A rapid and non-invasive approach to assess tuberculosis treatment efficacy in real-time in patients : toward a personalized medicine – TB-in-time

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) complex remains one of the most prevalent deadly infectious diseases worldwide. TB treatments are long, and patients’ adherence is hampered by frequent side effects, entailing premature treatment arrest and exposing to disease relapse. To date, the only prognostic marker for end-of-treatment outcome remains the culture conversion status after 2 months of anti-TB treatment, though the sensitivity for prediction of treatment success is poor. The difficulties in diagnosing and monitoring tuberculosis in patients translates in big delays to detect unsuccessful treatment and therefore to modify it when necessary. In addition, they constitute a strong limitation for the development of novel drug combos and personalized treatments.
Through the TB-in-time project, we aim at improving the current detection and management of TB in patients. More specifically, based on a solid set of preliminary data, we propose an integrated approach to explore the value of sampling exhaled breath condensate (EBC), an easily accessible sample, for a rapid and non-invasive assessment of anti-TB treatment efficacy in real-time. To achieve this objective, we aim to i) collect EBCs from TB patients enrolled in a cohort with state-of-the art TB management, ii) analyze quantitatively Mtb (glyco)lipids and proteins, as well as human proteins, as prognostic biomarkers, and iii) determine antibiotic concentration in these samples.
This proposal relies on the strong complementary expertise of two partners in infectious disease, clinical microbiology, pharmacology, and glycolipid and protein biochemistry. It has the potential to improve the diagnostics, the appropriateness of drug regimen and the follow-up of TB patients. The results will open new routes toward a personalized medicine for TB, a prerequisite for better intervention, allocation of health resources, and ultimately TB control.