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, Catharina C; Nicol, Mark P; Nabeta, Pamela; Michael, Joy S; Gotuzzo, Eduardo; Tahirli, Rasim; Gler, Ma Tarcela; Blakemore, Robert; Worodria, William; Gray, Christen; Huang, Laurence; Caceres, Tatiana; Mehdiyev, Rafail; Raymond, Lawrence; Whitelaw, Andrew; Sagadevan, Kalaiselvan; Alexander, Heather; Albert, Heidi; Cobelens, Frank; Cox, Helen; Alland, David; Perkins, Mark 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, Catharina Cen
dc.contributor.authorNicol, Mark Pen
dc.contributor.authorNabeta, Pamelaen
dc.contributor.authorMichael, Joy Sen
dc.contributor.authorGotuzzo, Eduardoen
dc.contributor.authorTahirli, Rasimen
dc.contributor.authorGler, Ma Tarcelaen
dc.contributor.authorBlakemore, Roberten
dc.contributor.authorWorodria, Williamen
dc.contributor.authorGray, Christenen
dc.contributor.authorHuang, Laurenceen
dc.contributor.authorCaceres, Tatianaen
dc.contributor.authorMehdiyev, Rafailen
dc.contributor.authorRaymond, Lawrenceen
dc.contributor.authorWhitelaw, Andrewen
dc.contributor.authorSagadevan, Kalaiselvanen
dc.contributor.authorAlexander, Heatheren
dc.contributor.authorAlbert, Heidien
dc.contributor.authorCobelens, Franken
dc.contributor.authorCox, Helenen
dc.contributor.authorAlland, Daviden
dc.contributor.authorPerkins, Mark 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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