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Whole genome sequence analysis of Salmonella Typhi isolated in Thailand before and after the introduction of a national immunization program

View ORCID ProfileZoe A. Dyson, Duy Pham Thanh, Ladaporn Bodhidatta, Carl Jeffries Mason, Apichai Srijan, Maia A. Rabaa, Phat Voong Vinh, Tuyen Ha Thanh, Guy E. Thwaites, Stephen Baker, View ORCID ProfileKathryn E. Holt
doi: https://doi.org/10.1101/076422
Zoe A. Dyson
1Centre for Systems Genomics, University of Melbourne, Parkville, Victoria 3052, Australia
2Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia
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Duy Pham Thanh
3The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
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Ladaporn Bodhidatta
4Department of Enteric Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
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Carl Jeffries Mason
4Department of Enteric Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
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Apichai Srijan
4Department of Enteric Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
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Maia A. Rabaa
3The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
5Centre for Tropical Medicine and Global Health, Oxford University, Oxford, United Kingdom
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Phat Voong Vinh
3The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
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Tuyen Ha Thanh
3The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
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Guy E. Thwaites
3The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
5Centre for Tropical Medicine and Global Health, Oxford University, Oxford, United Kingdom
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Stephen Baker
3The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
5Centre for Tropical Medicine and Global Health, Oxford University, Oxford, United Kingdom
6The London School of Hygiene and Tropical Medicine, London, United Kingdom
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Kathryn E. Holt
1Centre for Systems Genomics, University of Melbourne, Parkville, Victoria 3052, Australia
2Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia
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Abstract

Vaccines against Salmonella Typhi, 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 of S. 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 in Shigella sonnei and Escherichia coli. The majority of S. Typhi genotypes observed prior to the immunization program were not observed following it. Post-vaccine era isolates were more closely related to S. Typhi isolated from neighbouring countries than to earlier Thai isolates, providing no evidence for the local persistence of endemic S. 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 bacterium Salmonella Typhi. 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 of S. 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 44 S. Typhi obtained from hospitals in Thailand before and after the immunization program. The genome sequences showed that isolates of S. 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 into S. Typhi in Thailand during the 1970s, and provides a model for the impact of immunization on S. Typhi populations.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted December 15, 2016.
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Whole genome sequence analysis of Salmonella Typhi isolated in Thailand before and after the introduction of a national immunization program
Zoe A. Dyson, Duy Pham Thanh, Ladaporn Bodhidatta, Carl Jeffries Mason, Apichai Srijan, Maia A. Rabaa, Phat Voong Vinh, Tuyen Ha Thanh, Guy E. Thwaites, Stephen Baker, Kathryn E. Holt
bioRxiv 076422; doi: https://doi.org/10.1101/076422
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Whole genome sequence analysis of Salmonella Typhi isolated in Thailand before and after the introduction of a national immunization program
Zoe A. Dyson, Duy Pham Thanh, Ladaporn Bodhidatta, Carl Jeffries Mason, Apichai Srijan, Maia A. Rabaa, Phat Voong Vinh, Tuyen Ha Thanh, Guy E. Thwaites, Stephen Baker, Kathryn E. Holt
bioRxiv 076422; doi: https://doi.org/10.1101/076422

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