A70-06 When Negative Doesn’t Mean Safe: IGRA-Negative Active Tuberculosis in an Immunocompetent Host

Abstract Introduction The utility of interferon-gamma release assays (IGRAs) for diagnosing active pulmonary tuberculosis (TB) is limited; a negative result does not reliably exclude disease. Meta-analyses show sensitivities as low as 60% among immunocompromised and around 75-80% in general populations. The Centers for Disease Control and Prevention (CDC) notes that negative TB blood test results cannot exclude TB disease, especially in those with epidemiologic risk factors. We present a case of IGRA-negative, immunocompetent active pulmonary TB in a BCG-vaccinated immigrant to emphasize the importance of empirical therapy when clinical suspicion is high despite a negative IGRA. Case Presentation A 50-year-old male with hypertension, type 2 diabetes, chronic sinus disease, GERD, and chronic bronchitis presented with a six-month history of progressive productive cough, chest tightness, and unintentional weight loss of six pounds. He denied fever, night sweats, dyspnea, or recent sick contacts. He reported prior exposure to a family member with TB more than a decade earlier, received BCG vaccination in India, and immigrated to the U.S. 15 years ago (last visit three years prior). Chest CT revealed a large cavitary mass in the right lung apex with irregular thickened nodular wall and right paratracheal lymphadenopathy. Despite a high pre-test probability, IGRA was negative. The patient and his wife requested a bronchoscopy due to cancer concerns. Given imaging, epidemiologic exposure, and risk profile, empiric anti-tuberculous therapy was initiated while awaiting sputum AFB, culture, and NAAT results, which later confirmed Mycobacterium tuberculosis. Discussion This case highlights that IGRAs cannot reliably rule out active TB. Approximately 20-25% of culture-confirmed TB cases can be IGRA-negative. False-negative results are linked to advanced age, diabetes, lymphopenia, or immunosuppression. ATS/IDSA/CDC guidelines emphasize that IGRAs and TSTs are not diagnostic for active TB—they do not distinguish latent infection from disease and should not exclude TB when suspicion remains high. The combination of epidemiologic risk, characteristic imaging (apical cavitary lesion), and chronic cough warranted empiric treatment rather than awaiting full microbiologic confirmation. Delay in therapy may worsen morbidity and facilitate transmission. Though BCG vaccination may complicate TST interpretation, it does not cause IGRA false negatives. Clinical judgment must override false reassurance from negative assays. Conclusion Active TB can present with a negative IGRA, even in immunocompetent patients. When clinical and radiographic suspicion is high, empiric therapy should begin while awaiting confirmatory results. Early treatment prevents progression and transmission, reinforcing that timely clinical judgment remains essential. This abstract is funded by: None