Dataset Information

Epidemiology of Clostridium difficile in infants in Oxfordshire, UK: Risk factors for colonization and carriage, and genetic overlap with regional C. difficile infection strains.

ABSTRACT: Background: Approximately 30-40% of children <1 year of age are Clostridium difficile colonized, and may represent a reservoir for adult C. difficile infections (CDI). Risk factors for colonization with toxigenic versus non-toxigenic C. difficile strains and longitudinal acquisition dynamics in infants remain incompletely characterized.

Methods: Predominantly healthy infants (?2 years) were recruited in Oxfordshire, UK, and provided ?1 fecal samples. Independent risk factors for toxigenic/non-toxigenic C. difficile colonization and acquisition were identified using multivariable regression. Infant C. difficile isolates were whole-genome sequenced to assay genetic diversity and prevalence of toxin-associated genes, and compared with sequenced strains from Oxfordshire CDI cases.

Results: 338/365 enrolled infants provided 1332 fecal samples, representing 158 C. difficile colonization or carriage episodes (107[68%] toxigenic). Initial colonization was associated with age, and reduced with breastfeeding but increased with pet dogs. Acquisition was associated with older age, Caesarean delivery, and diarrhea. Breastfeeding and pre-existing C. difficile colonization reduced acquisition risk. Overall 13% of CDI C. difficile strains were genetically related to infant strains. 29(18%) infant C. difficile sequences were consistent with recent direct/indirect transmission to/from Oxfordshire CDI cases (?2 single nucleotide variants [SNVs]); 79(50%) shared a common origin with an Oxfordshire CDI case within the last ~5 years (0-10 SNVs). The hypervirulent, epidemic ST1/ribotype 027 remained notably absent in infants in this large study, as did other lineages such as STs 10/44 (ribotype 015); the most common strain in infants was ST2 (ribotype 020/014)(22%).

Conclusions: In predominantly healthy infants without significant healthcare exposure C. difficile colonization and acquisition reflect environmental exposures, with pet dogs identified as a novel risk factor. Genetic overlap between some infant strains and those isolated from CDI cases suggest common community reservoirs of these C. difficile lineages, contrasting with those lineages found only in CDI cases, and therefore more consistent with healthcare-associated spread.

SUBMITTER: Stoesser N

PROVIDER: S-EPMC5559064 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Epidemiology of Clostridium difficile in infants in Oxfordshire, UK: Risk factors for colonization and carriage, and genetic overlap with regional C. difficile infection strains.

Stoesser Nicole N Eyre David W DW Quan T Phuong TP Godwin Heather H Pill Gemma G Mbuvi Emily E Vaughan Alison A Griffiths David D Martin Jessica J Fawley Warren W Dingle Kate E KE Oakley Sarah S Wanelik Kazimierz K Finney John M JM Kachrimanidou Melina M Moore Catrin E CE Gorbach Sherwood S Riley Thomas V TV Crook Derrick W DW Peto Tim E A TEA Wilcox Mark H MH Walker A Sarah AS

PloS one 20170816 8

<h4>Background</h4>Approximately 30-40% of children <1 year of age are Clostridium difficile colonized, and may represent a reservoir for adult C. difficile infections (CDI). Risk factors for colonization with toxigenic versus non-toxigenic C. difficile strains and longitudinal acquisition dynamics in infants remain incompletely characterized.<h4>Methods</h4>Predominantly healthy infants (≤2 years) were recruited in Oxfordshire, UK, and provided ≥1 fecal samples. Independent risk factors for tox ...[more]

PMID: 28813461

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Project description:BACKGROUND:The hypervirulent Clostridium difficile ribotype 027 can be classified into subtypes, but it unknown if these differ in terms of severity of C. difficile infection (CDI). Genomic studies of C. difficile 027 strains have established that they are rich in mobile genetic elements including prophages. This study combined physiological studies, electron microscopy analysis and molecular biology to determine the potential role of temperate bacteriophages in disease and diversity of C. difficile 027. METHODOLOGY/PRINCIPAL FINDINGS:We induced prophages from 91 clinical C. difficile 027 isolates and used transmission electron microscopy and pulsed-field gel electrophoresis to characterise the bacteriophages present. We established a correlation between phage morphology and subtype. Morphologically distinct tailed bacteriophages belonging to Myoviridae and Siphoviridae were identified in 63 and three isolates, respectively. Dual phage carriage was observed in four isolates. In addition, there were inducible phage tail-like particles (PT-LPs) in all isolates. The capacity of two antibiotics mitomycin C and norfloxacin to induce prophages was compared and it was shown that they induced specific prophages from C. difficile isolates. A PCR assay targeting the capsid gene of the myoviruses was designed to examine molecular diversity of C. difficile myoviruses. Phylogenetic analysis of the capsid gene sequences from eight ribotypes showed that all sequences found in the ribotype 027 isolates were identical and distinct from other C. difficile ribotypes and other bacteria species. CONCLUSION/SIGNIFICANCE:A diverse set of temperate bacteriophages are associated with C. difficile 027. The observed correlation between phage carriage and the subtypes suggests that temperate bacteriophages contribute to the diversity of C. difficile 027 and may play a role in severity of disease associated with this ribotype. The capsid gene can be used as a tool to identify C. difficile myoviruses present within bacterial genomes.

Dataset Information

Epidemiology of Clostridium difficile in infants in Oxfordshire, UK: Risk factors for colonization and carriage, and genetic overlap with regional C. difficile infection strains.

Publications

Epidemiology of Clostridium difficile in infants in Oxfordshire, UK: Risk factors for colonization and carriage, and genetic overlap with regional C. difficile infection strains.

Similar Datasets

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