Journal Article > ResearchFull Text
Clin Infect Dis. 13 March 2025; Online ahead of print; DOI:10.1093/cid/ciaf068
Singla R, Khan S, Silsarma A, Chavan V, Mahajan R, et al.
Clin Infect Dis. 13 March 2025; Online ahead of print; DOI:10.1093/cid/ciaf068
BACKGROUND
Bedaquiline (BDQ) resistance presents a critical challenge in the fight against tuberculosis (TB), particularly multidrug-resistant (MDR) strains. The emergence of resistance to BDQ, a key drug in treating MDR-TB, poses significant threats to TB treatment effectiveness.
METHODS
The National Institute of Tuberculosis and Respiratory Diseases in Delhi and the Médecins Sans Frontières clinic in Mumbai provide BDQ, delamanid, and carbapenem-based regimens for patients with suspected or confirmed treatment failure. BDQ phenotypic drug-susceptibility testing (DST) was performed for all BDQ-exposed patients. Treatment regimens were individualized based on exposure history, comorbidities, drug interactions, prior adverse drug reactions, and DST results.
RESULTS
Of 117 BDQ-exposed patients from December 2020–December 2022, 42 (36%) exhibited a BDQ-resistant strain. Median (IQR) age was 24 (22–32) years, with 63 (54%) females and 94% with pulmonary TB. Patients with a BDQ-resistant strain were older (median age: 27 vs 23 years; P = .04), more likely to have lung cavities (risk ratio [RR]: 1.8; 95%-CI: 1.1–3.1; P = .02), and be resistant to clofazimine (RR: 2.3; 95%-CI: 1.5–3.6; P = .001). Overall, 102 patients initiated treatment. Patients with BDQ-resistance had higher risk of unfavorable outcomes compared with BDQ-susceptible patients (RR:2.1; 95%-CI: 1.5–2.8; P < .001). Overall, 87% (33/38) of patients with BDQ-resistance experienced unfavorable treatment outcomes: 15 (40%) died, 15 (40%) had treatment failure, and 3 (8%) were lost-to-follow-up.
CONCLUSIONS
The study highlights a concerning rate of BDQ-resistance among previously treated patients, resulting in poor treatment outcomes. To prevent treatment failure, we recommend implementing BDQ-DST, developing affordable and accurate rapid tests for BDQ-resistance, and intensifying research and development efforts for newer TB drugs.
Journal Article > LetterFull Text
IJTLD OPEN. 1 February 2025; Volume 2 (Issue 2); 107-109.; DOI:10.5588/ijtldopen.24.0600
Chavan V, Silsarma A, Mahajan R, Khan S, Singh P, et al.
IJTLD OPEN. 1 February 2025; Volume 2 (Issue 2); 107-109.; DOI:10.5588/ijtldopen.24.0600
Conference Material > Poster
Chavan V, Silsarma A, Khan S, Singh P, Iyer A, et al.
MSF Scientific Days Asia 2024. 8 November 2024
Journal Article > ResearchFull Text
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.
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.
Conference Material > Poster
Singh SN, Singh P, Silsarma A, Iyer AS, Galindo MA, et al.
MSF Paediatric Days 2022. 30 November 2022; DOI:10.57740/jnqv-bc66
Journal Article > ResearchFull Text
PLOS One. 16 June 2020 (Issue 6); DOI:10.1371/journal.pone.0234651.
Chavan VV, Dalal A, Nagaraja SB, Thekkur P, Mansoor H, et al.
PLOS One. 16 June 2020 (Issue 6); DOI:10.1371/journal.pone.0234651.
Background
Imipenem, an intravenous antibiotic is recommended for use in drug resistant tuberculosis (DR-TB) when an effective regimen with combination of other second line drugs is not possible. Though the treatment success rates with carbapenems are promising, the twice daily injection of Imipenem usually requires patients to be hospitalized. The Médecins Sans Frontières independent clinic in Mumbai, India implemented ambulatory and home based management of patients receiving Imipenem through the use of port-a-cath.
Objective
We aimed to describe the adverse events and treatment outcomes of ambulatory pre- and XDR-TB patients initiated on imipenem through port-a-cath between January 2015 and June 2018 and to explore the challenges with this regimen as perceived by healthcare providers and patients.
Methods
A convergent mixed methods study with quantitative (longitudinal descriptive study using the routine data) and qualitative (descriptive study) part conducted concurrently. For the quantitative component, all XDR-TB and pre-XDR-TB initiated on imipenem containing regimen during January 2015-June 2018 were included. For qualitative component, interviews were carried out including patients who initiated on imipenem (n = 5) and healthcare providers (n = 7) involved in providing treatment. Treatment outcomes, culture conversion and adverse events during treatment were described. Thematic analysis was carried out for qualitative component.
Results
Of the 70 patients included, the mean age was 28.1 (standard deviation: 11.2) years and 36 (51.4%) were females. Fifty one (72.9%) had XDR-TB. All patients were resistant to fluoroquinilone, levofloxacin. Vomiting was reported by 55 (78.6%) patients and at least one episode of QTC prolongation (more than 500 msec by Fredrecia method) was detected in 25 (35.7%). Port-a-cath block and infection was seen in 11 (15.7%) and 20 (28.6%) patients respectively. Favourable outcomes were seen in 43 (61.4%) patients. Mortality was seen in 22 (31.4%) patients, 2 (2.9%) were lost-to-follow-up and 3 (4.3%) were declared as treatment failure. The overarching theme of the qualitative analysis was: Challenges in delivering Imipenem via port-a-cath device in ambulatory care. Major challenges identified were difficulties in adhering to drug dose timelines, vomiting, restricted mobility due to port-a-cath, paucity of infection control and space constraints at patients’ home for optimal care.
Conclusion
Administration of imipenem was feasible through port-a-cath. Though outcomes with ambulatory based imipenem containing regimens were promising, there were several challenges in providing care. The feasibility of infusion at day care facilities needs to explored to overcome challenges in infusion at patients home.
Imipenem, an intravenous antibiotic is recommended for use in drug resistant tuberculosis (DR-TB) when an effective regimen with combination of other second line drugs is not possible. Though the treatment success rates with carbapenems are promising, the twice daily injection of Imipenem usually requires patients to be hospitalized. The Médecins Sans Frontières independent clinic in Mumbai, India implemented ambulatory and home based management of patients receiving Imipenem through the use of port-a-cath.
Objective
We aimed to describe the adverse events and treatment outcomes of ambulatory pre- and XDR-TB patients initiated on imipenem through port-a-cath between January 2015 and June 2018 and to explore the challenges with this regimen as perceived by healthcare providers and patients.
Methods
A convergent mixed methods study with quantitative (longitudinal descriptive study using the routine data) and qualitative (descriptive study) part conducted concurrently. For the quantitative component, all XDR-TB and pre-XDR-TB initiated on imipenem containing regimen during January 2015-June 2018 were included. For qualitative component, interviews were carried out including patients who initiated on imipenem (n = 5) and healthcare providers (n = 7) involved in providing treatment. Treatment outcomes, culture conversion and adverse events during treatment were described. Thematic analysis was carried out for qualitative component.
Results
Of the 70 patients included, the mean age was 28.1 (standard deviation: 11.2) years and 36 (51.4%) were females. Fifty one (72.9%) had XDR-TB. All patients were resistant to fluoroquinilone, levofloxacin. Vomiting was reported by 55 (78.6%) patients and at least one episode of QTC prolongation (more than 500 msec by Fredrecia method) was detected in 25 (35.7%). Port-a-cath block and infection was seen in 11 (15.7%) and 20 (28.6%) patients respectively. Favourable outcomes were seen in 43 (61.4%) patients. Mortality was seen in 22 (31.4%) patients, 2 (2.9%) were lost-to-follow-up and 3 (4.3%) were declared as treatment failure. The overarching theme of the qualitative analysis was: Challenges in delivering Imipenem via port-a-cath device in ambulatory care. Major challenges identified were difficulties in adhering to drug dose timelines, vomiting, restricted mobility due to port-a-cath, paucity of infection control and space constraints at patients’ home for optimal care.
Conclusion
Administration of imipenem was feasible through port-a-cath. Though outcomes with ambulatory based imipenem containing regimens were promising, there were several challenges in providing care. The feasibility of infusion at day care facilities needs to explored to overcome challenges in infusion at patients home.
Journal Article > ResearchFull Text
PLOS One. 5 May 2020; Volume 15 (Issue 5); e0232576.; DOI:10.1371/journal.pone.0232576
Laxmeshwar C, Acharya S, Das M, Keskar P, Pazare A, et al.
PLOS One. 5 May 2020; Volume 15 (Issue 5); e0232576.; DOI:10.1371/journal.pone.0232576
BACKGROUND
Routine viral-load (VL) measurements along with enhanced adherence counselling (EAC) are recommended to achieve virological suppression among people living with HIV/AIDS (PLHA) on anti-retroviral therapy (ART). The Mumbai Districts AIDS Control Society along with Médecins Sans Frontières has provided routine VL measurements and EAC to PLHA on ART at King Edward Memorial (KEM) hospital, Mumbai since October-2016. This study aims to describe the initial VL results and impact of EAC on viral suppression and factors associated with initial viral non-suppression among patients with an initial detectable VL, in a cohort of patients tested between October-2016 and September-2018.
METHODS
This is a descriptive study of PLHA on ART who received VL testing and EAC during October-2016 to September-2018. Log-binomial regression was used to identify factors associated with a high VL.
RESULTS
Among 3849 PLHA who underwent VL testing, 1603(42%) were female and median age was 42 years (IQR:35–48). Majority were referred for routine testing (3432(89%)) and clinical/immunological failure (233(6%)). Overall, 3402(88%) PLHA had suppressed VL at initial testing. Among 3432 tested for routine monitoring, 3141(92%) had VL suppressed. Of 291 with VL>1000c/ml, 253(87%) received EAC and after repeat VL, 70(28%) had VL<1000c/ml. Among 233 referred for clinical/immunological failure, 122(52%) had VL>1000c/ml and 109 have been switched to second-line ART.
CD4 count<500 (aOR-5.0[95%CI 3.8–6.5]), on ART for<5 years (aOR-1.5[1.1–2.0]) and age<15 years (aOR-5.2[3.0–8.9]) were associated with an initial VL>1000c/ml. Factors associated with follow-up VL suppression included EAC (p<0.05) and being on second-line ART (p<0.05).
CONCLUSION
Results from a routine VL program in public sector in India were encouraging and in line with UNAIDS 90-90-90 targets. Routine VL monitoring along with EAC resulted in early switch to alternative optimised regimens while also preventing unnecessary switches. Along with the vital scale up of routine VL monitoring, implementation of enhanced adherence strategies for patients with detectable viral load should be ensured.
Routine viral-load (VL) measurements along with enhanced adherence counselling (EAC) are recommended to achieve virological suppression among people living with HIV/AIDS (PLHA) on anti-retroviral therapy (ART). The Mumbai Districts AIDS Control Society along with Médecins Sans Frontières has provided routine VL measurements and EAC to PLHA on ART at King Edward Memorial (KEM) hospital, Mumbai since October-2016. This study aims to describe the initial VL results and impact of EAC on viral suppression and factors associated with initial viral non-suppression among patients with an initial detectable VL, in a cohort of patients tested between October-2016 and September-2018.
METHODS
This is a descriptive study of PLHA on ART who received VL testing and EAC during October-2016 to September-2018. Log-binomial regression was used to identify factors associated with a high VL.
RESULTS
Among 3849 PLHA who underwent VL testing, 1603(42%) were female and median age was 42 years (IQR:35–48). Majority were referred for routine testing (3432(89%)) and clinical/immunological failure (233(6%)). Overall, 3402(88%) PLHA had suppressed VL at initial testing. Among 3432 tested for routine monitoring, 3141(92%) had VL suppressed. Of 291 with VL>1000c/ml, 253(87%) received EAC and after repeat VL, 70(28%) had VL<1000c/ml. Among 233 referred for clinical/immunological failure, 122(52%) had VL>1000c/ml and 109 have been switched to second-line ART.
CD4 count<500 (aOR-5.0[95%CI 3.8–6.5]), on ART for<5 years (aOR-1.5[1.1–2.0]) and age<15 years (aOR-5.2[3.0–8.9]) were associated with an initial VL>1000c/ml. Factors associated with follow-up VL suppression included EAC (p<0.05) and being on second-line ART (p<0.05).
CONCLUSION
Results from a routine VL program in public sector in India were encouraging and in line with UNAIDS 90-90-90 targets. Routine VL monitoring along with EAC resulted in early switch to alternative optimised regimens while also preventing unnecessary switches. Along with the vital scale up of routine VL monitoring, implementation of enhanced adherence strategies for patients with detectable viral load should be ensured.
Journal Article > ResearchFull Text
Trop Med Infect Dis. 26 May 2020; Volume 5 (Issue 2); 83.; DOI:10.3390/tropicalmed5020083
Paryani R, Gupta V, Singh P, Verma M, Sheikh S, et al.
Trop Med Infect Dis. 26 May 2020; Volume 5 (Issue 2); 83.; DOI:10.3390/tropicalmed5020083
While risk of tuberculosis (TB) is high among household contacts (HHCs) of pre-extensively drug resistant (pre-XDR) TB and XDR-TB, data on yield of systematic longitudinal screening are lacking. We aim to describe the yield of systematic longitudinal TB contact tracing among HHCs of patients with pre-XDR-TB and XDR-TB. At the Médecins Sans Frontières (MSF) clinic, Mumbai, India a cohort comprising 518 HHCs of 109 pre-XDR and XDR index cases was enrolled between January 2016 and June 2018. Regular HHC follow-ups were done till one year post treatment of index cases. Of 518 HHCs, 23 had TB (21 on TB treatment and two newly diagnosed) at the time of first visit. Of the rest, 19% HHCs had no follow-ups. Fourteen (3.5%) TB cases were identified among 400 HHCs; incidence rate: 2072/100,000 person-years (95% CI: 1227-3499). The overall yield of household contact tracing was 3% (16/518). Of 14 who were diagnosed with TB during follow-up, six had drug susceptible TB (DSTB); six had pre-XDR-TB and one had XDR-TB. Five of fourteen cases had resistance patterns concordant with their index case. In view of the high incidence of TB among HHCs of pre-XDR and XDR-TB cases, follow-up of HHCs for at least the duration of index cases' treatment should be considered.
Conference Material > Poster
Mongia H, Mansoor H, Mamnoon F, Silsarma A, Davuluri P, et al.
MSF Scientific Days International 2022. 9 May 2022; DOI:10.57740/4qe4-m903
Journal Article > ResearchFull Text
Clin Infect Dis. 2 November 2021; Volume 73 (Issue 9); e3496-e3504.; DOI:10.1093/cid/ciaa1577
Das M, Dalal A, Laxmeshwar C, Ravi S, Mamnoon F, et al.
Clin Infect Dis. 2 November 2021; Volume 73 (Issue 9); e3496-e3504.; DOI:10.1093/cid/ciaa1577
BACKGROUND
The Médecins Sans Frontières clinic in Mumbai, India, has been providing concomitant bedaquiline (BDQ) and delamanid (DLM) in treatment regimen for patients with drug-resistant tuberculosis (DR-TB) and limited therapeutic options, referred from other healthcare institutions, since 2016. The study documents the end-of-treatment outcomes, culture-conversion rates, and serious adverse events (SAEs) during treatment.
METHODS
This was a retrospective cohort study based on routinely collected program data. In clinic, treatment regimens are designed based on culture drug sensitivity test patterns and previous drug exposures, and are provided for 20-22 months. BDQ and DLM are extended beyond 24 weeks as off-label use. Patients who initiated DR-TB treatment including BDQ and DLM (concomitantly for at least 4 weeks) during February 2016-February 2018 were included.
RESULTS
Of the 70 patients included, the median age was 25 (interquartile range [IQR], 22-32) years and 56% were females. All except 1 were fluoroquinolone resistant. The median duration of exposure to BDQ and DLM was 77 (IQR, 43-96) weeks. Thirty-nine episodes of SAEs were reported among 30 (43%) patients, including 5 instances of QTc prolongation, assessed as possibly related to BDQ and/or DLM. The majority (69%) had culture conversion before 24 weeks of treatment. In 61 (87%), use of BDQ and DLM was extended beyond 24 weeks. Successful end-of-treatment outcomes were reported in 49 (70%) patients.
CONCLUSIONS
The successful treatment outcomes of this cohort show that regimens including concomitant BDQ and DLM for longer than 24 weeks are effective and can be safely administered on an ambulatory basis. National TB programs globally should scale up access to life-saving DR-TB regimens with new drugs.
The Médecins Sans Frontières clinic in Mumbai, India, has been providing concomitant bedaquiline (BDQ) and delamanid (DLM) in treatment regimen for patients with drug-resistant tuberculosis (DR-TB) and limited therapeutic options, referred from other healthcare institutions, since 2016. The study documents the end-of-treatment outcomes, culture-conversion rates, and serious adverse events (SAEs) during treatment.
METHODS
This was a retrospective cohort study based on routinely collected program data. In clinic, treatment regimens are designed based on culture drug sensitivity test patterns and previous drug exposures, and are provided for 20-22 months. BDQ and DLM are extended beyond 24 weeks as off-label use. Patients who initiated DR-TB treatment including BDQ and DLM (concomitantly for at least 4 weeks) during February 2016-February 2018 were included.
RESULTS
Of the 70 patients included, the median age was 25 (interquartile range [IQR], 22-32) years and 56% were females. All except 1 were fluoroquinolone resistant. The median duration of exposure to BDQ and DLM was 77 (IQR, 43-96) weeks. Thirty-nine episodes of SAEs were reported among 30 (43%) patients, including 5 instances of QTc prolongation, assessed as possibly related to BDQ and/or DLM. The majority (69%) had culture conversion before 24 weeks of treatment. In 61 (87%), use of BDQ and DLM was extended beyond 24 weeks. Successful end-of-treatment outcomes were reported in 49 (70%) patients.
CONCLUSIONS
The successful treatment outcomes of this cohort show that regimens including concomitant BDQ and DLM for longer than 24 weeks are effective and can be safely administered on an ambulatory basis. National TB programs globally should scale up access to life-saving DR-TB regimens with new drugs.