Seven-year DOTS-Plus pilot experience in India: results, constraints and issues.

BACKGROUND: India is initiating the DOTS-Plus strategy at the national level. OBJECTIVES: To highlight the results, constraints and issues of a pilot DOTS-Plus experience in an urban setting in India. METHODS: Records of 126 patients with multidrug-resistant tuberculosis (MDR-TB) enrolled from January 2002 to December 2006, who received a daily fully supervised standardised treatment regimen under a pilot DOTS-Plus study in India, were analysed retrospectively. RESULTS: Of the 126 patients enrolled, 61% were cured, 19% died, 18% defaulted and 3% failed treatment. There was an average delay of 5 months in the diagnosis of MDR-TB and a subsequent delay of approximately 3.3 months in initiating treatment. Of the 24 patients who died, 29% did so within a month of starting treatment. Migration was the most common reason for default. Cycloserine (CYC) had to be stopped in 15 patients and kanamycin (KM) in five due to major adverse effects. CONCLUSIONS: The DOTS-Plus programme in resource-poor settings may provide reasonable results; however, it may confront significant operational difficulties in the timely diagnosis and early initiation of treatment. Early diagnosis and start of treatment may prevent some deaths. Default is commonly due to migration. CYC proved to be the most toxic drug, followed by KM.

Risk factors for new pulmonary tuberculosis patients failing treatment under the Revised National Tuberculosis Control Programme, India.

SETTING: Tertiary level tuberculosis (TB) institute in Delhi, India. OBJECTIVE: To study the risk factors for new pulmonary TB (PTB) patients failing treatment. DESIGN: Prospective case-control study. The profile of new PTB patients failing treatment (i.e., sputum smear-positive at 5 months of treatment) and responders under the Revised National Tuberculosis Control Programme (RNTCP) were compared and risk factors associated with treatment failure were analysed. RESULTS: A total of 42 treatment failure cases and 76 controls were enrolled in the study. The presence of cavity on chest X-ray (CXR), sputum acid-fast bacilli (AFB) smear positivity at 2 months of treatment and the number of interruptions in treatment were independently associated with failures. Among failure patients at 5 months, 17 (40.5%) had negative sputum culture for Mycobacterium tuberculosis, and only six (14.3%) had multidrug-resistant TB (MDR-TB). When put on retreatment, patients with smear-positive, culture-negative sputum had cure rates of 88.2% compared to 28.6% among culture-positive patients. CONCLUSIONS: The presence of cavity on CXR, sputum smear positivity at 2 months of treatment and the number of interruptions of treatment are risk factors for failure. Among failures based on smear examination, the prevalence of MDR-TB is low and many patients have negative cultures for M. tuberculosis. Smear positivity at the end of treatment may not be a reliable indicator of treatment failure.

Early efficacy and safety of Bedaquiline and Delamanid given together in a "Salvage Regimen" for treatment of drug-resistant tuberculosis.

BACKGROUND: Drug-Resistant Tuberculosis (DR-TB) patients for whom a WHO recommended regimen along with Bedaquiline (BDQ) cannot be prescribed, Delamanid (DLM) was added along with other drugs to provide a "Salvage Regimen". The experience of the Institute in respect of early efficacy and safety of both drugs given together is presented. OBJECTIVE: To ascertain the early efficacy, safety and tolerability of Bedaquline and Delamanid given together as a part of salvage regimen. METHODS: BDQ and DLM were used together to make regimens along with other drugs where four effective anti TB drugs could not be prescribed as per WHO recommendations. Patients were followed up for sputum smear and culture conversion and adverse events during the treatment. RESULTS: In this cohort study, 53 DR-TB patients (Median age-24) were initiated on regimens containing both BDQ and DLM. Sputum smear conversion was seen in 35% and 94% patients at the end of 1st week and 3rd month respectively. 84% patients had culture conversion at the end of 4th month. 29 adverse events (AE) were reported among 17 patients and there were 11 deaths. QTc prolongation more than 500 MS was seen in only 1 patient. CONCLUSION: BDQ and DLM given together in a salvage regimen is efficacious with low rate of adverse events. The combination provides hope to DR-TB patients with limited treatment options and should be provided as a life saving option.

Initial experience of bedaquiline implementation under the National TB Programme at NITRD, Delhi, India.

BACKGROUND: Bedaquiline (BDQ) was approved for treatment of drug resistant TB (DR-TB) under Conditional Access Programme (CAP) of Revised National Tuberculosis Control Programme (RNTCP) and was also implemented in the National Institute of TB and Respiratory Diseases (NITRD). We present early efficacy and safety of BDQ containing regimens for DR-TB. OBJECTIVE: To ascertain the early efficacy and safety of Bedaquline containing regimens in treatment of DR-TB. METHODS: BDQ containing regimens along with other drugs were designed as per WHO recommendations for DR-TB patients. They were followed up for sputum smear and culture conversion, adverse events during the treatment. RESULTS: A cohort of 290 DR-TB patients (Median age-29.77) were initiated on BDQ containing regimens. Of the available Sputum results, smear conversion was seen in 51% and 91% patients at the end of 1st week and 3rd month respectively. Similarly, 93% and 98% patients had culture conversion at the end of 3rd and 6th month respectively. 201 adverse events (AE) including 47 deaths were reported among 109 patients. QTc prolongation was seen in 29% patients but only 4 required discontinuation of BDQ. Lost to follow up of treatment was about 6%. CONCLUSION: Bedaquiline along with an optimized background regimen has shown early sputum conversion in larger number of difficult to treat patients having additional resistance of second line drugs along with INH and Rifampicin. The regimen is feasible in programmatic conditions and is relatively safe.

The DOTS strategy for treatment of paediatric pulmonary tuberculosis in South Delhi, India.

SETTING: Paediatric Pulmonology Department, TB Institute, New Delhi, India. OBJECTIVE: To evaluate the outcome of the DOTS strategy for paediatric pulmonary tuberculosis (TB). DESIGN: Retrospective analysis of 1098 children. RESULTS: The mean age of the children included in the study was 11.2 years, with more females (61.7%) than males (38.3%). In the 0-5, 6-10 and 11-14 year age groups, the percentage of patients was respectively 18.3%, 26.6% and 55.1%. Patients were registered as new cases (87.7%), relapses (1.9%), failures (1.0%), defaulters (5.0%), transferred in (0.9%) and others (3.5%). Of the total number of cases, 414 were smear-positive and 404 smear-negative, while sputum status was not known for 280 patients. Sputum positivity increased with age. Category I, II and III regimens were started by respectively 50.6%, 10.5% and 38.9% patients. The cure rate was 92.4% (302/327) for new and 92% (80/87) for retreatment cases (chi(2)(1) = 0.02, P = 0.901), but the treatment completion rate was significantly higher for new cases (97%, 636/656) than retreatment cases (53.6%, 15/28) (chi(2)(1) = 100.8, P < 0.001). The overall success rate was 95.4% and 82.6% for new and retreatment cases, respectively (chi(2)(1) = 30.35, P < 0.001). Overall, the rates for default, failure and death in the study were respectively 3%, 1.9% and 1%. CONCLUSION: DOTS appears to be a highly efficacious treatment strategy.

Prevalence of pulmonary tuberculosis among adults in selected slums of Delhi city.

BACKGROUND: A survey was carried out to estimate the point prevalence of bacteriologically positive pulmonary tuberculosis (PTB) among persons ≥15 years of age residing in Jhuggi-Jhopri (JJ) colonies - urban slums in Delhi, India implementing Directly Observed Treatment strategy since 1998. METHODS: Among 12 JJ colonies selected by simple random sampling, persons having persistent cough for ≥2 weeks at the time of the survey or cough of any duration along with history of contact/currently on ant-TB treatment/known HIV positive were subjected to sputum examination - 2 specimens, by smear microscopy for Acid Fast Bacilli and culture for Mycobacterium tuberculosis. Persons with at least one specimen positive were labelled as bacteriologically confirmed PTB. Prevalence was estimated after imputing missing values to correct bias introduced by incompleteness of data and corrected for non-screening by X-ray by a multiplication factor derived from recently conducted surveys. RESULTS: Of 40,756 persons registered, 40,529 (99.4%) were screened. Of them, 691 (2%) were eligible for sputum examination. Spot specimens were collected from 659 (99.2%) and early morning sputum specimens from 647 (98.1%). Using screening by interview alone, prevalence of bacteriologically positive PTB in persons ≥15 years of age was estimated at 160.4 (123.7-197.1) per 100,000 populations and210.0 (CI: 162.5-258.2) after correcting for non-screening by X-ray. CONCLUSION: Observed prevalence suggests further strengthening of TB control program in urban slums.

Clinical profile and treatment outcome of tuberculous lymphadenitis in children using DOTS strategy.

BACKGROUND: Extra pulmonary TB (EPTB) including tuberculous lymphadenitis is becoming more common probably due to human immuno deficiency virus (HIV) co-infection. While children do experience a high TB related morbidity and mortality, management of TB in children is challenging. The present study was designed to study the treatment outcome of DOTS strategy for pediatric tuberculous lymphadenitis. OBJECTIVE: To study the efficacy of DOTS strategy for pediatric lymphhnode tuberculosis. METHODS: Retrospective analysis of 669 children of lymphnode tuberculosis treated with DOTS strategy over 9 1/2 years. RESULTS: Mean age was 9.8 years with significantly more girls (61.3%) than boys (38.7%) {chi2=34.08, P<0.001 (S)}. Most of the patients were in the age group of 11-14 years (48.0%) followed by 6-10 years (34.5%) and 0-5 years (17.5%) respectively. Cervical tuberculous lymphadenitis (88.2%) was the commonest form for all ages followed by axillary lymphadenitis in 3.3%. TB of other sites was seen in only 57 (8.5%) cases. Out of total 622 (93%) cases of lymphnode TB where fine needle aspiration and/or excisional biopsy was done, it was positive (84.2%) and negative (15.6%) respectively for AFB/cytology, while it could not be done in 47 patients due to inaccessible sites. Category I, II and III was started on 15.4%, 7.5% and 77.1% patients respectively. Overall, treatment completion rate was 94.9% and the default rate was 2.2% with a failure rate of 2.5%. Death rate was 0.3%. CONCLUSION: The study confirms the efficacy of DOTS strategy for pediatric TB lymphadenitis.

Smear microscopy as surrogate for culture during follow up of pulmonary MDR-TB patients on DOTS Plus treatment.

BACKGROUND: DOTS Plus site at LRS Institute, New Delhi, covering 1.8 million population. AIMS: To ascertain if sputum smear could be used as a surrogate for culture during intensive phase of treatment of MDR-TB patients thereby enabling early shift from intensive phase to continuation phase, reducing the need for frequent cultures and saving time and cost in their management. METHODS: The study is a retrospective analysis of 138 MDR-TB patients on DOTS Plus treatment whose sputum samples were simultaneously subjected to smear microscopy and culture, monthly during Intensive Phase and once in two months during Continuation Phase. Sputum results in the treatment card were supplemented from laboratory register, if required, and analyzed. Predictive values, sensitivity and specificity of smear were compared with culture results. RESULTS: The Negative Predictive Value (NPV) of smear was high from the 3rd month onwards (above 91%), at four months 98% or more and approached 100% from eight months onwards. The specificity of smear test gradually increased during treatment and from five months onwards, it was above 90%. CONCLUSIONS: Considerable correlation was observed between sputum smear and culture during follow up of DOTS Plus treatment in the Intensive Phase. Accordingly, sputum smears can be recommended instead of culture.

Clinical profile and treatment outcome of tubercular pleurisy in pediatric age group using DOTS strategy.

BACKGROUND: A significant proportion of global tuberculosis (TB) caseload is contributed by children. Management of pediatric TB especially EPTB is challenging. The present study was designed to study demographic, clinical profile and treatment outcome of DOTS strategy for pediatric tubercular pleurisy. AIM: To study the efficacy of DOTS strategy. METHODS: Retrospective analysis of 106 TB pleurisy children treated with DOTS. RESULTS: Mean age was 10.8 years (median age 12.2 years) with more females (51.9%) than males (48.1%) chi1(2) = 0.15; P = 0.698 (NS). In the age group of 0-5, 6-10 and 11-14 years, there were 15.1%, 30.2% and 54.7% patients respectively. Fever was the commonest symptom (98.1%) followed by cough (77.4%) and chest pain (55.7%). History of contact could be elicited only in 2/3rd of cases unilateral effusion (61.3%) was commonest, followed by empyema (22.6%), massive effusion and broncho-pleural fistula each in 13.2% cases respectively. Bilateral effusion was seen in 3.8% cases only. Conventional methods (mantoux, radiograph, ultrasound, pleural aspiration) and minimal invasive surgical techniques, percutaneous pleural biopsy were done to arrive at the diagnosis. Diagnosis was made by X-ray Chest in 92.5%, exudative pleural fluid (100%) predominantly lymphocytic in 85.8%, positive AFB smear and culture in 4.7 and 5.7% cases respectively. Category I, II and III was started on 35.9%, 2.8% and 61.3% patients respectively. Overall treatment completion rate was 94.3%, 4.7% default rate, 0.9% failure rate and no deaths. CONCLUSION: The study confirms early detection by simple tests and ensuring complete treatment using DOTS strategy.