The Xpert MTB/RIF assay: A game-changer, but not infallible

Abstract

Tuberculosis (TB) is a major problem in South Africa and increasing varieties of drug-resistant strains add to the burden. The roll-out of the rapid molecular diagnostic test – the Xpert Mycobacterium tuberculosis/ rifampicin (MTB/RIF) assay (Cepheid, USA) – was a major game-changer in its ability to not only confirm MTB but also rifampicin resistance within a few hours. However, two caveats have emerged in the recent literature that necessitate that we reconsider. These refer to the ability to detect all rifampicin-resistant strains and, since the test is so sensitive, the duration that the test remains positive after a diagnosis of TB. The first investigators, in a study from Swaziland, used 24-loci mycobacterial interspersed repetitive unit – variable number tandem repeat (MIRU-VNTR) analysis and spoligotyping to perform classic genotypic analysis of MTB complex strains from their most recent national survey of tuberculosis drug resistance. [1] They found that 38 of 125 multidrug-resistant strains (30%) carried the rpoB I491F mutation, which confers resistance to rifampicin. This mutation, which was previously reported with low frequency in clinical isolates from other parts of the world, is not detected by the Xpert MTB/RIF assay. Xpert is designed to identify rifampicin-resistance mutations in an 81-base pair region of rpoB (codons 426 to 452). Its inability to detect the rpoB I491F outbreak strain will result in underdiagnosis of rifampicin-resistant MTB and potentially lead to inadequate treatment.