Epidemiology of Mycobacterium abscessus in England: an observational study

Abstract

Background Mycobacterium abscessus has emerged as a significant clinical concern following reports that it is readily transmissible in health-care settings between patients with cystic fibrosis. We linked routinely collected whole-genome sequencing and health-care usage data with the aim of investigating the extent to which such transmission explains acquisition in patients with and without cystic fibrosis in England.Methods In this retrospective observational study, we analysed consecutive M abscessus whole-genome sequencing data from England (beginning of February, 2015, to Nov 14, 2019) to identify genomically similar isolates. Linkage to a national health-care usage database was used to investigate possible contacts between patients. Multivariable regression analysis was done to investigate factors associated with acquisition of a genomically clustered strain (genomic distance <25 single nucleotide polymorphisms [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 isolates from ten or more patients, all but one contained patients with cystic fibrosis and patients without cystic fibrosis. Patients with cystic fibrosis were equally likely to have clustered isolates (258 [60%] of 431 patients) as those without cystic fibrosis (322 [63%] of 513 patients; p=0•38). Highdensity phylogenetic clusters were randomly distributed over a wide geographical area. Most 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 (adjusted odds ratio 1•14 per 10 years, 95% CI 1•04-1•26), but not time spent as an hospital inpatient or outpatient. We identified two sibling pairs with cystic fibrosis with genetically highly divergent isolates and one pair with closely related isolates, and 25 uninfected presumed household contacts with cystic fibrosis.Interpretation Previously identified widely disseminated dominant clones of M abscessus are not restricted to patients with cystic fibrosis and occur in other chronic respiratory diseases. Although our analysis showed a small number of cases where person-to-person transmission could not be excluded, it did not support this being a major mechanism for M abscessus dissemination at a national level in England. Overall, these data should reassure patients and clinicians that the risk of acquisition from other patients in health-care settings is relatively low and motivate future research efforts to focus on identifying routes of acquisition outside of the cystic fibrosis healthcare-associated niche.

Whole Genome Sequencing in the Management of Non-Tuberculous Mycobacterial Infections

“…These clones are associated with poorer clinical outcomes and showed increased intracellular survival, pathogenicity, and virulence in macrophage and mouse models [99]. Interestingly, the study of Lipworth et al showed that most genetically related M. abscessus clones isolated from CF patients had no identifiable relevant epidemiological traceback [100]. In addition, Bronson et al performed a comparative genomic analysis of 1279 M. abscessus complex genomes from CF and non-CF patients.…”

Mutation rates and adaptive variation among the clinically dominant clusters ofMycobacterium abscessus

“…However, a number of epidemiological studies have refuted personto-person transmission as a major mode of Mab dissemination. [5][6][7][8][9][10][11] Reconciling these conflicting lines of evidence is important as they dictate public health practice and allocation of resources to protect vulnerable populations from infection. However, it is still unclear what role transmission plays in the emergence of Mab clusters.…”

“…4 Interpreting tree structures in the context of population history is aided by phylogenetic dating, which translates genetic distances into time scale. Previous studies 4,9,12,13 have estimated molecular clock rates in Mab but these have been limited to subpopulations within clusters. Here we report on molecular clock rate estimation for the deep branches of the M. a. abscessus phylogeny and for within-host isolates belonging to clusters.…”

Comparison of Isogenic Strains Shows No Evidence of Altered Nosocomial Transmission-Competency of Rough, GPL-Negative Mycobacterium abscessus Strains

“…Whole genome sequencing (WGS) analysis of a global collection of clinical isolates has suggested many acquisitions of M. abscessus infections are humanly transmitted through direct contact, aerosol, or fomites ( 4 ). However, other epidemiologic and WGS analyses have shown that while patient-to-patient transmission exists, it does not account for the majority of cases of M. abscessus infections among cystic fibrosis patients ( 5 – 8 ).The question of infectivity and spread of different isolates is therefore of paramount importance to infection-control measures in hospitals and outpatient clinics, especially in highly susceptible populations.…”