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Ausceptibility testing and resistance mechanisms to second-line agents against Mycobacterium tuberculosis in Pretoria, South Africa
Thesis (PhD)--University of Pretoria, 2012.
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University of Pretoria
2013
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| _version_ | 1867613549660995584 |
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| access_status_str | Open Access |
| author2 | Kock, Martha Magdalena |
| author_browse | Kock, Martha Magdalena |
| author_facet | Kock, Martha Magdalena |
| collection | Thesis |
| dc_rights_str_mv | © 2012 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| description | Thesis (PhD)--University of Pretoria, 2012. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/31324 |
| institution | University of Pretoria (South Africa) |
| last_indexed | 2026-06-10T12:37:55.093Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2013 |
| publishDateRange | 2013 |
| publishDateSort | 2013 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/31324 Ausceptibility testing and resistance mechanisms to second-line agents against Mycobacterium tuberculosis in Pretoria, South Africa Kock, Martha Magdalena Ehlers, M.M. (Marthie Magdaleen) Said, H.M. (Halima Mohammed) UCTD Thesis (PhD)--University of Pretoria, 2012. Multidrug-resistant (MDR) and extensively drug-resistant tuberculosis (XDR-TB) is a serious problem in South Africa. Standardised and accurate drug susceptibility testing for first-line and second-line anti-TB drugs are critical elements in battling the MDR- and XDR-TB epidemic. Furthermore, understanding of the population structure and transmission patterns of circulating drug-resistant Mycobacterium tuberculosis (M. tuberculosis) strains is of utmost importance. Previous studies have shown that different genotypes of M. tuberculosis strains predominate in different geographical regions and strain to strain variations may have important consequences when it comes to transmissibility, diagnostics and management. Despite the high prevalence of MDR- and XDR-TB in South Africa, data with regard to the population structure of drug-resistant strains is lacking in many regions. Therefore, the aim of the study was to evaluate phenotypic and genotypic methods for susceptibility testing of firstline and second-line anti-TB drugs and molecular characterisation of drug-resistant strains from high-burden TB areas in South Africa. Consecutive MDR-TB isolates from four provinces were included in this study. The results of routine drug susceptibility testing of ethambutol, streptomycin, kanamycin and ofloxacin using the BACTEC MGIT 960 system in MDR-TB isolates was compared to the agar proportion method. The GenoType® MTBDRsl assay was evaluated for the detection of resistance against ethambutol, capreomycin, kanamycin and ofloxacin. Finally, the study investigated the population structure and transmission patterns of drug-resistant M. tuberculosis isolates using spoligotyping and MIRU-VNTR typing. Additionally, the possible association of genotypes with drug-resistance patterns and demographic information were explored. The sensitivity and specificity of the BACTEC MGIT 960 system using the agar proportion method as a gold standard was 18.8% and 96.5% for ethambutol, 95.2% and 37.4% for streptomycin, 54.6% and 91.8% for kanamycin and 100% and 89% for ofloxacin, respectively. The GenoType® MTBDRsl assay gave comparable results for ofloxacin; however, a low performance was found for the detection of resistance to capreomycin, kanamycin and ethambutol. In order to resolve the discrepancies between the two methods, DNA sequencing was done for the target genes (gyrA, rrs, embB) from the discrepant results as well as two additional genes (gyrB, tlyA) that were not included in the assay. The DNA sequencing identified mutations in the gyrA, gyrB, rrs and tlyA genes that were not detected by the GenoType® MTBDRsl assay. The prevalence of XDR-TB and pre-XDR TB was 7.1% and 9.5%, respectively. A highdiversity of M. tuberculosis strains were found in this study, with the Beijing and EAI1_SOM families being predominant. No association was found between genotypes and specific drugresistance or demographic information. The sensitivity of the BACTEC MGIT 960 system for ofloxacin and streptomycin was excellent; however, the sensitivity was low for ethambutol and kanamycin. The GenoType® MTBDRsl assay was promising for the detection of ofloxacin; however, the sensitivity of the assay needs to be improved for capreomycin, kanamycin and ethambutol. The high-level of diversity and the geographical distribution of the drug-resistant M. tuberculosis isolates in this study suggested that the transmission of drug-resistant TB in these study settings is not caused by clonal spread of a specific M. tuberculosis strain. Medical Microbiology Unrestricted 2013-09-09T12:11:12Z 2012-10-01 2013-09-09T12:11:12Z 2012-09-07 2012-10-01 2012-09-30 Thesis Said, HM 2012, Ausceptibility testing and resistance mechanisms to second-line agents against Mycobacterium tuberculosis in Pretoria, South Africa, PhD thesis, University of Pretoria, Pretoria, viewed yymmdd < http://upetd.up.ac.za/thesis/available/etd-09302012-130754/ > D12/9/203/ag http://hdl.handle.net/2263/31324 http://upetd.up.ac.za/thesis/available/etd-09302012-130754/ © 2012 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria |
| spellingShingle | UCTD Ausceptibility testing and resistance mechanisms to second-line agents against Mycobacterium tuberculosis in Pretoria, South Africa |
| title | Ausceptibility testing and resistance mechanisms to second-line agents against Mycobacterium tuberculosis in Pretoria, South Africa |
| title_full | Ausceptibility testing and resistance mechanisms to second-line agents against Mycobacterium tuberculosis in Pretoria, South Africa |
| title_fullStr | Ausceptibility testing and resistance mechanisms to second-line agents against Mycobacterium tuberculosis in Pretoria, South Africa |
| title_full_unstemmed | Ausceptibility testing and resistance mechanisms to second-line agents against Mycobacterium tuberculosis in Pretoria, South Africa |
| title_short | Ausceptibility testing and resistance mechanisms to second-line agents against Mycobacterium tuberculosis in Pretoria, South Africa |
| title_sort | ausceptibility testing and resistance mechanisms to second line agents against mycobacterium tuberculosis in pretoria south africa |
| topic | UCTD |
| url | http://hdl.handle.net/2263/31324 http://upetd.up.ac.za/thesis/available/etd-09302012-130754/ |