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Widespread use of incorrect PCR ramp rate negatively impacts multidrug-resistant tuberculosis diagnosis (MTBDRplus)

dc.contributor.authorDerendinger, B.en_ZA
dc.contributor.authorDe Vos, M.en_ZA
dc.contributor.authorNathavitharana, R. R.en_ZA
dc.contributor.authorDolby, T.en_ZA
dc.contributor.authorSimpson, J. A.en_ZA
dc.contributor.authorVan Helden, P. D.en_ZA
dc.contributor.authorWarren, R. M.en_ZA
dc.contributor.authorTheron, G.en_ZA
dc.date.accessioned2018-02-27T09:34:40Z
dc.date.available2018-02-27T09:34:40Z
dc.date.issued2018
dc.identifier.citationDerendinger, B., et al. 2018. Widespread use of incorrect PCR ramp rate negatively impacts multidrug-resistant tuberculosis diagnosis (MTBDRplus). Scientific Reports, 8:3206, doi:10.1038/s41598-018-21458-y
dc.identifier.issn2045-2322 (Online)
dc.identifier.otherdoi:10.1038/s41598-018-21458-y
dc.identifier.urihttp://hdl.handle.net/10019.1/103192
dc.descriptionCITATION: Derendinger, B., et al. 2018. Widespread use of incorrect PCR ramp rate negatively impacts multidrug-resistant tuberculosis diagnosis (MTBDRplus). Scientific Reports, 8:3206, doi:10.1038/s41598-018-21458-y.
dc.descriptionThe original publication is available at http://www.nature.com
dc.descriptionPublication of this article was funded by the Stellenbosch University Open Access Fund.
dc.description.abstractENGLISH ABSTRACT: The scale-up of rapid drug resistance testing for TB is a global priority. MTBDRplus is a WHO-endorsed multidrug-resistant (MDR)-TB PCR assay with suboptimal sensitivities and high indeterminate rates on smear-negative specimens. We hypothesised that widespread use of incorrect thermocycler ramp rate (speed of temperature change between cycles) impacts performance. A global sample of 72 laboratories was surveyed. We tested 107 sputa from Xpert MTB/RIF-positive patients and, separately, dilution series of bacilli, both at the manufacturer-recommended ramp rate (2.2 °C/s) and the most frequently reported incorrect ramp rate (4.0 °C/s). Mycobacterium tuberculosis-complex DNA (TUB-band)-detection, indeterminate results, accuracy, and inter-reader variability (dilution series only) were compared. 32 respondents did a median (IQR) of 41 (20–150) assays monthly. 78% used an incorrect ramp rate. On smear-negative sputa, 2.2 °C/s vs. 4.0 °C/s improved TUB-band positivity (42/55 vs. 32/55; p = 0.042) and indeterminate rates (1/42 vs. 5/32; p = 0.039). The actionable results (not TUB-negative or indeterminate; 41/55 vs. 28/55) hence improved by 21% (95% CI: 9–35%). Widespread use of incorrect ramp rate contributes to suboptimal MTBDRplus performance on smear-negative specimens and hence limits clinical utility. The number of diagnoses (and thus the number of smear-negative patients in whom DST is possible) will improve substantially after ramp rate correction.en_ZA
dc.description.urihttps://www.nature.com/articles/s41598-018-21458-y
dc.format.extent8 pagesen_ZA
dc.language.isoen_ZAen_ZA
dc.publisherNature Publishing Groupen_ZA
dc.subjectMultidrug-resistant tuberculosisen_ZA
dc.subjectTuberculosis -- Diagnosisen_ZA
dc.subjectRamp rateen_ZA
dc.subjectPolymerase chain reaction -- Diagnostic useen_ZA
dc.titleWidespread use of incorrect PCR ramp rate negatively impacts multidrug-resistant tuberculosis diagnosis (MTBDRplus)en_ZA
dc.typeArticleen_ZA
dc.description.versionPublisher's version
dc.rights.holderAuthors retain copyrighten_ZA


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