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dc.contributor.authorMurphy, Michael E.
dc.contributor.authorPhillips, Patrick P. J.
dc.contributor.authorMendel, Carl M.
dc.contributor.authorBongard, Emily
dc.contributor.authorBateson, Anna L. C.
dc.contributor.authorHunt, Robert
dc.contributor.authorMurthy, Saraswathi
dc.contributor.authorSingh, Kasha P.
dc.contributor.authorBrown, Michael
dc.contributor.authorCrook, Angela M.
dc.contributor.authorNunn, Andrew J.
dc.contributor.authorMeredith, Sarah K.
dc.contributor.authorLipman, Marc
dc.contributor.authorMcHugh, Timothy D.
dc.contributor.authorGillespie, Stephen H.
dc.contributor.authorREMoxTB Consortium
dc.identifier.citationMurphy , M E , Phillips , P P J , Mendel , C M , Bongard , E , Bateson , A L C , Hunt , R , Murthy , S , Singh , K P , Brown , M , Crook , A M , Nunn , A J , Meredith , S K , Lipman , M , McHugh , T D , Gillespie , S H & REMoxTB Consortium 2017 , ' Spot sputum samples are at least as good as early morning samples for identifying Mycobacterium tuberculosis ' , BMC Medicine , vol. 15 , 192 .
dc.identifier.otherPURE: 251439321
dc.identifier.otherPURE UUID: b8846996-5ed2-4fd4-9e2a-d014c6f96cbc
dc.identifier.otherRIS: urn:BDBDED2359E2AD26B857D2A3A5929B2C
dc.identifier.otherRIS: Murphy2017
dc.identifier.otherScopus: 85032331829
dc.identifier.otherORCID: /0000-0001-6537-7712/work/39477820
dc.identifier.otherWOS: 000413767900001
dc.descriptionSupported by the Global Alliance for TB Drug Development with support from the Bill and Melinda Gates Foundation, the European and Developing Countries Clinical Trials Partnership (Grant IP.2007.32011.011), US Agency for International Development, UK Department for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, National Institutes of Health, AIDS Clinical Trials Group. The study was also supported by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (UM1AI068634, UM1 AI068636, and UM1AI106701) and by NIAID grants to the University of KwaZulu Natal, South Africa, AIDS Clinical Trials Group (ACTG) site 31422 (1U01AI069469); to the Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, South Africa, ACTG site 12301 (1U01AI069453); and to the Durban International Clinical Trials Unit, South Africa, ACTG site 11201 (1U01AI069426). Bayer Healthcare for donated moxifloxacin and Sanofi donated rifampin.en
dc.description.abstractBackground:  The use of early morning sputum samples (EMS) to diagnose tuberculosis (TB) can result in treatment delay given the need for the patient to return to the clinic with the EMS, increasing the chance of patients being lost during their diagnostic workup. However, there is little evidence to support the superiority of EMS over spot sputum samples. In this new analysis of the REMoxTB study, we compare the diagnostic accuracy of EMS with spot samples for identifying Mycobacterium tuberculosis pre- and post-treatment. Methods:  Patients who were smear positive at screening were enrolled into the study. Paired sputum samples (one EMS and one spot) were collected at each trial visit pre- and post-treatment. Microscopy and culture on solid LJ and liquid MGIT media were performed on all samples; those missing corresponding paired results were excluded from the analyses. Results:  Data from 1115 pre- and 2995 post-treatment paired samples from 1931 patients enrolled in the REMoxTB study were analysed. Patients were recruited from South Africa (47%), East Africa (21%), India (20%), Asia (11%), and North America (1%); 70% were male, median age 31 years (IQR 24–41), 139 (7%) co-infected with HIV with a median CD4 cell count of 399 cells/μL (IQR 318–535). Pre-treatment spot samples had a higher yield of positive Ziehl–Neelsen smears (98% vs. 97%, P = 0.02) and LJ cultures (87% vs. 82%, P = 0.006) than EMS, but there was no difference for positivity by MGIT (93% vs. 95%, P = 0.18). Contaminated and false-positive MGIT were found more often with EMS rather than spot samples. Surprisingly, pre-treatment EMS had a higher smear grading and shorter time-to-positivity, by 1 day, than spot samples in MGIT culture (4.5 vs. 5.5 days, P < 0.001). There were no differences in time to positivity in pre-treatment LJ culture, or in post-treatment MGIT or LJ cultures. Comparing EMS and spot samples in those with unfavourable outcomes, there were no differences in smear or culture results, and positive results were not detected earlier in Kaplan–Meier analyses in either EMS or spot samples. Conclusions:  Our data do not support the hypothesis that EMS samples are superior to spot sputum samples in a clinical trial of patients with smear positive pulmonary TB. Observed small differences in mycobacterial burden are of uncertain significance and EMS samples do not detect post-treatment positives any sooner than spot samples.
dc.relation.ispartofBMC Medicineen
dc.rights© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver eve( applies to the data made available in this article, unless otherwise stated.en
dc.subjectSmear microscopyen
dc.subjectEarly morning sputumen
dc.subjectSpot sputumen
dc.subjectRA0421 Public health. Hygiene. Preventive Medicineen
dc.subjectSDG 3 - Good Health and Well-beingen
dc.titleSpot sputum samples are at least as good as early morning samples for identifying Mycobacterium tuberculosisen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Global Health Implementation Groupen
dc.contributor.institutionUniversity of St Andrews. Gillespie Groupen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. Infection Groupen
dc.contributor.institutionUniversity of St Andrews. Infection and Global Health Divisionen
dc.description.statusPeer revieweden

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