Impact of COVID-19 on Tuberculosis Prevention and Treatment in Canada: A Multicenter Analysis of 10 833 Patients.

We assessed the COVID-19 pandemic's impact on treatment of latent tuberculosis, and of active tuberculosis, at 3 centers in Montreal and Toronto, using data from 10 833 patients (8685 with latent tuberculosis infection, 2148 with active tuberculosis). Observation periods prior to declarations of COVID-19 public health emergencies ranged from 219 to 744 weeks, and after declarations, from 28 to 33 weeks. In the latter period, reductions in latent tuberculosis infection treatment initiation rates ranged from 30% to 66%. At 2 centers, active tuberculosis treatment rates fell by 16% and 29%. In Canada, cornerstone measures for tuberculosis elimination weakened during the COVID-19 pandemic.

Chest X-ray Analysis With Deep Learning-Based Software as a Triage Test for Pulmonary Tuberculosis: An Individual Patient Data Meta-Analysis of Diagnostic Accuracy.

BACKGROUND: Automated radiologic analysis using computer-aided detection software (CAD) could facilitate chest X-ray (CXR) use in tuberculosis diagnosis. There is little to no evidence on the accuracy of commercially available deep learning-based CAD in different populations, including patients with smear-negative tuberculosis and people living with human immunodeficiency virus (HIV, PLWH). METHODS: We collected CXRs and individual patient data (IPD) from studies evaluating CAD in patients self-referring for tuberculosis symptoms with culture or nucleic acid amplification testing as the reference. We reanalyzed CXRs with three CAD programs (CAD4TB version (v) 6, Lunit v3.1.0.0, and qXR v2). We estimated sensitivity and specificity within each study and pooled using IPD meta-analysis. We used multivariable meta-regression to identify characteristics modifying accuracy. RESULTS: We included CXRs and IPD of 3727/3967 participants from 4/7 eligible studies. 17% (621/3727) were PLWH. 17% (645/3727) had microbiologically confirmed tuberculosis. Despite using the same threshold score for classifying CXR in every study, sensitivity and specificity varied from study to study. The software had similar unadjusted accuracy (at 90% pooled sensitivity, pooled specificities were: CAD4TBv6, 56.9% [95% confidence interval {CI}: 51.7-61.9]; Lunit, 54.1% [95% CI: 44.6-63.3]; qXRv2, 60.5% [95% CI: 51.7-68.6]). Adjusted absolute differences in pooled sensitivity between PLWH and HIV-uninfected participants were: CAD4TBv6, -13.4% [-21.1, -6.9]; Lunit, +2.2% [-3.6, +6.3]; qXRv2: -13.4% [-21.5, -6.6]; between smear-negative and smear-positive tuberculosis was: were CAD4TBv6, -12.3% [-19.5, -6.1]; Lunit, -17.2% [-24.6, -10.5]; qXRv2, -16.6% [-24.4, -9.9]. Accuracy was similar to human readers. CONCLUSIONS: For CAD CXR analysis to be implemented as a high-sensitivity tuberculosis rule-out test, users will need threshold scores identified from their own patient populations and stratified by HIV and smear status.

Gender-based differences in community-wide screening for pulmonary tuberculosis in Karachi, Pakistan: an observational study of 311 732 individuals undergoing screening.

We describe gender-based differences in a community-wide TB screening programme in Karachi, Pakistan, in which 311 732 individuals were screened in mobile camps using symptom questionnaires and van-mounted digital chest X-ray, between 1 January 2018 and 31 December 2019. Only 22.4% (69 869) of camp attendees were women. Female attendees were less likely to have sputum collected and tested (31.5% (95% CI 30.4% to 32.7%) vs 38.5% (95% CI 37.6% to 39.1%)) or to initiate TB treatment (75.9% (95% CI 68.1% to 82.6%) vs 82.8% (95% CI 78.9% to 86.2%)), when indicated. Among the participants, the age-standardised prevalence of active TB was higher among women (prevalence ratio 1.4, 95% CI 1.1 to 1.7). These findings underscore the importance of integrating gender into the design and monitoring of TB screening programmes to ensure that women and men benefit equally from this important intervention.

Standardised shorter regimens versus individualised longer regimens for rifampin- or multidrug-resistant tuberculosis.

We sought to compare the effectiveness of two World Health Organization (WHO)-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis (TB): a standardised regimen of 9-12 months (the "shorter regimen") and individualised regimens of ≥20 months ("longer regimens").We collected individual patient data from observational studies identified through systematic reviews and a public call for data. We included patients meeting WHO eligibility criteria for the shorter regimen: not previously treated with second-line drugs, and with fluoroquinolone- and second-line injectable agent-susceptible RR/MDR-TB. We used propensity score matched, mixed effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRDs) for failure or relapse, death within 12 months of treatment initiation and loss to follow-up.We included 2625 out of 3378 (77.7%) individuals from nine studies of shorter regimens and 2717 out of 13 104 (20.7%) individuals from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions 80.0% versus 75.3%), due to less loss to follow-up with the former (aRD -0.15, 95% CI -0.17- -0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (aRD 0.02, 95% CI 0-0.05) and greater in magnitude with baseline resistance to pyrazinamide (aRD 0.12, 95% CI 0.07-0.16), prothionamide/ethionamide (aRD 0.07, 95% CI -0.01-0.16) or ethambutol (aRD 0.09, 95% CI 0.04-0.13).In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment compared with individualised longer regimens and with more failure or relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.

Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline.

Background: The American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America jointly sponsored this new practice guideline on the treatment of drug-resistant tuberculosis (DR-TB). The document includes recommendations on the treatment of multidrug-resistant TB (MDR-TB) as well as isoniazid-resistant but rifampin-susceptible TB.Methods: Published systematic reviews, meta-analyses, and a new individual patient data meta-analysis from 12,030 patients, in 50 studies, across 25 countries with confirmed pulmonary rifampin-resistant TB were used for this guideline. Meta-analytic approaches included propensity score matching to reduce confounding. Each recommendation was discussed by an expert committee, screened for conflicts of interest, according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.Results: Twenty-one Population, Intervention, Comparator, and Outcomes questions were addressed, generating 25 GRADE-based recommendations. Certainty in the evidence was judged to be very low, because the data came from observational studies with significant loss to follow-up and imbalance in background regimens between comparator groups. Good practices in the management of MDR-TB are described. On the basis of the evidence review, a clinical strategy tool for building a treatment regimen for MDR-TB is also provided.Conclusions: New recommendations are made for the choice and number of drugs in a regimen, the duration of intensive and continuation phases, and the role of injectable drugs for MDR-TB. On the basis of these recommendations, an effective all-oral regimen for MDR-TB can be assembled. Recommendations are also provided on the role of surgery in treatment of MDR-TB and for treatment of contacts exposed to MDR-TB and treatment of isoniazid-resistant TB.

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.

Turning Off the Tap: Using the FAST Approach to Stop the Spread of Drug-Resistant Tuberculosis in the Russian Federation.

Background: We report the association of the FAST strategy (find cases actively, separate safely, and treat effectively) with reduction of hospital-based acquisition of multidrug-resistant tuberculosis in the Russian Federation. Methods: We used preintervention and postintervention cohorts in 2 Russian hospitals to determine whether the FAST strategy was associated with a reduced odds of converting MDR tuberculosis within 12 months among patients with tuberculosis susceptible to isoniazid and rifampin at baseline. Results: Sixty-three of 709 patients (8.9%) with isoniazid and rifampin-susceptible tuberculosis acquired MDR tuberculosis; 55 (12.2%) were in the early cohort, and 8 (3.1%) were in the FAST cohort. The FAST strategy was associated with a reduced odds (adjusted odds ratio, 0.16; 95% confidence interval, .07-.39) and 9.2% absolute reduction in the risk of MDR tuberculosis acquisition. Conclusion: Use of the FAST strategy in 2 Russian hospitals was associated with significantly less MDR tuberculosis 12 months after implementation.

Screening for tuberculosis in migrants and visitors from high-incidence settings: present and future perspectives.

In most settings with a low incidence of tuberculosis (TB), foreign-born people make up the majority of TB cases, but the distribution of the TB risk among different migrant populations is often poorly quantified. In addition, screening practices for TB disease and latent TB infection (LTBI) vary widely. Addressing the risk of TB in international migrants is an essential component of TB prevention and care efforts in low-incidence countries, and strategies to systematically screen for, diagnose, treat and prevent TB among this group contribute to national and global TB elimination goals.This review provides an overview and critical assessment of TB screening practices that are focused on migrants and visitors from high to low TB incidence countries, including pre-migration screening and post-migration follow-up of those deemed to be at an increased risk of developing TB. We focus mainly on migrants who enter the destination country via application for a long-stay visa, as well as asylum seekers and refugees, but briefly consider issues related to short-term visitors and those with long-duration multiple-entry visas. Issues related to the screening of children and screening for LTBI are also explored.

Effectiveness and safety of standardised shorter regimens for multidrug-resistant tuberculosis: individual patient data and aggregate data meta-analyses.

We assessed the effectiveness and safety of standardised, shorter multidrug-resistant tuberculosis (MDR-TB) regimens by pooling data from observational studies.Published studies were identified from medical databases; unpublished studies were identified from expert consultation. We conducted aggregate data meta-analyses to estimate pooled proportions of treatment outcomes and individual patient data (IPD) meta-regression to identify risk factors for unsuccessful treatment in patients treated with 9- to 12-month MDR-TB regimens composed of a second-line injectable, gatifloxacin/moxifloxacin, prothionamide, clofazimine, isoniazid, pyrazinamide and ethambutol.We included five studies in which 796 out of 1279 (62.2%) individuals with confirmed MDR-TB (98.4%) or rifampin-resistant TB (1.6%), and not previously exposed to second-line drugs, were eligible for shorter regimens. 669 out of 796 participants were successfully treated (83.0%, 95% CI 71.9-90.3%). In IPD meta-regression (three studies, n=497), failure/relapse was associated with fluoroquinolone resistance (crude OR 46, 95% CI 8-273), pyrazinamide resistance (OR 8, 95% CI 2-38) and no culture conversion by month 2 of treatment (OR 7, 95% CI 3-202). Two participants acquired extensive drug resistance. Four studies reported grade 3 or 4 adverse events in 55 out of 304 (18.1%) participants.Shorter regimens were effective in treating MDR-TB; however, there is uncertainty surrounding the generalisability of the high rate of treatment success to less selected populations, to programmatic settings and in the absence of drug susceptibility tests to key component drugs.

Aggressive Regimens Reduce Risk of Recurrence After Successful Treatment of MDR-TB.

BACKGROUND: We sought to determine whether treatment with a "long aggressive regimen" was associated with lower rates of relapse among patients successfully treated for pulmonary multidrug-resistant tuberculosis (MDR-TB) in Tomsk, Russia. METHODS: We conducted a retrospective cohort study of adult patients that initiated MDR-TB treatment with individualized regimens between September 2000 and November 2004, and were successfully treated. Patients were classified as having received "aggressive regimens" if their intensive phase consisted of at least 5 likely effective drugs (including a second-line injectable and a fluoroquinolone) used for at least 6 months post culture conversion, and their continuation phase included at least 4 likely effective drugs. Patients that were treated with aggressive regimens for a minimum duration of 18 months post culture conversion were classified as having received "long aggressive regimens." We used recurrence as a proxy for relapse because genotyping was not performed. After treatment, patients were classified as having disease recurrence if cultures grew MDR-TB or they re-initiated MDR-TB therapy. Data were analyzed using Cox proportional hazard regression. RESULTS: Of 408 successfully treated patients, 399 (97.5%) with at least 1 follow-up visit were included. Median duration of follow-up was 42.4 months (interquartile range: 20.5-59.5), and there were 27 recurrence episodes. In a multivariable complete case analysis (n = 371 [92.9%]) adjusting for potential confounders, long aggressive regimens were associated with a lower rate of recurrence (adjusted hazard ratio: 0.22, 95% confidence interval, .05-.92). CONCLUSIONS: Long aggressive regimens for MDR-TB treatment are associated with lower risk of disease recurrence.

Tweaking algorithms. Technopolitical issues associated with artificial intelligence based tuberculosis detection in global health.

Computer-aided detection algorithms based on artificial intelligence are increasingly being tested and used as a means for detecting tuberculosis in countries where the epidemic is still present. Computer-aided detection tools are often presented as a global solution that can be deployed in all the geographical areas concerned by tuberculosis, but at the same time, they need to be adjusted and calibrated according to local populations' characteristics. The aim of this article is to analyze the tensions between the standardization of computer-aided detection algorithms and their local adaptation and the political issues associated with these tensions. We undertook a qualitative analysis of practices associated with tuberculosis detection algorithms in different contexts, contrasting the perspectives of various stakeholders. Algorithms embed the promise of standardization through automation and the bypassing of variable human expertise such as that of radiologists, they are nonetheless objects of local practices that we have characterized as "tweaking." This work of tweaking reveals how the technology is situated but also the many concerns of the users and workers (insertion in care, control over infrastructure, and political ownership). This should be better considered to truly make computer-aided detection innovative tools for tuberculosis management in global health.

Respiratory health and its determinants among Nunavimmiut: results from the Qanuilirpitaa? 2017 Nunavik Health Survey.

OBJECTIVES: Respiratory diseases are the leading cause of hospitalization in Nunavik (northern Québec, Canada) and contribute to disparities in life expectancy with the rest of Canada. As part of Qanuilirpitaa? 2017, a cross-sectional population-based health survey, we sought to describe the prevalence of respiratory health indicators, including the first estimate of airway obstruction based on spirometry in an Inuit population, and explore their associated characteristics. METHODS: We analyzed data from 1296 participants aged 16 years and older, using multivariate logistic regression to assess characteristics associated with spirometry-determined airway obstruction and self-reported respiratory symptoms, i.e., wheezing in the last year and chronic cough during at least 3 months. RESULTS: In this relatively young population (83% aged 16 to 54), the prevalences of wheezing, chronic cough, and airway obstruction were, respectively, 27% (95% CI 24-30), 21% (18-23), and 17% (14-20). These estimates are prone to biases due to the relatively low participation rate (about 37%). The most consistent associations were with smoking (≥ 15 pack-years; odds ratio [OR] 3.13, 3.39, and 2.86 for the three indicators, respectively) and food security (OR 0.55 with wheezing and OR 0.26 with chronic cough), as defined in the Household Food Security Survey Module. Wheezing was also associated with allergic sensitization to dogs (2.60) and obesity (2.18). Chronic cough was associated with respiratory infections during childhood (2.12), housing in need of major repairs (1.72), and housing crowding (1.50), and was negatively associated with participation to traditional activities (0.62) and going on the land (0.64). Airway obstruction was associated with being underweight (3.84) and post-secondary education (0.40). Among young adults and women, wheezing was also associated with any inhalation of solvents for recreational purposes during their lifetime (2.62 and 1.56, respectively), while airway obstruction was associated with regular marijuana use (2.22 and 1.84, respectively). CONCLUSION: Smoking and food insecurity are both highly prevalent and strongly associated with respiratory symptoms in Nunavik. Together with essential smoking prevention and cessation programs, our findings suggest that solving food security and housing crises, improving socioeconomic conditions, and promoting traditional lifestyle may improve respiratory health in Nunavik.

RéSUMé: OBJECTIFS: Les maladies respiratoires sont la première cause d'hospitalisation au Nunavik (Nord-du-Québec, Canada) et contribuent aux écarts d'espérance de vie avec le reste du Canada. Dans le cadre de l'enquête transversale et populationnelle Qanuilirpitaa? 2017, cette étude décrit la prévalence d'indicateurs de santé respiratoire et explore les caractéristiques qui leur sont associées. Elle fournit le premier estimé de la prévalence d'obstruction respiratoire par spirométrie dans la population inuite. MéTHODES: Les données de 1 296 participants âgés de 16 ans et plus ont été analysées par régression logistique multivariée pour évaluer les caractéristiques associées avec le wheezing (dans la dernière année), la toux chronique (durant au moins 3 mois) et l'obstruction bronchique (mesurée par spirométrie). RéSULTATS: Dans cette population relativement jeune (83 % entre 16 et 54 ans), les prévalences de wheezing, de toux chronique et d'obstruction bronchique étaient de 27 % (IC95% 24-30), 21 % (18-23) et 17 % (14-20). Ces estimés pourraient être biaisés puisque le taux de participation à l'enquête était relativement faible (environ 37 %). Les associations les plus fortes et consistantes sont observées avec le tabagisme (≥ 15 paquets-années; RC 3,13, 3,39 et 2,86 pour les trois indicateurs, respectivement) et avec la sécurité alimentaire (RC 0,55 avec le wheezing et 0,26 avec la toux chronique), définie à partir du Module d'enquête sur la sécurité alimentaire des ménages. Le wheezing était notamment associé avec la sensibilisation allergique aux chiens (2,60) et l'obésité (2,18). La toux chronique était associée avec les infections respiratoires sévères dans l'enfance (2,12), un logement ayant besoin de réparations majeures (1,72) et un logement surpeuplé (1,50); tandis que participer aux activités traditionnelles (0,62) et aller souvent dans la nature (0,64) semblaient protecteurs. L'obstruction bronchique était associée avec un faible indice de masse corporelle (3,84) et un niveau de scolarité postsecondaire (0,40). Le wheezing était aussi associé avec le fait d'avoir déjà inhalé des solvants chez les jeunes adultes (2,62) et chez les femmes (1,56), tandis que l'obstruction bronchique était associée avec la consommation régulière de cannabis chez les jeunes adultes (2,22) et chez les femmes (1,84). CONCLUSION: Le tabagisme et l'insécurité alimentaire sont fort prévalents et fortement associés avec des symptômes respiratoires au Nunavik. En plus de rappeler l'importance de la prévention du tabagisme, ces résultats supportent la pertinence des efforts communautaires et gouvernementaux pour résoudre les crises de l'insécurité alimentaire et du logement, améliorer les conditions socioéconomiques et promouvoir la culture inuite afin d'améliorer la santé respiratoire au Nunavik.

Self-tests for COVID-19: What is the evidence? A living systematic review and meta-analysis (2020-2023).

COVID-19 self-testing strategy (COVIDST) can rapidly identify symptomatic and asymptomatic SARS-CoV-2-infected individuals and their contacts, potentially reducing transmission. In this living systematic review, we evaluated the evidence for real-world COVIDST performance. Two independent reviewers searched six databases (PubMed, Embase, Web of Science, World Health Organization database, Cochrane COVID-19 registry, Europe PMC) for the period April 1st, 2020, to January 18th, 2023. Data on studies evaluating COVIDST against laboratory-based conventional testing and reported on diagnostic accuracy, feasibility, acceptability, impact, and qualitative outcomes were abstracted. Bivariate random effects meta-analyses of COVIDST accuracy were performed (n = 14). Subgroup analyses (by sampling site, symptomatic/asymptomatic infection, supervised/unsupervised strategy, with/without digital supports) were conducted. Data from 70 included studies, conducted across 25 countries with a median sample size of 817 (range: 28-784,707) were pooled. Specificity and DOR was high overall, irrespective of subgroups (98.37-99.71%). Highest sensitivities were reported for: a) symptomatic individuals (73.91%, 95%CI: 68.41-78.75%; n = 9), b) mid-turbinate nasal samples (77.79%, 95%CI: 56.03-90.59%; n = 14), c) supervised strategy (86.67%, 95%CI: 59.64-96.62%; n = 13), and d) use of digital interventions (70.15%, 95%CI: 50.18-84.63%; n = 14). Lower sensitivity was attributed to absence of symptoms, errors in test conduct and absence of supervision or a digital support. We found no difference in COVIDST sensitivity between delta and omicron pre-dominant period. Digital supports increased confidence in COVIDST reporting and interpretation (n = 16). Overall acceptability was 91.0-98.7% (n = 2) with lower acceptability reported for daily self-testing (39.5-51.1%). Overall feasibility was 69.0-100.0% (n = 5) with lower feasibility (35.9-64.6%) for serial self-testing. COVIDST decreased closures in school, workplace, and social events (n = 4). COVIDST is an effective rapid screening strategy for home-, workplace- or school-based screening, for symptomatic persons, and for preventing transmission during outbreaks. These data will guide COVIDST policy. Our review demonstrates that COVIDST has paved the way for self-testing in pandemics worldwide.

Tuberculosis-Associated Respiratory Disability in Children, Adolescents, and Adults: Protocol for a Systematic Review and Individual Participant Data Meta-Analysis.

Background: Approximately 2% of the global population has survived tuberculosis (TB). Increasing evidence indicates that a significant proportion of pulmonary TB survivors develop TB-associated respiratory disability, commonly referred to as post-TB lung disease (PLTD) and marked by impaired respiratory function, persistent symptoms, and activity limitations. However, the prevalence, risk factors, and progression of TB-associated respiratory disability throughout the life course are not well understood. To address these gaps, we will undertake a systematic review and individual participant-level data meta-analysis (IPD-MA) focusing on TB-associated respiratory disability in children, adolescents, and adults successfully treated for pulmonary TB. Methods and analysis: We will systematically search MEDLINE, Embase, CENTRAL, Global Index Medicus, and medRxiv for original studies investigating TB-associated respiratory disability in people of all ages who have completed treatment for microbiologically confirmed or clinically diagnosed pulmonary TB. Authors of eligible studies will be invited to contribute de-identified data and form a collaborative group. Primary outcomes will be (1) abnormal lung function based on spirometry parameters and (2) chronic respiratory symptoms. We will estimate the overall and subgroup-specific prevalence of each outcome through IPD meta-analysis. Next, we will develop clinical prediction tools assessing the risk of future TB-associated respiratory disability at (i) the start of TB treatment and (ii) end of TB treatment for those without existing signs of disability. Finally, we will use stepwise hierarchical modelling to identify epidemiological determinants of respiratory disability. Ethics and dissemination: This study has been approved by the ethics review boards at the Rhode Island Hospital (2138217-2) and the Research Institute of the McGill University Health Centre (2024-10345). Individual study authors will be required to obtain institutional approval prior to sharing data. Results will be disseminated through open-access, peer-reviewed publications and conference presentations. Prospero registration number: CRD42024529906.

Breaking the threshold: Developing multivariable models using computer-aided chest X-ray analysis for tuberculosis triage.

OBJECTIVES: Computer-aided detection (CAD) software packages quantify tuberculosis (TB)-compatible chest X-ray (CXR) abnormality as continuous scores. In practice, a threshold value is selected for binary CXR classification. We assessed the diagnostic accuracy of an alternative approach to applying CAD for TB triage: incorporating CAD scores in multivariable modeling. METHODS: We pooled individual patient data from four studies. Separately, for two commercial CAD, we used logistic regression to model microbiologically confirmed TB. Models included CAD score, study site, age, sex, human immunodeficiency virus status, and prior TB. We compared specificity at target sensitivities ≥90% between the multivariable model and the current threshold-based approach for CAD use. RESULTS: We included 4,733/5,640 (84%) participants with complete covariate data (median age 36 years; 45% female; 22% with prior TB; 22% people living with human immunodeficiency virus). A total of 805 (17%) had TB. Multivariable models demonstrated excellent performance (areas under the receiver operating characteristic curve [95% confidence interval]: software A, 0.91 [0.90-0.93]; software B, 0.92 [0.91-0.93]). Compared with threshold scores, multivariable models increased specificity (e.g., at 90% sensitivity, threshold vs model specificity [95% confidence interval]: software A, 71% [68-74%] vs 75% [74-77%]; software B, 69% [63-75%] vs 75% [74-77%]). CONCLUSION: Using CAD scores in multivariable models outperformed the current practice of CAD-threshold-based CXR classification for TB diagnosis.

Diagnostic Accuracy of Computer-Aided Detection During Active Case Finding for Pulmonary Tuberculosis in Africa: A Systematic Review and Meta-analysis.

Background: Computer-aided detection (CAD) may be a useful screening tool for tuberculosis (TB). However, there are limited data about its utility in active case finding (ACF) in a community-based setting, and particularly in an HIV-endemic setting where performance may be compromised. Methods: We performed a systematic review and evaluated articles published between January 2012 and February 2023 that included CAD as a screening tool to detect pulmonary TB against a microbiological reference standard (sputum culture and/or nucleic acid amplification test [NAAT]). We collected and summarized data on study characteristics and diagnostic accuracy measures. Two reviewers independently extracted data and assessed methodological quality against Quality Assessment of Diagnostic Accuracy Studies-2 criteria. Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines were followed. Results: Of 1748 articles reviewed, 5 met with the eligibility criteria and were included in this review. A meta-analysis revealed pooled sensitivity of 0.87 (95% CI, 0.78-0.96) and specificity of 0.74 (95% CI, 0.55-0.93), just below the World Health Organization (WHO)-recommended target product profile (TPP) for a screening test (sensitivity ≥0.90 and specificity ≥0.70). We found a high risk of bias and applicability concerns across all studies. Subgroup analyses, including the impact of HIV and previous TB, were not possible due to the nature of the reporting within the included studies. Conclusions: This review provides evidence, specifically in the context of ACF, for CAD as a potentially useful and cost-effective screening tool for TB in a resource-poor HIV-endemic African setting. However, given methodological concerns, caution is required with regards to applicability and generalizability.

Artificial intelligence-based computer aided detection (AI-CAD) in the fight against tuberculosis: Effects of moving health technologies in global health.

Computer Aided Detection software based on Artificial Intelligence (AI-CAD), combined with chest X-rays have recently been promoted as an easy fix for a complex problem: ending TB by 2030. WHO has recommended the use of such imaging devices in 2021 and many partnerships have helped propose benchmark analysis and technology comparisons to facilitate their "market access". Our aim is to examine the socio-political and health issues that stem from using AI-CAD technology in a global health context conceptualized as a set of practice and ideas organizing global intervention "in the life of others". We also question how this technology, which is not yet fully implemented in routine use, may limit or amplify some inequalities in the care of tuberculosis. We describe AI-CAD through Actor-Network-Theory framework to understand the global assemblage and composite activities associated with detection through AI-CAD, and interrogate how the technology itself may consolidate a specific configuration of "global health". We explore the various dimensions of AI-CAD "health effects model": technology design, development, regulation, institutional competition, social interaction and health cultures. On a broader level, AI-CAD represents a new version of global health's accelerationist model centered on "moving and autonomous-presumed technologies". We finally present key aspects in our research which help discuss the theories mobilized: AI-CAD ambivalent insertion in global health, the social lives of its data: from efficacy to markets and AI-CAD human care and maintenance it requires. We reflect on the conditions that will affect AI-CAD use and its promises. In the end, the risk of new detection technologies such as AI-CAD is indeed that the fight against TB could be reduced to one that is purely technical and technological, with neglect to its social determinants and effects.

Artificial intelligence-reported chest X-ray findings of culture-confirmed pulmonary tuberculosis in people with and without diabetes.

Objectives: We applied computer-aided detection (CAD) software for chest X-ray (CXR) analysis to determine if diabetes affects the radiographic presentation of tuberculosis. Methods: From March 2017-July 2018, we consecutively enrolled adults being evaluated for pulmonary tuberculosis in Karachi, Pakistan. Participants had same-day CXR, two sputum mycobacterial cultures, and random blood glucose measurement. We identified diabetes through self-report or glucose >11.1mMol/L. We included participants with culture-confirmed tuberculosis for this analysis. We used linear regression to estimate associations between CAD-reported tuberculosis abnormality score (range 0.00 to 1.00) and diabetes, adjusting for age, body mass index, sputum smear-status, and prior tuberculosis. We also compared radiographic abnormalities between participants with and without diabetes. Results: 63/272 (23%) of included participants had diabetes. After adjustment, diabetes was associated with higher CAD tuberculosis abnormality scores (p < 0.001). Diabetes was not associated with frequency of CAD-reported radiographic abnormalities apart from cavitary disease; participants with diabetes were more likely to have cavitary disease (74.6% vs 61.2% p = 0.07), particularly non-upper zone cavitary disease (17% vs 7.8%, p = 0.09). Conclusions: CAD analysis of CXR suggests diabetes is associated with more extensive radiographic abnormalities and with greater likelihood of cavities outside upper lung zones.

The association of SARS-CoV-2 infection and tuberculosis disease with unfavorable treatment outcomes: A systematic review.

BACKGROUND: Whether SARS-CoV-2 infection and its management influence tuberculosis (TB) treatment outcomes is uncertain. We synthesized evidence on the association of SARS-CoV-2 coinfection (Coinfection Review) and its management (Clinical Management Review) on treatment outcomes among people with tuberculosis (TB) disease. METHODS: We systematically searched the literature from 1 January 2020 to 6 February 2022. Primary outcomes included: unfavorable (death, treatment failure, loss-to-follow-up) TB treatment outcomes (Coinfection and Clinical Management Review) and/or severe or critical COVID-19 or death (Clinical Management Review). Study quality was assessed with an adapted Newcastle Ottawa Scale. Data were heterogeneous and a narrative review was performed. An updated search was performed on April 3, 2023. FINDINGS: From 9,529 records, we included 11 studies and 7305 unique participants. No study reported data relevant to our review in their primary publication and data had to be contributed by study authors after contact. Evidence from all studies was low quality. Eight studies of 5749 persons treated for TB (286 [5%] with SARS-CoV-2) were included in the Coinfection Review. Across five studies reporting our primary outcome, there was no significant association between SARS-CoV-2 coinfection and unfavorable TB treatment outcomes. Four studies of 1572 TB patients-of whom 291 (19%) received corticosteroids or other immunomodulating treatment-were included in the Clinical Management Review, and two addressed a primary outcome. Studies were likely confounded by indication and discordant findings existed among studies. When updating our search, we still did not identify any study reporting data relevant to this review in their primary publication. INTERPRETATION: No study was designed to answer our research questions of interest. It remains unclear whether TB/SARS-CoV-2 and its therapeutic management are associated with unfavorable outcomes. Research is needed to improve our understanding of risk and optimal management of persons with TB and SARS-CoV-2 infection. TRIAL REGISTRATION: Registration: PROSPERO (CRD42022309818).