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Introduction Delaying care-seeking for tuberculosis (TB) symptoms is a major contributor to mortality, leading to worse outcomes and spread. To reduce delays, it is essential to identify barriers to care-seeking and target populations most at risk of delaying. Previous work identifies barriers only in people within the health system, often long after initial care-seeking.Methods We conducted a community-based survey of 84 625 households in Chennai, India, to identify 1667 people with TB-indicative symptoms in 2018–2019. Cases were followed prospectively to observe care-seeking behaviour. We used a comprehensive survey to identify care-seeking drivers, then performed multivariate analyses to identify care-seeking predictors. To identify profiles of individuals most at risk to delay care-seeking, we segmented the sample using unsupervised clustering. We then estimated the per cent of the TB-diagnosed population in Chennai in each segment.Results Delayed care-seeking characteristics include smoking, drinking, being employed, preferring different facilities than the community, believing to be at lower risk of TB and believing TB is common. Respondents who reported fever or unintended weight loss were more likely to seek care. Clustering analysis revealed seven population segments differing in care-seeking, from a retired/unemployed/disabled cluster, where 70% promptly sought care, to a cluster of employed men who problem-drink and smoke, where only 42% did so. Modelling showed 54% of TB-diagnosed people who delay care-seeking might belong to the latter segment, which is most likely to acquire TB and least likely to promptly seek care.Conclusion Interventions to increase care-seeking should move from building general awareness to addressing treatment barriers such as lack of time and low-risk perception. Care-seeking interventions should address specific beliefs through a mix of educational, risk perception-targeting and social norms-based campaigns. Employed men who problem-drink and smoke are a prime target for interventions. Reducing delays in this group could dramatically reduce TB spread.

Background: Tuberculosis (TB) lymphadenitis is the most common form of extra-pulmonary TB, and the treatment duration is six months. This non-inferiority based randomized clinical trial in South India evaluated the efficacy and safety of a four-month ofloxacin containing regimen in tuberculosis lymphadenitis (TBL) patients., Methods: New, adult, HIV-negative, microbiologically and or histopathologically confirmed superficial lymph node TB patients were randomized to either four-month oflaxacin containing test regimen [ofloxacin (O), isoniazid (H), rifampicin (R), pyrazinamide (Z) -2RHZO daily/ 2RHO thrice-weekly] or a six-month thrice-weekly control regimen (2HRZ, ethambutol/4RH). The treatment was directly observed. Clinical progress was monitored monthly during and up to 12 months post-treatment, and thereafter every three months up to 24 months. The primary outcome was determined by response at the end of treatment and TB recurrence during the 24 months post-treatment., Results: Of the 302 patients randomized, 298 (98.7%) were eligible for modified intention-to-treat (ITT) analysis and 294 (97%) for per-protocol (PP) analysis. The TB recurrence-free favourable response in the PP analysis was 94.0% (95% CI: 90.1-97.8) and 94.5% (95% CI: 90.8-98.2) in the test and control regimen respectively, while in the ITT analysis, it was 92.7% and 93.2%. The TB recurrence-free favourable response in the test regimen was non-inferior to the control regimen 0.5% (95% CI: -4.8-5.9) in the PP analysis based on the 6% non-inferiority margin. Treatment was modified for drug toxicity in two patients in the test regimen, while one patient had a paradoxical reaction., Conclusion: The 4-month ofloxacin containing regimen was found to be non-inferior and as safe as the 6-month thrice-weekly control regimen., (© 2024. The Author(s).)

Background: Diagnosis of extra pulmonary TB (EPTB) remains a big challenge. While data on utility of Xpert testing in EPTB diagnosis is enormous, there is limited data on Truenat MTB testing., Aim: In this study we aimed to evaluate the usefulness of Truenat in EPTB diagnosis., Materials and Methods: The study included patients suspected and/or treated for EPTB located from Chennai district during the year 2021-2022. All processed EPTB samples were subjected to smear microscopy, culture and Truenat MTB testing., Results: Of the 195 samples tested, 38 (19.4%) samples were positive for EPTB by any one of the diagnostic methods (smear, culture, microscopy). Out of these 38, 16 (42.1 %) were positive for MTB by Truenat and negative by Culture, 12 (31.5%) were positive by culture but negative by Truenat and 8 (21%) were positive by both Truenat and/or smear and culture. The sensitivity and specificity of the test was calculated with the composite reference standard (Culture (exclusion of colonies as positives), clinical conditions, and smear) and was found to be 60% and 100% respectively., Conclusion: Truenat MTB test is a cost-effective rapid molecular test that can be used only for the diagnosis of presumptive EPTB and not on follow-up samples., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Siva Kumar Shanmugam reports article publishing charges, equipment, drugs, or supplies, and statistical analysis were provided by National Institute for Research in Tuberculosis. Siva Kumar Shanmugam reports a relationship with National Institute for Research in Tuberculosis that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Background: Information on genotypic with comparison of phenotypic drug sensitivity test of anti-tuberculosis (TB) has been reported in several studies, which have variable results. The present study aimed to assess the Genotype MTBDRsl version 2.0/Line probe assay (LPA) for the detection of fluoroquinolones (FQ) and aminoglycosides (AMGs) resistance mutations among drug-resistant Mycobacterium TB (MTB) strains and also to compare the patterns of genotypic mutations of gyrA/B, rrs, and eis with mycobacteria growth indicator tube (MGIT 960)., Methods: A total of 1416 samples were subjected to Genotype MTBDRsl version 2.0 assay. One hundred and twenty sputum smear positive MTB isolates and 37 sputum smear negative MTB isolates confirmed multiple drug resistance resistant to FQ and AMG by the Genotype MTBDRsl version 2.0 were subjected to phenotypic drug susceptibility testing (DST) were analyzed., Results: The association sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for the resistance detection between MGIT (DST) and the Genotype MTBDRsl version 2.0 assay was significant (P < 0.01) of moxifloxacin (MFX) concentration. Sensitivity and specificity value for kanamycin (KAN) resistance was 76% and 89%; 47% and 94% for capreomycin (CAP); and 60% and 76% for low-level KAN, respectively., Conclusion: Our results indicate that MFX (0.25and 1 μg/mL), KAN (2.5 μg/mL), and CAP (2.5 μg/mL) significantly (P < 0.01) and support the World Health Organization guidance to test FQ and AMG by genotypic test., Competing Interests: None

Background : Patients with first-line drug resistance (DR) to rifampicin (RIF) or isoniazid (INH) as a first-line (FL) line probe assay (LPA) were subjected to genotypic DST using second-line (SL) LPA to identify SL-DR (including pre-XDR) under the National TB Elimination Program (NTEP), India. SL-DR patients were initiated on different DR-TB treatment regimens and monitored for their outcomes. The objective of this retrospective analysis was to understand the mutation profile and treatment outcomes of SL-DR patients. Materials and Methods : A retrospective analysis of mutation profile, treatment regimen, and treatment outcome was performed for SL-DR patients who were tested at ICMR-NIRT, Supra-National Reference Laboratory, Chennai between the years 2018 and 2020. All information, including patient demographics and treatment outcomes, was extracted from the NTEP Ni-kshay database. Results : Between 2018 and 2020, 217 patients out of 2557 samples tested were identified with SL-DR by SL-LPA. Among them, 158/217 were FQ-resistant, 34/217 were SLID-resistant, and 25/217 were resistant to both. D94G (Mut3C) of gyrA and a1401g of rrs were the most predominant mutations in the FQ and SLID resistance types, respectively. Favorable (cured and treatment complete) and unfavorable outcomes (died, lost to follow up, treatment failed, and treatment regimen changed) were recorded in a total of 82/217 and 68/217 patients in the NTEP Ni-kshay database. Conclusions : As per the testing algorithm, SL- LPA is used for genotypic DST following identification of first-line resistance, for early detection of SL-DR in India. The fluoroquinolone resistance pattern seen in this study population corelates with the global trend. Early detection of fluoroquinolone resistance and monitoring of treatment outcome can help achieve better patient management.

Tuberculosis (TB) diagnosis still remains to be a challenge with the currently used immune based diagnostic methods particularly Interferon Gamma Release Assay due to the sensitivity issues and their inability in differentiating stages of TB infection. Immune markers are valuable sources for understanding disease biology and are easily accessible. Chemokines, the stimulant, and the shaper of host immune responses are the vital hub for disease mediated dysregulation and their varied levels in TB disease are considered as an important marker to define the disease status. Hence, we wanted to examine the levels of chemokines among the individuals with drug-resistant, drug-sensitive, and latent TB compared to healthy individuals. Our results demonstrated that the differential levels of chemokines between the study groups and revealed that CXCL10 and CXCL9 as potential markers of drug-resistant and drug-sensitive TB with better stage discriminating abilities., (© 2023. The Author(s).)

Tuberculosis (TB) elimination is possible with the discovery of accurate biomarkers that define the stages of infection. Drug-resistant TB impair the current treatment strategies and worsen the unfavourable outcomes. The knowledge on host immune responses between drug-sensitive and drug-resistant infection is inadequate to understand the pathophysiological differences and disease severity. The secreted proteins, cytokines display versatile behaviour upon infection with Mycobacterium tuberculosis (MTB) and their imbalances often tend to assist disease pathology than protection. Therefore, studying these soluble proteins across TB infection spectrum (drug-resistant TB, drug-sensitive TB, and latent TB) may unveil the disease mediated responses and unique stage specific cytokine signatures. Thus, we sought to determine the plasma cytokine levels from healthy, latently infected, drug-sensitive, and drug-resistant TB individuals. Our study revealed top 8 cytokines (IL-17, IL-1α, IL-2, IL-10, IL-5, IFN-γ, TNF-α and IL-6) and their biomarker abilities to discriminate different stages of infection., (© 2023. The Author(s).)

Introduction: Early initiation of drug susceptibility testing (DST) guided anti-tuberculosis treatment benefits the patient in terms of better treatment outcomes and possibly reduces the transmission of tuberculosis (TB) disease in the community. To determine the status of universal DST (UDST) coverage in smear-positive pulmonary TB patients (PTB) initiated on treatment under the TB program in Greater Chennai Corporation. In addition, the barriers and facilitators for UDST were explored., Material and Methods: The data of PTB patients who were initiated on anti-TB treatment from July to December 2019 was abstracted from the NI-KSHAY database of TB Program. The barriers and facilitators for UDST were explored in 5 focus group discussions (FGDs) among the TB program healthcare workers (HCW). UDST coverage was based on the availability of Cartridge-based Nucleic Acid Amplification test (CBNAAT) results in the NI-KSHAY database., Results: The CBNAAT result was available for 1628 (82.6%) of the 1970 smear-positive PTB patients. Non-availability of CBNAAT results was significantly higher among the older age group (>50 years), in female PTB patients, and the Private Sector. Issues with sputum collection, transport of specimens, and receipt of results were highlighted by the HCWs for the non-availability of UDST results., Conclusion: Universal DST coverage in smear-positive PTB patients initiated on treatment in 2019 in Chennai was optimal as per National Strategic Plan for TB elimination UDST target of 80% for the year 2020 but with scope for improvement. The low UDST coverage in the private sector, among female patients and older age groups, needs to be addressed., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Community Medicine.)

The rampant increase in drug-resistant tuberculosis (TB) remains a major challenge not only for treatment management but also for diagnosis, as well as drug design and development. Drug-resistant mycobacteria affect the quality of life owing to the delayed diagnosis and require prolonged treatment with multiple and toxic drugs. The phenotypic modulations defining the immune status of an individual during tuberculosis are well established. The present study aims to explore the phenotypic changes of monocytes & dendritic cells (DC) as well as their subsets across the TB disease spectrum, from latency to drug-sensitive TB (DS-TB) and drug-resistant TB (DR-TB) using traditional immunophenotypic analysis and by uniform manifold approximation and projection (UMAP) analysis. Our results demonstrate changes in frequencies of monocytes (classical, CD14 ++ CD16 - , intermediate, CD14 ++ CD16 + and non-classical, CD14 +/- CD16 ++ ) and dendritic cells (DC) (HLA-DR + CD11c + myeloid DCs, cross-presenting HLA-DR + CD14 - CD141 + myeloid DCs and HLA-DR + CD14 - CD16 - CD11c - CD123 + plasmacytoid DCs) together with elevated Monocyte to Lymphocyte ratios (MLR)/Neutrophil to Lymphocyte ratios (NLR) and alteration of cytokine levels between DS-TB and DR-TB groups. UMAP analysis revealed significant differential expression of CD14 + , CD16 + , CD86 + and CD64 + on monocytes and CD123 + on DCs by the DR-TB group. Thus, our study reveals differential monocyte and DC subset frequencies among the various TB disease groups towards modulating the immune responses and will be helpful to understand the pathogenicity driven by Mycobacterium tuberculosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sampath, Natarajan, Moideen, Kathamuthu, Hissar, Dhanapal, Jayabal, Ramesh, Tripathy, Ranganathan, Babu and Bethunaickan.)

Background: At present, there are no validated quantitative scales available to measure patient-centred quality of care in health facilities providing services for tuberculosis (TB) patients in India and low-income and middle-income countries., Methods: Initial themes and items reflective of TB patient's perceived quality of care were developed using qualitative interviews. Content adequacy of the items were ascertained through Content validity Index (CVI) and content validity ratio (CVR). Pilot testing of the questionnaire for assessing validity and reliability was undertaken among 714 patients with TB. Sampling adequacy and sphericity were tested by Kaiser-Meyer-Olkin and Bartlett's test, respectively. Exploratory and confirmatory factor analysis was undertaken to test validity. Cronbach's α and test-retest scores were used to test reliability., Results: A 32-item tool measuring patient-perceived quality of TB distributed across five domains was developed initially based on a CVI and CVR cut-off score of 0.78 and cognitive interviews with patients with TB. Bartlett's test results showed a strong significance f (χ 2 =3756 and p<0.001) and Kaiser-Meyer-Olkin was measured to be 0.698 highlighting data adequacy and correlation between the variables. Exploratory factor analysis with varimax rotation extracted 4 factors related to 14 items with Eigen values >1 which accounted for 60.9% of the total variance of items. Correlation (z-value >1.96) between items and factors was highly significant and Cronbach's α was acceptable for the global scale (0.76) for the four factors. Intraclass correlation coefficient and the test retest scores for four factors were (<0.001) significant., Conclusion: We validated a measurement tool for patient-perceived quality of care for TB (PPQCTB) which measured the patient's satisfaction with healthcare provider and services. PPQCTB tool could enrich quality of care evaluation frameworks for TB health services in India., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Climate factors such as dew point temperature, relative humidity and atmospheric temperature may be crucial for the spread of tuberculosis. This study was conducted for the first time to investigate the relationship of climatic factors with TB occurrence in an Indian setting. Daily tuberculosis notification data during 2008-2015 were generated from the National Treatment Elimination Program, and analogous daily climatic data were obtained from the Regional Meteorological Centre at Chennai city, Tamil Nadu, India. The decomposition method was adopted to split the series into deterministic and non-deterministic components, such as seasonal, non-seasonal, trend and cyclical, and non-deterministic climate factors. A generalized linear model was used to assess the relation independently. TB disease progression from latent stage infection to active was supported by higher dew point temperature and moderate temperature. It had a significant association with TB progression in the summer and monsoon seasons. The relative humidity may be favored in the winter and post-monsoon. The water tiny dew droplets may support the TB bacterium to recuperate in the environment., (© 2022. The Author(s).)

India has a high burden of drug-resistant tuberculosis (DR TB) and many cases go undetected by current drug susceptibility tests (DSTs). This study was conducted to identify rifampicin (RIF) and isoniazid (INH) resistance associated genetic mutations undetected by current clinical diagnostics amongst persons with DR TB in Chennai, India. Retrospectively stored 166 DR TB isolates during 2013-2016 were retrieved and cultured in Löwenstein-Jensen medium. Whole genome sequencing (WGS) and MGIT DST for RIF and INH were performed. Discordant genotypic and phenotypic sensitivity results were repeated for confirmation and the discrepant results considered final. Further, drug resistance-conferring mutations identified through WGS were analyzed for their presence as targets in current WHO-recommended molecular diagnostics. WGS detected additional mutations for rifampicin and isoniazid resistance than WHO-endorsed line probe assays. For RIF, WGS was able to identify an additional 10% (15/146) of rpoB mutant isolates associated with borderline rifampicin resistance compared to MGIT DST. WGS could detect additional DR TB cases than commercially available and WHO-endorsed molecular DST tests. WGS results reiterate the importance of the recent WHO revised critical concentrations of current MGIT DST to detect low-level resistance to rifampicin. WGS may help inform effective treatment selection for persons at risk of, or diagnosed with, DR TB., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tamilzhalagan, Shanmugam, Selvaraj, Suba, Suganthi, Moonan, Surie, Sathyanarayanan, Gomathi, Jayabal, Sachdeva, Selvaraju, Swaminathan, Tripathy, Hall and Ranganathan.)

Objectives: With the introduction of newer molecular diagnostic tools to identify Mycobacterium tuberculosis , an increasing number of nontuberculous mycobacterium (NTM) is being identified. However, the drug resistance pattern of the NTM species identified is less explored. The objective of this study is to study the drug resistance patterns of Mycobacterium kansasii species isolated in a tuberculosis-endemic setting at South India., Methods: A wide profile of NTM species were reported earlier from a prospective cohort of adults during 2017-2020. Out of this profile, a total of 22 M. kansasii species were subjected to drug susceptibility testing by two different methods: proportion sensitivity testing method and Sensititre testing method., Results: Out of the 18 strains of M. kansasii subjected to Sensititre method of testing, the resistance pattern was demonstrated to be high for doxycycline (13) followed by rifampicin and trimethoprim/sulfamethoxazole (7). Out of the 22 strains subjected to proportion sensitivity testing method, 20 and 10 were resistant to isoniazid and ethambutol, respectively., Conclusion: There was a poor correlation between the treatment outcome and the resistance pattern of the antibiotics tested. With increasing numbers of NTM being reported, early and correct identification of NTM species is essential for the prompt initiation of appropriate treatment to achieve better outcome., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Annals of Thoracic Medicine.)

Tuberculosis prevalence surveys have demonstrated the benefit of screening with chest x-ray (CXR) and sensitive diagnostic tests compared to symptoms and smear microscopy. However, in programmatic practice there is little evidence on the yield of different algorithms. We implemented contact tracing in Chennai, India for adult sputum-positive TB patients registered from January 2015 to March 2016. Patients with symptoms or abnormal X-ray findings further underwent testing using Xpert MTB/RIF (Xpert) and smear microscopy. A retrospective cohort study was done to summarize the key findings. We verbally screened 5553 contacts for symptoms, CXR through private sector collaboration, Xpert, and smear microscopy. Overall, 1312 (23.6%) contacts screened positive. CXR alone identified 531 (40.5%) of them, 679 (51.8%) were symptom-positive only, while 102 (7.8%) were positive on both the symptom and CXR screen. Overall, 35 bacteriologically positive cases were identified (0.7%). A standard approach of symptoms screening followed by microscopy identified only 9 (25.7%) of the total number of bacteriologically positive cases, whereas the combination of a CRX screening followed by microscopy identified 13 (37.1%) of the cases. The algorithm of symptoms screening followed by Xpert testing, detected 20 cases, whereas the combination of symptoms and CXR followed by Xpert increased this number to 35 (75% increase compared to symptoms and Xpert). Optimal use of more sensitive screening tests, better diagnostic tests, and novel private sector engagement can improve diagnostic yield in a programmatic setting., Competing Interests: The authors have declared that no competing interests exist.

Background: Household contacts (HHC) of tuberculosis (TB) patients are at risk of TB infection and disease. The study assessed the utility of "Household contact card and register" for screening of HHC of pulmonary TB (PTB) patients for TB and explored the reasons for HHC not being screened and followed-up., Methods: The "Household contact card and register" was implemented by the Health Care Workers (HCW) of the TB Control Programme in Chennai District for screening HHC of index PTB patients initiated on treatment between June and August, 2018. Contacts were required to be screened within 2 months of treatment initiation of the index patient. Details collected included age, gender, smoking, alcohol use, immunosuppressive conditions and TB treatment. Symptom screening along with chest radiograph and or sputum examination was attempted. Follow-up TB screening at 6 and 12 months were performed. Screening of HHC was compared pre and post implementation phase. Proportions were computed for the data analysed., Results: HHC information was documented for 93% (1268/1364) of Index PTB patients. The main reasons of non-listing of HHC in 96 PTB patients were HCW non-availability or non-co-operation of the HHC. There were 2150 (80%) contacts who were screened for TB. Inconvenient time, feeling healthy, stigma, out-station visit were the main reasons for 537 contacts not undergoing TB screening. Anti-TB treatment was initiated in 21 (1%) of contacts diagnosed with TB. Preventive therapy was initiated in 59% (81/138) of contacts aged <6 years. The screening of HHC improved from 36% to 80% during the implementation phase. Follow-up TB screening at 12 months was performed in 50% of HHC and 2 incident TB cases were identified., Conclusion: "Household contact card and register" is a useful tool for HCWs for TB screening in HHC of PTB patients. Reasons for non-adherence to contact screening needs to be addressed., Competing Interests: The authors have declared that no competing interests exist.

Background: Shortening tuberculosis (TB) treatment duration is a research priority. We tested the efficacy and safety of 3- and 4-month regimens containing moxifloxacin in a randomised clinical trial in pulmonary TB (PTB) patients in South India., Methods: New, sputum-positive, adult, HIV-negative, non-diabetic PTB patients were randomised to 3- or 4-month moxifloxacin regimens [moxifloxacin (M), isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E)] or to a control regimen (2H 3 R 3 Z 3 E 3 /4R 3 H 3 ) [C]. The 4 test regimens were 3R 7 H 7 Z 7 E 7 M 7 [M3], 2R 7 H 7 Z 7 E 7 M 7 /2R 7 H 7 M 7 [M4], 2R 7 H 7 Z 7 E 7 M 7 /2R 3 H 3 M 3 [M4-I] or 2R 7 H 7 Z 7 E 7 M 7 /2R 3 H 3 E 3 M 3 [M4-IE]. Treatment was directly observed. Clinical and bacteriological assessments were done monthly during treatment and for 24 months post-treatment. The primary end point was TB recurrence post-treatment., Results: Of 1371 patients, randomised, modified intention-to-treat (ITT) analysis was done in 1329 and per-protocol (PP) analysis in 1223 patients. Regimen M3 was terminated due to high TB recurrence rates. 'Favourable' response at end of treatment was 96-100% in the moxifloxacin regimens and 93% in the control  regimen. Among these, the TB recurrence occurred in 4.1% in the M4 regimen and in 4.5% in the control regimen and demonstrated equivalence within a 5% margin (95% CI -3.68, 4.55). Similar findings were observed in modified ITT analysis. The TB recurrence rates in the M4-I and M4-IE regimens did not show equivalence with the control regimen. Sixteen (1.4%) of 1087 patients in the moxifloxacin regimens required treatment modification., Conclusion: The 4-month daily moxifloxacin regimen [M4] was found to be equivalent and as safe as the 6-month thrice-weekly control regimen., (© 2020 John Wiley & Sons Ltd.)

Introduction: There is lack of information on the proportion of new smear-positive pulmonary tuberculosis (PTB) patients treated with a 6-month thrice-weekly regimen under Revised National Tuberculosis Control Programme (RNTCP) who develop recurrent TB after successful treatment outcome., Objective: To estimate TB recurrence among newly diagnosed PTB patients who have successfully completed treatment and to document endogenous reactivation or re-infection. Risk factors for unfavourable outcomes to treatment and TB recurrence were determined., Methodology: Adult (aged ≥ 18 yrs) new smear positive PTB patients initiated on treatment under RNTCP were enrolled from sites in Tamil Nadu, Karnataka, Delhi, Maharashtra, Madhya Pradesh and Kerala. Those declared "treatment success" at the end of treatment were followed up with 2 sputum examinations each at 3, 6 and 12 months after treatment completion. MIRU-VNTR genotyping was done to identify endogenous re-activation or exogenous re-infection at TB recurrence. TB recurrence was expressed as rate per 100 person-years (with 95% confidence interval [95%CI]). Regression models were used to identify the risk factors for unfavourable response to treatment and TB recurrence., Results: Of the1577 new smear positive PTB patients enrolled, 1565 were analysed. The overall cure rate was 77% (1207/1565) and treatment success was 77% (1210 /1565). The cure rate varied from 65% to 86%. There were 158 of 1210 patients who had TB recurrence after treatment success. The pooled TB recurrence estimate was 10.9% [95%CI: 0.2-21.6] and TB recurrence rate per 100 person-years was 12.7 [95% CI: 0.4-25]. TB recurrence per 100 person-years varied from 5.4 to 30.5. Endogenous reactivation was observed in 56 (93%) of 60 patients for whom genotyping was done. Male gender was associated with TB recurrence., Conclusion: A substantial proportion of new smear positive PTB patients successfully treated with 6 -month thrice-weekly regimen have TB recurrence under program settings., Competing Interests: The authors have declared that no competing interests exist.

Importance: The benefit of daily over thrice-weekly antituberculosis therapy among HIV-positive patients with pulmonary tuberculosis (TB) who are receiving antiretroviral therapy remains unproven., Objective: To compare the efficacy and safety of daily, part-daily, and intermittent antituberculosis therapy regimens in the treatment of HIV-associated pulmonary TB., Design, Setting, and Participants: This open-label, randomized clinical trial was conducted by the National Institute for Research in Tuberculosis, south India. Adults infected with HIV with newly diagnosed, culture-positive, pulmonary TB were enrolled between September 14, 2009, and January 18, 2016., Interventions: Patients were randomized to daily, part-daily, and intermittent antituberculosis therapy regimens, stratified by baseline CD4 lymphocyte count and sputum smear grade. Antiretroviral therapy was initiated as per national guidelines. Clinical and sputum microbiological examinations of patients were performed monthly until 18 months after randomization. Adverse events were recorded using standard criteria., Main Outcomes and Measures: The primary outcome was favorable response, defined as treatment completion with all available sputum cultures negative for Mycobacterium tuberculosis during the last 2 months of treatment. Unfavorable responses included treatment failures, dropouts, deaths, and toxic effects among regimens., Results: Of 331 patients (251 [76%] male; mean [SD] age, 39 [9] years; mean [SD] HIV viral load, 4.9 [1.2] log10 copies/mL; and median [interquartile range] CD4 lymphocyte count, 138 [69-248] cells/μL), favorable responses were experienced by 91% (89 of 98), 80% (77 of 96), and 77% (75 of 98) in the daily, part-daily, and intermittent regimens, respectively. With the difference in outcome between daily and intermittent regimens crossing the O'Brien-Fleming group sequential boundaries and acquired rifampicin resistance emergence (n = 4) confined to the intermittent group, the data safety monitoring committee halted the study. A total of 18 patients died and 18 patients dropped out during the treatment period in the 3 regimens. Six, 4, and 6 patients in the daily, part-daily, and intermittent regimens, respectively, had TB recurrence., Conclusions and Relevance: Among HIV-positive patients with pulmonary TB receiving antiretroviral therapy, a daily anti-TB regimen proved superior to a thrice-weekly regimen in terms of efficacy and emergence of rifampicin resistance., Trial Registration: clinicaltrials.gov Identifier: NCT00933790.

Background: Pretreatment loss to follow-up (PTLFU) is used as performance indicator of Revised National Tuberculosis Control Programme (RNTCP) of India., Objective: To document the PTLFU, identify additional indicators and examine documentation of all the diagnosed sputum positive pulmonary tuberculosis (PTB) patients under RNTCP., Methodology: Tuberculosis (TB) laboratory, referral for treatment registers, and referral forms were perused for information on sputum positive PTB patients diagnosed from January to June 2014, in 3 TB Units in Chennai., Results: PTLFU was 24% (572 out of 2361). However, in pursuance with the principle of ensuring that all diagnosed patients must be started on treatment following referral, it was inflated to 44% (1046 out of 2361)., Conclusion: The existing PTLFU indicator does not reflect the proportion of treatment initiation of all diagnosed smear-positive PTB patients. We propose additional indicators for monitoring referral and treatment initiation of all diagnosed sputum positive PTB patients., Competing Interests: There are no conflicts of interest.

Objective: Tuberculosis (TB) is a major source of mortality in urban India, with many structural challenges to optimal care delivery. In the government TB program in Chennai, India's fourth most populous city, there is a 49% gap between the official number of smear-positive TB patients diagnosed and the official number registered in TB treatment within the city in 2014. We hypothesize that this "urban registration gap" is partly due to rural patients temporarily visiting the city for diagnostic evaluation., Methods: We collected data for one month (May 2015) from 22 government designated microscopy centers (DMCs) in Chennai where 90% of smear-positive TB patients are diagnosed and coded patient addresses by location. We also analyzed the distribution of chest symptomatics (i.e., patients screened for TB because of pulmonary symptoms) and diagnosed smear-positive TB patients for all of Chennai's 54 DMCs in 2014., Results: At 22 DMCs in May 2015, 565 of 3,543 (15.9%) chest symptomatics and 71 of 412 (17.2%) diagnosed smear-positive patients had an address outside of Chennai. At the city's four high patient volume DMCs, 54 of 270 (20.0%) smear-positive patients lived out-of-city. At one of these high-volume DMCs, 31 of 59 (52.5%) smear-positive patients lived out-of-city. Out of 6,135 smear-positive patients diagnosed in Chennai in 2014, 3,498 (57%) were diagnosed at the four high-volume DMCs. The 32 DMCs with the lowest patient volume diagnosed 10% of all smear-positive patients., Conclusions: TB case detection in Chennai is centralized, with four high-volume DMCs making most diagnoses. One-sixth of patients are from outside the city, most of whom get evaluated at these high-volume DMCs. This calls for better coordination between high-volume city DMCs and rural TB units where many patients may take TB treatment. Patient mobility only partly explains Chennai's urban registration gap, suggesting that pretreatment loss to follow-up of patients who live within the city may also be a major problem.

Background: The Government of India declared TB as a notifiable disease in 2012. There is a paucity of information on the government's mandatory TB notification order from the perspective of private medical practitioners (PPs)., Objective: To understand the awareness, perception and barriers on TB notification among PPs in Chennai, India., Methods: Total of 190 PPs were approached in their clinics by trained field staff who collected data using a semi-structured and pre-coded questionnaire after getting informed consent. The data collected included PPs' specialization, TB management practices, awareness about the TB notification order, barriers in its implementation and their suggestions to improve notification., Results: Of 190 PPs from varied specializations, 138 (73%) had diagnosed TB cases in the prior three months, of whom 78% referred these patients to government facilities. Of 138 PPs, 73% were aware of the order on mandatory TB notification, of whom 46 (33%) had ever notified a TB case. Of 120 PPs, 63% reported reasons for not notifying TB cases. The main reasons reported for not notifying were lack of time (50%), concerns regarding patients' confidentiality (24%) and fear of offending patients (11%). Of 145 PPs, 76% provided feedback about information they felt uncomfortable reporting during notification. PPs felt most uncomfortable reporting patient's government-issued Aadhar number (77%), followed by patient's phone number (37%) and residential address (26%). The preferred means of notification was through mobile phone communication (24%), SMS (18%) and e-mail (17%)., Conclusion: This study highlights that one-fourth of PPs were not aware of the TB notification order and not all those who were aware were notifying. While it is important to sensitize PPs on the importance of TB notification it is also important to understand the barriers faced by PPs and to make the process user-friendly in order to increase TB notification.

Introduction: Tuberculosis (TB) is a notifiable disease and health care providers are required to notify every TB case to local authorities. We conducted a pilot study to determine the usefulness and feasibility of mobile interface in TB notification (MITUN) voice based system for notification of TB cases by private medical practitioners., Methodology: The study was conducted during September 2013 to October 2014 in three zones of Chennai, an urban setting in South India. Private clinics wherein services are provided by single private medical practitioners were approached. The steps involved in MITUN included: Registration of the practitioners and notification of TB cases by them through voice interactions. Pre and post-intervention questionnaires were administered to collect information on TB notification practices and feasibility of MITUN after an implementation period of 6 months., Results: A total of 266 private medical practitioners were approached for the study. Of them, 184 (69%) participated in the study; of whom 11 (6%) practitioners used MITUN for TB notification. Reasons for not using MITUN include lack of time, referral of patients to government facility, issues related to patient confidentiality and technical problems. Suggestions for making mobile phone based TB notification process user-friendly included reducing call duration, including only crucial questions and using missed call or SMS options., Conclusion: The performance (feasibility and usefulness) of MITUN voice based system for TB notification in the present format was sub-optimal. Perceived problems, logistical and practical issues preclude scale-up of notification of TB by private practitioners.