Molecular Epidemiological Study of Pyrazinamide-Resistance in Clinical Isolates of Mycobacterium tuberculosis from South India

Muthuraj, Muthusivaramapandian; Jagadeesan, Sridharan; Ayalusamy, Nisha; Sreenivasan, Manupriya; Prabhu, Sambamurthy Sangamesvara; Muthuraj, Usharani; Senthilkumar, Kamatchiyammal; Veerappan, Saroja

doi:10.3390/ijms11072670

Cited by 22 publications

(12 citation statements)

References 23 publications

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“…There was no pncA mutation in all 109 PZAsusceptible isolates (0%), but 44 out of 52 (84.6%) PZA-resistant isolates showed pncA mutations (Table 1), which showed the strong correlation between mutations in pncA and phenotypic resistance to PZA and supported the finding that a pncA mutation could cause PZA resistance in M. tuberculosis (2). The pncA gene mutation frequency in the PZA phenotypically resistant strains here is much higher than those reported previously in other provinces of China (27 to 48.1%) (13-17) but similar to those from other countries (69% to 98.8%) in which the PZA phenotypic resistance was determined by the BT960 or 460TB system (18)(19)(20)(21). It is well known that testing for the susceptibility of PZA in vitro is very hard (3) because PZA only has very weak activity even in an acid-pH environment, in which even the control without PZA could not grow well.…”

contrasting

confidence: 41%

Role of pncA and rpsA Gene Sequencing in Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis Isolates from Southern China

Tan

Zhang

et al. 2014

J Clin Microbiol

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contrasting

confidence: 41%

Role of pncA and rpsA Gene Sequencing in Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis Isolates from Southern China

Tan

Zhang

et al. 2014

J Clin Microbiol

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“…tuberculosis clinical isolates. According to WHO regions, 8 [ 39 , 59 , 60 , 68 , 69 , 78 ] studies were from African region, 20 [ 29 , 30 , 38 , 40 , 41 , 43 – 47 , 59 , 70 – 72 , 79 – 83 ] from the Americas, 3 [ 31 , 48 , 80 ] from the Eastern Mediterranean, 20 [ 32 , 33 , 49 – 54 , 59 , 61 , 62 , 84 – 86 ] from European, 17 [ 34 – 36 , 47 , 55 , 56 , 59 , 63 , 73 , 80 ] from South East Asia, and 23 [ 37 , 42 , 57 , 58 , 64 – 67 , 74 – 77 , 80 , 86 – 90 ] from the Western Pacific region ( Fig 2 ). Most (53/91) [ 30 , 35 , …”

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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“…1 illustrates the breakdown of the number of articles excluded because of the specified criteria. Of the 61 studies, the earliest study was from 1996, while 20 (33%) were published in the last 3 years (8,25,30,31,35,41,43,47,60,70,73,75,77,(81)(82)(83)(84)(85). In total, there were 6,089 isolates, 2,760 phenotypically PZA r and 3,329 phenotypically PZA s , in the 61 articles that had at least the pncA coding region sequenced.…”

Section: Description Of Included Studies a Search Through Pubmed (Mementioning

confidence: 99%

Systematic Review of Mutations in Pyrazinamidase Associated with Pyrazinamide Resistance in Mycobacterium tuberculosis Clinical Isolates

Ramirez-Busby

Valafar

2015

Antimicrob Agents Chemother

105

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Pyrazinamide (PZA) is an important first-line drug in the treatment of tuberculosis (TB) and of significant interest to the HIV-infected community due to the prevalence of TB-HIV coinfection in some regions of the world. The mechanism of resistance to PZA is unlike that of any other anti-TB drug. The gene pncA, encoding pyrazinamidase (PZase), is associated with resistance to PZA. However, because single mutations in PZase have a low prevalence, the individual sensitivities are low. Hundreds of distinct mutations in the enzyme have been associated with resistance, while some only appear in susceptible isolates. This makes interpretation of molecular testing difficult and often leads to the simplification that any PZase mutation causes resistance. This systematic review reports a comprehensive global list of mutations observed in PZase and its promoter region in clinical strains, their phenotypic association, their global frequencies and diversity, the method of phenotypic determination, their MIC values when given, and the method of MIC determination and assesses the strength of the association between mutations and phenotypic resistance to PZA. In this systematic review, we report global statistics for 641 mutations in 171 (of 187) codons from 2,760 resistant strains and 96 mutations from 3,329 susceptible strains reported in 61 studies. For diagnostics, individual mutations (or any subset) were not sufficiently sensitive. Assuming similar error profiles of the 5 phenotyping platforms included in this study, the entire enzyme and its promoter provide a combined estimated sensitivity of 83%. This review highlights the need for identification of an alternative mechanism(s) of resistance, at least for the unexplained 17% of cases.

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Molecular Epidemiological Study of Pyrazinamide-Resistance in Clinical Isolates of Mycobacterium tuberculosis from South India

Cited by 22 publications

References 23 publications

Role of pncA and rpsA Gene Sequencing in Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis Isolates from Southern China

Role of pncA and rpsA Gene Sequencing in Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis Isolates from Southern China

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

Systematic Review of Mutations in Pyrazinamidase Associated with Pyrazinamide Resistance in Mycobacterium tuberculosis Clinical Isolates

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