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Objectives Globally, drug-resistant tuberculosis (DR-TB) is the leading cause of death globally related to antimicrobial resistance, affecting 500,000 emergent cases annually. In 2018, the first United Nations High-Level Meeting (UNHLM) on tuberculosis declared DR-TB a global public health priority. Bold country targets were established for 2018–2022. This study reviews the DR-TB situation in 2018, and the UNHLM target accomplishments in 10 high-burden countries (HBCs). Methods An ecological descriptive analysis of the top 10 DR-TB HBCs (Bangladesh, China, India, Indonesia, Myanmar, Nigeria, Pakistan, Philippines, Russian Federation, and South Africa), which share 70% of the global DR-TB burden, was undertaken, complemented by a cascade-of-care analysis and a survey gathering additional information on key advances and setbacks 2 years after the UNHLM declaration. Results Most countries are showing historic advances and are on track for the 2018 and 2019 targets. However, according to the cascade-of-care, none of the countries are capable of providing effective care for 50% of the estimated patients. Increasing levels of fluoroquinolone resistance and access to timely susceptibility testing can jeopardize ongoing adoption of shorter, all-oral treatment regimens. The programmatic management of DR-TB in children remains minimal. Achievements for 2020 and beyond may be affected significantly by the coronavirus disease 2019 (COVID-19) pandemic. Conclusion Triggered by the COVID-19 pandemic, there is a global risk of recoil in DR-TB care with long-term consequences in terms of deaths, suffering and wider transmission. Investment to support DR-TB services is more important now than ever to meet the aspirations of the UNHLM declaration.

Children had better treatment outcomes and lower mortality rates than adults., Extensively drug-resistant tuberculosis (XDR TB) has extremely poor treatment outcomes in adults. Limited data are available for children. We report on clinical manifestations, treatment, and outcomes for 37 children (

In 2021, WHO revised its tuberculosis treatment outcome definitions, making them uniformly applicable for different lengths of treatment for both drug-susceptible and drug-resistant diseasehttps://bit.ly/3jFFgOu

Rifampicin-resistant tuberculosis (RR-TB) and multidrug-resistant tuberculosis (MDR-TB) are characterised by higher rates of mortality, complexity and resource utilisation. There were an estimated half million cases of these drug-resistant forms of tuberculosis in 2018, with 186,772 cases being notified and only 156,701 started on treatment. Within the last decade the use of repurposed and new MDR-TB drugs have been assessed and optimised with a reduction of poorer outcomes including death and better regimen tolerability. Newer all-oral shorter treatment regimens are now being recommended and implemented worldwide, in the hope all MDR-TB patients can be treated and the gap can be filled rapidly through the use of a more simplified, cheaper, less toxic regimen which is easier to take, complete and result in fewer side effects, defaults and higher treatment success rates.

The definition of extensively drug resistant tuberculosis has been updated by the World Health Organization and pre-extensively drug-resistant tuberculosis has been definedhttps://bit.ly/30Fdffc

Antimicrobial resistance is a major public health problem globally. Likewise, forms of tuberculosis (TB) resistant to first- and second-line TB medicines present a major challenge for patients, healthcare workers and healthcare services. In November 2019, the World Health Organization (WHO) convened an independent international expert panel to review new evidence on the treatment of multidrug- (MDR) and rifampicin-resistant (RR) TB, using the Grading of Recommendations Assessment, Development and Evaluation approach. Updated WHO guidelines emerging from this review, published in June 2020, recommend a shorter treatment regimen for patients with MDR/RR-TB not resistant to fluoroquinolones (of 9–11 months), with the inclusion of bedaquiline instead of an injectable agent, making the regimen all oral. For patients with MDR-TB and additional fluoroquinolone resistance, a regimen composed of bedaquiline, pretomanid and linezolid may be used under operational research conditions (6–9 months). Depending on the drug-resistance profile, extent of TB disease or disease severity, a longer (18–20 months) all-oral, individualised treatment regimen may be used. In addition, the review of new data in 2019 allowed the WHO to conclude that there are no major safety concerns on the use of bedaquiline for >6 months’ duration, the use of delamanid and bedaquiline together and the use of bedaquiline during pregnancy, although formal recommendations were not made on these topics. The 2020 revision has highlighted the ongoing need for high-quality evidence and has reiterated the need for clinical trials and other research studies to contribute to the development of evidence-based policy., New WHO guidelines on the treatment of drug-resistant tuberculosis (TB) contain the latest recommendations on shorter or longer all oral treatment regimens for patients with drug-resistant TB, including the medicines to be used and other supportive measures https://bit.ly/2UJeib7

The aim of this study was to analyse temporal changes in treatments for and outcomes of multidrug-resistant (MDR)/rifampin-resistant (RR)-tuberculosis (TB) in the context of national economic status.We analysed data collected by the Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB Treatment on MDR/RR-TB patients from 37 countries. The data were stratified by three national income levels (low-/lower-middle, upper-middle and high) and grouped by time of treatment initiation (2001–2003, 2004–2006, 2007–2009, 2010–2012 and 2013–2015). Temporal trends over the study period were analysed. The probability of treatment success in different income groups over time was calculated using generalised linear mixed models with random effects.In total, 9036 patients were included in the analysis. Over the study period, use of group A drugs (levofloxacin/moxifloxacin, bedaquiline and linezolid) recommended by the World Health Organization increased and treatment outcomes improved in all income groups. Between 2001–2003 and 2013–2015, treatment success rates increased from 60% to 78% in low-/lower-middle-income countries, from 40% to 67% in upper-middle-income countries, and from 73% to 81% in high-income countries. In earlier years, the probability of treatment success in upper-middle-income countries was lower than that in low-/lower-middle-income countries, but no difference was observed after 2010. However, high-income countries had persistently higher probability of treatment success compared to upper-middle income countries.Improved treatment outcomes and greater uptake of group A drugs were observed over time for patients with MDR/RR-TB at all income levels. However, treatment outcomes are still unsatisfactory, especially in upper-middle-income countries.

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.

Background An estimated 32,000 children develop multidrug-resistant tuberculosis (MDR-TB; Mycobacterium tuberculosis resistant to isoniazid and rifampin) each year. Little is known about the optimal treatment for these children. Methods and findings To inform the pediatric aspects of the revised World Health Organization (WHO) MDR-TB treatment guidelines, we performed a systematic review and individual patient data (IPD) meta-analysis, describing treatment outcomes in children treated for MDR-TB. To identify eligible reports we searched PubMed, LILACS, Embase, The Cochrane Library, PsychINFO, and BioMedCentral databases through 1 October 2014. To identify unpublished data, we reviewed conference abstracts, contacted experts in the field, and requested data through other routes, including at national and international conferences and through organizations working in pediatric MDR-TB. A cohort was eligible for inclusion if it included a minimum of three children (aged, In a systematic review and meta-analysis conducted to inform World Health Organization guidelines, Elizabeth Harausz and colleagues investigate different treatment regimens and outcomes for children with multidrug-resistant tuberculosis., Author summary Why was this study done? Treatment for multidrug-resistant tuberculosis (MDR TB) affects 32,000 children per year, requires longer treatment with much more toxic medications than drug-susceptible tuberculosis. Unfortunately, little is know about the optimal treatment for children with MDR TB. This study reviewed treatment and outcome data from children around the world in order to better understand the management of MDR-TB in children. This study also sought to understand the risk factors for poor treatment outcomes in children with MDR-TB. This study informed the World Health Organization guidelines on treatment of MDR-TB in children. What did the researchers do and find? We performed a systematic review and individual patient data meta-analysis on clinical characteristics and treatment outcomes on 975 children from across 18 countries. Children were analyzed in two separate groups, those with bacteriologically confirmed MDR-TB and those who were clinically diagnosed with MDR-TB. We found that, in general, children do well when treated with the second-line MDR-TB medications (78% overall had successful treatment outcomes), despite the fact that there was a high burden of severe disease. Malnutrition and not being treated for HIV (if the child was HIV-positive) during TB treatment significantly increased the risk of poor outcomes. Second-line injectable agents and high-dose isoniazid were associated with treatment success. However, a high proportion of children with non-severe disease who received no second-line injectable agents still did well; therefore, children with non-severe disease may be able to be spared from these toxic medications. What do these findings mean? Consideration should be given to using high-dose isoniazid in treatment regimens, and if children have non-severe disease, the possibility of excluding second-line injectable agents from the treatment regimen should be considered. HIV treatment should be started as soon as is possible, and malnutrition should be aggressively treated.

Funding: World Health Organization and Canadian Institutes of Health Research. Background: Isoniazid-resistant, rifampicin-susceptible (INH-R) tuberculosis is the most common form of drug resistance, and is associated with failure, relapse, and acquired rifampicin resistance if treated with first-line anti-tuberculosis drugs. The aim of the study was to compare success, mortality, and acquired rifampicin resistance in patients with INH-R pulmonary tuberculosis given different durations of rifampicin, ethambutol, and pyrazinamide (REZ); a fluoroquinolone plus 6 months or more of REZ; and streptomycin plus a core regimen of REZ. Methods: Studies with regimens and outcomes known for individual patients with INH-R tuberculosis were eligible, irrespective of the number of patients if randomised trials, or with at least 20 participants if a cohort study. Studies were identified from two relevant systematic reviews, an updated search of one of the systematic reviews (for papers published between April 1, 2015, and Feb 10, 2016), and personal communications. Individual patient data were obtained from authors of eligible studies. The individual patient data meta-analysis was performed with propensity score matched logistic regression to estimate adjusted odds ratios (aOR) and risk differences of treatment success (cure or treatment completion), death during treatment, and acquired rifampicin resistance. Outcomes were measured across different treatment regimens to assess the effects of: different durations of REZ (≤6 months vs >6 months); addition of a fluoroquinolone to REZ (fluoroquinolone plus 6 months or more of REZ vs 6 months or more of REZ); and addition of streptomycin to REZ (streptomycin plus 6 months of rifampicin and ethambutol and 1–3 months of pyrazinamide vs 6 months or more of REZ). The overall quality of the evidence was assessed using GRADE methodology. Findings: Individual patient data were requested for 57 cohort studies and 17 randomised trials including 8089 patients with INH-R tuberculosis. We received 33 datasets with 6424 patients, of which 3923 patients in 23 studies received regimens related to the study objectives. Compared with a daily regimen of 6 months of (H)REZ (REZ with or without isoniazid), extending the duration to 8–9 months had similar outcomes; as such, 6 months or more of (H)REZ was used for subsequent comparisons. Addition of a fluoroquinolone to 6 months or more of (H)REZ was associated with significantly greater treatment success (aOR 2·8, 95% CI 1·1–7·3), but no significant effect on mortality (aOR 0·7, 0·4–1·1) or acquired rifampicin resistance (aOR 0·1, 0·0–1·2). Compared with 6 months or more of (H)REZ, the standardised retreatment regimen (2 months of streptomycin, 3 months of pyrazinamide, and 8 months of isoniazid, rifampicin, and ethambutol) was associated with significantly worse treatment success (aOR 0·4, 0·2–0·7). The quality of the evidence was very low for all outcomes and treatment regimens assessed, owing to the observational nature of most of the data, the diverse settings, and the imprecision of estimates. Interpretation: In patients with INH-R tuberculosis, compared with treatment with at least 6 months of daily REZ, addition of a fluoroquinolone was associated with better treatment success, whereas addition of streptomycin was associated with less treatment success; however, the quality of the evidence was very low. These results support the conduct of randomised trials to identify the optimum regimen for this important and common form of drug-resistant tuberculosis. Funding World Health Organization and Canadian Institutes of Health Research. Postprint

The goals of the End TB strategy, which aims to achieve a 90% reduction in tuberculosis (TB) incidence and a 95% reduction in TB mortality by 2035, will not be achieved without new tools to fight TB. These include improved point of care (POC) diagnostic tests that are meant to be delivered at the most decentralised levels of care where the patients make the initial contact with the health system, as well as within the community. These tests should be able to be performed on an easily accessible sample and provide results in a timely manner, allowing a quick treatment turnaround time of a few minutes or hours (in a single clinical encounter), hence avoiding patient loss-to-follow-up. There have been exciting developments in recent years, including the WHO endorsement of Xpert MTB/RIF, Xpert MTB/RIF Ultra, loop-mediated isothermal amplification (TB-LAMP) and lateral flow lipoarabinomannan (LAM). However, these tests have limitations that must be overcome before they can be optimally applied at the POC. Furthermore, worrying short- to medium-term gaps exist in the POC diagnostic test development pipeline. Thus, not only is better implementation of existing tools and algorithms needed, but new research is required to develop new POC tests that allow the TB community to truly make an impact and find the "missed TB cases".

Summary Background The results of some reports have suggested that treatment of isoniazid-resistant tuberculosis with the recommended regimens of first-line drugs might be suboptimal. We updated a previous systematic review of treatment outcomes associated with use of first-line drugs in patients with tuberculosis resistant to isoniazid but not rifampicin. Methods In this systematic review, we updated the results of a previous review to include randomised trials and cohort studies published in English, French, or Spanish to March 31, 2015, containing results of standardised treatment of patients with bacteriologically confirmed isoniazid-resistant tuberculosis (but not multidrug-resistant tuberculosis—ie, not resistant to rifampicin) in whom failure and relapse were bacteriologically confirmed. Results in patients with drug-sensitive tuberculosis included in the same studies were also analysed. We pooled treatment outcomes with random-effects meta-analysis. Findings We identified 19 cohort studies and 33 trials with 3744 patients with isoniazid-resistant tuberculosis and 19 012 patients with drug-sensitive disease. The pooled rates of failure or relapse, or both, and acquired drug resistance with all drug regimens were 15% (95% CI 12–18) and 3·6% (2–5), respectively, in patients with isoniazid-resistant tuberculosis and 4% (3–5) and 0·6% (0·3–0·9) in those with drug-sensitive tuberculosis. Of patients with initial isoniazid-resistant tuberculosis with acquired drug resistance, 96% (93–99) had acquired multidrug-resistant disease. Treatment of isoniazid-resistant tuberculosis with the WHO standard regimen for new patients resulted in treatment failure, relapse, and acquired multidrug resistance in 11% (6–17), 10% (5–15) and 8% (3–13), respectively; treatment with the standard WHO regimen for previously treated patients resulted in treatment failure in 6% (2–10), relapse in 5% (2–8), and acquisition of multidrug resistance in 3% (0–6). For patients with drug-sensitive disease treated with the standard retreatment regimen the rates were 1% (0–2), 5% (4–7), and 0·3% (0–0·6). Interpretation Treatment of isoniazid-resistant tuberculosis with first-line drugs resulted in suboptimal outcomes, supporting the need for better regimens. Standardised empirical treatment of new cases could be contributing substantially to the multidrug-resistant epidemic, particularly in settings where the prevalence of isoniazid resistance is high. Funding Canadian Institutes of Health Research.

DRUG-RESISTANT TUBERCULOSIS (TB) is a significant global problem.1 Although multidrug-resistant TB (MDR-TB) has been written about extensively, there is a gap in the literature on management of monoresistant forms of TB, particularly isoniazid (INH) resistant TB.2 INH monoresistance is defined as strains of Mycobacterium tuberculosis that have documented resistance to INH;3 some definitions also include strains of M. tuberculosis with resistance to INH and streptomycin (SM), as the addition of SM resistance does not affect current programmatic treatment recommendations.4 INH-monoresistant TB is the most common form of TB monoresistance.5 The optimal management of INH-monoresistant TB has been widely debated:6–8 current global recommendations are that INH-monoresistant TB (including INH+SM-resistant strains) should be treated with a 9-month regimen of daily rifampin (R, RMP), pyrazinamide (Z, PZA) and ethambutol (E, EMB; i.e., 9RZE).9,10 This recommendation is based largely on the results of a prospective clinical study conducted in the United States, in which there were no differences in outcomes between patients with INH monoresistance and those with pansusceptible TB, provided that those with INH monoresistance took their medications daily for the total 9-month course of treatment.11 The study’s applicability to settings outside of the United States, where there are different health care systems and high rates of drug-resistant TB, has been questioned. In contrast to the favorable results of this study, a recent global meta-analysis of outcomes among patients with INH monoresistance found poor treatment outcomes, with failure rates ranging from 18% to 44%.12 This article reports the outcomes of patients with INH-monoresistant TB treated under program conditions in the country of Georgia between 2007 and 2009.

SummaryObjectivesTo determine risk factors for poor outcomes among patients with pulmonary multidrug- or extensively drug-resistant (M/XDR) tuberculosis (TB) in Georgia.MethodsThis was a prospective, population-based observational cohort study.ResultsAmong 380M/XDR-TB patients (mean age 38 years), 179 (47%) had a poor outcome: 59 (16%) died, 37 (10%) failed, and 83 (22%) defaulted. Newly diagnosed M/XDR-TB cases were significantly more likely to have a favorable outcome than retreatment cases (odds ratio (OR) 4.26, 95% confidence interval (CI) 1.99–9.10, p

PROBLEM: The category II retreatment regimen for management of tuberculosis in previously treated patients was first introduced in the early 1990s. It consists of 8 months of total therapy with the addition of streptomycin to standard first-line medications. A review of 6500 patients on category II therapy in Georgia showed poor outcomes and high rates of streptomycin resistance. APPROACH: The National Tuberculosis Program used an evidence-based analysis of national data to convince policy-makers that category II therapy should be eliminated from national guidelines in Georgia. LOCAL SETTING: The World Health Organization tuberculosis case-notification rate in Georgia is 102 per 100 000 population. All patients receive culture and drug susceptibility testing as a standard part of tuberculosis diagnosis. In 2009, routine surveillance found multidrug-resistant tuberculosis in 10.6% of newly diagnosed patients and 32.5% of previously treated cases. RELEVANT CHANGES: Category II retreatment regimen is no longer used in Georgia. Treatment is guided by results of drug susceptibility testing - using rapid, molecular tests where possible - for all previously treated tuberculosis patients. LESSONS LEARNT: There was little resistance to policy change because the review was initiated and led by the National Tuberculosis Program. This experience can serve as a successful model for other countries to make informed decisions about the use of category II therapy.

High rates and transmission of multidrug-resistant (MDR) tuberculosis (TB) have been associated with the Mycobacterium tuberculosis complex (MTBC) Beijing lineage, pointing to the importance of pathogen genetic factors for the modulation of infection outcome and epidemiology. We present here an in-depth analysis of the population structure of MTBC strains from the Republic of Georgia, a high-incidence setting at the Black Sea Coast. Phylogenetic lineages were identified based on 24-locus MIRU-VNTR (for mycobacterial interspersed repetitive unit-variable number tandem repeat) and spoligotyping analysis. Clusters of strains with identical genotyping profiles were determined as an indicator for the rate of recent transmission. Among the 183 M. tuberculosis isolates investigated, the most prominent lineage found was Beijing (26%), followed by the LAM (18%), Ural (12%), and Haarlem (5%) strains. A closely related previously undefined phylogenetic group (62 strains) showed a genotyping pattern similar to laboratory strain H37RV and was denominated as “Georgia-H37RV-like.” Although isoniazid resistance was found among strains of different lineages, MDR TB was nearly completely restricted to Beijing strains ( P < 0.0001). Approximately 50% of the isolates were grouped in clusters, indicating a high rate of recent transmission. Our data indicate that, in addition to the confirmation of the importance of Beijing genotype strains for the TB epidemiology in former Soviet Union countries, a high-population diversity with strains of the LAM, Ural, Haarlem, and a previously undefined lineage represents nearly two-thirds of the strains found in Georgia. Higher rates among previously treated and MDR TB patients point to a higher potential of lineage Beijing to escape therapy and develop MDR TB.

Background: Current laboratory methods for monitoring the response to therapy for tuberculosis (TB) rely on mycobacterial culture. Their clinical usefulness is therefore limited by the slow growth rate of Mycobacterium tuberculosis. Rapid methods to reliably quantify the response to anti-TB drugs are desirable. Methods: We developed 2 real-time PCR assays that use hydrolysis probes to target DNA of the IS6110 insertion element and mRNA for antigen 85B. The nucleic acids are extracted directly from concentrated sputum samples decontaminated with sodium hydroxide and N-acetyl-l-cysteine. We prospectively compared these assays with results obtained by sputum mycobacterial culture for patients receiving anti-TB therapy. Results: Sixty-five patients with newly diagnosed TB and receiving a standardized first-line anti-TB drug regimen were evaluated at week 2 and at months 1, 2, and 4 after therapy initiation. Both the DNA PCR assay (98.5% positive) and the mRNA reverse-transcription PCR (RT-PCR) assay (95.4% positive) were better than standard Ziehl–Neelsen staining techniques (83.1%) for detecting M. tuberculosis in culture-positive sputum samples. The overall agreement between culture and mRNA RT-PCR results for all 286 sputum samples was 87.1%, and compared with culture, the mRNA RT-PCR assay’s diagnostic sensitivity and specificity were 85.2% and 88.6%, respectively. For monitoring efficacy of therapy, mRNA RT-PCR results paralleled those of culture at the follow-up time points. Conclusions: The continued presence of viable M. tuberculosis according to culture and results obtained by RT-PCR analysis of antigen 85B mRNA correlated clinically with resistance to anti-TB drugs, whereas the DNA PCR assay showed a high false-positive rate. This mRNA RT-PCR assay may allow rapid monitoring of the response to anti-TB therapy.

To assess the effect of tobacco smoking on the outcome of tuberculosis treatment in Tbilisi, Georgia.We conducted a prospective cohort study of adults with laboratory-confirmed tuberculosis from May 2011 to November 2013. History of tobacco smoking was collected using a standardized questionnaire adapted from the global adult tobacco survey. We considered tuberculosis therapy to have a poor outcome if participants defaulted, failed treatment or died. We used multivariable regressions to estimate the risk of a poor treatment outcome.Of the 591 tuberculosis patients enrolled, 188 (31.8%) were past smokers and 271 (45.9%) were current smokers. Ninety (33.2%) of the current smokers and 24 (18.2%) of the participants who had never smoked had previously been treated for tuberculosis (P 0.01). Treatment outcome data were available for 524 of the participants, of whom 128 (24.4%) - including 80 (32.9%) of the 243 current smokers and 21 (17.2%) of the 122 individuals who had never smoked - had a poor treatment outcome. Compared with those who had never smoked, current smokers had an increased risk of poor treatment outcome (adjusted relative risk, aRR: 1.70; 95% confidence interval, CI: 1.00-2.90). Those who had ceased smoking more than two months before enrolment did not have such an increased risk (aRR: 1.01; 95% CI: 0.51-1.99).There is a high prevalence of smoking among patients with tuberculosis in Georgia and smoking increases the risk of a poor treatment outcome.Évaluer l'effet du tabagisme sur les résultats des traitements antituberculeux à Tbilissi, en Géorgie.Nous avons réalisé une étude de cohorte prospective chez des adultes atteints de tuberculose confirmée en laboratoire, de mai 2011 à novembre 2013. Les antécédents de tabagisme ont été recueillis à l'aide d'un questionnaire standardisé, adapté de l'enquête mondiale sur le tabagisme des adultes. Nous avons considéré que les résultats du traitement antituberculeux étaient mauvais si les participants ne l'avaient pas respecté, n'avaient pas répondu au traitement ou étaient décédés. Nous avons utilisé des régressions multivariées pour estimer le risque de mauvais résultats thérapeutiques.Sur les 591 patients atteints de tuberculose, 188 (31,8%) étaient d'anciens fumeurs et 271 (45,9%) fumaient encore. Quatre-vingt-dix (33,2%) fumeurs actuels et 24 (18,2%) participants n'ayant jamais fumé avaient précédemment pris un traitement contre la tuberculose (P 0,01). Les données sur les résultats des traitements étaient disponibles pour 524 des participants, sur lesquels 128 (24,4%) – dont 80 (32,9%) des 243 fumeurs actuels et 21 (17,2%) des 122 personnes n'ayant jamais fumé – montraient de mauvais résultats thérapeutiques. Comparés aux personnes n'ayant jamais fumé, les fumeurs actuels présentaient un risque accru de mauvais résultats thérapeutiques (risque relatif ajusté, RRa : 1,70 ; intervalle de confiance de 95%, IC : 1,00-2,90). Les personnes qui avaient arrêté de fumer plus de deux mois avant leur inclusion à l'étude ne présentaient pas une telle augmentation du risque (RRa : 1,01 ; IC de 95% : 0,51-1,99).Il existe une forte prévalence de tabagisme chez les patients atteints de tuberculose en Géorgie et le tabagisme augmente le risque de mauvais résultats thérapeutiques.Evaluar los efectos del consumo de tabaco en los resultados del tratamiento de la tuberculosis en Tbilisi, Georgia.Se llevó a cabo un estudio de cohortes prospectivo en adultos con tuberculosis confirmada mediante pruebas de laboratorio de mayo de 2011 a noviembre de 2013. Se recopiló información sobre el consumo de tabaco mediante un cuestionario normalizado adaptado a partir de la Encuesta Mundial sobre el Tabaco y los Adultos. Se consideró que los resultados de la terapia antituberculosa eran deficientes si los participantes incumplían el tratamiento, no lo realizaban o morían. Se utilizaron regresiones multivariables para estimar el riesgo de obtener unos resultados deficientes del tratamiento.De los 591 pacientes con tuberculosis inscritos, 188 (31,8%) eran antiguos fumadores y 271 (45,9%) eran fumadores actuales. Noventa (33,2%) de los fumadores actuales y 24 (18,2%) de los participantes que no habían fumado nunca habían recibido tratamiento para la tuberculosis anteriormente (P0,01). Los datos sobre los resultados del tratamiento estuvieron disponibles para 524 de los participantes, de los cuales 128 (24,4%) (incluyendo los 80 (32,9%) de los 243 fumadores y 21 (17,2%) de las 122 personas que nunca habían fumado) obtuvieron unos resultados deficientes del tratamiento. En comparación con las personas que no habían fumado nunca, los fumadores actuales tenían un riesgo superior de obtener unos resultados deficientes del tratamiento (riesgo relativo ajustado, RRa: 1,70; intervalo de confianza, IC, del 95%: 1,00–2,90). Aquellas personas que habían dejado de fumar más de dos meses antes de la inscripción no experimentaban un aumento del riesgo tan elevado (RRa: 1,01 (IC del 95%: 0,51–1,99).Existe una elevada prevalencia de consumo de tabaco entre los pacientes con tuberculosis en Georgia y el consumo de tabaco aumenta el riesgo de obtener unos resultados deficientes del tratamiento.لتقييم التأثير الناتج عن تدخين التبغ على حصيلة علاج مرض السل في تبلّيسي، جورجيا.لقد أجرينا دراسة أترابية استباقية على البالغين الذين يعانون من مرض السل المؤكد مختبريًا في الفترة ما بين أيار/مايو 2011 إلى تشرين الثاني/نوفمبر 2013. وقد تم تجميع تاريخ تدخين التبغ باستخدام استبيان معياري معتمد من المسح العالمي لاستهلاك التبغ لدى البالغين. لقد وجدنا أن علاج السل ينتج عنه حصيلة سيئة إذا تخلف المشاركون عن المعالجة، أو فشل علاجهم، أو توفوا. لقد استخدمنا تحوفات متعددة المتغيرات لتقدير الاختطار الناتج عن حصيلة العلاج السيئة.من بين 591 من مرضى السل المسجلين، كان 188 (31.8٪) من المرضى مدخنين سابقين وكان 271 (45.9٪) من المرضى مدخنين حاليين. لقد سبق لتسعين (33.2٪) من المدخنين الحاليين، و 24 (18.2٪) من المشاركين الذين لم يدخنوا أبدًا، العلاج من مرض السل (الاحتمال0.01). وتوفرت بيانات حصيلة العلاج لعدد 524 من المشاركين، من بينهم 128 (24.4٪) كانت حصيلة العلاج الخاصة بهم سيئة، بما في ذلك 80 (32.9٪) من 243 من المدخنين الحاليين و21 (17.2٪) من 122 من الأفراد الذين لم يدخنوا أبدًا. مقارنة مع أولئك الذين لم يدخنوا أبدًا، كان هناك اختطار زائد على المدخنين الحاليين لحدوث حصيلة علاج سيئة (الاختطار النسبي المصحح، aRR: 1.70؛ بنسبة أرجحية مقدارها 95%: 1.00 إلى 2.90).أولئك الذين قد أقلعوا عن التدخين لمدة أكثر من شهرين قبل التسجيل، لم يكن لديهم مثل ذلك الاختطار الزائد (:aRR 1.01؛ بنسبة أرجحية مقدارها 95%: 0.50 إلى 1.99).هناك انتشار مرتفع للتدخين بين المرضى الذين يعانون من مرض السل في جورجيا، ويزيد التدخين من اختطار حصيلة العلاج السيئة.旨在评价格鲁吉亚第比利斯境内吸烟对结核病治疗效果的影响。.从 2011 年 5 月至 2013 年 11 月，我们在经实验室确诊患有结核病的成人中开展了一项前瞻性群组研究，并且通过改编自全球成人烟草调查的标准化问卷收集了吸烟史资料。我们认为如果参与者违约、不进行治疗或死亡，那么结核病治疗会有不良的效果。我们采用多变量回归分析的方法评估了不良治疗效果的风险。.在参与调查的 591 名结核病患者中，其中 188 名 (31.8%) 是既往吸烟者，271 名 (45.9%) 是目前吸烟者。目前吸烟者中有 90 名 (33.2%)、从未吸烟者中有 24 名 (18.2%) 曾在之前因结核病接受过治疗 (P 0.01)。治疗效果数据对 524 名参与者均为有效可用，其中 128 名 (24.4%) 参与者的治疗效果不良，包括 243 名目前吸烟者中的 80 名 (32.9%) 和 122 名从未吸烟者中的 21 名 (17.2%)。与从未吸烟者相比，目前吸烟者产生不良治疗效果的风险较高（调整过的相对风险，aRR：1.70；95% 置信区间，CI：1.00–2.90）。那些在参与调查之前已戒烟两个月以上的人并未增加该风险 (aRR:1.01；95% CI： 0.51–1.99)。.格鲁吉亚境内结核病患者吸烟流行率很高，并且吸烟增加了产生不良治疗效果的风险。.Оценка воздействия табакокурения на исход лечения туберкулеза в Тбилиси, Грузия.В период с мая 2011 г. по ноябрь 2013 г. было проведено проспективное когортное исследование взрослого населения с диагнозом туберкулеза, подтвержденным данными лабораторных анализов. С помощью стандартизированной анкеты, разработанной на основе Глобального опроса взрослого населения о потреблении табака (GATS), была собрана история табакокурения участников. Исход лечения туберкулеза рассматривался нами как плохой, если участник исследования не доводил лечение до конца, лечение не было эффективным или участник исследования умирал. Для оценки риска плохого исхода лечения использовались многопараметрические регрессии.В исследовании принял участие 591 пациент с туберкулезом, из которых 188 человек (31,8 %) ранее были курильщиками, а 271 человек (45,9 %) курил на момент начала исследования. Девяносто человек (33,2 %) из числа активных курильщиков и 24 человека (18,2 %) из числа тех участников, которые никогда не курили, ранее получали лечение от туберкулеза (P0,01). Данные по исходу лечения были доступны для 524 участников, из которых исход лечения был плохим у 128 человек (24,4 %). В это число входили 80 человек (32,9 %) из числа 243 активных курильщиков и 21 (17,2 %) из тех 122, кто никогда не курил. По сравнению с теми, кто никогда не курил, у активных курильщиков был выявлен повышенный риск плохого исхода лечения (скорректированный относительный риск, ОР: 1,70; 95 % доверительный интервал, ДИ: 1,00–2,90). У тех, кто бросил курить более чем за два месяца до вступления в исследование, риск был не таким высоким (скорректированный ОР: 1,01; 95 % ДИ: 0,51–1,99).У пациентов с туберкулезом в Грузии широко распространено курение, и курение увеличивает риск плохого исхода лечения.

In 2011, Georgia, in the Caucasus, reported that 11% of new and 32% of previously treated tuberculosis (TB) cases nationally had multidrug-resistant TB (MDR-TB). To help understand the mechanisms driving these high risks of drug-resistance and plan for targeted interventions, we identified geographical variability in the MDR-TB burden in Georgia and patient-level MDR-TB risk factors. We used routinely collected surveillance data on notified TB cases to estimate the MDR-TB incidence/100,000 people and the percentage of TB cases with MDR-TB for each of 65 districts and regression modelling to identify patient-level MDR-TB risk factors. 1,795 MDR-TB cases were reported (January 2009–June 2011); the nationwide notified MDR-TB incidence was 16.2/100,000 but far higher (837/100,000) in the penitentiary system. We found substantial geographical heterogeneity between districts in the average annual MDR-TB incidence/100,000 (range: 0.0–5.0 among new and 0.0–18.9 among previously treated TB cases) and the percentage of TB cases with MDR-TB (range: 0.0%–33.3% among new and 0.0%–75.0% among previously treated TB cases). Among treatment-naïve individuals, those in cities had greater MDR-TB risk than those in rural areas (increased odds: 43%; 95% confidence interval: 20%–72%). These results suggest that interventions for interrupting MDR-TB transmission are urgently needed in prisons and urban areas.

Setting The study was conducted at the National Center for Tuberculosis and Lung Diseases (NCTBLD) in Tbilisi, Georgia. Objective To assess the utility of contact investigation for tuberculosis (TB) case detection. We also assessed the prevalence and risk factors for active TB disease and latent TB infection (LTBI) among contacts of active pulmonary TB cases. Design A retrospective cohort study was conducted among the contacts of active pulmonary TB cases registered in 2010–2011 at the NCTBLD in Tbilisi, Georgia. Contacts of active TB patients were investigated according to an “invitation model”: they were referred to the NCTBLD by the index case; were queried about clinical symptoms suggestive of active TB disease; tuberculin skin testing and chest radiographs were performed. Demographic, laboratory, and clinical data of TB patients and their contacts were abstracted from existing records up to February 2013. Results 869 contacts of 396 index cases were enrolled in the study; a median of 2 contacts were referred per index case. Among the 869 contacts, 47 (5.4%) were found to have or developed active TB disease: 30 (63.8%) were diagnosed with TB during the baseline period (co-prevalent cases) and 17 (36.2%) developed active TB disease during the follow-up period (mean follow up of 21 months) (incident TB cases). The incidence rate of active TB disease among contacts was 1126.0 per 100 000 person years (95% CI 655.7–1802.0 per 100,000 person-years). Among the 402 contacts who had a tuberculin skin test (TST) performed, 52.7% (95% CI 47.7–57.7%) had LTBI. Conclusions A high prevalence of LTBI and active TB disease was found among the contacts of TB cases in Tbilisi, Georgia. Our findings demonstrated that an “invitation” model of contact investigation was an effective method of case detection. Therefore, contact investigation should be scaled up in Georgia.

We developed a QIAplex system for the simultaneous detection of 24 Mycobacterium tuberculosis gene mutations responsible for resistance to isoniazid (INH), rifampin (RIF), streptomycin (STM), and ethambutol (EMB) in 196 M. tuberculosis isolates recovered in the Republic of Georgia. In comparison to phenotypic susceptibility tests, the QIAplex showed sensitivity and specificity of 85.4% and 96.1% for INH, 94.4% and 99.4% for RIF, 69.6% and 99.2% for STM, 50.0% and 98.8% for EBM, and 86.7% and 100.0% for multidrug resistance, respectively. The dominant resistance mutations revealed were a mutation in katG resulting in S315T ( katG S315T), rpsL K43R, and rpoB S531L. Mutations katG S315G and S315T and rpoB S531L were detected with higher frequencies in pretreated patients than in naive patients ( P < 0.05). Simultaneous detection of 24 common drug resistance-related mutations provides a molecular tool for studying and monitoring M. tuberculosis resistance mechanism and epidemiology.