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Karen Shean,
Elizabeth Streicher,
Elize Pieterson,
Greg Symons,
Richard van Zyl Smit,
Grant Theron,
Rannakoe Lehloenya,
Xavier Padanilam,
Paul Wilcox, Tommie C Victor,
Paul van Helden,
Martin P Grobusch,
Robin Warren,
Motasim Badri,
Keertan Dheda
PLoS ONE 01/2013; 8(5). · 4.09 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Background. Diagnosis of drug resistance and timely initiation of MDR TB therapy are essential to reduce transmission and improve patient outcomes. We sought to determine whether implementation of the rapid MTBDRplus diagnostic shortened the time from specimen collection to patient MDR TB therapy initiation.Methods. We conducted a retrospective cohort analysis of 197 MDR TB patients treated at Brewelskloof, a rural TB hospital in the Western Cape Province, South Africa, between 2007 and 2011.Results. Eighty-nine patients (45%) received conventional liquid culture and DST on solid medium and 108 (55%) the MTBDRplus assay after positive AFB or culture. Median time from sample taken to therapy initiation was reduced from 80 days (IQR 62-100) for conventional DST to 55 days (IQ 37.5-78) with the MTBDRplus. Although the laboratory processing time declined significantly, operational delays persisted both in the laboratory and the clinical infrastructure for getting patients started on treatment. In multivariate analysis, patients with a MTBDRplus test had a reduced risk of starting treatment 60 days or more after sputum collection of 0.52 (p<0.0001) compared to patients with culture based DST, after adjustment for smear status and site of disease.Conclusions. Use of MTBDRplus significantly reduced time to MDR TB treatment initiation. However, DST reporting to clinics was delayed by more than 1 week, due in part to laboratory operational delays, including dependence on smear and culture positivity prior to MTBDRplus performance. In addition, once MDR TB was reported, delays in contacting patients and initiating therapy require improvements in clinical infrastructure.
Clinical Infectious Diseases 10/2012; · 9.15 Impact Factor
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Violet N Chihota,
Borna Müller,
Charmaine K Mlambo,
Manormoney Pillay,
Marisa Tait,
Elizabeth M Streicher,
Else Marais,
Gian D van der Spuy,
Madeleine Hanekom,
Gerrit Coetzee,
Andre Trollip,
Cindy Hayes,
Marlein E Bosman,
Nico C Gey van Pittius, Tommie C Victor,
Paul D van Helden,
Robin M Warren
[show abstract]
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ABSTRACT: Genotyping of multidrug-resistant (MDR) Mycobacterium tuberculosis strains isolated from tuberculosis (TB) patients in four South African provinces (Western Cape, Eastern Cape, KwaZulu-Natal, and Gauteng) revealed a distinct population structure of the MDR strains in all four regions, despite the evidence of substantial human migration between these settings. In all analyzed provinces, a negative correlation between strain diversity and an increasing level of drug resistance (from MDR-TB to extensively drug-resistant TB [XDR-TB]) was observed. Strains predominating in XDR-TB in the Western and Eastern Cape and KwaZulu-Natal Provinces were strongly associated with harboring an inhA promoter mutation, potentially suggesting a role of these mutations in XDR-TB development in South Africa. Approximately 50% of XDR-TB cases detected in the Western Cape were due to strains probably originating from the Eastern Cape. This situation may illustrate how failure of efficient health care delivery in one setting can burden health clinics in other areas.
Journal of clinical microbiology 12/2011; 50(3):995-1002. · 4.16 Impact Factor
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Ben J Marais, Tommie C Victor,
Anneke C Hesseling,
Madeleine Barnard,
Annemie Jordaan,
Wendy Brittle,
Helmuth Reuter,
Nulda Beyers,
Paul D van Helden,
Rob M Warren,
H Simon Schaaf
[show abstract]
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ABSTRACT: Drug resistance among children with culture-confirmed tuberculosis (TB) provides an accurate measure of transmitted drug resistance within the community. We describe the genotype diversity in children with culture-confirmed TB and investigate the relationship between genotype and drug resistance. A prospective study was conducted from March 2003 through August 2005 at Tygerberg Children's Hospital, in the Western Cape Province of South Africa. All children (<13 years of age) diagnosed with culture-confirmed TB were included. Genotype analysis and phenotypic drug susceptibility testing were performed on the first culture-positive isolate from each patient. Mutation analysis was performed on all drug-resistant isolates. Spoligotyping was successfully performed on isolates from 391/399 (98%) children diagnosed with culture-confirmed TB. Drug susceptibility testing was also performed on 391 isolates; 49 (12.5%) were resistant to isoniazid, and 20 (5.1%) of these were resistant to both isoniazid and rifampin. Beijing was the most common genotype family, identified in 130/391 (33.2%) cases, followed by LAM in 114/391 (29.2%) cases. The presence of both Beijing and Haarlem genotype families was significantly associated with drug resistance (26/49 [53.1%] versus 113/342 [33.0%]; odds ratio, 1.7; 95% confidence interval, 1.0 to 2.9). The high prevalence of Beijing and LAM in children with culture-confirmed TB reflects considerable transmission of these genotype families within the community. The overrepresentation of Beijing and Haarlem genotype families in children with drug-resistant TB demonstrates their contribution to transmitted drug resistance and their potential importance in the emergent drug-resistant TB epidemic.
Journal of Clinical Microbiology 10/2006; 44(10):3539-43. · 4.15 Impact Factor
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Karine Brudey,
Jeffrey R Driscoll,
Leen Rigouts,
Wolfgang M Prodinger,
Andrea Gori,
Sahal A Al-Hajoj,
Caroline Allix,
Liselotte Aristimuño,
Jyoti Arora,
Viesturs Baumanis, [......],
Enrico Tortoli,
Tatjana Tracevska,
Véronique Vincent, Tommie C Victor,
Robin M Warren,
Sook Fan Yap,
Khadiza Zaman,
Françoise Portaels,
Nalin Rastogi,
Christophe Sola
[show abstract]
[hide abstract]
ABSTRACT: The Direct Repeat locus of the Mycobacterium tuberculosis complex (MTC) is a member of the CRISPR (Clustered regularly interspaced short palindromic repeats) sequences family. Spoligotyping is the widely used PCR-based reverse-hybridization blotting technique that assays the genetic diversity of this locus and is useful both for clinical laboratory, molecular epidemiology, evolutionary and population genetics. It is easy, robust, cheap, and produces highly diverse portable numerical results, as the result of the combination of (1) Unique Events Polymorphism (UEP) (2) Insertion-Sequence-mediated genetic recombination. Genetic convergence, although rare, was also previously demonstrated. Three previous international spoligotype databases had partly revealed the global and local geographical structures of MTC bacilli populations, however, there was a need for the release of a new, more representative and extended, international spoligotyping database.
The fourth international spoligotyping database, SpolDB4, describes 1939 shared-types (STs) representative of a total of 39,295 strains from 122 countries, which are tentatively classified into 62 clades/lineages using a mixed expert-based and bioinformatical approach. The SpolDB4 update adds 26 new potentially phylogeographically-specific MTC genotype families. It provides a clearer picture of the current MTC genomes diversity as well as on the relationships between the genetic attributes investigated (spoligotypes) and the infra-species classification and evolutionary history of the species. Indeed, an independent Naïve-Bayes mixture-model analysis has validated main of the previous supervised SpolDB3 classification results, confirming the usefulness of both supervised and unsupervised models as an approach to understand MTC population structure. Updated results on the epidemiological status of spoligotypes, as well as genetic prevalence maps on six main lineages are also shown. Our results suggests the existence of fine geographical genetic clines within MTC populations, that could mirror the passed and present Homo sapiens sapiens demographical and mycobacterial co-evolutionary history whose structure could be further reconstructed and modelled, thereby providing a large-scale conceptual framework of the global TB Epidemiologic Network.
Our results broaden the knowledge of the global phylogeography of the MTC complex. SpolDB4 should be a very useful tool to better define the identity of a given MTC clinical isolate, and to better analyze the links between its current spreading and previous evolutionary history. The building and mining of extended MTC polymorphic genetic databases is in progress.
BMC Microbiology 02/2006; 6:23. · 3.04 Impact Factor
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Karine Brudey,
Jeffrey R Driscoll,
Leen Rigouts,
Wolfgang M Prodinger,
Andrea Gori,
Sahal A M Al-Hajoj,
Caroline Allix,
Liselotte Aristimuno,
Jyoti Arora,
Viesturs Baumanis, [......],
Enrico Tortoli,
Tatjana Tracevska,
Veronique Vincent, Tommie C Victor,
Robin Warren,
Sook Fan Yap,
Kadiza Zaman,
Francoise Portaels,
Nalin Rastogi,
Christophe Sola
[show abstract]
[hide abstract]
ABSTRACT: Background: The Direct Repeat locus of the Mycobacterium tuberculosis complex (MTC) is a member of the CRISPR (Clustered regularly interspaced short palindromic repeats) sequences family. Spoligotyping is the widely used PCR-based reverse-hybridization blotting technique that assays the genetic diversity of this locus and is useful both for clinical laboratory, molecular epidemiology, evolutionary and population genetics. It is easy, robust, cheap, and produces highly diverse portable numerical results, as the result of the combination of (1) Unique Events Polymorphism (UEP) (2) Insertion-Sequence-mediated genetic recombination. Genetic convergence, although rare, was also previously demonstrated. Three previous international spoligotype databases had partly revealed the global and local geographical structures of MTC bacilli populations, however, there was a need for the release of a new, more representative and extended, international spoligotyping database. Results: The fourth international spoligotyping database, SpolDB4, describes 1939 shared-types (STs) representative of a total of 39,295 strains from 122 countries, which are tentatively classified into 62 clades/lineages using a mixed expert-based and bioinformatical approach. The SpolDB4 update adds 26 new potentially phylogeographically-specific MTC genotype families. It provides a clearer picture of the current MTC genomes diversity as well as on the relationships between the genetic attributes investigated (spoligotypes) and the infra-species classification and evolutionary history of the species. Indeed, an independent Naïve-Bayes mixture-model analysis has validated main of the previous supervised SpolDB3 classification results, confirming the usefulness of both supervised and unsupervised models as an approach to understand MTC population structure. Updated results on the epidemiological status of spoligotypes, as well as genetic prevalence maps on six main lineages are also shown. Our results suggests the existence of fine geographical genetic clines within MTC populations, that could mirror the passed and present Homo sapiens sapiens demographical and mycobacterial co-evolutionary history whose structure could be further reconstructed and modelled, thereby providing a large-scale conceptual framework of the global TB Epidemiologic Network. Conclusion: Our results broaden the knowledge of the global phylogeography of the MTC complex. SpolDB4 should be a very useful tool to better define the identity of a given MTC clinical isolate, and to better analyze the links between its current spreading and previous evolutionary history. The building and mining of extended MTC polymorphic genetic databases is in progress. Includes bibliography
