A novel molecular strategy for surveillance of multidrug resistant tuberculosis in high burden settings

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dc.contributor.author Said, Halima M.
dc.contributor.author Kushner, Nicole
dc.contributor.author Omar, Shaheed V.
dc.contributor.author Dreyer, Andries W.
dc.contributor.author Koornhof, Hendrik
dc.contributor.author Erasmus, Linda
dc.contributor.author Gardee, Yasmin
dc.contributor.author Rukasha, Ivy
dc.contributor.author Shashkina, Elena
dc.contributor.author Beylis, Natalie
dc.contributor.author Kaplan, Gilla
dc.contributor.author Fallows, Dorothy
dc.contributor.author Ismail, Nazir Ahmed
dc.date.accessioned 2016-05-11T14:29:40Z
dc.date.available 2016-05-11T14:29:40Z
dc.date.issued 2016-01-11
dc.description Supporting Information. S1 File. (XLSX) en_ZA
dc.description.abstract BACKGROUND In South Africa and other high prevalence countries, transmission is a significant contributor to rising rates of multidrug resistant tuberculosis (MDR-TB). Thus, there is a need to develop an early detection system for transmission clusters suitable for high burden settings. We have evaluated the discriminatory power and clustering concordance of a novel and simple genotyping approach, combining spoligotyping with pncA sequencing (SpoNC), against two well-established methods: IS6110-RFLP and 24-loci MIRU-VNTR. METHODS A total of 216 MDR-TB isolates collected from January to June 2010 from the NHLS Central TB referral laboratory in Braamfontein, Johannesburg, representing a diversity of strains from South Africa, were included. The isolates were submitted for genotyping, pncA sequencing and analysis to the Centre for Tuberculosis in South Africa and the Public Health Research Institute Tuberculosis Center at Rutgers University in the United States. Clustering rates, Hunter-Gaston Discriminatory Indexes (HGI) and Wallace coefficients were compared between the methods. RESULTS Overall clustering rates were high by both IS6110-RFLP (52.8%) and MIRU-VNTR (45.8%), indicative of on-going transmission. Both 24-loci MIRU-VNTR and IS6110-RFLP had similar HGI (0.972 and 0.973, respectively), with close numbers of unique profiles (87 vs. 70), clustered isolates (129 vs. 146), and cluster sizes (2 to 26 vs. 2 to 25 isolates). Spoligotyping alone was the least discriminatory (80.1% clustering, HGI 0.903), with 28 unique types. However, the discriminatory power of spoligotyping was improved when combined with pncA sequencing using the SpoNC approach (61.8% clustering, HGI 0.958). A high proportion of MDR-TB isolates had mutations in pncA (68%, n = 145), and pncA mutations were significantly associated with clustering (p = 0.007 and p = 0.0013 by 24-loci MIRU-VNTR and IS6110-RFLP, respectively), suggesting high rates of resistance to pyrazinamide among all MDR-TB cases and particularly among clustered cases. CONCLUSION We conclude that SpoNC provides good discrimination for MDR-TB surveillance and early identification of outbreaks in South Africa, with 24-loci MIRU-VNTR applied for pncA wildtype strains as needed. en_ZA
dc.description.department Medical Microbiology en_ZA
dc.description.librarian am2016 en_ZA
dc.description.uri http://www.plosone.org en_ZA
dc.identifier.citation Said HM, Kushner N, Omar SV, Dreyer AW, Koornhof H, Erasmus L, et al. (2016) A Novel Molecular Strategy for Surveillance of Multidrug Resistant Tuberculosis in High Burden Settings. PLoS ONE 11(1): e0146106. DOI: 10.1371/journal. pone.0146106. en_ZA
dc.identifier.issn 1932-6203
dc.identifier.other 10.1371/journal.pone.0146106
dc.identifier.uri http://hdl.handle.net/2263/52572
dc.language.iso en en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights © 2016 Said et al. This is an open access article distributed under the terms of the Creative Commons Attribution License. en_ZA
dc.subject Transmission en_ZA
dc.subject Detection system en_ZA
dc.subject Multidrug resistant tuberculosis (MDR-TB). en_ZA
dc.subject Tuberculosis (TB) en_ZA
dc.subject South Africa (SA) en_ZA
dc.title A novel molecular strategy for surveillance of multidrug resistant tuberculosis in high burden settings en_ZA
dc.type Article en_ZA


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