Long-Term Intake of Linezolid Elevates Drug Exposure and Reduces Drug Clearance and Elimination in Adults With Drug-Resistant Pulmonary Tuberculosis.

PURPOSE: Pharmacokinetic (PK) studies are critical for dose optimization, and there is a paucity of linezolid (LZD) PK data for prolonged use in drug-resistant tuberculosis (DR-TB). Therefore, the authors evaluated the pharmacokinetics of LZD at two-time intervals in DR-TB during long-term use. METHODS: PK evaluation of LZD was performed at the end of the 8th and 16th weeks of treatment in a randomly selected subset of adult pre-extensively drug-resistant pulmonary tuberculosis patients (n = 18) from a multicentric interventional study (Building Evidence to Advance Treatment of TB/BEAT study; CTRI/2019/01/017310), wherein a daily dose of 600 mg LZD was used for 24 weeks. Plasma LZD levels were measured using a validated high-pressure liquid chromatography (HPLC) method. RESULTS: The LZD median plasma C max was comparable between the 8th and 16th weeks [18.3 mg/L, interquartile range (IQR: 15.5-20.8 and 18.8 mg/L, IQR: 16.0-22.7, respectively)]. However, the trough concentration increased significantly in the 16th week (3.16 mg/L, IQR: 2.30-4.76), compared with the 8th week (1.98 mg/L, IQR: 0.93-2.75). Furthermore, compared with the 8th week, in the 16th week, there was a significant increase in drug exposure (AUC 0-24 = 184.2 mg*h/L, IQR: 156.4-215.8 versus 233.2 mg*h/L, IQR: 187.9-277.2), which corroborated with a longer elimination half-life (6.94 hours, IQR: 5.55-7.99 versus 8.47 hours, IQR:7.36-11.35) and decreased clearance (2.91 L/h, IQR: 2.45-3.33 versus 2.19 L/h, IQR: 1.49-2.78). CONCLUSIONS: Long-term daily intake of 600 mg LZD resulted in a significant elevation in trough concentration (>2.0 mg/L) in 83% of the study participants. Furthermore, increased LZD drug exposure may be partly because of decreased clearance and elimination. Overall, the PK data underscore the need for dose adjustment when LZDs are intended for long-term treatment.

Factors affecting the treatment outcome of injection based shorter MDR-TB regimen at a referral centre in India.

Rifampicin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB) is a significant burden on global tuberculosis (TB) prevention and eradication efforts. MDR-TB can be treated, but it is expensive, takes a long time (typically two years) and contains potentially toxic drugs. Under certain conditions, the WHO recommends standard regimens lasting 9 to 11 months rather than individual regimens lasting at least 18-20 months. The current study sought to identify factors associated with treatment outcomes in RR/MDR-TB patients receiving an injection-based regimen for 9-11 months. This ambispective (prospective and retrospective) observational study was conducted at a tertiary tuberculosis institute in New Delhi, India. Between February 2021 and March 2022, patients with RR/MDR-pulmonary TB who received an injection-based shorter regimen were enrolled. Factors related to treatment outcomes were investigated and compared in patients who had a successful outcome versus those who did not. A total of 55 patients were enrolled, with 50.91% being successful (cured/treatment completed) and 49.09% failing (including failure, lost to follow up, death, and regimen change). The following factors were significantly associated with the unsuccessful outcome, according to univariate analysis: BMI (<18.5 kg/m2), anaemia, previous anti-TB treatment, bilateral chest X-ray involvement, and far advanced disease on chest X-ray. BMI (<18.5 kg/m2), anaemia, and far advanced disease on chest X-ray were all significantly associated with mortality. Anaemia was associated with an unsuccessful outcome (p=0.049) and mortality (p=0.048) in the multiple logistic regression analysis. Early treatment initiation, improved nutrition and anaemia, and regular monitoring can all improve RR/MDR-TB patients' outcomes and prognoses.

Trends & treatment outcomes of multidrug-resistant tuberculosis in Delhi, India (2009-2014): A retrospective record-based study.

Background & objectives: The increase in the burden of multidrug-resistant tuberculosis (MDR-TB) is a matter of grave concern. The present study was undertaken to describe MDR-TB treatment outcome trends in Delhi and their epidemiological correlates, to assess the adequacy of treatment records and to also generate evidence towards influencing and improving practices related to the MDR-TB control programme. Methods: A retrospective record-based study (2009-2014) was conducted in three major drug resistance TB treatment centres of Delhi. Treatment outcomes and adverse effects were extracted from the existing programme records including patients' treatment cards and laboratory registers. Results: A total of 2958 MDR-TB patients were identified from the treatment cards, of whom 1749 (59.12%) were males. The mean (±standard deviation) age was 30.56±13.5 years. Favourable treatment outcomes were reported in 1371 (53.28%) patients, but they showed a declining trend during the period of observation. On binomial logistic regression analysis, patients with age ≥35 yr, male sex and undernourishment (body mass index <18.5) at the time of treatment initiation had a significantly increased likelihood of unfavourable MDR-TB treatment outcome (P <0.001). Interpretation & conclusions: The study showed an increasing burden of MDR-TB patients, especially in the young population with increased risk of transmission posing a major challenge in achieving TB elimination targets.

Situation Analysis of Early Implementation of Programmatic Management of Tuberculosis Preventive Treatment among Household Contacts of Pulmonary TB Patients in Delhi, India.

Tuberculosis Preventive Treatment (TPT) is a powerful tool for preventing the TB infection from developing into active TB disease, and has recently been expanded to all household contacts of TB cases in India. This study employs a mixed-methods approach to conduct a situational analysis of the initial phase of TPT implementation among household contacts of pulmonary TB patients in three districts of Delhi, India. It was completed using a checklist based assessments, care cascade data, and qualitative analysis. Our observations indicated that organizational structure and planning were established, but implementation of TPT was suboptimal with issues in drug availability and procurement, budget, human resources, and training. Awareness and motivation, and shorter regimen, telephonic assessment, and collaboration with NGOs emerged as enablers. Apprehension about taking TPT, erratic drug supply, long duration of treatment, side effects, overburden, large population, INH resistance, data entry issues, and private provider reluctance emerged as barriers. The study revealed potential solutions for optimizing TPT implementation. It is evident that, while progress has been made in TPT implementation, there is room for improvement and refinement across various domains.

Chronic pulmonary aspergillosis in a tertiary tuberculosis institute: A common entity missed commonly.

The disease chronic pulmonary aspergillosis (CPA), which has 3 million cases globally, has a substantial impact on global health. The morbidity and mortality it cause are also rather severe. Patients with modest immune suppression or those with underlying structural and chronic lung illnesses are more likely to develop this condition. CPA pose a diagnostic and management challenge to clinicians. The condition causes patients to have persistent respiratory difficulties, which lowers their quality of life, and the therapy is lengthy and offers few choices. Particularly in a nation like India, where tuberculosis (TB) is prevalent and patients exhibit identical signs and symptoms, a strong index of suspicion is required. Treated pulmonary TB patients, presenting with symptoms or chest x-ray abnormalities, especially those with presence of cavity are also more prone to develop CPA. The constellation of symptoms together with presence of microbiological criteria and suggestive radiology can help to reach at the diagnosis. The field of mycology has made major developments, but there is still much to understand about this illness and to establish timely diagnoses and make the best use of the existing treatment choices. The burden of CPA in patients with treated TB is highlighted in this article along with the most recent research and clinical guidelines.

Outcomes and Challenges in the Programmatic Implementation of Tuberculosis Preventive Therapy among Household Contacts of Pulmonary TB Patients: A Mixed-Methods Study from a Rural District of Karnataka, India.

The National TB Elimination Programme (NTEP) of India is implementing tuberculosis preventive treatment (TPT) for all household contacts (HHCs) of pulmonary tuberculosis patients (index patients) aged <5 years and those HHCs aged >5 years with TB infection (TBI). We conducted an explanatory mixed-methods study among index patients registered in the Kolar district, Karnataka during April-December 2022, to assess the TPT cascade and explore the early implementation challenges for TPT provision. Of the 301 index patients, contact tracing home visits were made in 247 (82.1%) instances; a major challenge was index patients' resistance to home visits fearing stigma, especially among those receiving care from the private sector. Of the 838 HHCs, 765 (91.3%) were screened for TB; the challenges included a lack of clarity on HHC definition and the non-availability of HHCs during house visits. Only 400 (57.8%) of the 692 eligible HHCs underwent an IGRA test for TBI; the challenges included a shortage of IGRA testing logistics and the perceived low risk among HHCs. As HHCs were unaware of their IGRA results, a number of HHCs actually eligible for TPT could not be determined. Among the 83 HHCs advised of the TPT, 81 (98%) initiated treatment, of whom 63 (77%) completed treatment. Though TPT initiation and completion rates are appreciable, the NTEP needs to urgently address the challenges in contact identification and IGRA testing.

Test and Treat Model for Tuberculosis Preventive Treatment among Household Contacts of Pulmonary Tuberculosis Patients in Selected Districts of Maharashtra: A Mixed-Methods Study on Care Cascade, Timeliness, and Early Implementation Challenges.

Tuberculosis preventive treatment (TPT) is an important intervention in preventing infection and reducing TB incidence among household contacts (HHCs). A mixed-methods study was conducted to assess the "Test and Treat" model of TPT care cascade among HHCs aged ≥5 years of pulmonary tuberculosis (PTB) patients (bacteriologically/clinically confirmed) being provided TPT care under Project Axshya Plus implemented in Maharashtra (India). A quantitative phase cohort study based on record review and qualitative interviews to understand the challenges and solutions in the TPT care cascade were used. Of the total 4181 index patients, 14,172 HHCs were screened, of whom 36 (0.3%) HHCs were diagnosed with tuberculosis. Among 14,133 eligible HHCs, 10,777 (76.3%) underwent an IGRA test. Of them, 2468 (22.9%) tested positive for IGRA and were suggested for chest X-ray. Of the eligible 2353 HHCs, 2159 (91.7%) were started on TPT, of whom 1958 (90.6%) completed the treatment. The median time between treatment initiation of index PTB patient and (a) HHC screening was 31 days; (b) TPT initiation was 64 days. The challenges in and suggested solutions for improving the TPT care cascade linked to subthemes were tuberculosis infection testing, chest X-ray, human resources, awareness and engagement, accessibility to healthcare facilities, TPT drugs, follow-up, and assessment. A systematic monitoring and time-based evaluation of TPT cascade care delivery followed by prompt corrective actions/interventions could be a crucial strategy for its effective implementation and for the prevention of tuberculosis.

Preparedness for establishing COVID-19 services during acute emergency of COVID-19 pandemic: Experience of a tertiary care TB and respiratory diseases hospital.

BACKGROUND: The ongoing coronavirus disease 2019 (COVID-19) calls for setting up of well-equipped and dedicated health facilities to manage sick patients while protecting healthcare workers and the environment. An ideal high-level isolation unit requires a high level of administrative commitment, availability of space, human resource and logistics. METHOD: The experience of setting up COVID-19 care facilities on a noticeably short period in a tertiary TB and respiratory diseases institute in wake of the COVID-19 pandemic is being shared here. RESULT: All the essential COVID-19 services were set up in record time of 8 days. A total of 115 COVID-19 patients were admitted. Out of these 89 patients were discharged in a satisfactory condition. There were 19 deaths, and 4 patients became critical and had to be referred to level 3 facility for ICU care. CONCLUSION: This experience will help other hospitals in planning out the strategies and solve the difficulties they may face while opening a COVID-19 care facility under limited resources on an urgent basis.

Treatment interruption patterns and adverse events among patients on bedaquiline containing regimen under programmatic conditions in India.

BACKGROUND: The study aimed to analyze frequency and severity of adverse events (AEs) and other reasons for interruption of treatment and loss to follow up (LTFU) during first six months of treatment among tuberculosis patients on bedaquiline containing regimens. METHODS: This pilot exploratory observational study included 275 patients enrolled consecutively over two years who received bedaquiline containing regimen under programmatic conditions in India. RESULTS: Among 275 patients with median age of 25 years, 86 (31.3%) patients had at least one interruption with 122 total episodes of interruption. Among these 70 were temporary, 35 were permanent interruptions and 17 were LTFU. The AEs due to drugs were the commonest reason for interruption observed in 81.4% of temporary interruption group and 97.1% of permanent interruption group. Among a total 192 adverse event episodes, (49.5%) were minor (grade 1-2) and (50.5%) were serious (grade 3-5). Personal factors were the commonest reason for interruption observed in LTFU (94.1%) group. The most common temporarily interrupted drug was bedaquiline in 8.7% and permanently stopped drug was linezolid in 5% of patients. CONCLUSIONS: Our study observed that drug related AEs are important risk factors associated with treatment interruptions in bedaquiline containing regimens. Bedaquiline is the most common temporarily interrupted drug due to AEs.

Appreciative inquiry and the co-creation of an evaluation framework for Extension for Community Healthcare Outcomes (ECHO) implementation: a two-country experience.

Persistent gaps exist in healthcare workers' capacity to address HIV and tuberculosis in Asia and Africa due to constraints in resources and knowledge. Project ECHO (Extension for Community Healthcare Outcomes) leverages video-enabled technology to build workforce capacity and promote collaboration through mentorship and case-based learning. To understand current perceptions of ECHO participants and develop a comprehensive evaluation framework for ECHO implementation, we utilized modified appreciative inquiry guided focus group discussions (FGD) in India and Tanzania and called it SCORE (Strengths, Challenges, Opportunities, Results, and Evaluation). Content and thematic analysis of transcripts from FGDs and key-informant interviews triangulated perceptions of diverse stakeholders about ECHO implementation and identified key elements for development of the framework. The perceived strengths (S) were capacity building and establishing communities of practice. The perceived challenges (C) included securing resources, engaging leadership, and building systems for monitoring impact. Improved internet connectivity, addressing logistical challenges, encouraging session interactivity, and having strategic scale-up plans were perceived opportunities (O). Additionally, gathering measurable results (R) led to development of a comprehensive evaluation (E) framework. Contextualizing and facilitating SCORE with qualitative analysis of findings 6-12 months post-ECHO implementation may serve as a best practice to assess mid-course corrections to improve ECHO implementation quality.

Suppressors of cytokine signaling inhibit effector T cell responses during Mycobacterium tuberculosis infection.

Protective immune responses during Mycobacterium tuberculosis (M. tuberculosis) infection are regulated at multiple levels and critically dependent on the balance in the secretion of pro-inflammatory and regulatory cytokines. A key factor that governs this balance at the cellular level is suppressors of cytokine signaling (SOCS). We recently demonstrated that toll-like receptor 2 and dendritic cell (DC)-SIGNR1 differentially regulate SOCS1 expression in DCs during M. tuberculosis infection. This consecutively regulated IL-12 production and determined M. tuberculosis survival. In this study, we characterized the role of SOCS1 in regulating effector responses from CD4(+) and CD8(+) T cells during M. tuberculosis infection. Our data indicate that T cells from M. tuberculosis-infected mice show increased and differential association of SOCS1 with CD3 and CD28, when compared with uninfected mice. While SOCS1 displays increased association with CD3 than CD28 in CD4(+) T cells; SOCS1 is associated more with CD28 than CD3 in CD8(+) T cells. Further, SOCS1 shows increased association with IL-12 and IL-2 receptors in both CD4(+) and CD8(+) T cells from infected mice when compared with naive mice. Silencing SOCS1 in T cells increased signal transduction from T cell receptor (TCR) and CD28 with enhanced activation of key signaling molecules and proliferation. Significantly, SOCS1-silenced T cells mediated enhanced clearance of M. tuberculosis inside macrophages. Finally, adoptive transfer of SOCS1-silenced T cells in M. tuberculosis-infected mice mediated significant reduction in M. tuberculosis loads in spleen. These results exemplify the negative role played by SOCS1 during T cell priming and effector functions during M. tuberculosis infection.

"99DOTS"techno-supervision for tuberculosis treatment - A boon or a bane? Exploring challenges in its implementation at a tertiary centre in Delhi, India.

BACKGROUND: In India, daily regimen with fixed-dose combination along with 99DOTS adherence tool and one-stop service at Anti-Retroviral Treatment (ART) centres for HIV infected Tuberculosis (TB) patients was launched in 2017. No systematic evaluation of its implementation has been done so far in a tertiary care setting in urban India. METHODS: A mixed-methods study was conducted at National Institute of Tuberculosis and Respiratory Diseases, Delhi in 2018-19. Missed doses, average adherence and treatment outcomes were compared across 99DOTS dashboard and TB treatment card. In-depth interviews of patients and health care providers were conducted to explore the implementation challenges and benefits. RESULTS: Median of missed doses recorded during intensive and continuation phase were 56 and 68 respectively in 99DOTS as compared to 0 in the TB Treatment card (p<0.0001). Average adherence was observed to be 27% in 99DOTS versus 99% in the TB treatment card (p<0.0001). Technical issues like software malfunction, logistic difficulties such as missing custom envelops and patient's inability to give call were reported. Role clarity among ART and TB program staff was ambiguous, which contributed to poor information flow between them. Patient benefits such as reduced stigma, less travel costs and reduced work absenteeism were reported. CONCLUSION: Success of 99DOTS program under programmatic condition needs webtool stability, uninterrupted logistic supplies (envelops), training of staff and better coordination between TB and HIV program personnel. Despite the challenges in its implementation, the benefit of this tool in terms of greater convenience and reduced stigma for patients is encouraging.

Nikshay Poshan Yojana (NPY) for tuberculosis patients: Early implementation challenges in Delhi, India.

BACKGROUND: Nutrition support is one of the essential factors for envisioning Tuberculosis (TB) elimination in India by 2025. In this regard, Government of India introduced Nikshay Poshan Yojana (NPY) through Direct Benefit Transfer (DBT) as monthly financial assistance towards nutrition for TB patients in April, 2018. Assessment of early implementation challenges of the scheme is essential. OBJECTIVE: (a) To determine the number (proportion) of TB patients who received the benefits (b) to explore the challenges encountered by the health care providers in delivering the NPY through DBT (c) to explore the ways the incentives were utilised by the patients. MATERIAL AND METHODS: It was a cross-sectional study conducted among patients registered for TB treatment at Ladosarai and Mehrauli DOTS centre between July-September, 2018.Health providers engaged in implementation of NPY at the study sites were also interviewed. The data were collected through structured questionnaires, double entered and analyzed in Epi Data. RESULTS: Out of 119 patients registered, we interviewed 57 (47.9%) patients. Of which, 30 (52.6%) had received NPY for 2 months in the fourth and fifth month of treatment. The health providers reported increased workload, lack of training and complex reporting formats as main hurdles in implementation of the scheme. While, the patients cited non-availability of bank accounts and unlinked bank account with Aadhar card as difficulties to receive NPY through DBT. CONCLUSION: Nearly half of the interviewed TB patients received nutritional incentives of NPY through DBT for 2 months. Non-availability of bank accounts and unlinked bank accounts were some challenges faced by both health providers and patient. It is recommended to address these implementation on time in order to reap the benefit of scheme in improving nutritional status of TB patients. Further studies are needed to determine the effect of nutrition support on TB patients.

Identifying costs contributing to catastrophic expenditure among TB patients registered under RNTCP in Delhi metro city in India.

BACKGROUND: Tuberculosis (TB) patients often incur large costs related to illness, as well as for seeking and receiving health care. Despite TB treatment being free under RNCTP, out of pocket expenditure incurred (OOP) by patients for TB diagnosis and treatment impoverishes the households. This expenditure may turn catastrophic (more than 20% of their family income) impacting adherence and leading to poor treatment outcomes. OBJECTIVE: To estimate the proportion of households experiencing catastrophic expenditure due to TB and also to find out the various costs contributing to catastrophic expenditure. METHODS: In this cohort study, 450 TB patients (including 96 children) registered under Revised National Tuberculosis Control Programme (RNTCP) in Delhi were interviewed at three different time points (in the beginning of treatment, end of intensive phase, end of treatment). Interview schedule was used to collect information on direct medical and non-medical, and indirect costs. The TB-specific indicator of "catastrophic total costs" incorporates both, direct medical and non-medical payments for treatment such as transportation, lodging charges and indirect costs such as wage loss. RESULTS: A total of 450 patients were enrolled in this study, out of which 425 were followed up to the end of treatment. It was observed that 7% of TB patients registered under RNTCP in Delhi experienced catastrophic expenditure due to TB. The total mean cost to patients with TB was Rs. 12165 (Rs. 1406 during diagnosis and Rs. 10759 during treatment). The indirect cost was higher compared to direct cost i.e.Rs. 7564 and Rs. 4601 respectively). CONCLUSION: This information will be useful for policy makers to design an intervention to provide financial protection to TB patients. In addition, findings of this study will aid in providing baseline evidence to periodically measure the OOP which is the one of the End TB strategy target.

Pattern and trends of drug sensitivity in MDR-TB cases in Delhi (2009-2014): A record based study.

BACKGROUND: This study was conducted with the objective to understand pattern and trends in drug sensitivity among MDR-TB cases in Delhi from 2009 to 2014 using existing records. METHODS: A retrospective record-based study was conducted at three Drug-resistant TB (DR-TB) treatment centers in Delhi. For data collection, patient treatment cards and TB registers were accessed. All multidrug-resistant (DR) TB patients registered, and initiated on treatment from January 2009 to December 2014 in three DR-TB centers were included in the study. RESULTS: A cumulative total of 2958 MDR-TB cases were registered in the three DR-TB centers during the period from Jan 2009 to December 2014. The median value time interval between culture test result and initiation of treatment was 82 days. High resistance was found against Streptomycin (70%), Ethambutol (40.1%), Ofloxacin (42.4%) and Kanamycin (12%). Favorable treatment outcomes ranged from 52.5% to 56.9% in cases resistant to only first-line anti-TB drugs but was much lower in the pre XDR-TB cases (26.3%) and XDR-TB cases (12.5%). CONCLUSION: The proportion of cases with additional resistance to ofloxacin, kanamycin, ethionamide, and streptomycin increased over time from 2009 to 2014. Reducing the time to treatment initiation from initial diagnosis of MDR-TB could further improve treatment outcomes.

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.

Sequelae of pulmonary multidrug-resistant tuberculosis at the completion of treatment.

BACKGROUND: Treatment of multidrug-resistant (MDR-TB) mainly focuses on bacteriological cure. However, only limited studies have evaluated the sequelae left after the completion of treatment among MDR-TB patients. OBJECTIVE: To assess the persistent symptoms, radiological sequelae, pulmonary function impairment and quality of life at the completion of treatment among MDR-TB patients. METHODS: Forty six MDR-TB patients were enrolled, who completed two years of treatment under programmatic management of Drug Resistant tuberculosis at a tertiary referral institute in Delhi, India. Detailed clinical history was taken. X-ray chest, 6 Minute Walk Test and pulmonary function tests were attempted in all patients. Quality of life was evaluated using Seattle obstructive lung disease questionnaire. RESULTS: At the completion of MDR-TB treatment 95.7% patients had residual symptoms; 100% patients had residual bilateral chest x-ray abnormality with 82.6% patients showing far advanced disease. PFT was abnormal in 97.6% patients with mixed pattern being the commonest abnormality. Quality of Life was impaired with mean physical function of 46%. CONCLUSION: At the completion of MDR-TB treatment, significant numbers of patients are left with post treatment sequelae. The medical management and social support for these patients should be incorporated in the national programs.

Recurrence of tuberculosis among newly diagnosed sputum positive pulmonary tuberculosis patients treated under the Revised National Tuberculosis Control Programme, India: A multi-centric prospective study.

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.

Efficacy and Safety of Mycobacterium indicus pranii as an adjunct therapy in Category II pulmonary tuberculosis in a randomized trial.

Prolonged treatment of tuberculosis (TB) often leads to poor compliance, default and relapse, converting primary TB patients into category II TB (Cat IITB) cases, many of whom may convert to multi-drug resistant TB (MDR-TB). We have evaluated the immunotherapeutic potential of Mycobacterium indicus pranii (MIP) as an adjunct to Anti-Tubercular Treatment (ATT) in Cat II pulmonary TB (PTB) patients in a prospective, randomized, double blind, placebo controlled, multicentric clinical trial. 890 sputum smear positive Cat II PTB patients were randomized to receive either six intra-dermal injections (2 + 4) of heat-killed MIP at a dose of 5 × 108 bacilli or placebo once in 2 weeks for 2 months. Sputum smear and culture examinations were performed at different time points. MIP was safe with no adverse effects. While sputum smear conversion did not show any statistically significant difference, significantly higher number of patients (67.1%) in the MIP group achieved sputum culture conversion at fourth week compared to the placebo (57%) group (p = 0.0002), suggesting a role of MIP in clearance of the bacilli. Since live bacteria are the major contributors for sustained incidence of TB, the potential of MIP in clearance of the bacilli has far reaching implications in controlling the spread of the disease.