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BackgroundThe prevalence of tuberculosis infection (TBI) is critical to designing tuberculosis (TB) prevention strategies, yet it is unknown in Canada. We estimated TBI prevalence among foreign-born Canadians.MethodsUsing a previously developed Gaussian process regression model, annual risk of infection trends abroad were constructed and used to estimate TBI prevalence by age and year of migration to Canada for persons from each of 168 countries. These stratified TBI prevalence estimates were combined with Canadian census data to estimate overall TBI prevalence among foreign-born residents during census years 2001, 2006, 2011, and 2016. We also estimated TBI prevalence according to age, WHO-estimated TB incidence in country of origin, and province/territory of residence. Finally, we estimated the prevalence of TBI acquired within the two preceding years.ResultsEstimated TBI prevalence among foreign-born Canadians overall was 25% (95% uncertainty interval [UI]: 20-35%), 24% (20-33%), 23% (19-30%), and 22% (19-28%) for census years 2001, 2006, 2011, and 2016, respectively. TBI prevalence increased with age at migration and TB incidence in the country of origin. In 2016, estimated TBI prevalence was lowest in Quebec (19%, 95% UI: 16-25) and highest in Alberta and British Columbia, at 24% each. Among all foreign-born Canadian residents with TBI in 2016, we estimated that only 1 in 440 were infected within the two preceding years.InterpretationApproximately 1 in 4 foreign-born Canadians has TBI; estimated prevalence has remained quite stable over the last two decades. However, a very small minority of people with TBI were infected within the last two years—the highest risk period for progression to TB disease. These data may inform future TBI screening policies.

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.

Background Active screening for tuberculosis (TB) involves systematic detection of previously undiagnosed TB disease or latent TB infection (LTBI). It may be an important step toward elimination of TB among Inuit in Canada. We aimed to evaluate the cost-effectiveness of community-wide active screening for TB infection and disease in 2 Inuit communities in Nunavik. Methods We incorporated screening data from the 2 communities into a decision analysis model. We predicted TB-related health outcomes over a 20-year time frame, beginning in 2019. We assessed the cost-effectiveness of active screening in the presence of varying outbreak frequency and intensity. We also considered scenarios involving variation in timing, impact and uptake of screening programs. Results Given a single large outbreak in 2019, we estimated that 1 round of active screening reduced TB disease by 13% (95% uncertainty range -3% to 27%) and was cost saving compared with no screening, over 20 years. In the presence of simulated large outbreaks every 3 years thereafter, a single round of active screening was cost saving, as was biennial active screening. Compared with a single round, we also determined that biennial active screening reduced TB disease by 59% (95% uncertainty range 52% to 63%) and was estimated to cost Can$6430 (95% uncertainty range -$29 131 to $13 658 in 2019 Can$) per additional active TB case prevented. With smaller outbreaks or improved rates of treatment initiation and completion for people with LTBI, we determined that biennial active screening remained reasonably cost-effective compared with no active screening. Interpretation Active screening is a potentially cost-saving approach to reducing disease burden in Inuit communities that have frequent TB outbreaks.

BACKGROUND Deep learning-based radiological image analysis could facilitate use of chest x-rays as triage tests for pulmonary tuberculosis in resource-limited settings. We sought to determine whether commercially available chest x-ray analysis software meet WHO recommendations for minimal sensitivity and specificity as pulmonary tuberculosis triage tests. METHODS We recruited symptomatic adults at the Indus Hospital, Karachi, Pakistan. We compared two software, qXR version 2.0 (qXRv2) and CAD4TB version 6.0 (CAD4TBv6), with a reference of mycobacterial culture of two sputa. We assessed qXRv2 using its manufacturer prespecified threshold score for chest x-ray classification as tuberculosis present versus not present. For CAD4TBv6, we used a data-derived threshold, because it does not have a prespecified one. We tested for non-inferiority to preset WHO recommendations (0·90 for sensitivity, 0·70 for specificity) using a non-inferiority limit of 0·05. We identified factors associated with accuracy by stratification and logistic regression. FINDINGS We included 2198 (92·7%) of 2370 enrolled participants. 2187 (99·5%) of 2198 were HIV-negative, and 272 (12·4%) had culture-confirmed pulmonary tuberculosis. For both software, accuracy was non-inferior to WHO-recommended minimum values (qXRv2 sensitivity 0·93 [95% CI 0·89-0·95], non-inferiority p=0·0002; CAD4TBv6 sensitivity 0·93 [0·90-0·96], p

BackgroundChest X-ray (CXR) screening is a useful diagnostic tool to test individuals at high risk of tuberculosis (TB), yet image interpretation requires trained human readers who are in short supply in many high TB burden countries. Therefore, CXR interpretation by computer-aided detection software (CAD) may overcome some of these challenges, but evidence on its accuracy is still limited.We established a CXR library with images and metadata from individuals and risk groups that underwent TB screening in a variety of countries to assess the diagnostic accuracy of three commercial CAD solutions through an individual participant meta-analysis.Methods and findingsWe collected digital CXRs and demographic and clinical data from 6 source studies involving a total of 2756 participants, 1753 (64%) of whom also had microbiological test information. All CXR images were analyzed with CAD4TB v6 (Delft Imaging), Lunit Insight CXR TB algorithm v4.9.0 (Lunit Inc.), and qXR v2 (Qure.ai) and re-read by an expert radiologist who was blinded to the initial CXR reading, the CAD scores, and participant information. While the performance of CAD varied across source studies, the pooled, meta-analyzed summary receiver operating characteristic (ROC) curves of the three products against a microbiological reference standard were similar, with area under the curves (AUCs) of 76.4 (95% CI 72.1-80.3) for CAD4TB, 83.3 (95% CI 78.4-87.2) for Lunit, and 76.4 (95% CI 72.1-80.3) for qXR. None of the CAD products, or the radiologists, met the targets for a triage test of 90% sensitivity and 70% specificity. At the same sensitivity of the expert radiologist (94.0%), all CAD had slightly lower point estimates for specificity (22.4% (95% CI 16.9-29.0) for CAD4TB, 34.6% (95% CI 25.3-45.1) for qXR, and 41.0% (95% CI 30.1-53.0) for Lunit compared to 45.6% for the expert radiologist). At the same specificity of 45.6%, all CAD products had lower point estimates for sensitivity but overlapping CIs with the sensitivity estimate of the radiologist.ConclusionsWe showed that, overall, three commercially available CAD products had a reasonable diagnostic accuracy for microbiologically confirmed pulmonary TB and may achieve a sensitivity and specificity that approximates those of experienced radiologists. While threshold setting and cost-effectiveness modelling are needed to inform the optimal implementation of CAD products as part of screening programs, the availability of CAD will assist in scaling up active case finding for TB and hence contribute to TB elimination in these settings.

Background Before August 2021, the only regimen recommended by the World Health Organization (WHO) to treat pediatric drug-susceptible tuberculous meningitis was a 12-month regimen consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide (2HRZE/10HR). The comparative effectiveness of shorter regimens is unknown. Methods To inform a WHO guideline update, we undertook a systematic review and meta-analysis to evaluate outcomes from regimens of 6- to less than 12-months’ duration that included, at a minimum, isoniazid, rifampicin, and pyrazinamide. We included studies that applied rigorous diagnostic criteria and reported outcomes for ≥10 children or adolescents. Using generalized linear mixed models, we estimated the random effects pooled proportions of patients with key outcomes. Results Of 7 included studies, none compared regimens head-to-head. Three studies (724 patients) used a 6-month intensive regimen, which includes isoniazid and rifampicin at higher doses, pyrazinamide, and ethionamide instead of ethambutol (6HRZEto). Outcomes for this versus the 12-month regimen (282 patients, 3 studies) were, respectively, as follows: death, 5.5% (95% confidence interval [CI], 2.1%–13.4%) vs 23.9% (95% CI, 17.5%–31.7%); treatment success (survival with or without sequelae), 94.6% (95% CI, 73.9%–99.1%) vs 75.4% (95% CI, 68.7%–81.1%); and neurological sequelae among survivors, 66.0% (95% CI, 55.3%–75.3%) vs 36.3% (95% CI, 30.1%–43.0%). Relapse did not occur among 148 patients followed-up for 2 years after completing the 6-month intensive regimen. Conclusions Our findings are limited by the small number of studies and substantial potential for confounding. Nonetheless, the 6HRZEto regimen was associated with high treatment success and is now recommended by WHO as an alternative to the 12-month regimen.

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.

Background In settings without access to rapid expert radiographic interpretation, artificial intelligence (AI)–based chest radiograph (CXR) analysis can triage persons presenting with possible tuberculosis (TB) symptoms, to identify those who require additional microbiological testing. However, there is limited evidence of the cost-effectiveness of this technology as a triage tool. Methods A decision analysis model was developed to evaluate the cost-effectiveness of triage strategies with AI-based CXR analysis for patients presenting with symptoms suggestive of pulmonary TB in Karachi, Pakistan. These strategies were compared to the current standard of care using microbiological testing with smear microscopy or GeneXpert, without prior triage. Positive triage CXRs were considered to improve referral success for microbiologic testing, from 91% to 100% for eligible persons. Software diagnostic accuracy was based on a prospective field study in Karachi. Other inputs were obtained from the Pakistan TB Program. The analysis was conducted from the healthcare provider perspective, and costs were expressed in 2020 US dollars. Results Compared to upfront smear microscopy for all persons with presumptive TB, triage strategies with AI-based CXR analysis were projected to lower costs by 19%, from $23233 per 1000 persons, and avert 3%–4% disability-adjusted life-years (DALYs), from 372 DALYs. Compared to upfront GeneXpert, AI-based triage strategies lowered projected costs by 37%, from $34346 and averted 4% additional DALYs, from 369 DALYs. Reinforced follow-up for persons with positive triage CXRs but negative microbiologic tests was particularly cost-effective. Conclusions In lower-resource settings, the addition of AI-based CXR triage before microbiologic testing for persons with possible TB symptoms can reduce costs, avert additional DALYs, and improve TB detection., We evaluated the cost-effectiveness of artificial intelligence–based chest radiograph analysis for tuberculosis detection, based on a trial in Pakistan. Compared to upfront sputum testing, use of this technology to triage people with symptoms reduced costs and averted disability-adjusted life-years.

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.

Summary 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 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.

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.

Background: The WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population. Methods: In this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895. Findings: We identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72–89) and specificity was 42% (29–57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61–88]), but higher specificity (74% [61–83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (2), and lymphadenopathy had high specificities (80–90%) but low sensitivities (29–43%). The WHO-recommended algorithm had a sensitivity of 58% (50–66) and a specificity of 99% (98–100); Xpert for all had a sensitivity of 68% (57–76) and a specificity of 99% (98–99). In the one study that assessed both, the sensitivity of sputum Xpert Ultra was higher than sputum Xpert (73% [62–81] vs 57% [47–67]) and specificities were similar (98% [96–98] vs 99% [98–100]). Among outpatients on ART (4309 [99·1%] of 4347 people on ART), W4SS sensitivity was 53% (35–71) and specificity was 71% (51–85). In this population, a parallel strategy (two tests done at the same time) of W4SS with any chest x-ray abnormality had higher sensitivity (89% [70–97]) and lower specificity (33% [17–54]; n=2670) than W4SS alone; at a tuberculosis prevalence of 5%, this strategy would require 379 more rapid diagnostic tests per 1000 people living with HIV than W4SS but detect 18 more tuberculosis cases. Among outpatients not on ART (11 160 [71·8%] of 15 541 outpatients), W4SS sensitivity was 85% (76–91) and specificity was 37% (25–51). C-reactive protein (≥10 mg/L) alone had a similar sensitivity to (83% [79–86]), but higher specificity (67% [60–73]; n=3187) than, W4SS and a sequential strategy (both test positive) of W4SS then C-reactive protein (≥5 mg/L) had a similar sensitivity to (84% [75–90]), but higher specificity than (64% [57–71]; n=3187), W4SS alone; at 10% tuberculosis prevalence, these strategies would require 272 and 244 fewer rapid diagnostic tests per 1000 people living with HIV than W4SS but miss two and one more tuberculosis cases, respectively. Interpretation: C-reactive protein reduces the need for further rapid diagnostic tests without compromising sensitivity and has been included in the updated WHO tuberculosis screening guidelines. However, C-reactive protein data were scarce for outpatients on ART, necessitating future research regarding the utility of C-reactive protein in this group. Chest x-ray can be useful in outpatients on ART when combined with W4SS. The WHO-recommended algorithm has suboptimal sensitivity; Xpert for all offers slight sensitivity gains and would have major resource implications. Funding: World Health Organization.

The COVID-19 pandemic and response measures, including lockdowns and the reorientation of health services, have disrupted essential health services for other diseases, including TB, HIV and malaria. For TB, reductions in case detection due to the COVID-19 pandemic are projected to result in increased TB transmission, morbidity and mortality. Active case-finding (ACF) for TB using community-based approaches is a potential strategy to offset reductions in TB detection by obviating the need for patients to seek care at a health facility. A number of approaches can be used to conduct TB ACF safely and screen designated target populations while managing the risks of SARS-CoV-2 transmission for staff, individuals and the community. We present a framework of options for and experience of adapting TB ACF services in response to the challenges of COVID-19 in our programme in Yogyakarta, Indonesia. Key changes have included revised prioritisation of target populations focusing on household contacts, reducing case-finding throughput, implementation of additional infection control measures and precautions, and integration of COVID-19 screening among those being screened for TB. Our approach could inform other programmes seeking to adapt TB ACF services to mitigate the negative impact of COVID-19 on TB case detection.La pandémie de COVID-19 et les mesures de riposte incluant des confinements et une réorientation des services de santé ont perturbé les services de santé essentiels destinés aux autres maladies comme la TB, le VIH et le paludisme. En ce qui concerne la TB, les réductions de la détection des cas dues à la pandémie de COVID-19 devrait entraîner une augmentation de la transmission, morbidité et mortalité de la TB. La recherche active des cas (ACF) de TB grâce à des approches communautaires est une stratégie potentielle visant à compenser pour les réductions de détection de la TB en écartant le besoin pour les patients de solliciter des soins dans un structure de santé. Plusieurs approches peuvent être utilisées pour réaliser l’ACF TB de façon sûre et de dépister des populations cibles désignées tout en gérant les risques de transmission du SARS-CoV-2 pour le personnel, les individus et la communauté. Nous présentons un cadre d’options et d’expériences d’adaptation des services TB ACF en réponse aux défis du COVID-19 dans notre programme à Yogyakarta, Indonésie. Les changements majeurs ont inclus une révision des priorités des populations cibles focalisée sur les contacts domiciliaires ; une réduction de la cadence de la recherche de cas ; la mise en œuvre de mesures supplémentaires de lutte contre l’infection et de précautions ; et l’intégration du dépistage de COVID-19 parmi ceux dépistés pour la TB. Notre approche pourrait informer d’autres programmes voulant adapter les services TB ACF afin d’atténuer l’impact négatif du COVID-19 sur la détection des cas de TB.

ObjectiveTo determine the diagnostic accuracy of serological tests for coronavirus disease-2019 (covid-19).DesignSystematic review and meta-analysis.Data sourcesMedline, bioRxiv, and medRxiv from 1 January to 30 April 2020, using subject headings or subheadings combined with text words for the concepts of covid-19 and serological tests for covid-19.Eligibility criteria and data analysisEligible studies measured sensitivity or specificity, or both of a covid-19 serological test compared with a reference standard of viral culture or reverse transcriptase polymerase chain reaction. Studies were excluded with fewer than five participants or samples. Risk of bias was assessed using quality assessment of diagnostic accuracy studies 2 (QUADAS-2). Pooled sensitivity and specificity were estimated using random effects bivariate meta-analyses.Main outcome measuresThe primary outcome was overall sensitivity and specificity, stratified by method of serological testing (enzyme linked immunosorbent assays (ELISAs), lateral flow immunoassays (LFIAs), or chemiluminescent immunoassays (CLIAs)) and immunoglobulin class (IgG, IgM, or both). Secondary outcomes were stratum specific sensitivity and specificity within subgroups defined by study or participant characteristics, including time since symptom onset.Results5016 references were identified and 40 studies included. 49 risk of bias assessments were carried out (one for each population and method evaluated). High risk of patient selection bias was found in 98% (48/49) of assessments and high or unclear risk of bias from performance or interpretation of the serological test in 73% (36/49). Only 10% (4/40) of studies included outpatients. Only two studies evaluated tests at the point of care. For each method of testing, pooled sensitivity and specificity were not associated with the immunoglobulin class measured. The pooled sensitivity of ELISAs measuring IgG or IgM was 84.3% (95% confidence interval 75.6% to 90.9%), of LFIAs was 66.0% (49.3% to 79.3%), and of CLIAs was 97.8% (46.2% to 100%). In all analyses, pooled sensitivity was lower for LFIAs, the potential point-of-care method. Pooled specificities ranged from 96.6% to 99.7%. Of the samples used for estimating specificity, 83% (10 465/12 547) were from populations tested before the epidemic or not suspected of having covid-19. Among LFIAs, pooled sensitivity of commercial kits (65.0%, 49.0% to 78.2%) was lower than that of non-commercial tests (88.2%, 83.6% to 91.3%). Heterogeneity was seen in all analyses. Sensitivity was higher at least three weeks after symptom onset (ranging from 69.9% to 98.9%) compared with within the first week (from 13.4% to 50.3%).ConclusionHigher quality clinical studies assessing the diagnostic accuracy of serological tests for covid-19 are urgently needed. Currently, available evidence does not support the continued use of existing point-of-care serological tests.Study registrationPROSPERO CRD42020179452.

Summary Background Reaching the UN General Assembly High-Level Meeting on Tuberculosis target of providing tuberculosis preventive treatment to at least 30 million people by 2022, including 4 million children under the age of 5 years and 20 million other household contacts, will require major efforts to strengthen health systems. The aim of this study was to evaluate the effectiveness and cost-effectiveness of a health systems intervention to strengthen management for latent tuberculosis infection (LTBI) in household contacts of confirmed tuberculosis cases. Methods ACT4 was a cluster-randomised, open-label trial involving 24 health facilities in Benin, Canada, Ghana, Indonesia, and Vietnam randomly assigned to either a three-phase intervention (LTBI programme evaluation, local decision making, and strengthening activities) or control (standard LTBI care). Tuberculin and isoniazid were provided to control and intervention sites if not routinely available. Randomisation was stratified by country and restricted to ensure balance of index patients with tuberculosis by arm and country. The primary outcome was the number of household contacts who initiated tuberculosis preventive treatment at each health facility within 4 months of the diagnosis of the index case, recorded in the first or last 6 months of our 20-month study. To ease interpretation, this number was standardised per 100 newly diagnosed index patients with tuberculosis. Analysis was by intention to treat. Masking of staff at the coordinating centre and sites was not possible; however, those analysing data were masked to assignment of intervention or control. An economic analysis of the intervention was done in parallel with the trial. ACT4 is registered at ClinicalTrials.gov , NCT02810678 . Findings The study was done between Aug 1, 2016, and March 31, 2019. During the first 6 months of the study the crude overall proportion of household contacts initiating tuberculosis preventive treatment out of those eligible at intervention sites was 0·21. After the implementation of programme strengthening activities, the proportion initiating tuberculosis preventive treatment increased to 0·35. Overall, the number of household contacts initiating tuberculosis preventive treatment per 100 index patients with tuberculosis increased between study phases in intervention sites (adjusted rate difference 60, 95% CI 4 to 116), while control sites showed no statistically significant change (−12, −33 to 10). There was a difference in rate differences of 72 (95% CI 10 to 134) contacts per 100 index patients with tuberculosis initiating preventive treatment associated with the intervention. The total cost for the intervention, plus LTBI clinical care per additional contact initiating treatment was estimated to be CA$1348 (range 724 to 9708). Interpretation A strategy of standardised evaluation, local decision making, and implementation of health systems strengthening activities can provide a mechanism for scale-up of tuberculosis prevention, particularly in low-income and middle-income countries. Funding Canadian Institutes of Health Research

BackgroundRelapse 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.MethodsA 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.ResultsIndividual 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.ConclusionDespite 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.

Nosocomial transmission contributes to the spread of multidrug-resistant (MDR) tuberculosis to patients with drug-susceptible tuberculosis. Use of the FAST strategy in 2 Russian hospitals was associated with significantly less MDR tuberculosis after 12 months., 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.

We agree wholeheartedly with Drs. Batt and Khan’s description of rifampin as “unequivocally the most important drug in the global fight against [tuberculosis] TB.”[1][1] However, using a drug effectively requires that it be available in the first place. Disturbingly, rifampin is becoming

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%

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., 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.

The ability to treat fracture with open reduction and internal fixation (OR/IF) has dramatically revolutionized the approach to mandible fracture. With OR/IF, the postoperative role of rigid maxilla mandibular fixation (MMF) has declined, but it is used to maintain proper occlusion until internal fixation of the fracture is achieved. Objectives: The main objective of the study is to compare treatment outcomes of mandibular fractures in 3D vs conventional miniplates in patients presenting in tertiary care hospital. Methodology of the study: This is randomized controlled trial conducted in the Department of Oral and Maxillofacial Surgery, University Dental Hospital, The University of Lahore. This study was carried out over a period of six months from 23-11-2017 to 22-05-2018.A total of 66 cases (33 in each group) were included in the study. In Group-A, patients were treated with 3-Dimensional miniplates of 2mm thickness while in Group-B, patients were treated with conventional miniplates (2D) of 2mm thickness. Results: Mean age of the patients was 33.7±11.1 and 33.8±10.8 years in group-A and B, respectively. In group-A 30 patients (90.9%) and in group-B 29 patients (87.9%) were male while 3 patients (9.1%) of group-A and 4 patients (12.1%) of group-B were female. Mean duration of procedure in group-A was 53.9±3.8 and in group-B 62.2±3.1 minutes. Anatomical reduction in group-A was statistically significant as compared to group-B (p=0.020). Optimal occlusion was better in group-A when compared with group-B. Distribution of patients by diagnosis in group-A and B, as follows: Symphysis 4 (12.3%) vs 6 (18.2%), parasymphysis 23 (69.7%) vs 19 (57.6%), body 1 (3%) vs 2 (6%) and angle 5 (15%) vs 6 (18.2%). Stratification with regard to age, gender and duration of procedure was also carried out. Conclusion: In conclusion, 3D titanium miniplates are effective in the treatment of mandibular fractures as compared to conventional miniplates in terms of anatomical reduction and optimal occlusion. Thus, 3D plate can be used as an alternative to conventional miniplates. The system is reliable and effective treatment modality for mandibular fractures Key Words: 3D miniplates, Conventional miniplates Mandibular fractures, Internalf ixation, Open reduction

We undertook a systematic review of the diagnostic accuracy of artificial intelligence-based software for identification of radiologic abnormalities (computer-aided detection, or CAD) compatible with pulmonary tuberculosis on chest x-rays (CXRs). We searched four databases for articles published between January 2005-February 2019. We summarized data on CAD type, study design, and diagnostic accuracy. We assessed risk of bias with QUADAS-2. We included 53 of the 4712 articles reviewed: 40 focused on CAD design methods (“Development” studies) and 13 focused on evaluation of CAD (“Clinical” studies). Meta-analyses were not performed due to methodological differences. Development studies were more likely to use CXR databases with greater potential for bias as compared to Clinical studies. Areas under the receiver operating characteristic curve (median AUC [IQR]) were significantly higher: in Development studies AUC: 0.88 [0.82–0.90]) versus Clinical studies (0.75 [0.66–0.87]; p-value 0.004); and with deep-learning (0.91 [0.88–0.99]) versus machine-learning (0.82 [0.75–0.89]; p = 0.001). We conclude that CAD programs are promising, but the majority of work thus far has been on development rather than clinical evaluation. We provide concrete suggestions on what study design elements should be improved.

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.

Item does not contain fulltext BACKGROUND: Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis. METHODS: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration. FINDINGS: Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0.15, 95% CI 0.11 to 0.18), levofloxacin (0.15, 0.13 to 0.18), carbapenems (0.14, 0.06 to 0.21), moxifloxacin (0.11, 0.08 to 0.14), bedaquiline (0.10, 0.05 to 0.14), and clofazimine (0.06, 0.01 to 0.10). There was a significant association between reduced mortality and use of linezolid (-0.20, -0.23 to -0.16), levofloxacin (-0.06, -0.09 to -0.04), moxifloxacin (-0.07, -0.10 to -0.04), or bedaquiline (-0.14, -0.19 to -0.10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I(2) method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses. INTERPRETATION: Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

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.

Introduction: Ceramics are still the most aesthetically pleasing materials available for restorative dentistry. However, due to the metal infrastructure of metal-supported ceramic systems, which were developed to increase the physical properties, esthetic and biological adaptations cannot be fully obtained. Objective of the study: The main objective of the study is to find the evidence on resin bonding related to long-term clinical outcomes of tooth- and implant-supported high-strength ceramic restorations. Methodology of the study: Four different surface processes were used as surface-treatment procedures. The first three procedures were applied to samples of IPS Empress and IPS Empress 2 ceramic discs. Sandblasting with Al2O3, blasting with soda and glass beads, and the Bateman etch retention system were applied to samples of In-Ceram ceramic discs. The discs were cemented to composite bars. Two types of cement were used; Rely X adhesive resin cement and Rely X modified glass ionomer cement and, all the samples were subjected to a shear test to evaluate their bond strengths. Results: With the IPS Empress and the IPS Empress 2 ceramic discs, the best bonding was obtained in the group etched with Al2O3 sandblasting and hydrofluoric acid after cementation using the Rely X adhesive resin cement. Conclusion: The in vitro findings from this study indicate that surface-treatment procedures applied to the IPS Empress and the IPS Empress 2 fullceramic systems are important when cement types are considered. In contrast, cement types and surface-treatment methods had no effect on changing the bond strength of the In-Ceram ceramic system. Key words: Ceramics, cement, treatment, bonding.

Objective: In this study, rabbit bone marrow cells were used to evaluate different titanium, tantalum and alloys for dental implant surfaces. Bone marrow stromal cells of femora from young adult rabbits produce bone-like mineralized tissue in culture. We evaluated three implant materials (pure titanium, tantalum and alloy of Ti-Al-Va), as to their ability to provide an environment for marrow cells to differentiate into osteoblasts and function as suitable for mineralized tissue formation. Materials and methods: Rabbit bone marrow cells were cultured on the disc-shaped test substrates for 15 days. The culture medium was changed daily and examined for calcium and phosphate concentrations. After 15 days specimens were examined by different methods The DNA content, alkaline phosphatase (ALP) activity and aluminium (Al) content in culture were also studied. Results: DNA measurement showed no difference between each material, but alkaline phosphatase activity and aluminium content in the culture on hydroxyapatite and glass-ceramics was higher than on Ti-Al-Va alloy and the control. All test substrates facilitated rabbit bone marrow growth of extracellular matrix formation.

Key gaps limit the evidence base for computer-aided reading of TB on CXR. We describe a research agenda to fill themhttp://ow.ly/JkmQ30cynWR

Summary Background Tuberculous meningitis disproportionately affects young children. We aimed to characterise treatment outcomes for this deadliest and most debilitating form of tuberculosis. Methods We did a systematic review and meta-analysis of childhood tuberculous meningitis studies published up to Oct 12, 2012. We included study reports that applied predefined diagnostic criteria and described treatment regimens and outcomes. We pooled risks of death during treatment and neurological sequelae among survivors. As secondary objectives, we assessed study-level characteristics as sources of heterogeneity, and we pooled frequencies of presenting symptoms and diagnostic findings. For all meta-analyses we used random-effects models with the exact binomial likelihood method. Findings 19 studies met our inclusion criteria, with reported treatment outcomes for 1636 children. Risk of death was 19·3% (95% CI 14·0–26·1) and probability of survival without neurological sequelae was 36·7% (27·9–46·4). Among survivors, risk of neurological sequelae was 53·9% (95% CI 42·6–64·9). Diagnosis in the most advanced disease stage (3) occurred in 307 (47%) of 657 patients and was associated with worse outcomes than was earlier diagnosis. The most common findings at presentation were cerebrospinal fluid (CSF) leucocytosis (frequency 99·9%, 95% CI 68·5–100·0), CSF lymphocytosis (97·9%, 51·9–100·0), fever (89·8%, 79·8–95·2), and hydrocephalus (86·1%, 68·6–94·6). Frequency of CSF acid-fast-bacilli smear positivity was 8·9% (95% CI 5·0–15·4), and frequency of CSF culture positivity for Mycobacterium tuberculosis was 35·1% (16·8–59·2). Interpretation Despite treatment, childhood tuberculous meningitis has very poor outcomes. Poor prognosis and difficult early diagnosis emphasise the importance of preventive therapy for child contacts of patients with tuberculosis and low threshold for empirical treatment of tuberculous meningitis suspects. Implementation of consensus definitions, standardised reporting of data, and high-quality clinical trials are needed to clarify optimum therapy. Funding None.

BACKGROUND Between November 2011 and November 2012, an Inuit village in Nunavik, Quebec experienced a surge in the occurrence of active TB; contact investigations showed that TB infection was highly prevalent (62.6%), particularly among those over age 14 years (78.8%). A nested case-control study showed that nutritional inadequacy was associated with acquisition of infection but not progression to disease. We performed a study to determine whether characteristics of one's dwelling were associated with 1) acquisition of newly diagnosed TB infection and 2) progression to confirmed or probable disease among those with TB infection. METHODS In this nested case-control study, we enrolled 200 people who were household or social contacts of at least 1 person with active TB or had received a diagnosis of active TB and assessed whether characteristics of their dwellings were associated with their odds of having newly diagnosed TB infection and/or odds of progression to disease between November 2011 and November 2012. For our first objective, we compared participants with newly diagnosed TB infection (regardless of their disease status) to a control group of contacts who were uninfected. For the second objective, we compared participants with confirmed or probable disease to a control group consisting of those with infection but no disease. We used information collected during investigation of the contacts and from study questionnaires to determine whether participants may have been exposed to TB in their own home (if they had shared a dwelling with someone who had smear-positive TB during the outbreak) or in other dwellings that they visited at least weekly. RESULTS The participants lived in 79 dwellings. The mean number of people per room was 1.1 (standard deviation [SD] 0.5). The mean room size and ventilation level of the common living space (kitchen and living/dining rooms) were 67.9 (SD 9.4) m3 and 1.69 (SD 0.26) air changes per hour, respectively. After adjustment for potential confounders, the number of people per room was positively associated with the odds of newly diagnosed infection and odds of disease, but only among participants who lived with someone with smear-positive TB (the minority of participants). Other dwelling characteristics were not associated with either outcome. INTERPRETATION Reducing household crowding may contribute to TB prevention. Overall, our investigations have not identified associations that explain the elevated disease risk in this village. In light of our results and considering the high prevalence of TB infection, treatment of latent infection is an essential intervention for long-term reduction of TB incidence in this village.

Background. Human immunodeficiency virus (HIV) infection increases the risk of poor outcomes in active tuberculosis. We updated a systematic review and meta-analysis assessing the effects of duration of rifamycins, schedule of dosing, and antiretroviral therapy (ART) on failure, relapse, death during treatment, and acquired drug resistance (ADR) in patients with HIV and active tuberculosis. Methods. We searched for randomized control trials (RCTs) and observational studies published between January 2008 and November 2011. We pooled risk differences (RD) from RCTs comparing rifampin for >= 9 months and 6 months. Within strata of the 3 treatment covariates, we calculated pooled risks and adjusted odds ratios (aORs) using outcomes from RCTs and observational studies. Results. After screening 2293 citations, 7 studies were added in the update. Risk of relapse was lowered with rifampin treatment for >= 9 months compared with 6 months (pooled RD = -9.1%; 95% CI, -16.5, -1.8). Odds of relapse were higher with shorter durations of rifamycins (aOR 2 vs >= 8 months = 5.0 [1.9, 13.2]; 6 vs >= 8 months = 2.4 [1.2, 5.0]) and in the absence of ART (aOR = 14.3, [2.1, 97.8]). Post hoc meta-regression restricted to arms with ART demonstrated no associations between rifamycin duration, dosing schedule, and outcomes. Conclusions. In patients with HIV and active tuberculosis, ART reduces the risk of TB relapse. Use of rifamycins for >= 8 months and daily dosing in the intensive phase also improve TB treatment outcomes; however, a paucity of evidence makes their importance less clear for patients on ART. There is an urgent need to increase the number of coinfected patients receiving ART.

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 countryviaapplication 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.

An estimated 9 million new tuberculosis (TB) cases and 1.5 million deaths were caused by Mycobacterium tuberculosis in 2013 [1], more than 80% of which occurred in the 22 highest TB burden countries (HBCs). Among the confirmed incident cases, 4.9 million were pulmonary TB (PTB), of which 58% were bacteriologically confirmed. For many of these cases, chest radiography (CXR) was used as an important tool for triaging, particularly in smear-negative patients, to select patients for further microbiological workup with culture or Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) [2, 3]. For the diagnosis of 42% of PTB cases who were microbiologically negative, CXR was often used to support the clinical decision, particularly in children [1, 4]. CXR is used widely in the 22 highest TB burden countries but we need strategies for cost and human resources We thank all participants of the 22 high TB burden countries for their time and support. We additionally would like to thank Yogesh Jha (Medecins sans Frontieres, Paris, France) and Faiz Ahmad Khan (Montreal Chest Institute, Montreal, QC, Canada) for contacting additional participants in countries where it was difficult to receive a response. Srinath Satyanarayana (McGill University, Montreal, QC, Canada), Neeraj Raizada (Foundation for Innovative Diagnostics, Geneva, Switzerland), Sandra Kik (KNCV Tuberculosis Foundation, The Hague, The Netherlands) and Sarder Hossain (TB control program, BRAC, Dhaka, Bangladesh) helped greatly in improving the survey instrument.

Background Little is known about the epidemiology of interstitial lung disease (ILD) amongst Canada's Indigenous populations. Clinicians working in Eeyou Istchee (the Cree territory of the James Bay region of Quebec, population 17, 956) suspected that ILD was more common in this area. We sought to identify all prevalent and incident cases of ILD in Eeyou Istchee between 2006 and 2013, to describe characteristics of affected patients, distribution of subtypes, and estimate disease incidence. Methods Potential ILD cases amongst Eeyou Istchee residents were identified by searching hospitalization databases and lists of patients on long term home oxygen in the region's nine communities, and surveying physicians and nurses. Clinical, radiological and pathological data were reviewed. Potential cases were classified as 'Definite ILD' if an open lung biopsy demonstrated ILD or, in the absence of histopathologic confirmation, if their thoracic CT imaging was deemed consistent with ILD by a panel of two respirologists and a chest radiologist. Potential cases for whom CT images could not be retrieved for our review were not eligible for classification as Definite ILD, unless they had undergone open lung biopsy. The Definite ILD group was further categorized by subtype of ILD. For usual interstitial pneumonia and non-specific interstitial pneumonitis patterns, we assumed cases were idiopathic in the absence of documentation of connective tissue disease or occupational exposures in the medical chart. For Definite ILD and the most common subtype, we calculated the average annual incidence rates, age-standardized to the province of Quebec, for 2006 to 2013, using a gamma distribution to calculate 95% confidence intervals. Results Of 167 potential cases, 52 were categorized as Definite ILD: 14 on the basis of histopathology and 38 on the basis of CT imaging alone. Six patients had a prior history of connective tissue disease. Information on occupation was recorded in the charts of 18/52 (35%) cases, and missing in the remainder. We found the most common subtype was idiopathic pulmonary fibrosis (27/52, 52%), followed by idiopathic non-specific interstitial pneumonia (13/52, 25%), and secondary usual interstitial pneumonia associated with connective tissue diseases (5/52, 10%). The age-standardized annual incidence between 2006-2013 was 80 per 100,000 person-years observed (PYO) for ILD, and 46 per 100,000 PYO for idiopathic pulmonary fibrosis. Interpretation The incidence of ILD and of idiopathic pulmonary fibrosis in Eeyou Istchee may be higher than rates reported in other populations; however, cautious interpretation is required due to the lack of histopathological confirmation in the majority of cases, and our reliance on chart review to exclude secondary causes. A prospective study of incident cases with standardized assessments to establish the types of ILD and to assess for potential causes could overcome some of the limitations of the present analysis. Studies evaluating ILD incidence and subtype distribution in other Indigenous populations would also be of interest.

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.