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Open accessJournal ArticleDOI: 10.2807/1560-7917.ES.2021.26.9.1900606

Economic evaluation of whole genome sequencing for pathogen identification and surveillance - results of case studies in Europe and the Americas 2016 to 2019

04 Mar 2021-Eurosurveillance (European Centre for Disease Prevention and Control)-Vol. 26, Iss: 9, pp 1900606
Abstract: BackgroundWhole genome sequencing (WGS) is increasingly used for pathogen identification and surveillance.AimWe evaluated costs and benefits of routine WGS through case studies at eight reference laboratories in Europe and the Americas which conduct pathogen surveillance for avian influenza (two laboratories), human influenza (one laboratory) and food-borne pathogens (five laboratories).MethodsThe evaluation focused on the institutional perspective, i.e. the 'investment case' for implementing WGS compared with conventional methods, based on costs and benefits during a defined reference period, mostly covering at least part of 2017. A break-even analysis estimated the number of cases of illness (for the example of Salmonella surveillance) that would need to be avoided through WGS in order to 'break even' on costs.ResultsOn a per-sample basis, WGS was between 1.2 and 4.3 times more expensive than routine conventional methods. However, WGS brought major benefits for pathogen identification and surveillance, substantially changing laboratory workflows, analytical processes and outbreaks detection and control. Between 0.2% and 1.1% (on average 0.7%) of reported salmonellosis cases would need to be prevented to break even with respect to the additional costs of WGS.ConclusionsEven at cost levels documented here, WGS provides a level of additional information that more than balances the additional costs if used effectively. The substantial cost differences for WGS between reference laboratories were due to economies of scale, degree of automation, sequencing technology used and institutional discounts for equipment and consumables, as well as the extent to which sequencers are used at full capacity.

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5 results found

Open accessJournal ArticleDOI: 10.1371/JOURNAL.PONE.0258262
06 Oct 2021-PLOS ONE
Abstract: The U.S. Food and Drug Administration (FDA) created the GenomeTrakr Whole Genome Sequencing (WGS) Network in 2013, as a tool to improve food safety. This study presents an analysis of Whole Genome source tracking implementation on potential food contamination and related illnesses through theoretical, empirical, and cost benefit analyses. We conduct empirical tests using data from FDA regulated food commodity outbreaks garnering FDA response from 1999 through 2019 and examine the effect of the National Center for Biotechnology Information (NCBI) Pathogen detection program of source tracking WGS isolates collected in the U.S. on outbreak illnesses for three pilot pathogens (E. coli, Listeria, and Salmonella). Empirical results are consistent with the theoretical model and suggest that each additional 1,000 WGS isolates added to the public NCBI database is associated with a reduction of approximately 6 illnesses per WGS pathogen, per year. Empirical results are connected to existing literature for a Monte Carlo analysis to estimate benefits and costs. By 2019, annual health benefits are estimated at nearly $500 million, compared to an approximately $22 million investment by public health agencies. Even under conservative assumptions, the program likely broke even in its second year of implementation and could produce increasing public health benefits as the GenomeTrakr network matures.

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1 Citations

Open accessJournal ArticleDOI: 10.1371/JOURNAL.PONE.0256820
26 Aug 2021-PLOS ONE
Abstract: Introduction The surveillance of human salmonellosis in Belgium is dependent on the referral of human Salmonella isolates to the National Reference Center (NRC). Knowledge of current diagnostic practices and the coverage of the national Salmonella surveillance system are important to correctly interpret surveillance data and trends over time, to estimate the true burden of salmonellosis in Belgium, and to evaluate the appropriateness of implementing whole-genome sequencing (WGS) at this central level. Methods The coverage of the NRC was defined as the proportion of all diagnosed human Salmonella cases in Belgium reported to the NRC and was assessed for 2019 via a survey among all licensed Belgian medical laboratories in 2019, and for 2016–2020 via a capture-recapture study using the Sentinel Network of Laboratories (SNL) as the external source. In addition, the survey was used to assess the impact of the implementation of culture-independent diagnostic tests (CIDTs) at the level of peripheral laboratory sites, as a potential threat to national public health surveillance programs. Results The coverage of the NRC surveillance system was estimated to be 83% and 85%, based on the results of the survey and on the two-source capture-recapture study, respectively. Further, the results of the survey indicated a limited use of CIDTs by peripheral laboratories in 2019. Conclusion Given the high coverage and the limited impact of CIDTs on the referral of isolates, we may conclude that the NRC can confidently monitor the epidemiological situation and identify outbreaks throughout the country. These findings may guide the decision to implement WGS at the level of the NRC and may improve estimates of the true burden of salmonellosis in Belgium.

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Journal ArticleDOI: 10.1016/J.MIMET.2021.106350
Ahmed Gaballa1, Rachel A. Cheng1, Aljosa Trmcic1, Jasna Kovac2  +4 moreInstitutions (2)
Abstract: Aerobic spore-forming Bacillales are a highly diverse and ubiquitous group that includes organisms that cause foodborne illnesses and food spoilage. Classical microbiological and biochemical identification of members of the order Bacillales represents a challenge due to the diversity of organisms in this group as well as the fact that the phenotypic-based taxonomic assignment of some named species in this group is not consistent with their phylogenomic characteristics. DNA-sequencing-based tools, on the other hand, can be fast and cost-effective, and can provide for a more reliable identification and characterization of Bacillales isolates. In comparison to 16S rDNA , rpoB was shown to better discriminate between Bacillales isolates and to allow for improved taxonomic assignment to the species level. However, the lack of a publicly accessible rpoB database, as well as the lack of standardized protocols for rpoB-based typing and strain identification, is a major challenge. Here, we report (i) the curation of a DNA sequence database for rpoB-based subtype classification of Bacillales isolates; (ii) the development of standardized protocols for generating rpoB sequence data, and a scheme for rpoB- based initial taxonomic identification of Bacillales isolates at the species level; and (iii) the integration of the database in a publicly accessible online platform that allows for the analysis of rpoB sequence data from uncharacterized Bacillales isolates. Specifically, we curated a database of DNA sequences for a 632-nt internal variable region within the rpoB gene from representative Bacillales reference type strains and a large number of isolates that we have previously isolated and characterized through multiple projects. As of May 21, 2021, the rpoB database contained more than 8350 rpoB sequences representing 1902 distinct rpoB allelic types that can be classified into 160 different genera. The database also includes 1129 rpoB sequences for representative Bacillales reference type strains as available on May 21, 2021 in the NCBI database. The rpoB database is integrated into the online Food Microbe Tracker platform ( ) and can be queried using the integrated BLAST tool to initially subtype and taxonomically identify aerobic and facultative anaerobic spore-formers. While whole-genome sequencing is increasingly used in bacterial taxonomy , the rpoB sequence-based identification scheme described here provides a valuable tool as it allows for rapid and cost-effective initial isolate characterization, which can help to identify and characterize foodborne pathogens and food spoilage bacteria. In addition, the database and primers described here can also be adopted for metagenomics approaches that include rpoB as a target, improving discriminatory power and identification over what can be achieved using 16S rDNA as a target.

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Topics: rpoB (63%), Sequence database (53%), Bacillales (53%)

Open accessJournal ArticleDOI: 10.1016/J.LANEPE.2021.100210
01 Oct 2021-
Abstract: The majority of emerging infectious diseases originate in animals. Current routine surveillance is focused on known diseases and clinical syndromes, but the increasing likelihood of emerging disease outbreaks shows the critical importance of early detection of unusual illness or circulation of pathogens - prior to human disease manifestation. In this Viewpoint, we focus on one key pillar of preparedness-the need for early warning surveillance at the human, animal, environmental interface. The COVID-19 pandemic has revolutionized the scale of sequencing of pathogen genomes, and the current investments in global genomic surveillance offer great potential for a novel, truly integrated Disease X (with epidemic or pandemic potential) surveillance arm provided we do not make the mistake of developing them solely for the case at hand. Generic tools include metagenomic sequencing as a catch-all technique, rather than detection and sequencing protocols focusing on what we know. Developing agnostic or more targeted metagenomic sequencing to assess unusual disease in humans and animals, combined with random sampling of environmental samples capturing pathogen circulation is technically challenging, but could provide a true early warning system. Rather than rebuilding and reinforcing the pre-existing silo's, a real step forward would be to take the lessons learned and bring in novel essential partnerships in a One Health approach to preparedness.

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Topics: Early warning system (51%), Preparedness (51%)

Open accessJournal ArticleDOI: 10.1136/BMJGH-2021-006597
02 Sep 2021-BMJ Global Health
Abstract: ### Summary box With the global increase in population density, urbanisation, and global travel and trade, the threat of widespread outbreaks of infectious diseases has increased relentlessly,1 as evidenced by recent examples of COVID-19 and Ebola. Further, although the most important causes of death shifted to non-communicable diseases, in some poorer parts of the world, communicable diseases remain the most important cause of death.2 Crucial in the prevention of and reaction to these threats is early detection, which demands an infectious disease surveillance system that can signal unusual events. How to set up and improve surveillance and how to prioritise investments are questions that need input from different scientific disciplines. Here, we focus on some economic considerations. The best recognised purpose of disease surveillance is the (early) detection of epidemics and other health threats. New diagnostic tools such as unbiased and targeted next-generation sequencing (NGS) are being explored as options to improve surveillance as these allow to determine causes of unexplained disease outbreaks, trace and link sources of disease transmission, and facilitate a better understanding of how viruses and bacteria pass from animal to humans. With NGS, the same platforms and sometimes even the same protocols can be …

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10 results found

Open accessJournal ArticleDOI: 10.1136/BMJ.326.7385.357
Stephen J. W. Evans1Institutions (1)
15 Feb 2003-BMJ
Abstract: Objectives: To determine the excess mortality associated with infections with Salmonella, Campylobacter, Yersiniaenterocolitica, and Shigella and to examine the effect of pre-existing illness. Design: Registry based, matched cohort study. Setting: Denmark. Participants: 48 857 people with gastrointestinal infections plus 487 138 controls from the general population. Main outcome measure: One year mortality among patients with gastrointestinal infections compared with controls after adjustment for comorbidity. Results: 1071 (2.2%) people with gastrointestinal infections died within one year after infection compared with 3636 (0.7%) controls. The relative mortality within one year was 3.1 times higher in patients than in controls. The relative mortality within 30 days of infection was high in all four bacterial groups. Furthermore, there was excess mortality one to six months after infection with Yersinia enterocolitica (relative risk 2.53, 95% confidence interval 1.38 to 4.62) and from six months to one year after infection with Campylobacter (1.35, 1.02 to 1.80) and Salmonella (1.53, 1.31 to 1.79). Conclusions: Infections with all these bacteria were associated with an increased short term risk of death, even after pre-existing illnesses were taken into account. Salmonella, Campylobacter, and Yersinia enterocolitica infections were also associated with increased long term mortality.

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Topics: Poison control (51%), Population (51%), Campylobacter (51%)

209 Citations

Open accessJournal ArticleDOI: 10.3201/EID/1811.120453
Abstract: The rapid advancement of genome technologies holds great promise for improving the quality and speed of clinical and public health laboratory investigations and for decreasing their cost. The latest generation of genome DNA sequencers can provide highly detailed and robust information on disease-causing microbes, and in the near future these technologies will be suitable for routine use in national, regional, and global public health laboratories. With additional improvements in instrumentation, these next- or third-generation sequencers are likely to replace conventional culture-based and molecular typing methods to provide point-of-care clinical diagnosis and other essential information for quicker and better treatment of patients. Provided there is free-sharing of information by all clinical and public health laboratories, these genomic tools could spawn a global system of linked databases of pathogen genomes that would ensure more efficient detection, prevention, and control of endemic, emerging, and other infectious disease outbreaks worldwide.

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92 Citations

Open accessJournal ArticleDOI: 10.2217/PGS.13.183
15 Nov 2013-Pharmacogenomics
Abstract: Aim: Genomic interventions could enable improved disease stratification and individually tailored therapies. However, they have had a limited impact on clinical practice to date due to a lack of evidence, particularly economic evidence. This is partly because health economists are yet to reach consensus on whether existing methods are sufficient to evaluate genomic technologies. As different approaches may produce conflicting adoption decisions, clarification is urgently required. This article summarizes the methodological issues associated with conducting economic evaluations of genomic interventions. Materials & methods: A structured literature review was conducted to identify references that considered the methodological challenges faced when conducting economic evaluations of genomic interventions. Results: Methodological challenges related to the analytical approach included the choice of comparator, perspective and timeframe. Challenges in costing centered around the need to collect a broad range of...

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Topics: Economic evaluation (52%), Systematic review (51%)

85 Citations

Open accessJournal ArticleDOI: 10.1099/JMM.0.000296
Abstract: Shigella spp., including Shigella dysenteriae, Shigella boydii, Shigella flexneri and Shigella sonnei, are the most common cause of bacterial dysentery (bloody diarrhoea) worldwide (Kotloff et al., 1999). Although all species of Shigella contribute to the high burden of diarrhoeal disease in lowincome regions, S. sonnei is the most commonly reported species in middleand high-income countries (Thompson et al., 2015). In England and Wales, foodborne outbreaks of S. sonnei are rare with transmission most commonly associated with person-to-person spread (McDonnell et al., 2013; Morgan et al., 2006; Simms et al., 2015). Historically, schools and nurseries were regarded as the epidemic centres of domestically acquired S. sonnei infection (Evans & Maguire, 1996). More recently, outbreaks of S. sonnei amongst men who have sex with men (MSM) have been described, and the increasing incidence of S. sonnei infection in this community is a challenging public health problem (Morgan et al., 2006; Simms et al., 2015).

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Topics: Shigella sonnei (68%), Whole genome sequencing (54%), Public health surveillance (52%) ... show more

39 Citations

Journal ArticleDOI: 10.1016/J.FM.2017.04.005
18 Apr 2017-Food Microbiology
Abstract: Analysis of whole genome sequencing data uncovered a previously undetected outbreak of Salmonella Enteritidis that had been on-going for four years. Cases were resident in all countries of the United Kingdom and 40% of the cases were aged less than 11 years old. Initial investigations revealed that 30% of cases reported exposure to pet snakes. A case-control study was designed to test the hypothesis that exposure to reptiles or their feed were risk factors. A robust case-definition, based on the single nucleotide polymorphism (SNP) profile, increased the power of the analytical study. Following univariable and multivariable analysis, exposure to snakes was the only variable independently associated with infection (Odds ratio 810 95% CI (85-7715) p < 0.001). Isolates of S. Enteritidis belonging to the outbreak profile were recovered from reptile feeder mice sampled at the retail and wholesale level. Control measures included improved public health messaging at point of sale, press releases and engagement with public health and veterinary counterparts across Europe. Mice destined to be fed to reptiles are not regarded as pet food and are not routinely tested for pathogenic bacteria. Routine microbiological testing to ensure feeder mice are free from Salmonella is recommended.

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Topics: Salmonella enteritidis (58%), Outbreak (52%), Salmonella (50%)

33 Citations