An Integrated Approach to Identifying International Foodborne Norovirus Outbreaks1

Surveillance gaps can be bridged through analysis of combined molecular and epidemiologic data

Overview of virus metagenomic classification methods and their biological applications

Metagenomics poses opportunities for clinical and public health virology applications by offering a way to assess complete taxonomic composition of a clinical sample in an unbiased way. However, the techniques required are complicated and analysis standards have yet to develop. This, together with the wealth of different tools and workflows that have been proposed, poses a barrier for new users. We evaluated 49 published computational classification workflows for virus metagenomics in a literature review. To this end, we described the methods of existing workflows by breaking them up into five general steps and assessed their ease-of-use and validation experiments. Performance scores of previous benchmarks were summarized and correlations between methods and performance were investigated. We indicate the potential suitability of the different workflows for (1) time-constrained diagnostics, (2) surveillance and outbreak source tracing, (3) detection of remote homologies (discovery), and (4) biodiversity studies. We provide two decision trees for virologists to help select a workflow for medical or biodiversity studies, as well as directions for future developments in clinical viral metagenomics

Usability of the international HAVNet hepatitis A virus database for geographical annotation, backtracing and outbreak detection

BackgroundHAVNet is an international laboratory network sharing sequences and corresponding metadata on hepatitis A virus in an online database. Aim: We give an overview of the epidemiological and genetic data and assess the usability of the present dataset for geographical annotation, backtracing and outbreak detection. Methods: A descriptive analysis was performed on the timeliness, completeness, epidemiological data and geographic coverage of the dataset. Length and genomic region of the sequences were reviewed as well as the numerical and geographical distribution of the genotypes. The geographical signal in the sequences was assessed based on a short common nt stretch using a 100% identity analysis. Results: The 9,211 reports were heterogeneous for completeness and timeliness, and for length and genomic region of the sequences. Some parts of the world were not represented by the sequences. Geographical differences in prevalence of HAV genotypes described previously could be confirmed with this dataset and for a third (1,075/3,124) of the included sequences, 100% identity of the short common sequence coincided with an identical country of origin. Conclusion: Analysis of a subset of short, shared sequences indicates that a geographical annotation on the level of individual countries is possible with the HAVNet data. If the current incompleteness and heterogeneity of the data can be improved on, HAVNet could become very useful as a worldwide reference set for geographical annotation and for backtracing and outbreak detection

Emergence of New Norovirus Variants on Spring Cruise Ships and Prediction of Winter Epidemics

A reporting system could provide early warning

Laboratory-based surveillance in the molecular era: The typened model, a joint data-sharing platform for clinical and public health laboratories

Laboratory-based surveillance, one of the pillars of monitoring infectious disease trends, relies on data produced in clinical and/or public health laboratories. Currently, diagnostic laboratories worldwide submit strains or samples to a relatively small number of reference laboratories for characterisation and typing. However, with the introduction of molecular diagnostic methods and sequencing in most of the larger diagnostic and university hospital centres in high-income countries, the distinction between diagnostic and reference/public health laboratory functions has become less clear-cut. Given these developments, new ways of networking and data sharing are needed. Assuming that clinical and public health laboratories may be able to use the same data for their own purposes when sequence-based testing and typing are used, we explored ways to develop a collaborative approach and a jointly owned database (TYPENED) in the Netherlands. The rationale was that sequence data - whether produced to support clinical care or for surveillance -can be aggregated to meet both needs. Here we describe the development of the TYPENED approach and supporting infrastructure, and the implementation of a pilot laboratory network sharing enterovirus sequences and metadata

Selection of a phylogenetically informative region of the norovirus genome for outbreak linkage

The recognition of a common source norovirus outbreak is supported by finding identical norovirus sequences in patients. Norovirus sequencing has been established in many (national) public health laboratories and academic centers, but often partial and different genome sequences are used. Therefore, agreement on a target sequence of sufficient diversity to resolve links between outbreaks is crucial. Although harmonization of laboratory methods is one of the keystone activities of networks that have the aim to identify common source norovirus outbreaks, this has proven difficult to accomplish, particularly in the international context. Here, we aimed at providing a method enabling identification of the genomic region informative of a common source norovirus outbreak by bio-informatic tools. The data set of 502 unique full length capsid gene sequences available from the public domain, combined with epidemiological data including linkage information was used to build over 3,000 maximum likelihood (ML) trees for different sequence lengths and regions. All ML trees were evaluated for robustness and specificity of clustering of known linked norovirus outbreaks against the background diversity of strains. Great differences were seen in the robustness of commonly used PCR targets for cluster detection. The capsid gene region spanning nucleotides 900–1,400 was identified as the region optimally substituting for the full length capsid region. Reliability of this approach depends on the quality of the background data set, and we recommend periodic reassessment of this growing data set. The approach may be applicable to multiple sequence-based data sets of other pathogens

Elevated risk of infection with SARS-CoV-2 Beta, Gamma, and Delta variants compared with Alpha variant in vaccinated individuals

The extent to which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) break through infection- or vaccine-induced immunity is not well understood. We analyzed 28,578 sequenced SARS-CoV-2 samples from individuals with known immune status obtained through national community testing in the Netherlands from March to August 2021. We found evidence of an increased risk of infection by the Beta (B.1.351), Gamma (P.1), or Delta (B.1.617.2) variants compared with the Alpha (B.1.1.7) variant after vaccination. No clear differences were found between vaccines. However, the effect was larger in the first 14 to 59 days after complete vaccination compared with ≥60 days. In contrast to vaccine-induced immunity, there was no increased risk for reinfection with Beta, Gamma, or Delta variants relative to the Alpha variant in individuals with infection-induced immunity.</p