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High-throughput bacterial SNP typing identifies distinct clusters of Salmonella Typhi causing typhoid in Nepalese children

Kathryn E Holt12*, Stephen Baker34, Sabina Dongol5, Buddha Basnyat5, Neelam Adhikari5, Stephen Thorson5, Anoop S Pulickal6, Yajun Song7, Julian Parkhill1, Jeremy J Farrar34, David R Murdoch89, Dominic F Kelly6, Andrew J Pollard6 and Gordon Dougan1

Author Affiliations

1 Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK

2 Department of Microbiology and Immunology, University of Melbourne, Royal Parade, Melbourne, 3010, Australia

3 Wellcome Trust Major Overseas Programme & Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam

4 Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, OX3 7LJ, UK

5 Oxford University Clinical Research Unit - Nepal, Patan Hospital, Kathmandu, Nepal

6 Oxford Vaccine Group, Department of Paediatrics, University of Oxford, OX3 9DU, UK

7 Environmental Research Institute, University College Cork, Lee Road, Cork, Ireland

8 Department of Pathology, University of Otago, Christchurch, New Zealand

9 Canterbury Health Laboratories, Christchurch, New Zealand

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BMC Infectious Diseases 2010, 10:144  doi:10.1186/1471-2334-10-144

Published: 31 May 2010



Salmonella Typhi (S. Typhi) causes typhoid fever, which remains an important public health issue in many developing countries. Kathmandu, the capital of Nepal, is an area of high incidence and the pediatric population appears to be at high risk of exposure and infection.


We recently defined the population structure of S. Typhi, using new sequencing technologies to identify nearly 2,000 single nucleotide polymorphisms (SNPs) that can be used as unequivocal phylogenetic markers. Here we have used the GoldenGate (Illumina) platform to simultaneously type 1,500 of these SNPs in 62 S. Typhi isolates causing severe typhoid in children admitted to Patan Hospital in Kathmandu.


Eight distinct S. Typhi haplotypes were identified during the 20-month study period, with 68% of isolates belonging to a subclone of the previously defined H58 S. Typhi. This subclone was closely associated with resistance to nalidixic acid, with all isolates from this group demonstrating a resistant phenotype and harbouring the same resistance-associated SNP in GyrA (Phe83). A secondary clone, comprising 19% of isolates, was observed only during the second half of the study.


Our data demonstrate the utility of SNP typing for monitoring bacterial populations over a defined period in a single endemic setting. We provide evidence for genotype introduction and define a nalidixic acid resistant subclone of S. Typhi, which appears to be the dominant cause of severe pediatric typhoid in Kathmandu during the study period.