HEVnet network & database. A global network of scientists sharing molecular & epidemiological data on hepatitis E virus. Presented by Agnetha Hofhuis, on behalf of HEVnet. @hev expert meeting ECDC November 2018

1. HEVnet
Sharing sequences &
metadata of hepatitis E virus
Developed & maintained by RIVM
www.HEVnet.nl HEVnet@rivm.nl
Supported by ECDC, EJP, MVNA, RIVM
Sequences provided & analysed
by all HEVnet members
Presented by Agnetha Hofhuis

2. ECDC HEV-expert meeting 2015:
“We need a better understanding
of the emergence of hepatitis E”
“Develop a joint sequence database
accompanied by a metadata set
for the support of molecular
epidemiology investigations”
C. Adlhoch et al, J Clin Vir 2016

3. HEVnet network & database
A global network of scientists sharing molecular &
epidemiological data on HEV.
Developed & maintained by RIVM (NL)
Based on success of HAVnet & Noronet
Virology laboratory
Annelies Kroneman & Harry Vennema
Epidemiology department
Agnetha Hofhuis & Eelco Franz
Financial support:
Cornelia Adlhoch H2020 EJP-project ORION & RIVM
Steering committee: Annelies Kroneman, Cornelia Adlhoch, Ilaria Di Bartolo, Samreen Ijaz,
Sally A. Baylis, Ana Avellón, Wim van der Poel, Eelco Franz, Agnetha Hofhuis

4. HEVnet network
HEVnet members form a voluntary network of HEV experts
across Europe, fostering collaboration to perform
supranational studies between experts from:
– national public health reference laboratories
– veterinary research
– food safety
– blood safety
– environmental research
This zoonosis requires
a One Health approach.
HEV does not cause disease in animals;
is not considered a relevant veterinary issue,
requiring animal disease control measures.
N. Pavio et al,
Vet Res. 2017

5. HEVnet network meetings
October 2017: 1st meeting with all members &
RIVM-HEVnet team, ECDC and EFSA representatives.
March 2019: 2nd meeting with all members.
• Consolidate collaboration & recapitulate achievements.
• Generate ideas on:
– Research for & with HEVnet data
– Funding opportunities, alignment to existing & future
programmes (e.g. EJP One Health, Horizon2020).
– HEVnet advertisement: also attract veterinary, food,
environmental members.
• Identify needs for further harmonization,
e.g. HEV detection & subtyping, nomenclature, WGS & NGS.

6. HEVnet database
● A safe space online (since April 2017); password is granted
after confidentiality agreement.
● Quid pro quo principle for using the HEVnet data.
Data ownership remains with the data provider.
● International repository database for HEV sequences:
– Microbiological data: genetic sequences & typing results.
– Publicly accessible HEV typing tool: standardized typing of
all submitted sequences
– Combined with metadata: source, time, place, clinical info.
– Data can be queried, analysed and visualised with online
tools: phylogenetic tree tool, geographical plot, incidence
plots, pie charts.

7. HEV Genotyping tool
Publicly available
www.hevnet.nl

8. Typing according to a standardized nomenclature
Sequences of any part of the hepatitis E (HEV) genome can be
assigned to a HEV genotype.
Sequences of other ssRNA viruses are also recognized by the
tool and are assigned to their family.
HEV Genotyping tool
www.hevnet.nl

9. Aims with HEVnet data
1. Trends of human HEV using molecular typing to assess trends in
circulating HEV geno- & subtypes in humans
2. Molecular epidemiology through analysis of the distribution of HEV
subtypes in humans, for a better understanding of the underlying
epidemiology of HEV in Europe
3. Cluster investigation & outbreak detection through
comparison across countries of human HEV sequence data with provided
metadata
4. Source tracing/attribution tracing the most likely reservoirs and
sources of HEV, through identification of connections between human and
nonhuman samples from food, animals and the environment via source
attribution studies
5. Population genetics studies into the spread and evolution of HEV
6. Pathogenicity of strains through relations between viral subtypes
and severity of disease, looking at symptoms, hospitalization and mortality
Higher #aims  more meta data needed

10. HEVnet database

11. HEVnet database

12. HEVnet members from 30 institutes in 12 European countries
provide & have access to all sequences.
Nov 2018: 1400 entries from 10 countries.
Varying amount of metadata:
100% sample origin: human/ animal/ food/ environmental
90% sequencing method
69% patient sex, 67% patient year of birth
47% region of sampling
~95% genotype 3
Several new subtypes have been identified
87% human sample, 7% animal, 5% food, 0,3% environment
Sample date 2000-2014, 2015, 2016, 2017, 2018
HEVnet database

13. HEVnet database

14. Regional distribution of HEV patients
2016 (n=141)2015 (n=160)
HEVnet database

15. HEV3 subtype distribution & NL, 2015
HEVnet database

16. First descriptive analyses with 1015 HEVnet sequences:
Analysis of the association of hepatitis E virus genotype 3
clade/subtype with gender and age in Europe
Lorenzo Subissi (EUPHEM-fellow), Samreen Ijaz, Jacques Izopet,
Eelco Franz, Harry Vennema, Annelies Kroneman, Steven Van Gucht,
Vanessa Suin, Cornelia Adlhoch, Anna Rita Ciccaglione, Roberto Bruni.
• What is the subtype distribution in Belgium, France, UK,
Netherlands, Italy and Bulgaria?
• Do HEV-3 main clades (3efg versus 3abcjhi) affect different
populations in terms of age and gender?
HEVnet database

17. Thank you for your attention!
HEV expert scientists are invited to join HEVnet
Email to hevnet@rivm.nl with a short explanation:
What can you contribute to the network and database?
Your ideas are welcome:
• Research for & with HEVnet data
• Funding opportunities, alignment to existing & future
programmes (e.g. EJP One Health, Horizon2020).
• Need more veterinary, food, environmental members.

18. List of HEVnet members,
November 2018
Austria Medical University Vienna: Stephan Aberle
Belgium Sciensano: Vanessa Suin & Lorenzo Subissi (EUPHEM)
Denmark SSI: Sofie Midgley
Estonia National Institute for Health Development: Tatiana Kuznetsova
United Kingdom PHE: Samreen Ijaz
Royal Cornwall Hospital: Harry Dalton
France ANSES: Nicole Pavio
Toulouse University Hospital: Jacques Izopet
Germany PEI: Sally A. Baylis & Christel Kamp
University of Veterinary Medicine Hannover: Christine Baechlein
Institute of Virology Charité: Victor M. Corman
RKI: Mirko Faber
BfR: Reimar Johne
IMHR: Jürgen Wenzel
Ireland University College Dublin: Suzie Coughlan
This list continues on the next page…

19. (continued)
List of HEVnet members
November 2018
Italy ISS: Ilaria di Bartolo, Anna Rita Ciccaglione, Elisabetta Suffredini
Bulgarian focal point: Roberto Bruni
Lab of virology INMI Spallanzani IRCCs: Anna Rosa Garbuglia
Netherlands RIVM: Harry Vennema, Annelies Kroneman, Agnetha Hofhuis
NVWA: Ingeborg Boxman
WBVR: Wim van der Poel
Sanquin Blood Supply Foundation: Boris Hogema & Hans Zaaijer
Portugal INSA: Rita de Sousa
Spain isciii: Ana Avellon
Hospital Universitario Valle Hebron: Maria Buti
Vall d'Hebron Institut Research: Josep Quer
Biology University of Barcelona: Rosina Girones
Sweden National Veterinary Institute (SVA): Frederik Widén
Switzerland Vetsuisse, University of Zürich: Claudia Bachofen
Centre Hospitalier Universitaire Vaudois: Sahli Roland
ECDC European Centre for Disease Prevention and Control: Cornelia Adlhoch
EFSA European Food Safety Authority: Valentina Rizzi