title: The spread of hepatitis C virus genotype 1a in North America: a retrospective phylogenetic study.
abstract: The timing of the initial spread of hepatitis C virus genotype 1a in North America is controversial. In particular, how and when hepatitis C virus reached extraordinary prevalence in specific demographic groups remains unclear. We quantified, using all available hepatitis C virus sequence data and phylodynamic methods, the timing of the spread of hepatitis C virus genotype 1a in North America.
  
  
  
  We screened 45 316 publicly available sequences of hepatitis C virus genotype 1a for location and genotype, and then did phylogenetic analyses of available North American sequences from five hepatitis C virus genes (E1, E2, NS2, NS4B, NS5B), with an emphasis on including as many sequences with early collection dates as possible. We inferred the historical population dynamics of this epidemic for all five gene regions using Bayesian skyline plots.
  
  
  
  Most of the spread of genotype 1a in North America occurred before 1965, and the hepatitis C virus epidemic has undergone relatively little expansion since then. The effective population size of the North American epidemic stabilised around 1960. These results were robust across all five gene regions analysed, although analyses of each gene separately show substantial variation in estimates of the timing of the early exponential growth, ranging roughly from 1940 for NS2, to 1965 for NS4B.
  
  
  
  The expansion of genotype 1a before 1965 suggests that nosocomial or iatrogenic factors rather than past sporadic behavioural risk (ie, experimentation with injection drug use, unsafe tattooing, high risk sex, travel to high endemic areas) were key contributors to the hepatitis C virus epidemic in North America. Our results might reduce stigmatisation around screening and diagnosis, potentially increasing rates of screening and treatment for hepatitis C virus.
  
  
  
  The Canadian Institutes of Health Research, Michael Smith Foundation for Health Research, and BC Centre for Excellence in HIV/AIDS.
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada; Department of Medicine, University of British Columbia, Vancouver, BC, Canada. Electronic address: jjoy@cfenet.ubc.ca.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Joy
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
authors.forename: Rosemary M
authors.initials: RM
authors.lastname: McCloskey
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
authors.forename: Thuy
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Liang
authors.affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Yury
authors.initials: Y
authors.lastname: Khudyakov
authors.affiliation: BC Centre for Disease Control, Vancouver, BC, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Olmstead
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; BC Centre for Disease Control, Vancouver, BC, Canada.
authors.forename: Mel
authors.initials: M
authors.lastname: Krajden
authors.affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Ward
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada; Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada; Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Julio S G
authors.initials: JSG
authors.lastname: Montaner
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada; Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Art F Y
authors.initials: AFY
authors.lastname: Poon
mesh_terms: D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics*; D006526:Hepatitis C / Q000453:epidemiology* / Q000635:transmission / Q000821:virology; D006801:Humans; D008137:Longitudinal Studies; D009656:North America / Q000453:epidemiology; D010802:Phylogeny; D015995:Prevalence; D012367:RNA, Viral; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D013997:Time Factors
chemical_list: D012367:RNA, Viral