intervention. Methods: We conducted a follow-up study from May 1, 2018 until April 30, 2019, as part of a multinational cluster randomized trial. Eight sites in 4 countries that had received the intervention in the original trial received no further intervention; eight other sites in the same countries that had not received the intervention (control sites in the original trial) now received a simplified version of the intervention. This consisted of repeated local evaluation of the Cascade of care for TB infection, and stakeholder decision making. The number of HHC identified and starting TPT were repeatedly measured at all 16 sites and expressed as rates per 100 newly diagnosed index TB patients. The sustained effect of the original intervention was estimated by comparing these rates after the intervention in the original trial with the last 6 months of the follow-up study. The reproducibility was estimated by comparing the pre-post intervention changes in rates at sites receiving the original intervention with the pre-post changes in rates at sites receiving the later, simplified intervention. Findings: With regard to the sustained impact of the original intervention, compared to the original post-intervention period, the number of HHC identified and treated per 100 newly diagnosed TB patients was 10 more (95% confidence interval: 84 fewer to 105 more), and 1 fewer (95% CI: 22 fewer to 20 more) respectively up to 14 months after the end of the original intervention. With regard to the reproducibility of the simplified intervention, at sites that had initially served as control sites, the number of HHC identified and treated per 100 TB patients increased by 33 (95% CI: -32, 97), and 16 (-69, 100) from 3 months before, to up to 6 months after receiving a streamlined intervention, although differences were larger, and significant if the post-intervention results were compared to all pre-intervention periods. Interpretation: Up to one year after it ended, a health system intervention resulted in sustained increases in the number of HHC identified and starting TPT. A simplified version of the intervention was associated with non-significant increases in the identification and treatment of HHC. Inferences are limited by potential bias due to other temporal effects, and the small number of study sites. Funding: Funded by the Canadian Institutes of Health Research (Grant number 143350).

Distinct healthcare utilization profiles of high healthcare use tuberculosis survivors: A latent class analysis.

BACKGROUND: Recent data have demonstrated that healthcare use after treatment for respiratory tuberculosis (TB) remains elevated in the years following treatment completion. However, it remains unclear which TB survivors are high healthcare users and whether any variation exists within this population. Thus, the primary objective of this study was to identify distinct profiles of high healthcare-use TB survivors to help inform post-treatment support and care. METHODS: Using linked health administrative data from British Columbia, Canada, we identified foreign-born individuals who completed treatment for incident respiratory TB between 1990 and 2019. We defined high healthcare-use TB survivors as those in the top 10% of annual emergency department visits, hospital admissions, or general practitioner visits among the study population during the five-year period immediately following TB treatment completion. We then used latent class analysis to categorize the identified high healthcare-use TB survivors into subgroups. RESULTS: Of the 1,240 people who completed treatment for respiratory TB, 258 (20.8%) people were identified as high post- TB healthcare users. Latent class analysis results in a 2-class solution. Class 1 (n = 196; 76.0%) included older individuals (median age 71.0; IQR 59.8, 79.0) with a higher probability of pre-existing hypertension and diabetes (41.3% and 33.2%, respectively). Class 2 (n = 62; 24.0%) comprised of younger individuals (median age 31.0; IQR 27.0, 41.0) with a high probability (61.3%) of immigrating to Canada within five years of their TB diagnosis and a low probability (11.3%) of moderate to high continuity of primary care. DISCUSSION: Our findings suggest that foreign-born high healthcare-use TB survivors in a high-resource setting may be categorized into distinct profiles to help guide the development of person-centred care strategies targeting the long-term health impacts TB survivors face.

Using a theory-informed approach to guide the initial development of a post-tuberculosis care package in British Columbia, Canada.

BACKGROUND: The importance of addressing the long-term needs of tuberculosis (TB) survivors is gaining increasing attention. One promising approach to improving post-TB care is implementing a post-TB care package. With a specific focus on the perspectives of healthcare providers in British Columbia, Canada, this study aimed to (1) determine a set of components to be included in a post-TB care package, (2) explore barriers and facilitators influencing their implementation, and (3) propose potential solutions to overcome identified challenges. METHODS: Employing a multi-method approach guided by the Theoretical Domains Framework, we first conducted virtual workshops with TB care providers and utilized a modified Delphi process to establish a preliminary list of care package components. Then, we surveyed healthcare providers using closed-ended, Likert-scale questions to identify implementation barriers and enablers. Lastly, we mapped the identified barriers and enablers to establish behaviour change techniques to identify possible solutions to overcome the challenges identified. RESULTS: Eleven participants attended virtual workshops, and 23 of 51 (45.1%) healthcare providers completed questionnaires. Identified components of the post-TB care package included: 1. Linking people with TB to a primary care provider if they do not have one. 2. Referring people with pulmonary TB for an end-of-treatment chest x-ray and pulmonary function testing. 3. Referring people with TB who smoke to a smoking cessation specialist. 4. Sharing a one-page post-TB information sheet with the patient's primary care provider, including a summary of post-TB health concerns, complications, and recommendations to prioritize age-appropriate screening for cardiovascular disease, lung cancer, and depression. Survey results indicated that domain scores for 'environment, context, and resources' were the lowest, suggesting potential implementation barriers. Care navigation services to help individuals overcome health system barriers while transitioning from TB care, information leaflets, and checklists summarizing key post-TB health concerns for patients and healthcare providers to help facilitate discussions may help overcome the identified barriers. CONCLUSION: Healthcare providers in British Columbia acknowledge that post-TB care is integral to comprehensive health care but are limited by time and resources. Care navigation services, a post-TB checklist, and patient information leaflets may help resolve some of these barriers.

Risk of Tuberculosis Disease in People With Chronic Kidney Disease Without Kidney Failure: A Systematic Review and Meta-analysis.

BACKGROUND: Kidney failure is an established risk factor for tuberculosis (TB), but little is known about TB risk in people with chronic kidney disease (CKD) who have not initiated kidney replacement therapy (CKD without kidney failure). Our primary objective was to estimate the pooled relative risk of TB disease in people with CKD stages 3-5 without kidney failure compared with people without CKD. Our secondary objectives were to estimate the pooled relative risk of TB disease for all stages of CKD without kidney failure (stages 1-5) and by each CKD stage. METHODS: This review was prospectively registered (PROSPERO CRD42022342499). We systematically searched MEDLINE, Embase, and Cochrane databases for studies published between 1970 and 2022. We included original observational research estimating TB risk among people with CKD without kidney failure. Random-effects meta-analysis was performed to obtain the pooled relative risk. RESULTS: Of the 6915 unique articles identified, data from 5 studies were included. The estimated pooled risk of TB was 57% higher in people with CKD stages 3-5 than in people without CKD (adjusted hazard ratio: 1.57; 95% CI: 1.22-2.03; I2 = 88%). When stratified by CKD stage, the pooled rate of TB was highest in stages 4-5 (incidence rate ratio: 3.63; 95% CI: 2.25-5.86; I2 = 89%). CONCLUSIONS: People with CKD without kidney failure have an increased relative risk of TB. Further research and modeling are required to understand the risks, benefits, and CKD cutoffs for screening people for TB with CKD prior to kidney replacement therapy.

Comparing Mycobacterium tuberculosis transmission reconstruction models from whole genome sequence data.

Genomic epidemiology is routinely used worldwide to interrogate infectious disease dynamics. Multiple computational tools exist that reconstruct transmission networks by coupling genomic data with epidemiological models. Resulting inferences can improve our understanding of pathogen transmission dynamics, and yet the performance of these tools has not been evaluated for tuberculosis (TB), a disease process with complex epidemiology including variable latency and within-host heterogeneity. Here, we performed a systematic comparison of six publicly available transmission reconstruction models, evaluating their accuracy when predicting transmission events in simulated and real-world Mycobacterium tuberculosis outbreaks. We observed variability in the number of transmission links that were predicted with high probability (P ≥ 0.5) and low accuracy of these predictions against known transmission in simulated outbreaks. We also found a low proportion of epidemiologically supported case-contact pairs were identified in our real-world TB clusters. The specificity of all models was high, and a relatively high proportion of the total transmission events predicted by some models were true links, notably with TransPhylo, Outbreaker2, and Phybreak. Our findings may inform the choice of tools in TB transmission analyses and underscore the need for caution when interpreting transmission networks produced using probabilistic approaches.

Healthcare Utilization After Respiratory Tuberculosis: A Controlled Interrupted Time Series Analysis.

BACKGROUND: Despite data suggesting elevated morbidity and mortality among people who have survived tuberculosis disease, the impact of respiratory tuberculosis on healthcare utilization in the years following diagnosis and treatment remains unclear. METHODS: Using linked health administrative data from British Columbia, Canada, we identified foreign-born individuals treated for respiratory tuberculosis between 1990 and 2019. We matched each person with up to four people without a tuberculosis diagnosis from the same source cohort using propensity score matching. Then, using a controlled interrupted time series analysis, we measured outpatient physician encounters and inpatient hospital admissions in the 5 years following respiratory tuberculosis diagnosis and treatment. RESULTS: We matched 1216 individuals treated for respiratory tuberculosis to 4864 non-tuberculosis controls. Immediately following the tuberculosis diagnostic and treatment period, the monthly rate of outpatient encounters in the tuberculosis group was 34.0% (95% confidence interval [CI]: 30.7%, 37.2%) higher than expected, and this trend was sustained for the duration of the post-tuberculosis period. The excess utilization represented an additional 12.2 (95% CI: 10.6, 14.9) outpatient encounters per person over the post-tuberculosis period, with respiratory morbidity a large contributor to the excess healthcare utilization. Results were similar for hospital admissions, with an additional 0.4 (95% CI: .3, .5) hospital admissions per person over the post-tuberculosis period. CONCLUSIONS: Respiratory tuberculosis appears to have long-term impacts on healthcare utilization beyond treatment. These findings underscore the need for screening, assessment, and treatment of post-tuberculosis sequelae, as it may provide an opportunity to improve health and reduce resource use.

Role of latent tuberculosis infection on elevated risk of cardiovascular disease: a population-based cohort study of immigrants in British Columbia, Canada, 1985-2019.

We investigated cardiovascular disease (CVD) risk associated with latent tuberculosis infection (LTBI) (Aim-1) and LTBI therapy (Aim-2) in British Columbia, a low-tuberculosis-incidence setting. 49,197 participants had valid LTBI test results. Cox proportional hazards model was fitted, adjusting for potential confounders. Compared with the participants who tested LTBI negative, LTBI positive was associated with an 8% higher CVD risk in complete case data (adjusted hazard ratio (HR): 1.08, 95% CI: 0.99-1.18), a statistically significant 11% higher risk when missing confounder values were imputed using multiple imputation (HR: 1.11, 95% CI: 1.02-1.20), and 10% higher risk when additional proxy variables supplementing known unmeasured confounders were incorporated in the highdimensional disease risk score technique to reduce residual confounding (HR: 1.10, 95% CI: 1.01-1.20). Also, compared with participants who tested negative, CVD risk was 27% higher among people who were LTBI positive but incomplete LTBI therapy (HR: 1.27, 95% CI: 1.04-1.55), whereas the risk was similar in people who completed LTBI therapy (HR: 1.04, 95% CI: 0.87-1.24). Findings were consistent in different sensitivity analyses. We concluded that LTBI is associated with an increased CVD risk in low-tuberculosis-incidence settings, with a higher risk associated with incomplete LTBI therapy and attenuated risk when therapy is completed.

Tuberculosis and risk of cancer: A systematic review and meta-analysis.

INTRODUCTION: Cancer is a major cause of death among people who experience tuberculosis (TB), but little is known about its timing and incidence following TB treatment. Our primary objectives were to estimate the pooled risk of all and site-specific malignancies in people with TB compared to the general population or suitable controls. Our secondary objective was to describe the pooled risk of cancer at different time points following TB diagnosis. METHODS: This study was prospectively registered (PROSPERO: CRD42021277819). We systematically searched MEDLINE, Embase, and the Cochrane Database for studies published between 1980 and 2021. We included original observational research articles that estimated cancer risk among people with TB compared to controls. Studies were excluded if they had a study population of fewer than 50 individuals; used cross-sectional, case series, or case report designs; and had a follow-up period of less than 12 months. Random-effects meta-analysis was used to obtain the pooled risk of cancer in the TB population. RESULTS: Of the 5,160 unique studies identified, data from 17 studies were included. When compared to controls, the pooled standardized incidence ratios (SIR) of all cancer (SIR 1.62, 95% CI 1.35-1.93, I2 = 97%) and lung cancer (SIR 3.20, 95% CI 2.21-4.63, I2 = 90%) was increased in the TB population. The pooled risk of all cancers and lung cancer was highest within the first year following TB diagnosis (SIR 4.70, 95% CI 1.80-12.27, I2 = 99%) but remained over five years of follow-up. CONCLUSIONS: People with TB have an increased risk of both pulmonary and non-pulmonary cancers. Further research on cancer following TB diagnosis is needed to develop effective screening and early detection strategies. Clinicians should have a high index of suspicion for cancer in people with TB, particularly in the first year following TB diagnosis.

Costs of Tuberculosis at 3 Treatment Centers, Canada, 2010-2016.

We estimated costs of managing different forms of tuberculosis (TB) across Canada by conducting a retrospective chart review and cost assessment of patients treated for TB infection, drug-susceptible TB (DS TB), isoniazid-resistant TB, or multidrug-resistant TB (MDR TB) at 3 treatment centers. We included 90 patients each with TB infection and DS TB, 71 with isoniazid-resistant TB, and 62 with MDR TB. Median per-patient costs for TB infection (in 2020 Canadian dollars) were $804 (interquartile range [IQR] $587-$1,205), for DS TB $12,148 (IQR $4,388-$24,842), for isoniazid-resistant TB $19,319 (IQR $7,117-$41,318), and for MDR TB $119,014 (IQR $80,642-$164,015). Compared with costs for managing DS TB, costs were 11.1 (95% CI 9.1-14.3) times lower for TB infection, 1.7 (95% CI 1.3-2.1) times higher for isoniazid-resistant TB, and 8.1 (95% CI 6.1-10.6) times higher for MDR TB. Broadened TB infection treatment could avert high costs associated with managing TB disease.

High-dose rifamycins in the treatment of TB: a systematic review and meta-analysis.

BACKGROUND: There is growing interest in using high-dose rifamycin (HDR) regimens in TB treatment, but the safety and efficacy of HDR regimens remain uncertain. We performed a systematic review and meta-analysis comparing HDR to standard-dose rifamycin (SDR) regimens. METHODS: We searched MEDLINE, Embase, CENTRAL, Cochrane Database of Systematic Reviews and clinicaltrials.gov for prospective studies comparing daily therapy with HDRs to SDRs. Rifamycins included rifampicin, rifapentine and rifabutin. Our primary outcome was the rate of severe adverse events (SAEs), with secondary outcomes of death, all adverse events, SAE by organ and efficacy outcomes of 2-month culture conversion and relapse. This study was prospectively registered in the International Prospective Register of Systematic Reviews (CRD42020142519). RESULTS: We identified 9057 articles and included 13 studies with 6168 participants contributing 7930 person-years (PY) of follow-up (HDR: 3535 participants, 4387 PY; SDR: 2633 participants, 3543 PY). We found no significant difference in the pooled incidence rate ratio (IRR) of SAE between HDR and SDR (IRR 1.00, 95% CI 0.82 to 1.23, I 2=41%). There was no significant difference when analysis was limited to SAE possibly, probably or likely medication-related (IRR 1.07, 95% CI 0.82 to 1.41, I 2=0%); studies with low risk of bias (IRR 0.98, 95% CI 0.79 to 1.20, I 2=44%); or studies using rifampicin (IRR 1.00, 95% CI 0. 0.75-1.32, I 2=38%). No significant differences were noted in pooled outcomes of death, 2-month culture conversion and relapse. CONCLUSIONS: HDRs were not associated with a significant difference in SAEs, 2-month culture conversion or death. Further studies are required to identify specific groups who may benefit from HDR.

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.

Using Whole-genome Sequencing to Determine the Timing of Secondary Tuberculosis in British Columbia, Canada.

Combined with epidemiological data, whole-genome sequencing (WGS) can help better resolve individual tuberculosis (TB) transmission events to a degree not possible with traditional genotyping. We combine WGS data with patient-level data to calculate the timing of secondary TB among contacts of people diagnosed with active TB in British Columbia, Canada.

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.

Discovery and validation of a personalized risk predictor for incident tuberculosis in low transmission settings.

The risk of tuberculosis (TB) is variable among individuals with latent Mycobacterium tuberculosis infection (LTBI), but validated estimates of personalized risk are lacking. In pooled data from 18 systematically identified cohort studies from 20 countries, including 80,468 individuals tested for LTBI, 5-year cumulative incident TB risk among people with untreated LTBI was 15.6% (95% confidence interval (CI), 8.0-29.2%) among child contacts, 4.8% (95% CI, 3.0-7.7%) among adult contacts, 5.0% (95% CI, 1.6-14.5%) among migrants and 4.8% (95% CI, 1.5-14.3%) among immunocompromised groups. We confirmed highly variable estimates within risk groups, necessitating an individualized approach to risk stratification. Therefore, we developed a personalized risk predictor for incident TB (PERISKOPE-TB) that combines a quantitative measure of T cell sensitization and clinical covariates. Internal-external cross-validation of the model demonstrated a random effects meta-analysis C-statistic of 0.88 (95% CI, 0.82-0.93) for incident TB. In decision curve analysis, the model demonstrated clinical utility for targeting preventative treatment, compared to treating all, or no, people with LTBI. We challenge the current crude approach to TB risk estimation among people with LTBI in favor of our evidence-based and patient-centered method, in settings aiming for pre-elimination worldwide.

Effectiveness of Latent TB Screening and Treatment in People Initiating Dialysis in British Columbia, Canada.

BACKGROUND: People undergoing chronic dialysis are at an increased risk of active tuberculosis (TB). In 2012, the Canadian province of British Columbia began systematically screening people initiating dialysis for latent TB using interferon-gamma release assay (IGRA), and treating when appropriate. OBJECTIVE: The objective of this study was to compare active TB rate in people who initiated dialysis and were screened using an IGRA compared with those not screened during the same period. DESIGN: Retrospective cohort study. SETTING: British Columbia (BC), a Canadian province of 5.0 million people with an active TB incidence of 5.1 per 100 000 population. PARTICIPANTS: All people in BC who initiated at least 90 days of dialysis between January 2012 and May 2017 were included in the study. People were excluded if they were <18 years of age or had a prior history of active TB diagnosis or treatment for latent TB. METHODS: A retrospective cohort was created of British Columbians who initiated dialysis between 2012 and 2017. Individuals were stratified into a screened and nonscreened group. Multivariable Cox regression was used to determine the association between latent TB screening and the development of active TB. The primary outcome was incident active TB, either microbiologically confirmed or clinically diagnosed. RESULTS: Of the 3190 people included in the study, 1790 (56.1%) were screened, of which 152 (8.5%) initiated latent TB treatment postscreening. During follow-up, incident active TB was diagnosed in 6 (0.3%) of the 1790 people screened, compared with 11 (0.8%) of the 1400 people who received no screening. In multivariable analysis, latent TB screening and treatment was associated with a significant reduction in the rate of active TB (adjusted hazard ratio = 0.3, 95% confidence interval = 0.1-0.8; P < .01). LIMITATIONS: This was an observational retrospective study and the potential for unmeasured confounding should be carefully assessed. CONCLUSIONS: These findings suggest that systematically screening and treating people initiating dialysis can significantly decrease the rate of active TB in this high-risk population. Given the importance of screening high-risk groups, the results from this analysis could inform scale-up of TB screening in dialysis programs in other low incidence regions. Trial registration is not applicable as this was a retrospective cohort analysis and not a randomized trial.

CONTEXTE: Les patients sous dialyse chronique sont plus susceptibles de développer une tuberculose (TB) active. En 2012, la Colombie-Britannique (province canadienne) a entrepris de dépister systématiquement la TB latente chez les patients qui amorcent un traitement de dialyse. Le dépistage s'effectue à l'aide du test sanguin de libération d'interféron gamma (test IGRA­Interferon Gamma Release Assay) et les patients sont traités lorsque nécessaire. OBJECTIF: L'objectif de l'étude était de comparer le taux de TB active chez les patients dépistés par le test IGRA à celui des individus non testés au cours de la même période. TYPE D'ÉTUDE: Étude de cohorte rétrospective. CADRE: L'étude s'est tenue en Colombie-Britannique, une province canadienne de cinq millions d'habitants dont l'incidence de TB active est de 5,1 cas pour 100 000 habitants. PARTICIPANTS: Ont été inclus tous les Britanno-Colombiens ayant amorcé une dialyse de plus de 90 jours entre janvier 2012 et mai 2017. Les mineurs et les individus avec des antécédents de TB active ou ayant déjà été traités pour une TB latente ont été exclus. MÉTHODOLOGIE: Une étude de cohorte rétrospective a été menée auprès des Britanno-Colombiens ayant amorcé une dialyse entre 2012 et 2017. Les individus ont été divisés en deux groupes: un groupe dépisté et un groupe non dépisté. Une régression de Cox à variables multiples a servi à établir l'association entre une TB latente et le développement d'une TB active. Le principal résultat d'intérêt était une TB active confirmée par analyse microbiologique ou diagnostiquée cliniquement. RÉSULTATS: Des 3 190 individus retenus pour l'étude, 1 790 (56,1 %) ont été testés et de ceux-ci, 152 (8,5 %) ont été traités pour une TB latente après l'examen. Pendant le suivi, parmi les 1 790 individus dépistés, 6 patients (0,3 %) ont reçu un diagnostic de TB active comparativement à onze (0,8 %) parmi les 1400 qui n'avaient pas été examinés. Dans l'analyse multivariée, le traitement et le dépistage de la TB latente ont été associés à une réduction significative du taux de TB active (aHR 0,3; IC 95%: 0,1 à 0,8; p <0,01). LIMITES: Il s'agit d'une étude observationnelle rétrospective et le risque de confusion devrait être rigoureusement évalué. CONCLUSION: Ces résultats suggèrent que le taux de TB active chez les patients dialysés pourrait être réduit significativement par le dépistage et le traitement systématique des individus qui entreprennent un traitement de dialyse. Vu l'importance du dépistage des populations à haut risque, les résultats de cette étude sont susceptibles d'éclairer l'augmentation du dépistage de la TB au sein des programmes de dialyse dans d'autres régions de faible incidence.

Cardiovascular morbidity and mortality among persons diagnosed with tuberculosis: A systematic review and meta-analysis.

INTRODUCTION: The emerging epidemiological evidence of increased cardiovascular disease (CVD) risk among persons diagnosed with tuberculosis (TB) has not been systematically reviewed to date. Our aim was to review the existing epidemiological evidence for elevated risk of CVD morbidity and mortality among persons diagnosed with TB compared to controls. MATERIALS AND METHODS: EMBASE, MEDLINE, and Cochrane databases were searched (inception to January 2020) for terms related to "tuberculosis" and "cardiovascular diseases". Inclusion criteria: trial, cohort, or case-control study design; patient population included persons diagnosed with TB infection or disease; relative risk (RR) estimate and confidence interval reported for CVD morbidity or mortality compared to suitable controls. Exclusion criteria: no TB or CVD outcome definition; duplicate study; non-English abstract; non-human participants. Two reviewers screened studies, applied ROBINS-I tool to assess risk of bias, and extracted data independently. Random effects meta-analysis estimated a pooled RR of CVD morbidity and mortality for persons diagnosed with TB compared to controls. RESULTS: 6,042 articles were identified, 244 full texts were reviewed, and 16 were included, meta-analyzing subsets of 8 studies' RR estimates. We estimated a pooled RR of 1.51 (95% CI: 1.16-1.97) for major adverse cardiac events among those diagnosed with TB compared to non-TB controls (p = 0.0024). A 'serious' pooled risk of bias was found across studies with between-study heterogeneity (I2 = 75.3%). CONCLUSIONS: TB appears to be a marker for increased CVD risk; however, the literature is limited and is accompanied by serious risk of confounding bias and evidence of publication bias. Further retrospective and prospective studies are needed. Pending this evidence, best practice may be to consider persons diagnosed with TB at higher risk of CVD as a precautionary measure.

Long-term all-cause mortality in people treated for tuberculosis: a systematic review and meta-analysis.

BACKGROUND: Accurate estimates of long-term mortality following tuberculosis treatment are scarce. This systematic review and meta-analysis aimed to estimate the post-treatment mortality among tuberculosis survivors, and examine differences in mortality risk by demographic and clinical characteristics. METHODS: We systematically searched Embase, MEDLINE, and the Cochrane Database of Systematic Reviews for cohort studies published in English between Jan 1, 1997, and May 31, 2018. We included research papers that used a cohort study design, included bacteriological or clinical confirmation of tuberculosis disease for all participants, and reported, or provided enough data to calculate, mortality estimates for people with tuberculosis and a valid control group representative of the general population. We excluded studies that reported duplicate data, had a study population of fewer than 50 people overall, had a follow-up period shorter than 12 months after treatment completion, or had a loss to follow-up of more than 30%. From eligible studies, we extracted standardised mortality ratios (SMRs), or calculated them when the data were sufficient, by dividing the sum of the observed deaths by the sum of the expected deaths. For studies that did not report SMR as their mortality estimate, either mortality hazard ratios or mortality rate ratios were extracted and pooled with SMRs. Random-effects meta-analysis was used to obtain pooled SMRs. Between-study heterogeneity was estimated with I2. This study was prospectively registered in PROSPERO (CRD42018092592). FINDINGS: Of the 7283 unique studies identified, data from ten studies, reporting on 40 781 individuals and 6922 deaths, were included. The pooled SMR for all-cause mortality among people with tuberculosis, compared with the control group, was 2·91 (95% CI 2·21-3·84; I2=99%, pheterogeneity<0·0001). When restricted to people with confirmed treatment completion or cure, the pooled SMR was 3·76 (95% CI 3·04-4·66; I2=95%). Effect estimates were similar when stratified by tuberculosis type, sex, age, and country income category. Causes of mortality were extracted for 4226 deaths that occurred post-treatment, with most deaths attributable to cardiovascular disease (20% [95% CI 15-26]; I2=92%). INTERPRETATION: People treated for tuberculosis have significantly increased mortality following treatment compared with the general population or matched controls. These findings support the need for further research to understand and address the biomedical and social factors that affect the long-term prognosis of this population. FUNDING: None.