Journal Article > LetterFull Text
Am J Respir Crit Care Med. 2015 February 1; Volume 191 (Issue 3); 355-358.; DOI:10.1164/rccm.201407-1302LE
Bastard M, Bonnet MMB, du Cros PAK, Khamraev AK, Hayrapetyan A, et al.
Am J Respir Crit Care Med. 2015 February 1; Volume 191 (Issue 3); 355-358.; DOI:10.1164/rccm.201407-1302LE
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
Public Health Action. 2022 June 21; Volume 12 (Issue 2); 96-101.; DOI:10.5588/pha.22.0002
Kirakosyan O, Melikyan N, Falcao J, Khachatryan N, Atshemyan H, et al.
Public Health Action. 2022 June 21; Volume 12 (Issue 2); 96-101.; DOI:10.5588/pha.22.0002
BACKGROUND
Direct-acting antivirals (DAAs) are not widely used for patients with chronic hepatitis C virus (HCV) infection and multidrug- or rifampicin-resistant TB (MDR/RR-TB). We describe the implementation aspects of a new integrated model of care in Armenia and the perceptions of the healthcare staff and patients.
METHODS
We used qualitative methods, including a desktop review and semi-structured individual interviews with healthcare staff and with patients receiving HCV and MDR/RR-TB treatment.
RESULTS
The new integrated model resulted in simplified management of HCV and MDR/RR-TB at public TB facilities. Training on HCV was provided for TB clinic staff. All MDR/RR-TB patients were systematically offered HCV testing and those diagnosed with HCV, offered treatment with DAAs. Treatment monitoring was performed by TB staff in coordination with a hepatologist. The staff interviewed had a positive opinion of the new model. They suggested that additional training should be provided. Most patients were fully satisfied with the care received. Some were concerned about the increased pill burden.
CONCLUSION
Integrating HCV treatment into MDR/ RR-TB care was feasible and appreciated by patients and staff. This new model facilitated HCV diagnosis and treatment among people with MDR/RR-TB. Our results encourage piloting this model in other settings.
Direct-acting antivirals (DAAs) are not widely used for patients with chronic hepatitis C virus (HCV) infection and multidrug- or rifampicin-resistant TB (MDR/RR-TB). We describe the implementation aspects of a new integrated model of care in Armenia and the perceptions of the healthcare staff and patients.
METHODS
We used qualitative methods, including a desktop review and semi-structured individual interviews with healthcare staff and with patients receiving HCV and MDR/RR-TB treatment.
RESULTS
The new integrated model resulted in simplified management of HCV and MDR/RR-TB at public TB facilities. Training on HCV was provided for TB clinic staff. All MDR/RR-TB patients were systematically offered HCV testing and those diagnosed with HCV, offered treatment with DAAs. Treatment monitoring was performed by TB staff in coordination with a hepatologist. The staff interviewed had a positive opinion of the new model. They suggested that additional training should be provided. Most patients were fully satisfied with the care received. Some were concerned about the increased pill burden.
CONCLUSION
Integrating HCV treatment into MDR/ RR-TB care was feasible and appreciated by patients and staff. This new model facilitated HCV diagnosis and treatment among people with MDR/RR-TB. Our results encourage piloting this model in other settings.
Journal Article > ResearchFull Text
J Infect Dis. 2014 October 13; Volume 211 (Issue 10); DOI:10.1093/infdis/jiu551
Bastard M, Sanchez-Padilla E, Hewison CCH, Hayrapetyan A, Khurkhumal S, et al.
J Infect Dis. 2014 October 13; Volume 211 (Issue 10); DOI:10.1093/infdis/jiu551
The success of the current treatment regimen for multidrug-resistant tuberculosis (MDR-TB) is poor partly due to a high defaulter rate. Many studies explored predictors of poor outcomes, but very few assessed the impact of treatment interruptions on MDR-TB treatment outcomes.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2014 February 1; Volume 18 (Issue 2); 160-167.; DOI:10.5588/ijtld.13.0369
Sanchez-Padilla E, Marquer C, Kalon S, Qayyum S, Hayrapetyan A, et al.
Int J Tuberc Lung Dis. 2014 February 1; Volume 18 (Issue 2); 160-167.; DOI:10.5588/ijtld.13.0369
SETTING
Armenia, a country with a high prevalence of drug-resistant tuberculosis (DR-TB).
OBJECTIVE
To identify factors related to default from DR-TB treatment in Yerevan.
DESIGN
Using a retrospective cohort design, we compared defaulters with patients who were cured, completed or failed treatment. Patients who initiated DR-TB treatment from 2005 to 2011 were included in the study. A qualitative survey was conducted including semi-structured interviews with defaulters and focus group discussions with care providers.
RESULTS
Of 381 patients, 193 had achieved treatment success, 24 had died, 51 had failed treatment and 97 had defaulted. The number of drugs to which the patient was resistant at admission (aRR 1.16, 95%CI 1.05–1.27), the rate of treatment interruption based on patient's decision (aRR 1.03, 95%CI 1.02–1.05), the rate of side effects (aRR 1.18, 95%CI 1.09–1.27), and absence of culture conversion during the intensive phase (aRR 0.47, 95%CI 0.31–0.71) were independently associated with default from treatment. In the qualitative study, poor treatment tolerance, a perception that treatment was inefficient, lack of information, incorrect perception of being cured, working factors and behavioural problems were factors related to treatment default.
CONCLUSION
In addition to economic reasons, poor tolerance of and poor response to treatment were the main factors associated with treatment default.
Armenia, a country with a high prevalence of drug-resistant tuberculosis (DR-TB).
OBJECTIVE
To identify factors related to default from DR-TB treatment in Yerevan.
DESIGN
Using a retrospective cohort design, we compared defaulters with patients who were cured, completed or failed treatment. Patients who initiated DR-TB treatment from 2005 to 2011 were included in the study. A qualitative survey was conducted including semi-structured interviews with defaulters and focus group discussions with care providers.
RESULTS
Of 381 patients, 193 had achieved treatment success, 24 had died, 51 had failed treatment and 97 had defaulted. The number of drugs to which the patient was resistant at admission (aRR 1.16, 95%CI 1.05–1.27), the rate of treatment interruption based on patient's decision (aRR 1.03, 95%CI 1.02–1.05), the rate of side effects (aRR 1.18, 95%CI 1.09–1.27), and absence of culture conversion during the intensive phase (aRR 0.47, 95%CI 0.31–0.71) were independently associated with default from treatment. In the qualitative study, poor treatment tolerance, a perception that treatment was inefficient, lack of information, incorrect perception of being cured, working factors and behavioural problems were factors related to treatment default.
CONCLUSION
In addition to economic reasons, poor tolerance of and poor response to treatment were the main factors associated with treatment default.
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
Arch Dis Child. 2018 December 6; Volume 104 (Issue 7); 622-628.; DOI:10.1136/archdischild-2018-315411
Huerga H, Sanchez-Padilla E, Melikyan N, Atshemyan H, Ulumyan A, et al.
Arch Dis Child. 2018 December 6; Volume 104 (Issue 7); 622-628.; DOI:10.1136/archdischild-2018-315411
OBJECTIVE
We aimed to measure the prevalence and incidence of latent tuberculosis infection (LTBI) and tuberculosis (TB) disease in children in close contact with patients with drug-resistant TB (DR-TB) in a country with high DR-TB prevalence.
DESIGN AND SETTING
This is a prospective cohort study of paediatric contacts of adult patients with pulmonary DR-TB in Armenia. Children were screened using tuberculin skin test, interferon-gamma release assay and chest X-ray at the initial consultation, and were reassessed every 3–6 months for a period of 24 months. Children did not receive preventive treatment.
MAIN OUTCOME MEASURES
Prevalence and incidence of LTBI and TB disease; factors associated with prevalent LTBI.
RESULTS
At initial evaluation, 3 of the 150 children included were diagnosed with TB disease (2.0%). The prevalence of LTBI was 58.7%. The incidence of LTBI was 19.9 per 100 children per year, and was especially high during the first 6 months of follow-up (33.3 per 100 children per year). No additional cases with incident disease were diagnosed during follow-up. After adjustment, prevalent LTBI was significantly associated with the child’s age, sleeping in the same house, higher household density, the index case’s age, positive smear result and presence of lung cavities.
CONCLUSIONS
Children in close contact with patients with DR-TB or in contact with very contagious patients had an increased risk of prevalent LTBI. Although none of the children developed TB disease during a 2-year follow-up period, screening for symptoms of TB disease, based on the prevalence of disease at recruitment, together with follow-up and repeated testing of non-infected contacts, is highly recommended in paediatric contacts of patients with DR-TB.
We aimed to measure the prevalence and incidence of latent tuberculosis infection (LTBI) and tuberculosis (TB) disease in children in close contact with patients with drug-resistant TB (DR-TB) in a country with high DR-TB prevalence.
DESIGN AND SETTING
This is a prospective cohort study of paediatric contacts of adult patients with pulmonary DR-TB in Armenia. Children were screened using tuberculin skin test, interferon-gamma release assay and chest X-ray at the initial consultation, and were reassessed every 3–6 months for a period of 24 months. Children did not receive preventive treatment.
MAIN OUTCOME MEASURES
Prevalence and incidence of LTBI and TB disease; factors associated with prevalent LTBI.
RESULTS
At initial evaluation, 3 of the 150 children included were diagnosed with TB disease (2.0%). The prevalence of LTBI was 58.7%. The incidence of LTBI was 19.9 per 100 children per year, and was especially high during the first 6 months of follow-up (33.3 per 100 children per year). No additional cases with incident disease were diagnosed during follow-up. After adjustment, prevalent LTBI was significantly associated with the child’s age, sleeping in the same house, higher household density, the index case’s age, positive smear result and presence of lung cavities.
CONCLUSIONS
Children in close contact with patients with DR-TB or in contact with very contagious patients had an increased risk of prevalent LTBI. Although none of the children developed TB disease during a 2-year follow-up period, screening for symptoms of TB disease, based on the prevalence of disease at recruitment, together with follow-up and repeated testing of non-infected contacts, is highly recommended in paediatric contacts of patients with DR-TB.
Journal Article > ResearchFull Text
Public Health Action. 2014 October 21; Volume 4 (Issue 2); S13-6.; DOI:10.5588/pha.14.0038
Davtyan K, Zachariah R, Davtyan H, Ramsay AR, Denisiuk O, et al.
Public Health Action. 2014 October 21; Volume 4 (Issue 2); S13-6.; DOI:10.5588/pha.14.0038
We assessed the performance of decentralised tuberculosis (TB) out-patient centres in tuberculosis (TB) case notification and treatment success in Armenia. An average threshold case notification of ⩾37/100 000 was seen in centres that had higher numbers of presumptive TB patients, where more TB was diagnosed by in-patient facilities and where TB contacts were examined. The number of doctors and/or TB specialists at centres did not influence case notification. Onsite smear microscopy was significantly associated with a treatment success rate of ⩾85% for new TB patients. Addressing specific characteristics of TB centres associated with lower case notification and treatment success and optimising their location may improve performance.