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Mycobacterium abscessus Genomic Clusters Span Geography and Patient Groups

28 Pages Posted: 19 Jan 2021

See all articles by Samuel Lipworth

Samuel Lipworth

University of Oxford - Nuffield Department of Medicine

Natasha Hough

Oxford University Hospitals NHS Foundation Trust

Natasha Weston

National Mycobacterial Reference Service- Central and North, Public Health England

Berit Muller-Pebody

Tuberculosis, Acute Respiratory, Gastrointestinal, Emerging/Zoonotic Infections and Travel Migrant Health Division, (T.A.R.G.E.T), National Infection Service, Public Health England

Nick Phin

Tuberculosis, Acute Respiratory, Gastrointestinal, Emerging/Zoonotic Infections and Travel Migrant Health Division, (T.A.R.G.E.T), National Infection Service, Public Health England

Richard Myers

Government of the United Kingdom - Public Health England

Stephen Chapman

Oxford University Hospitals NHS Foundation Trust

William Flight

Oxford University Hospitals NHS Foundation Trust

Eliza Alexander

Government of the United Kingdom - Public Health England

E. Grace Smith

Government of the United Kingdom - Public Health England

Esther Robinson

Government of the United Kingdom - Public Health England

Timothy E. A. Peto

University of Oxford, Nuffield Department of Medicine, John Radcliffe Hospital

Derrick W. Crook

University of Oxford - Nuffield Department of Medicine; University of Oxford - John Radcliffe Hospital

A. Sarah Walker

University of Oxford, Nuffield Department of Medicine, John Radcliffe Hospital

Susan Hopkins

University of Oxford - NIHR Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance; Public Health England Colindale

David William Eyre

Oxford University Hospitals NHS Foundation Trust

Timothy M. Walker

University of Oxford - Nuffield Department of Medicine

More...

Abstract

Background: Mycobacterium abscessus has emerged as a significant clinical concern following reports that it is readily transmissible in healthcare settings between patients with Cystic Fibrosis (CF).

Methods: We analysed consecutive M. abscessus whole-genome sequencing data from England (February-2015 to November-2019) to identify genomically similar isolates. Linkage to a national healthcare usage database was used to investigate possible contacts between patients. Multivariable regression analysis was performed to investigate factors associated with acquisition of a genomically clustered strain (within ≤25 SNPs).

Findings: 2297 isolates from 906 patients underwent whole-genome sequencing as part of the routine Public Health England diagnostic service. Of 14 genomic clusters containing ≥10 patients, all but one contained patients with CF and patients without CF. Patients with CF were equally likely to have clustered isolates as those without CF. High-density phylogenetic clusters were randomly distributed over a wide geographical area. The majority of isolates with a closest genetic neighbour consistent with potential transmission had no identifiable relevant epidemiological contacts. Having a clustered isolate was independently associated with increasing age but not time spent as an hospital inpatient/outpatient. We identified two CF sibling pairs with genetically highly divergent isolates and 1 pair with closely related isolates, as well as 25 uninfected presumed household contacts with CF.

Interpretation: Previously identified widely disseminated dominant clones of M. abscessus are not restricted to CF patients and occur in other chronic respiratory diseases. Our analysis does not support person-to-person transmission as an important mechanism in M. abscessus dissemination at a national level in England.

Funding Statement: The research was supported by the National Institute for Health Research (NIHR) Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance (HPRU 2012-10041) at the University of Oxford in partnership with Public Health England (PHE) and by Oxford NIHR Biomedical Research Centre. T Peto, AS Walker and DW Crook are NIHR Senior Investigators. Computation used the Oxford Biomedical Research Computing (BMRC) facility, a joint development between the Wellcome Centre for Human Genetics and the Big Data Institute supported by Health Data Research UK and the NIHR Oxford Biomedical Research Centre. The report presents independent research funded by NIHR.

Declaration of Interests: SL is supported by a Medical Research Council Clinical Research Training Fellowship. DWE declares lecture fees from Gilead, outside the submitted work. TMW is a Wellcome Trust Clinical Career Development Fellow (214560/Z/18/Z). The remaining authors declare no conflicts of interest.

Ethics Approval Statement: This work was carried out as a public health investigation with internal approval from Public Health England and therefore ethics committee approval was not required.

Suggested Citation

Lipworth, Samuel and Hough, Natasha and Weston, Natasha and Muller-Pebody, Berit and Phin, Nick and Myers, Richard and Chapman, Stephen and Flight, William and Alexander, Eliza and Smith, E. Grace and Robinson, Esther and Peto, Timothy E. A. and Crook, Derrick W. and Walker, A. Sarah and Hopkins, Susan and Eyre, David William and Walker, Timothy M., Mycobacterium abscessus Genomic Clusters Span Geography and Patient Groups. Available at SSRN: https://ssrn.com/abstract=3745118 or http://dx.doi.org/10.2139/ssrn.3745118

Samuel Lipworth (Contact Author)

University of Oxford - Nuffield Department of Medicine ( email )

New Road
Oxford, OX1 1NF
United Kingdom

Natasha Hough

Oxford University Hospitals NHS Foundation Trust ( email )

Natasha Weston

National Mycobacterial Reference Service- Central and North, Public Health England ( email )

Berit Muller-Pebody

Tuberculosis, Acute Respiratory, Gastrointestinal, Emerging/Zoonotic Infections and Travel Migrant Health Division, (T.A.R.G.E.T), National Infection Service, Public Health England ( email )

Nick Phin

Tuberculosis, Acute Respiratory, Gastrointestinal, Emerging/Zoonotic Infections and Travel Migrant Health Division, (T.A.R.G.E.T), National Infection Service, Public Health England ( email )

Richard Myers

Government of the United Kingdom - Public Health England

Wellington House
133-155 Waterloo Road
London, SE1 8UG
United Kingdom

Stephen Chapman

Oxford University Hospitals NHS Foundation Trust

William Flight

Oxford University Hospitals NHS Foundation Trust ( email )

Eliza Alexander

Government of the United Kingdom - Public Health England

Wellington House
133-155 Waterloo Road
London, SE1 8UG
United Kingdom

E. Grace Smith

Government of the United Kingdom - Public Health England

Wellington House
133-155 Waterloo Road
London, SE1 8UG
United Kingdom

Esther Robinson

Government of the United Kingdom - Public Health England

Wellington House
133-155 Waterloo Road
London, SE1 8UG
United Kingdom

Timothy E. A. Peto

University of Oxford, Nuffield Department of Medicine, John Radcliffe Hospital ( email )

Oxford, Oxfordshire, England
United Kingdom

Derrick W. Crook

University of Oxford - Nuffield Department of Medicine

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

University of Oxford - John Radcliffe Hospital ( email )

Oxford, Oxfordshire, England
United Kingdom

A. Sarah Walker

University of Oxford, Nuffield Department of Medicine, John Radcliffe Hospital ( email )

Oxford, Oxfordshire, England
United Kingdom

Susan Hopkins

University of Oxford - NIHR Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance ( email )

Oxford
United Kingdom

Public Health England Colindale ( email )

61 Colindale Avenue
London, NW9 5EQ
United Kingdom

David William Eyre

Oxford University Hospitals NHS Foundation Trust ( email )

Timothy M. Walker

University of Oxford - Nuffield Department of Medicine ( email )

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

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