Diagnosing active tuberculosis remains a challenge, especially in children. In this study, which included HIV-negative and HIV-positive children, a 51-transcript signature for active tuberculosis was evaluated as a potential diagnostic tool. Between 500,000 and 1 million new cases of childhood tuberculosis are diagnosed annually, but the true global burden of childhood tuberculosis is unknown because it is often difficult to confirm the diagnosis microbiologically. 1 – 3 Although most cases of tuberculosis in adults are diagnosed through detection of acid-fast bacilli on microscopic examination of a sputum specimen, in the majority of childhood cases, smears and cultures are negative for Mycobacterium tuberculosis, and the diagnosis is made solely on clinical grounds. 1 , 3 Since the symptoms and signs of childhood tuberculosis are seen in a range of other conditions, clinical diagnosis is unreliable. 4 Clinical . . .