Description du projet
Une meilleure compréhension de la transmission de la tuberculose pour de meilleurs programmes de contrôle
La lenteur des programmes de lutte contre la tuberculose (TB) à réduire l’incidence de la maladie découle de nombreuses causes, notamment des lacunes dans la chaîne des soins antituberculeux et d’une intégration insuffisante des nouvelles connaissances sur la transmission dans les efforts de lutte. Il est de plus en plus admis que les personnes asymptomatiques atteintes de tuberculose active sont susceptibles de transmettre la maladie. Le projet TB-RECONNECT, financé par l’UE, s’intéressera à la nature de la transmission de la tuberculose en relation avec la biologie de l’hôte et de l’agent pathogène afin d’améliorer les stratégies de lutte mondiales et locales. Les développements de recherche comprendront l’analyse transcriptomique du sang de l’hôte pour déterminer le statut de l’infection dans le groupe latent des individus. Le séquençage du génome de l’agent pathogène permettra une quantification de la transmission à haute résolution et une modélisation épidémiologique afin d’identifier le moment de la transmission et son impact sur le contrôle mondial de la tuberculose.
Objectif
The annual decline in tuberculosis (TB) incidence is not greatly different from that of the ‘90s, when no coordinated efforts in global tuberculosis control were in place. The failure of current TB control programmes to accelerate TB elimination has multiple causes, including losses of TB cases at the different steps of the TB care cascade, and a chronic lack of funding hampering innovation. Additionally, we have failed to halt transmission in many settings, as we have failed to incorporate our improved understanding of transmission in TB control programmes. Our current approach to controlling TB is focused on a narrow view of who is transmitting the disease (symptomatically active TB cases), while there is a growing consensus that the traditional latent/active dichotomy is no longer valid, and that asymptomatic individuals with active TB signatures are also likely to be transmitting the disease. There is a critical lack of high-resolution data from different settings on the contribution to the transmission burden of cases with different infection statuses. To fill this evidence gap, I propose synergizing three recent TB research developments; We can now use host blood transcriptomics to discriminate between infection status within the latent pool of individuals. We can now quantify transmission at a resolution not previously available, using pathogen genome sequencing. We can now use phylogenetic and epidemiological models to identify when transmission has happened. Combining these three key developments with TB cohorts from multiple settings, and available tools from bacterial population genetics, high-throughput functional genomics and infection biology, we will be in a key position to answer these burning questions about the nature of TB transmission and the host and pathogen biology behind this. More importantly, we will reconnect transmission to TB control, to inform major shifts in global and local control strategies.
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ERC-COG - Consolidator GrantInstitution d’accueil
28006 Madrid
Espagne