In 2015, the World Health Organization (WHO) included a health target in the newly adopted Sustainable Development Goals, striving to end the tuberculosis (TB) epidemic by the year 2030. In low-income countries, TB continues to be one of the most prevalent infectious diseases with leading mortality rates in the pediatric population. A key reason for these unacceptable high morbidity and mortality rates is the poor sensitivity of available diagnostic tests to detect TB. In these countries, pediatric TB is primarily diagnosed based on clinical signs and smear microscopy, consequently resulting in a large proportion of undiagnosed patients. This illustrates the need for new strategies towards tuberculosis control, including development of new diagnostic modalities. In the interesting article of Mgode et al.,1 the potential of olfactory sense of trained African giant pouched rats (Cricetomys ansorgei) was evaluated as a complementary method in the diagnostic workup of pediatric TB.1 They showed that implementation of trained rats could increase the detection rate of pediatric TB by 68%, compared to a single-test protocol using smear microscopy. Given the severe health implications of TB, such an increase in detection rate is of considerable clinical importance. Interestingly, already around the year 400 BC, the ancient Greek Hippocrates described the potential of the scent of sputum as diagnostic tool in TB.

Over the past years, an increasing number of studies demonstrated the potential of scent molecules, or more specifically volatile organic compounds (VOCs), as a diagnostic biomarker for a wide variety of clinical conditions, including metabolic, infectious, and inflammatory diseases and malignancies. VOCs are carbon-based chemicals, volatile at ambient temperatures, and source of the majority of surrounding odors. Being produced during metabolic processes and excreted through all conceivable bodily excrements (e.g., sputum, feces, sweat, urine), they may serve as an ideal clinical biomarker for several pathophysiological processes. VOCs derived from a particular bodily substrate may either have an endogenous (local or systemic) or exogenous origin. In order to discriminate diseased from healthy state, VOCs derived from different substrates usually provide different outcomes. For example, in intestinal diseases such as inflammatory bowel disease, the discriminative accuracy of fecal VOCs is superior over that of exhaled breath and urinary volatiles.

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