Performance Comparison of Two Commercial Tests for Rapid Molecular Diagnosis of Exprapulmonary Tuberculosis in a Low TB Incidence Country
Background: Extrapulmonary tuberculosis (EPTB) accounts for >20% of tuberculosis (TB) cases in low TB incidence countries. Unlike pulmonary TB, diagnosis of EPTB is difficult due to atypical presentation and low culture positivity due to lower bacterial load. This study evaluated the performance of Xpert MTB/RIF (Xpert) and ProbeTec ET (PTec-ET) assays in diagnosing EPTB.
Methods: A total of 1660 consecutive extrapulmonary clinical specimens from suspected patients during October 2011 to August 2013 were investigated. The specimens included cavitary fluids (n=890), fine needle aspirate (FNA), pus (n=482), tissue biopsy (n=102), cerebrospinal fluid (CSF) (n=85), urine (n=67), and others (n=36). All specimens were processed for acid-fast bacilli (AFB) smear microscopy by Ziehl-Neelsen staining, liquid culture in MGIT 960 system and nucleic acid detection by Xpert and PTec-ET. All procedures were performed according to manufacturer’s instructions and sensitivity and specificity of Xpert and PTec-ET was calculated in comparison with a reference standard comprising a combination of culture and clinical diagnosis of TB.
Results: Of 1660 specimens, 34 were AFB-SM positive, 157 were culture positive and 197 yielded a positive culture and/or a clinical diagnosis of TB. The overall sensitivity and specificity values for Xpert were 93% and 100%, respectively and for PTec-ET were 82% and 100%, respectively, while the sensitivity values for microscopy and culture alone were 17% and 80%, respectively. The sensitivity of Xpert was higher for biopsies, FNA and pus, urine and CSF than in cavitary fluids. Xpert was more sensitive than PTec-ET as it detected EPTB in 15 more AFB-SM-negative, culture-positive and 6 more AFB-SM-negative, culture-negative specimens. More importantly, Xpert detected EPTB in 40 samples with clear histological evidence of infection of which only 7 samples were AFB-SM-positive but none of these 40 samples yielded a positive culture.
Conclusions: Molecular methods can help in rapid diagnosis of extrapulmonary tuberculosis. The higher sensitivity of Xpert offers a better choice compared to PTec-ET or smear microscopy in rapidly diagnosing the disease. However the negative predictive value of Xpert in EPTB specimens remains suboptimal.
S. Ahmed, None