Hepatitis E Virus Enhanced Surveillance
Hepatitis E virus epidemiology in England and Wales: Identifying
risk factors for indigenous infection
Study team
Samreen Ijaz, Clinical Scientist, Virus Reference Department (VRD),
HPA Colindale
Bengü Said, Senior Scientist, Gastrointestinal, Emerging and Zoonotic
Infections (GEZI) Department, HPA Colindale
Meera Chand, Specialist Registrar, Medical Microbiology & Virology,
HPA Colindale
Dilys Morgan, Head, Gastrointestinal, Emerging and Zoonotic
Infections Department, HPA Colindale
Background
Hepatitis E virus (HEV) infections in Europe and North America were
believed to be associated with travel to endemic areas, however
autochthonous hepatitis E has been increasingly recognised.
Sequence analysis indicates that the genotype 3 HEV found in human
infections in non-endemic countries is very similar to that found in
swine and although contact with pigs and consumption of pig products
have been reported as risk factors for some infections and outbreaks,
a range of food sources and risk factors have been identified. 1,2
However, in most cases, the source of infection remains
undetermined.
Following the identification of non-travel associated cases of hepatitis
E in England and Wales in 2004 3, enhanced surveillance was carried
out in 2005 to identify potential risk factors for infections. That year
saw a significant increase in the number of cases and 329 cases were
confirmed of which 33 were established to be indigenous and a further
67 were likely to be indigenous infections. The majority were
Caucasian males over 55 years of age, but a specific risk factor could
not be identified.4
The number of confirmed cases dropped slightly in 2006 and
significantly in 2007, but then started to increase again from 2008,
showing a marked increase in 2010 (Table 1). Therefore it is felt that
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routes of acquisition should be re-investigated in order to try and
establish sources of infection and reduce the public health risk.
Table 1: Cases of Hepatitis E infection confirmed by Reference
Laboratories (Colindale and Birmingham) in England and Wales,
2005-2010.
Year
2004 2005 2006 2007 2008 2009 2010
Number of confirmed cases 150
329
292
165
178
180
278
Aims and objectives
Objective: To determine the possible risk factors for the acquisition of
indigenous HEV infection in England and Wales.
Our aim is for enhanced surveillance data to generate hypotheses on
risk factors that can be tested in subsequent studies.
Study Design and Methodology
Period of study: Enhanced surveillance of hepatitis E cases of possible
indigenous origin will commence June 2011. It will continue until a
hypothesis has been generated or complete data has been gathered
on a maximum of 25 non-travel-associated UK cases. This is
estimated at 3 months.
Design: Enhanced surveillance of cases diagnosed by reference
laboratory.
Cases for interview: HEV infection of possible indigenous origin will be
identified using the following definition:
A case that is confirmed by HPA Colindale VRD by
(i)
detection of HEV RNA
OR
(ii)
detection of HEV IgG and IgM
and
has ‘no travel’ stated on the laboratory request form
Or
2
if no travel information is given, patient is 50 years old or over with a
Caucasian name 1
Or
the virus is found to be genotype 3 through molecular characterisation
Sample: Cases fulfilling the eligibility above will be contacted and
interviewed until a maximum of 25 cases with full epidemiological
information and no evidence of travel to endemic areas have been
obtained.
Methodology:
(i) Surveillance procedure
 The regional hepatitis leads will be consulted regarding
conducting enhanced surveillance. Information will be
disseminated to Health Protection Units and Consultants in
Communicable Disease Control.
 For cases diagnosed from June 2011 onwards, patient
information will be passed securely from VRD to GEZI.
 GEZI will notify the appropriate Health Protection Unit.
 The protocol for obtaining surveillance information is shown in
Figure 1. Either the HPU or GEZI will conduct a telephoneadministered questionnaire.
 All data will be entered into a secure Excel spreadsheet at HPA
Colindale.
(ii) Questionnaire
The questionnaire has been developed following a review of literature
on hepatitis E acquisition and using knowledge of transmission of other
gastro-intestinal disease. Questions relating to demographic factors
and possible risk factors are included. The main risk factors to be
included are:

Travel: Travel to an endemic area within the incubation period
(in which case the interview will be terminated). For the
Based on the previous study which found that being male, having a
Caucasian name and being over 50 years was strongly predictive of being a
non-travel related case
1
3





purposes of this study, countries in Africa and Asia will be
considered endemic.
Contacts: Known contact with people who have travelled to an
endemic area.
Food: Possibilities include pork, other meat products, shellfish
and fresh vegetables.
Water: Recreational water contact.
Animals: Exposure to livestock, pets, or other animals.
Sexual exposure: A question regarding sexual orientation and
recent sexual partners is included. It is not felt to be appropriate
to take a detailed sexual history in a telephone interview.
As the incubation period of HEV varies between 2-9 weeks, gaining
information about the exposure variables will be difficult. A trawling
questionnaire will be used, asking open-ended question such as ‘Is it
likely that you ate the following foods in the 9 weeks before onset of
symptoms?’ Possible responses would be ‘yes, at home’, ‘yes, away
from home’ and ‘never’ with an option to specify which type and source
of food and if handled raw.
If potential sources or routes of infection are identified, then the
questionnaire will be modified for subsequent interviews to explore
these factors.
Rationale for design: Previous surveillance has not identified a route of
acquisition for HEV in the UK. In view of the increase in cases in 2010,
it is prudent to undertake detailed enhanced surveillance in order to
gain more information about potential sources of infection and risk
factors.
Data Processing and Handling
The data will be processed and handled by the study team in GEZI at
HPA Colindale. A system is to be set up whereby data from the
reference laboratory will be transferred in a timely way to GEZI so that
cases can be promptly followed up. Data will be entered into Excel.
Data Analysis
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Data will be analysed using Excel. As this study involves hypothesis
generation, analysis will predominantly be descriptive.
Ethics Committee Approval
Ethics Committee approval is not required for enhanced surveillance.
Preferred timetable
Critical stage
Enhanced surveillance commenced
Data collection completed
Analysis completed
Final report
Date
June 2011
September 2011
October 2011
November 2011
References
1 Lewis
HC, Wichmann O, Duizer E. Transmission routes and risk
factors for autochthonous hepatitis E virus infection in Europe: a
systematic review. Epidemiol Infect. 2010;138 :145-66..
2 Wilhelm BJ, Rajić A, Grieg J, et al. A systematic review/metaanalysis of primary research investigating swine, pork or pork products
as a source of zoonotic hepatitis E virus. Epidemiol Infect. 2011 Apr
18:1-18. [Epub ahead of print]
3
Ijaz S, Arnold E, Banks M, Bendall RP, Cramp ME, Cunningham R et
al. Non-travel-associated hepatitis E in England and Wales:
demographic, clinical, and molecular epidemiological characteristics. J
Infect Dis. 2005;192:1166-72.
4. Lewis
HC, Boisson S, Ijaz S, Hewitt K, Ngui SL, Boxall E, et al.
Hepatitis E in England and Wales. Emerg Infect Dis 2008; 14: 165-167
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Figure 1:
Process
for
enhance
d
surveilla
nce of
nontravelassociate
d
hepatitis
E in
England
and
Wales
VRD receives sample for
HEV testing
Results compatible with
or diagnostic of acute
HEV infection*
No evidence of acute HEV
infection
Request form: History of
travel outside the UK
Request form: ‘No travel’
stated or no travel
information and
Caucasian name and
aged 50 years or over
No further follow up
Case data referred to HEV
team
HEV team contacts HPU
to ask if they routinely
interview hepatitis E cases
If YES: send revised
questionnaire to HPU for
completion
If NO: HPU does not agree
to complete questionnaire
Upload questionnaire to
HPZone or email to
zoonoses@hpa.org.uk or
fax securely to 0208 905
9929
HEV team contacts patient
and completes
questionnaire
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*
A case that is confirmed by HPA Colindale VRD either by detection of HEV RNA
(diagnostic of acute HEV infection) OR by detection of HEV IgG and IgM
(compatible with acute HEV infection)
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