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. From 2020 to 2050 and based on current estimates (now disrupted by COVID-19) almost 30 million people will die of tuberculosis (Silva et al Lancet Global Health). It is estimated that this figure correspond to an economic loss of 17 trillion dollars. If the Sustainable development Goals for tuberculosis are met by 2030 then three trillion dolars will be saved. But the goal will not be achieved if we not advance in TB controls with innovations in healthcare. In particular, 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(symptomatically active TB cases), while there is a growing consensus that the traditional latent/active dichotomy is no longer valid, and that asymptomatic individuals with active TB signatures are also likely to be transmitting the disease.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, TB-RECONNECT 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. Our project can have a major impact at the societal level. By cutting transmission we can help to i) Break the poverty/tuberculosis vicious circle. Tuberculosis is a poverty disease and low- and middle-income countries are disproportionally affected by tuberculosis. In fact poverty and tuberculosis form a vicious cycle in continuous flux. The reason is that poverty influence tuberculosis through limited healthcare, sanitation, education, malnutrition and combordities like HIV or diabetes. Tuberculosis influences poverty through a devastating almost chronic disease including post-TB sequalae that impact the countries productivity. And to reduce ii) Individual financial burden. Household suffer of major reduction in income due to TB illness. For example, in a study in India the mean number of work days lost was 88 with mounting debts due to treatment costs and household financial burdens. To the point that in some countries leads to situations like the household income relying on children of school age. Therefore TB has a major societal impact which can be ameliorated if new ways to control TB are incorporated in global TB control estrategies. At least until a low-cost, effective vaccine is developed and make it to clinical settings.
