Clinical validation of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis

Abstract

Extrapulmonary tuberculosis (EPTB) accounts for more than 20% of tuberculosis (TB) cases. Xpert MTB/RIF (Xpert) (Cepheid, Sunnyvale, CA, USA) is a fully automated amplification system, for which excellent results in the diagnosis of pulmonary TB in highly endemic countries have been recently reported. We aimed to assess the performance of the Xpert system in diagnosing EPTB in a low incidence setting.We investigated with Xpert a large number of consecutive extrapulmonary clinical specimens (1,476, corresponding to 1,068 patients) including both paediatric (494) and adult samples.We found, in comparison with a reference standard consisting of combination of culture and clinical diagnosis of TB, an overall sensitivity and specificity of 81.3% and 99.8% for Xpert, while the sensitivity of microscopy was 48%. For biopsies, urines, pus and cerebrospinal fluids the sensitivity exceeded 85%, while it was slightly under 80% for gastric aspirates. It was, in contrast, lower than 50% for cavitary fluids. High sensitivity and specificity (86.9% and 99.7%, respectively) were also obtained for paediatric specimens.Although the role of culture remains central in the microbiological diagnosis of EPTB, the sensitivity of Xpert in rapidly diagnosing the disease makes it a much better choice compared to smear microscopy. The ability to rule out the disease still remains suboptimal.

Performance of Xpert MTB/RIF on pleural tissue for the diagnosis of pleural tuberculosis: Table 1–

“…Culture, however, is limited in its ability to detect EPTB and the comparison to only cultureconfirmed cases is likely to overestimate the sensitivity of Xpert. Nonetheless, in our study Xpert missed all cases with positive cultures on tissue.The low sensitivity in pleural fluid observed in this study has been described in previous studies [5][6][7]10]. Explanations for the limited sensitivity of Xpert in pleural fluid and tissue samples could relate to PCR inhibitors or insufficient sample volume in this paucibacillary disease.…”

“…Given the limitations of available tests for the diagnosis of pleural TB, several studies have evaluated the performance of Xpert using pleural fluid as a sample type. Overall, these studies show limited accuracy with sensitivity averaging around 44% [5][6][7]. However, the preferred specimen for the diagnosis of pleural TB is pleural tissue.…”

“…However, the preferred specimen for the diagnosis of pleural TB is pleural tissue. To date, the evaluation of Xpert performed on pleural tissue has been limited to isolated samples within larger studies [4,6,7].We enrolled consecutive adult patients that were evaluated for pleural TB in the pulmonary clinic and inpatient ward at the Christian Medical College, Vellore, India. Pleural TB was suspected based on clinical symptoms and radiographic evidence of a pleural effusion.…”

Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in children: A systematic review and meta-analysis

“…17,18,26,27 Using the total number of tuberculosis cases (culture-confirmed, plus cases meeting an author-defined diagnosis of clinical tuberculosis) as a denominator, the incremental yield of Xpert on a second specimen ranged from 8·3% to 17·5%, and from 0% to 12·5% on a third specimen. The incremental yield of culture (Löwenstein-Jensen or Mycobacteria Growth Indicator Tube values) ranged from 14·3% to 21·9% on the second specimen.…”

Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in children: A systematic review and meta-analysis

“…We selected 15 studies for inclusion (figure 1). [12][13][14][15][16][17][18][19][20][21][22][23][24][25] Five studies were done in low-income countries, two in lower middle-income, six in upper middle-income, and two in high-income countries (table 1). 26 12 studies were done at tertiary, university, or research facilities.…”