Factors associated with unfavourable treatment outcomes among people with rifampicin-resistant tuberculosis in Armenia, 2014-2017
Abstract
Rifampicin-Resistant/Multidrug-Resistant Tuberculosis (RR/MDR-TB) is recognized as a major public health concern globally. In Armenia, the proportion of RR/MDR-TB is increasing among all people affected with TB. We conducted a nationwide cohort study involving analysis of programmatic data to investigate the rates of and factors associated with unfavourable treatment outcomes among patients with RR/MDR-TB registered by the national TB programme from 2014 to 2017 in Armenia. We used Cox regression to identify factors associated with the outcome. Among 451 RR/MDR-TB patients, 80% were men and median age was 46 years. Of them, 53 (11.8%) had Extensively Drug-Resistant Tuberculosis (XDR-TB) and 132 (29.3%) had pre-XDR-TB. Almost half (224, 49.7%) of the patients had unfavourable treatment outcome, which included 26.8% Loss To Follow-Up (LTFU), 13.3% failures and 9.5% deaths. In multivariable analysis, people with pre-XDR-TB [adjusted Hazard Ratio [aHR] 3.13, 95% confidence intervals [CI] 2.16-4.55] and XDR-TB (aHR 4.08, 95% CI 2.45-6.79) had a higher risk of unfavourable outcomes. Patients receiving home-based treatment (71/451, 15.7%) and treatment with new drugs (172/451, 38.1%) had significantly lower risk (aHR 0.45, 95% CI 0.28-0.72 and aHR 0.26, 95% CI 0.18-0.39) of unfavourable treatment outcome. The proportion of MDR-TB patients reaching favourable treatment outcome in Armenia was substantially lower than the recommended level (75%). The most common treatment outcome was LTFU indicating the need for further assessment of underlying determinants. Home-based treatment looks promising and future studies are required to see if expanding it to all RR/MDR-TB patients is feasible and cost-effective.
References
- WHO. Global tuberculosis report 2019. Geneva: World Health Organization; 2019. Accessed on: 2019 Nov 22. Available from: https://www.who.int/tb/publications/global_report/en/
- Acosta CD, Dadu A, Ramsay A, et al. Drug-resistant tuberculosis in Eastern Europe: challenges and ways forward. Public Heal Action 2014;4:S3-12.
- WHO. Armenia country review report 2019. Geneva: World Health Organization; 2019.
- WHO Regional Office for Europe. Tuberculosis surveillance and monitoring report in Europe 2019. Accessed 2020 Jul 1. Available from: https://www.euro.who.int/en/health-topics/communicable-diseases/tuberculosis/publications/2019/tuberculosis-surveillance-and-monitoring-report-in-europe-2019
- WHO. Armenia TB profile 2018. Geneva: World Health Organization; 2019.
- Migliori GB, Tiberi S, Zumla A, et al. MDR/XDR-TB management of patients and contacts: challenges facing the new decade. The 2020 clinical update by the global tuberculosis network. Int J Infect Dis 2020;92:S15–25.
- Woldeyohannes D, Assefa T, Aman R, et al. Predictors of time to unfavorable treatment outcomes among patients with multidrug resistant tuberculosis in Oromia region, Ethiopia. PLoS One 2019;14:e0224025.
- Alffenaar JWC, Akkerman OW, Kim HY, et al. Precision and personalized medicine and anti-tb treatment: is tdm feasible for programmatic use? Int J Infect Dis 2020;92:S5–9.
- Sanchez-Padilla E, Marquer C, Kalon S, et al. Reasons for defaulting from drug-resistant tuberculosis treatment in armenia: a quantitative and qualitative study. Int J Tuberc Lung Dis 2014;18:160–7.
- Chem ED, Van Hout MC, Hope V. Treatment outcomes and antiretroviral uptake in multidrug-resistant tuberculosis and HIV co-infected patients in sub-Saharan Africa: a systematic review and meta-analysis. BMC Infect Dis 2019;19:723.
- Verdecchia M, Keus K, Blankley S, et al. Model of care and risk factors for poor outcomes in patients on multi-drug resistant tuberculosis treatment at two facilities in Eswatini (formerly Swaziland), 2011-2013. PLoS One 2018;13:e0205601.
- Huangfu P, Ugarte-Gil C, Golub J, et al. The effects of diabetes on tuberculosis treatment outcomes: an updated systematic review and meta-analysis. Int J Tuberc Lung Dis 2019;23:783-96.
- Choi H, Lee M, Chen RY, et al. Predictors of pulmonary tuberculosis treatment outcomes in South Korea: a prospective cohort study, 2005-2012. BMC Infect Dis 2014;14:360.
- Parmar MM, Sachdeva KS, Dewan PK, et al. Unacceptable treatment outcomes and associated factors among India’s initial cohorts of multidrug-resistant tuberculosis (MDR-TB) patients under the revised national TB control programme (2007–2011): evidence leading to policy enhancement. PLoS One 2018;13:e0193903.
- Htun YM, Khaing TMM, Aung NM, et al. Delay in treatment initiation and treatment outcomes among adult patients with multidrug-resistant tuberculosis at Yangon regional tuberculosis centre, Myanmar: a retrospective study. PLoS One 2018;13: e0209932.
- Phuong NTM, Nhung NV, Hoa NB, et al. Management and treatment outcomes of patients enrolled in mdr-tb treatment in viet nam. Public Heal Action 2016;6:25-31.
- Alegria-Flores K, Weiner BJ, Wiesen CA, et al. Innovative approach to the design and evaluation of treatment adherence interventions for drug-resistant TB. Int J Tuberc Lung Dis 2017;21:1160-1.
- Bastard M, Sanchez-Padilla E, Hewison C, et al. Effects of treatment interruption patterns on treatment success among patients with multidrug-resistant tuberculosis in Armenia and Abkhazia. J Infect Dis 2015;211:1607–15.
- Bastard M, Sanchez-Padilla E, Du Cros P, et al. Outcomes of HIV-infected versus HIV-non-infected patients treated for drug-resistance tuberculosis: multicenter cohort study. PLoS One 2018;13: e0193491.
- Ministry of Health of the Republic of Armenia. National tuberculosis strategy 2016-20. Accessed on: 2020 Aug 5. Available from: http://www.irtek.am/views/act.aspx?aid=84463
- WHO. Review of financial sustainability of tuberculosis activities in Armenia. Accessed on: 2020 Jul 1. Available from: https://www.euro.who.int/__data/assets/pdf_file/0006/376998/armenia-fin-sust-tb-eng.pdf
- WHO. Rapid communication: key changes to the treatment of drug-resistant tuberculosis. 2019. Accessed on: 2020 Jul 1. Available from: https://www.who.int/tb/publications/2019/WHO_RapidCommunicationMDR_TB2019.pdf?ua=1
- WHO. Introduction of bedaquiline for the treatment of multidrug-resistant tuberculosis at country level. Accessed on: 2020 Jul 1. Available from: https://www.who.int/tb/publications/2015/Bedaquiline_implementation_plan.pdf?ua=1
- WHO. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. 2016. Accessed on: 2020 Jul 1. Available from: https://apps.who.int/iris/bitstream/handle/10665/208825/9789241549684_eng.pdf;jsessionid=CFDC692E793B2858A95868810F57808A?sequence=1
- Avaliani Z, Gozalov O, Kuchukhidze G, et al. What is behind programmatic treatment outcome definitions for tuberculosis? Eur Res J 2020;56 2001751.
- International Labour Organization (ILO). Migration and development Armenia country study, 2009. Accessed on: 2020 Jun 29. Available from: http://www.un.am/up/library/Migr_Dev_Study_eng.pdf
- Muñnoz-Torrico M, Luna JC, Migliori GB, et al. Comparison of bacteriological conversion and treatment outcomes among mdr-tb patients with and without diabetes in mexico: preliminary data. Rev Port Pneumol 2017;23:27-30.
- Atif M, Bashir A, Ahmad N, et al. Predictors of unsuccessful interim treatment outcomes of multidrug resistant tuberculosis patients. BMC Infect Dis 2017;17:655.
- Leveri TH, Lekule I, Mollel E, et al. Predictors of treatment outcomes among multidrug resistant tuberculosis patients in Tanzania. Tuberc Res Treat 2019;2019:3569018.
- Makhmudova M, Maxsumova Z, Rajabzoda A, et al. Risk factors for unfavourable treatment outcomes among rifampicin-resistant tuberculosis patients in Tajikistan. Int J Tuberc Lung Dis 2019;23:331-6.
- Tola HH, Shojaeizadeh D, Garmaroudi G, et al. Psychological distress and its effect on tuberculosis treatment outcomes in Ethiopia. Glob Health Action 2015;8:29019.
- Merid MW, Gezie LD, Kassa GM, et al. Incidence and predictors of major adverse drug events among drug-resistant tuberculosis patients on second-line anti-tuberculosis treatment in Amhara regional state public hospitals; Ethiopia: a retrospective cohort study. BMC Infect Dis 2019;19:286.
- Zhang Y, Wu S, Xia Y, et al. Adverse events associated with treatment of multidrug-resistant tuberculosis in china: an ambispective cohort study. Med Sci Monit 2017;23:2348-56.
- Alene KA, Yi H, Viney K, et al. Treatment outcomes of patients with multidrug-resistant and extensively drug resistant tuberculosis in Hunan Province, China. BMC Infect Dis 2017;17:573.
- Migliori GB, Nardell E, Yedilbayev A, et al. Reducing tuberculosis transmission: a consensus document from the World Health Organization Regional Office for Europe. Eur Respir J 2019;53:1900391.
- Khachadourian V, Truzyan N, Harutyunyan A, et al. People-centered tuberculosis care versus standard directly observed therapy: study protocol for a cluster randomized controlled trial. Trials 2015;16:281.
- Ravenscroft L, Kettle S, Persian R, et al. Video-observed therapy and medication adherence for tuberculosis patients: randomised controlled trial in Moldova. Eur Respir J 2020;56:2000493.
- Sinkou H, Hurevich H, Rusovich V, et al. Video-observed treatment for tuberculosis patients in Belarus: findings from the first programmatic experience. Eur Res J 2017;49: 1602049.
- Wade VA, Karnon J, Eliott JA, et al. Home videophones improve direct observation in tuberculosis treatment: a mixed methods evaluation. PLoS One 2012;7:e50155.
- Horter S, Stringer B, Reynolds L, et al. “Home is where the patient isâ€: a qualitative analysis of a patient-centred model of care for multi-drug resistant tuberculosis. BMC Health Serv Res 2014;14:81.
- Mhimbira F, Hella J, Maroa T, et al. Home-based and facility-based directly observed therapy of tuberculosis treatment under programmatic conditions in urban Tanzania. PLoS One 2016;11:e0161171.
- Bastard M, Guglielmetti L, Huerga H, et al. Bedaquiline and repurposed drugs for fluoroquinolone-resistant multidrug-resistant tuberculosis: how much better are they? Am J Res Care 2018;198:1228-31.
- Hewison C, Bastard M, Khachatryan N, et al. Is 6 months of bedaquiline enough? Results from the compassionate use of bedaquiline in Armenia and Georgia. Int J Tuberc Lung Dis 2018;22:766–72.
- Mbuagbaw L, Guglielmetti L, Hewison C, et al. Outcomes of bedaquiline treatment in patients with multidrug-resistant tuberculosis. Emerg Infect Dis 2019;25:936–43.
- Bonnet M, Bastard M, Du Cros P, et al. Identification of patients who could benefit from bedaquiline or delamanid: a multisite MDR-TB cohort study. Int J Tuberc Lung Dis 2016;20:177–86.
- Skripconoka V, Danilovits M, Pehme L, et al. Delamanid improves outcomes and reduces mortality in multidrug-resistant tuberculosis. Eur Respir J 2013;41:1393–400.
- Kuksa L, Barkane L, Hittel N, et al. Final treatment outcomes of multidrugand extensively drug-resistant tuberculosis patients in Latvia receiving delamanid-containing regimens. Eur Res J 2017;50.
- List of essential medicines of ra [Internet]. Accessed on: 2020 Jul 1. Available from: http://digicollection.org/hss/documents/s17079e/s17079e.pdf
- Truzyan N, Crape B, Grigoryan R, et al. Increased risk for multidrug-resistant tuberculosis in migratory workers, Armenia. Emerg Infect Dis 2015;21:474–6.
Metrics
Citations and online attention from Dimensions, Altmetric and PlumX.
License
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.