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Published on: May 25, 2017
Clostridium difficile Whole Genome Sequencing Reveals Limited Transmission Among Symptomatic Children: A
Larry K Kociolek1,2, Dale N Gerding3,4, Robyn O Espinosa2
1Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago.
Insights
Pediatric Clostridium difficile infections (CDIs) are rising, but transmission is rare. Whole genome sequencing revealed diverse strains, with few cases linked to healthcare or community spread, suggesting limited Clostridium difficile transmission among children.
Area of Science:
- Infectious Diseases
- Microbiology
- Genomics
Background:
- Pediatric Clostridium difficile infections (CDIs) are increasing globally.
- Understanding transmission patterns of C. difficile in children is crucial but limited.
Purpose of the Study:
- To investigate C. difficile transmission dynamics in pediatric patients using whole genome sequencing (WGS).
- To identify the frequency and sources of C. difficile transmission among children with CDI.
Main Methods:
- Whole genome sequencing (WGS) of C. difficile isolates from children diagnosed with CDI.
- Comparison of genome sequences to identify isogenic strains (≤2-3 core genome single nucleotide variants).
- Investigation of healthcare exposures for patients with isogenic isolates.
Main Results:
- 104 genetically distinct C. difficile isolates were identified from 131 CDIs in 107 children.
- Only 11.9% of incident CDIs occurring ≥8 weeks after study initiation were linked to transmission events.
- Transmission events were infrequent across all CDI classes (hospital-onset healthcare facility-associated, community-associated, recurrent).
- Shared healthcare exposures were identified in only 7 of 10 putative transmission events.
- No evidence of community transmission was found based on postal code data.
Conclusions:
- Whole genome sequencing revealed high diversity of C. difficile strains in pediatric CDI cases.
- C. difficile transmission among symptomatic children is uncommon.
- Identified transmission events often lacked clear links to shared healthcare exposures, indicating challenges in pinpointing sources.
Background:
Although pediatric Clostridium difficile infections (CDIs) are increasing, C. difficile transmission patterns among children are poorly understood.
Methods:
We performed whole genome sequencing (WGS) on C. difficile isolates collected from children diagnosed with CDI between December 2012 and December 2013 at a single academic medical center. Genome sequences of isolates from CDIs diagnosed ≥8 weeks after study initiation were compared to all study isolate genome sequences. Among patients with isogenic isolates (≤2-3 core genome single nucleotide variants [SNVs] identified by pairwise SNV analyses), common inpatient and/or outpatient healthcare exposures were investigated.
Results:
Among 131 CDIs in 107 children, WGS identified 104 genetically distinct isolates. Of 84 incident CDIs occurring ≥8 weeks after study initiation, only 10 (11.9%) were caused by a strain isogenic to another cohort CDI isolate (putative transmission events). Proportions of each CDI class putatively associated with transmission were hospital-onset healthcare facility-associated (HCFA), 2/16 (12.5%); community-onset HCFA, 1/17 (5.9%); indeterminate, 1/11 (9.1%); community-associated (CA), 5/40 (12.5%); and recurrent, 1/21 (4.8%). Transmission events among CA and HCFA CDIs were similarly infrequent (5/40 [12.5%] vs 3/33 [9.1%]; P = .64). Shared healthcare facility exposures were only identified among 7/10 putative transmission events. Potential community transmission (same postal code) was not identified.
Conclusions:
WGS identified a highly diverse group of C. difficile isolates among children with CDI, including those with HCFA CDI. Clostridium difficile transmission among symptomatic children was very uncommon. Among putatively transmitted cases, investigation of shared healthcare exposures often did not identify a potential transmission source.
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