Two Distinct <i>Yersinia pestis</i> Populations Causing Plague among Humans in the West Nile Region of Uganda

<div><p>Background</p><p>Plague is a life-threatening disease caused by the bacterium, <i>Yersinia pestis</i>. Since the 1990s, Africa has accounted for the majority of reported human cases. In Uganda, plague cases occur in the West Nile region, near the border with Democratic Republic of Congo. Despite the ongoing risk of contracting plague in this region, little is known about <i>Y</i>. <i>pestis</i> genotypes causing human disease.</p><p>Methodology/Principal Findings</p><p>During January 2004–December 2012, 1,092 suspect human plague cases were recorded in the West Nile region of Uganda. Sixty-one cases were culture-confirmed. Recovered <i>Y</i>. <i>pestis</i> isolates were analyzed using three typing methods, single nucleotide polymorphisms (SNPs), pulsed field gel electrophoresis (PFGE), and multiple variable number of tandem repeat analysis (MLVA) and subpopulations analyzed in the context of associated geographic, temporal, and clinical data for source patients. All three methods separated the 61 isolates into two distinct 1.ANT lineages, which persisted throughout the 9 year period and were associated with differences in elevation and geographic distribution.</p><p>Conclusions/Significance</p><p>We demonstrate that human cases of plague in the West Nile region of Uganda are caused by two distinct 1.ANT genetic subpopulations. Notably, all three typing methods used, SNPs, PFGE, and MLVA, identified the two genetic subpopulations, despite recognizing different mutation types in the <i>Y</i>. <i>pestis</i> genome. The geographic and elevation differences between the two subpopulations is suggestive of their maintenance in highly localized enzootic cycles, potentially with differing vector-host community composition. This improved understanding of <i>Y</i>. <i>pestis</i> subpopulations in the West Nile region will be useful for identifying ecologic and environmental factors associated with elevated plague risk.</p></div

AscI PFGE patterns for <i>Y</i>. <i>pestis</i> isolates from the West Nile region of Uganda.

<p>Lane (1) <i>Salmonella braenderup</i> H9812 molecular marker in kilobases. Lane (2) PFGE Group A pattern. Lane (3) PFGE Group B pattern.</p

Cluster analysis of PFGE patterns for <i>Y</i>. <i>pestis</i> isolates from the West Nile region of Uganda.

<p>UPGMA of AscI PFGE patterns for 61 <i>Y</i>. <i>pestis</i> strains isolated from human plague cases in the West Nile region of Uganda. PFGE groups A (solid line) and B (dashed line) are indicated. <i>Y</i>. <i>pestis</i> CO92 and A1122 strains (1.ORI: North America) were included as outgroups.</p

VNTR analysis of <i>Y</i>. <i>pestis</i> isolates from the West Nile region of Uganda.

<p>UPGMA based on 18 VNTRs in the 61 <i>Y</i>. <i>pestis</i> strains. MLVA groups I (solid line) and II (dashed line) are indicated. <i>Y</i>. <i>pestis</i> CO92 and A1122 strains (1.ORI: North America) were included as outgroups.</p

SNP genotypes in the West Nile region of Uganda.

<p>SNP genotypes in the West Nile region of Uganda.</p

Geographic distribution of SNP genotypes.

<p>Map of Vurra and Okoro counties in the Arua and Zombo districts, respectively, in northwestern Uganda. <i>Y</i>. <i>pestis</i> isolates in SNP Groups 1 and 2 are shown. Isolates were plotted based on GPS coordinates of the source patient’s residence. Light to dark shading represents a high to low elevation gradient.</p

Human plague cases West Nile region of Uganda 2004–2012.

<p>Suspect (gray) and culture confirmed (black) cases are indicated for the time period from January 2004 through December 2012.</p