inhA promoter mutations: A gateway to extensively drug-resistant tuberculosis in South Africa?

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dc.contributor.authorMuller B.
dc.contributor.authorStreicher E.M.
dc.contributor.authorHoek K.G.P.
dc.contributor.authorTait M.
dc.contributor.authorTrollip A.
dc.contributor.authorBosman M.E.
dc.contributor.authorCoetzee G.J.
dc.contributor.authorChabula-Nxiweni E.M.
dc.contributor.authorHoosain E.
dc.contributor.authorGey Van Pittius N.C.
dc.contributor.authorVictor T.C.
dc.contributor.authorVan Helden P.D.
dc.contributor.authorWarren R.M.
dc.date.accessioned2011-05-15T15:53:44Z
dc.date.available2011-05-15T15:53:44Z
dc.date.issued2011
dc.description.abstractSETTING: Western Cape and Eastern Cape Provinces, South Africa. OBJECTIVE: To assess the potential association between the evolution of extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis and mutations in the inhA promoter or the katG gene. DESIGN: Analysis of the frequency distribution of isoniazid (INH) resistance conferring mutations in a population sample of drug-resistant isolates of M. tuberculosis. RESULTS: In the Western Cape and Eastern Cape Provinces, the percentage of isolates exhibiting inhA promoter mutations increased significantly from respectively 48.4% and 62.4% in multidrug-resistant tuberculosis (MDR-TB) isolates to 85.5% and 91.9% in XDR isolates. Data from the Western Cape revealed that significantly more XDR-TB isolates showed mutations in the inhA promoter than in katG (85.5% vs. 60.9%, P < 0.01), while the respective proportions were equal for INH-resistant non-MDR-TB isolates (∼30%). CONCLUSIONS: inhA promoter mutations are strongly associated with XDR-TB in South Africa. We suggest that this is due to the dual resistance to ethionamide and (low-dose) INH conferred by inhA promoter mutations. The use of molecular probe assays such as the Geno-Type® MTBDRplus assay, which allows the detection of inhA promoter mutations, could enable treatment regimens to be adjusted depending on the pharmacogenetic properties of the mutations detected. © 2011 The Union.
dc.description.versionArticle
dc.identifier.citationInternational Journal of Tuberculosis and Lung Disease
dc.identifier.citation15
dc.identifier.citation3
dc.identifier.issn10273719
dc.identifier.urihttp://hdl.handle.net/10019.1/8785
dc.titleinhA promoter mutations: A gateway to extensively drug-resistant tuberculosis in South Africa?
dc.typeArticle
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