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.author Shenai, Shubhada en_ZA
dc.contributor.author Ronacher, Katharina en_ZA
dc.contributor.author Malherbe, Stefanus en_ZA
dc.contributor.author Stanley, Kim en_ZA
dc.contributor.author Kriel, Magdalena en_ZA
dc.contributor.author Winter, Jill en_ZA
dc.contributor.author Peppard, Thomas en_ZA
dc.contributor.author Barry, Charles E en_ZA
dc.contributor.author Wang, Jing en_ZA
dc.contributor.author Dodd, Lori E en_ZA
dc.contributor.author Via, Laura E en_ZA
dc.contributor.author Walzl, Gerhard en_ZA
dc.contributor.author Alland, David en_ZA
dc.date.accessioned 2016-10-31T07:38:05Z
dc.date.available 2016-10-31T07:38:05Z
dc.date.issued 2016 en_ZA
dc.identifier.citation Shenai, 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.0160062 en_ZA
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0160062 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/22356
dc.description.abstract 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. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This 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.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plosone en_ZA
dc.subject.other Tuberculosis en_ZA
dc.subject.other Sputum en_ZA
dc.subject.other Biomarkers en_ZA
dc.subject.other Mycobacterium tuberculosis en_ZA
dc.subject.other Drug therapy en_ZA
dc.subject.other Extensively drug-resistant tuberculosis en_ZA
dc.subject.other Specimen preparation and treatment en_ZA
dc.subject.other Clinical trials en_ZA
dc.title Bacterial loads measured by the Xpert MTB/RIF assay as markers of culture conversion and bacteriological cure in pulmonary TB en_ZA
dc.type Journal Article en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Institute of Infectious Disease and Molecular Medicine en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Shenai, 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/11427/22356 en_ZA
dc.identifier.chicagocitation Shenai, 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/11427/22356 en_ZA
dc.identifier.vancouvercitation Shenai 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.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


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This 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. Except where otherwise noted, this item's license is described as This 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.