Temporal fluctuation of multidrug resistant salmonella typhi haplotypes in the mekong river delta region of Vietnam.
BACKGROUND
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 Salmonella enterica serovar Typhi (S. 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 S. Typhi isolated from 267 typhoid fever patients in the Mekong delta region participating in a randomized trial conducted between 2004 and 2005.


RESULTS
the population of S. Typhi circulating during the study was highly clonal, with 91% of isolates belonging to a single clonal complex of the S. Typhi H58 haplogroup. The patterns of disease were consistent with the presence of an endemic haplotype H58-C and a localised outbreak of S. 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 S. Typhi were nalidixic acid resistant and carried a Ser83Phe amino acid substitution in the gyrA gene.


CONCLUSIONS
the H58 haplogroup dominates S. 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 S. 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 S. Typhi in southern Vietnam.
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom. kholt@unimelb.edu.au
Kathryn E
KE
Holt
Christiane
C
Dolecek
Tran Thuy
TT
Chau
Pham Thanh
PT
Duy
Tran Thi Phi
TT
La
Nguyen Van Minh
NV
Hoang
Tran Vu Thieu
TV
Nga
James I
JI
Campbell
Bui Huu
BH
Manh
Nguyen Van
NV
Vinh Chau
Tran Tinh
TT
Hien
Jeremy
J
Farrar
Gordon
G
Dougan
Stephen
S
Baker
D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D005838:Genotype; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008297:Male; D010957:Plasmids; D012485:Salmonella typhi / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D014435:Typhoid Fever / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology*; D014744:Vietnam / Q000453:epidemiology
D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial
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