Bacterial loads measured by the Xpert MTB/RIF assay as markers of culture conversion and bacteriological cure in pulmonary TB

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dc.contributor.authorShenai, Shubhadaen_ZA
dc.contributor.authorRonacher, Katharinaen_ZA
dc.contributor.authorMalherbe, Stefanusen_ZA
dc.contributor.authorStanley, Kimen_ZA
dc.contributor.authorKriel, Magdalenaen_ZA
dc.contributor.authorWinter, Jillen_ZA
dc.contributor.authorPeppard, Thomasen_ZA
dc.contributor.authorBarry, Charles Een_ZA
dc.contributor.authorWang, Jingen_ZA
dc.contributor.authorDodd, Lori Een_ZA
dc.contributor.authorVia, Laura Een_ZA
dc.contributor.authorWalzl, Gerharden_ZA
dc.contributor.authorAlland, Daviden_ZA
dc.date.accessioned2016-10-31T07:38:05Z
dc.date.available2016-10-31T07:38:05Z
dc.date.issued2016en_ZA
dc.description.abstractIntroduction Biomarkers are needed to monitor tuberculosis (TB) treatment and predict treatment outcomes. We evaluated the Xpert MTB/RIF (Xpert) assay as a biomarker for TB treatment during and at the end of the 24 weeks therapy. METHODS: Sputum from 108 HIV-negative, culture-positive pulmonary TB patients was analyzed using Xpert at time points before and during anti-TB therapy. Results were compared against culture. Direct Xpert cycle-threshold (Ct), a change in the Ct (delta Ct), or a novel "percent closing of baseline Ct deficit" (percent closing) were evaluated as classifiers of same-day and end-of-treatment culture and therapeutic outcomes. RESULTS: Xpert was positive in 29/95 (30.5%) of subjects at week 24; and positive one year after treatment in 8/64 (12.5%) successfully-treated patients who remained free of tuberculosis. We identified a relationship between initial bacterial load measured by baseline Xpert Ct and time to culture conversion (hazard ratio 1.06, p = 0.0023), and to the likelihood of being among the 8 treatment failures at week 24 (AUC = 72.8%). Xpert Ct was even more strongly associated with culture conversion on the day the test was performed with AUCs 96.7%, 99.2%, 86.0% and 90.2%, at Day 7, Week 4, 8 and 24, respectively. Compared to baseline Ct measures alone, a combined measure of baseline Ct plus either Delta Ct or percent closing improved the classification of treatment failure status to a 75% sensitivity and 88.9% specificity. CONCLUSIONS: Genome loads measured by Xpert provide a potentially-useful biomarker for classifying same day culture status and predicting response to therapy.en_ZA
dc.identifier.apacitationShenai, S., Ronacher, K., Malherbe, S., Stanley, K., Kriel, M., Winter, J., ... Alland, D. (2016). Bacterial loads measured by the Xpert MTB/RIF assay as markers of culture conversion and bacteriological cure in pulmonary TB. <i>PLoS One</i>, http://hdl.handle.net/11427/22356en_ZA
dc.identifier.chicagocitationShenai, Shubhada, Katharina Ronacher, Stefanus Malherbe, Kim Stanley, Magdalena Kriel, Jill Winter, Thomas Peppard, et al "Bacterial loads measured by the Xpert MTB/RIF assay as markers of culture conversion and bacteriological cure in pulmonary TB." <i>PLoS One</i> (2016) http://hdl.handle.net/11427/22356en_ZA
dc.identifier.citationShenai, S., Ronacher, K., Malherbe, S., Stanley, K., Kriel, M., Winter, J., ... & Via, L. E. (2016). Bacterial loads measured by the Xpert MTB/RIF assay as markers of culture conversion and bacteriological cure in pulmonary TB. PloS one, 11(8), e0160062. doi:10.1371/journal.pone.0160062en_ZA
dc.identifier.ris TY - Journal Article AU - Shenai, Shubhada AU - Ronacher, Katharina AU - Malherbe, Stefanus AU - Stanley, Kim AU - Kriel, Magdalena AU - Winter, Jill AU - Peppard, Thomas AU - Barry, Charles E AU - Wang, Jing AU - Dodd, Lori E AU - Via, Laura E AU - Walzl, Gerhard AU - Alland, David AB - Introduction Biomarkers are needed to monitor tuberculosis (TB) treatment and predict treatment outcomes. We evaluated the Xpert MTB/RIF (Xpert) assay as a biomarker for TB treatment during and at the end of the 24 weeks therapy. METHODS: Sputum from 108 HIV-negative, culture-positive pulmonary TB patients was analyzed using Xpert at time points before and during anti-TB therapy. Results were compared against culture. Direct Xpert cycle-threshold (Ct), a change in the Ct (delta Ct), or a novel "percent closing of baseline Ct deficit" (percent closing) were evaluated as classifiers of same-day and end-of-treatment culture and therapeutic outcomes. RESULTS: Xpert was positive in 29/95 (30.5%) of subjects at week 24; and positive one year after treatment in 8/64 (12.5%) successfully-treated patients who remained free of tuberculosis. We identified a relationship between initial bacterial load measured by baseline Xpert Ct and time to culture conversion (hazard ratio 1.06, p = 0.0023), and to the likelihood of being among the 8 treatment failures at week 24 (AUC = 72.8%). Xpert Ct was even more strongly associated with culture conversion on the day the test was performed with AUCs 96.7%, 99.2%, 86.0% and 90.2%, at Day 7, Week 4, 8 and 24, respectively. Compared to baseline Ct measures alone, a combined measure of baseline Ct plus either Delta Ct or percent closing improved the classification of treatment failure status to a 75% sensitivity and 88.9% specificity. CONCLUSIONS: Genome loads measured by Xpert provide a potentially-useful biomarker for classifying same day culture status and predicting response to therapy. DA - 2016 DB - OpenUCT DO - 10.1371/journal.pone.0160062 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2016 T1 - Bacterial loads measured by the Xpert MTB/RIF assay as markers of culture conversion and bacteriological cure in pulmonary TB TI - Bacterial loads measured by the Xpert MTB/RIF assay as markers of culture conversion and bacteriological cure in pulmonary TB UR - http://hdl.handle.net/11427/22356 ER - en_ZA
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0160062en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/22356
dc.identifier.vancouvercitationShenai S, Ronacher K, Malherbe S, Stanley K, Kriel M, Winter J, et al. Bacterial loads measured by the Xpert MTB/RIF assay as markers of culture conversion and bacteriological cure in pulmonary TB. PLoS One. 2016; http://hdl.handle.net/11427/22356.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherSputumen_ZA
dc.subject.otherBiomarkersen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherDrug therapyen_ZA
dc.subject.otherExtensively drug-resistant tuberculosisen_ZA
dc.subject.otherSpecimen preparation and treatmenten_ZA
dc.subject.otherClinical trialsen_ZA
dc.titleBacterial loads measured by the Xpert MTB/RIF assay as markers of culture conversion and bacteriological cure in pulmonary TBen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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