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

André N H Bulabula; Jenna A Nelson; Eric M Musafiri; Rhoderick Machekano; Nadia A Sam-Agudu; Andreas H Diacon; Maunank Shah; Jacob Creswell; Grant Theron; Robin M Warren; Karen R Jacobson; Jean-Paul Chirambiza; Dieudonné Kalumuna; Bertin C Bisimwa; Patrick D M C Katoto; Michel K Kaswa; Freddy M Birembano; Liliane Kitete; Martin P Grobusch; Zacharie M Kashongwe; Jean B Nachega

doi:10.1093/cid/ciy1105

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

Clin Infect Dis. 2019 Sep 27;69(8):1278-1287. doi: 10.1093/cid/ciy1105.

Authors

André N H Bulabula^{1

2}, Jenna A Nelson³, Eric M Musafiri⁴, Rhoderick Machekano⁵, Nadia A Sam-Agudu^{6

7}, Andreas H Diacon⁸, Maunank Shah⁹, Jacob Creswell¹⁰, Grant Theron¹¹, Robin M Warren¹¹, Karen R Jacobson¹², Jean-Paul Chirambiza⁴, Dieudonné Kalumuna⁴, Bertin C Bisimwa¹³, Patrick D M C Katoto^{14

15}, Michel K Kaswa⁴, Freddy M Birembano⁴, Liliane Kitete¹⁶, Martin P Grobusch¹⁷, Zacharie M Kashongwe¹⁸, Jean B Nachega^{3

19

20

21}

Affiliations

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

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.

Keywords: eastern DR Congo; multidrug-resistant TB; predictors; prevalence; treatment outcomes.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antibiotics, Antitubercular / pharmacology*
Child
Cohort Studies
Democratic Republic of the Congo / epidemiology
Drug Resistance, Bacterial
Humans
Mycobacterium tuberculosis / drug effects*
Prevalence
Retrospective Studies
Rifampin / pharmacology*
Sputum / microbiology
Treatment Outcome
Tuberculosis, Multidrug-Resistant / drug therapy
Tuberculosis, Multidrug-Resistant / epidemiology*
Tuberculosis, Multidrug-Resistant / microbiology
Tuberculosis, Pulmonary / drug therapy
Tuberculosis, Pulmonary / epidemiology*
Tuberculosis, Pulmonary / microbiology

Substances

Antibiotics, Antitubercular
Rifampin

Abstract

Publication types

MeSH terms

Substances

Grants and funding