title: Phylogeography and molecular epidemiology of Yersinia pestis in Madagascar.
abstract: BACKGROUND
  Plague was introduced to Madagascar in 1898 and continues to be a significant human health problem. It exists mainly in the central highlands, but in the 1990s was reintroduced to the port city of Mahajanga, where it caused extensive human outbreaks. Despite its prevalence, the phylogeography and molecular epidemiology of Y. pestis in Madagascar has been difficult to study due to the great genetic similarity among isolates. We examine island-wide geographic-genetic patterns based upon whole-genome discovery of SNPs, SNP genotyping and hypervariable variable-number tandem repeat (VNTR) loci to gain insight into the maintenance and spread of Y. pestis in Madagascar.
  
  
  RESULTS
  We analyzed a set of 262 Malagasy isolates using a set of 56 SNPs and a 43-locus multi-locus VNTR analysis (MLVA) system. We then analyzed the geographic distribution of the subclades and identified patterns related to the maintenance and spread of plague in Madagascar. We find relatively high levels of VNTR diversity in addition to several SNP differences. We identify two major groups, Groups I and II, which are subsequently divided into 11 and 4 subclades, respectively. Y. pestis appears to be maintained in several geographically separate subpopulations. There is also evidence for multiple long distance transfers of Y. pestis, likely human mediated. Such transfers have resulted in the reintroduction and establishment of plague in the port city of Mahajanga, where there is evidence for multiple transfers both from and to the central highlands.
  
  
  CONCLUSIONS
  The maintenance and spread of Y. pestis in Madagascar is a dynamic and highly active process that relies on the natural cycle between the primary host, the black rat, and its flea vectors as well as human activity.
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, USA.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Vogler
authors.forename: Fabien
authors.initials: F
authors.lastname: Chan
authors.forename: David M
authors.initials: DM
authors.lastname: Wagner
authors.forename: Philippe
authors.initials: P
authors.lastname: Roumagnac
authors.forename: Judy
authors.initials: J
authors.lastname: Lee
authors.forename: Roxanne
authors.initials: R
authors.lastname: Nera
authors.forename: Mark
authors.initials: M
authors.lastname: Eppinger
authors.forename: Jacques
authors.initials: J
authors.lastname: Ravel
authors.forename: Lila
authors.initials: L
authors.lastname: Rahalison
authors.forename: Bruno W
authors.initials: BW
authors.lastname: Rasoamanana
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Beckstrom-Sternberg
authors.forename: Mark
authors.initials: M
authors.lastname: Achtman
authors.forename: Suzanne
authors.initials: S
authors.lastname: Chanteau
authors.forename: Paul
authors.initials: P
authors.lastname: Keim
mesh_terms: D000704:Analysis of Variance; D016000:Cluster Analysis; D004269:DNA, Bacterial / Q000737:chemistry; D006801:Humans; D008270:Madagascar / Q000453:epidemiology; D018598:Minisatellite Repeats / Q000235:genetics; D017720:Molecular Epidemiology / Q000379:methods; D058889:Molecular Typing; D058974:Phylogeography; D010930:Plague / Q000453:epidemiology* / Q000382:microbiology*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015010:Yersinia pestis / Q000235:genetics*
chemical_list: D004269:DNA, Bacterial