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Integrating genomics, epidemiology and evolution to accelerate tuberculosis eradication

Fact Sheet

Reporting

Results

Project information

TB-ACCELERATE

Grant agreement ID: 638553

Status

Ongoing project

Start date

1 July 2015
End date

30 June 2021

Funded under:

H2020-EU.1.1.

Overall budget:

€ 1 671 875
EU contribution

€ 1 671 875

Hosted by:

AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS

Spain

Objective

"When the scale of the tuberculosis (TB) epidemic was highlighted by its declaration as a ""Global Emergency"" by WHO in 1993, it was envisaged that the efficient use of existing tools would result in a progressive decline towards eradication. This has not occurred. At the current pace of decline in TB incidence the Millennium objective to eradicate it by 2050 will not be met. Predictions of epidemiological models were inaccurate and current control programs and technologies have shown their limitations to control the transmission of the disease. To overcome these limitations we need a technological, methodological and conceptual leap forward that can reveal the unknowns of TB epidemiology. I propose whole genome sequencing (WGS) as the technology that can mediate this advance. While WGS has been applied mostly to retrospective datasets I propose to use it in prospective samples from a low-burden region at a population scale. Genome information will fill the gap between epidemiology and evolution to have a direct impact on public health. This will allow to develop innovative methodologies to describe transmission at an unprecedented resolution and as a consequence to differentiate among risks factors associated to the bacteria, the host, the environment and their interactions. Elucidation of these factors will lead to better models used to design new strategies and accelerate global TB eradication. In addition, I will show how the real-time integration of data in public eHealth systems combined with in situ interventions will accelerate TB eradication. The strength of the project resides in its multidisciplinary approach to TB epidemiology that will provide answers to yet-out-of-reach questions. It will lead to improving health status at the local level as well as to epidemiological and control programs at a global scale. In summary, the project will open new ways to foster the long sought outcome of the tuberculosis community: TB eradication."

Field of Science

/medical and health sciences/health sciences/health care services/ehealth

/medical and health sciences/health sciences/public and environmental health

/medical and health sciences/clinical medicine/pneumology/tuberculosis

/medical and health sciences/health sciences/epidemiology

/natural sciences/biological sciences/genetics and heredity/genome

Programme(s)

H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)

Topic(s)

ERC-StG-2014 - ERC Starting Grant

Call for proposal

ERC-2014-STG

See other projects for this call

Funding Scheme

ERC-STG - Starting Grant

Host institution

AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS

Address

Calle Serrano 117
28006 Madrid

Spain

Activity type

Research Organisations

EU Contribution

€ 1 275 875

Website

Contact the organisation

Beneficiaries (2)

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AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS

Spain

EU Contribution

€ 1 275 875

FUNDACION PARA EL FOMENTO DE LA INVESTIGACION SANITARIA Y BIOMEDICA DE LA COMUNITAT VALENCIANA

Spain

EU Contribution

€ 396 000

Project information

TB-ACCELERATE

Grant agreement ID: 638553

Status

Ongoing project

Start date

1 July 2015
End date

30 June 2021

Funded under:

H2020-EU.1.1.

Overall budget:

€ 1 671 875
EU contribution

€ 1 671 875

Hosted by:

AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS

Spain

Project information

TB-ACCELERATE

Grant agreement ID: 638553

Status

Ongoing project

Start date

1 July 2015
End date

30 June 2021

Funded under:

H2020-EU.1.1.

Overall budget:

€ 1 671 875
EU contribution

€ 1 671 875

Hosted by:

AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS

Spain

Periodic Reporting for period 3 - TB-ACCELERATE (Integrating genomics, epidemiology and evolution to accelerate tuberculosis eradication)

Reporting period: 2017-09-01 to 2019-02-28

Summary of the context and overall objectives of the project

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.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

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.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Our developments has already led us to describe the TB population dynamics in the high burden country of Ethiopia where we show that TB was present before main colonial movements of the XIXth century. We are also using population-based genomic dataset to obtain a high resolution picture of tuberculosis transmission. For example, in Valencia Region (Spain) we have identified between 20-30% of on-going recent transmission. We have developed approaches to look at individual transmission cases so we can for the first time assign transmission risk potentials to individual cases. We have also studied the evolution of the bacteria during infection where we are estimating mutation rates in chronic patients. For example, we have been able to diagnose a multidrug resistant strain that was not detected by routine clinical approaches and which showed a highly unexpected population dynamics within the host. By analyzing global diversity and transmission datasets and comparing with other mycobacteria we have identified relevant mutations in a key virulence regulator that are important for transmission potential. The next steps in the project are aimed at transferring the tools to analyze transmission in high burden countries. We believe that a comparative phylodynamic approach will allow us to disentangle new key determinants of the epidemic in different settings. To do so we have team-up with laboratories across different continents as well with epidemiological modelers so we can quantitatively estimate differences across countries.

Project information

TB-ACCELERATE

Grant agreement ID: 638553

Status

Ongoing project

Start date

1 July 2015
End date

30 June 2021

Funded under:

H2020-EU.1.1.

Overall budget:

€ 1 671 875
EU contribution

€ 1 671 875

Hosted by:

AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS

Project information

TB-ACCELERATE

Grant agreement ID: 638553

Status

Ongoing project

Start date

1 July 2015
End date

30 June 2021

Funded under:

H2020-EU.1.1.

Overall budget:

€ 1 671 875
EU contribution

€ 1 671 875

Hosted by:

AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS

Spain

Deliverables

Deliverables not available

Publications

Peer reviewed articles (13)

Urgent Implementation in a Hospital Setting of a Strategy To Rule Out Secondary Cases Caused by Imported Extensively Drug-Resistant Mycobacterium tuberculosis Strains at Diagnosis

Author(s): Laura Pérez-Lago, Miguel Martínez-Lirola, Sergio García, Marta Herranz, Igor Mokrousov, Iñaki Comas, Llúcia Martínez-Priego, Emilio Bouza, Darío García-de-Viedma

Published in: Journal of Clinical Microbiology, Issue 54/12, 2016, Page(s) 2969-2974, ISSN 0095-1137

DOI: 10.1128/JCM.01718-16

Population Genomics of Mycobacterium tuberculosis in Ethiopia Contradicts the Virgin Soil Hypothesis for Human Tuberculosis in Sub-Saharan Africa

Author(s): Iñaki Comas, Elena Hailu, Teklu Kiros, Shiferaw Bekele, Wondale Mekonnen, Balako Gumi, Rea Tschopp, Gobena Ameni, R. Glyn Hewinson, Brian D. Robertson, Galo A. Goig, David Stucki, Sebastien Gagneux, Abraham Aseffa, Douglas Young, Stefan Berg

Published in: Current Biology, Issue 25/24, 2015, Page(s) 3260-3266, ISSN 0960-9822

DOI: 10.1016/j.cub.2015.10.061

Integrating standardized whole genome sequence analysis with a global Mycobacterium tuberculosis antibiotic resistance knowledgebase

Author(s): Matthew Ezewudo, Amanda Borens, Álvaro Chiner-Oms, Paolo Miotto, Leonid Chindelevitch, Angela M. Starks, Debra Hanna, Richard Liwski, Matteo Zignol, Christopher Gilpin, Stefan Niemann, Thomas Andreas Kohl, Robin M. Warren, Derrick Crook, Sebastien Gagneux, Sven Hoffner, Camilla Rodrigues, Iñaki Comas, David M. Engelthaler, David Alland, Leen Rigouts, Christoph Lange, Keertan Dheda, Rumina Hasan, Ruth McNerney, Daniela M. Cirillo, Marco Schito, Timothy C. Rodwell, James Posey

Published in: Scientific Reports, Issue 8/1, 2018, ISSN 2045-2322

DOI: 10.1038/s41598-018-33731-1

A standardised method for interpreting the association between mutations and phenotypic drug resistance in Mycobacterium tuberculosis

Author(s): Paolo Miotto, Belay Tessema, Elisa Tagliani, Leonid Chindelevitch, Angela M. Starks, Claudia Emerson, Debra Hanna, Peter S. Kim, Richard Liwski, Matteo Zignol, Christopher Gilpin, Stefan Niemann, Claudia M. Denkinger, Joy Fleming, Robin M. Warren, Derrick Crook, James Posey, Sebastien Gagneux, Sven Hoffner, Camilla Rodrigues, Iñaki Comas, David M. Engelthaler, Megan Murray, David Alland, Leen Rigouts, Christoph Lange, Keertan Dheda, Rumina Hasan, Uma Devi K. Ranganathan, Ruth McNerney, Matthew Ezewudo, Daniela M. Cirillo, Marco Schito, Claudio U. Köser, Timothy C. Rodwell

Published in: European Respiratory Journal, Issue 50/6, 2017, Page(s) 1701354, ISSN 0903-1936

DOI: 10.1183/13993003.01354-2017

Draft Genome Sequence of Mycobacterium brumae ATCC 51384

Author(s): Giuseppe D'Auria, Eduard Torrents, Marina Luquin, Iñaki Comas, Esther Julián

Published in: Genome Announcements, Issue 4/2, 2016, Page(s) e00237-16, ISSN 2169-8287

DOI: 10.1128/genomeA.00237-16

Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages

Author(s): David Stucki, Daniela Brites, Leïla Jeljeli, Mireia Coscolla, Qingyun Liu, Andrej Trauner, Lukas Fenner, Liliana Rutaihwa, Sonia Borrell, Tao Luo, Qian Gao, Midori Kato-Maeda, Marie Ballif, Matthias Egger, Rita Macedo, Helmi Mardassi, Milagros Moreno, Griselda Tudo Vilanova, Janet Fyfe, Maria Globan, Jackson Thomas, Frances Jamieson, Jennifer L Guthrie, Adwoa Asante-Poku, Dorothy Yeboah-Manu, Eddie Wampande, Willy Ssengooba, Moses Joloba, W Henry Boom, Indira Basu, James Bower, Margarida Saraiva, Sidra E G Vasconcellos, Philip Suffys, Anastasia Koch, Robert Wilkinson, Linda Gail-Bekker, Bijaya Malla, Serej D Ley, Hans-Peter Beck, Bouke C de Jong, Kadri Toit, Elisabeth Sanchez-Padilla, Maryline Bonnet, Ana Gil-Brusola, Matthias Frank, Veronique N Penlap Beng, Kathleen Eisenach, Issam Alani, Perpetual Wangui Ndung'u, Gunturu Revathi, Florian Gehre, Suriya Akter, Francine Ntoumi, Lynsey Stewart-Isherwood, Nyanda E Ntinginya, Andrea Rachow, Michael Hoelscher, Daniela Maria Cirillo, Girts Skenders, Sven Hoffner, Daiva Bakonyte, Petras Stakenas, Roland Diel, Valeriu Crudu, Olga Moldovan, Sahal Al-Hajoj, Larissa Otero, Francesca Barletta, E Jane Carter, Lameck Diero, Philip Supply, Iñaki Comas, Stefan Niemann, Sebastien Gagneux

Published in: Nature Genetics, Issue 48/12, 2016, Page(s) 1535-1543, ISSN 1061-4036

DOI: 10.1038/ng.3704

Mycobacterium tuberculosis Acquires Limited Genetic Diversity in Prolonged Infections, Reactivations and Transmissions Involving Multiple Hosts

Author(s): Marta Herranz, Ilva Pole, Iveta Ozere, Álvaro Chiner-Oms, Miguel Martínez-Lirola, Felipe Pérez-García, Paloma Gijón, María Jesús Ruiz Serrano, Laura Clotet Romero, Oscar Cuevas, Iñaki Comas, Emilio Bouza, Laura Pérez-Lago, Darío García-de-Viedma

Published in: Frontiers in Microbiology, Issue 8, 2018, ISSN 1664-302X

DOI: 10.3389/fmicb.2017.02661

In-Depth Characterization and Functional Analysis of Clonal Variants in a Mycobacterium tuberculosis Strain Prone to Microevolution

Author(s): Yurena Navarro, Laura Pérez-Lago, Marta Herranz, Olalla Sierra, Iñaki Comas, Javier Sicilia, Emilio Bouza, Darío García de Viedma

Published in: Frontiers in Microbiology, Issue 8, 2017, ISSN 1664-302X

DOI: 10.3389/fmicb.2017.00694

A novel strategy based on genomics and specific PCR reveals how a multidrug-resistant Mycobacterium tuberculosis strain became prevalent in Equatorial Guinea 15 years after its emergence

Author(s): L. Pérez-Lago, S. Izco, M. Herranz, G. Tudó, M. Carcelén, I. Comas, O. Sierra, J. González-Martín, M.J. Ruiz-Serrano, J. Eyene, E. Bouza, D. García de Viedma

Published in: Clinical Microbiology and Infection, Issue 23/2, 2017, Page(s) 92-97, ISSN 1198-743X

DOI: 10.1016/j.cmi.2016.10.006

The Troika Host–Pathogen–Extrinsic Factors in Tuberculosis: Modulating Inflammation and Clinical Outcomes

Author(s): Helder Novais Bastos, Nuno S. Osório, Sebastien Gagneux, Iñaki Comas, Margarida Saraiva

Published in: Frontiers in Immunology, Issue 8, 2018, ISSN 1664-3224

DOI: 10.3389/fimmu.2017.01948

Gene expression models based on a reference laboratory strain are poor predictors of Mycobacterium tuberculosis complex transcriptional diversity

Author(s): Álvaro Chiner-Oms, Fernando González-Candelas, Iñaki Comas

Published in: Scientific Reports, Issue 8/1, 2018, ISSN 2045-2322

DOI: 10.1038/s41598-018-22237-5

Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing

Author(s): CRyPTIC Consortium and the 100,000 Genomes Project, Allix-Béguec C, Arandjelovic I, Bi L, Beckert P, Bonnet M, Bradley P, Cabibbe AM, Cancino-Muñoz I, Caulfield MJ, Chaiprasert A, Cirillo DM, Clifton DA, Comas I, Crook DW, De Filippo MR, de Neeling H, Diel R, Drobniewski FA, Faksri K, Farhat MR, Fleming J, Fowler P, Fowler TA, Gao Q, Gardy J, Gascoyne-Binzi D, Gibertoni-Cruz AL, Gil-Brusola A, Golubchik T, Gonzalo X, Grandjean L, He G, Guthrie JL, Hoosdally S, Hunt M, Iqbal Z, Ismail N, Johnston J, Khanzada FM, Khor CC, Kohl TA, Kong C, Lipworth S, Liu Q, Maphalala G, Martinez E, Mathys V, Merker M, Miotto P, Mistry N, Moore DAJ, Murray M, Niemann S, Omar SV, Ong RT, Peto TEA, Posey JE, Prammananan T, Pym A, Rodrigues C, Rodrigues M, Rodwell T, Rossolini GM, Sánchez Padilla E, Schito M, Shen X, Shendure J, Sintchenko V, Sloutsky A, Smith EG, Snyder M, Soetaert K, Starks AM, Supply P, Suriyapol P, Tahseen S, Tang P, Teo YY, Thuong TNT, Thwaites G, Tortoli E, van Soolingen D, Walker AS, Walker TM, Wilcox M, Wilson DJ, Wyllie D, Yang Y, Zhang H, Zhao Y, Zhu B.

Published in: New England Journal of Medicine, Issue 379/15, 2018, Page(s) 1403-1415, ISSN 0028-4793

DOI: 10.1056/NEJMoa1800474

New Genome-Wide Algorithm Identifies Novel In-Vivo Expressed Mycobacterium Tuberculosis Antigens Inducing Human T-Cell Responses with Classical and Unconventional Cytokine Profiles

Author(s): Mariateresa Coppola, Krista E. van Meijgaarden, Kees L. M. C. Franken, Susanna Commandeur, Gregory Dolganov, Igor Kramnik, Gary K. Schoolnik, Inaki Comas, Ole Lund, Corine Prins, Susan J. F. van den Eeden, Gro E. Korsvold, Fredrik Oftung, Annemieke Geluk, Tom H. M. Ottenhoff

Published in: Scientific Reports, Issue 6/1, 2016, ISSN 2045-2322

DOI: 10.1038/srep37793

Book chapters (1)

Genomic epidemiology of tuberculosis

Author(s): Iñaki Comas

Published in: 2017, Page(s) 79-93

DOI: 10.1007/978-3-319-64371-7_4

Project information

TB-ACCELERATE

Grant agreement ID: 638553

Status

Ongoing project

Start date

1 July 2015
End date

30 June 2021

Funded under:

H2020-EU.1.1.

Overall budget:

€ 1 671 875
EU contribution

€ 1 671 875

Hosted by:

AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS

Project information

TB-ACCELERATE

Grant agreement ID: 638553

Status

Ongoing project

Start date

1 July 2015
End date

30 June 2021

Funded under:

H2020-EU.1.1.

Overall budget:

€ 1 671 875
EU contribution

€ 1 671 875

Hosted by:

AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS

Spain

Project information

TB-ACCELERATE

Grant agreement ID: 638553

Status

Ongoing project

Start date

1 July 2015
End date

30 June 2021

Funded under:

H2020-EU.1.1.

Overall budget:

€ 1 671 875
EU contribution

€ 1 671 875

Hosted by:

AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS

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Last update: 31 October 2019

Record number: 197839

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Periodic Reporting for period 3 - TB-ACCELERATE (Integrating genomics, epidemiology and evolution to accelerate tuberculosis eradication)

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