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. KashongweJean B. Nachega

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1278-1287
Number of pages10
JournalClinical Infectious Diseases
Volume69
Issue number8
DOIs
StatePublished - Sep 27 2019

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Democratic Republic of the Congo
Rifampin
Tuberculosis
Cohort Studies
Multidrug-Resistant Tuberculosis
Confidence Intervals
Odds Ratio
Sputum
Treatment Failure
Directly Observed Therapy
Retreatment
Kaplan-Meier Estimate
Proxy
Drug-Related Side Effects and Adverse Reactions
Microscopy
Therapeutics
Logistic Models
History
Lung

Keywords

  • eastern DR Congo
  • multidrug-resistant TB
  • predictors
  • prevalence
  • treatment outcomes

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

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

In: Clinical Infectious Diseases, Vol. 69, No. 8, 27.09.2019, p. 1278-1287.

Research output: Contribution to journalArticle

Bulabula, ANH, Nelson, JA, Musafiri, EM, MacHekano, R, Sam-Agudu, NA, Diacon, AH, Shah, M, Creswell, J, Theron, G, Warren, RM, Jacobson, KR, Chirambiza, JP, Kalumuna, D, Bisimwa, BC, Katoto, PDMC, Kaswa, MK, Birembano, FM, Kitete, L, Grobusch, MP, Kashongwe, ZM & Nachega, JB 2019, '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', Clinical Infectious Diseases, vol. 69, no. 8, pp. 1278-1287. https://doi.org/10.1093/cid/ciy1105
Bulabula, André N.H. ; Nelson, Jenna A. ; Musafiri, Eric M. ; MacHekano, Rhoderick ; Sam-Agudu, Nadia A. ; Diacon, Andreas H. ; Shah, Maunank ; Creswell, Jacob ; Theron, Grant ; Warren, Robin M. ; Jacobson, Karen R. ; Chirambiza, Jean Paul ; Kalumuna, Dieudonné ; Bisimwa, Bertin C. ; Katoto, Patrick D.M.C. ; Kaswa, Michel K. ; Birembano, Freddy M. ; Kitete, Liliane ; Grobusch, Martin P. ; Kashongwe, Zacharie M. ; Nachega, Jean B. / 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. In: Clinical Infectious Diseases. 2019 ; Vol. 69, No. 8. pp. 1278-1287.
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TY - JOUR

T1 - 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

T2 - A Retrospective Province-Wide Cohort Study

AU - Bulabula, André N.H.

AU - Nelson, Jenna A.

AU - Musafiri, Eric M.

AU - MacHekano, Rhoderick

AU - Sam-Agudu, Nadia A.

AU - Diacon, Andreas H.

AU - Shah, Maunank

AU - Creswell, Jacob

AU - Theron, Grant

AU - Warren, Robin M.

AU - Jacobson, Karen R.

AU - Chirambiza, Jean Paul

AU - Kalumuna, Dieudonné

AU - Bisimwa, Bertin C.

AU - Katoto, Patrick D.M.C.

AU - Kaswa, Michel K.

AU - Birembano, Freddy M.

AU - Kitete, Liliane

AU - Grobusch, Martin P.

AU - Kashongwe, Zacharie M.

AU - Nachega, Jean B.

PY - 2019/9/27

Y1 - 2019/9/27

N2 - 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.

AB - 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.

KW - eastern DR Congo

KW - multidrug-resistant TB

KW - predictors

KW - prevalence

KW - treatment outcomes

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