Accelerating extrapulmonary tuberculosis diagnosis with a rapid molecular assay

Abstract

Extrapulmonary tuberculosis (EPTB) is characterized by a very low bacterial load and could remain undiagnosed for a long time in a number of cases due to atypical presentation. Conventional methods and their time to results are not always helpful in rapidly making an EPTB diagnosis and initiating appropriate treatment. In order to accelerate the bacteriological confirmation, we evaluated the benefits of systematically using nucleic acid amplification test (NAAT) on extrapulmonary specimens for TB diagnosis in a developed country. From November 2017 to March 2021, all extrapulmonary samples received at the mycobacteriology department were subjected to both conventional methods and Xpert MTB/RIF Ultra. The time savings and the diagnostic performance of reflex tests were evaluated. During the study period, 691 samples were included, 85 (12.3%) were NAAT positive for Mycobacterium tuberculosis complex (MTBC), and only 1 for a rpoB mutation. The overall rate of invalid NAAT results was low, 0.9%. The average time to results of NAAT was 1.3 days compared to 18 days for positive culture, allowed to accelerate the EPTB diagnosis by 16 days. Overall NAAT sensitivity and specificity were 87.9% and 94.6%, respectively. No discrepancy was found among the 67 results involving the detection of rifampicin resistance. NAAT is a quick and consistent diagnostic test for EPTB with a potential turnaround time of 2 hours. Its systematic use could allow EPTB diagnosis and treatment faster by revealing results days to weeks before culture and drug susceptibility testing.IMPORTANCETuberculosis is considered the deadliest infectious disease in the world. Although tuberculosis most commonly affects the lungs, it also affects other sites referred to as extrapulmonary tuberculosis (EPTB). Diagnosis of EPTB is difficult and often delayed. We evaluated the benefits of systematically and routinely using a nucleic acid amplification test on all extrapulmonary specimens received at the mycobacterial core laboratory for EPTB diagnosis. Using a rapid (80 minutes) and easy-to-perform test, we accelerated the definitive diagnosis by an average of 16 days.

Keywords: Mycobacterium tuberculosis; Xpert MTB/RIF Ultra; extrapulmonary tuberculosis; lymph node tuberculosis; molecular methods; nucleic acid technology; rifampin resistance; time to result.

Fig 1

Summary of the results of the conventional methods and of NAATs for MTBC detection.

Fig 2

Time to positive result of NAAT, smear, and culture for three main sample categories.