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Study Describes Two Plague Pathogen Subpopulations in Uganda

NEW YORK (GenomeWeb) – In a study appearing online today in PLOS Neglected Tropical Diseases, researchers from the US and Uganda described two genetically distinct Yersinia pestis populations that they detected by scrutinizing human plague cases in Uganda's West Nile region over almost a decade.

The team sifted through more than 1,000 suspected plague cases, confirming 61 cases with cultured samples. Analyses of SNP patterns, pulse-field gel electrophoresis (PFGE) profiles, and multiple tandem repeat analysis (MLVA) all pointed to the present of two genetically separate Y. pestis subspecies that turned up in parts of the country with different elevation levels.

"This improved understanding of Y. pestis subpopulations in the West Nile region will be useful for identifying ecologic and environmental factors associated with elevated plague risk," senior author Jeannine Petersen, a vector-borne diseases researcher at the US Centers of Disease Control and Prevention, and colleagues wrote.

Past SNP- and genome-based analyses have described several Y. pestis populations, the researchers noted, with the antiqua, or 1.ANT, population often turning up in East and Central Africa. On the other hand, 2.ANT antiqua Y. pestis populations have been detected in Asia, while orientalis (1.ORI) populations have been isolated in Madagascar, the Americas, and Southeast Asia, and mediaevalis (2.MED) populations of Y. pestis have been linked to other cases in Asia.

Nevertheless, they explained, disease-causing Y. pestis has not been genetically characterized in Uganda's West Nile region, an area where plague cases are found at relatively high rates.

For the new analysis, the team considered samples from 1,092 potentially plague-infected individuals who were treated in Uganda's Arua or Zombo districts between early 2004 and late 2012. Peak plague occurred in 2007, the group noted, when more than 300 cases were suspected.

The researchers successfully cultured Y. pestis from 61 patient blood samples, using DNA from these cultures to perform PFGE, assess MLVA at 18 variable number tandem repeat loci, and type nine SNPs using melt mismatch amplification mutation assays.

As expected, all of the isolates belonged to the 1.ANT population of Y. pestis. Even so, the team consistently picked up two previously undescribed sub-populations using each of the typing strategies: a sub-population called group 1 that contained 22 isolates and a group 2 sub-population with the remaining 39 isolates.

The sub-populations were present in the earliest samples, suggesting they formed prior to 2004, and remained through the end of the period considered.

When they incorporated patient's clinical and demographic information, the researchers found that individuals from lower elevations in northern Uganda were mainly infected with group 1 Y. pestis, while cases involving individuals from higher elevations more often involved Y. pestis from the group 2 sub-population.

The study's authors speculated that this genetic differentiation might reflect distinct populations of Y. pestis-carrying fleas and/or flea-carrying small mammals present in different parts of the country, though further research is needed to explore that possibility.

"Typing of Y. pestis strains isolated from small mammals and fleas across an elevation gradient will be important for determining what host and vector species are involved in enzoonotic maintenance of the two sub-populations," they wrote.