Implementing the Xpert® MTB/RIF Diagnostic Test for Tuberculosis and Rifampicin Resistance: Outcomes and Lessons Learned in 18 Countries

Abstract

BackgroundThe Xpert® MTB/RIF (Xpert) is an automated molecular test for simultaneous detection of tuberculosis (TB) and rifampicin resistance, recommended by the World Health Organization as the preferred diagnostic method for individuals presumed to have multi-drug resistant TB (MDR-TB) or HIV-associated TB. We describe the performance of Xpert and key lessons learned during two years of implementation under routine conditions in 33 projects located in 18 countries supported by Médecins Sans Frontières across varied geographic, epidemiological and clinical settings.MethodsXpert was used following three strategies: the first being as the initial test, with microscopy in parallel, for all presumptive TB cases; the second being only for patients at risk of MDR-TB, or with HIV- associated TB, or presumptive paediatric TB; and the third being as the initial test for these high-risk patients plus as an add-on test to microscopy in others. Routine laboratory data were collected, using laboratory registers. Qualitative data such as logistic aspects, human resources, and tool acceptance were collected using a questionnaire.FindingsIn total, 52,863 samples underwent Xpert testing from April 2011 to December 2012. The average MTB detection rate was 18.5%, 22.3%, and 11.6% for the three different strategies respectively. Analysis of the results on samples tested in parallel showed that using Xpert as add-on test to microscopy would have increased laboratory TB confirmation by 49.7%, versus 42.3% for Xpert replacing microscopy. The main limitation of the test was the high rate of inconclusive results, which correlated with factors such as defective modules, cartridge version (G3 vs. G4) and staff experience. Operational and logistical hurdles included infrastructure renovation, basic computer training, regular instrument troubleshooting and maintenance, all of which required substantial and continuous support.ConclusionThe implementation of Xpert was feasible and significantly increased TB detection compared to microscopy, despite the high rate of inconclusive results. Xpert implementation was accompanied by considerable operational and logistical challenges. To further decentralize diagnosis, simpler, low-cost TB technologies well-suited to low-resource settings are still urgently needed.

Performance of the G4 Xpert® MTB/RIF assay for the detection of Mycobacterium tuberculosis and rifampin resistance: a retrospective case-control study of analytical and clinical samples from high- and low-tuberculosis prevalence settings

“…In addition, we found high sensitivity and specificity for MTBc and RIF resistance detection that compared well to the previous versions of the assay [4]. Most published reports of Xpert assay performance were conducted using the previous versions of the assay; our findings represent one of the first large studies reporting G4 Xpert assay performance and add to the growing literature [19–22] in both high- and low-TB prevalence settings.…”

Genomic Analysis of the Evolution of Fluoroquinolone Resistance in Mycobacterium tuberculosis Prior to Tuberculosis Diagnosis

“…These molecular assays include PCR amplification of part or all of gyrA and gyrB, followed by Sanger sequencing, or the commercially licensed MTBDRsl line probe assay (Hain Lifescience). Additionally, Cepheid, whose current rapid PCR-based Xpert MTB/RIF assay (31) has been successfully implemented in clinical settings globally (32), is developing an expanded assay (Xtend XDR) to detect mutations conferring resistance to FQs, INH, amikacin, and kanamycin (33). The specificity of molecular diagnostic methods is high; the presence of any of a small number of mutations in the QRDR of gyrA (codons 94, 90, 91, 89, and 88) is strongly associated with FQ resistance.…”

Effect of previous treatment and sputum quality on diagnostic accuracy of Xpert® MTB/RIF

“…3 One of the reported advantages of Xpert is its high accuracy in detecting M. tuberculosis in culturepositive respiratory samples. [1][2][3][4] In a meta-analysis of early studies, Xpert demonstrated a pooled specificity of 99%, and a sensitivity of 98% in acid-fast bacilli (AFB) smear-positive sputum specimens and 67% in AFB-negative specimens, mostly in high TB prevalence settings. 5 However, recent studies in programmatic conditions have suggested lower specificities of Xpert in previously treated patients (~90%).…”