Use of a Whole Genome Sequencing-based approach for Mycobacterium tuberculosis surveillance in Europe in 2017–2019: an ECDC pilot study
- Elisa Tagliani1⇑,
- Richard Anthony2,11,
- Thomas A. Kohl3,4,11,
- Albert de Neeling2,
- Vlad Nikolayevskyy5,6,
- Csaba Ködmön7,
- Florian P. Maurer8,9,
- Stefan Niemann3,4,
- Dick van Soolingen2,
- Marieke J. van der Werf7,
- Daniela Maria Cirillo1 and
- on behalf of the ECDC molecular surveillance project participants10
- 1Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
- 2Tuberculosis reference laboratory, Infectious Diseases Research, Diagnostics and laboratory Surveillance (IDS), National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands
- 3Molecular and Experimental Mycobacteriology, National Reference Center for Mycobacteria, Research Center, Borstel, Germany
- 4German Center for Infection Research, partner site Borstel-Hamburg-Lübeck-Riems, Borstel, Germany
- 5Public Health England, London, United Kingdom
- 6Imperial College London, London, United Kingdom
- 7European Centre for Disease Prevention and Control, Stockholm, Sweden
- 8Diagnostic Mycobacteriology, National Reference Center for Mycobacteria, Borstel, Germany
- 9Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- 10The participants are listed at the end of the article
- 1111Contributed equally
- Elisa Tagliani, Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, via Olgettina 58, 20132 Milano, ITALY. E-mail: tagliani.elisa{at}hsr.it
Abstract
Whole genome sequencing (WGS) can be used for molecular typing and characterisation of Mycobacterium tuberculosis complex (MTBC) strains. We evaluated the systematic use of a WGS-based approach for MTBC surveillance involving all European Union/European Economic Area (EU/EEA) countries and highlight the challenges and lessons learned to be considered for the future development of a WGS-based surveillance system.
WGS and epidemiological data of patients with rifampicin (RR) and multi-drug resistant (MDR)-tuberculosis (TB) were collected from EU/EEA countries between January 2017 and December 2019. WGS-based genetic relatedness analysis was performed using a standardised approach including both core genome multilocus sequence typing (cgMLST), and single nucleotide polymorphism (SNP)-based calculation of distances on all WGS data that fulfilled minimum quality criteria to ensure data comparability.
From 25 countries, 2218 RR/MDR-MTBC isolates were collected. Fifty-six cross-border clusters with increased likelihood of recent transmission (≤5 SNPs distance) comprising a total of 316 RR/MDR-MTBC isolates were identified. The cross-border clusters included between two and thirty resistant isolates from two to six countries unravelling different RR/MDR-TB transmission patterns in Western and Eastern EU.
This pilot study shows that a WGS-based surveillance system is not only feasible but can efficiently elucidate the dynamics of in-country and cross-border RR/MDR-TB transmission across EU/EEA countries. Lessons learned from this study highlight how the establishment of an EU/EEA centralised WGS-based surveillance system for TB will require strengthening of national integrated systems performing prospective WGS surveillance and the development of clear procedures to facilitate international collaboration for the investigation of cross-border clusters.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. TAGLIANI reports grants from ECDC public tender: OJ/2017/OCS/7766
Conflict of interest: Dr. Anthony reports grants from ECDC public tender: OJ/2017/OCS/7766 “Pilot study on the use of Whole Genome Sequencing for molecular typing and characterization of M. tuberculosis in the EU/EEA”, during the conduct of the study;.
Conflict of interest: Dr. Kohl has nothing to disclose.
Conflict of interest: Dr. de Neeling reports grants from ECDC public tender: OJ/2017/OCS/7766 “Pilot study on the use of Whole Genome Sequencing for molecular typing and characterization of M. tuberculosis in the EU/EEA”, during the conduct of the study;.
Conflict of interest: Dr. Nikolayevskyy reports grants from ECDC, during the conduct of the study;.
Conflict of interest: Dr. Ködmön has nothing to disclose.
Conflict of interest: Dr. Maurer has nothing to disclose.
Conflict of interest: Dr. Niemann reports grants from German Center for Infection Research, grants from Excellenz Cluster Precision Medicine in Chronic Inflammation EXC 2167, grants from Leibniz Science Campus Evolutionary Medicine of the LUNG (EvoLUNG), grants from ECDC public tender: OJ/2017/OCS/7766
Conflict of interest: Dr. van Soolingen has nothing to disclose.
Conflict of interest: Dr. van der Werf has nothing to disclose.
Conflict of interest: Dr. CIRILLO reports grants from ECDC public tender: OJ/2017/OCS/7766
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- Received June 11, 2020.
- Accepted July 17, 2020.
- Copyright ©ERS 2020