Prevalence and drivers of false-positive rifampicin-resistant Xpert MTB/RIF results: a prospective observational study in Rwanda
Summary: Background: The Xpert MTB/RIF (Xpert) assay is used globally to rapidly diagnose tuberculosis and resistance to rifampicin. We investigated the frequency and predictors of false-positive findings of rifampicin resistance with Xpert. Methods: We did a prospective, observational study of ind...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-06-01
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| Series: | The Lancet Microbe |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666524720300070 |
| _version_ | 1819046262741139456 |
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| author | Jean Claude Semuto Ngabonziza, MSc Tom Decroo, PhD Patrick Migambi, MSc Yves Mucyo Habimana, MD Armand Van Deun, PhD Conor J Meehan, PhD Gabriela Torrea, PhD Faridath Massou, PharmD Willem Bram de Rijk, BS Bertin Ushizimpumu, BS Esdras Belamo Niyigena, BS Emil Ivan, PhD Jules Mugabo Semahore, MD Jean Baptiste Mazarati, PhD Corinne Simone Merle, PhD Philip Supply, PhD Dissou Affolabi, ProfPhD Leen Rigouts, PhD Bouke Catherine de Jong, ProfPhD |
| author_facet | Jean Claude Semuto Ngabonziza, MSc Tom Decroo, PhD Patrick Migambi, MSc Yves Mucyo Habimana, MD Armand Van Deun, PhD Conor J Meehan, PhD Gabriela Torrea, PhD Faridath Massou, PharmD Willem Bram de Rijk, BS Bertin Ushizimpumu, BS Esdras Belamo Niyigena, BS Emil Ivan, PhD Jules Mugabo Semahore, MD Jean Baptiste Mazarati, PhD Corinne Simone Merle, PhD Philip Supply, PhD Dissou Affolabi, ProfPhD Leen Rigouts, PhD Bouke Catherine de Jong, ProfPhD |
| author_sort | Jean Claude Semuto Ngabonziza, MSc |
| collection | DOAJ |
| description | Summary: Background: The Xpert MTB/RIF (Xpert) assay is used globally to rapidly diagnose tuberculosis and resistance to rifampicin. We investigated the frequency and predictors of false-positive findings of rifampicin resistance with Xpert. Methods: We did a prospective, observational study of individuals who were enrolled in a Rwandan nationwide diagnostic cohort study (DIAMA trial; NCT03303963). We included patients identified to have rifampicin resistance on initial Xpert testing. We did a repeat Xpert assay and used rpoB Sanger and deep sequencing alongside phenotypic drug susceptibility testing (pDST) to ascertain final rifampicin susceptibility status, with any (hetero)resistant result overriding. We used multivariable logistic regression to assess predictors of false rifampicin resistance on initial Xpert testing, adjusted for HIV status, tuberculosis treatment history, initial Xpert semi-quantitative bacillary load, and initial Xpert probe. Findings: Between May 4, 2017, and April 30, 2019, 175 people were identified with rifampicin resistance at initial Xpert testing, of whom 154 (88%) underwent repeat Xpert assay. 54 (35%) patients were confirmed as rifampicin resistant on repeat testing and 100 (65%) were not confirmed with resistance. After further testing and sequencing, 121 (79%) of 154 patients had a final confirmed status for rifampicin susceptibility. 57 (47%) of 121 patients were confirmed to have a false rifampicin resistance result and 64 (53%) had true rifampicin resistance. A high pretest probability of rifampicin resistance did not decrease the odds of false rifampicin resistance (adjusted odds ratio [aOR] 6·0, 95% CI 1·0–35·0, for new tuberculosis patients vs patients who needed retreatment). Ten (16%) of the 64 patients with true rifampicin resistance did not have confirmed rifampicin resistance on repeat Xpert testing, of whom four had heteroresistance. Of 63 patients with a very low bacillary load on Xpert testing, 54 (86%) were falsely diagnosed with rifampicin-resistant tuberculosis. Having a very low bacillary load on Xpert testing was strongly associated with false rifampicin resistance at the initial Xpert assay (aOR 63·6, 95% CI 9·9–410·4). Interpretation: The Xpert testing algorithm should include an assessment of bacillary load and retesting in case rifampicin resistance is detected on a paucibacillary sputum sample. Only when rifampicin resistance has been confirmed on repeat testing should multidrug-resistant tuberculosis treatment be started. When rifampicin resistance has not been confirmed on repeat testing, we propose that patients should be given first-line anti-tuberculosis drugs and monitored closely during treatment, including by baseline culture, pDST, and further Xpert testing. Funding: The European & Developing Countries Clinical Trials Partnership 2 programme, and Belgian Directorate General for Development Cooperation. |
| first_indexed | 2024-12-21T10:41:41Z |
| format | Article |
| id | doaj.art-77bfaae837f3401fad6757b6a7eea198 |
| institution | Directory Open Access Journal |
| issn | 2666-5247 |
| language | English |
| last_indexed | 2024-12-21T10:41:41Z |
| publishDate | 2020-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | The Lancet Microbe |
| spelling | doaj.art-77bfaae837f3401fad6757b6a7eea1982022-12-21T19:06:55ZengElsevierThe Lancet Microbe2666-52472020-06-0112e74e83Prevalence and drivers of false-positive rifampicin-resistant Xpert MTB/RIF results: a prospective observational study in RwandaJean Claude Semuto Ngabonziza, MSc0Tom Decroo, PhD1Patrick Migambi, MSc2Yves Mucyo Habimana, MD3Armand Van Deun, PhD4Conor J Meehan, PhD5Gabriela Torrea, PhD6Faridath Massou, PharmD7Willem Bram de Rijk, BS8Bertin Ushizimpumu, BS9Esdras Belamo Niyigena, BS10Emil Ivan, PhD11Jules Mugabo Semahore, MD12Jean Baptiste Mazarati, PhD13Corinne Simone Merle, PhD14Philip Supply, PhD15Dissou Affolabi, ProfPhD16Leen Rigouts, PhD17Bouke Catherine de Jong, ProfPhD18National Reference Laboratory Division, Department of Biomedical Services, Rwanda Biomedical Centre, Kigali, Rwanda; Mycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Correspondence to: Mr Jean Claude Semuto Ngabonziza, Rwanda Biomedical Centre, PO Box 7162, Kigali, RwandaDepartment of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Research Foundation Flanders, Brussels, BelgiumTuberculosis and Other Respiratory Diseases Division, Institute of HIV/AIDS Disease Prevention and Control, Rwanda Biomedical Centre, Kigali, RwandaTuberculosis and Other Respiratory Diseases Division, Institute of HIV/AIDS Disease Prevention and Control, Rwanda Biomedical Centre, Kigali, RwandaDamian Foundation, Brussels, BelgiumMycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; School of Chemistry and Biosciences, University of Bradford, UKMycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, BelgiumLaboratoire de Référence des Mycobactéries, Cotonou, BeninMycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, BelgiumNational Reference Laboratory Division, Department of Biomedical Services, Rwanda Biomedical Centre, Kigali, RwandaNational Reference Laboratory Division, Department of Biomedical Services, Rwanda Biomedical Centre, Kigali, RwandaNational Reference Laboratory Division, Department of Biomedical Services, Rwanda Biomedical Centre, Kigali, RwandaHIV, STIs, Hepatitis and Tuberculosis Programmes, WHO Country Office, Kigali, RwandaDepartment of Biomedical Services, Rwanda Biomedical Centre, Kigali, RwandaUNICEF/UNDP/World Bank/WHO Special Programme on Research and Training in Tropical Diseases, Geneva, Switzerland; London School of Hygiene & Tropical Medicine, London, UKUniversity of Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, FranceLaboratoire de Référence des Mycobactéries, Cotonou, BeninMycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, BelgiumMycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, BelgiumSummary: Background: The Xpert MTB/RIF (Xpert) assay is used globally to rapidly diagnose tuberculosis and resistance to rifampicin. We investigated the frequency and predictors of false-positive findings of rifampicin resistance with Xpert. Methods: We did a prospective, observational study of individuals who were enrolled in a Rwandan nationwide diagnostic cohort study (DIAMA trial; NCT03303963). We included patients identified to have rifampicin resistance on initial Xpert testing. We did a repeat Xpert assay and used rpoB Sanger and deep sequencing alongside phenotypic drug susceptibility testing (pDST) to ascertain final rifampicin susceptibility status, with any (hetero)resistant result overriding. We used multivariable logistic regression to assess predictors of false rifampicin resistance on initial Xpert testing, adjusted for HIV status, tuberculosis treatment history, initial Xpert semi-quantitative bacillary load, and initial Xpert probe. Findings: Between May 4, 2017, and April 30, 2019, 175 people were identified with rifampicin resistance at initial Xpert testing, of whom 154 (88%) underwent repeat Xpert assay. 54 (35%) patients were confirmed as rifampicin resistant on repeat testing and 100 (65%) were not confirmed with resistance. After further testing and sequencing, 121 (79%) of 154 patients had a final confirmed status for rifampicin susceptibility. 57 (47%) of 121 patients were confirmed to have a false rifampicin resistance result and 64 (53%) had true rifampicin resistance. A high pretest probability of rifampicin resistance did not decrease the odds of false rifampicin resistance (adjusted odds ratio [aOR] 6·0, 95% CI 1·0–35·0, for new tuberculosis patients vs patients who needed retreatment). Ten (16%) of the 64 patients with true rifampicin resistance did not have confirmed rifampicin resistance on repeat Xpert testing, of whom four had heteroresistance. Of 63 patients with a very low bacillary load on Xpert testing, 54 (86%) were falsely diagnosed with rifampicin-resistant tuberculosis. Having a very low bacillary load on Xpert testing was strongly associated with false rifampicin resistance at the initial Xpert assay (aOR 63·6, 95% CI 9·9–410·4). Interpretation: The Xpert testing algorithm should include an assessment of bacillary load and retesting in case rifampicin resistance is detected on a paucibacillary sputum sample. Only when rifampicin resistance has been confirmed on repeat testing should multidrug-resistant tuberculosis treatment be started. When rifampicin resistance has not been confirmed on repeat testing, we propose that patients should be given first-line anti-tuberculosis drugs and monitored closely during treatment, including by baseline culture, pDST, and further Xpert testing. Funding: The European & Developing Countries Clinical Trials Partnership 2 programme, and Belgian Directorate General for Development Cooperation.http://www.sciencedirect.com/science/article/pii/S2666524720300070 |
| spellingShingle | Jean Claude Semuto Ngabonziza, MSc Tom Decroo, PhD Patrick Migambi, MSc Yves Mucyo Habimana, MD Armand Van Deun, PhD Conor J Meehan, PhD Gabriela Torrea, PhD Faridath Massou, PharmD Willem Bram de Rijk, BS Bertin Ushizimpumu, BS Esdras Belamo Niyigena, BS Emil Ivan, PhD Jules Mugabo Semahore, MD Jean Baptiste Mazarati, PhD Corinne Simone Merle, PhD Philip Supply, PhD Dissou Affolabi, ProfPhD Leen Rigouts, PhD Bouke Catherine de Jong, ProfPhD Prevalence and drivers of false-positive rifampicin-resistant Xpert MTB/RIF results: a prospective observational study in Rwanda The Lancet Microbe |
| title | Prevalence and drivers of false-positive rifampicin-resistant Xpert MTB/RIF results: a prospective observational study in Rwanda |
| title_full | Prevalence and drivers of false-positive rifampicin-resistant Xpert MTB/RIF results: a prospective observational study in Rwanda |
| title_fullStr | Prevalence and drivers of false-positive rifampicin-resistant Xpert MTB/RIF results: a prospective observational study in Rwanda |
| title_full_unstemmed | Prevalence and drivers of false-positive rifampicin-resistant Xpert MTB/RIF results: a prospective observational study in Rwanda |
| title_short | Prevalence and drivers of false-positive rifampicin-resistant Xpert MTB/RIF results: a prospective observational study in Rwanda |
| title_sort | prevalence and drivers of false positive rifampicin resistant xpert mtb rif results a prospective observational study in rwanda |
| url | http://www.sciencedirect.com/science/article/pii/S2666524720300070 |
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