Pro viding tools to prevent emergence of enteric viruses
Gastroenteritis is one of the most common diseases worldwide. The majority of episodes are caused by pathogens, such as viruses, bacteria and parasites, of which the main transmission route is faecal-oral. This can result in personto- person spread, but it is also spread via faecal contaminated surfaces, food or water. Although food and water is monitored for bacterial contamination, a large proportion of outbreaks of food-related illness are caused by viruses, especially Norovirus and hepatitis A. There is growing evidence that viruses slip through the food quality control net. In the EVENT project, the partners are developing methods and a database infrastructure to unravel modes of transmission by understanding genetic diversity and evolution of enteric viruses that are or may be transmitted through the food chain.
Noroviruses are the major cause of outbreaks of acute vomiting and diarrhoea, many of which are reported particularly during winter. Although the main mode of transmission is from person to person, waterborne and particularly foodborne spreads are common as well. Norovirus can cause large international outbreaks, and international food-borne and waterborne transmission may play an important role in the dissemination of new genetic variants, which additionally spread in the population by personto- person transmission. As such, Noroviruses serve as model pathogens, illustrating where and how food-borne transmission may occur.
More challenging are other viruses with a longer incubation time and lower rate of clinical infection, such as hepatitis A and E. These viruses may cause severe illness, but linking this to food-borne transmission is very difficult without the use of molecular characterisation and linking of data.
A challenge is that the viruses involved evolve rapidly through mutation and recombination. This may have an effect on epidemiology but also on the ability to detect and link virus strains from different cases. Therefore, understanding the population structure and patterns of change of these RNA viruses is important, including the possible contribution of animal viruses to the population diversity of human pathogens. Foodborne and waterborne outbreaks are excellent opportunities for exposure of humans to animal and human viruses simultaneously and as such may contribute to generating a more diverse range of viruses through recombination. The lack of understanding of the transmission patterns of viruses with this potential gives cause for concern, and is addressed through EVENT.
Overall objectives of EVENT:
Contributions to standards for detection
of enteric viruses
Protocols were developed for detection and characterisation of a range of enteric viruses. For Norovirus and hepatitis A viruses, established links exist with groups developing robust virus detection methods for shellfish, which is supported by advice on primers. Similarly, standardised protocols for detection of Noroviruses in routine outbreak surveillance were developed and made available to the appropriate surveillance networks (i.e. DIVINENet and others). The harmonisation effort underlying central data collection is a major step towards developing standards for Europe: without knowledge about how data can be compared, the collection becomes less valuable, and this realisation has been a stimulus for the project partners to work towards harmonisation. Finally, a globally accessible genotyping tool has been made available via the Internet.
An integrated outbreak surveillance
The network managed to develop a fully integrated collection and analysis of laboratory and epidemiological data that was used in the DIVINE project. Using the same basic principles, databases were developed for collection of data on hepatitis A and hepatitis E. This data is currently being analysed, and will be made accessible to a broader public in the last phase of the project.
The partners also found that genotyping information can help dissect food-borne from person-to-person outbreaks, and systematic implementation of this would increase the quality of data collected on food-borne outbreaks. This is needed, because food-borne outbreaks were found to be common, including diffuse, international outbreaks for which no control system is in place. Also, the European Food Safety Authority (EFSA) has indicated the need for such an outbreak-based surveillance system.
Through the EVENT collaboration it became clear that hepatitis E is a significant cause of unexplained hepatitis that was not previously recognised in several of the countries. Molecular characterisation revealed that similar viruses are present in a high proportion of pigs and that the human and animal viruses are interspersed, suggesting a common mode of transmission. The exact source(s) of infection of humans with these viruses, however, remains to be established, although food-borne and waterborne infections have been described. Understanding this is important, because hepatitis E may cause a highly lethal infection in pregnancy.
Full analysis of data on other possible zoonotic pathogens as causes of unexplained illness is still ongoing.
Contribution to policy developments
Partners from the EVENT network have served as a resource for questions on a range of pathogens that can be transmitted via the faecaloral route. Some of the participants, including the coordinator, have directly been involved with risk assessment of transmission of SARScausing coronavirus and Avian Influenza viruses via this route.
The coordinator advises the World Health Organization (WHO) on the exchange of data on food-borne viruses and has co-organised and hosted a Joint FAO/WHO Expert Meeting on Viruses in Food (21 to 24 May 2007, Bilthoven, the Netherlands), in which several partners of the FBVE (Food-borne viruses in Europe) network participated (M. Koopmans, E. Duizer, A. Bosch, F. LeGuyader, D. Brown, C-H. von Bonsdorf).
The understanding of the pattern of evolution of Noroviruses of genotype II.4, the most prevalent genotype, in a manner similar to influenza has sparked discussions about the potential for a vaccine, as well as a global collaboration to study this issue on a wider scale. For hepatitis E, data found are essential for assessing the potential impact of the presence of this virus in pigs.
The expertise developed in building, collecting and analysing complex datasets including genetic data of a range of pathogens is valuable, because the genome databases are ever expanding and the mining and meaningful sorting of pathogen genetic data is increasingly important. In EVENT, the partners managed to develop an open exchange of strain information, based on agreed confidentiality rules and publication rights. This is a model for other diseases.