Prevalence, Predictors, and Successful Treatment Outcomes of Xpert MTB/RIF–identified Rifampicin-resistant Tuberculosis in Post-conflict Eastern Democratic Republic of the Congo, 2012–2017: A Retrospective Province-Wide Cohort Study

Author:

Bulabula André N H12,Nelson Jenna A3,Musafiri Eric M4,Machekano Rhoderick5,Sam-Agudu Nadia A67,Diacon Andreas H8,Shah Maunank9,Creswell Jacob10,Theron Grant11,Warren Robin M11,Jacobson Karen R12,Chirambiza Jean-Paul4,Kalumuna Dieudonné4,Bisimwa Bertin C13,Katoto Patrick D M C1415,Kaswa Michel K4,Birembano Freddy M4,Kitete Liliane16,Grobusch Martin P17,Kashongwe Zacharie M18,Nachega Jean B3192021

Affiliation:

1. Department of Global Health, Division of Health Systems and Public Health, Unit for Infection Prevention and Control, Faculty of Medicine and Health Sciences, Stellenbosch University

2. Infection Control Africa Network, Cape Town, South Africa

3. Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pennsylvania

4. National Tuberculosis Program, Provincial Leprosy and Tuberculosis Coordination, South Kivu Branch, Bukavu, Democratic Republic of the Congo

5. Department of Global Health, Center for Evidence-Based Health Care, Biostatistics Unit, Faculty of Medicine and Health Sciences, Cape Town, South Africa

6. International Research Center of Excellence and Pediatric and Adolescent Human Immunodeficiency Virus Unit, Institute of Human Virology Nigeria, Abuja

7. Division of Epidemiology and Prevention, Institute of Human Virology, University of Maryland School of Medicine, Baltimore

8. Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

9. Center for Tuberculosis Research & Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland

10. Stop TB Partnership, TB REACH Initiative, Geneva, Switzerland

11. South African Department of Science and Technology and the National Research Foundation, Centre of Excellence for Biomedical Tuberculosis Research and South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

12. Department of Medicine, Division of Infectious Diseases, Boston University School of Medicine, Massachusetts

13. Biomedical Laboratory Professor A. Z. Lurhuma, Mycobacterium Unit, Université Catholique de Bukavu, Democratic Republic of the Congo

14. Centre for Environment and Health, Department of Public Health and Primary Care, Laboratory of Pulmonology, The Katholieke Universiteit Leuven, Belgium

15. Department of Internal Medicine, Faculty of Medicine, Catholic University of Bukavu

16. The Union Against Tuberculosis and Lung Diseases, Challenge Tuberculosis Initiative, Bukavu, Democratic Republic of the Congo

17. Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Amsterdam University Medical Centers, The Academic Medical Center, The Netherlands

18. Department of Medicine, University Hospital of Kinshasa, Democratic Republic of the Congo

19. Department of Medicine and Center for Infectious Diseases, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

20. Departments of Epidemiology and International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

21. International Centre for Advanced Research and Training, Panzi, Bukavu, Democratic Republic of the Congo

Abstract

Abstract Background Multidrug-resistant tuberculosis (MDR-TB) jeopardizes global TB control. The prevalence and predictors of Rifampicin-resistant (RR) TB, a proxy for MDR-TB, and the treatment outcomes with standard and shortened regimens have not been assessed in post-conflict regions, such as the South Kivu province in the eastern Democratic Republic of the Congo (DRC). We aimed to fill this knowledge gap and to inform the DRC National TB Program. Methods of adults and children evaluated for pulmonary TB by sputum smear microscopy and Xpert MTB/RIF (Xpert) from February 2012 to June 2017. Multivariable logistic regression, Kaplan–Meier estimates, and multivariable Cox regression were used to assess independent predictors of RR-TB and treatment failure/death. Results Of 1535 patients Xpert-positive for TB, 11% had RR-TB. Independent predictors of RR-TB were a positive sputum smear (adjusted odds ratio [aOR] 2.42, 95% confidence interval [CI] 1.63–3.59), retreatment of TB (aOR 4.92, 95% CI 2.31–10.45), and one or more prior TB episodes (aOR 1.77 per episode, 95% CI 1.01–3.10). Over 45% of RR-TB patients had no prior TB history or treatment. The median time from Xpert diagnosis to RR-TB treatment initiation was 12 days (interquartile range 3–60.2). Cures were achieved in 30/36 (83%) and 84/114 (74%) of patients on 9- vs 20/24-month MDR-TB regimens, respectively (P = .06). Predictors of treatment failure/death were the absence of directly observed therapy (DOT; adjusted hazard ratio [aHR] 2.77, 95% CI 1.2–6.66) and any serious adverse drug event (aHR 4.28, 95% CI 1.88–9.71). Conclusions Favorable RR-TB cure rates are achievable in this post-conflict setting with a high RR-TB prevalence. An expanded Xpert scale-up; the prompt initiation of shorter, safer, highly effective MDR-TB regimens; and treatment adherence support are critically needed to optimize outcomes.

Funder

Canadian Government

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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