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
J. Infect.. 2021 July 1; Volume 83 (Issue 1); 84-91.; DOI:10.1016/j.jinf.2021.04.013
Farooq HZ, Davies E, Brown B, Whitfield T, Tilston P, et al.
J. Infect.. 2021 July 1; Volume 83 (Issue 1); 84-91.; DOI:10.1016/j.jinf.2021.04.013
OBJECTIVES
SARS-CoV-2 emerged in South Asia in 2019 and has resulted in a global pandemic. Public Health England (PHE) Manchester rapidly escalated testing for SARS-CoV-2 in the highest COVID-19 incidence location in England. The results of the PHE Manchester SARS-CoV-2 surveillance during the first wave are presented.
METHODS
Retrospective data were collected for patients fitting the PHE SARS-CoV-2 case definition from 11th February to 31st August 2020. Respiratory tract, tissue, faecal, fluid and cerebrospinal (CSF) samples were tested for SARS-CoV-2 by a semi-quantitative real-time reverse-transcription PCR.
RESULTS
Of the 204,083 tests for SARS-CoV-2, 18,011 were positive demonstrating a positivity of 8.90%. Highest positivity was in nasal swabs (20.99%) followed by broncheo-alveolar lavage samples (12.50%). None of the faecal, fluid or CSF samples received were positive for SARS-CoV-2.
CONCLUSIONS
There was a high incidence of SARS-CoV-2 patients in the North-West of England during the first UK wave of the Covid-19 pandemic. Highest positivity rate was in nasal specimens suggesting this is the optimum sample type within this dataset for detecting SARS-CoV-2. Further studies are warranted to assess the utility of testing faecal, fluid and CSF samples. Rapid escalation of testing via multiple platforms was required to ensure prompt diagnosis and isolate infected cases to reduce transmission of the virus.
SARS-CoV-2 emerged in South Asia in 2019 and has resulted in a global pandemic. Public Health England (PHE) Manchester rapidly escalated testing for SARS-CoV-2 in the highest COVID-19 incidence location in England. The results of the PHE Manchester SARS-CoV-2 surveillance during the first wave are presented.
METHODS
Retrospective data were collected for patients fitting the PHE SARS-CoV-2 case definition from 11th February to 31st August 2020. Respiratory tract, tissue, faecal, fluid and cerebrospinal (CSF) samples were tested for SARS-CoV-2 by a semi-quantitative real-time reverse-transcription PCR.
RESULTS
Of the 204,083 tests for SARS-CoV-2, 18,011 were positive demonstrating a positivity of 8.90%. Highest positivity was in nasal swabs (20.99%) followed by broncheo-alveolar lavage samples (12.50%). None of the faecal, fluid or CSF samples received were positive for SARS-CoV-2.
CONCLUSIONS
There was a high incidence of SARS-CoV-2 patients in the North-West of England during the first UK wave of the Covid-19 pandemic. Highest positivity rate was in nasal specimens suggesting this is the optimum sample type within this dataset for detecting SARS-CoV-2. Further studies are warranted to assess the utility of testing faecal, fluid and CSF samples. Rapid escalation of testing via multiple platforms was required to ensure prompt diagnosis and isolate infected cases to reduce transmission of the virus.
Journal Article > LetterFull Text
Int J Tuberc Lung Dis. 2023 July 1; Volume 27 (Issue 7); 567-569.; DOI:10.5588/ijtld.22.0632
Vengurlekar D, Walker C, Mahajan R, Dalal A, Chavan VV, et al.
Int J Tuberc Lung Dis. 2023 July 1; Volume 27 (Issue 7); 567-569.; DOI:10.5588/ijtld.22.0632
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.
Conference Material > Poster
Mohan Kumar H, Lin Oo W, Gurung P, Spencer H, Shougrakpam J, et al.
MSF Scientific Days International 2021: Research. 2021 May 18
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
Journal Article > ResearchFull Text
Journal of Clinical Tuberculosis and Other Mycobacterial Diseases. 2024 April 1; 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. 2024 April 1; 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.