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Xpert MTB/XDR assay for the rapid diagnosis of TB resistance. A country wide cross sectional observational prospective study from Pakistan

F Saluzzo(1) F Masood(2) V Batignani(1) A Hussein(2) D M Cirillo(1) S Tahseen(2)

1:San Raffael Scientific Institute; 2:National TB Reference Laboratory, National Tuberculosis Control Program Pakistan

Pakistan is among top five high Drug Resistant Tuberculosis (TB) countries. Innovative tools for the rapid detection of isoniazid and fluoroquinolones resistance in this setting may play a pivotal role in increasing the rate of early appropriate treatment, finally reducing the disease burden.

In this cross sectional observational prospective study, clinical samples from 23 different sites among Pakistan have been tested to evaluate the performance of Xpert MTB/XDR assay and if Xpert MTB/XDR assay (XDR) could replace Line Probe Assay (LPA) in routine settings.

A total of 525 clinical samples were collected from people recently with TB regardless of rifampicin resistance result. XDR, LPA and phenotypic Drug Susceptibility Test (pDST) have been performed. Strains with discordant results for isoniazid and fluoroquinolones resistance at XDR and pDST have been analysed with Whole Genome Sequencing (WGS) and/or targeted Next Generation Sequencing (tNGS).

Xpert MTB/XDR provided interpretable results in 95,8% of all the analysed samples, while LPA provided an interpretable result in less than 80% of the analysed strains.

The overall sensitivity and specificity of XDR were 90,3 % (CI 95% 87,7-92,4%) and 98.5% (CI 95% 97,1-99,2%). WGS and tNGS outputs analysed according to the WHO catalogue confirmed XDR result in 3/11 discordant results for isoniazid, in 1/11 a frameshift mutation was detected confirming pDST result. In 4/11 cases mutations of uncertain significance were identified in strains resulted resistant at pDST and sensitive at XDR.

In conclusion, XDR proved to be a reliable tool for the rapid diagnosis of isoniazid and fluoroquinolone resistance.

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