Download Hepatitis E virus sero-prevalence: Does locally acquired

Hepatitis E virus sero-prevalence:
Does locally acquired infection occur more
frequently than we think?
Helen Faddy, Ashish Shrestha, Robert Flower
31st Annual NRL workshop on infectious diseases
31st July 2014
Hepatitis E Virus (HEV)

Morphology: Icosahedral, 27-34 nm, non-enveloped virus1

Genome: ssRNA, three ORFs

Genotypes: 1-4 (24 subgenotypes)

Case fatality rate: 0.2-4% (epidemics)1

Clinical features: Epigastric pain, diarrhoea, jaundice, hepatomegaly
1. Kamar N., et al., Lancet 379, 2477-2488 (2012).
Modes of transmission
Drinking contaminated water
Transfusion-transmission
Congenital
Consumption of uncooked infected meat
Contact with infected animals
Organ transplantation
Immune Response
Virus (RNA) in blood
Virus in Stool
Jaundice
Titre
Serum Transaminase
HEV IgG (persists: 2-12+ years)
HEV IgM (persists: 6 months)
0
1
2
3
4
5
6
7
8
9
Number of weeks post-infection
1. Kamar N., et al., Lancet 379, 2477-2488 (2012).
10
11
12
13
14
Source: Kamar et al., 2012
Confidential
Global HEV IgG seroprevalence
4.7% (Scotland)2
15.8% (UK)3
32.6%6 (China)
18.8%(USA)4
52.5% (France)5
15.2%8 (PNG)
4.2%7 (New Zealand)
Source: Kamar et al., 2012
1. Kamar N., et al., Lancet 379, 2477-2488 (2012); 2. Cleland A., et al., Vox Sang 105(4),283-289 (2013); 3. Dalton HR., et al., Clin Microbiol
Infect Dis 27(7), 579-585 (2008); 4. Xu C., et al., Transfusion 53(10Pt2),2505-2511 (2013); 5. Mansuy JM., et al., Emerg Infect Dis 17(12),
2309-2312 (2011); 6. Guo QS., et al., J Clin Microbiol 48(1), 317-318 (2010); 7. Dalton HR., et al., J Gastroenterol Hepatol 22(8),1236-1240
(2007); 8. Halliday JS., et la., Emerg Infect Dis 6(20), (2004)
HEV in Australia
National yearly notifications1

50
Number of notified cases
45
Nationally notifiable disease1
•
40
•
35
30
25
•
20
15
Average of 25 cases nationally/year
Majority in NSW (41%) and VIC
(31%)
Majority in adults >20 years
10
5

WA
8%
2013
2012
Majority in who reported recent travel
to areas where the disease was
endemic2
•
NSW
42%
QLD
13%
2011
2010
ACT
4%
VIC
31%
TAS SA
1% 0%
2009
2008
2007
2006
2005
2004
2003
2002
2001
2000
1999
0
NT
1%

Locally acquired infection described in
NT3
Asymptomatic infection is possible
thus incidence of the disease is
unknown
Cases notified by state/territory
1. Australia’s Notifiable Diseases Status: Annual report of the National Notifiable Diseases Surveillance system (2014); 2. Cowie, B.
et al., Emerging Infectious Diseases 11, 482-484 (2005); 3. Heath, T., et al., Medical Journal of Australia 162 318-319 (1995)
Prevalence in Australia – little is known

Humans1:
•

Pigs2:
•

Sero-prevalence ranges from 0.4% blood
donors (n=279) to 7.7% refugees (n=182)
and patients (non-A, non-B hepatitis; n=13)
Sero-prevalence ranges from 30-95% in
piggeries to 17% in wild pigs
Birds3:
•
HEV strains detected in Australian chickens
1. Moaven, L., et al., Journal of Medical Virology 45, 326-330 (1995); 2. Chandler, J. D., et al., Veterinary Microbiology 68, 95-105
(1999); 3. Bilic, I., et al., Journal of General Virology 90, 863-873 (2009)
HEV & blood safety

HEV RNA detected in blood donors from China, UK,
Germany, Japan, the Netherlands, Scotland1

Documented TT-HEV in UK, France, Japan, Saudi
Arabia, and Germany1-6
•

Including in Intercept PRT treated plasma7
Chronic HEV cases reported in immunocompromised
patients1
Screening blood donors for HEV RNA has been proposed in
Germany, Sweden, and France8
 Screening of donations in the Hokkaido region of Japan9

1. Kamar N., et al., Lancet 379, 2477-2488 (2012); 2. Colson P., et al., Emerging Infectious Diseases 13, 648-649 (2007); 3. Boxall E., et
al., Transfusion Medicine 16, 79-83 (2006); 4. Matsubayashi K., et al., Transfusion 44, 934-940 (2004); 5. Khuroo MS., et al., J
Gastroenterol Hepatol 19(7), 778-84 (2004); 6. Huzly et al., Transfusion-transmitted hepatitis E in Germany, 2013. Eurosurveillance 19(21)
(2014); 7. Hauser, et al., Blood 128, 796 (2014); 8. Féray, C., et al., The Lancet. 383(9913), 218 (2014); 9. IBPN 31(9) 130-131 (2014)
RESEARCH AIM:
Determine the current sero-prevalence of
antibodies to HEV in Australian blood
donors
HEV IgG seroprevalence

194/3,237 (5.99%; 95% CI 5.18-6.18) donors HEV IgG positive
Donors tested
HEV IgG positive
n
% (95% CI)
Odds ratio*
p-value*
Gender
Female
1,453
78
5.37 (4.21-6.53)
†
-
Male
1,784
116
6.50 (5.36-7.65)
1.23 (0.91-1.65)
0.177
ACT
406
25
6.16 (3.82-8.50)
†
-
NSW
405
23
5.68 (3.42-7.93)
0.92 (0.51-1.64)
0.773
NT
407
26
6.39 (4.01-8.76)
1.04 (0.59-1.83)
0.892
QLD
402
18
4.48 (2.46-6.50)
0.71 (0.38-1.33)
0.289
SA
404
32
7.92 (5.29-10.55)
1.31 (0.76-2.25)
0.328
TAS
401
20
4.99 (2.86-7.12)
0.80 (0.43-1.46)
0.800
VIC
411
23
5.60 (3.37-7.82)
0.90 (0.50-1.62)
0.733
WA
401
27
6.73 (4.28-9.19)
1.10 (0.63-1.93)
0.739
State/Territory
* Calculated using univariate analysis, † reference group
Confidential
HEV IgG seroprevalence: age
* indicates (p< 0.05); multivariate analysis
HEV IgG seroprevalence: overseas travel
Donors
tested
HEV IgG positive
Univariate analysis
n
% (95% CI)
Odds ratio
p-value
14
3.37
†
-
6.38
1.96
0.017
(5.48-7.28)
(1.12-3.40)
Overseas travel
No
416
(1.63-5.10)
Yes
2,821
180
† reference group
HEV IgG seroprevalence: no travel
Donors
tested
HEV IgG positive
n
% (95% CI)
Gender
Female
180
6
3.33 (0.71-5.96)
Male
236
8
3.39 (1.08-5.70)
<45
254
5
1.97 (0.26-3.68)
≥45
162
9
5.56 (2.03-9.08)
† reference group
NSW
61
5
-
NT
30
2
-
QLD
75
1
-
SA
66
4
-
TAS
104
2
-
VIC/WA/ACT
80
-
-
Age (years)
State/Territory
HEV IgM and RNA
HEV IgM in IgG seropositive donors: 4/194 (2.06%; 95% CI 0.06-4.06)
Sample
Travel outside
State
Age
Sex
N62
NSW
60
M
Y
Malaria-related
A177
NSW
72
M
Y
-
W137
WA
45
F
Y
Malaria-related
S122
SA
63
M
Y
Malaria related, food poisoning
number
Australia
Prior deferrals
Confidential
Summary
•
~6% of Australian donors had prior HEV infection
•
•

Greatest in:
- older donors
- donors who traveled outside Australia
HEV IgG in donors who did not report overseas travel
A larger study (n=14,000 donations) based on detection of
HEV RNA is planned to allow us to predict the risk of
transfusion-transmitted HEV in Australia
Acknowledgements
Australian Red Cross Blood Service

•
R&D: Prof. Robert Flower, A/Prof. Catherine Hyland, Ashish
Shrestha, Jesse Fryk, Kelly Rooks
•
MT&QS: Dr Clive Seed, Dr Anthony Keller, Dr Robert
Harley, Dr Mark Chan, Dr Hung-Sing Yang, Philip Kiely
•
Manufacturing: Sue Ismay, Albert Fadel, Leo Lycett, Brian
Fisher, Rebecca Rodda
•
Donor services staff
Australian governments fully fund the Australian Red Cross Blood Service for the
provision of blood products and services to the Australian community