Browsing by Author "Van Der Spuy G.D."
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- ItemClonal expansion of a globally disseminated lineage of Mycobacterium tuberculosis with low IS6110 copy numbers(2004) Warren R.M.; Victor T.C.; Streicher E.M.; Richardson M.; Van Der Spuy G.D.; Johnson R.; Chihota V.N.; Locht C.; Supply P.; Van Helden P.D.Knowledge of the clonal expansion of Mycobacterium tuberculosis and accurate identification of predominant evolutionary lineages in this species remain limited, especially with regard to low-IS6110-copy-number strains. In this study, 170 M. tuberculosis isolates with ≤6 IS6110 insertions identified in Cape Town, South Africa, were characterized by principal genetic grouping, restriction fragment length polymorphism analysis, spoligotyping, IS6110 insertion site mapping, and variable-number tandem repeat (VNTR) typing. These analyses indicated that all but one of the isolates analyzed were members of principal genetic group 2 and of the same low-IS6110-copy-number lineage. The remaining isolate was a member of principal genetic group 1 and a different low-IS6110-copy-number lineage. Phylogenetic reconstruction suggests clonal expansion through sequential acquisition of additional IS6110 copies, expansion and contraction of VNTR sequences, and the deletion of specific direct-variable-repeat sequences. Furthermore, comparison of the genotypic data of 91 representative low-IS6110-copy-number isolates from Cape Town, other southern African regions, Europe, and the United States suggests that certain low-IS6110-copy-number strain spoligotypes and IS6110 fingerprints were acquired in the distant past. These clones have subsequently become widely disseminated and now play an important role in the global tuberculosis epidemic.
- ItemDrug-resistant tuberculosis epidemic in the Western Cape driven by a virulent Beijing genotype strain(2010) Johnson R.; Warren R.M.; Van Der Spuy G.D.; Van Pittius N.C.G.; Theron D.; Streicher E.M.; Bosman M.; Coetzee G.J.; Van Helden P.D.; Victor T.C.Temporal analysis of drug-resistant tuberculosis (TB) cases in the Western Cape, South Africa, showed a 1.5-fold increase over a 2-year period, suggesting a doubling time of 8.2 years. This increase was strongly associated with multidrug resistance and the Beijing genotype. Forty-two per cent of the overall increase was due to the Beijing genotype strain R220, suggesting that this strain had evolved unique properties that allowed for both acquisition and transmission of drug resistance. To curb the drug-resistant TB epidemic in this setting, it will be essential to implement rapid diagnostics and efficient infection control measures, improve contact screening and ensure treatment adherence. ©2010 The Union.
- ItemFluorometric assay for testing rifampin susceptibility of Mycobacterium tuberculosis complex(2008) Hoek K.G.P.; Gey Van Pittius N.C.; Moolman-Smook H.; Carelse-Tofa K.; Jordaan A.; Van Der Spuy G.D.; Streicher E.; Victor T.C.; Van Helden P.D.; Warren R.M.The emergence and transmission of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) have raised concern about diagnostic delay associated with culture-based drug susceptibility testing methods. The association between rifampin resistance and MDR-TB or XDR-TB makes it an important genetic marker for genotypic drug susceptibility testing. In this article, we describe the analysis of the physical properties of the rifampin resistance-determining region (RRDR) in the rpoB gene by high-resolution thermal melt analysis as a method for detecting rifampin resistance in Mycobacterium tuberculosis complex. The RRDR from the M. tuberculosis complex was amplified by PCR from DNA templates extracted from sputum cultures of M. tuberculosis or the laboratory strain (H37Rv) in the presence of a fluorescent DNA binding dye. Subsequent mixing of the amplification products from the respective sputum cultures and the laboratory strain and thermocycling allowed the formation of DNA duplexes. The thermal denaturation properties of these DNA duplexes were determined by measuring the derivative of the intensity of fluorescence at different temperatures. Analysis of DNA extracted from 153 sputum cultures showed a sensitivity of 98% and a specificity of 100% for the detection of rifampin resistance compared to the "gold standard" culture-based phenotyping method. No statistical difference was detected in the performance of the method when applied to crude DNA from 134 boiled cultures. This method, named "FAST-Rif" ("fluorometric assay for susceptibility iesting of rifampin"), allowed the rapid, reliable, and easy detection of genotypic rifampin resistance as a marker for MDR-TB and XDR-TB. Copyright © 2008, American Society for Microbiology. All Rights Reserved.
- ItemGenotypic and Phenotypic Characterization of Drug-Resistant Mycobacterium tuberculosis Isolates from Rural Districts of the Western Cape Province of South Africa(2004) Streicher E.M.; Warren R.M.; Kewley C.; Simpson J.; Rastogi N.; Sola C.; Van Der Spuy G.D.; Van Helden P.D.; Victor T.C.Genotypic and phenotypic analysis of drug-resistant Mycobacterium tuberculosis isolates from the Western Cape Province of South Africa showed that drug resistance is widespread and recently transmitted. Multidrug-resistant (MDR) isolates comprise 40% of this collection, and a large pool of isoniazid monoresistance may be a future source of MDR tuberculosis.
- ItemImproving nutritional status of children with cystic fibrosis at Red Cross War Memorial Children's Hospital(2011) Van Der Spuy D.A.; Cader S.; Van Der Spuy G.D.; Westwood A.T.Aim: To determine the nutritional status of children attending a cystic fibrosis clinic in a tertiary hospital in South Africa and compare it to previously reported 10-year rates. Methods: Weights and heights were measured of 69 (37 male and 32 female) children aged between 1 year and 18 years. Expected weight-for-age, expected height-for-age, expected weight-for-height and body mass index (BMI) were compared with international standards for underweight, stunting, wasting and BMI goal. Results: The nutritional status of the patients has improved over the last 10 years, most significantly for wasting, which decreased from 58.3% in 1996 to 15.9% in 2006 (95% confidence interval (CI), 1.315-14.09, P < 0.05). Fifty-two percent of the children were underweight in 2006, compared with 66.7% in 1996 (95% CI, 0.044-13.96, P < 0.05). Stunting was found in 31.9% of the current sample. Females over 15 years had expected weight-for-age 25.9% lower than those between 10 years and 15 years, while no difference was found between the male age groups. Female height-for-age was 7.06 percentage points greater than males between 10 years and 15 years (95% CI, 2.16-11.96, P < 0.01). Males between 10 years and 15 years had significantly lower BMIs than the corresponding female group. Coloured patients had significantly lower BMIs than white patients in all age groups. Conclusions: These children demonstrated continuing improvement in nutritional status, although deficits remain. The normalisation of mean weight-for-age and weight-for-height with far fewer wasted patients is encouraging. Interventions are needed in some areas to ensure that all children show progress. © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).
- ItemPopulation structure of multi- and extensively drug-resistant Mycobacterium tuberculosis strains in South Africa(2012) Chihota V.N.; Muller B.; Mlambo C.K.; Pillay M.; Tait M.; Streicher E.M.; Marais E.; Van Der Spuy G.D.; Hanekom M.; Coetzee G.; Trollip A.; Hayes C.; Bosman M.E.; Gey Van Pittius N.C.; Victor T.C.; Van Helden P.D.; Warren R.M.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. Copyright © 2012, American Society for Microbiology. All Rights Reserved.
- ItemRise in rifampicin-monoresistant tuberculosis in Western Cape, South Africa(2012) Mukinda, Fidele K.; Theron D.; Van Der Spuy G.D.; Jacobson K.R.; Roscher M.; Streicher E.M.; Musekiwa A.; Coetzee G.J.; Victor T.C.; Marais B.J.; Nachega J.B.; Warren R.M.; Schaaf H.S.SETTING: Brewelskloof Hospital, Western Cape, South Africa. OBJECTIVES: To verify the perceived increase in rifampicin monoresistant tuberculosis (RMR-TB) in the Cape Winelands-Overberg region and to identify potential risk factors. DESIGN: A retrospective descriptive study of trends in RMR-TB over a 5-year period (2004-2008), followed by a case-control study of RMR and isoniazid (INH) monoresistant TB cases, diagnosed from April 2007 to March 2009, to assess for risk factors. RESULTS: The total number of RMR-TB cases more than tripled, from 31 in 2004 to 98 in 2008. The calculated doubling time was 1.63 years (95%CI 1.18-2.66). For the assessment of risk factors, 95 RMR-TB cases were objectively verified on genotypic and phenotypic analysis. Of 108 specimens genotypically identified as RMR cases, 13 (12%) were misidentified multidrugresistant TB. On multivariate analysis, previous use of antiretroviral therapy (OR 6.4, 95%CI 1.3-31.8), alcohol use (OR 4.8, 95%CI 2.0-11.3) and age ≥40 years (OR 5.8, 95%CI 2.4-13.6) were significantly associated with RMR-TB. CONCLUSION: RMR-TB is rapidly increasing in the study setting, particularly among patients with advanced human immunodeficiency virus (HIV) disease. Routine drug susceptibility testing should be considered in all TB-HIV co-infected patients, and absence of INH resistance should be confirmed phenotypically if genotypic RMR-TB is detected. © 2012 The Union.
- ItemSpread of an emerging Mycobacterium tuberculosis drug-resistant strain in the Western Cape of South Africa(2007) Victor T.C.; Streicher E.M.; Kewley C.; Jordaan A.M.; Van Der Spuy G.D.; Bosman M.; Louw H.; Murray M.; Young D.; Van Helden P.D.; Warren R.M.BACKGROUND: South Africa has a high burden of drug-resistant tuberculosis (TB). METHODS: Routine drug susceptibility testing was performed prospectively over a 2-year period on Mycobacterium tuberculosis isolates in two health districts of the Western Province, South Africa. A cluster of drug-resistant strains that shared a rare mutation in katG315 was found in 64 of the 450 cases identified as having been infected with drug-resistant TB. Isolates belonging to this cluster were phenotypically and genotypically characterised. Epidemiological and clinical characteristics were used to identify mechanisms leading to the acquisition and spread of this drug-resistant strain. RESULTS: An outbreak of an emerging non-Beijing drug-resistant strain infecting 64 pulmonary tuberculosis (PTB) cases was identified. This previously undetected genotype (now designated DRF150) is characterised by five IS6110 insertions, specific spoligotypes and high levels of resistance to the first-line TB medications isoniazid, streptomycin and rifampicin. In 45% of the cases it is also resistant to ethambutol and pyrazinamide. Key factors leading to the development and spread of this drug-resistant genotype were inappropriate chemotherapy, poor adherence to treatment and prolonged periods of infectiousness due to delays in susceptibility testing. CONCLUSIONS: Molecular markers allowed early identification of an emerging non-Beijing drug-resistant strain. © 2007 The Union.
- ItemThe role of molecular epidemiology in low-income, high-burden countries(2009) Van Der Spuy G.D.; Warren R.M.; Van Helden P.D.[No abstract available]