Abstract:A fundamental assumption in the use and interpretation of microbial subtyping results for public health investigations is that isolates that appear to be related based on molecular subtyping data are expected to share commonalities with respect to their origin, history, and distribution. Critically, there is currently no approach for systematically assessing the underlying epidemiology of subtyping results. Our aim was to develop a method for directly quantifying the similarity between bacterial isolates using… Show more
“…For QMRA purposes, a range of thresholds capturing the uncertainty around the degree of relatedness between isolates can be used and integrated into a QMRA model using a combination of scenario-based and stochastic approaches. In the future, the use of WGS for outbreak investigation and its increasing use in surveillance of foodborne pathogens will likely improve our knowledge of the structure of bacterial populations, and the collection of isolates from large and representative samples of the global population into open-source databases will provide a scientific basis to define appropriate distance thresholds, i.e., combining good epidemiological concordance (i.e., ability to group epidemiologically related isolates) and discriminatory power (i.e., ability to distinguish non-epidemiologically related isolates) (Van Belkum et al, 2007; Hetman et al, 2017). The uncertainty around the degree of relatedness between isolates, and therefore around risk estimates, will decrease accordingly.…”
Whole-genome sequencing (WGS) will soon replace traditional phenotypic methods for routine testing of foodborne antimicrobial resistance (AMR). WGS is expected to improve AMR surveillance by providing a greater understanding of the transmission of resistant bacteria and AMR genes throughout the food chain, and therefore support risk assessment activities. At this stage, it is unclear how WGS data can be integrated into quantitative microbial risk assessment (QMRA) models and whether their integration will impact final risk estimates or the assessment of risk mitigation measures. This review explores opportunities and challenges of integrating WGS data into QMRA models that follow the Codex Alimentarius Guidelines for Risk Analysis of Foodborne AMR. We describe how WGS offers an opportunity to enhance the next-generation of foodborne AMR QMRA modeling. Instead of considering all hazard strains as equally likely to cause disease, WGS data can improve hazard identification by focusing on those strains of highest public health relevance. WGS results can be used to stratify hazards into strains with similar genetic profiles that are expected to behave similarly, e.g., in terms of growth, survival, virulence or response to antimicrobial treatment. The QMRA input distributions can be tailored to each strain accordingly, making it possible to capture the variability in the strains of interest while decreasing the uncertainty in the model. WGS also allows for a more meaningful approach to explore genetic similarity among bacterial populations found at successive stages of the food chain, improving the estimation of the probability and magnitude of exposure to AMR hazards at point of consumption. WGS therefore has the potential to substantially improve the utility of foodborne AMR QMRA models. However, some degree of uncertainty remains in relation to the thresholds of genetic similarity to be used, as well as the degree of correlation between genotypic and phenotypic profiles. The latter could be improved using a functional approach based on prediction of microbial behavior from a combination of ‘omics’ techniques (e.g., transcriptomics, proteomics and metabolomics). We strongly recommend that methodologies to incorporate WGS data in risk assessment be included in any future revision of the Codex Alimentarius Guidelines for Risk Analysis of Foodborne AMR.
“…For QMRA purposes, a range of thresholds capturing the uncertainty around the degree of relatedness between isolates can be used and integrated into a QMRA model using a combination of scenario-based and stochastic approaches. In the future, the use of WGS for outbreak investigation and its increasing use in surveillance of foodborne pathogens will likely improve our knowledge of the structure of bacterial populations, and the collection of isolates from large and representative samples of the global population into open-source databases will provide a scientific basis to define appropriate distance thresholds, i.e., combining good epidemiological concordance (i.e., ability to group epidemiologically related isolates) and discriminatory power (i.e., ability to distinguish non-epidemiologically related isolates) (Van Belkum et al, 2007; Hetman et al, 2017). The uncertainty around the degree of relatedness between isolates, and therefore around risk estimates, will decrease accordingly.…”
Whole-genome sequencing (WGS) will soon replace traditional phenotypic methods for routine testing of foodborne antimicrobial resistance (AMR). WGS is expected to improve AMR surveillance by providing a greater understanding of the transmission of resistant bacteria and AMR genes throughout the food chain, and therefore support risk assessment activities. At this stage, it is unclear how WGS data can be integrated into quantitative microbial risk assessment (QMRA) models and whether their integration will impact final risk estimates or the assessment of risk mitigation measures. This review explores opportunities and challenges of integrating WGS data into QMRA models that follow the Codex Alimentarius Guidelines for Risk Analysis of Foodborne AMR. We describe how WGS offers an opportunity to enhance the next-generation of foodborne AMR QMRA modeling. Instead of considering all hazard strains as equally likely to cause disease, WGS data can improve hazard identification by focusing on those strains of highest public health relevance. WGS results can be used to stratify hazards into strains with similar genetic profiles that are expected to behave similarly, e.g., in terms of growth, survival, virulence or response to antimicrobial treatment. The QMRA input distributions can be tailored to each strain accordingly, making it possible to capture the variability in the strains of interest while decreasing the uncertainty in the model. WGS also allows for a more meaningful approach to explore genetic similarity among bacterial populations found at successive stages of the food chain, improving the estimation of the probability and magnitude of exposure to AMR hazards at point of consumption. WGS therefore has the potential to substantially improve the utility of foodborne AMR QMRA models. However, some degree of uncertainty remains in relation to the thresholds of genetic similarity to be used, as well as the degree of correlation between genotypic and phenotypic profiles. The latter could be improved using a functional approach based on prediction of microbial behavior from a combination of ‘omics’ techniques (e.g., transcriptomics, proteomics and metabolomics). We strongly recommend that methodologies to incorporate WGS data in risk assessment be included in any future revision of the Codex Alimentarius Guidelines for Risk Analysis of Foodborne AMR.
“…This can be quite labour intensive, especially if there are many identified clusters stretching across multiple regions. Only recently, a study has been published that introduced a framework for computing epidemiological concordance of microbial subtyping data of Campylobacter jejuni [19]. Epidemiological cluster cohesion is based on time, geographical location, and environmental source distances with adjustable weights.…”
Introduction
With growing amounts of data available, identification of clusters of persons linked to each other by transmission of an infectious disease increasingly relies on automated algorithms. We propose cluster finding to be a two-step process: first, possible transmission clusters are identified using a cluster algorithm, second, the plausibility that the identified clusters represent genuine transmission clusters is evaluated.
Aim
To introduce visual tools to assess automatically identified clusters.
Methods
We developed tools to visualise: (i) clusters found in dimensions of time, geographical location and genetic data; (ii) nested sub-clusters within identified clusters; (iii) intra-cluster pairwise dissimilarities per dimension; (iv) intra-cluster correlation between dimensions. We applied our tools to notified mumps cases in the Netherlands with available disease onset date (January 2009 – June 2016), geographical information (location of residence), and pathogen sequence data (n = 112). We compared identified clusters to clusters reported by the Netherlands Early Warning Committee (NEWC).
Results
We identified five mumps clusters. Three clusters were considered plausible. One was questionable because, in phylogenetic analysis, genetic sequences related to it segregated in two groups. One was implausible with no smaller nested clusters, high intra-cluster dissimilarities on all dimensions, and low intra-cluster correlation between dimensions. The NEWC reports concurred with our findings: the plausible/questionable clusters corresponded to reported outbreaks; the implausible cluster did not.
Conclusion
Our tools for assessing automatically identified clusters allow outbreak investigators to rapidly spot plausible transmission clusters for mumps and other human-to-human transmissible diseases. This fast information processing potentially reduces workload.
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