Nucleic acid amplification testing for the diagnosis of osteo-articular tuberculosis

Abstract

Osteo-articular tuberculosis constitutes a significant burden of extrapulmonary tuberculosis infection. The identification of Mycobacterium tuberculosis (Mtb) in osteo-articular specimens by traditional microscopy and culture is difficult, due to the paucibacillary nature of disease. The use of nucleic acid amplification tests (NAATs) may improve the detection of Mtb in tissue specimens, allowing for prompt diagnosis and treatment initiation. Methods We prospectively evaluated the use of NAATs as compared to traditional tests for the diagnosis of osteo-articular tuberculosis. The study population consisted of adult and paediatric patients at Chris Hani Baragwanath Academic Hospital (CHBAH), suspected of having osteo-articular tuberculosis. Results Twenty-nine patients were assessed by using routine histopathology, microscopy and culture, together with two NAAT assays: the Xpert MTB/Rif assay and Line Probe Assay (LPA). In comparison to mycobacterial culture, the Xpert MTB/Rif assay and LPA demonstrated a sensitivity of 90% and 100% respectively; and a specificity of 72% and 79% respectively. In comparison to histopathologic assessment, mycobacterial culture had 69% sensitivity and 100% specificity. Compared to histology, the Xpert MTB/Rif assay demonstrated a sensitivity of 94% and specificity of 100%, whilst the LPA had sensitivity and specificity of 100%. Xpert MTB/Rif assay results were available at three days on average and LPA results were available viii at five days, versus 15 days for routine microscopy and culture, and 17 days for histological confirmation. In HIV-infected patients, both the Xpert MTB/Rif and LPA tests, had sensitivity and specificity of 100% in detecting patients with both culture- and histologically-proven osteo-articular tuberculosis. One patient had rifampicin-resistant tuberculosis infection. This case was detected by the Xpert MTB/Rif assay by day two post-biopsy, while culture was available on day 11. Conclusion The use of NAAT testing in the diagnosis of osteo-articular tuberculosis, demonstrated good sensitivity and specificity for the identification of Mtb-associated osteo-articular infection, in both HIV-infected and -uninfected patients. Furthermore, NAAT provides a more rapid time to identification of Mtb, and rapid identification of drug resistant infection as compared to traditional diagnostic tests.