Temporal phylogeography of Yersinia pestis in Madagascar: Insights into the long-term maintenance of plague

Abstract

BackgroundYersinia pestis appears to be maintained in multiple, geographically separate, and phylogenetically distinct subpopulations within the highlands of Madagascar. However, the dynamics of these locally differentiated subpopulations through time are mostly unknown. To address that gap and further inform our understanding of plague epidemiology, we investigated the phylogeography of Y. pestis in Madagascar over an 18 year period.Methodology/Principal findingsWe generated whole genome sequences for 31 strains and discovered new SNPs that we used in conjunction with previously identified SNPs and variable-number tandem repeats (VNTRs) to genotype 773 Malagasy Y. pestis samples from 1995 to 2012. We mapped the locations where samples were obtained on a fine geographic scale to examine phylogeographic patterns through time. We identified 18 geographically separate and phylogenetically distinct subpopulations that display spatial and temporal stability, persisting in the same locations over a period of almost two decades. We found that geographic areas with higher levels of topographical relief are associated with greater levels of phylogenetic diversity and that sampling frequency can vary considerably among subpopulations and from year to year. We also found evidence of various Y. pestis dispersal events, including over long distances, but no evidence that any dispersal events resulted in successful establishment of a transferred genotype in a new location during the examined time period.Conclusions/SignificanceOur analysis suggests that persistent endemic cycles of Y. pestis transmission within local areas are responsible for the long term maintenance of plague in Madagascar, rather than repeated episodes of wide scale epidemic spread. Landscape likely plays a role in maintaining Y. pestis subpopulations in Madagascar, with increased topographical relief associated with increased levels of localized differentiation. Local ecological factors likely affect the dynamics of individual subpopulations and the associated likelihood of observing human plague cases in a given year in a particular location.

Ancient pathogen genomics as an emerging tool for infectious disease research

“…Early evolution: plague in prehistory. The time of divergence between Y. pestis and Y. pseudotuberculosis has been difficult to determine given the wide temporal interval produced by recent molecular dating attempts 92,130,[169][170][171][172][173][187][188][189][190][191][192][193][194][195][196][197][198][199]200 , are shown as grey circles within their geographical country or region of isolation, and the size of each circle is proportional to the number of strains sequenced from each location (number indicated when more than one genome is shown). The areas highlighted in brown are regions that contain active plague foci as determined by contemporary or historical data.…”

“…The more phylogenetically derived branches 1-4 were formed through a rapid population expan sion event and are today found in Asia, Africa and the Americas 130 . Their wide distribution mainly reflects the geographical breadth of branch 1, which is associated with the third plague pandemic that spread worldwide during the 19th and 20th centuries 92 and is still respon sible for more confined epidemics such as those reported in Madagascar 173 .…”

Outbreak of Pneumonic Plague in 2017 on Madagascar

“…мадагаскарские штаммы представляют собой третью ветвь иррадиации восточного биовара (1.ORI3). она была завезена из индии на мадагаскар и укоренилась там, в то время как первая ветвь иррадиации (1.ORI1) распространилась по территории северной америки, а вторая (1.ORI2) получила множественное распространение в европе, Южной америке, африке и Юго-восточной азии [28,36].…”

“…анализ выделенных на о. мадагаскар штаммов Y. pestis был проведен с помощью различных методов молекулярного типирования. выявлено значительное генетическое разнообразие этих штаммов [21,34,36]. полногеномный SNP-анализ показал, что все мадагаскарские штаммы Y. pestis распадаются на два специфических для мадагаскара кластера: 1.ORI.3.k и его производный 1.ORI.3.d.…”

“…полногеномное секвенирование 31 штамма Y. pestis, а также VNTR-генотипирование 773 малагасийских образцов Y. pestis, выделенных с 1995 по 2012 год [36], подтвердило разделение штаммов на группы I (k) и II (d), с выявлением дополнительных линий в пределах каждой группы. в целом идентифицировано 18 основных филогенетических субгрупп, включая 13 SNP-линий (субгруппы h, j, l, q-z) и 5 MLVA (субгруппы I.C, I.G, I.E, I.L и II.D.1).…”