Studying Infection Transmission Dynamics Amongst Individuals with Cystic Fibrosis
Date
2023-11-27
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Abstract
Cystic fibrosis (CF) impairs the natural immune defenses of the lungs and leaves affected individuals susceptible to incident and chronic lung infections by a variety of microbial pathogens. The potential for patient-to-patient transmission of lung infections between persons with CF (pwCF) was first realized in the 1980's with incident infections caused by members of the Burkholderia cepacia complex, followed in the 1990’s by the recognition of epidemic strains of the archetypal CF pathogen, Pseudomonas aeruginosa. To mitigate this risk, progressively stringent infection prevention and control (IPC) guidelines have been implemented to prevent further spread amongst pwCF. However, few longitudinal studies assessing the potential for transmission of CF pathogens have been performed. Accordingly, the primary objective of this thesis was to investigate the natural history and potential for transmission of four key CF pathogens amongst pwCF attending the Southern Alberta Adult CF Clinic (SAACFC) in Calgary, Canada between 2002-2020: Escherichia coli, Haemophilus influenzae, Stenotrophomonas maltophilia, and P. aeruginosa. Whole-genome sequencing +/- pulse field gel electrophoresis were utilized for investigating infection transmission to achieve maximal resolution. A wide variety of genomic approaches were investigated for the inference of patient-to-patient transmission from genomic data, including several measures of genetic relatedness, phylogenetics, and pangenome analyses. These were combined with investigations of epidemiological linkages between pwCF to identify potential transmission opportunities. While a high degree of strain sharing was observed for all examined species, healthcare associated patient-to-patient transmission was rare through two decades. No instances of potential transmission were observed between 2002-2020 for E. coli, H. influenzae, or S. maltophilia, while infrequent transmission was postulated for P. aeruginosa. However, evidence of widespread historical transmission of epidemic P. aeruginosa strains was observed prior to patients entering the SAACFC. These findings corroborate the paradigm that most lung infections in pwCF in the current era of rigorous IPC mandates are acquired by independent acquisition events from independent environmental sources. Overall, the findings of this thesis contribute not only to CF and infection control literature, but also to the application of whole-genome sequencing to the study of infection transmission.
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Keywords
cystic fibrosis, infection transmission, genomic epidemiology
Citation
Izydorczyk, C. (2023). Studying infection transmission dynamics amongst individuals with cystic fibrosis (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.