A case of pleural Mycobacterium tuberculosis infection with reversion of Quantiferon Gold Plus results from positive to negative

<b>Introduction.</b> <i>Mycobacterium tuberculosis</i> (MTB) infections continue to have a high mortality and morbidity burden globally. Interferon-gamma release assays such as Quantiferon Gold Plus (QFG-Plus) aid in diagnosis of latent TB but diagnosis of pleural TB remains challenging. We present a case of active pleural MTB infection with reversion from positive to negative of IGRA result as well as negative Xpert MTB/RIF Ultra PCR result from tissues obtained from pleural biopsy. <b>Case summary.</b> A 52-year-old otherwise healthy male presented in August 2022 with a 2 week history of pleuritic chest pain associated with modest elevation in inflammatory markers. The patient had had a positive QFG-Plus result in 2018, however QFG-Plus during this admission was negative. Computed-tomography pulmonary angiogram and needle thoracocentesis showed an exudative left pleural effusion with predominant lymphocytes. The patient's symptoms failed to resolve with empiric antimicrobial therapy for community-acquired pneumonia. Broncho-alveolar lavage as well as biopsies of pleural tissues via video-assisted thoracoscopic surgery from the left lower lobe yielded negative results on routine microbiological culture as well as Xpert Ultra PCR. Growth of acid-fast bacilli was noted from mycobacterial cultures of pleural tissues which was identified as MTB. <b>Conclusion.</b> Despite significant technological advances, microbiological diagnosis of MTB infections remains challenging. We document QFG-Plus reversion during development from latent to active pleural TB. Decline in the ability of CD4⁺ and CD8⁺ T cells to produce interferon gamma in response to TB antigens (ESAT-6 and CFP-10) was likely associated with loss of host control of latent MTB. This case serves as a reminder that despite exhaustive testing with state-of-art diagnostic platforms, MTB infections can still elude discovery.