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Treatment outcomes for multidrug- and rifampicin-resistant tuberculosis in Central and West Africa: a systematic review and meta-analysis

Open AccessPublished:August 22, 2022DOI:https://doi.org/10.1016/j.ijid.2022.08.015

      Highlights

      • Multidrug-resistant/rifampicin-resistant tuberculosis remains a major threat to global health, mainly in low-income settings.
      • We found a successful treatment outcome of 74.6% in Central and West Africa.
      • The World Health Organization reported an average global success rate of 59% in 2018.
      • Shorter and standardized regimens may have contributed to better success rates.
      • Treatment outcome data of multidrug-resistant/rifampicin-resistant tuberculosis is sparse in this region and further investigation is warranted.

      Abstract

      Objectives

      We aimed to investigate published data on treatment outcomes of multidrug-resistant (MDR)/rifampicin-resistant tuberculosis (TB) in Central and West Africa because these, to the best of our knowledge, are sparsely available.

      Methods

      Systematic review and meta-analysis.

      Results

      A total of 14 studies were included, representing 4268 individuals in 14 of the 26 countries. Using a random-effects model meta-analysis, we observed a pooled success rate of 80.8% (95% confidence interval [CI] 56.0-93.3) for the Central African subgroup and 69.2% (95% CI 56.3-79.7) for the West African subgroup (P = 0.0522). The overall treatment success for all studies was 74.6% (95% CI 65.0-82.2). We found high heterogeneity among included studies (I2 = 96.1%). The estimated proportion of successfully treated individuals with MDR/rifampicin-resistant TB was considerably higher than the global estimate provided by the World Health Organization (59%), reaching the 2015 World Health Organization target of at least 75% treatment success for MDR-TB.

      Conclusion

      The use of shorter treatment regimens and the standardized treatment conditions, including directly observed therapy in these studies, could have contributed to a high treatment success. Yet, the available literature was not fully representative of the regions, possibly highlighting the sparse resources in many of these countries.
      The review was registered at PROSPERO (https://www.crd.york.ac.uk/prospero/) (CRD42022353163).

      Keywords

      Introduction

      Multidrug-resistant (MDR) and rifampicin-resistant (RR) tuberculosis (TB) remains a major threat to disease control and health worldwide (World Health Organization [
      World Health Organization
      Global tuberculosis report 2021.
      ). MDR-TB is defined as Mycobacterium tuberculosis (MTB) strains that are resistant to the first-line drugs, isoniazid and rifampicin (
      World Health Organization
      Meeting report of the WHO expert consultation on the definition of extensively drug-resistant tuberculosis.
      ). In many settings, Xpert MTB and rifampin (MTB/RIF) Assay (GeneXpert) is the only diagnostic tool available to measure RR and is consequently considered a proxy for MDR-TB (
      • Pandey P
      • Pant ND
      • Rijal KR
      • Shrestha B
      • Kattel S
      • Banjara MR
      • et al.
      Diagnostic accuracy of GeneXpert MTB/RIF Assay in comparison to conventional drug susceptibility testing method for the diagnosis of multidrug-resistant tuberculosis.
      ;
      World Health Organization
      Automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance: Xpert MTB/RIF system [policy statement].
      ). Drug-resistance is associated with protracted and complicated treatments, expensive drug regimens, severe adverse effects, and higher mortality rates (
      • Lange C
      • Aarnoutse RE
      • Alffenaar JWC
      • Bothamley G
      • Brinkmann F
      • Costa J
      • et al.
      Management of patients with multidrug-resistant tuberculosis.
      ;
      • Migliori GB
      • Tiberi S
      • Zumla A
      • Petersen E
      • Chakaya JM
      • Wejse C
      • et al.
      MDR/XDR-TB management of patients and contacts: challenges facing the new decade. The 2020 clinical update by the Global Tuberculosis Network.
      ). In those who are coinfected with HIV, the mortality can be as high as 50% (
      • Efsen AMW
      • Schultze A
      • Miller RF
      • Panteleev A
      • Skrahin A
      • Podlekareva DN
      • et al.
      Management of MDR-TB in HIV co-infected patients in Eastern Europe: results from the TB:HIV study.
      ). Concerningly, the World Health Organization (WHO) assumed 465,000 incident cases of MDR/RR-TB in 2019 (before the COVID-19 pandemic), of which only one-third is presumed treated (
      • Migliori GB
      • Tiberi S
      • Zumla A
      • Petersen E
      • Chakaya JM
      • Wejse C
      • et al.
      MDR/XDR-TB management of patients and contacts: challenges facing the new decade. The 2020 clinical update by the Global Tuberculosis Network.
      ;
      World Health Organization
      Global tuberculosis report 2020.
      ). The treatment of MDR/RR-TB poses numerous challenges that are not necessarily apparent in high-income countries. Logistical, economic, and technological barriers complicate the matter, and treatment relies on an adequate diagnosis and drug-susceptibility testing as well as availability of medications (
      • Lange C
      • Aarnoutse RE
      • Alffenaar JWC
      • Bothamley G
      • Brinkmann F
      • Costa J
      • et al.
      Management of patients with multidrug-resistant tuberculosis.
      ;
      • Migliori GB
      • Tiberi S
      • Zumla A
      • Petersen E
      • Chakaya JM
      • Wejse C
      • et al.
      MDR/XDR-TB management of patients and contacts: challenges facing the new decade. The 2020 clinical update by the Global Tuberculosis Network.
      ).
      As of May 2022, WHO has endorsed a promising 6-month, all-oral regimen for MDR-TB, and previously, a 9-month oral regimen (
      World Health Organization
      Rapid communication: key changes to the treatment of drug-resistant tuberculosis.
      ). Unfortunately, most patients are still treated for at least 18-20 months in many regions due to a high cost and low availability of medications (
      • Lange C
      • Barry Iii CE
      • Horsburgh Jr, CR
      Treatments of multidrug-resistant tuberculosis: light at the end of the tunnel.
      ). In many African countries, a short regimen including injectables has been widely used (
      • Schwœbel V
      • Trébucq A
      • Kashongwe Z
      • Bakayoko AS
      • Kuaban C
      • Noeske J
      • et al.
      Outcomes of a nine-month regimen for rifampicin-resistant tuberculosis up to 24 months after treatment completion in nine African countries.
      ) and was previously recommended by WHO (
      World Health Organization
      WHO treatment guidelines for drug-resistant tuberculosis, 2016 update.
      ). Despite efforts to control the disease worldwide, the number of detected MDR/RR-TB cases increased by 10% between 2018 and 2019 (
      World Health Organization
      Global tuberculosis report 2020.
      ). However, this increase may also have been caused by intensified screening and improved detection. Worldwide, treatment success was still suboptimal, with a point prevalence of 59% for MDR/RR-TB in 2018 (
      World Health Organization
      Global tuberculosis report 2021.
      ). Treatment success was 69% in 2018 for patients in the African region who were started on second-line treatment (
      World Health Organization
      Global tuberculosis report 2020.
      ). Unsettlingly, only 36% of all new patients with TB were tested with rapid diagnostics (Xpert MTB/RIF and Xpert MTB/RIF Ultra) at the time of diagnosis, potentially masking an overestimation (
      World Health Organization
      Global tuberculosis report 2020.
      ). Drug-susceptibility testing coverage has expanded between 2018 and 2019 in five of the six WHO regions, except in the African region (
      World Health Organization
      Global tuberculosis report 2020.
      ). Still, it is our impression that data and literature on treatment outcomes of MDR/RR-TB in Central and West Africa are sparse, despite being a region with a massive burden of TB (
      • Dean AS
      • Tosas Auguet O
      • Glaziou P
      • Zignol M
      • Ismail N
      • Kasaeva T
      • et al.
      25 years of surveillance of drug-resistant tuberculosis: achievements, challenges, and way forward.
      ;
      • Knight GM
      • McQuaid CF
      • Dodd PJ
      • Houben RMGJ.
      Global burden of latent multidrug-resistant tuberculosis: trends and estimates based on mathematical modelling.
      ;
      • Lange C
      • Barry Iii CE
      • Horsburgh Jr, CR
      Treatments of multidrug-resistant tuberculosis: light at the end of the tunnel.
      ). With the continued emergence of drug-resistant MTB as a huge barrier to the goals of the WHO's End TB Strategy (
      World Health Organization
      ), we aimed to evaluate treatment outcomes of MDR/RR-TB in Central and West Africa based on the available literature.

      Methods

      A systematic review was conducted using the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement (
      • Page MJ
      • McKenzie JE
      • Bossuyt PM
      • Boutron I
      • Hoffmann TC
      • Mulrow CD
      • et al.
      The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.
      ). A Preferred Reporting Items for Systematic Reviews and Meta-analyses flow chart (Figure 1) and checklist are provided (Appendix 1). The review was registered at the International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/prospero/) (CRD42022353163).
      Figure 1
      Fig. 1Flow chart of study inclusion and exclusion.
      Abbreviation: MDR-TB, multidrug-resistant-tuberculosis.

      Search strategy

      A systematic review was conducted to identify eligible studies on MDR/RR-TB treatment outcomes in Embase, Web of Science, Scopus, and PubMed/MEDLINE databases. The search was performed on March 13, 2022. The databases were searched with a combination of the following keywords: “tuberculosis”, “TB”, “multidrug-resistant”, “MDR” “extensively drug-resistant”, “XDR” “drug-resistant tuberculosis”, “Africa” and “treatment outcome”, among others (search string available in Appendix 2). The search string was combined with the name of the countries in Central and West Africa. Country members of the Economic Community of Central African States and Central Africa of the Economic Community of West African States were included in studies from Central and West Africa, respectively (

      ECCAS. Economic Community of Central African States member states. https://ceeac-eccas.org/pays-membres/Date, 2022 (accessed 9 May 2022).

      ;

      ECOWAS. Economic Community of West African States member states. https://ecowas.int/member-states/Date, 2022 (accessed 9 May 2022).

      ). There were no filters applied and no language restrictions to ensure a broad search and reduce the risk of language bias. Reviews and reference lists were screened to identify relevant literature.

      Selection of studies

      Studies obtained from the literature search were screened by title and abstract by ALT and VND, using covidence.org, a browser-based software for literature review. Full texts were examined if the articles were considered relevant. A preliminary manuscript for an ongoing unpublished study was included in the review (Sifna et al., unpublished). Studies were included if they were original articles with information on MDR/RR-TB treatment outcomes as defined by WHO or adaptations thereof. Studies using treatment outcome measures, such as mortality or culture conversion only were excluded. Other exclusion criteria included studies solely including patients who are still on treatment, relapse among patients with MDR/RR-TB without reconfirmation of MDR/RR-TB, patients with only pre-extensively drug-resistant (XDR)/XDR-TB, small sample size (n <25), case reports/series, reviews, and studies using first-line treatment for MDR-TB.

      Eligibility assessment

      Studies using the recommended outcomes of MDR-TB treatment or adaptations thereof were included for analysis. The adapted outcome definitions were assessed before inclusion to ensure cross-comparability. Studies with overlapping cohorts were identified to the best of our ability and the study (i) containing the most cases in the same cohort, (ii) with most elaborate outcome classification, (iii) and/or with the most recent update to end of treatment outcomes was included and prioritized in that order. Multiple authors were contacted to preclude overlapping data, and results stratified by country were provided, allowing exclusion of overlapping data from the multiple-country study (
      • Schwœbel V
      • Trébucq A
      • Kashongwe Z
      • Bakayoko AS
      • Kuaban C
      • Noeske J
      • et al.
      Outcomes of a nine-month regimen for rifampicin-resistant tuberculosis up to 24 months after treatment completion in nine African countries.
      ).

      Outcome measures

      According to WHO, treatment completion and cure were defined as successful outcomes, whereas treatment failure, consisting of lost to follow-up (LTFU), and death during treatment were considered unsuccessful outcomes (
      Eurosurveillance editorial team
      WHO Revised definitions and reporting framework for tuberculosis.
      ). Patients categorized as ‘relapses’ during follow-up were counted, if available, as treatment failures and unsuccessful outcomes. ‘Transferred out’ was categorized as not evaluated. If the studies did not provide a summation of cured and completed, this was calculated by the authors. For studies not presenting a pooled unsuccessful outcome, a worst-case scenario, including failure, death, LTFU, and not evaluated was estimated. The studies using adaptations of the WHO outcomes are available in Appendix 3.

      Data extraction

      Data were extracted into a preformed Excel spreadsheet (Microsoft, Redmond, WA, USA). Information collected included data on first author, year of publication, study design, period, country, population size, age, percentage of males/females, percentage of HIV-positive individuals, drug-resistance patterns, treatment regimens (Appendix 4), length of treatment, information on previous treatment, use of directly observed therapy (DOT), stratified treatment outcomes if available, and definitions of treatment outcome. The distribution of treatment outcomes in the individual studies was calculated before stratification by country and random-effects analysis. If a study had multiple cohorts with different treatment regimes, and the results were available, the results were stratified based on the regime. Successful outcomes, defined as the sum of ‘cured’ and ‘completed’, were pooled and the proportions relative to the cohort sizes were calculated. Study characteristics and treatment outcomes by reference and country were summarized in tables. Mapchart.net was used to create a figure of Central and West Africa to provide an overview of the included countries.

      Statistical analyses

      Statistical analyses were performed using the meta package (version 5.2-0) in R (version 4.1.3).
      Because we anticipated considerable between-study heterogeneity, a random-effects model was used to pool the proportion of successful outcomes, using logit transformation and inverse variance method. We used Knapp-Hartung adjustments to calculate the confidence interval (CI) around the pooled effect. Clopper-Pearson CIs were calculated for individual studies. A pooled success rate was also calculated for the Central and West African subgroups. A pooled unsuccessful outcome was also calculated. A sensitivity analysis with removal of outliers was conducted, where studies were considered outliers if their CI did not overlap with the CI of the pooled effect. Moreover, an analysis of studies using only WHO treatment outcomes and adapted treatment outcome definitions was performed. Heterogeneity was quantified with I2 statistics.
      We assessed publication bias using a funnel plot. Based on the shape of the plot, a symmetrical plot was interpreted as suggestive of no publication bias and conversely. In addition, we constructed a contour-enhanced funnel plot to distinguish between publication bias and other causes of funnel plot asymmetry (
      • Sterne JA
      • Sutton AJ
      • Ioannidis JP
      • Terrin N
      • Jones DR
      • Lau J
      • et al.
      Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials.
      ). All estimates were presented with 95% CI, and a P-value less than 5% was considered statistically significant.

      Results

      In total, 867 records were identified through databases, of which 84 full-text articles were examined for relevance (Figure 1). Two additional articles were obtained from other sources (
      • Kamara RF
      • Saunders MJ
      • Sahr F
      • Losa-Garcia JE
      • Foray L
      • Davies G
      • et al.
      Social and health factors associated with adverse treatment outcomes among people with multidrug-resistant tuberculosis in Sierra Leone: a national, retrospective cohort study.
      , Sifna et al., unpublished). Of the remaining articles, 14 were included for quantitative analysis (
      • Akinsola OJ
      • Yusuf OB
      • Ige OM
      • Okonji PE.
      Models for predicting time to sputum conversion among multi-drug resistant tuberculosis patients in Lagos, South-West Nigeria.
      ,
      • Aznar ML
      • Rando Segura A
      • Moreno MM
      • Espasa M
      • Sulleiro E
      • Bocanegra C
      • et al.
      Treatment outcomes and adverse events from a standardized multidrug-resistant tuberculosis regimen in a rural setting in Angola.
      ,
      • Bakare AM
      • Udunze OC
      • Bamidele JO
      • Omoniyi A
      • Osman E
      • Daniel OJ.
      Outcome of community-initiated treatment of drug-resistant tuberculosis patients in Lagos.
      ,
      • Bulabula ANH
      • Nelson JA
      • Musafiri EM
      • Machekano R
      • Sam-Agudu NA
      • Diacon AH
      • et al.
      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.
      ,
      • Ciza F
      • Gils T
      • Sawadogo M
      • Decroo T
      • Roggi A
      • Piubello A
      • et al.
      Course of adverse events during short treatment regimen in patients with rifampicin-resistant tuberculosis in Burundi.
      ,
      • Hassane-Harouna S
      • Cherif GF
      • Ortuno-Gutierrez N
      • Cisse D
      • Camara LM
      • Diallo BD
      • et al.
      Better programmatic outcome with the shorter regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) in Guinea: a retrospective cohort study.
      ,
      • Ige OM
      • Oladokun RE.
      Time to sputum culture conversion and treatment outcome among the first cohort of multidrug resistant tuberculosis patients in a high burden country.
      ,
      • Kamara RF
      • Saunders MJ
      • Sahr F
      • Losa-Garcia JE
      • Foray L
      • Davies G
      • et al.
      Social and health factors associated with adverse treatment outcomes among people with multidrug-resistant tuberculosis in Sierra Leone: a national, retrospective cohort study.
      ,
      • Kuaban C
      • Noeske J
      • Rieder HL
      • Aït-Khaled N
      • Abena Foe JL
      • Trébucq A
      High effectiveness of a 12-month regimen for MDR-TB patients in Cameroon.
      ,
      • Ngabonziza JS
      • Habimana YM
      • Decroo T
      • Migambi P
      • Dushime A
      • Mazarati JB
      • et al.
      Reduction of diagnostic and treatment delays reduces rifampicin-resistant tuberculosis mortality in Rwanda.
      ,
      • Piubello A
      • Souleymane MB
      • Hassane-Harouna S
      • Yacouba A
      • Lempens P
      • Assao-Neino MM
      • et al.
      Management of multidrug-resistant tuberculosis with shorter treatment regimen in Niger: nationwide programmatic achievements.
      ,
      • Schwœbel V
      • Trébucq A
      • Kashongwe Z
      • Bakayoko AS
      • Kuaban C
      • Noeske J
      • et al.
      Outcomes of a nine-month regimen for rifampicin-resistant tuberculosis up to 24 months after treatment completion in nine African countries.
      , Sifna et al., unpublished,
      • Souleymane MB
      • Piubello A
      • Lawan IM
      • Hassane-Harouna S
      • Assao-Neino MM
      • Soumana A
      • et al.
      High rifampicin-resistant TB cure rates and prevention of severe ototoxicity after replacing the injectable by linezolid in early stage of hearing loss.
      ). Several articles contained overlapping data and were excluded.
      The 14 studies included for analysis represented 14 of 26 countries in the two regions (Figure 2). The largest study included data from both Benin, Burkina Faso, Burundi, Cameroon, Central African Republic, Côte d'Ivoire, Democratic Republic of Congo, Niger, and Rwanda (
      • Schwœbel V
      • Trébucq A
      • Kashongwe Z
      • Bakayoko AS
      • Kuaban C
      • Noeske J
      • et al.
      Outcomes of a nine-month regimen for rifampicin-resistant tuberculosis up to 24 months after treatment completion in nine African countries.
      ). However, data from Burundi, Niger, and Rwanda were excluded from this study due to overlapping data.
      Figure 2
      Fig. 2Map of Central and West Africa countries with (green) and without (gray) data on multidrug-resistant tuberculosis treatment outcome.
      Study periods ranged from 2005 to 2020 (
      • Ngabonziza JS
      • Habimana YM
      • Decroo T
      • Migambi P
      • Dushime A
      • Mazarati JB
      • et al.
      Reduction of diagnostic and treatment delays reduces rifampicin-resistant tuberculosis mortality in Rwanda.
      , Sifna et al.). A total of 11 studies were retrospective cohort studies (
      • Akinsola OJ
      • Yusuf OB
      • Ige OM
      • Okonji PE.
      Models for predicting time to sputum conversion among multi-drug resistant tuberculosis patients in Lagos, South-West Nigeria.
      ,
      • Bakare AM
      • Udunze OC
      • Bamidele JO
      • Omoniyi A
      • Osman E
      • Daniel OJ.
      Outcome of community-initiated treatment of drug-resistant tuberculosis patients in Lagos.
      ,
      • Bulabula ANH
      • Nelson JA
      • Musafiri EM
      • Machekano R
      • Sam-Agudu NA
      • Diacon AH
      • et al.
      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.
      ,
      • Ciza F
      • Gils T
      • Sawadogo M
      • Decroo T
      • Roggi A
      • Piubello A
      • et al.
      Course of adverse events during short treatment regimen in patients with rifampicin-resistant tuberculosis in Burundi.
      ,
      • Hassane-Harouna S
      • Cherif GF
      • Ortuno-Gutierrez N
      • Cisse D
      • Camara LM
      • Diallo BD
      • et al.
      Better programmatic outcome with the shorter regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) in Guinea: a retrospective cohort study.
      ,
      • Ige OM
      • Oladokun RE.
      Time to sputum culture conversion and treatment outcome among the first cohort of multidrug resistant tuberculosis patients in a high burden country.
      ,
      • Kamara RF
      • Saunders MJ
      • Sahr F
      • Losa-Garcia JE
      • Foray L
      • Davies G
      • et al.
      Social and health factors associated with adverse treatment outcomes among people with multidrug-resistant tuberculosis in Sierra Leone: a national, retrospective cohort study.
      ,
      • Ngabonziza JS
      • Habimana YM
      • Decroo T
      • Migambi P
      • Dushime A
      • Mazarati JB
      • et al.
      Reduction of diagnostic and treatment delays reduces rifampicin-resistant tuberculosis mortality in Rwanda.
      ,
      • Piubello A
      • Souleymane MB
      • Hassane-Harouna S
      • Yacouba A
      • Lempens P
      • Assao-Neino MM
      • et al.
      Management of multidrug-resistant tuberculosis with shorter treatment regimen in Niger: nationwide programmatic achievements.
      , Sifna et al., unpublished,
      • Souleymane MB
      • Piubello A
      • Lawan IM
      • Hassane-Harouna S
      • Assao-Neino MM
      • Soumana A
      • et al.
      High rifampicin-resistant TB cure rates and prevention of severe ototoxicity after replacing the injectable by linezolid in early stage of hearing loss.
      ) and three were prospective (
      • Aznar ML
      • Rando Segura A
      • Moreno MM
      • Espasa M
      • Sulleiro E
      • Bocanegra C
      • et al.
      Treatment outcomes and adverse events from a standardized multidrug-resistant tuberculosis regimen in a rural setting in Angola.
      ;
      • Kuaban C
      • Noeske J
      • Rieder HL
      • Aït-Khaled N
      • Abena Foe JL
      • Trébucq A
      High effectiveness of a 12-month regimen for MDR-TB patients in Cameroon.
      ;
      • Schwœbel V
      • Trébucq A
      • Kashongwe Z
      • Bakayoko AS
      • Kuaban C
      • Noeske J
      • et al.
      Outcomes of a nine-month regimen for rifampicin-resistant tuberculosis up to 24 months after treatment completion in nine African countries.
      ). The mean study population size was 304.9 (range 115-845); most patients were males (range 51.3-84.1%) (
      • Kuaban C
      • Noeske J
      • Rieder HL
      • Aït-Khaled N
      • Abena Foe JL
      • Trébucq A
      High effectiveness of a 12-month regimen for MDR-TB patients in Cameroon.
      ;
      • Souleymane MB
      • Piubello A
      • Lawan IM
      • Hassane-Harouna S
      • Assao-Neino MM
      • Soumana A
      • et al.
      High rifampicin-resistant TB cure rates and prevention of severe ototoxicity after replacing the injectable by linezolid in early stage of hearing loss.
      ), and the median age ranged from 28 to 35 years (
      • Bulabula ANH
      • Nelson JA
      • Musafiri EM
      • Machekano R
      • Sam-Agudu NA
      • Diacon AH
      • et al.
      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.
      ;
      • Hassane-Harouna S
      • Cherif GF
      • Ortuno-Gutierrez N
      • Cisse D
      • Camara LM
      • Diallo BD
      • et al.
      Better programmatic outcome with the shorter regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) in Guinea: a retrospective cohort study.
      ;
      • Kamara RF
      • Saunders MJ
      • Sahr F
      • Losa-Garcia JE
      • Foray L
      • Davies G
      • et al.
      Social and health factors associated with adverse treatment outcomes among people with multidrug-resistant tuberculosis in Sierra Leone: a national, retrospective cohort study.
      ). All studies reported the number patients coinfected with HIV, ranging from 4.1% to 39.9% (
      • Ngabonziza JS
      • Habimana YM
      • Decroo T
      • Migambi P
      • Dushime A
      • Mazarati JB
      • et al.
      Reduction of diagnostic and treatment delays reduces rifampicin-resistant tuberculosis mortality in Rwanda.
      ;
      • Souleymane MB
      • Piubello A
      • Lawan IM
      • Hassane-Harouna S
      • Assao-Neino MM
      • Soumana A
      • et al.
      High rifampicin-resistant TB cure rates and prevention of severe ototoxicity after replacing the injectable by linezolid in early stage of hearing loss.
      ). Seven studies reported using DOT (
      • Aznar ML
      • Rando Segura A
      • Moreno MM
      • Espasa M
      • Sulleiro E
      • Bocanegra C
      • et al.
      Treatment outcomes and adverse events from a standardized multidrug-resistant tuberculosis regimen in a rural setting in Angola.
      ;
      • Bakare AM
      • Udunze OC
      • Bamidele JO
      • Omoniyi A
      • Osman E
      • Daniel OJ.
      Outcome of community-initiated treatment of drug-resistant tuberculosis patients in Lagos.
      ;
      • Bulabula ANH
      • Nelson JA
      • Musafiri EM
      • Machekano R
      • Sam-Agudu NA
      • Diacon AH
      • et al.
      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.
      ;
      • Ige OM
      • Oladokun RE.
      Time to sputum culture conversion and treatment outcome among the first cohort of multidrug resistant tuberculosis patients in a high burden country.
      ;
      • Kuaban C
      • Noeske J
      • Rieder HL
      • Aït-Khaled N
      • Abena Foe JL
      • Trébucq A
      High effectiveness of a 12-month regimen for MDR-TB patients in Cameroon.
      ;
      • Piubello A
      • Souleymane MB
      • Hassane-Harouna S
      • Yacouba A
      • Lempens P
      • Assao-Neino MM
      • et al.
      Management of multidrug-resistant tuberculosis with shorter treatment regimen in Niger: nationwide programmatic achievements.
      ;
      • Schwœbel V
      • Trébucq A
      • Kashongwe Z
      • Bakayoko AS
      • Kuaban C
      • Noeske J
      • et al.
      Outcomes of a nine-month regimen for rifampicin-resistant tuberculosis up to 24 months after treatment completion in nine African countries.
      ). Five studies used adaptations of treatment outcomes (
      • Aznar ML
      • Rando Segura A
      • Moreno MM
      • Espasa M
      • Sulleiro E
      • Bocanegra C
      • et al.
      Treatment outcomes and adverse events from a standardized multidrug-resistant tuberculosis regimen in a rural setting in Angola.
      ;
      • Ciza F
      • Gils T
      • Sawadogo M
      • Decroo T
      • Roggi A
      • Piubello A
      • et al.
      Course of adverse events during short treatment regimen in patients with rifampicin-resistant tuberculosis in Burundi.
      ;
      • Ige OM
      • Oladokun RE.
      Time to sputum culture conversion and treatment outcome among the first cohort of multidrug resistant tuberculosis patients in a high burden country.
      ;
      • Piubello A
      • Souleymane MB
      • Hassane-Harouna S
      • Yacouba A
      • Lempens P
      • Assao-Neino MM
      • et al.
      Management of multidrug-resistant tuberculosis with shorter treatment regimen in Niger: nationwide programmatic achievements.
      ;
      • Schwœbel V
      • Trébucq A
      • Kashongwe Z
      • Bakayoko AS
      • Kuaban C
      • Noeske J
      • et al.
      Outcomes of a nine-month regimen for rifampicin-resistant tuberculosis up to 24 months after treatment completion in nine African countries.
      ). A single study was included, although 11.3% (n = 47/413) of patients had XDR-TB (
      • Akinsola OJ
      • Yusuf OB
      • Ige OM
      • Okonji PE.
      Models for predicting time to sputum conversion among multi-drug resistant tuberculosis patients in Lagos, South-West Nigeria.
      ).
      Treatment outcomes by study are presented in Table 1, and outcomes stratified by country are presented in Table 2 and Figure 2. Of the 4268 individuals included, 74.3% fulfilled the definition of a successful outcome, whereas 3.4%, 12.3%, 7.1%, and 2.9% were classified as failure/relapse, death during treatment, LTFU, or not evaluated, respectively, corresponding to a rate of unsuccessful outcome of 25.7%. The proportion of successful outcomes was pooled and weighted using a random-effects model, resulting in an overall treatment success of 74.6% (95% CI 65.0-82.2) for all studies (Figure 3). Our analysis revealed high heterogeneity among the included studies (I2 = 96.1%; P <0.01). Treatment success rate was 80.8% (95% CI 56.0-93.3) for the Central African subgroup and 69.2% (95% CI 56.3-79.7) for the West African subgroup (P = 0.0522). Taking treatment outcome definition into account, the treatment success rate was 72.3% (95% CI 59.4-82.4) and 78.4% (95% CI 54.2-91.7) (P = 0.492) when using only WHO definitions (n = 9) and adaptations (n = 5) hereof, respectively. Excluding outliers (
      • Aznar ML
      • Rando Segura A
      • Moreno MM
      • Espasa M
      • Sulleiro E
      • Bocanegra C
      • et al.
      Treatment outcomes and adverse events from a standardized multidrug-resistant tuberculosis regimen in a rural setting in Angola.
      ,
      • Ciza F
      • Gils T
      • Sawadogo M
      • Decroo T
      • Roggi A
      • Piubello A
      • et al.
      Course of adverse events during short treatment regimen in patients with rifampicin-resistant tuberculosis in Burundi.
      ,
      • Kuaban C
      • Noeske J
      • Rieder HL
      • Aït-Khaled N
      • Abena Foe JL
      • Trébucq A
      High effectiveness of a 12-month regimen for MDR-TB patients in Cameroon.
      , Sifna et al., unpublished) revealed a similar pooled success rate of 75.1% (95% CI 69.8-79.7). The pooled unsuccessful treatment outcome was 25.4% (95% CI 17.8-35.0) and 18.9% (95% CI 11.2-30.3) and 28.1% (95% CI 20.3-37.5) for the Central (n = 8) and West African (n = 11) subgroup (P = 0.1137), respectively. The funnel plot for assessment of publication bias was asymmetrical (Appendix 5), suggesting probable publication bias. A contour-enhanced funnel plot indicated that missing studies were mainly in the region of higher statistical significance, with only one study missing in the region of low statistical significance, implying that the asymmetry was not caused solely by publication bias but other causes, such as small study effect sizes and differences in participant characteristics.
      Table 1Treatment outcomes by references
      Author and countryStudy designStudy periodOutcome definition
      See Appendix 3 for specified adaptations.
      Median age, yearsMales, %Population,nSuccessful outcome, n (%)Unsuccessful outcome, n (%)Cure, nComplete, nFailure/relapse, nDeath, nLTFU, nNE,n
      Aznar et al., AngolaP2013-2015Adapted30.0 (IQR 24.2-38.0)57.414779 (53.7)68 (46.3)4237324410
      Ciza et al., BurundiR2013-2017AdaptedN/A66.2225209 (92.9)16 (7.1)1852421130
      Kuaban et al., CameroonP2008-2011WHO33.7**(range 17-68)51.3150134 (89.3)16 (10.7)132211050
      Schwœbell et al., multipleP2013-2015Adapted33(IQR 26-41)65.4845
      Data were only included from Benin, Burkina Faso, Cameroon, the Central African Republic, Côte d'Ivoire, and the Democratic Republic of Congo to avoid overlapping data.
      676 (80.0)169 (20.0)608686663382
      Bulabula et al.
      Successful outcome was not stratifiable by cure and complete but was considered as completed due to the limited availability of culture in DRC.
      , DRC
      R2012-2017WHO35 (IQR 27-44)67.6170120 (70.6)50 (29.4)-1200241511
      Hassane-Harouna et al., GuineaR2016-2017WHO28 (23-38)72.0271189 (69.7)82 (30.3)154351041310
      Sifna et al. (unpublished), Guinea-BissauR2012-2020WHON/A58.227397 (35.5)176 (64.5)0970554081
      Piubello et al., NigerR2008-2016Adapted32 (IQR 25-40)82.7249207 (83.1)42 (16.9)2070122370
      Souleymane et al., NigerR2016-2019WHO33(IQR 26-41)84.3153
      Data of 2016 cohort are analyzed in Piubello et al. and not included here.
      124 (81.0)29 (19.0)124072020
      Akinsola et al.
      47 XDR patients were included in this cohort.
      , Nigeria
      R2012-2016WHO36.8
      mean.
      (+/- 12.6)
      60.8413268 (64.9)145 (35.1)6420422307221
      Bakare et al., NigeriaR2015-2016WHON/A60.7150105 (70.0)45 (30.0)5154814194
      Ige and Oladokun,

      Nigeria
      R2010-2013Adapted37.3/30.5
      male:female ratio. Abbreviations: LTFU: Lost to follow-up, NE: Not evaluated, N/A: Not available, WHO: World Health Organization, R: retrospective, P: prospective, DRC: Democratic Republic of Congo; XDR, extensively drug-resistant.
      (males/females)
      66.111579 (68.7)36 (31.3)4237125100
      Ngabonziza et al., RwandaR2005-2016WHO34 (IQR 27-43)57.5742618 (83.3)124 (16.7)457161411280
      Kamara et al., Sierra LeoneR2017-2019WHO35 (IQR 26-45)72.1365267 (73.2)98 (26.8)29238875123
      Total, n (%)4268 (100)3172 (74.3)1096 (25.7)2095(49.1)1077 (25.2)144(3.4)527 (12.3)303 (7.1)122(2.9)
      a Successful outcome was not stratifiable by cure and complete but was considered as completed due to the limited availability of culture in DRC.
      b 47 XDR patients were included in this cohort.
      c Data were only included from Benin, Burkina Faso, Cameroon, the Central African Republic, Côte d'Ivoire, and the Democratic Republic of Congo to avoid overlapping data.
      d Data of 2016 cohort are analyzed in Piubello et al. and not included here.
      e See Appendix 3 for specified adaptations.
      f mean.
      g male:female ratio.Abbreviations: LTFU: Lost to follow-up, NE: Not evaluated, N/A: Not available, WHO: World Health Organization, R: retrospective, P: prospective, DRC: Democratic Republic of Congo; XDR, extensively drug-resistant.
      Table 2Summarized treatment outcomes by country of origin and region
      Reference(s)CountryPopulation, nSuccessful outcome, n (%)Unsuccessful outcome, n (%)Cure, nComplete, nFailure/relapse, nDeath, nLTFU, nNE, n
      Aznar et al.Angola14779 (53.7)68 (46.3)4237324410
      Ciza et al.Burundi225209 (92.9)16 (7.1)1852421130
      Kuaban et al., Schwœbell et al.Cameroon326283 (86.8)43 (13.2)2803726100
      Schwœbell et al.CAR4536 (80.0)9 (20.0)3602520
      Bulabula et al.
      Successful outcome was not stratifiable by cure and complete but was considered completed due to the limited availability of culture in DRC.
      , Schwœbell et al.
      DRC471359 (76.2)112 (23.8)22013921413812
      Ngabonziza et al.Rwanda742618 (83.3)124 (16.7)457161411280
      Total, n (%)1956 (100)1584 (81.0)372(19.0)1220 (62.4)364 (18.6)39 (2.0)219 (11.2)102 (5.2)12 (0.6)
      Schwœbell et al.Benin2925 (86.2)4 (13.8)2501300
      Schwœbell et al.Burkina Faso3426 (76.5)8 (23.5)2066011
      Schwœbell et al.Côte d'Ivoire260201 (77.3)59 (22.7)15942302270
      Hassane-Harouna et al.Guinea271189 (69.7)82 (30.3)154351041310
      Sifna et al. (unpublished)Guinea-Bissau27397 (35.5)176 (64.5)0970554081
      Piubello et al., Souleymane et al.
      Including data from 2016 to June 2019 without overlapping data.
      Niger402331 (82.3)71 (17.7)3310194390
      Akinsolaet al.
      47 XDR patients were included in this cohort. Abbreviations: LTFU: Lost to follow-up, NE: Not evaluated, CAR: Central African Republic, DRC: Democratic Republic of Congo; XDR, extensively drug-resistant.
      , Bakare et al., Ige and Oladokun.
      Nigeria678452 (66.7)226 (33.3)157295316910125
      Kamara et al.Sierra Leone365267 (73.2)98 (26.8)29238875123
      Total, n (%)2312(100)1588 (68.7)724(31.3)875 (37.8)713 (30.8)105(4.5)308 (13.3)201 (8.7)110(4.8)
      a Successful outcome was not stratifiable by cure and complete but was considered completed due to the limited availability of culture in DRC.
      b Including data from 2016 to June 2019 without overlapping data.
      c 47 XDR patients were included in this cohort.Abbreviations: LTFU: Lost to follow-up, NE: Not evaluated, CAR: Central African Republic, DRC: Democratic Republic of Congo; XDR, extensively drug-resistant.
      Figure 3
      Fig. 3Forest plot of the proportion of successful treatment outcomes for each study and a pooled estimate (random-effects model).
      Footnote: a47 XDR patients were included in this cohort.
      bData were only included from Benin, Burkina Faso, Cameroon, the Central African Republic, Côte d'Ivoire, and the Democratic Republic of Congo to avoid overlapping data.
      cData of 2016 cohort are analyzed in Piubello et al. and not included here.
      Abbreviations: DRC: Democratic Republic of Congo; XDR, extensively drug-resistant.
      Only four studies had treatment outcome data stratified for treatment length (
      • Bulabula ANH
      • Nelson JA
      • Musafiri EM
      • Machekano R
      • Sam-Agudu NA
      • Diacon AH
      • et al.
      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.
      ;
      • Hassane-Harouna S
      • Cherif GF
      • Ortuno-Gutierrez N
      • Cisse D
      • Camara LM
      • Diallo BD
      • et al.
      Better programmatic outcome with the shorter regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) in Guinea: a retrospective cohort study.
      ;
      • Kamara RF
      • Saunders MJ
      • Sahr F
      • Losa-Garcia JE
      • Foray L
      • Davies G
      • et al.
      Social and health factors associated with adverse treatment outcomes among people with multidrug-resistant tuberculosis in Sierra Leone: a national, retrospective cohort study.
      ;
      • Piubello A
      • Souleymane MB
      • Hassane-Harouna S
      • Yacouba A
      • Lempens P
      • Assao-Neino MM
      • et al.
      Management of multidrug-resistant tuberculosis with shorter treatment regimen in Niger: nationwide programmatic achievements.
      ). All of them used shorter treatment regimens, including injectables versus various longer regimens. Kamara et al. found a higher success rate of 80% versus 54% among patients treated with the shorter regimen (9-11 months) than the longer regimen (18-24 months) (see Appendix 3 for treatment regimens) (
      • Kamara RF
      • Saunders MJ
      • Sahr F
      • Losa-Garcia JE
      • Foray L
      • Davies G
      • et al.
      Social and health factors associated with adverse treatment outcomes among people with multidrug-resistant tuberculosis in Sierra Leone: a national, retrospective cohort study.
      ). Similar results were reported by
      • Hassane-Harouna S
      • Cherif GF
      • Ortuno-Gutierrez N
      • Cisse D
      • Camara LM
      • Diallo BD
      • et al.
      Better programmatic outcome with the shorter regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) in Guinea: a retrospective cohort study.
      who found a successful outcome in 74% with the shorter regimen versus 59% with the longer regimen. They also found that a more patients were LFTU if treated with the longer regimen.
      • Piubello A
      • Souleymane MB
      • Hassane-Harouna S
      • Yacouba A
      • Lempens P
      • Assao-Neino MM
      • et al.
      Management of multidrug-resistant tuberculosis with shorter treatment regimen in Niger: nationwide programmatic achievements.
      found a success rate of 83% and 70% for the short versus long regimen.
      • Bulabula ANH
      • Nelson JA
      • Musafiri EM
      • Machekano R
      • Sam-Agudu NA
      • Diacon AH
      • et al.
      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.
      observed a smaller and not significant difference between the regimens of 83% for the shorter regimen and 74% for the longer regimen. The success rate in Angola, only using the previously recommended longer treatment regimen, was considerably lower than other studies (
      • Aznar ML
      • Rando Segura A
      • Moreno MM
      • Espasa M
      • Sulleiro E
      • Bocanegra C
      • et al.
      Treatment outcomes and adverse events from a standardized multidrug-resistant tuberculosis regimen in a rural setting in Angola.
      ) (Figure 3). Patients treated with a modified shorter treatment regimen with linezolid replacing kanamycin had similar favorable outcomes (
      • Souleymane MB
      • Piubello A
      • Lawan IM
      • Hassane-Harouna S
      • Assao-Neino MM
      • Soumana A
      • et al.
      High rifampicin-resistant TB cure rates and prevention of severe ototoxicity after replacing the injectable by linezolid in early stage of hearing loss.
      ).

      Discussion

      In this study, we investigated MDR/RR-TB treatment outcomes in Central and West Africa in 14 available studies representing 4268 individuals in 14 of the 26 countries in the region. The results revealed considerable intraregional variations of MDR-TB treatment outcome and almost significant interregional variations, with a treatment success rate of 81% for Central Africa and 69% for West Africa, respectively. Surprisingly, the overall treatment success for the regions collectively was 74.6%, which was considerably higher than the global estimate of 59% provided by the WHO (
      World Health Organization
      Global tuberculosis report 2021.
      ), reaching the 2015 WHO target of at least 75% treatment success for MDR-TB (
      World Health Organization
      ).
      Interestingly, comparing to drug-susceptible TB (DS-TB), a recent review of treatment outcomes in nine African countries, including 26 studies, found a comparable success rate of 79%, ranging from 53% in Nigeria to 92% in Ethiopia (
      • Teferi MY
      • El-Khatib Z
      • Boltena MT
      • Andualem AT
      • Asamoah BO
      • Biru M
      • et al.
      Tuberculosis treatment outcome and predictors in Africa: a systematic review and meta-analysis.
      ). Only two of the studies were from Central and West Africa, with a treatment success rate of 79% and 89% (Rwanda and Benin), respectively (
      • Ade S
      • Adjibodé O
      • Wachinou P
      • Toundoh N
      • Awanou B
      • Agodokpessi G
      • et al.
      Characteristics and treatment outcomes of retreatment tuberculosis patients in Benin.
      ;
      • Kayigamba FR
      • Bakker MI
      • Mugisha V
      • De Naeyer L
      • Gasana M
      • Cobelens F
      • et al.
      Adherence to tuberculosis treatment, sputum smear conversion and mortality: a retrospective cohort study in 48 Rwandan clinics.
      ). Torres et al. also reviewed the treatment success rate for adults with DS-TB and found a rate of 80% and only a little bit lower for the African region (79%) (
      • Chaves Torres NM
      • Quijano Rodríguez JJ
      • Porras Andrade PS
      • Arriaga MB
      • Netto EM
      Factors predictive of the success of tuberculosis treatment: A systematic review with meta-analysis.
      ). Also in this study, only two studies from Cameroon and three from Nigeria, respectively, were included. Among the patients with MDR-TB, the success rate was as low as 58.4%. Much in line with the studies above, another review of DS-TB among adults in sub-Saharan Africa, including nine studies from Nigeria, reported a pooled treatment success of 76% (
      • Izudi J
      • Semakula D
      • Sennono R
      • Tamwesigire IK
      • Bajunirwe F.
      Treatment success rate among adult pulmonary tuberculosis patients in sub-Saharan Africa: a systematic review and meta-analysis.
      ).
      Compared with literature on drug-resistant TB (DR-TB), an older review of MDR-TB outcomes from 1973 to 2006, where no African studies were included, observed an overall treatment success of 62% (
      • Orenstein EW
      • Basu S
      • Shah NS
      • Andrews JR
      • Friedland GH
      • Moll AP
      • et al.
      Treatment outcomes among patients with multidrug-resistant tuberculosis: systematic review and meta-analysis.
      ). Studies combining treatment for at least 18 months and DOT had significantly higher pooled success proportions (69%) than other studies of treatment outcomes (58%). Individualized treatment regimens had higher success rates than standardized but were insignificant (64% vs 54%) (
      • Orenstein EW
      • Basu S
      • Shah NS
      • Andrews JR
      • Friedland GH
      • Moll AP
      • et al.
      Treatment outcomes among patients with multidrug-resistant tuberculosis: systematic review and meta-analysis.
      ). A review of 17 studies from Ethiopia with data from 2009 to 2019 on DR-TB found a similar success rate of 64% (
      • Alemu A
      • Bitew ZW
      • Worku T.
      Poor treatment outcome and its predictors among drug-resistant tuberculosis patients in Ethiopia: a systematic review and meta-analysis.
      ). A review of 1343 children with MDR-TB, obtained from 17 studies (no studies from Central or West Africa), reported a pooled success rate of 77% (
      • Tola HH
      • Khadoura KJ
      • Jimma W
      • Nedjat S
      • Majdzadeh R.
      Multidrug resistant tuberculosis treatment outcome in children in developing and developed countries: a systematic review and meta-analysis.
      ).
      Although not directly comparable with the findings above, our estimates of MDR/RR-TB treatment outcomes in Central and West Africa seem promising, reaching WHO's success target. A possible explanation is the early introduction of the shorter Bangladesh regimen in many of the included countries (2008 in Cameroon, Niger, and Benin and 2013 in many of the other countries) (
      • Kuaban C
      • Noeske J
      • Rieder HL
      • Aït-Khaled N
      • Abena Foe JL
      • Trébucq A
      High effectiveness of a 12-month regimen for MDR-TB patients in Cameroon.
      ;
      • Piubello A
      • Harouna SH
      • Souleymane MB
      • Boukary I
      • Morou S
      • Daouda M
      • et al.
      High cure rate with standardised short-course multidrug-resistant tuberculosis treatment in Niger: no relapses.
      ;
      • Trébucq A
      • Decroo T
      • Van Deun A
      • Piubello A
      • Chiang CY
      • Koura KG
      • et al.
      Short-course regimen for multidrug-resistant tuberculosis: a decade of evidence.
      ,
      • Trébucq A
      • Schwoebel V
      • Kashongwe Z
      • Bakayoko A
      • Kuaban C
      • Noeske J
      • et al.
      Treatment outcome with a short multidrug-resistant tuberculosis regimen in nine African countries.
      ) because shorter and standardized regimens are more easily implemented in resource-constrained settings (
      • Abidi S
      • Achar J
      • Assao Neino MM
      • Bang D
      • Benedetti A
      • Brode S
      • et al.
      Standardised shorter regimens versus individualised longer regimens for rifampin- or multidrug-resistant tuberculosis.
      ).
      DR-TB is associated with inadequate treatment and poorer outcomes (
      • Lange C
      • Aarnoutse RE
      • Alffenaar JWC
      • Bothamley G
      • Brinkmann F
      • Costa J
      • et al.
      Management of patients with multidrug-resistant tuberculosis.
      ;
      • Migliori GB
      • Tiberi S
      • Zumla A
      • Petersen E
      • Chakaya JM
      • Wejse C
      • et al.
      MDR/XDR-TB management of patients and contacts: challenges facing the new decade. The 2020 clinical update by the Global Tuberculosis Network.
      ). Patient adherence issues during prolonged treatment regimens, insufficient verification of the diagnosis, and limited resources in health care systems are all drivers of drug-resistant disease (
      • Goldman RC
      • Plumley KV
      • Laughon BE.
      The evolution of extensively drug resistant tuberculosis (XDR-TB): history, status and issues for global control.
      ). Among the studies we included, several determinants of poor outcomes were discussed.
      • Aznar ML
      • Rando Segura A
      • Moreno MM
      • Espasa M
      • Sulleiro E
      • Bocanegra C
      • et al.
      Treatment outcomes and adverse events from a standardized multidrug-resistant tuberculosis regimen in a rural setting in Angola.
      found that adverse effects were associated with poor treatment outcomes, whereas
      • Bulabula ANH
      • Nelson JA
      • Musafiri EM
      • Machekano R
      • Sam-Agudu NA
      • Diacon AH
      • et al.
      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.
      only found that severe adverse effects with treatment interruption were associated with poor outcomes. On the contrary,
      • Ciza F
      • Gils T
      • Sawadogo M
      • Decroo T
      • Roggi A
      • Piubello A
      • et al.
      Course of adverse events during short treatment regimen in patients with rifampicin-resistant tuberculosis in Burundi.
      did not find any significant association between adverse effects or HIV and poor outcomes.
      • Kuaban C
      • Noeske J
      • Rieder HL
      • Aït-Khaled N
      • Abena Foe JL
      • Trébucq A
      High effectiveness of a 12-month regimen for MDR-TB patients in Cameroon.
      observed that patients with an unsuccessful outcome tended to be somewhat older and male. However, these differences disappeared after adjustment for age, sex, and HIV status (
      • Kuaban C
      • Noeske J
      • Rieder HL
      • Aït-Khaled N
      • Abena Foe JL
      • Trébucq A
      High effectiveness of a 12-month regimen for MDR-TB patients in Cameroon.
      ), whereas another study concluded that HIV was associated with an unsuccessful outcome as well as higher age and chronic lung disease (
      • Kamara RF
      • Saunders MJ
      • Sahr F
      • Losa-Garcia JE
      • Foray L
      • Davies G
      • et al.
      Social and health factors associated with adverse treatment outcomes among people with multidrug-resistant tuberculosis in Sierra Leone: a national, retrospective cohort study.
      ). Initial fluoroquinolone resistance was reported by
      • Schwœbel V
      • Trébucq A
      • Kashongwe Z
      • Bakayoko AS
      • Kuaban C
      • Noeske J
      • et al.
      Outcomes of a nine-month regimen for rifampicin-resistant tuberculosis up to 24 months after treatment completion in nine African countries.
      and
      • Piubello A
      • Souleymane MB
      • Hassane-Harouna S
      • Yacouba A
      • Lempens P
      • Assao-Neino MM
      • et al.
      Management of multidrug-resistant tuberculosis with shorter treatment regimen in Niger: nationwide programmatic achievements.
      to be significantly associated with an increased risk of failure/relapse and of any unfavorable outcome. Very severe underweight was also associated with poor outcomes (
      • Kamara RF
      • Saunders MJ
      • Sahr F
      • Losa-Garcia JE
      • Foray L
      • Davies G
      • et al.
      Social and health factors associated with adverse treatment outcomes among people with multidrug-resistant tuberculosis in Sierra Leone: a national, retrospective cohort study.
      ;
      • Piubello A
      • Souleymane MB
      • Hassane-Harouna S
      • Yacouba A
      • Lempens P
      • Assao-Neino MM
      • et al.
      Management of multidrug-resistant tuberculosis with shorter treatment regimen in Niger: nationwide programmatic achievements.
      ). Treatment delay after sputum sampling for more than 100 days was associated with two-fold higher odds of dying (
      • Ngabonziza JS
      • Habimana YM
      • Decroo T
      • Migambi P
      • Dushime A
      • Mazarati JB
      • et al.
      Reduction of diagnostic and treatment delays reduces rifampicin-resistant tuberculosis mortality in Rwanda.
      ).
      • Bakare AM
      • Udunze OC
      • Bamidele JO
      • Omoniyi A
      • Osman E
      • Daniel OJ.
      Outcome of community-initiated treatment of drug-resistant tuberculosis patients in Lagos.
      found only treatment adherence to be predictive of treatment success, whereas
      • Bulabula ANH
      • Nelson JA
      • Musafiri EM
      • Machekano R
      • Sam-Agudu NA
      • Diacon AH
      • et al.
      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.
      correspondingly found that absence of DOT was a predictor of treatment failure/death. Among our included studies, a variety of DOT strategies were used (
      • Aznar ML
      • Rando Segura A
      • Moreno MM
      • Espasa M
      • Sulleiro E
      • Bocanegra C
      • et al.
      Treatment outcomes and adverse events from a standardized multidrug-resistant tuberculosis regimen in a rural setting in Angola.
      ;
      • Ige OM
      • Oladokun RE.
      Time to sputum culture conversion and treatment outcome among the first cohort of multidrug resistant tuberculosis patients in a high burden country.
      ;
      • Kuaban C
      • Noeske J
      • Rieder HL
      • Aït-Khaled N
      • Abena Foe JL
      • Trébucq A
      High effectiveness of a 12-month regimen for MDR-TB patients in Cameroon.
      ;
      • Piubello A
      • Souleymane MB
      • Hassane-Harouna S
      • Yacouba A
      • Lempens P
      • Assao-Neino MM
      • et al.
      Management of multidrug-resistant tuberculosis with shorter treatment regimen in Niger: nationwide programmatic achievements.
      ;
      • Schwœbel V
      • Trébucq A
      • Kashongwe Z
      • Bakayoko AS
      • Kuaban C
      • Noeske J
      • et al.
      Outcomes of a nine-month regimen for rifampicin-resistant tuberculosis up to 24 months after treatment completion in nine African countries.
      ). DOT usage varied in both length and type. Some used DOT for the entire duration of treatment, whereas others (
      • Ige OM
      • Oladokun RE.
      Time to sputum culture conversion and treatment outcome among the first cohort of multidrug resistant tuberculosis patients in a high burden country.
      ;
      • Kuaban C
      • Noeske J
      • Rieder HL
      • Aït-Khaled N
      • Abena Foe JL
      • Trébucq A
      High effectiveness of a 12-month regimen for MDR-TB patients in Cameroon.
      ;
      • Schwœbel V
      • Trébucq A
      • Kashongwe Z
      • Bakayoko AS
      • Kuaban C
      • Noeske J
      • et al.
      Outcomes of a nine-month regimen for rifampicin-resistant tuberculosis up to 24 months after treatment completion in nine African countries.
      ) only had daily DOT during the intensive phase and weekly DOT during the continuation phase (
      • Piubello A
      • Souleymane MB
      • Hassane-Harouna S
      • Yacouba A
      • Lempens P
      • Assao-Neino MM
      • et al.
      Management of multidrug-resistant tuberculosis with shorter treatment regimen in Niger: nationwide programmatic achievements.
      ). One study had DOT performed by relatives after the first 8 months of treatment but also had the highest rate of LTFU (27.9%) (
      • Aznar ML
      • Rando Segura A
      • Moreno MM
      • Espasa M
      • Sulleiro E
      • Bocanegra C
      • et al.
      Treatment outcomes and adverse events from a standardized multidrug-resistant tuberculosis regimen in a rural setting in Angola.
      ). This was attributed to patients living far away from the hospital and a high proportion of adverse effects. Adverse effects have been known to affect the proportion of patients that are LTFU (
      • Huerga H
      • Bastard M
      • Kamene M
      • Wanjala S
      • Arnold A
      • Oucho N
      • et al.
      Outcomes from the first multidrug-resistant tuberculosis programme in Kenya.
      ). The study from Guinea (
      • Hassane-Harouna S
      • Cherif GF
      • Ortuno-Gutierrez N
      • Cisse D
      • Camara LM
      • Diallo BD
      • et al.
      Better programmatic outcome with the shorter regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) in Guinea: a retrospective cohort study.
      ), where DOT was not applied, also found a higher rate of LTFU among patients on the longer treatment regime (20% vs 8.2%), in agreement with the proposition that shorter treatment regimens will have a positive effect on the treatment default rate due to fewer adverse effects and smaller burden of pills (
      • Schwœbel V
      • Trébucq A
      • Kashongwe Z
      • Bakayoko AS
      • Kuaban C
      • Noeske J
      • et al.
      Outcomes of a nine-month regimen for rifampicin-resistant tuberculosis up to 24 months after treatment completion in nine African countries.
      ;
      • Trébucq A
      • Schwoebel V
      • Kashongwe Z
      • Bakayoko A
      • Kuaban C
      • Noeske J
      • et al.
      Treatment outcome with a short multidrug-resistant tuberculosis regimen in nine African countries.
      ). The largest study (n = 845) had a low rate of LTFU of 4.5% in comparison to the other studies in light of the considerable cohort size (
      • Schwœbel V
      • Trébucq A
      • Kashongwe Z
      • Bakayoko AS
      • Kuaban C
      • Noeske J
      • et al.
      Outcomes of a nine-month regimen for rifampicin-resistant tuberculosis up to 24 months after treatment completion in nine African countries.
      ). However, the investigators provided food and money for transport for participants if possible (
      • Schwœbel V
      • Trébucq A
      • Kashongwe Z
      • Bakayoko AS
      • Kuaban C
      • Noeske J
      • et al.
      Outcomes of a nine-month regimen for rifampicin-resistant tuberculosis up to 24 months after treatment completion in nine African countries.
      ;
      • Trébucq A
      • Schwoebel V
      • Kashongwe Z
      • Bakayoko A
      • Kuaban C
      • Noeske J
      • et al.
      Treatment outcome with a short multidrug-resistant tuberculosis regimen in nine African countries.
      ). Moreover, patients were reminded about follow-up appointments by phone and those who had not attended their appointments 12 months after treatment would be actively searched for by phone and the reason for not attending would be recorded (
      • Trébucq A
      • Schwoebel V
      • Kashongwe Z
      • Bakayoko A
      • Kuaban C
      • Noeske J
      • et al.
      Treatment outcome with a short multidrug-resistant tuberculosis regimen in nine African countries.
      ). Such conditions are unlikely to be implemented in most settings. Yet, it suggests which factors are relevant to consider when trying to decrease the rate of LTFU. Overall, DOT is a well-documented and valuable strategy for optimizing treatment adherence (
      • Alipanah N
      • Jarlsberg L
      • Miller C
      • Linh NN
      • Falzon D
      • Jaramillo E
      • et al.
      Adherence interventions and outcomes of tuberculosis treatment: a systematic review and meta-analysis of trials and observational studies.
      ), but more modern approaches could be incorporated to minimize LTFU.
      Five of the 15 included studies used adapted definitions of WHO outcomes, possibly interfering with the evaluation of treatment success and treatment completion (
      • Aznar ML
      • Rando Segura A
      • Moreno MM
      • Espasa M
      • Sulleiro E
      • Bocanegra C
      • et al.
      Treatment outcomes and adverse events from a standardized multidrug-resistant tuberculosis regimen in a rural setting in Angola.
      ;
      • Ciza F
      • Gils T
      • Sawadogo M
      • Decroo T
      • Roggi A
      • Piubello A
      • et al.
      Course of adverse events during short treatment regimen in patients with rifampicin-resistant tuberculosis in Burundi.
      ;
      • Ige OM
      • Oladokun RE.
      Time to sputum culture conversion and treatment outcome among the first cohort of multidrug resistant tuberculosis patients in a high burden country.
      ;
      • Piubello A
      • Souleymane MB
      • Hassane-Harouna S
      • Yacouba A
      • Lempens P
      • Assao-Neino MM
      • et al.
      Management of multidrug-resistant tuberculosis with shorter treatment regimen in Niger: nationwide programmatic achievements.
      ;
      • Schwœbel V
      • Trébucq A
      • Kashongwe Z
      • Bakayoko AS
      • Kuaban C
      • Noeske J
      • et al.
      Outcomes of a nine-month regimen for rifampicin-resistant tuberculosis up to 24 months after treatment completion in nine African countries.
      ). The ‘cured’ and ‘failure’ definitions were adjusted in the largest study because the study used a shorter treatment regimen (
      • Schwœbel V
      • Trébucq A
      • Kashongwe Z
      • Bakayoko AS
      • Kuaban C
      • Noeske J
      • et al.
      Outcomes of a nine-month regimen for rifampicin-resistant tuberculosis up to 24 months after treatment completion in nine African countries.
      ). Piubello et al. adapted ‘failure’ to include smear results if cultures were unavailable (
      • Piubello A
      • Souleymane MB
      • Hassane-Harouna S
      • Yacouba A
      • Lempens P
      • Assao-Neino MM
      • et al.
      Management of multidrug-resistant tuberculosis with shorter treatment regimen in Niger: nationwide programmatic achievements.
      ), whereas outcomes were based exclusively on smear results in another study (
      • Aznar ML
      • Rando Segura A
      • Moreno MM
      • Espasa M
      • Sulleiro E
      • Bocanegra C
      • et al.
      Treatment outcomes and adverse events from a standardized multidrug-resistant tuberculosis regimen in a rural setting in Angola.
      ). In many African settings, culturing methods are simply not available. However, in the study by Piubello et al. and Schwœbell et al., almost all patients with a successful outcome were bacteriologically confirmed cured. Sputum smear-based treatment outcomes may lead to bias because microscopy does not differentiate between live and dead bacilli. Smear microscopy has been evaluated in resource-poor settings as a surrogate for follow-up on MDR-TB cases due to a lower cost and faster test result. Finally, Ige and Oladokun defined ‘cured’ with one less positive culture than recommended by WHO (
      • Ige OM
      • Oladokun RE.
      Time to sputum culture conversion and treatment outcome among the first cohort of multidrug resistant tuberculosis patients in a high burden country.
      ). Nonetheless, the success rate was similar when accounting for definitions.
      The study has several limitations. The absence of data from most countries in the region (46%, n = 12/26) leaves the data nonrepresentative for all countries in the region. We excluded studies solely focusing on death as the outcome because we would not have been able to compare these studies with the rest because other reasons for unfavorable treatment outcomes (and favorable outcomes) were unavailable. Also, study periods varied and spanned from 2005 to 2020. Moreover, outcome and diagnostic access bias are likely to be present. The percentage of confirmed DR-TB was not presented in most studies as well as numbers of and reasons for exclusion, potentially leading to selection bias. Countries with less resources and presumably poorer treatment outcomes may have a smaller capacity for TB surveillance, research, and publication, potentially leading to an overestimation of treatment success. The performance of each country should be evaluated individually because of the heterogeneity in demographics, the availability of drug-susceptibility testing, availability of medications, use of DOT, and general differences in health care systems. The high level of heterogeneity represents uncertainty in our estimates, but we believe it is likely due to the large and diverse populations and we think that all studies not excluded represent important parts of the background population, which is undoubtedly diverse. This population diversity, the lack of overall estimates of MDR/RR-TB treatment outcomes from Central and West Africa, the noticeable differences in HIV prevalences, and accessibility of rapid diagnostic tests across Africa are also the main reasons for investigating these regions specifically. These differences also make the overall estimate for the whole continent provided by WHO less generalizable. The wide CI of our estimate also implies that the treatment outcome success rate is likely to vary across the region but also within the countries. More data presenting the current success rate in the region is simply warranted. A strength of this study is that outcomes were obtained in routine conditions, including the multicountry study of
      • Schwœbel V
      • Trébucq A
      • Kashongwe Z
      • Bakayoko AS
      • Kuaban C
      • Noeske J
      • et al.
      Outcomes of a nine-month regimen for rifampicin-resistant tuberculosis up to 24 months after treatment completion in nine African countries.
      . We believe our study supports the available WHO data and helps clarify the situation in a region with relatively sparse data accessible.
      In conclusion, the treatment outcome in Central and West Africa observed in our study was considerably higher than the estimate reported by WHO. Whether this reflects the true rate of treatment success or whether the rate is skewed due to underreporting remains unknown. With an enormous pool of potential DR-TB worldwide (
      • Cohen A
      • Mathiasen VD
      • Schön T
      • Wejse C.
      The global prevalence of latent tuberculosis: a systematic review and meta-analysis.
      ;
      • Knight GM
      • McQuaid CF
      • Dodd PJ
      • Houben RMGJ.
      Global burden of latent multidrug-resistant tuberculosis: trends and estimates based on mathematical modelling.
      ), continued attention to prevention and management of DR-TB should be of the highest priority, especially in poorer regions with sparse resources to manage, such a clinically challenging infection. Future studies should adhere to the outcome definitions set forth by the WHO to minimize bias and ensure data comparability. With this paper, as the first available, we have presented an overview of MDR/RR-TB treatment outcomes in Central and West Africa and discussed determinants of outcome that are essential to consider when trying to improve treatment success.

      Transparency declaration

      This article is part of a supplement entitled Commemorating World Tuberculosis Day March 24th, 2022: “Invest to End TB. Save Lives” published with support from an unrestricted educational grant from QIAGEN Sciences Inc.

      Declarations of competing interest

      The authors have no competing interests to declare.

      Funding source

      This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

      Ethical statement

      This study is exempt from ethical approval.

      Author contributions

      ALT and CW conceived and designed the study. Literature search, study screening, and selection of studies were performed by ALT and VND. VS, AS, and AP provided data from included studies. VND conducted statistical analyses. ALT drafted the first manuscript, with major contributions from VND. All authors interpreted data as well as contributed with intellectual content to the final manuscript. All authors agree with the results and conclusion of this article.

      Appendix. Supplementary materials

      References

        • Abidi S
        • Achar J
        • Assao Neino MM
        • Bang D
        • Benedetti A
        • Brode S
        • et al.
        Standardised shorter regimens versus individualised longer regimens for rifampin- or multidrug-resistant tuberculosis.
        Eur Respir J. 2020; 551901467
        • Ade S
        • Adjibodé O
        • Wachinou P
        • Toundoh N
        • Awanou B
        • Agodokpessi G
        • et al.
        Characteristics and treatment outcomes of retreatment tuberculosis patients in Benin.
        Tuberc Res Treat. 2016; 20161468631
        • Akinsola OJ
        • Yusuf OB
        • Ige OM
        • Okonji PE.
        Models for predicting time to sputum conversion among multi-drug resistant tuberculosis patients in Lagos, South-West Nigeria.
        Front Public Health. 2018; 6: 347
        • Alemu A
        • Bitew ZW
        • Worku T.
        Poor treatment outcome and its predictors among drug-resistant tuberculosis patients in Ethiopia: a systematic review and meta-analysis.
        Int J Infect Dis. 2020; 98: 420-439
        • Alipanah N
        • Jarlsberg L
        • Miller C
        • Linh NN
        • Falzon D
        • Jaramillo E
        • et al.
        Adherence interventions and outcomes of tuberculosis treatment: a systematic review and meta-analysis of trials and observational studies.
        PLOS Med. 2018; 15e1002595
        • Aznar ML
        • Rando Segura A
        • Moreno MM
        • Espasa M
        • Sulleiro E
        • Bocanegra C
        • et al.
        Treatment outcomes and adverse events from a standardized multidrug-resistant tuberculosis regimen in a rural setting in Angola.
        Am J Trop Med Hyg. 2019; 101: 502-509
        • Bakare AM
        • Udunze OC
        • Bamidele JO
        • Omoniyi A
        • Osman E
        • Daniel OJ.
        Outcome of community-initiated treatment of drug-resistant tuberculosis patients in Lagos.
        Nigeria. Trans R Soc Trop Med Hyg. 2021; 115: 1061-1065
        • Bulabula ANH
        • Nelson JA
        • Musafiri EM
        • Machekano R
        • Sam-Agudu NA
        • Diacon AH
        • et al.
        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; 69: 1278-1287
        • Chaves Torres NM
        • Quijano Rodríguez JJ
        • Porras Andrade PS
        • Arriaga MB
        • Netto EM
        Factors predictive of the success of tuberculosis treatment: A systematic review with meta-analysis.
        PLoS One. 2019; 14e0226507
        • Ciza F
        • Gils T
        • Sawadogo M
        • Decroo T
        • Roggi A
        • Piubello A
        • et al.
        Course of adverse events during short treatment regimen in patients with rifampicin-resistant tuberculosis in Burundi.
        J Clin Med. 2020; 9: 1873
        • Cohen A
        • Mathiasen VD
        • Schön T
        • Wejse C.
        The global prevalence of latent tuberculosis: a systematic review and meta-analysis.
        Eur Respir J. 2019; 54
        • Dean AS
        • Tosas Auguet O
        • Glaziou P
        • Zignol M
        • Ismail N
        • Kasaeva T
        • et al.
        25 years of surveillance of drug-resistant tuberculosis: achievements, challenges, and way forward.
        Lancet Infect Dis. 2022; 22: e191-e196
      1. ECCAS. Economic Community of Central African States member states. https://ceeac-eccas.org/pays-membres/Date, 2022 (accessed 9 May 2022).

      2. ECOWAS. Economic Community of West African States member states. https://ecowas.int/member-states/Date, 2022 (accessed 9 May 2022).

        • Efsen AMW
        • Schultze A
        • Miller RF
        • Panteleev A
        • Skrahin A
        • Podlekareva DN
        • et al.
        Management of MDR-TB in HIV co-infected patients in Eastern Europe: results from the TB:HIV study.
        J Infect. 2018; 76: 44-54
        • Eurosurveillance editorial team
        WHO Revised definitions and reporting framework for tuberculosis.
        Euro Surveill. 2013; 18: 20455
        • Goldman RC
        • Plumley KV
        • Laughon BE.
        The evolution of extensively drug resistant tuberculosis (XDR-TB): history, status and issues for global control.
        Infect Disord Drug Targets. 2007; 7: 73-91
        • Hassane-Harouna S
        • Cherif GF
        • Ortuno-Gutierrez N
        • Cisse D
        • Camara LM
        • Diallo BD
        • et al.
        Better programmatic outcome with the shorter regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) in Guinea: a retrospective cohort study.
        PLoS One. 2020; 15e0237355
        • Huerga H
        • Bastard M
        • Kamene M
        • Wanjala S
        • Arnold A
        • Oucho N
        • et al.
        Outcomes from the first multidrug-resistant tuberculosis programme in Kenya.
        Int J Tuberc Lung Dis. 2017; 21: 314-319
        • Ige OM
        • Oladokun RE.
        Time to sputum culture conversion and treatment outcome among the first cohort of multidrug resistant tuberculosis patients in a high burden country.
        Indian J Tuberc. 2018; 65: 322-328
        • Izudi J
        • Semakula D
        • Sennono R
        • Tamwesigire IK
        • Bajunirwe F.
        Treatment success rate among adult pulmonary tuberculosis patients in sub-Saharan Africa: a systematic review and meta-analysis.
        BMJ, (Open). 2019; 9e029400
        • Kamara RF
        • Saunders MJ
        • Sahr F
        • Losa-Garcia JE
        • Foray L
        • Davies G
        • et al.
        Social and health factors associated with adverse treatment outcomes among people with multidrug-resistant tuberculosis in Sierra Leone: a national, retrospective cohort study.
        Lancet Glob Health. 2022; 10: e543-e554
        • Kayigamba FR
        • Bakker MI
        • Mugisha V
        • De Naeyer L
        • Gasana M
        • Cobelens F
        • et al.
        Adherence to tuberculosis treatment, sputum smear conversion and mortality: a retrospective cohort study in 48 Rwandan clinics.
        PLoS One. 2013; 8: e73501
        • Knight GM
        • McQuaid CF
        • Dodd PJ
        • Houben RMGJ.
        Global burden of latent multidrug-resistant tuberculosis: trends and estimates based on mathematical modelling.
        Lancet Infect Dis. 2019; 19: 903-912
        • Kuaban C
        • Noeske J
        • Rieder HL
        • Aït-Khaled N
        • Abena Foe JL
        • Trébucq A
        High effectiveness of a 12-month regimen for MDR-TB patients in Cameroon.
        Int J Tuberc Lung Dis. 2015; 19: 517-524
        • Lange C
        • Aarnoutse RE
        • Alffenaar JWC
        • Bothamley G
        • Brinkmann F
        • Costa J
        • et al.
        Management of patients with multidrug-resistant tuberculosis.
        Int J Tuberc Lung Dis. 2019; 23: 645-662
        • Lange C
        • Barry Iii CE
        • Horsburgh Jr, CR
        Treatments of multidrug-resistant tuberculosis: light at the end of the tunnel.
        Am J Respir Crit Care Med. 2022; 205: 1142-1144
        • Migliori GB
        • Tiberi S
        • Zumla A
        • Petersen E
        • Chakaya JM
        • Wejse C
        • 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; 92S: S15-S25
        • Ngabonziza JS
        • Habimana YM
        • Decroo T
        • Migambi P
        • Dushime A
        • Mazarati JB
        • et al.
        Reduction of diagnostic and treatment delays reduces rifampicin-resistant tuberculosis mortality in Rwanda.
        Int J Tuberc Lung Dis. 2020; 24: 329-339
        • Orenstein EW
        • Basu S
        • Shah NS
        • Andrews JR
        • Friedland GH
        • Moll AP
        • et al.
        Treatment outcomes among patients with multidrug-resistant tuberculosis: systematic review and meta-analysis.
        Lancet Infect Dis. 2009; 9: 153-161
        • Page MJ
        • McKenzie JE
        • Bossuyt PM
        • Boutron I
        • Hoffmann TC
        • Mulrow CD
        • et al.
        The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.
        BMJ. 2021; 372: n71
        • Pandey P
        • Pant ND
        • Rijal KR
        • Shrestha B
        • Kattel S
        • Banjara MR
        • et al.
        Diagnostic accuracy of GeneXpert MTB/RIF Assay in comparison to conventional drug susceptibility testing method for the diagnosis of multidrug-resistant tuberculosis.
        PLoS One. 2017; 12e0169798
        • Piubello A
        • Harouna SH
        • Souleymane MB
        • Boukary I
        • Morou S
        • Daouda M
        • et al.
        High cure rate with standardised short-course multidrug-resistant tuberculosis treatment in Niger: no relapses.
        Int J Tuberc Lung Dis. 2014; 18: 1188-1194
        • Piubello A
        • Souleymane MB
        • Hassane-Harouna S
        • Yacouba A
        • Lempens P
        • Assao-Neino MM
        • et al.
        Management of multidrug-resistant tuberculosis with shorter treatment regimen in Niger: nationwide programmatic achievements.
        Respir Med. 2020; 161105844
        • Schwœbel V
        • Trébucq A
        • Kashongwe Z
        • Bakayoko AS
        • Kuaban C
        • Noeske J
        • et al.
        Outcomes of a nine-month regimen for rifampicin-resistant tuberculosis up to 24 months after treatment completion in nine African countries.
        EClinicalmedicine. 2020; 20100268
        • Souleymane MB
        • Piubello A
        • Lawan IM
        • Hassane-Harouna S
        • Assao-Neino MM
        • Soumana A
        • et al.
        High rifampicin-resistant TB cure rates and prevention of severe ototoxicity after replacing the injectable by linezolid in early stage of hearing loss.
        Eur Respir J. 2021; 57
        • Sterne JA
        • Sutton AJ
        • Ioannidis JP
        • Terrin N
        • Jones DR
        • Lau J
        • et al.
        Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials.
        BMJ. 2011; 343: d4002
        • Teferi MY
        • El-Khatib Z
        • Boltena MT
        • Andualem AT
        • Asamoah BO
        • Biru M
        • et al.
        Tuberculosis treatment outcome and predictors in Africa: a systematic review and meta-analysis.
        Int J Environ Res Public Health. 2021; 18
        • Tola HH
        • Khadoura KJ
        • Jimma W
        • Nedjat S
        • Majdzadeh R.
        Multidrug resistant tuberculosis treatment outcome in children in developing and developed countries: a systematic review and meta-analysis.
        Int J Infect Dis. 2020; 96: 12-18
        • Trébucq A
        • Decroo T
        • Van Deun A
        • Piubello A
        • Chiang CY
        • Koura KG
        • et al.
        Short-course regimen for multidrug-resistant tuberculosis: a decade of evidence.
        J Clin Med. 2019; 9
        • Trébucq A
        • Schwoebel V
        • Kashongwe Z
        • Bakayoko A
        • Kuaban C
        • Noeske J
        • et al.
        Treatment outcome with a short multidrug-resistant tuberculosis regimen in nine African countries.
        Int J Tuberc Lung Dis. 2018; 22: 17-25
        • World Health Organization
        The WHO end TB strategy. 2010;
        • World Health Organization
        Automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance: Xpert MTB/RIF system [policy statement].
        World Health Organization, Geneva2011
        • World Health Organization
        WHO treatment guidelines for drug-resistant tuberculosis, 2016 update.
        World Health Organization, Geneva2016
        • World Health Organization
        Global tuberculosis report 2020.
        World Health Organization, Geneva2020
        • World Health Organization
        Meeting report of the WHO expert consultation on the definition of extensively drug-resistant tuberculosis.
        World Health Organization, Geneva2020
        • World Health Organization
        Global tuberculosis report 2021.
        World Health Organization, Geneva2021
        • World Health Organization
        Rapid communication: key changes to the treatment of drug-resistant tuberculosis.
        World Health Organization, Geneva2022