New approaches for the quantitative detection of human pathogenic viruses within the freshwater-marine continuum

Lead Research Organisation: University of Liverpool
Department Name: Institute of Integrative Biology

Abstract

Viruses pose one of the biggest threats to human wellbeing being responsible for numerous infections and millions of deaths worldwide each year. Most of these viral diseases are passed via the faecal-oral route in which contaminated food and water are frequently implicated in the primary infectivity phase. Although many of these infections are self-limiting, the societal and economic burden should not be underestimated. For example, Norovirus (NoV) is estimated to cause over 2 million cases of illness in the UK each year resulting in millions of days of lost productivity and an economic burden estimated to exceed £100 million to the NHS directly and over £2 billion annually to the wider economy. Worryingly, it is clear from a range of critical reviews that the burden of waterborne disease is likely to increase in Europe in response to climate change. This increasing problem is being exacerbated by increased pressure on wastewater infrastructure (due to population rise), sewer misconnections and a greater incidence of storms and flood events causing the release of untreated sewage (stormwater discharge) into river networks and the coastal zone. Considering the magnitude of the problem and the disease burden forecast for the near future, it is timely to develop new strategic approaches for mitigating against viral contamination and to develop new and improved risk assessment tools for protecting human health.

In view of this, our proposal aims to address the critical need to develop and validate new tools for the detection and surveillance of human pathogenic viruses in freshwater, estuarine and coastal environments. Specifically, we will design and test experimental and modelling tools to permit the robust recovery and quantification of viral populations from contrasting matrices (e.g. seawater, freshwater, sediments, effluent, shellfish). These tools will be designed to capture the viral populations in both space and time. We will focus on viruses of strategic iortance from a human health perspective (e.g. Norovirus, Sapovirus, Hepatitis A/E), however, these will be placed in a wider context via metavirome analysis of RNA and DNA viral communities. These techniques will be deployed and demonstrated at the catchment-to-coast scale whilst simultaneously answering fundamental questions about the temporal and spatial dynamics of viral flow. This knowledge will be used to validate next generation mathematical models capable of predicting viral flow through the river network and coastal zone. Combined, this information will be used with key stakeholders (e.g. Cefas) in the implementation of new methods and guidelines for assessing infection risk (e.g. in recreational waters, beaches & shellfisheries) and for protecting human health.

Our proposal directly addresses the strategic aims of the NERC Environmental Microbiology and Human Health (EMHH) Programme. As requested by the call, we will provide "scientific evidence to support fast and efficient identification of pathogenic microorganisms in environmental media which can be used in appropriate tools and models for the protection of public health targeting the freshwater and coastal zone". The work is also directly relevant to the policy objectives and strategic aims of the Food Standards Agency, Defra and European Union (DG Sanco, and DG Mare).

Planned Impact

This proposal is designed to protect human health from the ever present threat of viral infection that exists in the environment. For example, Norovirus is estimated to cause over 2 million cases of illness in the UK each year, resulting in millions of days of lost productivity and an economic burden estimated to exceed £100 million to the NHS directly and over £2 billion annually to the wider economy. A reduction in the disease incidence would therefore be of great benefit to the UK economy. To ensure our project has lasting impact, a range of key stakeholders have been actively engaged in the formulation and writing of this proposal to ensure that it directly meets their needs, complements existing research and is fit for purpose. Specifically, this proposal will be of benefit to water quality managers and regulators, both national and international. The main UK beneficiaries will be the Food Standards Agency, Cefas (Defra), Environment Agency, water companies, local authorities and the shellfish industry as well as UK academia. Internationally, the work will directly inform the European Environment Agency, EU-DG MARE and EU-DG SANCO,however our project addresses an issue of global relevance, and therefore the impact will be far-reaching. Stakeholders will benefit as follows:

1. Human pathogenic viruses are rarely measured in river, estuarine and coastal waters and therefore are not used by the Environment Agency, Food Standards Agency or EU for regulatory purposes. Although ISO accredited methods of detection have been established by the team (e.g. NoV in shellfish by Cefas), uncertainty still remains on their detection in some matrices and additionally as to whether these PCR-detected viruses are still infective to humans. Therefore the formulation of regulatory standards for shellfish, bathing waters etc is currently a subject of considerable debate. As risk assessment must be based on robust scientific research, we will provide key underpinning data for polymakers and regulators.

2. Cefas work directly with the UK government and EU to monitor the marine environment and to demonstrate UK compliance with national and international marine legislation. A key part of Cefas' work is to detect and advise on the effects of anthropogenic drivers on the marine environment. Having Cefas embedded in the project will bring lasting benefits in ensuring that the information generated will have real impact. As an example, David Lees (Cefas) is Director of the European Union Reference Laboratory (EURL) monitoring bacteriological and viral contamination of bivalve molluscs which represents a primary forum for our findings. Our existing strong links with the UK Food Standards Agency and the European Union (Directorate-General for Maritime Affairs and Fisheries, DG-MARE; Directorate-General for Health and Consumer, DG-SANCO), the Consumers, Health and Food Executive Agency (CHAFEA), European Food Standards Agency (EFSA), European Centre for Environment and Human Health (ECEHH) means that we can disseminate and discuss the project findings with the regulatory and medical community through well-established channels.

3. Our project is highly relevant to water companies. Welsh Water are key stakeholders in our project while delivery to the wider water industry will be made through the UK Water Industries Research (UKWIR).

4. Key stakeholders are Public Health Wales, Public Health England and Scotland Public Health Network.

5. The Shellfish Association of Great Britain (SAGB) is an ideal vehicle to disseminate our findings to the shellfish industry and the aquaculture industry in general. Shelagh Malham attends regular SAGB meetings which bring together the shellfish industry including producers and processers, several government and non-governmental organisations and has lobby activity within Westminster for issues affecting the industry. This proposal addresses some of the top priority issues facing the industry.

Publications

10 25 50
 
Description We have demonstrated that metaviromics can be used to provide information on the RNA virus population of a watercourse, including sediments, and follow viruses from wastewater treatment plants into the riverine system and ultimately into the estuary. This is non trivial. We have been able to assemble viral genomes from environmental samples and demonstrate the presence of viral pathogens that had not been detected by conventional methods.We have provided comparative information on the viruses harboured by harvestable estuary shellfish and demonstrated that they do not simply mirror the virus population in the water. We have also provided some evidence that viruses concentrated by shellfish have undergone degradation and are therefore not necessarily infective.
Exploitation Route It is now possible to employ metaviromics in surveys of virus occurrence and dissemination in the aquatic environment, for both DNA and, importantly, RNA viruses. The methods developed have been rigorously tested and the importance of including subtractive controls demonstrated: https://doi.org/10.1128/mSystems.00025-18
Sectors Aerospace, Defence and Marine,Agriculture, Food and Drink,Environment,Healthcare,Leisure Activities, including Sports, Recreation and Tourism

URL http://www.viraqua.uk/
 
Description Applications for funding on microbial source tracking in Chinese watersheds with XJTLU, Souzhou 
Organisation Xi'an Jiaotong Liverpool University 
Country China 
Sector Academic/University 
PI Contribution Provision of expertise in formulating the application and acting as Co-investigators
Collaborator Contribution PI and host for grant application
Impact Key Programme Special Fund (KSF)' for exploratory research (any field) jointly funded by XJTLU and Suzhou Industrial Park Technology and Innovation Bureau. The funding amount is 200,000 RMB (20K GBP) for preliminary/exploratory research on CrAssphage for faecal source tracking our NSFC proposal. Award confirmed, start date TBA.
Start Year 2018
 
Description Meet the scientists at the World Museum in Liverpool: Outreach activity about viruses and bacteriophages. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Meet the scientists at the World Museum in Liverpool: Outreach activity about viruses and bacteriophages. All day activity event for children centred on hands on activities to teach children about the world of viruses.
Year(s) Of Engagement Activity 2018
URL https://news.liverpool.ac.uk/2018/11/23/new-series-of-meet-the-scientists-begins-this-weekend/
 
Description Pint of Science 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Pint of Science Festival event. Stand up routine to inform and entertain the audience.
Year(s) Of Engagement Activity 2018
URL https://pintofscience.co.uk/event/sex-faeces-and-ice-cream