Journal Article > ResearchFull Text
Clin Infect Dis. 18 February 2025; Online ahead of print; DOI:10.1093/cid/ciaf035
Sinha A, Klebe R, Rekart ML, Alvarez JL, Skrahina A, et al.
Clin Infect Dis. 18 February 2025; Online ahead of print; DOI:10.1093/cid/ciaf035
BACKGROUND
Only 63% of patients initiating multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment in 2020 were treated successfully. 24-Week all-oral bedaquiline, pretomanid, and linezolid (BPaL)–based regimens have demonstrated higher rates of treatment success and have been recommended by the World Health Organization. Operational research is urgently required to evaluate these regimens in non-trial settings.
METHODS
This was a prospective cohort study of patients with microbiologically confirmed MDR/RR-TB and pre–extensively drug-resistant TB (pre-XDR-TB) initiated on BPaL-based regimens in Belarus and Uzbekistan (February 2022–June 2023). All clinical care and research procedures were delivered by treating physicians. After treatment completion, patients were followed up at 6 and 12 months, including collecting sputum to ascertain recurrence. The primary objective was to estimate the effectiveness (cured or treatment completed) and safety (the occurrence of serious adverse events) of BPaL-based regimens.
RESULTS
A total of 677 patients initiated treatment with BPaL-based regimens during the study. We documented successful treatment outcomes in 95.3% (427/448) of patients with MDR/RR-TB treated with BPaL plus moxifloxacin and 90.4% (207/229) of patients with pre–XDR-TB treated with BPaL plus clofazimine. 10.2% (69/677) experienced serious adverse events including 24 deaths (3.5%), 11 of which occurred during treatment. 83.3% (20/24) of deaths were not related to TB or TB treatment. Of patients who were successfully treated and completed 12-month follow-up, 0.5% (2/383) had recurrence.
CONCLUSIONS
BPaL-based regimens for MDR/RR-TB and pre–XDR-TB are safe and highly effective in non-trial settings. These regimens should be considered for widespread implementation globally, and further research is needed to evaluate their performance in other key populations.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 1 October 2023; Volume 27 (Issue 10); 748-753.; DOI:10.5588/ijtld.23.0066
Rekart ML, Aung A, Cullip T, Mulanda WK, Mun L, et al.
Int J Tuberc Lung Dis. 1 October 2023; Volume 27 (Issue 10); 748-753.; DOI:10.5588/ijtld.23.0066
BACKGROUND
Tajikistan has a high burden of rifampicin-resistant TB (RR-TB), with 2,700 new cases estimated for 2021 (28/100,000 population). TB is spread among household members through close interaction and children exposed through household contact progress to disease rapidly and frequently.
METHODS
We retrospectively analysed programmatic data from household contact tracing in Dushanbe over 50 months. We calculated person-years of follow-up, contact tracing yield, number needed to screen (NNS) and number needed to test (NNT) to find one new case, and time to diagnosis.
RESULTS
We screened 6,654 household contacts of 830 RR-TB index cases; 47 new RR-TB cases were detected, 43 in Year 1 and 4 in Years 2 or 3. Ten were aged <5 years; 46/47 had TB symptoms, 34/45 had chest radiographs consistent with TB, 11/35 were Xpert Ultra-positive, 29/32 were tuberculin skin test-positive and 28/47 had positive TB culture and phenotypic drug susceptibility results. The NNS to find one RR-TB case was 141.57 and the NNT was 34.49. The yields for different types of contacts were as follows: 0.7% for screened contacts, 2.9% for tested contacts, 17.0% for symptomatic contacts and 12.1% for symptomatic contacts aged below 5 years.
CONCLUSION
RR-TB household contact tracing was feasible and productive in Tajikistan, a low middle-income country with an inefficient healthcare delivery system.
Tajikistan has a high burden of rifampicin-resistant TB (RR-TB), with 2,700 new cases estimated for 2021 (28/100,000 population). TB is spread among household members through close interaction and children exposed through household contact progress to disease rapidly and frequently.
METHODS
We retrospectively analysed programmatic data from household contact tracing in Dushanbe over 50 months. We calculated person-years of follow-up, contact tracing yield, number needed to screen (NNS) and number needed to test (NNT) to find one new case, and time to diagnosis.
RESULTS
We screened 6,654 household contacts of 830 RR-TB index cases; 47 new RR-TB cases were detected, 43 in Year 1 and 4 in Years 2 or 3. Ten were aged <5 years; 46/47 had TB symptoms, 34/45 had chest radiographs consistent with TB, 11/35 were Xpert Ultra-positive, 29/32 were tuberculin skin test-positive and 28/47 had positive TB culture and phenotypic drug susceptibility results. The NNS to find one RR-TB case was 141.57 and the NNT was 34.49. The yields for different types of contacts were as follows: 0.7% for screened contacts, 2.9% for tested contacts, 17.0% for symptomatic contacts and 12.1% for symptomatic contacts aged below 5 years.
CONCLUSION
RR-TB household contact tracing was feasible and productive in Tajikistan, a low middle-income country with an inefficient healthcare delivery system.
Conference Material > Slide Presentation
Yatskevich N, Hurevich H, Solodovnikova V, Garsevanidze E, Lachenal N, et al.
MSF Scientific Day International 2023. 7 June 2023; DOI:10.57740/3sk2-bf43
Conference Material > Abstract
Yatskevich N, Hurevich H, Solodovnikova V, Garsevanidze E, Lachenal N, et al.
MSF Scientific Day International 2023. 7 June 2023; DOI:10.57740/6r4t-kf45
INTRODUCTION
The total duration of treatment for rifampicin-resistant tuberculosis (RR-TB) in Belarus prior to December 2022 was 18-20 months. The efficacy of treatment with such regimens is low, with the WHO’s Global TB Report suggesting that efficacy was around 73% in Belarus in 2018. The development of effective short regimens for RR-TB treatment is urgent. In Belarus, six-month long treatment with all-oral regimens is used in patients with RR-TB, under operational research conditions, following WHO recommendations.
METHODS
A preliminary assessment of the effectiveness of six-month all-oral regimens containing bedaquiline, pretomanid, linezolid, and moxifloxacin or clofazimine (BPaLM/BPaLC), was performed in a cohort of RR-TB patients. Treatment outcomes, time to culture conversion, and time to adverse event (AE) occurrence, AE types, frequency, and outcomes are described.
ETHICS
This study was approved by the MSF Ethics Review Board (ERB) and by the Belarus Ministry of Health ERB.
RESULTS
Of 177 patients who were enrolled from February 2022 to July 2022, one patient was excluded due to linezolid resistance; this patient continued treatment under an individualised regimen. Of the rest of the cohort (133 (76%) male, 43 female (24%); median age, 44 years (interquartile range, IQR, 25-29 years), 93.2% (164/176) had a favourable treatment outcome, 11 patients were lost to follow-up, and one died. 52 (30%) patients had a sputum smear positive result at treatment start, 59 (34%) a cavitary lesion on chest X-ray, and 42 (24%) patients had been previously treated. 12 patients (7%) were HIV-positive; 23 (13%) had had hepatitis C infection; 45 (26%) abused alcohol, and 6 (3%) of patients had diabetes mellitus. Median time to culture conversion was 27 days (IQR, 25-29). In 96.0% of patients, culture conversion was achieved within 2 months of treatment. 9% of patients had serious AE’s (SAE). Out of total 19 SAE’s, 12 resolved, two resolved with sequelae, three were resolving at the time of assessment, one did not resolve, and one was fatal. Median time from treatment start to the first SAE was 92.5 days (IQR, 12.5-143). The most frequent SAE’s were elevated liver function (6 (32%) cases), acute kidney injury (4 (21%) cases), and amylase increased/pancreatitis (3 (16%) cases). Two cases also revealed cancer or progression of cancer; one showed QTcF prolongation; one, anemia, one, thrombotic cerebral infarction, and one, Clostridium difficile infection. Two cases of cancer and thrombotic cerebral infarction (a patient with a long-standing history of multiple strokes) were assessed as unrelated to study drugs. The one death from cancer was assessed as not related to treatment. Permanent withdrawal of one study drug (linezolid or clofazimine) was done only in three instances (15.8%).
CONCLUSION
The effectiveness of six-month all-oral regimens in this cohort was very high (93.2%). BPaLM/BPaLC regimens were observed to be characterised by a good safety profile. Further data are necessary to evaluate longer-term treatment outcomes.
CONFLICTS OF INTEREST
None declared
The total duration of treatment for rifampicin-resistant tuberculosis (RR-TB) in Belarus prior to December 2022 was 18-20 months. The efficacy of treatment with such regimens is low, with the WHO’s Global TB Report suggesting that efficacy was around 73% in Belarus in 2018. The development of effective short regimens for RR-TB treatment is urgent. In Belarus, six-month long treatment with all-oral regimens is used in patients with RR-TB, under operational research conditions, following WHO recommendations.
METHODS
A preliminary assessment of the effectiveness of six-month all-oral regimens containing bedaquiline, pretomanid, linezolid, and moxifloxacin or clofazimine (BPaLM/BPaLC), was performed in a cohort of RR-TB patients. Treatment outcomes, time to culture conversion, and time to adverse event (AE) occurrence, AE types, frequency, and outcomes are described.
ETHICS
This study was approved by the MSF Ethics Review Board (ERB) and by the Belarus Ministry of Health ERB.
RESULTS
Of 177 patients who were enrolled from February 2022 to July 2022, one patient was excluded due to linezolid resistance; this patient continued treatment under an individualised regimen. Of the rest of the cohort (133 (76%) male, 43 female (24%); median age, 44 years (interquartile range, IQR, 25-29 years), 93.2% (164/176) had a favourable treatment outcome, 11 patients were lost to follow-up, and one died. 52 (30%) patients had a sputum smear positive result at treatment start, 59 (34%) a cavitary lesion on chest X-ray, and 42 (24%) patients had been previously treated. 12 patients (7%) were HIV-positive; 23 (13%) had had hepatitis C infection; 45 (26%) abused alcohol, and 6 (3%) of patients had diabetes mellitus. Median time to culture conversion was 27 days (IQR, 25-29). In 96.0% of patients, culture conversion was achieved within 2 months of treatment. 9% of patients had serious AE’s (SAE). Out of total 19 SAE’s, 12 resolved, two resolved with sequelae, three were resolving at the time of assessment, one did not resolve, and one was fatal. Median time from treatment start to the first SAE was 92.5 days (IQR, 12.5-143). The most frequent SAE’s were elevated liver function (6 (32%) cases), acute kidney injury (4 (21%) cases), and amylase increased/pancreatitis (3 (16%) cases). Two cases also revealed cancer or progression of cancer; one showed QTcF prolongation; one, anemia, one, thrombotic cerebral infarction, and one, Clostridium difficile infection. Two cases of cancer and thrombotic cerebral infarction (a patient with a long-standing history of multiple strokes) were assessed as unrelated to study drugs. The one death from cancer was assessed as not related to treatment. Permanent withdrawal of one study drug (linezolid or clofazimine) was done only in three instances (15.8%).
CONCLUSION
The effectiveness of six-month all-oral regimens in this cohort was very high (93.2%). BPaLM/BPaLC regimens were observed to be characterised by a good safety profile. Further data are necessary to evaluate longer-term treatment outcomes.
CONFLICTS OF INTEREST
None declared
Journal Article > ResearchFull Text
Microbiol Spectr. 9 January 2023; Volume 11 (Issue 1); DOI:10.1128/spectrum.03698-22
Rekart ML, Mun L, Aung A, Gomez D, Mulanda WK, et al.
Microbiol Spectr. 9 January 2023; Volume 11 (Issue 1); DOI:10.1128/spectrum.03698-22
We report the findings of a prospective laboratory diagnostic accuracy study to evaluate the sensitivity, specificity, and predictive values of the Xpert MTB/RIF Ultra assay for Mycobacterium tuberculosis detection in fresh stool specimens from children under 15?years of age with confirmed tuberculosis (TB) disease from Dushanbe, Tajikistan. Six hundred eighty-eight (688) participants were enrolled from April 2019 to October 2021. We identified 16 participants (2.3%) with confirmed TB disease, defined as =1 TB sign/symptom plus microbiologic confirmation. With the Xpert MTB/RIF Ultra assay for stool, we found a sensitivity of 68.8% (95% CI, 46.0 to 91.5) and a specificity of 98.7% (95% CI, 97.8 to 99.5) in confirmed TB disease. Our results are comparable to other published studies; however, our cohort was larger and our confirmed TB disease rate lower than most. We also demonstrated that this assay was feasible to implement in a centralized hospital laboratory in a low-middle-income Central Asian country. However, we encountered obstacles such as lack of staffing, material ruptures, outdated government protocols, and decreased case presentation due to COVID-19. We found eight patients whose only positive test was an Xpert Ultra stool assay. None needed treatment during the study; however, three were treated later, suggesting such cases require close observation. Our report is the first from Central Asia and one of a few from a low-middle-income country. We believe our study demonstrates the generalizability of the Xpert MTB/RIF Ultra assay on fresh stool specimens from children and provides further evidence supporting WHO’s approval of this diagnostic strategy.
IMPORTANCE
The importance of this report is that it provides further support for WHO’s recent recommendation that fresh stool is an acceptable sample for GeneXpert TB testing in children, especially small children who often cannot produce an adequate sputum sample. Diagnosing TB in this age group is difficult, and many cases are missed, leading to unacceptable rates of TB illness and death. In our large cohort of children from Dushanbe, Tajikistan, the GeneXpert stool test was positive in 69% of proven cases of TB, and there were very few false-positive tests. We also showed that this diagnostic strategy was feasible to implement in a low-middle-income country with an inefficient health care delivery system. We hope that many more programs will adopt this form of diagnosing TB in children.
IMPORTANCE
The importance of this report is that it provides further support for WHO’s recent recommendation that fresh stool is an acceptable sample for GeneXpert TB testing in children, especially small children who often cannot produce an adequate sputum sample. Diagnosing TB in this age group is difficult, and many cases are missed, leading to unacceptable rates of TB illness and death. In our large cohort of children from Dushanbe, Tajikistan, the GeneXpert stool test was positive in 69% of proven cases of TB, and there were very few false-positive tests. We also showed that this diagnostic strategy was feasible to implement in a low-middle-income country with an inefficient health care delivery system. We hope that many more programs will adopt this form of diagnosing TB in children.
Journal Article > LetterFull Text
Lancet Global Health. 5 February 2017; Volume 5 (Issue 2); DOI:10.1016/S2214-109X(16)30287-X
Peyraud N, Rafael F, Parker LA, Quere M, Alcoba G, et al.
Lancet Global Health. 5 February 2017; Volume 5 (Issue 2); DOI:10.1016/S2214-109X(16)30287-X
Conference Material > Poster
Spina A, Lenglet AD, Keating P, Pereboom M, Van Boetzelaer E, et al.
MSF Scientific Days International 2021: Research. 18 May 2021