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Madagascar's Plague Phylogeography Points to Ongoing Local Transmission

NEW YORK (GenomeWeb) – A new genetic and genomic analysis is offering a look at local contributors to plague transmission in Madagascar.

Investigators from the US, Madagascar, and the UK tapped into a collection of Yersinia pestis isolates collected in Madagascar over nearly two decades, using SNPs uncovered by whole-genome sequencing and/or targeted genotyping to tease apart the plague-causing pathogen's phylogeographic history in the region. Their findings, published online yesterday in PLOS Neglected Tropical Diseases, highlighted 18 Y. pestis sub-populations that turned up in distinct geographic locales.

The team noted that these plague pathogen sub-populations appeared to remain relatively stable and geographically restricted over long periods of time, hinting that local transmission may be a much more common contributor to plague outbreaks than the introduction of new Y. pestis isolates from broader epidemics.

"Transfers of plague from one location to another definitely occur, but appear to seldom result in the transplanted phylogenetic group becoming successfully established in a new location," corresponding authors Minoarisoa Rajerison, with the Pasteur Institute of Madagascar's Plague Research Institute, and Northern Arizona University researcher David Wagner, and their co-authors wrote. "Persistent, local transmission cycles are likely responsible for the long term maintenance of plague in Madagascar, rather than repeated wide scale disease transmission events."

Using Illumina HiSeq instruments, the researchers did paired-end whole-genome sequencing on 31 Y. pestis strains from a large set of samples Madagascar collected at hundreds of Madagascar villages and dozens of districts from 1995 to 2012. They profiled another 773 strains by genotyping 63 known SNPs and dozens more multilocus variable number tandem repeat analysis (MLVA) loci.

From the new genome sequences, the team tracked down 170 previously unappreciated Y. pestis SNPs. With variants present across the plague pathogen collection, meanwhile, the group identified 13 main Y. pestis lineages defined by SNP patterns and five MLVA-defined lineages.

When they considered Y. pestis phylogeny alongside information on where the strains were collected, the researchers got a glimpse at the pathogen's phylogeography in Madagascar, where strain distribution tended to mirror genetic relationships between the Y. pestis lineages.

"Overall, spatial clustering of the individual nodes was consistent with the SNP phylogeny, with phylogenetically close nodes clustered near to each other spatially," the authors wrote, noting that "nodes that tended to be more geographically dispersed were also generally more basal within the phylogeny and/or contained larger numbers of samples with substantial MLVA diversity."

Likewise, the team found that Y. pestis sub-populations at each site were fairly consistent from one year to the next, despite some annual variations detected in some of the sampling sites. 

"Persistent endemic cycles of Y. pestis transmission within local areas of Madagascar result in strong, consistent spatial structuring that persists through time," the researchers added. "Landscape likely influence local diversity of Y. pestis with increased topographical relief associated with increased levels of local differentiation, and the maintenance of multiple phylogenetically distinct sub-populations even within relatively short geographic distances."