Revolutionising Public Health Reference Microbiology using Whole Genome Sequencing:Salmonellaas an exemplar

Abstract

Advances in whole genome sequencing (WGS) platforms and DNA library preparation have led to the development of methods for high throughput sequencing of bacterial genomes at a relatively low cost (Loman et al. 2012; Medini et al. 2008). WGS offers unprecedented resolution for determining degrees of relatedness between strains of bacterial pathogens and has proven a powerful tool for microbial population studies and epidemiological investigations (Harris et al. 2010; Lienau et al. 2011; Holt et al. 2009; Ashton, Peters, et al. 2015). The potential utility of WGS to public health microbiology has been highlighted previously (Koser et al. 2012; Kwong et al. 2013; Reuter et al. 2013; Joensen et al. 2014; Nair et al. 2014; Bakker et al. 2014; D Auria et al. 2014). Here we report, for the first time, the routine use of WGS as the primary test for identification, surveillance and outbreak investigation by a national reference laboratory. We present data on how this has revolutionised public health microbiology for one of the most common bacterial pathogens in the United Kingdom, the Salmonellae.

Online market research panel members as controls in case–control studies to investigate gastrointestinal disease outbreaks: early experiences and lessons learnt from the UK

“…Between 2013 and 2016, market research panel control groups were used in five investigations of diverse national outbreaks of gastrointestinal pathogens after observed increases in cases of: (study A) Salmonella Mikawasima with no clear excess among defined age or gender groups and no hypothesised exposures associated with illness identified from trawling questionnaires [2]; (study B) Shiga toxin-producing Escherichia coli (STEC) O157 with no clear excess among defined age or gender groups and handling or consumption of potatoes, root vegetables, tomatoes, apples or bananas identified as hypothesised exposures associated with illness [3]; (study C) Salmonella Enteritidis 5 single nucleotide polymorphism (SNP) single linkage cluster (methods for defining SNP profiles have been described previously [4]) with an excess observed among children and exposure to reptiles, particularly snakes, identified as hypothesised exposures associated with illness [5]; (study D) Cryptosporidium parvum IIdA24G1 with an excess observed among adult females and consumption of pre-prepared sandwiches with specific fillings, food bought from branches of two supermarkets and one coffee shop chain, specific dairy products or consumption and/or handling of specified salad vegetables identified as hypothesised exposures associated with illness [6]; and (study E) STEC O157 PT34 with an excess observed among adult females and consumption of salad vegetables, bagged salad, food purchased from a specific supermarket chain and salad items from catering premises identified as hypothesised exposures associated with illness [6] (Table 1). …”

Multi‐country outbreak of Salmonella Enteritidis phage type 8, MLVA profile 2‐9‐7‐3‐2 and 2‐9‐6‐3‐2 infections

“…Using the PHE in-house pipeline and nomenclature for WGS analysis, the threshold for inclusion in any of the WGS clusters was set to ≤5 single nucleotide polymorphisms (SNP) difference (t5 level) to at least one other case in the outbreak [7][8][9]. The SNP addresses at t5 level for the two WGS clusters were 1.2.3.175.175.175.% (WGS cluster 175, accession number SRR3285443) and 1.2.3.18.359.360.% (WGS cluster 360; accession number: SRR4063700).…”

Moving pathogen genomics out of the lab and into the clinic: what will it take?

“…WGS of a pathogen has enabled the resolution of a methicillin-resistant Staphylococcus aureus outbreak on a neonatal intensive care ward [1] and the successful identification of sources of Pseudomonas aeruginosa infections on a burns unit [2] and, most recently, it has been deployed for the real-time surveillance of the Ebola outbreak in West Africa [3]. Metagenomics has been successfully used to characterise the strain of Shiga-toxin-producing Escherichia coli (STEC) O104:H4 that was responsible for a pan-European outbreak [4] and in a diagnostic context to identify rare neurological infections [5] and transplant-related infections [6]. These striking examples of the power of genomics in this field of medicine have sparked considerable excitement within the healthcare sector.…”