Performance of Wayne assay for detection of pyrazinamide resistance in Mycobacterium tuberculosis: a meta-analysis study

Abstract

Conventional culture-based drug susceptibility testing (DST) of Mycobacterium tuberculosis to pyrazinamide (PZA) is time-consuming and difficult to perform. The current systematic review and meta-analysis was aimed to evaluate the diagnostic accuracy of Wayne assay against culture-based DSTs as the reference standard. We searched the MEDLINE/Pubmed, Embase, and Web of Science databases for the relevant records. The QUADAS-2 tool was used to assess the quality of the studies. Diagnostic accuracy measures (i.e., sensitivity and specificity) were pooled with a random-effects model. Statistical analyses were performed with STATA (version 14, Stata Corporation, College Station, TX, USA), RevMan (version 5.3; The Nordic Cochrane Centre, the Cochrane Collaboration, Copenhagen, Denmark), and Meta-DiSc (version 1.4, Cochrane Colloquium, Barcelona, Spain). A total of 31 articles comprising data for 2457 isolates of M. tuberculosis were included in the final analysis. The pooled sensitivity and specificity of the Wayne assay against all reference tests (the combination of BACTEC MGIT 960, BACTEC 460, and proportion method) were 86.6% (95% CI: 84.3-88.7) and 96.0% (95% CI: 94.8-97). The positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the curve (AUC) estimates were found to be 17.6 (95% CI: 10.5-29.3), 0.11 (95% CI: 0.06-0.20), 164 (95% CI: 83-320) and 97%, respectively. Deek's test result indicated no evidence for publication bias (P > 0.05). Although the current study shows that the Wayne test is sensitive and specific for detecting PZA resistance, it may be used in combination with conventional DSTs to diagnose PZA resistance accurately.

Exploring Diagnostic Methods for Drug-Resistant Tuberculosis: A Comprehensive Overview

“…However, applying less strict filters in WGS might cause more background noise and less specificity because sequencing artifacts or other contaminant bacteria could be reported as "true variants". The Wayne's test did not detect any HR [125]; these poor results are in contrast with a systematic review and meta-analysis, where Nasiri found that the sensitivity and specificity of the Wayne test were 86.6% and 96.0% [126].…”

Medicamento para Tuberculose em dose fixa combinada: um panorama dos fármacos rifampicina, isoniazida, pirazinamida e etambutol

“…As mutações no gene pncA do M. tuberculosis são o principal mecanismo de resistência a PZA, essas mutações alteram a dinâmica interna da enzima pirazinamidase / nicotinamidase e impedem a orientação correta da PZA para a enzima inibindo a conversão para sua forma ativa, o ácido pirazinóico (POA). No entanto, os testes de sensibilidade fenotípica a PZA atualmente aplicados são pouco confiáveis, demorados e difíceis de executar (CHE; BO;LIN;MODLIN;MARBACH;WERNGREN;MANSJO et al, 2021;NANGRAJ;UMBREEN;SAHARA et al, 2021;FARDSANEI;ARSHADI;DEIHIM et al, 2021;SHI, 2021).Embora seja responsável por menos efeitos adversos que INH e RIF, a PZA é conhecida por aumentar a produção de urato e, consequentemente, leva à hiperuricemia ao inibir a secreção de ácido úrico dos túbulos renais, aumentando o risco de outras doenças graves, como gota e formação de cálculos renais. A hiperuricemia induzida por PZA é uma queixa comum em pacientes, sendo um dos fatores que leva ao abandono do tratamento anti-TB (MUHAMMAD; MEHBOOB; ABBAS, 2021).3.4 SOBRE O FÁRMACO ETAMBUTOL O EMB é um agente antimicobacteriano usualmente administrado na forma de cloridrato em combinação com outros medicamentos anti-TB (NASIRI; FOOLADI; DABIRI; PORMOHAMMAD et al, 2016), que tem como vantagem sua ação sinérgica em combinação com PZA, INH ou RIF, inibindo a replicação do M. tuberculosis (GONZALEZ-TORRES; GUZMAN-BELTRAN; MATA-GOMEZ; LEYVA-GOMEZ et al, 2021).…”