2012 SwissTB Award

Dr. Alexandre Harari

Tuberculosis (TB) remains one of the most pressing public health priorities for the 21st century, with over one third of the world population infected. 
Screenings of Mycobacterium tuberculosis (Mtb) infection are traditionally performed by tuberculin skin tests. More recently, IFN-γ release assays (IGRAs) such as ELISpot (e.g. TB-SPOT) or ELISA (e.g. quantiferon), which are based on the identification of a cellular immune responses against Mtb antigens, became the most appropriate screening tools since these assays are highly sensitive and specific. However, none of these tests are associated to a diagnosis of active TB disease Vs. latent infection. These diagnosis are only achieved following extensive microbiological and clinical assays which are time and ressources consuming.

In the present study, the IGRA were complemented with polychromatic flow cytometry and specific immune signatures of active TB disease or latent Mtb infection were identified. In particular, the functional profiles, based on the simultaneous determination of several cytokines (i.e. TNF-α, IL-2 and IFN-γ), were used to develop a diagnosis tool allowing a quick and reliable identification of active TB disease in 24 hours. These results including the validation of the present diagnosis tool were publised in Nature Medicine in 2011. The new diagnosis tool developed by Pr. G. Pantaleo and Dr. A. Harari is currently implemented in Lausanne as a service for clinicians in Switzerland.

Publication

Dominant TNF-α+ Mycobacterium tuberculosis–specific CD4+ T cell responses discriminate between latent infection and active disease. 
Alexandre Harari1,2, Virginie Rozot1, Felicitas Bellutti Enders1, Matthieu Perreau1, Jesica Mazza Stalder3, Laurent P Nicod3, Matthias Cavassini4, Thierry Calandra4, Catherine Lazor Blanchet4, Katia Jaton6, Mohamed Faouzi7, Cheryl L Day8, Willem A Hanekom8, Pierre-Alexandre Bart1 & Giuseppe Pantaleo1,2

1Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland. 2Swiss Vaccine Research Institute, Lausanne, Switzerland. 3Division of Pneumology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland. 4Division of Infectious Diseases, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland. 5Division of Occupational Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland. 6Institute of Microbiology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland. 7Center of Clinical Epidemiology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland. 8South African Tuberculosis Vaccine Initiative, University of Cape Town, Cape Town, South Africa.© 2011 Nature America, Inc. All rights reserved.