Browsing by Author "Streicher E.M."
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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.
- ItemEmergence and treatment of multidrug resistant (MDR) and extensively drug-resistant (XDR) tuberculosis in South Africa(2011-10-13) Streicher E.M.; Muller B.; Chihota V.; Mlambo C.; Tait M.; Pillay M.; Trollip A.; Hoek K.G.P.; Sirgel F.A.; Gey van Pittius N.C.; van Helden P.D.; Victor T.C.; Warren R.M.Drug resistant tuberculosis (TB) has reached alarming proportions in South Africa, draining valuable resources that are needed to fight drug susceptible TB. It is currently estimated that 9.6% of all TB cases have multi-drug resistant (MDR)-TB, thereby ranking South Africa as one of the highest MDR-TB burden countries in the world. Molecular epidemiological studies have demonstrated the complexity of the epidemic and have clearly shown that the epidemic is driven by transmission as a consequence of low cases detection and diagnostic delay. The latter has in turn fueled the amplification of drug resistance, ultimately leading to the emergence of extensively drug resistant (XDR)-TB. Despite the introduction of new drugs to combat this scourge, culture conversion rates for XDR-TB remain below 20%. Failure to achieve cure may be explained from DNA sequencing results which have demonstrated mutations in 7 genes encoding resistance to at least 8 anti-TB drugs. This review shows how molecular epidemiology has provided novel insights into the MDR-TB epidemic in South Africa and thereby has highlighted the challenges that need to be addressed regarding the diagnosis and treatment of MDR-TB. An important step towards for curbing this epidemic will be collaboration between clinicians, laboratories and researchers to establish scientific knowledge and medical expertise to more efficiently guide public health policy.
- ItemErratum: Genotypic and Phenotypic Characterization of Drug-Resistant Mycobacterium tuberculosis Isolates from Rural Districts of the Western Cape Province of South Africa (Journal of Clinical Microbiology (2004) 42, 2 (891-894))(2004) Streicher E.M.; Warren R.M.; Kewley C.; Simpson J.; Rastogi N.; Sola C.; Filliol I.; Van Der Spuy G.D.; Van Helden P.D.; Victor T.C.[No abstract available]
- 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.
- ItemgyrA mutations and phenotypic susceptibility levels to ofloxacin and moxifloxacin in clinical isolates of Mycobacterium tuberculosis(2012) Sirgel F.A.; Warren R.M.; Streicher E.M.; Victor T.C.; Van helden P.D.; Bottger E.C.Objectives: To compare mutations in the quinolone resistance-determining region of the gyrA gene and flanking sequences with the MICs of ofloxacin and moxifloxacin for Mycobacterium tuberculosis. Methods: The presence of mutations in 177 drug-resistant M. tuberculosis isolates was determined by DNA sequencing and the MICs quantified by MGIT 960. Results: Single nucleotide polymorphisms were detected at codons 94 (n = 30), 90 (n = 12), 91 (n = 3), 89 (n = 1), 88 (n = 1) and 80 (n = 1). Four isolates with double mutations D94G plus A90V (n = 2) and D94G plus D94N (n = 2) reflect mixed populations. Agreement between genotypic and phenotypic susceptibility was high (≥97%) for both drugs. Mutant isolates had an MIC 50 of 8.0 mg/L and an MIC 90 of >10 mg/L for ofloxacin compared with an MIC 50 and MIC 90 of 2.0 mg/L for moxifloxacin. Codons 94 and 88 were linked to higher levels of fluoroquinolone resistance compared with codons 90, 91 and 89. The MIC distributions for the wild-type isolates ranged from ≤0.5 to 2.0 mg/L for ofloxacin and from ≤0.125 to 0.25 mg/L for moxifloxacin. However, 96% of the isolates with genetic alterations had MICs ≤2.0 mg/L for moxifloxacin, which is within its achievable serum levels. Conclusions: This study provides quantitative evidence that the addition of moxifloxacin to extensively drug-resistant tuberculosis (XDR-TB) regimens based on a clinical breakpoint of 2.0 mg/L has merit. The use of moxifloxacin in the treatment of multidrug-resistant tuberculosis may prevent the acquisition of additional mutations and development of XDR-TB. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
- ItemIdentification of MDR-TB Beijing/W and other Mycobacterium tuberculosis genotypes in Nairobi, Kenya(2004) Githui W.A.; Jordaan A.M.; Juma E.S.; Kinyanjui P.; Karimi F.G.; Kimwomi J.; Meme H.; Mumbi P.; Streicher E.M.; Warren R.; Van Helden P.D.; Victor T.C.SETTING: Suspected tuberculosis (TB) patients in Nairobi, Kenya. OBJECTIVE: To identify the presence of multidrug-resistant (MDR) Beijing/W type and other genotypes of Mycobacterium tuberculosis. METHODS: Thirty-three isolates resistant to one or more drugs (resistance ratio method), including 15 MDR isolates and 40 susceptible isolates selected at random, were analysed by dot-blot hybridisation for mutations associated with resistance to isoniazid, rifampicin, streptomycin and ethambutol. All strains were genotypically classified using spoligotyping. RESULTS: Of the 33 drug-resistant isolates, 21 (64%) were from males and 12 (36%) were from females. Mutations associated with resistance to isoniazid (katG 315) and rifampicin (rpoB526, 531) were confirmed in 83.3% and 100% of the isolates, respectively, and in 87% of the MDR isolates. Mutations were detected in 25% and 71.5% of the isolates resistant to streptomycin (rpsL43) and ethambutol (embB306), respectively. No mutations were detected in drug-susceptible isolates. Spoligotyping grouped the isolates into 25 groups. Ten of these groups corresponded to previously identified strain groups, including seven families in the international database. One of these families (CAS1) comprised six (40%) of the 15 MDR isolates. Another family (Beijing) had six (8.3%) isolates, of which two (33.3%) were MDR (Beijing/W). CONCLUSION: This study is the first in Kenya and the second in sub-Saharan Africa to report the presence of MDR Beijing/W type and other possible drug-resistant outbreak strains. Application of the molecular techniques and markers will allow us to monitor the spread of existing drug-resistant strains and the appearance of new ones.
- IteminhA promoter mutations: A gateway to extensively drug-resistant tuberculosis in South Africa?(2011) Muller B.; Streicher E.M.; Hoek K.G.P.; Tait M.; Trollip A.; Bosman M.E.; Coetzee G.J.; Chabula-Nxiweni E.M.; Hoosain E.; Gey Van Pittius N.C.; Victor T.C.; Van Helden P.D.; Warren R.M.SETTING: Western Cape and Eastern Cape Provinces, South Africa. OBJECTIVE: To assess the potential association between the evolution of extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis and mutations in the inhA promoter or the katG gene. DESIGN: Analysis of the frequency distribution of isoniazid (INH) resistance conferring mutations in a population sample of drug-resistant isolates of M. tuberculosis. RESULTS: In the Western Cape and Eastern Cape Provinces, the percentage of isolates exhibiting inhA promoter mutations increased significantly from respectively 48.4% and 62.4% in multidrug-resistant tuberculosis (MDR-TB) isolates to 85.5% and 91.9% in XDR isolates. Data from the Western Cape revealed that significantly more XDR-TB isolates showed mutations in the inhA promoter than in katG (85.5% vs. 60.9%, P < 0.01), while the respective proportions were equal for INH-resistant non-MDR-TB isolates (∼30%). CONCLUSIONS: inhA promoter mutations are strongly associated with XDR-TB in South Africa. We suggest that this is due to the dual resistance to ethionamide and (low-dose) INH conferred by inhA promoter mutations. The use of molecular probe assays such as the Geno-Type® MTBDRplus assay, which allows the detection of inhA promoter mutations, could enable treatment regimens to be adjusted depending on the pharmacogenetic properties of the mutations detected. © 2011 The Union.
- ItemMicroevolution of the direct repeat region of Mycobacterium tuberculosis: Implications for interpretation of spoligotyping data(2002) Warren R.M.; Streicher E.M.; Sampson S.L.; Van der Spuy G.D.; Richardson M.; Nguyen D.; Behr M.A.; Victor T.C.; Van Helden P.D.The direct repeat (DR) region has been determined to be an important chromosomal domain for studying the evolution of Mycobacterium tuberculosis. Despite this, very little is known about microevolutionary events associated with clonal expansion and how such events influence the interpretation of both restriction fragment length polymorphism (RFLP) and spoligotype data. This study examined the structure of the DR region in three independently evolving lineages of M. tuberculosis with a combination of DR-RFLP, spoligotyping, and partial DNA sequencing. The results show that the duplication of direct variable repeat (DVR) sequences and single-nucleotide polymorphisms is rare; conversely, the deletion of DVR sequences and IS6110-mediated mutation is observed frequently. Deletion of either single or contiguous DVR sequences was observed. The deletion of adjacent DVR sequences occurred in a dependent manner rather than as an accumulation of independent events. Insertion of IS6110 into either the direct repeat or spacer sequences influenced the spoligotype pattern, resulting in apparent deletion of DVR sequences. Homologous recombination between adjacent IS6110 elements led to extensive deletion in the DR region, again demonstrating a dependent evolutionary mechanism. Different isolates from the same strain family and isolates from different strain families were observed to converge to the same spoligotype pattern. In conclusion, the binary data of the spoligotype are unable to provide sufficient information to accurately establish genotypic relationships between certain clinical isolates of M. tuberculosis. This has important implications for molecular epidemiologic strain tracking and for the application of spoligotype data to phylogenetic analysis of M. tuberculosis isolates.
- ItemModification of the QuantiFERON-TB Gold (In-Tube) assay for the diagnosis of Mycobacterium bovis infection in African buffaloes (Syncerus caffer)(2011) Parsons S.D.C.; Cooper D.; McCall A.J.; McCall W.A.; Streicher E.M.; le Maitre N.C.; Muller A.; Gey van Pittius N.C.; Warren R.M.; van Helden P.D.African buffaloes (Syncerus caffer) are the most significant wildlife maintenance hosts of Mycobacterium bovis, the causative organism of bovine tuberculosis (BTB). Current diagnostic tests for the detection of M. bovis infection in free-ranging buffaloes have numerous limitations and we wished to evaluate a modification to a human TB assay, the QuantiFERON-TB Gold (In-Tube) assay (QFT), as a practical diagnostic test for BTB in buffaloes. One hundred and seventy-five buffaloes were tested using the single intradermal comparative tuberculin test (SICTT) and a modified QFT (mQFT). An appropriate cut-off point for the mQFT was derived from SICTT results using receiver operator characteristic curve analysis. Twenty-six SICTT-positive buffaloes were killed and subjected to necropsy, and selected tissues were processed for mycobacterial culture and speciation. An optimal cut-off point for the mQFT was calculated as 66. pg/ml. The assay correctly detected 39/40 SICTT-positive buffaloes and 129/134 TST-negative buffaloes and M. bovis was cultured from 21/26 slaughtered SICTT/mQFT-positive animals. The mQFT shows promise as a practical test for M. bovis infection in buffaloes and shows a sensitivity and specificity at least similar to that of the TST. © 2011 Elsevier B.V.
- ItemMutations in the rrs A1401G gene and phenotypic resistance to amikacin and capreomycin in mycobacterium tuberculosis(2012) Sirgel F.A.; Tait M.; Warren R.M.; Streicher E.M.; Bottger E.C.; Van Helden P.D.; Gey Van Pittius N.C.; Coetzee G.; Hoosain E.Y.; Chabula-Nxiweni M.; Hayes C.; Victor T.C.; Trollip A.The aminoglycosides amikacin (AMK)/kanamycin (KAN) and the cyclic polypeptide capreomycin (CAP) are important injectable drugs in the treatment of multidrug-resistant tuberculosis. Cross-resistance among these drug classes occurs and information on the minimum inhibitory concentrations (MICs), above the normal wild-type distribution, may be useful in identifying isolates that are still accessible to drug treatment. Isolates from the Eastern Cape Province of South Africa were subjected to DNA sequencing of the rrs (1400-1500 region) and tlyA genes. Sequencing data were compared with (i) conventional susceptibility testing at standard critical concentrations (CCs) on Middlebrook 7H11 agar and (ii) MGIT 960-based MIC determinations to assess the presence of AMK- and CAP-resistant mutants. Isolates with an rrs A1401G mutation showed high-level resistance to AMK (>20mg/L) and decreased phenotypic susceptibility to CAP (MICs 10-15mg/L). The MICs of CAP were below the bioavailability of the drug, which suggests that it may still be effective against multi- or extensively drug resistant tuberculosis [M(X)DR-TB]. Agar-based CC testing was found to be unreliable for resistance recognition of CAP in particular. © 2012 Mary Ann Liebert, Inc.
- ItemMycobacterium tuberculosis population structure determines the outcome of genetics-based second-line drug resistance testing(2012) Streicher E.M.; Bergval I.; Dheda K.; Bottger E.C.; Gey Van Pittius N.C.; Bosman M.; Coetzee G.; Anthony R.M.; Van Helden P.D.; Victor T.C.; Warren R.M.The global emergence of multidrug-resistant tuberculosis has highlighted the need for the development of rapid tests to identify resistance to second-line antituberculosis drugs. Resistance to fluoroquinolones and aminoglycosides develops through nonsynonymous single nucleotide polymorphisms in the gyrA and gyrB genes and the rrs gene, respectively. Using DNA sequencing as the gold standard for the detection of mutations conferring resistance, in conjunction with spoligotyping, we demonstrated heteroresistance in 25% and 16.3% of Mycobacterium tuberculosis isolates resistant to ofloxacin and amikacin, respectively. Characterization of follow-up isolates from the same patients showed that the population structure of clones may change during treatment, suggesting different phases in the emergence of resistance. The presence of underlying mutant clones was identified in isolates which failed to show a correlation between phenotypic resistance and mutation in the gyrA or rrs gene. These clones harbored previously described mutations in either the gyrA or rrs gene, suggesting that rare mutations conferring resistance to ofloxacin or amikacin may not be as important as was previously thought. We concluded that the absence of a correlation between genotypic and phenotypic resistance implies an early phase in the emergence of resistance within the patient. Thus, the diagnostic utility of genetics-based drug susceptibility tests will depend on the proportion of patients whose bacilli are in the process of acquiring resistance in the study setting. These data have implications for the interpretation of molecular and microbiological diagnostic tests for patients with drug-susceptible and drug-resistant tuberculosis who fail to respond to treatment and for those with discordant results. Copyright © 2012, American Society for Microbiology. All Rights Reserved.
- 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.
- ItemPredominance of a single genotype of Mycobacterium tuberculosis in regions of Southern Africa(2007) Chihota V.; Apers L.; Mungofa S.; Kasongo W.; Nyoni I.M.; Tembwe R.; Mbulo G.; Tembo M.; Streicher E.M.; Van Der Spuy G.D.; Victor T.C.; Van Helden P.; Warren R.M.SETTING: Zimbabwe and Zambia. OBJECTIVE: To determine the genetic diversity of Mycobacterium tuberculosis strains isolated from tuberculosis (TB) patients in Zimbabwe and Zambia. DESIGN: M. tuberculosis isolates cultured from TB patients presenting at referral hospitals in Zimbabwe and health care clinics in Zambia were characterised by IS6110 genotyping and/or spoligotyping using internationally standardised methods. Genotypic data were compared to those from Cape Town and the SpolDB3.0 database. RESULTS: A predominant group of strains could be identified among 116/246 (47.2%) Zimbabwean isolates by their characteristic IS6110-banding pattern and unique spoligotype signature, where spacers 21-24, 27-30 and 33-36 were deleted. Comparison with strains from Cape Town showed that they were closely related to a family of strains present in 2.3% of Cape Town patients. Comparison of the spoligotypes with those obtained from 114 isolates from Zambia showed that 74 (65%) of these isolates had the same spoligotype signature. Spoligotypes in the SpolDB3.0 database showed that this group of strains was rarely isolated in other parts of the world, but was commonly isolated in Southern Africa. CONCLUSION: A predominant group of strains infecting approximately half of the patients in the study are major contributors to the TB epidemic in this region. We have designated this group of strains the Southern Africa 1 (SAF1) family. © 2007 The Union.
- 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.
- ItemSpoligotype signatures in the Mycobacterium tuberculosis complex(2007) Streicher E.M.; Victor T.C.; Van Der Spuy G.; Sola C.; Rastogi N.; Van Helden P.D.; Warren R.M.Evolution of the direct repeat region in Mycobacterium tuberculosis has created unique spoligotype signatures specifically associated with IS6110-defined strain families. Spoligotyping signatures may enable the analysis of the strain population structure in different settings and will enable the rapid identification of strain families that acquire drug resistance or escape protective immunity in drug and vaccine trials. Copyright © 2007, American Society for Microbiology. All Rights Reserved.
- ItemSpread of a low-fitness drug-resistant Mycobacterium tuberculosis strain in a setting of high human immunodeficiency virus prevalence(2008) Strauss O.J.; Warren R.M.; Jordaan A.; Streicher E.M.; Hanekom M.; Falmer A.A.; Albert H.; Trollip A.; Hoosain E.; Van Helden P.D.; Victor T.C.The fitness cost associated with the evolution of resistance to rifampin in Mycobacterium tuberculosis may be different in clinical isolates compared to in vitro-generated mutants. An atypical Beijing strain (attenuated phenotype) demonstrated the ability to spread despite acquiring resistance to rifampin. Transmission was linked to human immunodeficiency virus coinfection (P = 0.029), raising concern for the spread of drug resistance in vulnerable populations. Copyright © 2008, American Society for Microbiology. All Rights Reserved.
- 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.
- ItemTreatment outcomes of isoniazid-resistant tuberculosis patients, Western Cape Province, South Africa(2011) Jacobson K.R.; Theron D.; Victor T.C.; Streicher E.M.; Warren R.M.; Murray M.B.We report treatment outcomes from a retrospective cohort of patients with isoniazid-monoresistant tuberculosis in rural South Africa. Sixteen percent of patients had poor outcomes, 61% of whom progressed to multidrug-resistant tuberculosis. These data reveal the need for early identification and aggressive follow-up of isoniazid monoresistance to increase treatment success. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
- ItemUse of spoligotyping for accurate classification of recurrent tuberculosis(2002) Warren R.M.; Streicher E.M.; Charalambous S.; Churchyard G.; Van der Spuy G.D.; Grant A.D.; Van Helden P.D.; Victor T.C.The spoligotyping method has become an important tool for the tracking of Mycobacterium tuberculosis strains in different epidemiological settings. In this study, we demonstrate the ability of the spoligotyping technique to accurately determine the pathogenetic mechanism of recurrent disease. This methodology has advantages over conventional restriction fragment length polymorphism methods which may be useful in large-scale intervention studies.