Detecting active pulmonary tuberculosis with a breath test using nanomaterial-based sensors

To the Editor: Detecting active tuberculosis (TB) remains a major global public health challenge [1]. The tuberculin skin test does not distinguish latent from active TB [2]. The interferon-γ release assays have similar limitations [3]. Acid-fast bacilli staining of sputum has a high false-negative rate (up to 50%) [4]. Nucleic acid amplification tests (NAATs), such as GeneXpert MTB/RIF (Cepheid, Sunnyvale, CA, USA), are accurate but require a good infrastructure and the necessity to obtain a good quality sputum sample, which is often unobtainable in more than a third of HIV-infected persons [5, 6]. Given these unmet needs, we explored the use of a novel, rapid, simple and inexpensive point-of-care test for the diagnosis of TB [7]. The approach is based on the detection of volatile organic compounds (VOCs) that are emitted from infected cells and released in exhaled breath [8, 9]. Using gas chromatography linked with mass spectrometry, researchers have previously reported identification of TB-related VOCs in the exhaled breath, though there has been low accuracy in detection (80–85%) [10]. In this study, we explore the possibility of active TB detection via the analysis of exhaled breath using a novel technology of organically modified nanomaterial-based sensors. Such cross-reactive sensors are highly sensitive to the collective changes in the VOCs spectrum [8]. Therefore, we designed a case–control study, in which breath and sputum sampling was performed in 210 adult participants, after informed consent, at three sites in Cape Town, South Africa, between November 2011 and March 2012. The study population consisted of two main subgroups. The first subgroup included those in …