Conference Material > Slide Presentation
Khan S, Silsarma A, Iyer AS, Galindo MA, Chavan VV, et al.
MSF Scientific Day International 2023. 2023 June 7; DOI:10.57740/0dpv-wz08
Journal Article > ResearchFull Text
PLOS One. 2022 February 11; 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. 2022 February 11; 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.
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.
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.
Journal Article > CommentaryFull Text
J Adolesc Health. 2023 March 1; Volume 72 (Issue 3); 323-331.; DOI:10.1016/j.jadohealth.2022.10.036
Chiang SS, Waterous PM, Atieno VF, Bernays S, Bondarenko Y, et al.
J Adolesc Health. 2023 March 1; Volume 72 (Issue 3); 323-331.; DOI:10.1016/j.jadohealth.2022.10.036
Conference Material > Poster
Mongia H, Mansoor H, Mamnoon F, Silsarma A, Davuluri P, et al.
MSF Scientific Days International 2022. 2022 May 9; DOI:10.57740/4qe4-m903
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 > Poster
Singh SN, Singh P, Silsarma A, Iyer AS, Galindo MA, et al.
MSF Paediatric Days 2022. 2022 November 30; DOI:10.57740/jnqv-bc66
Conference Material > Abstract
Khan S, Silsarma A, Iyer AS, Galindo MA, Chavan VV, et al.
MSF Scientific Day International 2023. 2023 June 7; DOI:10.57740/k4rh-s938
INTRODUCTION
Bedaquiline (BDQ) and linezolid (LZD) are Group A drugs and form part of shorter and longer BDQ-based regimens under India’s National Tuberculosis (TB) Programme. A systematic review including some data from India on acquired BDQ resistance reports 2.2% phenotypic and 4.4% genotypic resistance in patients treated with BDQ-based regimens. The pooled frequency of LZD resistance among drug-resistant tuberculosis (DR-TB) isolates was 4.2% in a different study. The emergence of resistance to BDQ is concerning as it results in difficulties in constructing regimens, and is associated with unsuccessful treatment outcomes among DR-TB patients. Since 2015, Médecins Sans Frontières (MSF) has provided treatment for TB patients in Mumbai with extensive resistance patterns, who need newer drugs and have limited treatment options under India’s National TB Elimination Programme.
METHODS
We carried out a descriptive retrospective study of routinely collected programmatic data from December 2020 to February 2022. The study population consisted of culture-positive DR-TB patients with BDQ and LZD exposure for over one month, referred to the MSF clinic with 1) suspected or confirmed treatment failure; 2) DR-TB diagnosed household contacts of BDQ-exposed DR-TB patients.
ETHICS
This research fulfilled the exemption criteria set by the MSF Ethics Review Board (ERB) for a posteriori analyses of routinely collected clinical data, and thus did not require MSF ERB review.
RESULTS
88 culture-positive samples were subjected to BDQ and LZD drug susceptibility testing (DST). Of these, 27 showed resistance to BDQ, LZD, or both. 22.7% (20/88) showed BDQ resistance, 17% (15/88) LZD resistance, and eight patients (9%) were simultaneously resistant to BDQ and LZD. Of 88 samples, two were DR-TB diagnosed contacts of BDQ-exposed index cases, and the remaining were BDQ-exposed patients (> one month). In the resistant cohort of 27, equal proportions were male and female, and mean exposure to all Group A drugs was 14 months. 74% (20/27) patients had bilateral disease; 26% (7/27) had unilateral disease, of which 67% (18/27) had lung cavities. Simultaneous resistance to clofazimine and fluoroquinolones was found among 30% (8/27) and 78% (21/27) patients respectively. Within the resistant cohort, two patients refused treatment and 25 started on treatment. Out of 25 patients starting treatment, 8% (2/25) successfully completed treatment, 48% (12/25) died, 20% (5/25) failed, 4% (1/25) were lost to follow-up, and 20% (5/25) were still on treatment at the time of analysis. Of the five patients still on treatment patients, two culture-converted and three are still culture-positive after three months of treatment.
CONCLUSION
We observed a high proportion of BDQ and LZD resistance in patients who previously failed on BDQ and LZD-based regimens. We observe high mortality and unsuccessful outcomes in treating such cases. Designing effective treatment regimens for patients with retreatment episodes and a history of BDQ and LZD exposure is extremely challenging. We urgently recommend increased programmatic access to DST for LZD and BDQ, to ensure early access to effective regimens.
CONFLICTS OF INTEREST
None declared
Bedaquiline (BDQ) and linezolid (LZD) are Group A drugs and form part of shorter and longer BDQ-based regimens under India’s National Tuberculosis (TB) Programme. A systematic review including some data from India on acquired BDQ resistance reports 2.2% phenotypic and 4.4% genotypic resistance in patients treated with BDQ-based regimens. The pooled frequency of LZD resistance among drug-resistant tuberculosis (DR-TB) isolates was 4.2% in a different study. The emergence of resistance to BDQ is concerning as it results in difficulties in constructing regimens, and is associated with unsuccessful treatment outcomes among DR-TB patients. Since 2015, Médecins Sans Frontières (MSF) has provided treatment for TB patients in Mumbai with extensive resistance patterns, who need newer drugs and have limited treatment options under India’s National TB Elimination Programme.
METHODS
We carried out a descriptive retrospective study of routinely collected programmatic data from December 2020 to February 2022. The study population consisted of culture-positive DR-TB patients with BDQ and LZD exposure for over one month, referred to the MSF clinic with 1) suspected or confirmed treatment failure; 2) DR-TB diagnosed household contacts of BDQ-exposed DR-TB patients.
ETHICS
This research fulfilled the exemption criteria set by the MSF Ethics Review Board (ERB) for a posteriori analyses of routinely collected clinical data, and thus did not require MSF ERB review.
RESULTS
88 culture-positive samples were subjected to BDQ and LZD drug susceptibility testing (DST). Of these, 27 showed resistance to BDQ, LZD, or both. 22.7% (20/88) showed BDQ resistance, 17% (15/88) LZD resistance, and eight patients (9%) were simultaneously resistant to BDQ and LZD. Of 88 samples, two were DR-TB diagnosed contacts of BDQ-exposed index cases, and the remaining were BDQ-exposed patients (> one month). In the resistant cohort of 27, equal proportions were male and female, and mean exposure to all Group A drugs was 14 months. 74% (20/27) patients had bilateral disease; 26% (7/27) had unilateral disease, of which 67% (18/27) had lung cavities. Simultaneous resistance to clofazimine and fluoroquinolones was found among 30% (8/27) and 78% (21/27) patients respectively. Within the resistant cohort, two patients refused treatment and 25 started on treatment. Out of 25 patients starting treatment, 8% (2/25) successfully completed treatment, 48% (12/25) died, 20% (5/25) failed, 4% (1/25) were lost to follow-up, and 20% (5/25) were still on treatment at the time of analysis. Of the five patients still on treatment patients, two culture-converted and three are still culture-positive after three months of treatment.
CONCLUSION
We observed a high proportion of BDQ and LZD resistance in patients who previously failed on BDQ and LZD-based regimens. We observe high mortality and unsuccessful outcomes in treating such cases. Designing effective treatment regimens for patients with retreatment episodes and a history of BDQ and LZD exposure is extremely challenging. We urgently recommend increased programmatic access to DST for LZD and BDQ, to ensure early access to effective regimens.
CONFLICTS OF INTEREST
None declared
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.