Journal Article > ResearchFull Text
PLOS One. 2021 February 18; 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. 2021 February 18; 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.
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.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2023 January 1; 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. 2023 January 1; 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.
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.
Conference Material > Poster
Mankar S, Vengurlekar D, Khan S, Silsarma A, Sutar N, et al.
MSF Scientific Days International 2022. 2022 May 9; DOI:10.57740/awnn-kh70
Journal Article > ResearchFull Text
Journal of Clinical Tuberculosis and Other Mycobacterial Diseases. 2024 October 12; Volume 37; 100481.; DOI:10.1016/j.jctube.2024.100481
Khan S, Silsarma A, Mahajan R, Davuluri P, Sutar N, et al.
Journal of Clinical Tuberculosis and Other Mycobacterial Diseases. 2024 October 12; Volume 37; 100481.; DOI:10.1016/j.jctube.2024.100481
BACKGROUND
Tuberculosis (TB) remains a significant cause of mortality globally, with India accounting for 27% of the estimated number of people with TB. Multidrug-resistant TB (MDR-TB) and isoniazid (INH) resistance pose additional challenges to effective treatment. We aimed to describe treatment outcomes of INH mono-resistant TB patients under programmatic conditions in Mumbai, India.
METHODS
This retrospective cohort study was conducted at Shatabdi Hospital in Mumbai between 2019-2021.We described the clinical and demographic characteristics, treatment outcomes, and risk factors for unfavourable outcomes among patients with INH mono-resistant TB treated with rifampicin, ethambutol, pyrazinamide, and levofloxacin (LfxREZ) for a duration of 6 months.
RESULTS
Among 3105 patients with drug-resistant TB initiated on treatment, 217 (7 %) had INH mono-resistant TB. Of these, 54 % (117/217) were female, with a median age of 26 years (interquartile range: 20-40). The majority (88 %; 191/217) presented with pulmonary TB, and most (87 %; 188/217) had favourable treatment outcomes, including treatment completion (52 %; 112/217) and cure (35 %; 76/217). Unfavourable outcomes, including treatment failure (2.3 %; 5/217), loss to follow-up (9.2 %; 20/217), or death (1.8 %; 4/217), were observed in 13 % (29/217) of patients. A total of ten (5 %) patients experienced at least one non-severe adverse drug reaction. Factors associated with unfavourable outcomes included severe thinness (p = 0.019) and male gender (p = 0.012).
CONCLUSION
Treating INH mono-resistant patients with LfxREZ resulted in satisfactory outcomes and low toxicity. It is important to rule out drug resistance to INH while determining the treatment regimen.
Journal Article > LetterFull Text
Int J Tuberc Lung Dis. 2020 October 1; Volume 24; DOI:10.5588/ijtld.20.0537
Meneguim A, Rebello L, Das M, Ravi S, Mathur T, et al.
Int J Tuberc Lung Dis. 2020 October 1; Volume 24; DOI:10.5588/ijtld.20.0537
Conference Material > Slide Presentation
Mansoor H, Hirani N, Chavan VV, Joshi A, Oswal V, et al.
MSF Scientific Days International 2022. 2022 May 11; DOI:10.57740/x7k7-xj13
Conference Material > Video
Mansoor H, Hirani N, Chavan VV, Joshi A, Oswal V, et al.
MSF Scientific Days International 2022. 2022 June 7; DOI:10.57740/3gdn-kn91
Conference Material > Abstract
Mansoor H, Hirani N, Chavan VV, Joshi A, Oswal V, et al.
MSF Scientific Days International 2022. 2022 May 11; DOI:10.57740/atfq-6s03
INTRODUCTION
In countries with a high tuberculosis (TB) burden, poor access to drug susceptibility testing is a major bottleneck in diagnosing drug-resistant (DR) TB. India is estimated to account for a quarter of multidrug-resistant (MDR)-TB patients globally, with around 124,000 cases in 2020. Mumbai, a densely populated city in Maharashtra State, is a DR-TB hotspot with 24% of treatment- naïve cases, and 41% of previously-treated cases, having MDR-TB, and a high frequency of fluoroquinolone resistance occurring among these MDR-TB cases. Targeted next- generation sequencing (tNGS) is a promising technology for rapid detection of resistance. We assessed the role of tNGS for diagnosis of DR-TB.
METHODS
We performed a laboratory-based study involving Mycobacterium tuberculosis (MTB)-positive samples from patients with presumptive TB or DR-TB identified by GeneXpert in Shatabdi Hospital, Mumbai. A total of 161 sputum samples from bacteriologically-confirmed TB cases were included in the study. The study was conducted at Sir JJ Hospital’s TB lab, with sample collection occurring from patients living in M-East Ward (MEW), Mumbai. Two sputum samples were collected from each presumptive TB patient at MEW. Spot samples with a positive result on Xpert MTB/Rif were sent for tNGS and conventional testing (phenotypic drug sensitivity testing (pDST), line probe assays (LPA), and mycobacteria growth indicator tubes (MGIT)) at Sir JJ Hospital’s TB lab. tNGS samples were processed using Deeplex MycTB-kit (GenoScreen, France) and sequenced on a MiSeq platform (Illumina, USA). These samples were also processed for pDST using 16 drugs on MGIT (Becton Dickinson, USA) and LPA (MTBDRplus and MTBDRsl, Hain Lifesciences, Germany). To ensure sequence quality, Xpert results with cycle threshold values <20 or direct smear results >2+ were prepared for tNGS using direct sputum sediments. Primary cultures were prepared for samples with lower bacterial loads.
ETHICS
This study was approved by the ethics committee of the Grant Medical College & Sir J J Group of Hospitals, Mumbai, India. Permission was granted by the Medical Director of MSF, Operational Centre Brussels.
RESULTS
The median age of patients with samples included was 24 years (interquartile range, 20-40), and 57% were female. Approximately 70% of cases had no previous history of TB. Of 161 samples evaluated, 15 (9.3%) were rifampicin-sensitive and 146 (90.7%) were rifampicin-resistant (RR). 161 samples with completed pDST, tNGS and LPA were analysed. Of these, 88.2% had RR/MDR-TB resistance per WHO definitions, 58.5% had additional fluoroquinolone-resistance (pre-XDR) and 9.2% had fluoroquinolone resistance plus resistance to either linezolid or bedaquiline (extensively drug-resistant (XDR). Thirteen of 161 samples (8%) were culture-negative, yet resistance to one or more drugs was demonstrated in 8/13 samples with tNGS. Resistance frequency was similar across methods, with discordance in drugs less reliable in pDST or limited mutational representation within databases. Sensitivities aligned with the WHO catalogue for most drugs. 10% of the sample showed hetero-resistance and 75% of strains were of lineages 2 and 3.
CONCLUSION
In countries with a high burden of DR-TB, and high transmission rates, tNGS can provide information to rapidly design individualised regimens for early initiation and effective case management. It also gives information regarding lineages, uncharacterized mutations, hetero-resistance and mixed infection status of TB cases. Potentially tNGS could provide a diagnostic tool for rapid initiation of treatment in high DR-TB settings.
CONFLICTS OF INTEREST
None declared.
In countries with a high tuberculosis (TB) burden, poor access to drug susceptibility testing is a major bottleneck in diagnosing drug-resistant (DR) TB. India is estimated to account for a quarter of multidrug-resistant (MDR)-TB patients globally, with around 124,000 cases in 2020. Mumbai, a densely populated city in Maharashtra State, is a DR-TB hotspot with 24% of treatment- naïve cases, and 41% of previously-treated cases, having MDR-TB, and a high frequency of fluoroquinolone resistance occurring among these MDR-TB cases. Targeted next- generation sequencing (tNGS) is a promising technology for rapid detection of resistance. We assessed the role of tNGS for diagnosis of DR-TB.
METHODS
We performed a laboratory-based study involving Mycobacterium tuberculosis (MTB)-positive samples from patients with presumptive TB or DR-TB identified by GeneXpert in Shatabdi Hospital, Mumbai. A total of 161 sputum samples from bacteriologically-confirmed TB cases were included in the study. The study was conducted at Sir JJ Hospital’s TB lab, with sample collection occurring from patients living in M-East Ward (MEW), Mumbai. Two sputum samples were collected from each presumptive TB patient at MEW. Spot samples with a positive result on Xpert MTB/Rif were sent for tNGS and conventional testing (phenotypic drug sensitivity testing (pDST), line probe assays (LPA), and mycobacteria growth indicator tubes (MGIT)) at Sir JJ Hospital’s TB lab. tNGS samples were processed using Deeplex MycTB-kit (GenoScreen, France) and sequenced on a MiSeq platform (Illumina, USA). These samples were also processed for pDST using 16 drugs on MGIT (Becton Dickinson, USA) and LPA (MTBDRplus and MTBDRsl, Hain Lifesciences, Germany). To ensure sequence quality, Xpert results with cycle threshold values <20 or direct smear results >2+ were prepared for tNGS using direct sputum sediments. Primary cultures were prepared for samples with lower bacterial loads.
ETHICS
This study was approved by the ethics committee of the Grant Medical College & Sir J J Group of Hospitals, Mumbai, India. Permission was granted by the Medical Director of MSF, Operational Centre Brussels.
RESULTS
The median age of patients with samples included was 24 years (interquartile range, 20-40), and 57% were female. Approximately 70% of cases had no previous history of TB. Of 161 samples evaluated, 15 (9.3%) were rifampicin-sensitive and 146 (90.7%) were rifampicin-resistant (RR). 161 samples with completed pDST, tNGS and LPA were analysed. Of these, 88.2% had RR/MDR-TB resistance per WHO definitions, 58.5% had additional fluoroquinolone-resistance (pre-XDR) and 9.2% had fluoroquinolone resistance plus resistance to either linezolid or bedaquiline (extensively drug-resistant (XDR). Thirteen of 161 samples (8%) were culture-negative, yet resistance to one or more drugs was demonstrated in 8/13 samples with tNGS. Resistance frequency was similar across methods, with discordance in drugs less reliable in pDST or limited mutational representation within databases. Sensitivities aligned with the WHO catalogue for most drugs. 10% of the sample showed hetero-resistance and 75% of strains were of lineages 2 and 3.
CONCLUSION
In countries with a high burden of DR-TB, and high transmission rates, tNGS can provide information to rapidly design individualised regimens for early initiation and effective case management. It also gives information regarding lineages, uncharacterized mutations, hetero-resistance and mixed infection status of TB cases. Potentially tNGS could provide a diagnostic tool for rapid initiation of treatment in high DR-TB settings.
CONFLICTS OF INTEREST
None declared.