Programmatically selected multidrug-resistant strains drive the emergence of extensively drug-resistant tuberculosis in South Africa

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dc.contributor.authorMuller, Bornaen_ZA
dc.contributor.authorChihota, Violet N.en_ZA
dc.contributor.authorPillay, Manormoneyen_ZA
dc.contributor.authorKlopper, Marisaen_ZA
dc.contributor.authorStreicher, Elizabeth M.en_ZA
dc.contributor.authorCoetzee, Gerriten_ZA
dc.contributor.authorTrollip, Andreen_ZA
dc.contributor.authorHayes, Cindyen_ZA
dc.contributor.authorBosman, Marlein E.en_ZA
dc.contributor.authorGey van Pittius, Nicolaas C.en_ZA
dc.contributor.authorVictor, Thomas C.en_ZA
dc.contributor.authorGagneux, Sebastienen_ZA
dc.contributor.authorVan Helden, Paul D.en_ZA
dc.contributor.authorWarren, Robin M.en_ZA
dc.date.accessioned2014-07-07T12:18:26Z
dc.date.available2014-07-07T12:18:26Z
dc.date.issued2013-08-23
dc.descriptionCITATION: Muller, B. et al. 2013. Programmatically selected multidrug-resistant strains drive the emergence of extensively drug-resistant tuberculosis in South Africa. PLoS ONE, 8(8): e70919. doi:10.1371/journal.pone.0070919.
dc.descriptionThe original publication is available at http://journals.plos.org
dc.description.abstractBackground: South Africa shows one of the highest global burdens of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). Since 2002, MDR-TB in South Africa has been treated by a standardized combination therapy, which until 2010 included ofloxacin, kanamycin, ethionamide, ethambutol and pyrazinamide. Since 2010, ethambutol has been replaced by cycloserine or terizidone. The effect of standardized treatment on the acquisition of XDR-TB is not currently known. Methods: We genetically characterized a random sample of 4,667 patient isolates of drug-sensitive, MDR and XDR-TB cases collected from three South African provinces, namely, the Western Cape, Eastern Cape and KwaZulu-Natal. Drug resistance patterns of a subset of isolates were analyzed for the presence of commonly observed resistance mutations. Results: Our analyses revealed a strong association between distinct strain genotypes and the emergence of XDR-TB in three neighbouring provinces of South Africa. Strains predominant in XDR-TB increased in proportion by more than 20-fold from drug-sensitive to XDR-TB and accounted for up to 95% of the XDR-TB cases. A high degree of clustering for drug resistance mutation patterns was detected. For example, the largest cluster of XDR-TB associated strains in the Eastern Cape, affecting more than 40% of all MDR patients in this province, harboured identical mutations concurrently conferring resistance to isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin, ethionamide, kanamycin, amikacin and capreomycin. Conclusions: XDR-TB associated genotypes in South Africa probably were programmatically selected as a result of the standard treatment regimen being ineffective in preventing their transmission. Our findings call for an immediate adaptation of standard treatment regimens for M/XDR-TB in South Africa.
dc.description.urihttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0070919
dc.description.versionPublisher's version
dc.format.extent9 pages
dc.identifier.citationMuller, B. et al. 2013. Programmatically selected multidrug-resistant strains drive the emergence of extensively drug-resistant tuberculosis in South Africa. PLoS ONE, 8(8): e70919. doi:10.1371/journal.pone.0070919.
dc.identifier.issn1932-6203 (online)
dc.identifier.otherdoi:10.1371/journal.pone.0070919
dc.identifier.urihttp://hdl.handle.net/10019.1/93350
dc.language.isoen
dc.publisherPublic Library of Science
dc.rights.holderAuthors retain copyright
dc.subjectTuberculosis -- South Africaen_ZA
dc.subjectTuberculosis -- Genetic aspects -- South Africaen_ZA
dc.titleProgrammatically selected multidrug-resistant strains drive the emergence of extensively drug-resistant tuberculosis in South Africaen_ZA
dc.typeArticle
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