Hepatitis E infections in Spain - VHPB News · HEPATITIS E VIRUS INFECTIONS IN SPAIN 29th VHPB...
Transcript of Hepatitis E infections in Spain - VHPB News · HEPATITIS E VIRUS INFECTIONS IN SPAIN 29th VHPB...
HEPATITIS E VIRUS INFECTIONS IN SPAIN
29th VHPB Meeting“Prevention and control of viral hepatitis in Spain:
Lessons learnt and the way forward” Madrid, Spain, 23-24 November, 2006
Dr. MT Pérez-GraciaDpt. Sanitary Attention, Public and Animal Health.CEU Cardenal Herrera University. Valencia. Spain
Viral HepatitisPrevention Board
Hepatitis E Virus (HEV)
Non-enveloped
27-34 nm in diameter
Fam. Hepeviridae: Genus Hepevirus
Positive-sense single-stranded RNA genome
7.5 kb long
3 ORFs
Genome Organization of HEV
7.5 kb
ORF1 (5079bp)ORF3 (369bp)
ORF2 (1980bp)
M Y P V X H R
Non-structural Structural
M: methyl transferase
Y : Y domain
P: papain-like cysteine protease
V: proline
X: domain
H: helicase
R: RNA-dependent RNA polymerase
Single Single serotypeserotype
ExtensiveExtensive genomicgenomic diversitydiversity: 4 : 4 majormajor genotypesgenotypesGenotypeGenotype 1: 5 1: 5 subtypessubtypesGenotypeGenotype 2: 2 2: 2 subtypessubtypesGenotypeGenotype 3: 10 3: 10 subtypessubtypesGenotypeGenotype 4: 7 4: 7 subtypessubtypes
(Lu et al, Rev Med Virol. 2006;16(1):5-36)
Hepatitis E Virus
Genotype 1 Genotype 2 Genotype 3 Genotype 4
Genotypes 1- 2 Genotypes 2-3 Genotypes 1-4 Genotypes 1-3- 4
•• Hepatitis E virus (HEV) Hepatitis E virus (HEV) isis thethe mainmaincausativecausative agentagent ofof nonnon--A nonA non--B B entericallyenterically transmittedtransmitted hepatitishepatitis
• Most outbreaks associated with fecallycontaminated drinking water
• Minimal person-to-person transmission
Hepatitis E - Epidemiologic Features
SPORADIC HEPATITIS E WITHOUT TRAVELLING HISTORY
ANIMAL RESERVOIR?
HE J et al. 2002HAQSHENAS G et
al. 2001
WANG et al. 2002 MENG XJ et al.1997
Hepatitis E - Epidemiologic Features
HEV causes HEV causes anan acuteacute andand selfself limitedlimited clinicalclinicalpresentationpresentation
• Incubation period: Average 40 daysRange 15-60 days
• Case-fatality rate: Overall, 1%-3%Pregnant women, 15%-25%
• Illness severity: Increased with age
• Chronic sequelae: None identified
Hepatitis E - Epidemiologic Features
Hepatitis E Virus InfectionTypical Serologic Course
Weeks after Exposure
Tite
r
Symptoms
ALTIgG anti-HEV
IgM anti-HEV
Virus in stool
0 1 2 3 4 5 6 7 8 9 10 11 12 13
Virus in serum
•• AntiAnti--HEVHEV IgGIgG
•• AntiAnti--HEVHEV IgMIgM
•• HEVHEV RNARNA nested RT-PCR
ORF3
ORF2
ORF1
Diagnostic Methods of HEVDiagnostic Methods of HEV
Commercial EIA (Recombinant Ags of Burma
and Mexico strains)
Immunoblotting (confirmation)
Enfermedades de Declaración Obligatoria. Centro Nacional de Epidemiología. Instituto de Salud Carlos III
DISTRIBUTION OF NOTIFIED CASES OF VIRAL HEPATITIS DISTRIBUTION OF NOTIFIED CASES OF VIRAL HEPATITIS IN SPAIN (1997IN SPAIN (1997--2004)2004)
47.442.3 41 42.3
45.2
36.9 35
43
05
101520253035404550
1997 1998 1999 2000 2001 2002 2003 2004
Hepatitis A Hepatitis B Hepatitis nonAnonB
2.9%
7.3%
0
2
4
6
8
10
Buti, 1995 Tarragó, 2000 Buti, 2006
5.5%
Anti-HEV in normal population of Spain
Anti-HEV in patients with acute hepatitis of Spain
Buti, 1994 Buti, 1995 Pina, 2000 Pérez-Gracia, 2004
0%
5.6%
8.1%7.7%
0
2
4
6
8
10
Age-specific prevalence of anti-HEV in patients with chronic liver disease in Spain
7.1%
25%
30.8%
37%34%
0
5
10
15
20
25
30
35
40
16-30years
31-40years
41-50years
51-60years
TOTAL
Abe et al. Southeast Asian J Trop Med Public Health, 2006; 37: 90-95
AntiAnti--HEV detection by ELISA and IBHEV detection by ELISA and IB
Echevarría-Mayo JM, Med Clin (Barc), 2006;126(6):234-6
Hepatitis E virus in pigs and sewage of Spain
Urban sewage
Feces samples
Sera samples
0%0%2.7%8.3%
50%43.5%
12.3% 10.1%
23.3%
13.7%
0
10
20
30
40
50
60
Pina, 19
98Pina,
2000
Clemen
te-Cas
ares,
2003
de Deu
s, 20
06Fern
ández
-Barr
edo, 2
006
50%
Slurry lagoons
HEV strains isolated in Spain
52 HEV 52 HEV strainsstrains
6 HEV human6 HEV humanstrainsstrains
29 HEV 29 HEV swineswinestrainsstrains
17 HEV 17 HEV sewagesewagestrainsstrains
Buti et al, J Hepatol 2004AY540115VH51
Pina et al, J Hepatol 2000AF195064-AF195065VH1-VH2
3
AF448920
AY540114
AY570904
ACCESION GENBANK
Pérez-Gracia et al, Acta Virol 2004Sp3
Buti et al, J Hepatol 2004VH4
Buti et al, J Hepatol 2004VH3
REFERENCEABREVIATIONGENOTYPE
HEV strains isolated in human in Spain
Travel Ethiopia
Non travel; HEV autochthonous
GENOTYPE ABREVIATION ACCESION GENBANK REFERENCE
Por 1 AF491002 Clemente-Casares et al, EID 2003
SpswCV2 AY323506 Fdez-Barredo et al, JVDI 2006
3
DQ093564-DQ093569
DQ141118-DQ141126
DQ141127
DQ383734-DQ383745
SpswCV3-8 Fdez-Barredo et al, Can J Vet Res 2006
SpswCV9-17 Fdez-Barredo et al, JVDI 2006
SpswCV19 Fdez-Barredo et al, JVDI 2006
UAB1-UAB12 De Deus et al, Vet Microbiol 2006
HEV strains isolated in swine in Spain
Pina et al, J Hepatol2000AF195063Slaugtherhouse
sewageSP-E11
3Clemente-Casares et
al, EID 2003AF491004-AF491003Urban sewageBCN2, BCN4
Urban sewage
Urban Sewage
ORIGIN
AF490985-AF490997
AF058679
ACCESION GENBANK
Clemente-Casares et al, EID 2003BCN3, BCN5-
BCN16
Pina et al, Appl EnvMicrobiol 1998BCN1
REFERENCEABREVIATIONGENOTYPE
HEV strains isolated in sewage in Spain
AF490997 BCN16 ORF2
AF490992 BCN11 ORF2
AF490988 BCN7 ORF2
AF490994 BCN13 ORF2
AF490986 BCN5 ORF2
AF490995 BCN14 ORF2
AF490990 BCN9 ORF2
AF490987 BCN6 ORF2
AF490985 BCN3 ORF2
AF490993 BCN12 ORF2
AF490989 BCN8 ORF2
AB248520 HE-JA04-1911
AB248522 swJ12-4
AB248521 swJ8-5
AY115488 Arkell
AB074918 JKN-Sap
AF490996 BCN15 ORF2
AF060669 HEV-US2
AF060668 HEV-US1
DQ079627 pig Japan
DQ079625 Human Japan
AB091394 JJT-Kan
AY575859 pSHEV-3
AF082843 Meng strain
AY575858 pSHEV-2
AY575857 pSHEV-1
AB246676 human Japan
AB222184 wild boar JYG1
AB236320 wild mongoose
AB222183 wild boar JTS1
DQ079630 wild boar
DQ079629 human Japan
DQ079632 G3--Swine
AB073912 swine japan
AF490991 BCN10 ORF2
DQ079626 HTN-0618
AB189075 JYO-Hyo03L
AB189074 JTH-Hyo03L
AB189071 JDEER-Hyo03L
AB189073 JSO-Hyo03L
AB189072 JMO-Hyo03L
Genotype 3
DQ450072 swCH31
AY594199 swCH25
DQ079628 W B1-Aichi
AY723745 IND-SW
DQ279091 DQ1
AB220974 HE-JA2
AB108537 CCC220
DQ079631 Li-G4-62
HEE272108 genotype 4
AB193178 JYN-Nii02L
AB099347 HE-JK4
AB193177 JYN-Sap01C
AB091395 JSN-Sap-FH
AB097812 HE-JA1
AB220971 HE-JF3
AB080575
AB220978 HE-JA37
AB220972 HE-JF4
AB161718 JTS-Sap02
AB161719 JYW -Sap02
AB220979 HE-JA41
AB220976 HE-JA28
AB220977 HE-JA36
AB161717 JSM-Sap95
AB220975 HE-JA19
AB220973 HE-JF5
Genotype 4
AY204877Chad
AY540115 VH5 ORF2
X98292 India
D11093 China Human
AF065061Morocco
DQ079624 Myanmar
E17107
D10330 HPEHEV
AF459438 India
AF051830 Nepal
AH006999 HEVBCN
Genotype 1
AY043166 Avian
99
98
96
94
94
85
81
93
91
90
74
89
88
82
0.05
Genotype 3
Genotype 4
Genotype 1
S P A N IS H S W IN E S A M P L E S
A P 0 0 3 4 3 0 J R A 1
A F 3 3 6 2 9 8 N L S W 1 0 5
A F 3 3 6 2 9 7 N L S W9 9
A F 3 3 6 2 9 0 N L S W2 0
A F 08 2843 s w -Men g
AF060 668 HEV -US1
AF060669 HEV-U
S2
AF336299 N
LSW122
AF336291 N
LSW
22
298 300
UK
Swin
e3-1
304
303
3 0 2
U K M a n N T 1 1
U K H u m a n N T 6
A F 5 0 3 5 1 1 P 3 5 4 /1 /0 2
U K H u m a n N T 1
U K H u m a n N T 5U K S w in e 1
A F 5 0 3 51 2 P 14 3 /1 1 /0 2
U K H u ma nN T 7UKHum
anNT8U KH um
a n N T 3
A J2 7 2 1 0 8 C h in a
A F151 962 Ch -T11
M7 4506 Mex ico
A F 06 5061 Mo r occ o
A Y2 0487 7 C had
AF051352 Egypt
D11093 Ja pan
M94177 H
ebei
D11092 X
injiang
X98292 India
X99441 Madras
AF170450 Vietnam
AF051830 Nepal
M73218 Pakistan
D10330 Myanmar
Genotype 3
Genotype 2
Genotype 1
Genotype 4
DQ383735 UAB2
AY323506 SpswCV2
AF195063 E11
DQ093569 SpswsCV8
DQ141126 SPSW SCV17
DQ141125 SPSW SCV16
DQ141123 SPSW SCV14
DQ141119 SPSW MCV10
DQ093565 SpswsCV4
DQ383743 UAB10
DQ383742 UAB9
DQ141124 SPSW SCV15
DQ141121 SPSW MCV12
DQ093566 SpswfCV5
DQ141122 SPSW SCV13
DQ141118 SPSW MCV9
DQ383745 UAB12
DQ383741 UAB8
DQ383736 UAB3
DQ093567 SpswmCV6
DQ093564 SpswfCV3
AF336296 NLSW 97
DQ383738 UAB5
AF195062 VH2 capsid
DQ383740 UAB7
DQ383744 UAB11
DQ383739 UAB6
AF195061 VH1 capsid
AF336295 NLSW 85
AF336292 NLSW 28
AF336294 NLSW 82
UKHumanNT4
DQ383737 UAB4
UKHumanNT2
DQ141120 SPSW MCV11
DQ093568 SpswmCV7
61
65
72
65
8890
63
0.01
Hepatitis E in Spain: Conclusions
HEV should be included in the routine diagnostics of acute and fulminant hepatitis even when no history of travel has been reported by the patient.The development of a reliable serological assay is crucial to estimate the real prevalence of HEV in “non-endemic” areas.HEV is circulating in swine herds of Spain as reported for other industrialized countries.The close relationship observed between swine and human isolates from Spain, supports that swine may be a reservoir of HEV.
Acknowledgements
Manuel RodríguezManuel Rodríguez--IglesiasIglesiasFátima GalánFátima Galán
•• UniversitaryUniversitary Hospital Hospital ofof Puerto Real (Puerto Real (UniversityUniversity ofof CadizCadiz))
•• CEU Cardenal Herrera CEU Cardenal Herrera UniversityUniversity (Valencia)(Valencia)
Salceda FernándezSalceda Fernández--BarredoBarredoCarolina GalianaCarolina GalianaÁngel GarcíaÁngel GarcíaMª Teresa GómezMª Teresa GómezSantiago VegaSantiago Vega