Journal Article > ResearchFull Text
PLOS One. 2016 March 28; Volume 11 (Issue 3); e0152283.; DOI:10.1371/journal.pone.0152283
Burtscher D, Van der Bergh R, Toktosunov U, Angmo N, Samieva N, et al.
PLOS One. 2016 March 28; Volume 11 (Issue 3); e0152283.; DOI:10.1371/journal.pone.0152283
Kyrgyzstan is one of the 27 high multidrug-resistant tuberculosis (MDR-TB) burden countries listed by the WHO. In 2012, Médecins Sans Frontières (MSF) started a drug-resistant tuberculosis (DR-TB) project in Kara Suu District. A qualitative study was undertaken to understand the perception of TB and DR-TB in order to improve the effectiveness and acceptance of the MSF intervention and to support advocacy strategies for an ambulatory model of care.
Journal Article > Short ReportFull Text
Clin Infect Dis. 2019 November 2; Volume 71 (Issue 2); 415-418.; DOI:10.1093/cid/ciz1084
Seung KJ, Khan PY, Franke MF, Ahmed SM, Aiylchiev S, et al.
Clin Infect Dis. 2019 November 2; Volume 71 (Issue 2); 415-418.; DOI:10.1093/cid/ciz1084
Delamanid should be effective against highly resistant strains of Mycobacterium tuberculosis, but uptake has been slow globally. In the endTB (expand new drug markets for TB) Observational Study, which enrolled a large, heterogeneous cohorts of patients receiving delamanid as part of a multidrug regimen, 80% of participants experienced sputum culture conversion within 6 months.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2023 January 1; Volume 27 (Issue 1); 34-40.; DOI:10.5588/ijtld.22.0324
Zeng C, Mitnick CD, Hewison CCH, Bastard M, Khan PY, et al.
Int J Tuberc Lung Dis. 2023 January 1; Volume 27 (Issue 1); 34-40.; DOI:10.5588/ijtld.22.0324
BACKGROUND
The WHO provides standardized outcome definitions for rifampicin-resistant (RR) and multidrug-resistant (MDR) TB. However, operationalizing these definitions can be challenging in some clinical settings, and incorrect classification may generate bias in reporting and research. Outcomes calculated by algorithms can increase standardization and be adapted to suit the research question. We evaluated concordance between clinician-assigned treatment outcomes and outcomes calculated based on one of two standardized algorithms, one which identified failure at its earliest possible recurrence (i.e., failure-dominant algorithm), and one which calculated the outcome based on culture results at the end of treatment, regardless of early occurrence of failure (i.e., success-dominant algorithm).
METHODS
Among 2,525 patients enrolled in the multi-country endTB observational study, we calculated the frequencies of concordance using cross-tabulations of clinician-assigned and algorithm-assigned outcomes. We summarized the common discrepancies.
RESULTS
Treatment success calculated by algorithms had high concordance with treatment success assigned by clinicians (95.8 and 97.7% for failure-dominant and success-dominant algorithms, respectively). The frequency and pattern of the most common discrepancies varied by country.
CONCLUSION
High concordance was found between clinician-assigned and algorithm-assigned outcomes. Heterogeneity in discrepancies across settings suggests that using algorithms to calculate outcomes may minimize bias.
The WHO provides standardized outcome definitions for rifampicin-resistant (RR) and multidrug-resistant (MDR) TB. However, operationalizing these definitions can be challenging in some clinical settings, and incorrect classification may generate bias in reporting and research. Outcomes calculated by algorithms can increase standardization and be adapted to suit the research question. We evaluated concordance between clinician-assigned treatment outcomes and outcomes calculated based on one of two standardized algorithms, one which identified failure at its earliest possible recurrence (i.e., failure-dominant algorithm), and one which calculated the outcome based on culture results at the end of treatment, regardless of early occurrence of failure (i.e., success-dominant algorithm).
METHODS
Among 2,525 patients enrolled in the multi-country endTB observational study, we calculated the frequencies of concordance using cross-tabulations of clinician-assigned and algorithm-assigned outcomes. We summarized the common discrepancies.
RESULTS
Treatment success calculated by algorithms had high concordance with treatment success assigned by clinicians (95.8 and 97.7% for failure-dominant and success-dominant algorithms, respectively). The frequency and pattern of the most common discrepancies varied by country.
CONCLUSION
High concordance was found between clinician-assigned and algorithm-assigned outcomes. Heterogeneity in discrepancies across settings suggests that using algorithms to calculate outcomes may minimize bias.
Journal Article > ResearchFull Text
PLOS One. 2018 March 8; Volume 13 (Issue 3); DOI:10.1371/journal.pone.0193491
Bastard M, Sanchez-Padilla E, du Cros PAK, Khamraev AK, Parpieva N, et al.
PLOS One. 2018 March 8; Volume 13 (Issue 3); DOI:10.1371/journal.pone.0193491
The emergence of resistance to anti-tuberculosis (DR-TB) drugs and the HIV epidemic represent a serious threat for reducing the global burden of TB. Although data on HIV-negative DR-TB treatment outcomes are well published, few data on DR-TB outcomes among HIV co-infected people is available despite the great public health importance.
Protocol > Research Study
BMC Infect Dis. 2019 August 20; Volume 19 (Issue 1); 733.; DOI:10.1186/s12879-019-4378-4
Khan UT, Huerga H, Khan AS, Mitnick CD, Hewison CCH, et al.
BMC Infect Dis. 2019 August 20; Volume 19 (Issue 1); 733.; DOI:10.1186/s12879-019-4378-4
BACKGROUND
At a time when programs were struggling to design effective regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB), the marketing authorization of bedaquiline and delamanid was a critical development in the MDR-TB treatment landscape. However, despite their availability for routine programmatic use, the uptake of these drugs has remained slow; concerns included a lack of evidence on safety and efficacy and the need to protect the new drugs from the development of acquired resistance. As part of the endTB Project, we aimed to address these barriers by generating evidence on safety and efficacy of bedaquiline or delamanid based MDR-TB regimens.
METHODS
This is a protocol for a multi-center prospective cohort study to enroll 2600 patients from April 2015 through September 2018 in 17 countries. The protocol describes inclusion of patients started on treatment with bedaquiline- or delamanid- containing regimens under routine care, who consented to participate in the endTB observational study. Patient follow-up was according to routine monitoring schedules recommended for patients receiving bedaquiline or delamanid as implemented at each endTB site. Therefore, no additional tests were performed as a part of the study. Data were to be collected in a customized, open-source electronic medical record (EMR) system developed as a part of the endTB Project across all 17 countries.
DISCUSSION
The endTB observational study will generate evidence on safety and efficacy of bedaquiline- and delamanid-containing regimens in a large, extremely heterogeneous group of MDR-TB patients, from 17 epidemiologically diverse countries. The systematic, prospective data collection of repeated effectiveness and safety measures, and analyses performed on these data, will improve the quality of evidence available to inform MDR-TB treatment and policy decisions. Further, the resources available to countries through implementation of the endTB project will have permitted countries to: gain experience with the use of these drugs in MDR-TB regimens, improve local capacity to record and report adverse events (pharmacovigilance), and enhance significantly the body of data available for safety evaluation of these drugs and other novel treatments.
At a time when programs were struggling to design effective regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB), the marketing authorization of bedaquiline and delamanid was a critical development in the MDR-TB treatment landscape. However, despite their availability for routine programmatic use, the uptake of these drugs has remained slow; concerns included a lack of evidence on safety and efficacy and the need to protect the new drugs from the development of acquired resistance. As part of the endTB Project, we aimed to address these barriers by generating evidence on safety and efficacy of bedaquiline or delamanid based MDR-TB regimens.
METHODS
This is a protocol for a multi-center prospective cohort study to enroll 2600 patients from April 2015 through September 2018 in 17 countries. The protocol describes inclusion of patients started on treatment with bedaquiline- or delamanid- containing regimens under routine care, who consented to participate in the endTB observational study. Patient follow-up was according to routine monitoring schedules recommended for patients receiving bedaquiline or delamanid as implemented at each endTB site. Therefore, no additional tests were performed as a part of the study. Data were to be collected in a customized, open-source electronic medical record (EMR) system developed as a part of the endTB Project across all 17 countries.
DISCUSSION
The endTB observational study will generate evidence on safety and efficacy of bedaquiline- and delamanid-containing regimens in a large, extremely heterogeneous group of MDR-TB patients, from 17 epidemiologically diverse countries. The systematic, prospective data collection of repeated effectiveness and safety measures, and analyses performed on these data, will improve the quality of evidence available to inform MDR-TB treatment and policy decisions. Further, the resources available to countries through implementation of the endTB project will have permitted countries to: gain experience with the use of these drugs in MDR-TB regimens, improve local capacity to record and report adverse events (pharmacovigilance), and enhance significantly the body of data available for safety evaluation of these drugs and other novel treatments.
Journal Article > ResearchFull Text
Public Health Action. 2017 September 1; Volume 7 (Issue 3); DOI:10.5588/pha.17.0002
Goncharova O, Denisiuk O, Zachariah R, Davtyan K, Nabirova D, et al.
Public Health Action. 2017 September 1; Volume 7 (Issue 3); DOI:10.5588/pha.17.0002
Setting: Twenty-two first-line, two second-line and one tertiary health facility in Bishkek, the capital of Kyrgyzstan. Objectives: Among migrants, a marginalised population at risk for acquiring and transmitting tuberculosis (TB), we determined the proportion with TB among all registered TB cases. For those registered at primary-level facilities, we then reported on their demographic and clinical profiles and TB treatment outcomes. Design: This was a retrospective cohort analysis of 2012-2013 programme data. Results: Of 2153 TB patients registered in all health facilities, 969 (45%) were migrants, of whom 454 were registered in first-line facilities. Of these, 27% were cross-border migrants, 50% had infectious TB and 12% had drug-resistant TB. Treatment success was 74% for new cases and 44% for retreatment TB (the World Health Organization target is ⩾85%). Failure in new and retreatment TB patients was respectively 8% and 25%. Twenty-six individuals started on a first-line anti-tuberculosis regimen failed due to multidrug-resistant TB. Eight (25%) of 32 individuals on a retreatment TB regimen also failed. Loss to follow-up was 10% for new and 19% for retreatment TB. Conclusion: Migrants constituted almost half of all TB patients, drug resistance is prevalent and treatment outcomes unsatisfactory. Fostering inter-country collaboration and prioritising rapid TB diagnostics (Xpert® MTB/RIF) and innovative ways forward for improving treatment outcomes is urgent.
Journal Article > ResearchFull Text
Public Health Action. 2019 September 21
England K, Masini T, Fajardo E
Public Health Action. 2019 September 21
The World Health Organization (WHO) currently recommends Xpert® MTB/RIF as the initial test for all people with presumptive tuberculosis (TB). A number of challenges have been reported, however, in using this technology, particularly in low-resource settings. Here we examine these challenges, and provide our perspective of the barriers to Xpert scale-up as assessed through a survey in 16 TB burden countries in which the Médecins Sans Frontières is present. We observed that the key barriers to scale-up include a lack of policy adoption and implementation of WHO recommendations for the use of Xpert, resulting from high costs, poor sensitisation of clinical staff and a high turnover of trained laboratory
staff; insufficient service and maintenance provision provided by the manufacturer; and inadequate resources for sustainability and expansion. Funding is a critical issue as countries begin to transition out of support from the Global Fund. While it is clear that there is still an urgent need for research into and development of a rapid, affordable point-of-care test for TB that is truly adapted for use in low-resource settings, countries in the meantime need to develop functional and sustainable Xpert networks in order to close the existing diagnostic gap.
staff; insufficient service and maintenance provision provided by the manufacturer; and inadequate resources for sustainability and expansion. Funding is a critical issue as countries begin to transition out of support from the Global Fund. While it is clear that there is still an urgent need for research into and development of a rapid, affordable point-of-care test for TB that is truly adapted for use in low-resource settings, countries in the meantime need to develop functional and sustainable Xpert networks in order to close the existing diagnostic gap.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2019 October 1; Volume 23 (Issue 10); 1060-1067(8).; DOI:10.5588/ijtld.18.0649
Bastard M, Sanchez-Padilla E, Hayrapetyan A, Kimenye K, Khurkhumal S, et al.
Int J Tuberc Lung Dis. 2019 October 1; Volume 23 (Issue 10); 1060-1067(8).; DOI:10.5588/ijtld.18.0649
INTRODUCTION
Identification of good prognostic marker for tuberculosis (TB) treatment response is a necessary step on the path towards a surrogate marker to reduce TB trial duration.
METHODS
We performed a retrospective analysis on routinely collected data in 6 drug-resistant TB (DRTB) programs. Culture conversion, defined as two consecutive negative cultures, was assessed, and performance of culture conversion at Month 2 and Month 6 to predict treatment success were explored. To explore factors associated with positive predicted value (PPV) and the specificity of culture conversion, a multinomial logistic regression was fitted.
RESULTS
This study included 634 patients: 68.5% were males; the median age was 35 years, 75.2% were previously treated for TB, 59.4% were resistant only to isoniazid and rifampicin and 18.1% resistant to fluoroquinolones. Culture conversion at Month 2 and 6 showed similar PPV while specificity was much higher for culture conversion at Month 2: 91.3% (95%CI 86.1–95.1). PPV of culture conversion at Month 2 did not vary strongly according to patients' characteristics, while specificity was slightly higher among patients with fluoroquinolone-resistant strains.
CONCLUSION
Culture conversion at Month 2 is an acceptable prognostic marker for MDR-TB treatment. Considering the advantage of using an earlier marker, further evaluation as a surrogate marker is warranted to shorten TB trials.
Identification of good prognostic marker for tuberculosis (TB) treatment response is a necessary step on the path towards a surrogate marker to reduce TB trial duration.
METHODS
We performed a retrospective analysis on routinely collected data in 6 drug-resistant TB (DRTB) programs. Culture conversion, defined as two consecutive negative cultures, was assessed, and performance of culture conversion at Month 2 and Month 6 to predict treatment success were explored. To explore factors associated with positive predicted value (PPV) and the specificity of culture conversion, a multinomial logistic regression was fitted.
RESULTS
This study included 634 patients: 68.5% were males; the median age was 35 years, 75.2% were previously treated for TB, 59.4% were resistant only to isoniazid and rifampicin and 18.1% resistant to fluoroquinolones. Culture conversion at Month 2 and 6 showed similar PPV while specificity was much higher for culture conversion at Month 2: 91.3% (95%CI 86.1–95.1). PPV of culture conversion at Month 2 did not vary strongly according to patients' characteristics, while specificity was slightly higher among patients with fluoroquinolone-resistant strains.
CONCLUSION
Culture conversion at Month 2 is an acceptable prognostic marker for MDR-TB treatment. Considering the advantage of using an earlier marker, further evaluation as a surrogate marker is warranted to shorten TB trials.
Journal Article > CommentaryFull Text
Eur J Microbiol Immunol (Bp). 2012 December 11; Volume 2 (Issue 4); 282-286.; DOI:10.1556/EuJMI.2.2012.4.6
Healy S, Dietrich S, Roth T, Nyang'wa BT, du Cros PAK
Eur J Microbiol Immunol (Bp). 2012 December 11; Volume 2 (Issue 4); 282-286.; DOI:10.1556/EuJMI.2.2012.4.6
Conference Material > Poster
Aiylchiev S, Sharshenova A, Nascarella M, Sulaimanov E, Inagbe D, et al.
MSF Scientific Days International 2022. 2022 May 9; DOI:10.57740/h10h-jk08