The Cost-Effectiveness of the BEAT-TB Regimen for Pre-Extensively Drug-Resistant TB

Objective: To measure the economic impacts of the longer pre-XDR-TB treatment regimen and the shorter BEAT-TB India regimen. Methods: In the current study, the economic impacts of the current 18-month pre-XDR-TB treatment regimen and the 6–9 month BEAT-TB regimen were evaluated using an economic model via a decision tree analysis from a societal perspective. The incremental costs and quality-adjusted life years (QALYs) gained from the introduction of the BEAT- TB regimen for pre-XDR-TB patients were estimated. Results: For a cohort of 1000 pre-XDR-TB patients, we found that the BEAT-TB India regimen yielded higher undiscounted life years (40,548 vs.21,009) and more QALYs gained (27,633 vs. 15,812) than the 18-month regimen. The BEAT-TB India regimen was found to be cost-saving, with an incremental cost of USD −128,651 when compared to the 18-month regimen. The current analysis did not consider the possibility of reduced TB recurrence after use of the BEAT-TB regimen, so it might have under-estimated the benefits. Conclusion: As a lower-cost intervention with improved health outcomes, the BEAT-TB India regimen is dominant when compared to the 18-month regimen

Bedaquiline, Delamanid, Linezolid and Clofazimine for Treatment of Pre-extensively Drug-Resistant Tuberculosis.

BACKGROUND Treatment success rates for multidrug-resistant tuberculosis (MDR-TB) remain low globally. Availability of newer drugs has given scope to develop regimens that can be patient-friendly, less toxic, with improved outcomes. We proposed to determine the effectiveness of an entirely oral, short-course regimen with Bedaquiline and Delamanid in treating MDR-TB with additional resistance to fluoroquinolones (MDR-TBFQ+) or second-line injectable (MDR-TBSLI+). METHODS We prospectively determined the effectiveness and safety of combining two new drugs with two repurposed drugs - Bedaquiline, Delamanid, Linezolid, and Clofazimine for 24-36 weeks in adults with pulmonary MDR-TBFQ+ or/and MDR-TBSLI+. The primary outcome was a favorable response at end of treatment, defined as two consecutive negative cultures taken four weeks apart. The unfavorable outcomes included bacteriologic or clinical failure during treatment period. RESULTS Of the 165 participants enrolled, 158 had MDR-TBFQ+. At the end of treatment, after excluding 12 patients due to baseline drug susceptibility and culture negatives, 139 of 153 patients (91%) had a favorable outcome. Fourteen patients (9%) had unfavorable outcomes: four deaths, seven treatment changes, two bacteriological failures, and one withdrawal. During treatment, 85 patients (52%) developed myelosuppression, 69 (42%) reported peripheral neuropathy, and none had QTc(F) prolongation >500msec. At 48 weeks of follow-up, 131 patients showed sustained treatment success with the resolution of adverse events in the majority. CONCLUSION After 24-36 weeks of treatment, this regimen resulted in a satisfactory favorable outcome in pulmonary MDR-TB patients with additional drug resistance. Cardiotoxicity was minimal, and myelosuppression, while common, was detected early and treated successfully

The Cost-Effectiveness of the BEAT-TB Regimen for Pre-Extensively Drug-Resistant TB

: To measure the economic impacts of the longer pre-XDR-TB treatment regimen and the shorter BEAT-TB India regimen. Methods: In the current study, the economic impacts of the current 18-month pre-XDR-TB treatment regimen and the 6–9 month BEAT-TB regimen were evaluated using an economic model via a decision tree analysis from a societal perspective. The incremental costs and quality-adjusted life years (QALYs) gained from the introduction of the BEATTB regimen for pre-XDR-TB patients were estimated. Results: For a cohort of 1000 pre-XDR-TB patients, we found that the BEAT-TB India regimen yielded higher undiscounted life years (40,548 vs. 21,009) and more QALYs gained (27,633 vs. 15,812) than the 18-month regimen. The BEAT-TB India regimen was found to be cost-saving, with an incremental cost of USD −128,651 when compared to the 18-month regimen. The current analysis did not consider the possibility of reduced TB recurrence after use of the BEAT-TB regimen, so it might have under-estimated the benefits. Conclusion: As a lower-cost intervention with improved health outcomes, the BEAT-TB India regimen is dominant when compared to the 18-month regimen

The Cost-Effectiveness of the BEAT-TB Regimen for Pre-Extensively Drug-Resistant TB

Objective: To measure the economic impacts of the longer pre-XDR-TB treatment regimen and the shorter BEAT-TB India regimen. Methods: In the current study, the economic impacts of the current 18-month pre-XDR-TB treatment regimen and the 6–9 month BEAT-TB regimen were evaluated using an economic model via a decision tree analysis from a societal perspective. The incremental costs and quality-adjusted life years (QALYs) gained from the introduction of the BEAT-TB regimen for pre-XDR-TB patients were estimated. Results: For a cohort of 1000 pre-XDR-TB patients, we found that the BEAT-TB India regimen yielded higher undiscounted life years (40,548 vs. 21,009) and more QALYs gained (27,633 vs. 15,812) than the 18-month regimen. The BEAT-TB India regimen was found to be cost-saving, with an incremental cost of USD −128,651 when compared to the 18-month regimen. The current analysis did not consider the possibility of reduced TB recurrence after use of the BEAT-TB regimen, so it might have under-estimated the benefits. Conclusion: As a lower-cost intervention with improved health outcomes, the BEAT-TB India regimen is dominant when compared to the 18-month regimen

Feasibility of decentralised deployment of Xpert MTB/RIF test at lower level of health system in India.

BackgroundXpert MTB/RIF is an automated cartridge-based nucleic acid amplification test that has demonstrated its potential to detect tuberculosis and rifampicin resistance with high accuracy. To assist scale-up decisions in India, a feasibility assessment of Xpert MTB/RIF implementation was conducted within microscopy centres of 18 RNTCP TB units.MethodsAs part of programme-based demonstration of Xpert MTB/RIF implementation, we recorded and analysed association between key implementation factors and the ability of test to produce valid results. Factors contributing to test failures were analysed from GeneXpert software data which provides 'failure codes' and causes for test failures.ResultsFrom March'12 to January'13, total 40,035 suspects were tested by Xpert MTB/RIF, and 39,680 (99.1%) received valid results (Cumulative: 37157 (92.8%) on first attempt, 39410 (98.4%) on second attempt, 39637 (99.0%) on third attempt and 39680 (99.1%) on more attempts). Overall initial test failure was 2,878 (7.2% (4%-17%)); of these, 2,594 (90.1%) were re-tested and produced valid results. Most frequent reason of test failure was inadequate sample processing or equipment malfunction (3.9%). Other reasons included power failure (1.1%), cartridge integrity/component failure (0.8%), device-computer communication error (0.5%), and temperature-related errors (0.08%). Significant variation was observed in failure rates both across instruments and over time; furthermore, substantial variation was observed in failure rate in two cartridges lots.ConclusionInstallation required minimal infrastructure modifications and concerns about adequacy of human resources under public sector facilities and temperature extremes proved unfounded. Under routine conditions, Xpert MTB/RIF provided 99.1% valid results in TB suspects with low overall failure rates (7.2% initial failure, 0.9% final failure); devices provided valuable real-time feedback on reasons for test failure, which were used for rapid corrective action. High modular replacement (32%) and inter-lot cartridge performance variation remain sources of concern, and warrant close monitoring of failure rates as a key quality indicator

Data_Sheet_1_Comprehensive assessment of invalid and indeterminate results in Truenat MTB-RIF testing across sites under the national TB elimination program of India.docx

IntroductionTruenat MTB-RIF assay (Truenat), a nucleic acid amplification test (NAAT), is a real-time polymerase chain reaction (RT-PCR) chip-based assay that can detect Mycobacterium tuberculosis (Mtb) and rifampicin (RIF) drug resistance using portable, battery-operated devices. The National TB Elimination Program (NTEP) in India introduced this novel tool at the district and subdistrict level in 2020. This study aimed to assess the level and causes of inconclusive results (invalid results, errors, and indeterminate results) in MTB and RIF testing at NTEP sites and the root causes of these in the programmatic setting.MethodsTruenat testing data from 1,690 functional Truenat sites under the NTEP from April to June 2021 were analyzed to assess the rates of errors, invalid MTB results, and indeterminate RIF results. Following this analysis, 12 Truenat sites were selected based on site performance in Truenat testing, diversity of climatic conditions, and geographical terrain. These sites were visited to assess the root causes of their high and low rates of inconclusive results using a structured checklist.ResultsA total of 327,649 Truenat tests performed for MTB and RIF testing were analyzed. The rate of invalid MTB results was 5.2% [95% confidence interval (CI): 5.11–5.26; n = 16,998] and the rate of errors was 2.5% (95% CI: 2.46–2.57; n = 8,240) in Truenat MTB chip testing. For Mtb-positive samples tested using the Truenat RIF chip for detection of RIF resistance (n = 40,926), the rate of indeterminate results was 15.3% (95% CI: 14.97–15.67; n = 6,267) and the rate of errors was 1.6% (95% CI: 1.53–1.78; n = 675). There was a 40.1% retesting gap for Mtb testing and a 78.2% gap for inconclusive RR results. Among the inconclusive results retested, 27.9% (95% CI: 27.23–28.66; n = 4,222) were Mtb-positive, and 9.2% (95% CI: 7.84–10.76; n = 139) were detected as RR.ConclusionThe main causes affecting Truenat testing performance include suboptimal adherence to standard operating procedures (SOPs), inadequate training, improper storage of testing kits, inadequate sputum quality, lack of quality control, and delays in the rectification of machine issues. Root cause analysis identified that strengthening of training, external quality control, and supervision could improve the rate of inconclusive results. Ensuring hands-on training of technicians for Truenat testing and retesting of samples with inconclusive results are major recommendations while planning for Truenat scale-up. The recommendations from the study were consolidated into technical guidance documents and videos and disseminated to laboratory staff working at the tiered network of TB laboratories under the NTEP in order to improve Truenat MTB-RIF testing performance.</p

Data_Sheet_2_Comprehensive assessment of invalid and indeterminate results in Truenat MTB-RIF testing across sites under the national TB elimination program of India.docx

IntroductionTruenat MTB-RIF assay (Truenat), a nucleic acid amplification test (NAAT), is a real-time polymerase chain reaction (RT-PCR) chip-based assay that can detect Mycobacterium tuberculosis (Mtb) and rifampicin (RIF) drug resistance using portable, battery-operated devices. The National TB Elimination Program (NTEP) in India introduced this novel tool at the district and subdistrict level in 2020. This study aimed to assess the level and causes of inconclusive results (invalid results, errors, and indeterminate results) in MTB and RIF testing at NTEP sites and the root causes of these in the programmatic setting.MethodsTruenat testing data from 1,690 functional Truenat sites under the NTEP from April to June 2021 were analyzed to assess the rates of errors, invalid MTB results, and indeterminate RIF results. Following this analysis, 12 Truenat sites were selected based on site performance in Truenat testing, diversity of climatic conditions, and geographical terrain. These sites were visited to assess the root causes of their high and low rates of inconclusive results using a structured checklist.ResultsA total of 327,649 Truenat tests performed for MTB and RIF testing were analyzed. The rate of invalid MTB results was 5.2% [95% confidence interval (CI): 5.11–5.26; n = 16,998] and the rate of errors was 2.5% (95% CI: 2.46–2.57; n = 8,240) in Truenat MTB chip testing. For Mtb-positive samples tested using the Truenat RIF chip for detection of RIF resistance (n = 40,926), the rate of indeterminate results was 15.3% (95% CI: 14.97–15.67; n = 6,267) and the rate of errors was 1.6% (95% CI: 1.53–1.78; n = 675). There was a 40.1% retesting gap for Mtb testing and a 78.2% gap for inconclusive RR results. Among the inconclusive results retested, 27.9% (95% CI: 27.23–28.66; n = 4,222) were Mtb-positive, and 9.2% (95% CI: 7.84–10.76; n = 139) were detected as RR.ConclusionThe main causes affecting Truenat testing performance include suboptimal adherence to standard operating procedures (SOPs), inadequate training, improper storage of testing kits, inadequate sputum quality, lack of quality control, and delays in the rectification of machine issues. Root cause analysis identified that strengthening of training, external quality control, and supervision could improve the rate of inconclusive results. Ensuring hands-on training of technicians for Truenat testing and retesting of samples with inconclusive results are major recommendations while planning for Truenat scale-up. The recommendations from the study were consolidated into technical guidance documents and videos and disseminated to laboratory staff working at the tiered network of TB laboratories under the NTEP in order to improve Truenat MTB-RIF testing performance.</p

Use of Xpert MTB/RIF in Decentralized Public Health Settings and Its Effect on Pulmonary TB and DR-TB Case Finding in India

Xpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in high-burden settings. This study assessed the impact of up-front Xpert MTB/RIF testing on detection of pulmonary tuberculosis (PTB) and rifampicin-resistant PTB (DR-TB) cases in India. This demonstration study was implemented in 18 sub-district level TB programme units (TUs) in India in diverse geographic and demographic settings covering a population of 8.8 million. A baseline phase in 14 TUs captured programmatic baseline data, and an intervention phase in 18 TUs had Xpert MTB/RIF offered to all presumptive TB patients. We estimated changes in detection of TB and DR-TB, the former using binomial regression models to adjust for clustering and covariates. In the 14 study TUs, which participated in both phases, 10,675 and 70,556 presumptive TB patients were enrolled in the baseline and intervention phase, respectively, and 1,532 (14.4%) and 14,299 (20.3%) bacteriologically confirmed PTB cases were detected. The implementation of Xpert MTB/RIF was associated with increases in both notification rates of bacteriologically confirmed TB cases (adjusted incidence rate ratio [aIRR] 1.39; CI 1.18-1.64), and proportion of bacteriological confirmed TB cases among presumptive TB cases (adjusted risk ratio (aRR) 1.33; CI 1.6-1.52). Compared with the baseline strategy of selective drug-susceptibility testing only for PTB cases at high risk of drug-resistant TB, Xpert MTB/RIF implementation increased rifampicin resistant TB case detection by over fivefold. Among, 2765 rifampicin resistance cases detected, 1055 were retested with conventional drug susceptibility testing (DST). Positive predictive value (PPV) of rifampicin resistance detected by Xpert MTB/RIF was 94.7% (CI 91.3-98.1), in comparison to conventional DST. Introduction of Xpert MTB/RIF as initial diagnostic test for TB in public health facilities significantly increased case-notification rates of all bacteriologically confirmed TB by 39% and rifampicin-resistant TB case notification by fivefol

Initial test results and final test results on Xpert MTB/RIF (N = 40,035 patients tested).

<p>* <i>Break up of test failure results - Error, Invalid, No results</i></p

Trend in error rates of modules.

<p>Trend in error rates of modules.</p