Phylogeography and Molecular Epidemiology of Yersinia pestis in Madagascar

Amy J Vogler,Paul Keim,Stephen M Beckstrom-Sternberg,Suzanne Chanteau,Jacques Ravel,Mark Eppinger,Roxanne Nera,Mark Achtman,Philippe Roumagnac,David M Wagner,Bruno W Rasoamanana,Lila Rahalison,Fabien Chan,Judy Lee

doi:10.1371/journal.pntd.0001319

Abstract

BackgroundPlague 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.Methodology/Principal FindingsWe 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/SignificanceThe 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.

Highlights

Throughout recorded history, Yersinia pestis, etiologic agent of plague, has spread multiple times from foci in Central Asia in greatly widening swaths as human-mediated transport became more efficient [1]
There is 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
Genetic Diversity of Y. pestis in Madagascar Our hypervariable-locus and genome-based approaches identified a relatively high level of genetic diversity among the 262 Malagasy isolates from 25 districts from 1939–2005

Summary

Introduction

Throughout recorded history, Yersinia pestis, etiologic agent of plague, has spread multiple times from foci in Central Asia in greatly widening swaths as human-mediated transport became more efficient [1]. 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. 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 variablenumber tandem repeat (VNTR) loci to gain insight into the maintenance and spread of Y. pestis in Madagascar

Methods

Results

Discussion

Conclusion