Periodic Reporting for period 5 - TB-ACCELERATE (Integrating genomics, epidemiology and evolution to accelerate tuberculosis eradication)
Reporting period: 2020-09-01 to 2021-06-30
Tuberculosis (TB) is already the main cause of death among infectious diseases and is among the top ten causes of death globally. At the rate at which global incidence of TB is declining elimination will not be achieved for the next 200 years. TB control starting in the nineties has reached a plateau, slow down is mainly contributed by our inability to stop transmission. Transmission is still significant in low-burden countries but rampant in high-burden countries. To accelerate TB elimination we need new control tools (diagnostics, vaccines, antibiotics) as well as new interventions based on sound epidemiological predictions. Whole genome sequencing of the pathogen, unlike previous molecular approaches, is a tool that in addition to measure transmission has the potential to redefine interventions and even be used in on-going interventions. TB-ACCELERATE is developing different approaches to make full use of whole genome sequence data to find new ways to stop transmission. Those approaches are aimed to 1. use whole genome sequencing data of the pathogen to evaluate transmission in low and high burden countries; 2. develop algorithms to obtain a high resolution picture on how transmission has occurred within transmission clusters; 3. identify pathogenic signatures of virulence by studying transmission across countries and by studying the evolution of the pathogen within the host and 4. develop methods to integrate culture negative samples in whole genome epidemiological studies. The overall aim is to contribute to global and local TB control by revealing the patterns on how transmission occurs and by direct action on active transmission clusters.
Our translational research involves a wide range of disciplines including clinical, epidemiological, genomic and evolutionary research. Because of that there is people in our project involved in genomics, bioinformatics, mathematical modelling, clinicians, public health officials, molecular and evolutionary biologist. The project has allowed to hire one postdoc and two lab managers for biosafety experiments in the BSL3 and for library preparation and whole genome sequencing. In our local setting (Spain, low-burden country) we have been working on transmission reconstruction algorithms to obtain a high-resolution picture of TB transmission. Those algorithms does not only allow to identify transmission clusters but also to assign index and secondary cases to individuals. In parallel we are working with datasets from high-burden countries where the TB epidemic is different to identify differences in the population dynamics. All together we are using the data to understand individual transmission risk factors and to identify new molecular determinants of virulence and transmission.
Our developments have already led us to new breakthroughs on TB transmission and drug resistance. For example, we have recently identify transmission during asymptomatic estages of the disease. We have used whole genome sequencing to aid in the treatment of specially difficult MDR-TB cases that had disease over nine years. We have also established genomic determinants important in the origin of the MTBC as well as identify mutations and genes involved in differences between circulating strains. On the other hand, we have developed methods to genome sequence directly from the diagnostic sample allowing culture-free diagnostics and epidemiology.