Utility of nucleic acid amplification tests in the diagnosis of osteoarticular tuberculosis

Osteoarticular TB (OATB) is a manifestation of extrapulmonary TB (EPTB), wherein spinal TB constitutes ∼50% of OATB individuals. Diagnosis of OATB is quite difficult owing to deep inaccessible lesions within tissues, scanty bacterial load and imitation of disease with other osteoarticular conditions. OATB diagnosis mostly relies on clinical features and imaging in endemic countries, however, it is difficult to distinguish between OATB and inflammatory arthritis, i.e. rheumatoid arthritis, gout, ankylosing spondylitis, etc. using these modalities. Other laboratory tests include bacteriological evaluation (smear/culture), histopathological examination (HPE), cytology, and response to anti-tubercular therapy (ATT). Meanwhile, several nucleic acid amplification tests (NAATs) have emerged for EPTB diagnosis including OATB, viz. in-house PCR/multiplex-PCR, nested PCR, real-time PCR including commercial tests (e.g. LightCycler) and loop-mediated isothermal amplification (LAMP). Markedly, the WHO has endorsed GeneXpert® MTB/RIF, GeneXpert® Ultra and Truenat® MTB/MTB Plus (TruPlus) for both pulmonary TB and EPTB diagnosis, albeit only a few reports are available on OATB diagnosis by Truenat/TruPlus. These commercial tests also monitor rifampicin-resistance, which represents a surrogate marker to monitor multidrug-resistance TB. In this review, we comprehensively studied several NAATs for OATB diagnosis that showed promising results. Since bacteriological tests (smear/culture) mostly yield low to moderate sensitivity for OATB diagnosis, multi-targeted LAMP or GeneXpert Ultra/Xpert may be incorporated in the diagnostic panel along with clinical features, imaging and HPE, so that an early ATT is initiated. This would reduce serious complications, like debilitating deformities and neurological deficits associated with disease.