Spectrum of
            <i>pncA</i>
            Mutations in Multidrug-Resistant
            <i>Mycobacterium tuberculosis</i>
            Isolates Obtained in Latvia

Tracevska, Tatjana; Jansone, Inta; Baumanis, Viesturs; Nodieva, Anda; Marga, Olgerts; Šķenders, Ģirts

doi:10.1128/aac.48.8.3209-3210.2004

Cited by 15 publications

(15 citation statements)

References 12 publications

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“…tuberculosis clinical isolates. According to WHO region, five [ 60 , 68 , 69 , 78 , 102 ] articles were from Africa, 14 [ 27 , 70 – 72 , 79 , 81 – 83 , 97 , 100 , 105 , 107 , 114 , 120 ] from the Americas, two [ 80 , 92 ] from the Eastern Mediterranean, 17 [ 61 , 62 , 84 – 86 , 93 , 96 , 103 , 104 , 106 , 108 – 110 , 115 – 117 , 119 ] from Europe, six [ 59 , 63 , 73 , 118 , 121 , 123 ] from South East Asia, and 22 [ 64 – 67 , 74 – 77 , 87 – 91 , 94 , 95 , 98 , 99 , 101 , 111 – 113 , 122 ] from the Western Pacific. A SNP in the ...…”

Section: Resultsmentioning

confidence: 99%

A Global Perspective on Pyrazinamide Resistance: Systematic Review and Meta-Analysis

et al. 2015

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BackgroundPyrazinamide (PZA) is crucial for tuberculosis (TB) treatment, given its unique ability to eradicate persister bacilli. The worldwide burden of PZA resistance remains poorly described.MethodsSystematic PubMed, Science Direct and Scopus searches for articles reporting phenotypic (liquid culture drug susceptibility testing or pyrazinamidase activity assays) and/or genotypic (polymerase chain reaction or DNA sequencing) PZA resistance. Global and regional summary estimates were obtained from random-effects meta-analysis, stratified by presence or risk of multidrug resistant TB (MDR-TB). Regional summary estimates were combined with regional WHO TB incidence estimates to determine the annual burden of PZA resistance. Information on single nucleotide polymorphisms (SNPs) in the pncA gene was aggregated to obtain a global summary.ResultsPooled PZA resistance prevalence estimate was 16.2% (95% CI 11.2-21.2) among all TB cases, 41.3% (29.0-53.7) among patients at high MDR-TB risk, and 60.5% (52.3-68.6) among MDR-TB cases. The estimated global burden is 1.4 million new PZA resistant TB cases annually, about 270,000 in MDR-TB patients. Among 1,815 phenotypically resistant isolates, 608 unique SNPs occurred at 397 distinct positions throughout the pncA gene.InterpretationPZA resistance is ubiquitous, with an estimated one in six incident TB cases and more than half of all MDR-TB cases resistant to PZA globally. The diversity of SNPs across the pncA gene complicates the development of rapid molecular diagnostics. These findings caution against relying on PZA in current and future TB drug regimens, especially in MDR-TB patients.

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Section: Resultsmentioning

confidence: 99%

A Global Perspective on Pyrazinamide Resistance: Systematic Review and Meta-Analysis

et al. 2015

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“…Globally reported pncA mutations (n=210) were obtained by compilation of the missense mutations associated with PZA-resistance, reported in the literature until December 2008 (Hirano et al, 1997; Scorpio et al, 1997; Sreevatsan et al, 1997; Lemaitre et al, 1999; Marttila et al, 1999; Mestdagh et al, 1999; Brown et al, 2000; Cheng et al, 2000; Hou et al, 2000; Bishop et al, 2001; Lemaitre et al, 2001; Park et al, 2001; Endoh et al, 2002; Lee et al, 2002; Suzuki et al, 2002; Huang et al, 2003; Miyagi et al, 2004; Portugal et al, 2004; Post et al, 2004; Tracevska et al, 2004; Denkin et al, 2005; McCammon et al, 2005; Rodrigues Vde et al, 2005; Barco et al, 2006; Martin et al, 2006; Aragon et al, 2007; Sekiguchi et al, 2007; Jureen et al, 2008; Mphahlele et al, 2008). …”

Section: Methodsmentioning

confidence: 99%

Peruvian and globally reported amino acid substitutions on the Mycobacterium tuberculosis pyrazinamidase suggest a conserved pattern of mutations associated to pyrazinamide resistance

Zimic¹,

Sheen²,

Quiliano³

et al. 2010

Infection, Genetics and Evolution

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Resistance to pyrazinamide in Mycobacterium tuberculosis is usually associated with a reduction of pyrazinamidase activity caused by mutations in pncA, the pyrazinamidase coding gene. Pyrazinamidase is a hydrolase that converts pyrazinamide, the antituberculous drug against the latent stage, to the active compound, pyrazinoic acid. To better understand the relationship between pncA mutations and pyrazinamide-resistance, it is necessary to analyze the distribution of pncA mutations from pyrazinamide resistant strains.We determined the distribution of Peruvian and globally reported pncA missense mutations from M. tuberculosis clinical isolates resistant to pyrazinamide. The distributions of the single amino acid substitutions were compared at the secondary-structure-domains level. The distribution of the Peruvian mutations followed a similar pattern as the mutations reported globally. A consensus clustering of mutations was observed in hot-spot regions located in the metal coordination site and to a lesser extent in the active site of the enzyme. Author's contributions MZ, PS and RHG conceived the general idea and participated in preparing the manuscript. AG and MQ carried out the searching of global pncA mutations, selected the sequences that meet the inclusion criteria and drafted the manuscript. MZ conducted the statistical analysis.

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“…The lack of validation by retesting may leave false resistance unidentified, thereby reducing sensitivity. This might partly account for the relatively low sensitivity estimates in the range of 67% to 85% from nine studies included in the initial meta-analysis (3,4,7,26,30,31,66,69,75). The same problem might also apply to the Wayne assay; only 16 out of 33 included studies on the Wayne assay mentioned retesting pyrazinamide-resistant isolates that had pyrazinamidase activity in the presence of a discrepancy between reference and tested assays (2,10,12,13,24,29,36,42,45,47,49,52,57,58,61,64).…”

Section: Findings and Conclusionmentioning

confidence: 99%

“…The median prevalence of pyrazinamide resistance in culture isolates of MDR M. tuberculosis, based on 14 studies included in the initial meta-analysis, was 51% (range, 31 to 89%) (1,2,4,6,8,17,24,26,42,49,59,63,69,75). The median prevalence of pyrazinamide resistance in culture isolates of M. tuberculosis susceptible to both isoniazid and rifampin, based on eight studies, was 5% (range, 0% to 9%) (6,17,24,26,34,49,59,63).…”

Section: Findings and Conclusionmentioning

confidence: 99%

Pyrazinamide Susceptibility Testing in Mycobacterium tuberculosis: a Systematic Review with Meta-Analyses

Chang

Yew

Zhang

2011

Antimicrob Agents Chemother

120

102

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3Standard culture-based testing of the susceptibility of Mycobacterium tuberculosis to pyrazinamide is difficult to perform. This systematic review with meta-analyses evaluated the roles of molecular assays targeting pncA and of pyrazinamidase assays. PubMed and Embase were searched for relevant publications in English. Sensitivity and specificity were estimated in bivariate random-effects models. Of 128 articles identified, 73 sets of data involving culture isolates were initially included in meta-analyses. Summary estimates of sensitivity and specificity, respectively, were 87% and 93% for PCR-DNA sequencing (n ‫؍‬ 29), 75% and 95% for PCR-singlestranded conformation polymorphism (SSCP) (n ‫؍‬ 5), 96% and 97% for a mixture of other molecular assays (n ‫؍‬ 6), and 89% and 97% for pyrazinamidase assays using the Wayne method (n ‫؍‬ 33). The median prevalence (range) of pyrazinamide resistance was 51% (31% to 89%) in multidrug-resistant M. tuberculosis isolates and 5% (0% to 9%) in non-multidrug-resistant isolates. Excluding studies with possibly considerable false resistance in the reference assay gave the following estimates of sensitivity and specificity, respectively: 92% and 93% for PCR-DNA sequencing (n ‫؍‬ 20), 98% and 96% for other molecular assays (n ‫؍‬ 5), and 91% and 97% for the Wayne assay (n ‫؍‬ 27). The Wayne assay had significant funnel plot asymmetry, so the test performance might have been overestimated. Considering the prevalence of pyrazinamide resistance in different clinical settings, PCR-DNA sequencing, and possibly other molecular assays targeting pncA, can detect pyrazinamide resistance in multidrug-resistant M. tuberculosis isolates, with predictive values largely exceeding 90%, and rule out pyrazinamide resistance in non-multidrug-resistant isolates, with predictive values exceeding 99%. Molecular assays are probably the way forward for detecting pyrazinamide resistance.

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Spectrum of pncA Mutations in Multidrug-Resistant Mycobacterium tuberculosis Isolates Obtained in Latvia

Cited by 15 publications

References 12 publications

A Global Perspective on Pyrazinamide Resistance: Systematic Review and Meta-Analysis

A Global Perspective on Pyrazinamide Resistance: Systematic Review and Meta-Analysis

Peruvian and globally reported amino acid substitutions on the Mycobacterium tuberculosis pyrazinamidase suggest a conserved pattern of mutations associated to pyrazinamide resistance

Pyrazinamide Susceptibility Testing in Mycobacterium tuberculosis: a Systematic Review with Meta-Analyses

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