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NOROPATROL: Why do Norovirus pandemics occur & how can we control them?

Norovirus is the commonest cause of vomiting and diarrhoea worldwide and the cause of more than 200,000 deaths every year affecting predominantly babies in developing countries.

3D graphical representation of Norovirus virions
'3D graphical representation of Norovirus virions', CDC/Illustrator: Alissa Eckert, MS [Public domain]
 

In the UK, norovirus outbreaks, particularly in winter months, are the most common reason for hospital ward closures, as well as affecting schools, care homes and even cruise ships. Although new vaccines are being developed, the worldwide spread every two to five years of a new ‘pandemic’ norovirus strain may reduce their effectiveness.

In this five-year multi-disciplinary study, we propose to analyse noroviruses collected over the last 20 years to work out how many different strains a vaccine would need to protect against. Using information on where and when each norovirus was collected will help us understand the time and place of origin for each new pandemic strain. By measuring antibodies to norovirus in stored blood samples from the same time period, we will work out how quickly new norovirus pandemics spread and whether children are the first to be infected.

We will analyse all the data together to work out who should be vaccinated, how often and whether we can predict which strains are more likely to cause problems.

Next generation sequencing of norovirus will be carried out using the automated high throughput pipeline within the UCL Pathogen Genomics Unit facility.

Sample collections

Electron micrograph of human norovirus virus like particles
Electron micrograph of human norovirus virus-like particles.

The study will use samples and associated data from current UK archives and is grateful to all providers of these samples:

Public Health England - National Outbreak strain collection

This unique archive will provide norovirus-positive stool specimen collected annually in England and Wales from 1997-2016 through national surveillance. Most are from hospital/healthcare-associated outbreaks and will be sequenced to determine the norovirus strains causing outbreaks during this time span.

Infectious Intestinal Disease (IID) Studies and the Liverpool Wellcome Trust/ Health Innovation Challenge Fund prospective study of GI infections in the community (Integrate)

This project will sequence norovirus-positive samples collected by these studies to determine the norovirus strains circulating within the community.  The IID studies were carried out in 1996-1998 and 2008-2009 while the Integrate study collected samples during 2015-2017.

Health Survey for England (HSE)

The HSE is an annual population health survey which has been running since 1995. Each year, HSE recruits 3000-6000 individuals from households in England providing a unique collection of highly representative sera from the general adult population.  The HSE will supply sera from 2008 – 2014 which will be used to determine population level immunity across the general adult population.

Public Health England Serum Epidemiology Unit

This collection of over 12,000 residual diagnostic sera from children aged 0-15 years spanning 1987-2016 will provide sera from 2008-2014 to this study to allow monitoring of population level immunity across childhood.

Patient and public engagement (PPI)

Chronic norovirus is a major problem for immunocompromised children, leading to malabsorption, requirement for artificial feeding and prolonged stays. No treatment exists, however, experimental repurposed drugs have been shown to be effective in some. To aid this we are using deep sequencing to determine whether clinical improvements are accompanied by drug induced changes in the virus (Ruis et al NEJM 2019).

To gauge parental and patient views on the burden of norovirus and their attitude to experimental treatments for this non-fatal but debilitating condition, we are establishing a focus group funded by Noropatrol. The results will inform our efforts to find and evaluate new treatments for norovirus. 

Our work in pictures

Study partners

University College London (UCL)

London School of Hygenie & Tropical Medicine (LSHTM)

University of Liverpool

University of North Carolina (UNC)

Public Health England (PHE)

Publications

2019
2018
2017