Whole genome sequence analysis ofSalmonellaTyphi isolated in Thailand before and after the introduction of a national immunization program
Authors: Dyson Zoe A. , Thanh Duy Pham , Bodhidatta Ladaporn , Mason Carl Jeffries , Srijan Apichai , Rabaa Maia A. , Vinh Phat Voong , Thanh Tuyen Ha , Thwaites Guy E. , Baker Stephen , Holt Kathryn E. 
Published: September 2016

Vaccines againstSalmonellaTyphi, the causative agent of typhoid fever, are commonly used by travellers, however, there are few examples of national immunization programs in endemic areas. There is therefore a paucity of data on the impact of typhoid immunization programs on localised populations ofS. Typhi. Here we have used whole genome sequencing (WGS) to characterise 44 historical bacterial isolates collected before and after a national typhoid immunization program that was implemented in Thailand in 1977 in response to a large outbreak; the program was highly effective in reducing typhoid case numbers. Thai isolates were highly diverse, including 10 distinct phylogenetic lineages or genotypes. Novel prophage and plasmids were also detected, including examples that were previously only reported inShigella sonneiandEscherichia coli. The majority ofS. Typhi genotypes observed prior to the immunization program were not observed following it. Post-vaccine era isolates were more closely related toS. Typhi isolated from neighbouring countries than to earlier Thai isolates, providing no evidence for the local persistence of endemicS. Typhi following the national immunization program. Rather, later cases of typhoid appeared to be caused by the occasional importation of common genotypes from neighbouring Vietnam, Laos, and Cambodia. These data show the value of WGS in understanding the impacts of vaccination on pathogen populations and provide support for the proposal that large-scale typhoid immunization programs in endemic areas could result in lasting local disease elimination, although larger prospective studies are needed to test this directly.

Author Summary

Typhoid fever is a systemic infection caused by the bacteriumSalmonellaTyphi. Typhoid fever is associated with inadequate hygiene in low-income settings and a lack of sanitation infrastructure. A sustained outbreak of typhoid fever occurred in Thailand in the 1970s, which peaked in 1975-1976. In response to this typhoid fever outbreak the government of Thailand initiated an immunization program, which resulted in a dramatic reduction in the number of typhoid cases in Thailand. To better understand the population ofS. Typhi circulating in Thailand at this time, as well as the impact of the immunization program on the pathogen population, we sequenced the genomes of 44S. Typhi obtained from hospitals in Thailand before and after the immunization program. The genome sequences showed that isolates ofS. Typhi bacteria isolated from post-immunization era typhoid cases were likely imported from neighbouring countries, rather than strains that have persisted in Thailand throughout the immunization period. Our work provides the first historical insights intoS. Typhi in Thailand during the 1970s, and provides a model for the impact of immunization onS. Typhi populations.