Temporal Fluctuation of Multidrug Resistant <em>Salmonella</em> Typhi Haplotypes in the Mekong River Delta Region of Vietnam

<div><h3>Background</h3><p>Typhoid fever remains a public health problem in Vietnam, with a significant burden in the Mekong River delta region. Typhoid fever is caused by the bacterial pathogen <em>Salmonella enterica</em> serovar Typhi (<em>S</em>. Typhi), which is frequently multidrug resistant with reduced susceptibility to fluoroquinolone-based drugs, the first choice for the treatment of typhoid fever. We used a GoldenGate (Illumina) assay to type 1,500 single nucleotide polymorphisms (SNPs) and analyse the genetic variation of <em>S</em>. Typhi isolated from 267 typhoid fever patients in the Mekong delta region participating in a randomized trial conducted between 2004 and 2005.</p><h3>Principal Findings</h3><p>The population of <em>S</em>. Typhi circulating during the study was highly clonal, with 91% of isolates belonging to a single clonal complex of the <em>S</em>. Typhi H58 haplogroup. The patterns of disease were consistent with the presence of an endemic haplotype H58-C and a localised outbreak of <em>S</em>. Typhi haplotype H58-E2 in 2004. H58-E2-associated typhoid fever cases exhibited evidence of significant geo-spatial clustering along the Sông H u branch of the Mekong River. Multidrug resistance was common in the established clone H58-C but not in the outbreak clone H58-E2, however all H58 <em>S</em>. Typhi were nalidixic acid resistant and carried a Ser83Phe amino acid substitution in the <em>gyrA</em> gene.</p><h3>Significance</h3><p>The H58 haplogroup dominates <em>S</em>. Typhi populations in other endemic areas, but the population described here was more homogeneous than previously examined populations, and the dominant clonal complex (H58-C, -E1, -E2) observed in this study has not been detected outside Vietnam. IncHI1 plasmid-bearing <em>S</em>. Typhi H58-C was endemic during the study period whilst H58-E2, which rarely carried the plasmid, was only transient, suggesting a selective advantage for the plasmid. These data add insight into the outbreak dynamics and local molecular epidemiology of <em>S</em>. Typhi in southern Vietnam.</p>