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Conference Material > Slide Presentation

Community based person-centered TB care by trained TB survivors under Unite to ACT project in India​ ​

Das M, Kalra A, Mohapatra S, Kumar S, Panda A,  et al.
MSF Scientific Days Asia 2024. 8 November 2024
Journal Article > ResearchFull Text

Concomitant bedaquiline and delamanid therapy in patients with drug-resistant extra-pulmonary tuberculosis in Mumbai, India

Journal of Clinical Tuberculosis and Other Mycobacterial Diseases. 1 April 2024; Volume 35; 100433.; DOI:10.1016/j.jctube.2024.100433
Mongia H, Mamnoon F, Silsarma A, Mahajan R, Dalal A,  et al.
Journal of Clinical Tuberculosis and Other Mycobacterial Diseases. 1 April 2024; Volume 35; 100433.; DOI:10.1016/j.jctube.2024.100433
BACKGROUND
World Health Organization suggests concurrent bedaquiline-delamanid (BDQ-DLM) as part of individualised regimens for eligible patients with pulmonary drug-resistant tuberculosis (DR-TB); however, data for patients with drug-resistant extrapulmonary tuberculosis (EPTB) is extremely limited. This study documents the treatment outcomes and adverse events associated with concurrent BDQ-DLM-based regimens in patients with drug-resistant EPTB at a Médecins Sans Frontières clinic in Mumbai, India.

METHODS
Retrospective cohort study based on routinely collected programmatic data. Individualised regimens were based on drug-susceptibility testing and previous drug exposure. Drug-resistant EPTB patients initiated on regimens containing concurrent BDQ and DLM from April 2016 to October 2019 were included. Patients who completed treatment were followed up at 12 months.

RESULTS
Of 17 patients, median age was 23 years (IQR = 21-30 years) and 12/17 (71 %) were female. Pre-extensively drug-resistant tuberculosis and extensively drug-resistant TB was reported in 13/17 (76.4 %) and 2/17 (11.7 %) patients respectively. Microbiological reports were unavailable for two patients with central nervous system TB. Lymph node TB was the commonest form of EPTB in 9/17 (53 %) of patients. Median duration of treatment was 18.9 months. At least one grade three or four severe adverse event (SAE) was reported by 13/17 (76.4 %) patients. Thirteen (76.4 %) patients had favourable outcomes. None of the patients relapsed or died in the one-year period of post-treatment follow-up.

CONCLUSION
Concurrent BDQ-DLM-based regimens in drug-resistant EPTB were effective and associated with manageable adverse events.
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Journal Article > ResearchFull Text

Operationalising targeted next-generation sequencing for routine diagnosis of drug-resistant TB

Public Health Action. 21 June 2023; Volume 13 (Issue 2); 43-49.; DOI:10.5588/pha.22.0041
Iyer AS, Ndlovu Z, Sharma J, Mansoor H, Bharati M,  et al.
Public Health Action. 21 June 2023; Volume 13 (Issue 2); 43-49.; DOI:10.5588/pha.22.0041
English
Français
BACKGROUND
Phenotypic drug susceptibility testing (pDST) for Mycobacterium tuberculosis can take up to 8 weeks, while conventional molecular tests identify a limited set of resistance mutations. Targeted next-generation sequencing (tNGS) offers rapid results for predicting comprehensive drug resistance, and this study sought to explore its operational feasibility within a public health laboratory in Mumbai, India.

METHODS
Pulmonary samples from consenting patients testing Xpert MTB-positive were tested for drug resistance by conventional methods and using tNGS. Laboratory operational and logistical implementation experiences from study team members are shared below.

RESULTS
Of the total number of patients tested, 70% (113/161) had no history of previous TB or treatment; however, 88.2% (n = 142) had rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB). There was a high concordance between resistance predictions of tNGS and pDST for most drugs, with tNGS more accurately identifying resistance overall. tNGS was integrated and adapted into the laboratory workflow; however, batching samples caused significantly longer result turnaround time, fastest at 24 days. Manual DNA extraction caused inefficiencies; thus protocol optimisations were performed. Technical expertise was required for analysis of uncharacterised mutations and interpretation of report templates. tNGS cost per sample was US$230, while for pDST this was US$119.

CONCLUSIONS
Implementation of tNGS is feasible in reference laboratories. It can rapidly identify drug resistance and should be considered as a potential alternative to pDST.
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Journal Article > ResearchFull Text

Clinical utility of target-based next-generation sequencing for drug-resistant TB

Int J Tuberc Lung Dis. 1 January 2023; Volume 27 (Issue 1); 41-48.; DOI:10.5588/ijtld.22.0138
Mansoor H, Hirani N, Chavan VV, Das M, Sharma J,  et al.
Int J Tuberc Lung Dis. 1 January 2023; Volume 27 (Issue 1); 41-48.; DOI:10.5588/ijtld.22.0138
BACKGROUND
In high TB burden countries, access to drug susceptibility testing is a major bottleneck. Targeted next-generation sequencing (tNGS) is a promising technology for rapid resistance detection. This study assessed the role of tNGS for the diagnosis of drug-resistant TB (DR-TB).

METHODS
A total of 161 samples from bacteriologically confirmed TB cases were subjected to tNGS using the Deeplex® Myc-TB kit and sequenced using the MiSeq platform. These samples were also processed for conventional phenotypic DST (pDST) using 13 drugs on Mycobacteria Growth Indicator Tube and line-probe assays (MTBDR plus and MTBDRsl).

RESULTS
There were 146 DR-TB and 15 drug-susceptible TB (DS-TB) samples. About 70% of patients with DR-TB had no previous TB treatment history. Overall, 88.2% had rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB), 58.5% pre-extensively drug-resistant TB (pre-XDR-TB) and 9.2% had XDR-TB as defined by the WHO (2020). Around 8% (n=13) of samples were non-culturable; however, identified 8 were resistant to first and second-line drugs using tNGS. Resistance frequency was similar across methods, with discordance in drugs less reliable using pDST or with limited mutational representation within databases. Sensitivities were aligned with literature reports for most drugs. We observed 10% heteroresistance, while 75% of strains were of Lineages 2 and 3.

CONCLUSIONS
Programme data supported tNGS in the diagnosis of DR-TB for early treatment using individualised regimens.
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Journal Article > ResearchFull Text

Impact of intensified case-finding strategies on childhood TB case registration in Nepal

Public Health Action. 21 June 2015; Volume 5 (Issue 2); 93-98.; DOI:10.5588/pha.15.0004
Joshi B, Chinnakali P, Shrestha A, Das M, Kumar AMV,  et al.
Public Health Action. 21 June 2015; Volume 5 (Issue 2); 93-98.; DOI:10.5588/pha.15.0004
SETTING
Seven intervention districts with intensified childhood tuberculosis (TB) case-finding strategies implemented by a non-governmental organisation and seven control districts under the National Tuberculosis Programme, Nepal.

OBJECTIVES
To assess the differences in childhood TB case registrations and case registration rates per 100 000 population between two time periods (Year 1 = March 2012-March 2013 and Year 2 = March 2013-March 2014) in intervention and control districts.

DESIGN
Retrospective record review using routinely collected data.

RESULTS
Childhood TB cases increased from 271 to 360 between Years 1 and 2 in the intervention districts (case registration rate from 18.2 to 24.2/100 000) and from 97 to 113 in the control districts (13.4 to 15.6/100 000): the increases were significantly higher in the intervention districts compared with the control districts. The increases were also significantly higher in children aged 0-4 years and in those with smear-negative pulmonary TB and extra-pulmonary TB. Of the various case-finding strategies, household contact screening, private-public mix services and mobile health chest camps produced the highest yield of TB.

CONCLUSION
A package of intensified case-finding strategies in children was associated with an increase in childhood TB case registrations in Nepal. Additional diagnostic approaches to increase case registrations also need to be considered.
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Journal Article > ResearchFull Text

Surgical interventions for pulmonary tuberculosis in Mumbai, India: Surgical outcomes and programmatic challenges India: surgical outcomes and programmatic challenges

Public Health Action. 21 September 2016; Volume 6 (Issue 3); 193-198.; DOI:10.5588/pha.16.0043
Shirodkar S, Anande L, Dalal A, Desai C, Correa G,  et al.
Public Health Action. 21 September 2016; Volume 6 (Issue 3); 193-198.; DOI:10.5588/pha.16.0043
SETTING
While surgery for pulmonary tuberculosis (PTB) is considered an important adjunct for specific cases, including drug-resistant tuberculosis, operational evidence on its feasibility and effectiveness is limited.

OBJECTIVE
To describe surgical outcomes and programmatic challenges of providing surgery for PTB in Mumbai, India.

DESIGN
A descriptive study of routinely collected data of surgical interventions for PTB from 2010 to 2014 in two Mumbai hospitals, one public, one private.

RESULTS
Of 85 patients, 5 (6%) died and 17 (20%) had complications, with wound infection being the most frequent. Repeat operation was required in 12 (14%) patients. Most procedures were performed on an emergency basis, and eligibility was established late in the course of treatment. Median time from admission to surgery was 51 days. Drug susceptibility test (DST) patterns and final treatment outcomes were not systematically collected.

CONCLUSION
In a high-burden setting such as Mumbai, important data on surgery for PTB were surprisingly limited in both the private and public sectors. Eligibility for surgery was established late, culture and DST were not systematically offered, the interval between admission and surgery was long and TB outcomes were not known. Systematic data collection would allow for proper evaluation of surgery as adjunctive therapy for all forms of TB under programmatic conditions.
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Journal Article > ResearchFull Text

Treatment outcomes of children and adolescents receiving drug-resistant TB treatment in a routine TB programme, Mumbai, India

PLOS One. 18 February 2021; Volume 16 (Issue 2); e0246639.; DOI:10.1371/journal.pone.0246639
Dhakulkar S, Das M, Sutar N, Oswal V, Shah D,  et al.
PLOS One. 18 February 2021; Volume 16 (Issue 2); e0246639.; DOI:10.1371/journal.pone.0246639
BACKGROUND
Childhood and adolescent drug-resistant TB (DR-TB) is one of the neglected infectious diseases. Limited evidence exists around programmatic outcomes of children and adolescents receiving DR-TB treatment. The study aimed to determine the final treatment outcomes, culture conversion rates and factors associated with unsuccessful treatment outcome in children and adolescents with DR-TB.

METHODS
This is a descriptive study including children (0-9 years) and adolescents (10-19 years) with DR-TB were who were initiated on ambulatory based treatment between January 2017-June 2018 in Shatabdi hospital, Mumbai, India where National TB elimination programme(NTEP) Mumbai collaborates with chest physicians and Médecins Sans Frontières(MSF) in providing comprehensive care to DR-TB patients. The patients with available end-of-treatment outcomes were included. The data was censored on February 2020.

RESULT
A total of 268 patients were included; 16 (6%) of them were children (0-9 years). The median(min-max) age was 17(4-19) years and 192 (72%) were females. Majority (199, 74%) had pulmonary TB. Most (58%) had MDR-TB while 42% had fluoroquinolone-resistant TB. The median(IQR) duration of treatment (n = 239) was 24(10-25) months. Median(IQR) time for culture-conversion (n = 128) was 3(3-4) months. Of 268 patients, 166(62%) had successful end-of-treatment outcomes (cured-112; completed treatment-54). Children below 10 years had higher proportion of successful treatment outcomes (94% versus 60%) compared to adolescents. Patients with undernutrition [adjusted odds-ratio, aOR (95% Confidence Interval, 95%CI): 2.5 (1.3-4.8) or those with XDR-TB [aOR (95% CI): 4.3 (1.3-13.8)] had higher likelihood of having unsuccessful DR-TB treatment outcome.

CONCLUSIONS
High proportion of successful treatment outcome was reported, better than global reports. Further, the nutritional support and routine treatment follow up should be strengthened. All oral short and long regimens including systematic use of new TB drugs (Bedaquiline and Delamanid) should be rapidly scaled up in routine TB programme, especially for the paediatric and adolescent population.
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Journal Article > ResearchFull Text

Comparing Yield and Relative Costs of WHO TB Screening Algorithms in Selected Risk Groups Among People Aged 65 Years and Over in China, 2013

PLOS One. 8 June 2017; Volume 12 (Issue 6); DOI:10.1371/journal.pone.0176581
Zhang C, Ruan Y, Cheng J, Zhao F, Xia Y,  et al.
PLOS One. 8 June 2017; Volume 12 (Issue 6); DOI:10.1371/journal.pone.0176581
To calculate the yield and cost per diagnosed tuberculosis (TB) case for three World Health Organization screening algorithms and one using the Chinese National TB program (NTP) TB suspect definitions, using data from a TB prevalence survey of people aged 65 years and over in China, 2013.More
Journal Article > Short ReportFull Text

Treating All Multidrug-Resistant Tuberculosis Patients, Not Just Bacteriologically Confirmed Cases

Public Health Action. 21 June 2016; Volume 6 (Issue 2); DOI:10.5588/pha.16.0023
Das M, Isaakidis P, Van der Bergh R, Kumar AMV, Sharath BN,  et al.
Public Health Action. 21 June 2016; Volume 6 (Issue 2); DOI:10.5588/pha.16.0023
Journal Article > ResearchFull Text

Psychiatric comorbidities among patients with complex drug-resistant tuberculosis in Mumbai, India

PLOS One. 11 February 2022; Volume 17 (Issue 2); e0263759.; DOI:10.1371/journal.pone.0263759
Laxmeshwar C, Das M, Mathur T, Israni T, Jha S,  et al.
PLOS One. 11 February 2022; Volume 17 (Issue 2); e0263759.; DOI:10.1371/journal.pone.0263759
BACKGROUND
People with drug-resistant tuberculosis (DR-TB) are known to suffer from many mental-health disorders. This study aims to describe the proportion of patients diagnosed with psychiatric comorbidities, the different psychiatric diagnoses made, and treatment outcomes among DR-TB patients with or without psychiatric comorbidity and initiated on DR-TB treatment between January 2012 and March 2019 at Médecins Sans Frontières independent clinic in Mumbai, India.

METHODS
This is a retrospective study using routinely collected clinical data. DR-TB care included individualised treatment, psychosocial support, and integrated psychiatric care.

RESULTS
During the study period, 341 DR-TB patients were enrolled, with a median age of 25 years (IQR:20.0-36.5 years), 185 (54.2%) females, 143 (41.9%) with PreXDR-TB, and 140 (41.0%) with XDR-TB. All 341 patients were screened by a counsellor, 119 (34.9%) were referred for psychiatric evaluation, and 102 (29.9% of 341) were diagnosed with a psychiatric comorbidity. Among 102 diagnosed with a psychiatric comorbidity, 48 (47.0%) were diagnosed at baseline, and 86 (84.3%), or 25.2% of all 341 patients enrolled, were treated with psychotropic drugs. Depressive disorders were diagnosed in 49 (48.0%), mixed anxiety and depression in 24 (23.5%), neurocognitive disorders and anxiety in five (4.9%), and medication induced psychosis in two (2.0%). No anti-TB drugs were significantly associated with psychiatric comorbidities developed during treatment. Of 102 DR-TB patients with a psychiatric comorbidity, 75.5% (77) had successful DR-TB treatment outcomes, compared to 61.1% (146/239) not diagnosed with a psychiatric comorbidity (p = 0.014).

CONCLUSION
In our setting, among people started on DR-TB treatment, and with a complex TB resistance profile, about one in three patients experienced a psychiatric comorbidity, of which half developed this comorbidity during treatment. With comprehensive psychiatric care integrated into DR-TB care delivery, treatment outcomes were at least as good among those with psychiatric comorbidities compared to those without such comorbidities.
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