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

Whitfield MG, Soeters HM, Warren RM, York T, Sampson SL, Streicher EM, van Helden PD, van Rie A - PLoS ONE (2015)

Bottom Line: Information on single nucleotide polymorphisms (SNPs) in the pncA gene was aggregated to obtain a global summary.Among 1,815 phenotypically resistant isolates, 608 unique SNPs occurred at 397 distinct positions throughout the pncA gene.The diversity of SNPs across the pncA gene complicates the development of rapid molecular diagnostics.

View Article: PubMed Central - PubMed

Affiliation: SA MRC Centre for TB Research, Stellenbosch University, South Africa; DST/NRF Centre of Excellence for Biomedical TB Research, Stellenbosch University, South Africa; Division of Molecular Biology and Human Genetics, Stellenbosch University, South Africa; Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa.

ABSTRACT

Background: Pyrazinamide (PZA) is crucial for tuberculosis (TB) treatment, given its unique ability to eradicate persister bacilli. The worldwide burden of PZA resistance remains poorly described.

Methods: Systematic 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.

Results: Pooled 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.

Interpretation: PZA 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.

No MeSH data available.


Related in: MedlinePlus

Forest plot for the summary estimates of pyrazinamide prevalence by WHO region and presence or risk of MDR-TB.Abbreviations: CI, confidence interval; DST, drug susceptibility test; MDR-TB, multi-drug resistant tuberculosis; N/A, not applicable; WHO, world health organization. MDR-TB was defined as an isolate being resistant to RIF and INH. High risk of MDR-TB was defined as an isolate being resistant to at least one anti-TB drug. *Any TB was defined as the inclusion of patients independent of drug resistance profile.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4517823&req=5

pone.0133869.g003: Forest plot for the summary estimates of pyrazinamide prevalence by WHO region and presence or risk of MDR-TB.Abbreviations: CI, confidence interval; DST, drug susceptibility test; MDR-TB, multi-drug resistant tuberculosis; N/A, not applicable; WHO, world health organization. MDR-TB was defined as an isolate being resistant to RIF and INH. High risk of MDR-TB was defined as an isolate being resistant to at least one anti-TB drug. *Any TB was defined as the inclusion of patients independent of drug resistance profile.

Mentions: PZA resistance is prevalent across the entire globe and has been reported in all six WHO-defined regions (Fig 3). The pooled summarized prevalence estimate of PZA resistance was 60.5% (95% CI 52.3–68.6%) in MDR-TB patients, 41.3% (95% CI 29.0–53.7%) in TB patients at high-risk of MDR-TB, and 16.2% (95% CI 11.2–21.2%) in studies including any TB patient irrespective of resistance profile. In all six WHO regions, the prevalence of PZA resistance was two to six times higher in MDR-TB patients compared to the population of all TB patients.


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

Whitfield MG, Soeters HM, Warren RM, York T, Sampson SL, Streicher EM, van Helden PD, van Rie A - PLoS ONE (2015)

Forest plot for the summary estimates of pyrazinamide prevalence by WHO region and presence or risk of MDR-TB.Abbreviations: CI, confidence interval; DST, drug susceptibility test; MDR-TB, multi-drug resistant tuberculosis; N/A, not applicable; WHO, world health organization. MDR-TB was defined as an isolate being resistant to RIF and INH. High risk of MDR-TB was defined as an isolate being resistant to at least one anti-TB drug. *Any TB was defined as the inclusion of patients independent of drug resistance profile.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4517823&req=5

pone.0133869.g003: Forest plot for the summary estimates of pyrazinamide prevalence by WHO region and presence or risk of MDR-TB.Abbreviations: CI, confidence interval; DST, drug susceptibility test; MDR-TB, multi-drug resistant tuberculosis; N/A, not applicable; WHO, world health organization. MDR-TB was defined as an isolate being resistant to RIF and INH. High risk of MDR-TB was defined as an isolate being resistant to at least one anti-TB drug. *Any TB was defined as the inclusion of patients independent of drug resistance profile.
Mentions: PZA resistance is prevalent across the entire globe and has been reported in all six WHO-defined regions (Fig 3). The pooled summarized prevalence estimate of PZA resistance was 60.5% (95% CI 52.3–68.6%) in MDR-TB patients, 41.3% (95% CI 29.0–53.7%) in TB patients at high-risk of MDR-TB, and 16.2% (95% CI 11.2–21.2%) in studies including any TB patient irrespective of resistance profile. In all six WHO regions, the prevalence of PZA resistance was two to six times higher in MDR-TB patients compared to the population of all TB patients.

Bottom Line: Information on single nucleotide polymorphisms (SNPs) in the pncA gene was aggregated to obtain a global summary.Among 1,815 phenotypically resistant isolates, 608 unique SNPs occurred at 397 distinct positions throughout the pncA gene.The diversity of SNPs across the pncA gene complicates the development of rapid molecular diagnostics.

View Article: PubMed Central - PubMed

Affiliation: SA MRC Centre for TB Research, Stellenbosch University, South Africa; DST/NRF Centre of Excellence for Biomedical TB Research, Stellenbosch University, South Africa; Division of Molecular Biology and Human Genetics, Stellenbosch University, South Africa; Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa.

ABSTRACT

Background: Pyrazinamide (PZA) is crucial for tuberculosis (TB) treatment, given its unique ability to eradicate persister bacilli. The worldwide burden of PZA resistance remains poorly described.

Methods: Systematic 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.

Results: Pooled 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.

Interpretation: PZA 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.

No MeSH data available.


Related in: MedlinePlus