Diagnostic Accuracy of Xpert MTB/RIF for Extrapulmonary Tuberculosis Specimens: Establishing a Laboratory Testing Algorithm for South Africa

Abstract

e South Africa implemented Xpert MTB/RIF as the initial diagnostic test for pulmonary tuberculosis (TB). Xpert MTB/RIF's accuracy for diagnosing extrapulmonary tuberculosis (EPTB) was investigated. EPTB specimens (n ‫؍‬ 7,916) from hospitalized patients received over a 6-month period at a high-throughput TB referral laboratory in Johannesburg were investigated. Largevolume specimens were centrifuged, tissue biopsy specimens homogenized, and all specimens checked for growth of contaminating bacteria on blood agar. Contaminated samples received NALC-NaOH (N-acetyl-L-cysteine-sodium hydroxide) decontamination prior to liquid culture. Residual specimens (volumes > 1 ml) after inoculation of culture (n ‫؍‬ 1,175) were tested using the Xpert MTB/RIF sputum protocol. Using culture as the reference, Xpert MTB/RIF's overall sensitivity was 59% (95% confidence interval [95% CI], 53% to 65%) and specificity was 92% (CI, 90% to 94%), with the highest sensitivities of 91% (95% CI, 78% to 97%) for pus, 80% (95% CI, 56% to 94%) for lymph node aspirates, and 51% (95% CI, 44% to 58%) for fluids ( ascitic, 59%; pleural, 47%). A difference in sensitivities was noticed between specimens classified as having a thick (87% [95% CI, 76% to 94%]) versus clear (watery) (48% [95% CI, 36% to 61%]) appearance. This was unchanged with traces of blood (52% [95% CI, 44% to 60%]) or precentrifugation (57% [95% CI, 28% to 82%]) among clear specimens. Xpert MTB/RIF generated an additional 124 specimen results that were contaminated by Mycobacterial Growth Indicator Tubes (MGIT; 10.5%) and diagnosed rifampin (RIF) resistance earlier (9.6% [25/260]). Xpert MTB/RIF's performance on EPTB specimens provides very promising results and should be considered for incorporation into national TB guidelines. Xpert MTB/RIF is less affected by contaminating bacteria and reduces laboratory labor and diagnostic delay compared to traditional methods. Evidence from 138 studies published before 2008 suggested that nucleic acid amplification technologies (NAAT) could not replace conventional mycobacterial tests (microscopy, culture) for diagnosing pulmonary and, especially, extrapulmonary tuberculosis (EPTB) (1). Only a few years later, GeneXpert technology (2) has changed this paradigm, with a recent systematic review showing pooled sensitivity of 88% and pooled specificity of 98% (3) for diagnosis of pulmonary TB, but evidence (as of March 2012) for using Xpert MTB/RIF for diagnosing EPTB is still comparatively weak (4). Globally, there is still a dearth of studies involving the use of Xpert MTB/RIF in EPTB specimens, and few provide definitive answers. This is due mostly to the studies having small sample sizes across a range of various specimen types and differences in preprocessing methodologies and in input volumes and to studies having been conducted in different populations (adults, children, HIV infected). In one large published study, the overall sensitivity of Xpert MTB/RIF on tissue biopsy specimens/fineneedle aspirates (FNA), pleural fluid, gastric aspir...

Evaluation of Xpert MTB/RIF assay performance in diagnosing extrapulmonary tuberculosis among adults in a tertiary care centre in India

“…Suboptimal performance of the assay was observed for various body fluids, with sensitivity ranging from 18% to 40%, which is consistent with several previous studies [7][8][9][10][11][12]. The present study also indicates exemplary performance of the assay in patients with cold abscesses and lymph nodes and these findings are similar to previously published literature [7][8][9]13].…”

“…The present study also indicates exemplary performance of the assay in patients with cold abscesses and lymph nodes and these findings are similar to previously published literature [7][8][9]13]. The difference in sensitivity could be attributed to the fact that in lymph nodes and its aspirates the bacteria are localised to the site of infection, whereas in body fluids, presence of PCR inhibitors and the paucibacillary nature of the specimens may result in lower sensitivity.…”

“…In the present study, we excluded patients who were already on anti-TB treatment for .2 weeks. The overall performance of Xpert MTB/RIF in our study might vary from different studies across the globe because of the variation in proportion of sample types [7][8][9][10][11][12][13][14][15].…”

Diagnostic Performance of Xpert MTB/RIF in Tuberculous Pleural Effusion: Systematic Review and Meta-analysis

“…Twenty-one studies (2,167 patients) and 10 studies (937 patients) used a microbiological standard (mycobacterial culture) (7, 8, 13-16, 19, 20, 22-34) or a composite reference standard (CRS) (7, 14-18, 21, 22, 24, 28), respectively, to assess the diagnostic accuracy of GeneXpert (see Table S3). Seven studies performed Xpert MTB/RIF on frozen pleural fluid (7,15,19,21,23,28,30), while the remaining used fresh samples (see Table S4). Nine studies concentrated the pleural fluid sample by centrifugation before performance of GeneXpert (7, 8, 16-18, 20, 22, 24, 29).…”

Rapid detection of Mycobacterium tuberculosis and Rifampicin Resistance in extra pulmonary samples using GeneXpert MTB/RIF assay

“…et al 12 in 2014, by Xpert MTB/RIF, which provided an early diagnosis of RIF resistance (9.6%) in 25/260 cases (with 100% specificity). In this study, only 3 samples were found to be rifampicin resistant out of 123 samples.…”