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Previous studies of <jats:italic>H. influenzae<\/jats:italic> infection dynamics and transmission in CF predominantly used molecular methods, lacking resolution. In this retrospective cohort study, representative yearly <jats:italic>H. influenzae<\/jats:italic> isolates from all pwCF attending the Calgary Adult CF Clinic with <jats:italic>H. influenzae<\/jats:italic> positive sputum cultures between 2002 and 2016 were typed by pulsed-field gel electrophoresis. Isolates with shared pulsotypes common to\u2009\u2265\u20092 pwCF were sequenced by Illumina MiSeq. Phylogenetic and pangenomic analyses were used to assess genetic relatedness within shared pulsotypes, and epidemiological investigations were performed to assess potential for healthcare associated transmission. <jats:italic>H. influenzae<\/jats:italic> infection was observed to be common (33% of patients followed) and dynamic in pwCF. Most infected pwCF exhibited serial infections with new pulsotypes (75% of pwCF with\u2009\u2265\u20092 positive cultures), with up to four distinct pulsotypes identified from individual patients. Prolonged infection by a single pulsotype was only rarely observed. Intra-patient genetic diversity was observed at the single-nucleotide polymorphism and gene content levels. Seven shared pulsotypes encompassing 39% of pwCF with <jats:italic>H. influenzae<\/jats:italic> infection were identified, but there was no evidence, within our sampling scheme, of direct patient-to-patient infection transmission.<\/jats:p>","DOI":"10.1038\/s41598-022-19240-2","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T19:02:50Z","timestamp":1663786970000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The natural history and genetic diversity of Haemophilus influenzae infecting the airways of adults with cystic fibrosis"],"prefix":"10.1038","volume":"12","author":[{"given":"Conrad","family":"Izydorczyk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara J.","family":"Waddell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"Weyant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Surette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjani","family":"Somayaji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey R.","family":"Rabin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Conly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deirdre L.","family":"Church","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Parkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"key":"19240_CR1","doi-asserted-by":"publisher","first-page":"26","DOI":"10.15172\/pneu.2015.6\/520","volume":"6","author":"MPE Slack","year":"2015","unstructured":"Slack, M. 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