Evaluation of community-based treatment for drug-resistant tuberculosis in Bangladesh.

OBJECTIVE: Drug-resistant tuberculosis (TB) threatens global TB control because it is difficult to diagnose and treat. Community-based programmatic management of drug-resistant TB (cPMDT) has made therapy easier for patients, but data on these models are scarce. Bangladesh initiated cPMDT in 2012, and in 2013, we sought to evaluate programme performance. METHODS: In this retrospective review, we abstracted demographic, clinical, microbiologic and treatment outcome data for all patients enrolled in the cPMDT programme over 6 months in three districts of Bangladesh. We interviewed a convenience sample of patients about their experience in the programme. RESULTS: Chart review was performed on 77 patients. Sputum smears and cultures were performed, on average, once every 1.35 and 1.36 months, respectively. Among 74 initially culture-positive patients, 70 (95%) converted their cultures and 69 (93%) patients converted the cultures before the sixth month. Fifty-two (68%) patients had evidence of screening for adverse events. We found written documentation of musculoskeletal complaints for 16 (21%) patients, gastrointestinal adverse events for 16 (21%), hearing loss for eight (10%) and psychiatric events for four (5%) patients; conversely, on interview of 60 patients, 55 (92%) reported musculoskeletal complaints, 54 (90%) reported nausea, 36 (60%) reported hearing loss, and 36 (60%) reported psychiatric disorders. CONCLUSIONS: The cPMDT programme in Bangladesh appears to be programmatically feasible and clinically effective; however, inadequate monitoring of adverse events raises some concern. As the programme is brought to scale nationwide, renewed efforts at monitoring adverse events should be prioritised.

Isoniazid resistance pattern among pulmonary tuberculosis patients in Bangladesh: an exploratory study.

OBJECTIVES: In high TB burden countries like Bangladesh, research and policies tend to focus on rifampicin (RIF)-resistant TB patients, leaving RIF sensitive but isoniazid (INH) resistant (Hr-TB) patients undiagnosed. Our study aims to determine the prevalence of INH resistance among pulmonary TB (PTB) patients in selected healthcare facilities in Bangladesh. METHODS: This study was conducted across nine TB Screening and Treatment Centers situated in Bangladesh. Sputum samples from 1084 Xpert-positive PTB patients were collected between April 2021 and December 2022, and cultured for drug susceptibility testing (DST). Demographic and clinical characteristics of Hr-TB and drug-susceptible TB patients were compared. RESULTS: Among available DST results of 998 culture positive isolates, resistance rate of any INH regardless of RIF susceptibility was 6.4% (64/998, 95% CI, 4.9-8.2). The rate was significantly higher in previously treated (21.1%, 16/76, 95% CI, 12.0-34.2) compared to newly diagnosed TB patients (5.2%, 48/922, 95% CI, 3.8-6.9) (p <0.001). The rate of Hr-TB was 4.5% (45/998, 95% CI, 3.3-6.0), which was also higher among previously treated (6.6%, 5/76, 95% CI, 1.4-13.5) compared to newly diagnosed TB patients (4.3%; 40/922, 95% CI, 3.1-5.9) (p=0.350). Most importantly, the rate of Hr-TB was more than double compared to MDR-TB (4.5%, 45/998, vs 1.9%, 19/998) found in the current study. CONCLUSIONS: This study reveals a high prevalence of Hr-TB, surpassing even that of the MDR-TB in Bangladesh. This emphasizes the urgent need to adopt WHO-recommended molecular tools at the national level for rapid detection of INH resistance so that patients receive timely and appropriate treatment.

Short, highly effective, and inexpensive standardized treatment of multidrug-resistant tuberculosis.

RATIONALE: Based on expert opinion, the global guidelines for management of multidrug-resistant tuberculosis impose lengthy and often poorly tolerated treatments. OBJECTIVES: This observational study evaluates the effectiveness of standardized regimens for patients with proven multidrug-resistant tuberculosis previously untreated with second-line drugs in low-income countries. METHODS: Consenting patients were sequentially assigned to one of six standardized treatment regimens. Subsequent cohorts were treated with regimens adapted according to results in prior cohorts. The study was designed to minimize failure and default while reducing total treatment duration without increasing relapse frequency. MEASUREMENTS AND MAIN RESULTS: We report the treatment outcome of all patients with laboratory-confirmed, multidrug-resistant tuberculosis enrolled from May 1997 to December 2007. The most effective treatment regimen required a minimum of 9 months of treatment with gatifloxacin, clofazimine, ethambutol, and pyrazinamide throughout the treatment period supplemented by prothionamide, kanamycin, and high-dose isoniazid during an intensive phase of a minimum of 4 months, giving a relapse-free cure of 87.9% (95% confidence interval, 82.7-91.6) among 206 patients. Major adverse drug reactions were infrequent and manageable. Compared with the 221 patients treated with regimens based on ofloxacin and commonly prothionamide throughout, the hazard ratio of any adverse outcome was 0.39 (95% confidence interval, 0.26-0.59). CONCLUSIONS: Serial regimen formulation guided by overall treatment effectiveness resulted in treatment outcomes comparable to those obtained with first-line treatment. Confirmatory formal trials in populations with high levels of human immunodeficiency virus coinfection and in populations with a higher initial prevalence of resistance to second-line drugs are required.

Decentralized, Community-Based Treatment for Drug-Resistant Tuberculosis: Bangladesh Program Experience.

BACKGROUND: Bangladesh is a highly populous country where the prevalence of drug-resistant tuberculosis (DR-TB) is growing. With the rapid increase in DR-TB notifications through GeneXpert technology, it was imperative to come up with a new treatment strategy that could keep up with the increase of patients diagnosed. INTERVENTION: Intervention was designed to support national transition of DR-TB management of World Health Organization-approved long course (20-to-24-month regimen) treatment from a hospital-based approach to the decentralized model of community-based programmatic management of DR-TB (cPMDT). In close coordination with the Ministry of Health and Family Welfare and National TB Program, patients were initiated into treatment at hospitals and then transferred to community-based care. A cadre of directly observed therapy providers supported treatment at the household level, supervised by the outpatient DR-TB teams. METHODS: We conducted a descriptive pre- and post-intervention study of all 1,946 DR-TB patients enrolled in treatment nationwide between May 2012 and June 2015. Data were collected from hospitals, patient cards, district records, and diagnostic laboratories through the National TB Program. Intervention results were assessed in comparison with the baseline (2011) indicators. RESULTS: During the intervention period, treatment enrollment of 1,946 diagnosed DR-TB patients through the national program increased from 50% in 2011 to 100% in 2015. The delay between diagnosis and treatment initiation decreased from 69 days in 2011 to 6 days in 2014. Most (95%) of the patients completed all scheduled follow-up smear and culture tests. By the sixth month of treatment, 99% of patients had negative smear conversion and 98% had negative culture conversion. The treatment success rate increased from 70% in 2011 to 76% in 2015 at the end of the intervention period. The results also indicate a decline between baseline and end line from 14% to 9% for patients died, 14% to 10% for loss to follow-up, and 1.7% to 0% for treatment failure. CONCLUSIONS: Community-based management is an effective approach for increasing access to quality-assured DR-TB treatment. Using existing structures and resources, the intervention demonstrated that favorable treatment outcomes can be achieved and sustained by treating patients with DR-TB at their homes.

Turning liabilities into resources: informal village doctors and tuberculosis control in Bangladesh.

In 1998, the Damien Foundation Bangladesh invited semi-qualified, private "gram dakter" (Bangla for "village doctors") to participate in tuberculosis (TB) programmes in a population of 26 million people in rural Bangladesh. The organization trained 12 525 village doctors to not only refer suspected TB cases for free diagnosis but also to provide directly observed treatment (DOT) free of charge. Source of referral and place of DOT was recorded as part of the standardized TB recording and reporting system, which enabled us to quantify the contribution of village doctors to case detection rates and also allowed disaggregated cohort analysis of treatment outcome. During 2002 and 2003, 11% of all TB cases with positive sputum smears in the study area had been referred by village doctors; the rate of positive tests in patients referred by village doctors was 14.4%. 18 792 patients received DOT from village doctors, accounting for between 20% and 45% of patients on treatment during the 1998-2003 period. The treatment success rate was about 90% throughout the period. Urine samples taken during random checks of treatment compliance were positive for isoniazid in 98% of patients treated by village doctors. Within the framework of Public-Private Mix DOTS, services provided by semi-qualified private health care providers are a feasible and effective way to improve access to affordable high quality TB treatment in poor rural populations. The large informal health workforce that exists in resource poor countries can be used to achieve public health goals. Involvement of village doctors in TB control has now become national policy in Bangladesh.