Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study

Hdl Handle:
http://hdl.handle.net/10144/129970
Title:
Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study
Authors:
Boehme, C C; Nicol, M P; Nabeta, P; Michael, J S; Gotuzzo, E; Tahirli, R; Gler, M T; Blakemore, R; Worodria, W; Gray, C; Huang, L; Caceres, T; Mehdiyev, R; Raymond, L; Whitelaw, A; Sagadevan, K; Alexander, H; Albert, H; Cobelens, F; Cox, H; Alland, D; Perkins, M D
Journal:
Lancet
Abstract:
BACKGROUND: The Xpert MTB/RIF test (Cepheid, Sunnyvale, CA, USA) can detect tuberculosis and its multidrug-resistant form with very high sensitivity and specificity in controlled studies, but no performance data exist from district and subdistrict health facilities in tuberculosis-endemic countries. We aimed to assess operational feasibility, accuracy, and effectiveness of implementation in such settings. METHODS: We assessed adults (≥18 years) with suspected tuberculosis or multidrug-resistant tuberculosis consecutively presenting with cough lasting at least 2 weeks to urban health centres in South Africa, Peru, and India, drug-resistance screening facilities in Azerbaijan and the Philippines, and an emergency room in Uganda. Patients were excluded from the main analyses if their second sputum sample was collected more than 1 week after the first sample, or if no valid reference standard or MTB/RIF test was available. We compared one-off direct MTB/RIF testing in nine microscopy laboratories adjacent to study sites with 2-3 sputum smears and 1-3 cultures, dependent on site, and drug-susceptibility testing. We assessed indicators of robustness including indeterminate rate and between-site performance, and compared time to detection, reporting, and treatment, and patient dropouts for the techniques used. FINDINGS: We enrolled 6648 participants between Aug 11, 2009, and June 26, 2010. One-off MTB/RIF testing detected 933 (90·3%) of 1033 culture-confirmed cases of tuberculosis, compared with 699 (67·1%) of 1041 for microscopy. MTB/RIF test sensitivity was 76·9% in smear-negative, culture-positive patients (296 of 385 samples), and 99·0% specific (2846 of 2876 non-tuberculosis samples). MTB/RIF test sensitivity for rifampicin resistance was 94·4% (236 of 250) and specificity was 98·3% (796 of 810). Unlike microscopy, MTB/RIF test sensitivity was not significantly lower in patients with HIV co-infection. Median time to detection of tuberculosis for the MTB/RIF test was 0 days (IQR 0-1), compared with 1 day (0-1) for microscopy, 30 days (23-43) for solid culture, and 16 days (13-21) for liquid culture. Median time to detection of resistance was 20 days (10-26) for line-probe assay and 106 days (30-124) for conventional drug-susceptibility testing. Use of the MTB/RIF test reduced median time to treatment for smear-negative tuberculosis from 56 days (39-81) to 5 days (2-8). The indeterminate rate of MTB/RIF testing was 2·4% (126 of 5321 samples) compared with 4·6% (441 of 9690) for cultures. INTERPRETATION: The MTB/RIF test can effectively be used in low-resource settings to simplify patients' access to early and accurate diagnosis, thereby potentially decreasing morbidity associated with diagnostic delay, dropout and mistreatment. FUNDING: Foundation for Innovative New Diagnostics, Bill & Melinda Gates Foundation, European and Developing Countries Clinical Trials Partnership (TA2007.40200.009), Wellcome Trust (085251/B/08/Z), and UK Department for International Development.
Affiliation:
Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland; National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa; Division of Medical Microbiology and Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Christian Medical College, Vellore, India; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru; Special Treatment Institution, Baku, Azerbaijan; Tropical Disease Foundation, Manila, Philippines; New Jersey Medical School and Division of Infectious Diseases, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA; Department of Medicine, Faculty of Medicine, Makerere University, Kampala, Uganda; Uganda Ministry of Health, Kampala, Uganda; Division of Pulmonary and Critical Care Medicine, and HIV/AIDS Division, San Francisco General Hospital, University of California, San Francisco, CA, USA; Azerbaijan Ministry of Justice, Baku, Azerbaijan; Lung Center of the Philippines, Manila, Philippines; Centers for Disease Control and Prevention, Division of Tuberculosis Elimination, Atlanta, GA, USA; Foundation for Innovative New Diagnostics (FIND), Kampala, Uganda; Department of Global Health and Amsterdam Institute of Global Health and Development, Academic Medical Center, Amsterdam, Netherlands; Medecins Sans Frontieres, Cape Town, South Africa
Issue Date:
18-Apr-2011
URI:
http://hdl.handle.net/10144/129970
DOI:
10.1016/S0140-6736(11)60438-8
PubMed ID:
21507477
Additional Links:
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60438-8/abstract
Submitted date:
2011-04-29
Type:
Article
Language:
en
ISSN:
1474-547X
Appears in Collections:
TB

Full metadata record

DC FieldValue Language
dc.contributor.authorBoehme, C Cen
dc.contributor.authorNicol, M Pen
dc.contributor.authorNabeta, Pen
dc.contributor.authorMichael, J Sen
dc.contributor.authorGotuzzo, Een
dc.contributor.authorTahirli, Ren
dc.contributor.authorGler, M Ten
dc.contributor.authorBlakemore, Ren
dc.contributor.authorWorodria, Wen
dc.contributor.authorGray, Cen
dc.contributor.authorHuang, Len
dc.contributor.authorCaceres, Ten
dc.contributor.authorMehdiyev, Ren
dc.contributor.authorRaymond, Len
dc.contributor.authorWhitelaw, Aen
dc.contributor.authorSagadevan, Ken
dc.contributor.authorAlexander, Hen
dc.contributor.authorAlbert, Hen
dc.contributor.authorCobelens, Fen
dc.contributor.authorCox, Hen
dc.contributor.authorAlland, Den
dc.contributor.authorPerkins, M Den
dc.date.accessioned2011-05-23T19:32:36Z-
dc.date.available2011-05-23T19:32:36Z-
dc.date.issued2011-04-18-
dc.date.submitted2011-04-29-
dc.identifier.citationLancet 2011;377(9776):1495-505en
dc.identifier.issn1474-547X-
dc.identifier.pmid21507477-
dc.identifier.doi10.1016/S0140-6736(11)60438-8-
dc.identifier.urihttp://hdl.handle.net/10144/129970-
dc.description.abstractBACKGROUND: The Xpert MTB/RIF test (Cepheid, Sunnyvale, CA, USA) can detect tuberculosis and its multidrug-resistant form with very high sensitivity and specificity in controlled studies, but no performance data exist from district and subdistrict health facilities in tuberculosis-endemic countries. We aimed to assess operational feasibility, accuracy, and effectiveness of implementation in such settings. METHODS: We assessed adults (≥18 years) with suspected tuberculosis or multidrug-resistant tuberculosis consecutively presenting with cough lasting at least 2 weeks to urban health centres in South Africa, Peru, and India, drug-resistance screening facilities in Azerbaijan and the Philippines, and an emergency room in Uganda. Patients were excluded from the main analyses if their second sputum sample was collected more than 1 week after the first sample, or if no valid reference standard or MTB/RIF test was available. We compared one-off direct MTB/RIF testing in nine microscopy laboratories adjacent to study sites with 2-3 sputum smears and 1-3 cultures, dependent on site, and drug-susceptibility testing. We assessed indicators of robustness including indeterminate rate and between-site performance, and compared time to detection, reporting, and treatment, and patient dropouts for the techniques used. FINDINGS: We enrolled 6648 participants between Aug 11, 2009, and June 26, 2010. One-off MTB/RIF testing detected 933 (90·3%) of 1033 culture-confirmed cases of tuberculosis, compared with 699 (67·1%) of 1041 for microscopy. MTB/RIF test sensitivity was 76·9% in smear-negative, culture-positive patients (296 of 385 samples), and 99·0% specific (2846 of 2876 non-tuberculosis samples). MTB/RIF test sensitivity for rifampicin resistance was 94·4% (236 of 250) and specificity was 98·3% (796 of 810). Unlike microscopy, MTB/RIF test sensitivity was not significantly lower in patients with HIV co-infection. Median time to detection of tuberculosis for the MTB/RIF test was 0 days (IQR 0-1), compared with 1 day (0-1) for microscopy, 30 days (23-43) for solid culture, and 16 days (13-21) for liquid culture. Median time to detection of resistance was 20 days (10-26) for line-probe assay and 106 days (30-124) for conventional drug-susceptibility testing. Use of the MTB/RIF test reduced median time to treatment for smear-negative tuberculosis from 56 days (39-81) to 5 days (2-8). The indeterminate rate of MTB/RIF testing was 2·4% (126 of 5321 samples) compared with 4·6% (441 of 9690) for cultures. INTERPRETATION: The MTB/RIF test can effectively be used in low-resource settings to simplify patients' access to early and accurate diagnosis, thereby potentially decreasing morbidity associated with diagnostic delay, dropout and mistreatment. FUNDING: Foundation for Innovative New Diagnostics, Bill & Melinda Gates Foundation, European and Developing Countries Clinical Trials Partnership (TA2007.40200.009), Wellcome Trust (085251/B/08/Z), and UK Department for International Development.en
dc.languageENG-
dc.language.isoenen
dc.relation.urlhttp://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60438-8/abstracten
dc.rightsReproduced on this site with permission of Elsevier Ltd. Please see [url]http://www.thelancet.com/[/url] for further relevant comment.en
dc.subject.meshTuberculosisen
dc.subject.meshDrug Resistanceen
dc.subject.meshHIVen
dc.subject.meshDeveloping Countriesen
dc.subject.meshResource-poor settingsen
dc.subject.meshSouth Africaen
dc.subject.meshRifampinen
dc.subject.meshMicroscopyen
dc.subject.meshDiagnosisen
dc.subject.meshDiagnosticsen
dc.subject.meshDiagnostic Testsen
dc.titleFeasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation studyen
dc.typeArticleen
dc.contributor.departmentFoundation for Innovative New Diagnostics (FIND), Geneva, Switzerland; National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa; Division of Medical Microbiology and Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Christian Medical College, Vellore, India; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru; Special Treatment Institution, Baku, Azerbaijan; Tropical Disease Foundation, Manila, Philippines; New Jersey Medical School and Division of Infectious Diseases, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA; Department of Medicine, Faculty of Medicine, Makerere University, Kampala, Uganda; Uganda Ministry of Health, Kampala, Uganda; Division of Pulmonary and Critical Care Medicine, and HIV/AIDS Division, San Francisco General Hospital, University of California, San Francisco, CA, USA; Azerbaijan Ministry of Justice, Baku, Azerbaijan; Lung Center of the Philippines, Manila, Philippines; Centers for Disease Control and Prevention, Division of Tuberculosis Elimination, Atlanta, GA, USA; Foundation for Innovative New Diagnostics (FIND), Kampala, Uganda; Department of Global Health and Amsterdam Institute of Global Health and Development, Academic Medical Center, Amsterdam, Netherlands; Medecins Sans Frontieres, Cape Town, South Africaen
dc.identifier.journalLanceten

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