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.

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.

Incidence of and Risk Factors for Active Tuberculosis Disease in Individuals With Glomerular Disease: A Canadian Cohort Study.

RATIONALE & OBJECTIVE: Kidney failure is an established risk factor for active tuberculosis (TB) but the risk of TB has not been reported in specific kidney diseases. We sought to determine the incidence of and risk factors for active TB in patients with glomerular disease. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: A provincial kidney pathology registry (2000-2012) was used to identify 3,079 adult patients with IgA nephropathy, focal segmental glomerulosclerosis (FSGS), antineutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis, lupus nephritis, membranous nephropathy, minimal change disease, or "other" glomerular diseases in British Columbia, Canada. EXPOSURE: Predictors included demographics, immigration status, comorbidities, immunosuppression use, estimated glomerular filtration rate (eGFR), and proteinuria. OUTCOME: A diagnosis of active TB was ascertained using administrative data linkages and defined based on (1) the dispensation of 1 or more unique combinations of medications used to treat active TB, or (2) physician or hospital visits for active TB. ANALYTICAL APPROACH: The definition of TB was validated in an external cohort linked to the Provincial TB registry at the BC Centre for Disease Control (BCCDC). Standardized incidence ratios were calculated using the age-matched general population. Risk factors for active TB were identified using Cox proportional hazards regression analysis. RESULTS: The sensitivity and specificity of the outcome definition of active TB were 87.6% and 99.5%, respectively. During a median follow-up of 6.2 years, 41 patients developed active TB with an incidence of 197 of 100,000 person-years, approximately 23 times as high as the general population and>6 times higher than the threshold of 30 per 100,000 used to define high TB incidence. A high incidence was observed in all glomerular diseases (range, 110-403 per 100,000), in both Canadian- and foreign-born patients (range, 124-424 per 100,000), and in patients exposed or not to immunosuppression (282 vs 147 per 100,000). Factors associated with higher TB risk included immigration from a high-incidence country (HR, 3.90 [95% CI, 1.75-8.68]), diminished eGFR (HR, 2.81 [95% CI, 1.18-6.69]), higher levels of proteinuria (HR, 1.15 [95% CI, 1.04-1.27]), lupus nephritis (HR, 2.79 [95% CI, 1.37-5.68]), and immunosuppression use (HR, 2.13 [95% CI, 1.13-4.03]). LIMITATIONS: A relatively low number of events contributed to uncertainty in risk estimates. CONCLUSIONS: Patients with glomerular disease have a high incidence of active TB irrespective of disease type, demographics, or use of immunosuppression. Prospective studies are needed to evaluate the utility of screening for latent TB infection in this population. PLAIN-LANGUAGE SUMMARY: Patients with kidney failure are at high risk of developing tuberculosis (TB), a major infection that can be prevented by identifying and treating patients who have had prior exposure to TB. The risk of TB in specific kidney diseases is unknown. In this Canadian study of 3,079 patients with glomerular disease, a group of autoimmune kidney conditions, the rate of TB was 23 times higher than in the general population. The rate was high irrespective of the use of immunosuppressive drugs or whether patients had immigrated to Canada from another country. These findings suggest that screening patients with glomerular disease for prior TB exposure may be beneficial; however, this needs to be evaluated in a prospective study.

The prevalence of tuberculosis infection among foreign-born Canadians: a modelling study.

BACKGROUND: The prevalence of tuberculosis infection is critical to the design of tuberculosis prevention strategies, yet is unknown in Canada. We estimated the prevalence of tuberculosis infection among Canadian residents born abroad. METHODS: We estimated the prevalence of tuberculosis infection by age and year of migration to Canada for people from each of 168 countries by constructing country-specific and calendar year-specific trends for annual risk of infection using a previously developed model. We combined country-specific prevalence estimates with Canadian Census data from 2001, 2006, 2011, 2016 and 2021 to estimate the overall prevalence of tuberculosis infection among foreign-born Canadian residents. RESULTS: The estimated overall prevalence of tuberculosis infection among foreign-born people in Canada was 25% (95% uncertainty interval [UI] 20%-35%) for census year 2001, 24% (95% UI 20%-33%) for 2006, 23% (95% UI 19%-30%) for 2011, 22% (95% UI 19%-28%) for 2016 and 22% (95% UI 19%-27%) for 2021. The prevalence increased with age at migration and incidence of tuberculosis in the country of origin. In 2021, the estimated prevalence of infection among foreign-born residents was lowest in Quebec (19%, 95% UI 16%-24%) and highest in Alberta (24%, 95% UI 21%-28%) and British Columbia (24%, 95% UI 20%-30%). Among all foreign-born Canadian residents with tuberculosis infection in 2021, we estimated that only 1 in 488 (95% UI 185-1039) had become infected within the 2 preceding years. INTERPRETATION: About 1 in 4 foreign-born Canadian residents has tuberculosis infection, but very few were infected within the 2 preceding years (the highest risk period for progression to tuberculosis disease). These data may inform future tuberculosis infection screening policies.

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.

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.

Post-COVID dyspnea: prevalence, predictors, and outcomes in a longitudinal, prospective cohort.

BACKGROUND: The pathophysiology, evolution, and associated outcomes of post-COVID dyspnea remain unknown. The aim of this study was to determine the prevalence, severity, and predictors of dyspnea 12 months following hospitalization for COVID-19, and to describe the respiratory, cardiac, and patient-reported outcomes in patients with post-COVID dyspnea. METHODS: We enrolled a prospective cohort of all adult patients admitted to 2 academic hospitals in Vancouver, Canada with PCR-confirmed SARS-CoV-2 during the first wave of COVID between March and June 2020. Dyspnea was measured 3, 6, and 12 months after initial symptom onset using the University of California San Diego Shortness of Breath Questionnaire. RESULTS: A total of 76 patients were included. Clinically meaningful dyspnea (baseline score > 10 points) was present in 49% of patients at 3 months and 46% at 12 months following COVID-19. Between 3 and 12 months post-COVID-19, 24% patients had a clinically meaningful worsening in their dyspnea, 49% had no meaningful change, and 28% had a clinically meaningful improvement in their dyspnea. There was worse sleep, mood, quality of life, and frailty in patients with clinically meaningful dyspnea at 12 months post-COVID infection compared to patients without dyspnea. There was no difference in PFT findings, troponin, or BNP comparing patients with and without clinically meaningful dyspnea at 12 months. Severity of dyspnea and depressive symptoms at 3 months predicted severity of dyspnea at 12 months. CONCLUSIONS: Post-COVID dyspnea is common, persistent, and negatively impacts quality of life. Mood abnormalities may play a causative role in post-COVID dyspnea in addition to potential cardiorespiratory abnormalities. Dyspnea and depression at initial follow-up predict longer-term post-COVID dyspnea, emphasizing that standardized dyspnea and mood assessment following COVID-19 may identify patients at high risk of post-COVID dyspnea and facilitating early and effective management.

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.

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.

How Well Does TSTin3D Predict Risk of Active Tuberculosis in the Canadian Immigrant Population? An External Validation Study.

BACKGROUND: The online Tuberculin Skin Test/Interferon Gamma Release Assay (TST/IGRA) Interpreter V3.0 (TSTin3D), a tool for estimating the risk of active tuberculosis (TB) in individuals with latent TB infection (LTBI), has been in use for more than a decade, but its predictive performance has never been evaluated. METHODS: People with a positive TST or IGRA result from 1985 to 2015 were identified using a health data linkage that involved migrants to British Columbia, Canada. Comorbid conditions at the time of LTBI testing were identified from physician claims, hospitalizations, vital statistics, outpatient prescriptions, and kidney and HIV databases. The risk of developing active TB within 2 and 5 years was estimated using TSTin3D. The discrimination and calibration of these estimates were evaluated. RESULTS: A total of 37 163 individuals met study inclusion criteria; 10.4% were tested by IGRA. Generally, the TSTin3D algorithm assigned higher risks to demographic and clinical groups known to have higher active TB risks. Concordance estimates ranged from 0.66 to 0.68 in 2- and 5-year time frames. Comparing predicted to observed counts suggests that TSTin3D overestimates active TB risks and that overestimation increases over time (with relative bias of 3% and 12% in 2- and 5-year periods, respectively). Calibration plots also suggest that overestimation increases toward the upper end of the risk spectrum. CONCLUSIONS: TSTin3D can discriminate adequately between people who developed and did not develop active TB in this linked database of migrants with predominately positive skin tests. Further work is needed to improve TSTin3D's calibration.

A prospective study of 12-week respiratory outcomes in COVID-19-related hospitalisations.

The long-term respiratory morbidity of COVID-19 remains unclear. We describe the clinical, radiological and pulmonary function abnormalities that persist in previously hospitalised patients assessed 12 weeks after COVID-19 symptom onset, and identify clinical predictors of respiratory outcomes. At least one pulmonary function variable was abnormal in 58% of patients and 88% had abnormal imaging on chest CT. There was strong association between days on oxygen supplementation during the acute phase of COVID-19 and both DLCO-% (diffusion capacity of the lung for carbon monoxide) predicted and total CT score. These findings highlight the need to develop treatment strategies and the importance of long-term respiratory follow-up after hospitalisation for COVID-19.

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.

Ethical challenges in the treatment of non-refugee migrants with tuberculosis in Canada.

While attention to the ethical issues that migrants face in accessing tuberculosis care has increased in the last few years, most of the attention has focused on challenges that refugees face when emigrating. Less attention has been given to ethical challenges that arise in the context of providing tuberculosis treatment and care to non-refugee migrants in high-income countries (HIC), particularly those that do not face immediate danger or violence. In this paper, we analyze some of the ethical challenges associated with treating migrants with tuberculosis in the Canadian context. In particular, we will discuss (i) inter- and intra-jurisdictional issues that challenge quotidian public health governance structures, and (ii) the ethical imperative for the Canadian government and its provinces to clearly differentiate access to healthcare from a person's immigration status to help overcome power imbalances that may exist between public health workers and their clients. The arguments presented herein could potentially apply to other HIC with some form of universal health coverage.

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

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

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

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

Predicting tuberculosis relapse in patients treated with the standard 6-month regimen: an individual patient data meta-analysis.

BACKGROUND: Relapse continues to place significant burden on patients and tuberculosis (TB) programmes worldwide. We aimed to determine clinical and microbiological factors associated with relapse in patients treated with the WHO standard 6-month regimen and then evaluate the accuracy of each factor at predicting an outcome of relapse. METHODS: A systematic review was performed to identify randomised controlled trials reporting treatment outcomes on patients receiving the standard regimen. Authors were contacted and invited to share patient-level data (IPD). A one-step IPD meta-analysis, using random intercept logistic regression models and receiver operating characteristic curves, was performed to evaluate the predictive performance of variables of interest. RESULTS: Individual patient data were obtained from 3 of the 12 identified studies. Of the 1189 patients with confirmed pulmonary TB who completed therapy, 67 (5.6%) relapsed. In multipredictor analysis, the presence of baseline cavitary disease with positive smear at 2 months was associated with an increased odds of relapse (OR 2.3(95% CI 1.3 to 4.2)) and a relapse risk of 10%. When area under the curve for each multipredictor model was compared, discrimination between low-risk and higher-risk patients was modest and similar to that of the reference model which accounted for age, sex and HIV status. CONCLUSION: Despite its poor predictive value, our results indicate that the combined presence of cavitary disease and 2-month positive smear status may be the best currently available marker for identifying individuals at an increased risk of relapse, particularly in resource-limited setting. Further investigation is required to assess whether this combined factor can be used to indicate different treatment requirements in clinical practice.

Diagnostic Accuracy of Stool Xpert MTB/RIF for Detection of Pulmonary Tuberculosis in Children: a Systematic Review and Meta-analysis.

Invasive collection methods are often required to obtain samples for the microbiological evaluation of children with presumptive pulmonary tuberculosis (PTB). Nucleic acid amplification testing of easier-to-collect stool samples could be a noninvasive method of diagnosing PTB. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of testing stool with the Xpert MTB/RIF assay ("stool Xpert") for childhood PTB. Four databases were searched for publications from January 2008 to June 2018. Studies assessing the diagnostic accuracy among children of stool Xpert compared to a microbiological reference standard of conventional specimens tested by mycobacterial culture or Xpert were eligible. Bivariate random-effects meta-analyses were performed to calculate pooled sensitivity and specificity of stool Xpert against the reference standard. From 1,589 citations, 9 studies (n = 1,681) were included. Median participant ages ranged from 1.3 to 10.6 years. Protocols for stool processing and testing varied substantially, with differences in reagents and methods of homogenization and filtering. Against the microbiological reference standard, the pooled sensitivity and specificity of stool Xpert were 67% (95% confidence interval [CI], 52 to 79%) and 99% (95% CI, 98 to 99%), respectively. Sensitivity was higher among children with HIV (79% [95% CI, 68 to 87%] versus 60% [95% CI, 44 to 74%] among HIV-uninfected children). Heterogeneity was high. Data were insufficient for subgroup analyses among children under the age of 5 years, the most relevant target population. Stool Xpert could be a noninvasive method of ruling in PTB in children, particularly those with HIV. However, studies focused on children under 5 years of age are needed, and generalizability of the evidence is limited by the lack of standardized stool preparation and testing protocols.

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

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

The effect of text messaging on latent tuberculosis treatment adherence: a randomised controlled trial.

There is limited high-quality evidence available to inform the use of text messaging to improve latent tuberculosis infection (LTBI) treatment adherence.We performed a parallel, randomised controlled trial at two sites to assess the effect of a two-way short message service on LTBI adherence. We enrolled adults initiating LTBI therapy from June 2012 to September 2015 in British Columbia, Canada. Participants were randomised in a 1:1 ratio to standard LTBI treatment (control) or standard LTBI treatment plus two-way weekly text messaging (intervention). The primary outcome was treatment completion, defined as taking ≥80% prescribed doses within 12 months (isoniazid) or 6 months (rifampin) of enrolment. The trial was unblinded except for the data analyst.A total of 358 participants were assigned to the intervention (n=170) and control (n=188) arms. In intention-to-treat analysis, the proportion of participants completing LTBI therapy in the intervention and control arms was 79.4% and 81.9%, respectively (RR 0.97, 95% CI 0.88-1.07; p=0.550). Results were similar for pre-specified secondary end-points, including time-to-completion of LTBI therapy, completion of >90% of prescribed LTBI doses and health-related quality of life.Weekly two-way text messaging did not improve LTBI completion rates compared to standard LTBI care; however, completion rates were high in both treatment arms.