Hepatitis E Prevalence in North American Blood Donors · Hepatitis E: Current Status Perez-Gracia...
17
Hepatitis E Prevalence in North American Blood Donors IPFA May 16 - 17, Athens Margaret Fearon, MD, Medical Director, Medical Microbiology, Canadian Blood Services
Transcript of Hepatitis E Prevalence in North American Blood Donors · Hepatitis E: Current Status Perez-Gracia...
Hepatitis E Prevalence in North American Blood Donors
IPFA May 16 - 17 AthensMargaret Fearon MD Medical Director Medical Microbiology Canadian Blood Services
Disclosures
bull Funding for all laboratory support and reagents provided byndash Roche Molecular Diagnostics
ndash National Microbiology Laboratory (NML) Public Health Agency of Canada (Canadian Study 1)
bull Testing performed byndash Screening American Red Cross Scientific Affairs
ndash Confirmatory Sanquin The Netherlands
ndash Sub-population antibody screening CDC
ndash NML (Canadian Study 1)
bull Samples provided byndash American Red Cross
ndash Hema-Quebec and Canadian Blood Services
2
Public Health Agency of Canada
Canadian Blood ServicesM FearonS OrsquoBrienV Scalia
American Red CrossS StramerM NguyenS Smith
Heacutema QueacutebecG DelageF BernierY Gregoire
SanquinB Hogema
Roche Molecular DiagnosticsJ DuncanN HuynhJ StanleyS Galel
Collaborators
Public Health Agency of Canada National Microbiology Laboratory A Andonov
Hepatitis E Current Status Perez-Gracia et al Reviews in Medical Virology 201323(6)
Hepatitis E PrevalenceGeographical Distribution of Hepatitis E virus Genotypes
gt 3 million casesyear mainly in developing countriesSeroprevalence 2 ndash 50 in developed countries
4
Clinical Presentation
Most cases asymptomatic
bull Acute hepatitis ndash more common in males gt 65 yrs and in pregnant women
ndash Incubation period 2 weeks ndash 2 months
ndash Jaundice fever malaise anorexia
ndash Viremia is transitory ndash disappears with symptom onset
bull Chronic hepatitisndash Chronic HEV infection reported in liver and kidney transplant recipients
(SOT) those with non-Hodgkins lymphoma in HIVAIDS patients stem-cell transplant (SCT) patients (all immunosuppressed patients)
ndash Almost all cases represent autochthonous HEV gt3
ndash Persistent viremia with titers 10^5-10^7 IUmL
ndash Evolution to cirrhosis occurs in up to 50 liver failure
5
Risk Profile of Hepatitis E Virus from Pigs or
Pork in CanadaWilhelm B1 Fazil A2 Rajić A1 Houde A3 McEwen SA1Send toTransbound Emerg Dis 2017 Dec64(6)1694-1708 doi 101111tbed12582 Epub 2016 Oct7
Survey of Canadian retail pork chops and
pork livers for detection of hepatitis E virus
norovirus and rotavirus using real time RT-
PCRWilhelm B1 Leblanc D2 Houde A2 Brassard J2 Gagneacute
MJ2 Plante D3 Bellon-Gagnon P3 Jones
TH4 Muehlhauser V4 Janecko N5 Avery B6 Rajić
A7 McEwen SA7
Int J Food Microbiol 2014 Aug 1818533-40 doi 101016jijfoodmicro201405006 Epub 2014 May 14
PIGS PEOPLE AND
HEPATITIS EResidue Chemistry and Predictive Microbiology Research Wyndmoor PA
Hepatitis E and Transfusion Transmission
bull Over 30 cases of reported cases of transfusion transmission
bull Cases reported in Japan UK France Saudi Arabia
bull To date no reported cases of TT HEV in North America
7
North American Donor Prevalence Studies 1
In 2013 CBS and Hema Quebec in collaboration with the National Microbiology Lab carried out a geographically limited HEV prevalence study on approximately 14000Canadian blood donors
ndash Antibody prevalence of 58
ndash 0 HEV NAT positive donors (pooled testing 48-100)
Fearon M OrsquoBrien S et al Hepatitis E in Canadian Blood Donors Transfusion 2017571420-142
Also in 2013 the American Red Cross surveyed approximately 19000 US blood donors
ndash 2 HEV NAT positive donors out of 18829 tested (ID NAT)
ndash Antibody prevalence of 77 of 4499 tested donors
Stramer S Moritz Eet al Hepatitis E virusseroprevalence and frequency of viral RNA detection among US blood donors Transfusion 201656481-488
8
North American Donor Prevalence Studies 2
bull Two independent RNA prevalence studies ndash target 100000 donations total
ndash US ndash between Feb 2015 - Feb 2016
ndash Canadian - between October 2016 - June 2017
bull 50000 US (ARC) donations throughout US but focus in Midwestndash Unlinked
bull 50000 (30000 CBS and 20000 HQ) donations from every province ndash Linked tested following product release
bull Donations tested for HEV RNA by ID-NAT at the ARC using the Roche cobasreg HEV test and the cobasreg 68008800 System (assay not approved for use in the US or Canada)
ndash Hemi-nested PCR from ampdetection plates at Roche
bull Additional testing on reactive samples performed at Sanquin and included
ndash HEV RNA quantitative PCR (74 bp ORF-3 LOD 103 IUmL)
ndash HEV genotyping (ORF-1 ORF-2)
ndash HEV antibody testing (Wantai)
bull Comparative antibody studies done on a subset of US samples at CDC9
10
Testing System
HEV Analytic Sensitivity
50 LOD (IUmL) (95 CI) 39 (34 - 43)
95 LOD (IUmL) (95 CI) 186 (159 ndash 226)
The cobasreg HEV test is not approved in the US or Canada but is available in countries that accept the CE mark
US Results3 positives50724 valid results
116908 (95 CI 15786-181987)
Sex Age State cobasregHEV Test(Ct valuemax = 50)
hn-PCR(Roche)
ViralLoad
(IUmL)2 reps
Geno-type
IgM (SCO)
IgG (SCO)
Male 65 IN 3854 Pos 15 30 3a 002 002
Male 21 CA 3738 Pos 13 58 3b 002 002
Female 55 KY 3442 Pos 1440 1400
na 1103 gt15
Prior published US study (Stramer et al Transfusion 2016)2 positives18829 valid results19500 (95CI 12580-156180)
66 yo Male IA (na IUmL Ab pos)71 yo Male IL (14 IUmL Ab neg)
11
HEV RNA Positive Donations
By Donor Residence
N=3 pos50724 (this study)
N=2 pos18829 (prior study)
12
Site Sex Age Province
cobasregHEV Test(Ct value max
= 50)
Viral load(IUmL)
IgM(SCO)
IgG(SCO)
IgM(SCO)
IgG(SCO)
HQ M 34 Quebec 3686 68 004 028 005 1355
HQ M 60 Quebec 3892 lt10 005 121 01 414
HQ M 59 Quebec 3889 55 001 004 025 1462
HQ M 70 Quebec 3889 lt10 047 gt15 005 276
HQ F 21 Quebec 3455 151 221 587 217 311
HQ M 39 Quebec 4041 28 933 1498 091 878
HQ F 41 Quebec 3829 20 001 026 202 924
CBS M 62 NS 3794 32 002 003 233 1473
CBS M 56 Alberta 3897 43 038 002 076 504
CBS M 17 Alberta 3235 3080 001 0 056 1491
CBS M 53 Ontario 3941 lt10 0 002 01 263
Genotype 3 (unique)
Canadian Results11 positives50765 valid results
Total 14615 (95 CI 12579-19244)HQ 12920 (95 CI 11417-17262)
CBS 17582 (95 CI 12961-127825)
13
Follow-up
2
1
7
1
Subset of 5040 RNA-negative samples tested for IgMIgG by 3 Commercial HEV antibody assays (CDC submitted)
Prevalence increases with age
114 prevalence(range 1065-1228)84 agreement between assays
18 prevalence(range 067-29)22 agreementbetween assays
15
Summary
bull HEV RNA is present in US and Canadian donors
ndash Frequency of all ID-NAT studies (RocheGrifols)
ndash 16 pos120318 tested or 17500
bull Wide 95 CIs no statistical difference amongst studies
bull Highest viral load = 3080 IUmL most too low to genotype lt 100 IUmL (all gt 3)
bull Most males (1316)
bull High performance of ID-NAT assays
ndash Ab positivity suggests higher frequencies of infection
bull IgM = 18 vs IgG = 118 =gt this study
bull IgM = 058 vs IgG = 77 =gt prior study
bull IgG = 59 Fearon et al Canada all significantly different
16
Summary
bull Absence of TT HEV in USCanada but clinical disease occurs -magnitude not well understood
ndash Kamar et al-chronic HEV after SOT 17-center survey 2011 Drobeniuc et al-CDC surveillance 2005-2012
ldquoHEV infection causes chronic hepatitis in gt60
recipients of solid organ transplantsrdquo
ndash Hewitt et al-UK mean viral load
bull TT = 453 log10 IUmL vs
bull non-TT = 257 log10 IUmL 95 CIs
overlap
bull Decision making underway in Canadandash RBDM
bull Should screened blood be used for ndash Solid organ stem cell transplant recipients
17
Disclosures
bull Funding for all laboratory support and reagents provided byndash Roche Molecular Diagnostics
ndash National Microbiology Laboratory (NML) Public Health Agency of Canada (Canadian Study 1)
bull Testing performed byndash Screening American Red Cross Scientific Affairs
ndash Confirmatory Sanquin The Netherlands
ndash Sub-population antibody screening CDC
ndash NML (Canadian Study 1)
bull Samples provided byndash American Red Cross
ndash Hema-Quebec and Canadian Blood Services
2
Public Health Agency of Canada
Canadian Blood ServicesM FearonS OrsquoBrienV Scalia
American Red CrossS StramerM NguyenS Smith
Heacutema QueacutebecG DelageF BernierY Gregoire
SanquinB Hogema
Roche Molecular DiagnosticsJ DuncanN HuynhJ StanleyS Galel
Collaborators
Public Health Agency of Canada National Microbiology Laboratory A Andonov
Hepatitis E Current Status Perez-Gracia et al Reviews in Medical Virology 201323(6)
Hepatitis E PrevalenceGeographical Distribution of Hepatitis E virus Genotypes
gt 3 million casesyear mainly in developing countriesSeroprevalence 2 ndash 50 in developed countries
4
Clinical Presentation
Most cases asymptomatic
bull Acute hepatitis ndash more common in males gt 65 yrs and in pregnant women
ndash Incubation period 2 weeks ndash 2 months
ndash Jaundice fever malaise anorexia
ndash Viremia is transitory ndash disappears with symptom onset
bull Chronic hepatitisndash Chronic HEV infection reported in liver and kidney transplant recipients
(SOT) those with non-Hodgkins lymphoma in HIVAIDS patients stem-cell transplant (SCT) patients (all immunosuppressed patients)
ndash Almost all cases represent autochthonous HEV gt3
ndash Persistent viremia with titers 10^5-10^7 IUmL
ndash Evolution to cirrhosis occurs in up to 50 liver failure
5
Risk Profile of Hepatitis E Virus from Pigs or
Pork in CanadaWilhelm B1 Fazil A2 Rajić A1 Houde A3 McEwen SA1Send toTransbound Emerg Dis 2017 Dec64(6)1694-1708 doi 101111tbed12582 Epub 2016 Oct7
Survey of Canadian retail pork chops and
pork livers for detection of hepatitis E virus
norovirus and rotavirus using real time RT-
PCRWilhelm B1 Leblanc D2 Houde A2 Brassard J2 Gagneacute
MJ2 Plante D3 Bellon-Gagnon P3 Jones
TH4 Muehlhauser V4 Janecko N5 Avery B6 Rajić
A7 McEwen SA7
Int J Food Microbiol 2014 Aug 1818533-40 doi 101016jijfoodmicro201405006 Epub 2014 May 14
PIGS PEOPLE AND
HEPATITIS EResidue Chemistry and Predictive Microbiology Research Wyndmoor PA
Hepatitis E and Transfusion Transmission
bull Over 30 cases of reported cases of transfusion transmission
bull Cases reported in Japan UK France Saudi Arabia
bull To date no reported cases of TT HEV in North America
7
North American Donor Prevalence Studies 1
In 2013 CBS and Hema Quebec in collaboration with the National Microbiology Lab carried out a geographically limited HEV prevalence study on approximately 14000Canadian blood donors
ndash Antibody prevalence of 58
ndash 0 HEV NAT positive donors (pooled testing 48-100)
Fearon M OrsquoBrien S et al Hepatitis E in Canadian Blood Donors Transfusion 2017571420-142
Also in 2013 the American Red Cross surveyed approximately 19000 US blood donors
ndash 2 HEV NAT positive donors out of 18829 tested (ID NAT)
ndash Antibody prevalence of 77 of 4499 tested donors
Stramer S Moritz Eet al Hepatitis E virusseroprevalence and frequency of viral RNA detection among US blood donors Transfusion 201656481-488
8
North American Donor Prevalence Studies 2
bull Two independent RNA prevalence studies ndash target 100000 donations total
ndash US ndash between Feb 2015 - Feb 2016
ndash Canadian - between October 2016 - June 2017
bull 50000 US (ARC) donations throughout US but focus in Midwestndash Unlinked
bull 50000 (30000 CBS and 20000 HQ) donations from every province ndash Linked tested following product release
bull Donations tested for HEV RNA by ID-NAT at the ARC using the Roche cobasreg HEV test and the cobasreg 68008800 System (assay not approved for use in the US or Canada)
ndash Hemi-nested PCR from ampdetection plates at Roche
bull Additional testing on reactive samples performed at Sanquin and included
ndash HEV RNA quantitative PCR (74 bp ORF-3 LOD 103 IUmL)
ndash HEV genotyping (ORF-1 ORF-2)
ndash HEV antibody testing (Wantai)
bull Comparative antibody studies done on a subset of US samples at CDC9
10
Testing System
HEV Analytic Sensitivity
50 LOD (IUmL) (95 CI) 39 (34 - 43)
95 LOD (IUmL) (95 CI) 186 (159 ndash 226)
The cobasreg HEV test is not approved in the US or Canada but is available in countries that accept the CE mark
US Results3 positives50724 valid results
116908 (95 CI 15786-181987)
Sex Age State cobasregHEV Test(Ct valuemax = 50)
hn-PCR(Roche)
ViralLoad
(IUmL)2 reps
Geno-type
IgM (SCO)
IgG (SCO)
Male 65 IN 3854 Pos 15 30 3a 002 002
Male 21 CA 3738 Pos 13 58 3b 002 002
Female 55 KY 3442 Pos 1440 1400
na 1103 gt15
Prior published US study (Stramer et al Transfusion 2016)2 positives18829 valid results19500 (95CI 12580-156180)
66 yo Male IA (na IUmL Ab pos)71 yo Male IL (14 IUmL Ab neg)
11
HEV RNA Positive Donations
By Donor Residence
N=3 pos50724 (this study)
N=2 pos18829 (prior study)
12
Site Sex Age Province
cobasregHEV Test(Ct value max
= 50)
Viral load(IUmL)
IgM(SCO)
IgG(SCO)
IgM(SCO)
IgG(SCO)
HQ M 34 Quebec 3686 68 004 028 005 1355
HQ M 60 Quebec 3892 lt10 005 121 01 414
HQ M 59 Quebec 3889 55 001 004 025 1462
HQ M 70 Quebec 3889 lt10 047 gt15 005 276
HQ F 21 Quebec 3455 151 221 587 217 311
HQ M 39 Quebec 4041 28 933 1498 091 878
HQ F 41 Quebec 3829 20 001 026 202 924
CBS M 62 NS 3794 32 002 003 233 1473
CBS M 56 Alberta 3897 43 038 002 076 504
CBS M 17 Alberta 3235 3080 001 0 056 1491
CBS M 53 Ontario 3941 lt10 0 002 01 263
Genotype 3 (unique)
Canadian Results11 positives50765 valid results
Total 14615 (95 CI 12579-19244)HQ 12920 (95 CI 11417-17262)
CBS 17582 (95 CI 12961-127825)
13
Follow-up
2
1
7
1
Subset of 5040 RNA-negative samples tested for IgMIgG by 3 Commercial HEV antibody assays (CDC submitted)
Prevalence increases with age
114 prevalence(range 1065-1228)84 agreement between assays
18 prevalence(range 067-29)22 agreementbetween assays
15
Summary
bull HEV RNA is present in US and Canadian donors
ndash Frequency of all ID-NAT studies (RocheGrifols)
ndash 16 pos120318 tested or 17500
bull Wide 95 CIs no statistical difference amongst studies
bull Highest viral load = 3080 IUmL most too low to genotype lt 100 IUmL (all gt 3)
bull Most males (1316)
bull High performance of ID-NAT assays
ndash Ab positivity suggests higher frequencies of infection
bull IgM = 18 vs IgG = 118 =gt this study
bull IgM = 058 vs IgG = 77 =gt prior study
bull IgG = 59 Fearon et al Canada all significantly different
16
Summary
bull Absence of TT HEV in USCanada but clinical disease occurs -magnitude not well understood
ndash Kamar et al-chronic HEV after SOT 17-center survey 2011 Drobeniuc et al-CDC surveillance 2005-2012
ldquoHEV infection causes chronic hepatitis in gt60
recipients of solid organ transplantsrdquo
ndash Hewitt et al-UK mean viral load
bull TT = 453 log10 IUmL vs
bull non-TT = 257 log10 IUmL 95 CIs
overlap
bull Decision making underway in Canadandash RBDM
bull Should screened blood be used for ndash Solid organ stem cell transplant recipients
17
Canadian Blood ServicesM FearonS OrsquoBrienV Scalia
American Red CrossS StramerM NguyenS Smith
Heacutema QueacutebecG DelageF BernierY Gregoire
SanquinB Hogema
Roche Molecular DiagnosticsJ DuncanN HuynhJ StanleyS Galel
Collaborators
Public Health Agency of Canada National Microbiology Laboratory A Andonov
Hepatitis E Current Status Perez-Gracia et al Reviews in Medical Virology 201323(6)
Hepatitis E PrevalenceGeographical Distribution of Hepatitis E virus Genotypes
gt 3 million casesyear mainly in developing countriesSeroprevalence 2 ndash 50 in developed countries
4
Clinical Presentation
Most cases asymptomatic
bull Acute hepatitis ndash more common in males gt 65 yrs and in pregnant women
ndash Incubation period 2 weeks ndash 2 months
ndash Jaundice fever malaise anorexia
ndash Viremia is transitory ndash disappears with symptom onset
bull Chronic hepatitisndash Chronic HEV infection reported in liver and kidney transplant recipients
(SOT) those with non-Hodgkins lymphoma in HIVAIDS patients stem-cell transplant (SCT) patients (all immunosuppressed patients)
ndash Almost all cases represent autochthonous HEV gt3
ndash Persistent viremia with titers 10^5-10^7 IUmL
ndash Evolution to cirrhosis occurs in up to 50 liver failure
5
Risk Profile of Hepatitis E Virus from Pigs or
Pork in CanadaWilhelm B1 Fazil A2 Rajić A1 Houde A3 McEwen SA1Send toTransbound Emerg Dis 2017 Dec64(6)1694-1708 doi 101111tbed12582 Epub 2016 Oct7
Survey of Canadian retail pork chops and
pork livers for detection of hepatitis E virus
norovirus and rotavirus using real time RT-
PCRWilhelm B1 Leblanc D2 Houde A2 Brassard J2 Gagneacute
MJ2 Plante D3 Bellon-Gagnon P3 Jones
TH4 Muehlhauser V4 Janecko N5 Avery B6 Rajić
A7 McEwen SA7
Int J Food Microbiol 2014 Aug 1818533-40 doi 101016jijfoodmicro201405006 Epub 2014 May 14
PIGS PEOPLE AND
HEPATITIS EResidue Chemistry and Predictive Microbiology Research Wyndmoor PA
Hepatitis E and Transfusion Transmission
bull Over 30 cases of reported cases of transfusion transmission
bull Cases reported in Japan UK France Saudi Arabia
bull To date no reported cases of TT HEV in North America
7
North American Donor Prevalence Studies 1
In 2013 CBS and Hema Quebec in collaboration with the National Microbiology Lab carried out a geographically limited HEV prevalence study on approximately 14000Canadian blood donors
ndash Antibody prevalence of 58
ndash 0 HEV NAT positive donors (pooled testing 48-100)
Fearon M OrsquoBrien S et al Hepatitis E in Canadian Blood Donors Transfusion 2017571420-142
Also in 2013 the American Red Cross surveyed approximately 19000 US blood donors
ndash 2 HEV NAT positive donors out of 18829 tested (ID NAT)
ndash Antibody prevalence of 77 of 4499 tested donors
Stramer S Moritz Eet al Hepatitis E virusseroprevalence and frequency of viral RNA detection among US blood donors Transfusion 201656481-488
8
North American Donor Prevalence Studies 2
bull Two independent RNA prevalence studies ndash target 100000 donations total
ndash US ndash between Feb 2015 - Feb 2016
ndash Canadian - between October 2016 - June 2017
bull 50000 US (ARC) donations throughout US but focus in Midwestndash Unlinked
bull 50000 (30000 CBS and 20000 HQ) donations from every province ndash Linked tested following product release
bull Donations tested for HEV RNA by ID-NAT at the ARC using the Roche cobasreg HEV test and the cobasreg 68008800 System (assay not approved for use in the US or Canada)
ndash Hemi-nested PCR from ampdetection plates at Roche
bull Additional testing on reactive samples performed at Sanquin and included
ndash HEV RNA quantitative PCR (74 bp ORF-3 LOD 103 IUmL)
ndash HEV genotyping (ORF-1 ORF-2)
ndash HEV antibody testing (Wantai)
bull Comparative antibody studies done on a subset of US samples at CDC9
10
Testing System
HEV Analytic Sensitivity
50 LOD (IUmL) (95 CI) 39 (34 - 43)
95 LOD (IUmL) (95 CI) 186 (159 ndash 226)
The cobasreg HEV test is not approved in the US or Canada but is available in countries that accept the CE mark
US Results3 positives50724 valid results
116908 (95 CI 15786-181987)
Sex Age State cobasregHEV Test(Ct valuemax = 50)
hn-PCR(Roche)
ViralLoad
(IUmL)2 reps
Geno-type
IgM (SCO)
IgG (SCO)
Male 65 IN 3854 Pos 15 30 3a 002 002
Male 21 CA 3738 Pos 13 58 3b 002 002
Female 55 KY 3442 Pos 1440 1400
na 1103 gt15
Prior published US study (Stramer et al Transfusion 2016)2 positives18829 valid results19500 (95CI 12580-156180)
66 yo Male IA (na IUmL Ab pos)71 yo Male IL (14 IUmL Ab neg)
11
HEV RNA Positive Donations
By Donor Residence
N=3 pos50724 (this study)
N=2 pos18829 (prior study)
12
Site Sex Age Province
cobasregHEV Test(Ct value max
= 50)
Viral load(IUmL)
IgM(SCO)
IgG(SCO)
IgM(SCO)
IgG(SCO)
HQ M 34 Quebec 3686 68 004 028 005 1355
HQ M 60 Quebec 3892 lt10 005 121 01 414
HQ M 59 Quebec 3889 55 001 004 025 1462
HQ M 70 Quebec 3889 lt10 047 gt15 005 276
HQ F 21 Quebec 3455 151 221 587 217 311
HQ M 39 Quebec 4041 28 933 1498 091 878
HQ F 41 Quebec 3829 20 001 026 202 924
CBS M 62 NS 3794 32 002 003 233 1473
CBS M 56 Alberta 3897 43 038 002 076 504
CBS M 17 Alberta 3235 3080 001 0 056 1491
CBS M 53 Ontario 3941 lt10 0 002 01 263
Genotype 3 (unique)
Canadian Results11 positives50765 valid results
Total 14615 (95 CI 12579-19244)HQ 12920 (95 CI 11417-17262)
CBS 17582 (95 CI 12961-127825)
13
Follow-up
2
1
7
1
Subset of 5040 RNA-negative samples tested for IgMIgG by 3 Commercial HEV antibody assays (CDC submitted)
Prevalence increases with age
114 prevalence(range 1065-1228)84 agreement between assays
18 prevalence(range 067-29)22 agreementbetween assays
15
Summary
bull HEV RNA is present in US and Canadian donors
ndash Frequency of all ID-NAT studies (RocheGrifols)
ndash 16 pos120318 tested or 17500
bull Wide 95 CIs no statistical difference amongst studies
bull Highest viral load = 3080 IUmL most too low to genotype lt 100 IUmL (all gt 3)
bull Most males (1316)
bull High performance of ID-NAT assays
ndash Ab positivity suggests higher frequencies of infection
bull IgM = 18 vs IgG = 118 =gt this study
bull IgM = 058 vs IgG = 77 =gt prior study
bull IgG = 59 Fearon et al Canada all significantly different
16
Summary
bull Absence of TT HEV in USCanada but clinical disease occurs -magnitude not well understood
ndash Kamar et al-chronic HEV after SOT 17-center survey 2011 Drobeniuc et al-CDC surveillance 2005-2012
ldquoHEV infection causes chronic hepatitis in gt60
recipients of solid organ transplantsrdquo
ndash Hewitt et al-UK mean viral load
bull TT = 453 log10 IUmL vs
bull non-TT = 257 log10 IUmL 95 CIs
overlap
bull Decision making underway in Canadandash RBDM
bull Should screened blood be used for ndash Solid organ stem cell transplant recipients
17
Hepatitis E Current Status Perez-Gracia et al Reviews in Medical Virology 201323(6)
Hepatitis E PrevalenceGeographical Distribution of Hepatitis E virus Genotypes
gt 3 million casesyear mainly in developing countriesSeroprevalence 2 ndash 50 in developed countries
4
Clinical Presentation
Most cases asymptomatic
bull Acute hepatitis ndash more common in males gt 65 yrs and in pregnant women
ndash Incubation period 2 weeks ndash 2 months
ndash Jaundice fever malaise anorexia
ndash Viremia is transitory ndash disappears with symptom onset
bull Chronic hepatitisndash Chronic HEV infection reported in liver and kidney transplant recipients
(SOT) those with non-Hodgkins lymphoma in HIVAIDS patients stem-cell transplant (SCT) patients (all immunosuppressed patients)
ndash Almost all cases represent autochthonous HEV gt3
ndash Persistent viremia with titers 10^5-10^7 IUmL
ndash Evolution to cirrhosis occurs in up to 50 liver failure
5
Risk Profile of Hepatitis E Virus from Pigs or
Pork in CanadaWilhelm B1 Fazil A2 Rajić A1 Houde A3 McEwen SA1Send toTransbound Emerg Dis 2017 Dec64(6)1694-1708 doi 101111tbed12582 Epub 2016 Oct7
Survey of Canadian retail pork chops and
pork livers for detection of hepatitis E virus
norovirus and rotavirus using real time RT-
PCRWilhelm B1 Leblanc D2 Houde A2 Brassard J2 Gagneacute
MJ2 Plante D3 Bellon-Gagnon P3 Jones
TH4 Muehlhauser V4 Janecko N5 Avery B6 Rajić
A7 McEwen SA7
Int J Food Microbiol 2014 Aug 1818533-40 doi 101016jijfoodmicro201405006 Epub 2014 May 14
PIGS PEOPLE AND
HEPATITIS EResidue Chemistry and Predictive Microbiology Research Wyndmoor PA
Hepatitis E and Transfusion Transmission
bull Over 30 cases of reported cases of transfusion transmission
bull Cases reported in Japan UK France Saudi Arabia
bull To date no reported cases of TT HEV in North America
7
North American Donor Prevalence Studies 1
In 2013 CBS and Hema Quebec in collaboration with the National Microbiology Lab carried out a geographically limited HEV prevalence study on approximately 14000Canadian blood donors
ndash Antibody prevalence of 58
ndash 0 HEV NAT positive donors (pooled testing 48-100)
Fearon M OrsquoBrien S et al Hepatitis E in Canadian Blood Donors Transfusion 2017571420-142
Also in 2013 the American Red Cross surveyed approximately 19000 US blood donors
ndash 2 HEV NAT positive donors out of 18829 tested (ID NAT)
ndash Antibody prevalence of 77 of 4499 tested donors
Stramer S Moritz Eet al Hepatitis E virusseroprevalence and frequency of viral RNA detection among US blood donors Transfusion 201656481-488
8
North American Donor Prevalence Studies 2
bull Two independent RNA prevalence studies ndash target 100000 donations total
ndash US ndash between Feb 2015 - Feb 2016
ndash Canadian - between October 2016 - June 2017
bull 50000 US (ARC) donations throughout US but focus in Midwestndash Unlinked
bull 50000 (30000 CBS and 20000 HQ) donations from every province ndash Linked tested following product release
bull Donations tested for HEV RNA by ID-NAT at the ARC using the Roche cobasreg HEV test and the cobasreg 68008800 System (assay not approved for use in the US or Canada)
ndash Hemi-nested PCR from ampdetection plates at Roche
bull Additional testing on reactive samples performed at Sanquin and included
ndash HEV RNA quantitative PCR (74 bp ORF-3 LOD 103 IUmL)
ndash HEV genotyping (ORF-1 ORF-2)
ndash HEV antibody testing (Wantai)
bull Comparative antibody studies done on a subset of US samples at CDC9
10
Testing System
HEV Analytic Sensitivity
50 LOD (IUmL) (95 CI) 39 (34 - 43)
95 LOD (IUmL) (95 CI) 186 (159 ndash 226)
The cobasreg HEV test is not approved in the US or Canada but is available in countries that accept the CE mark
US Results3 positives50724 valid results
116908 (95 CI 15786-181987)
Sex Age State cobasregHEV Test(Ct valuemax = 50)
hn-PCR(Roche)
ViralLoad
(IUmL)2 reps
Geno-type
IgM (SCO)
IgG (SCO)
Male 65 IN 3854 Pos 15 30 3a 002 002
Male 21 CA 3738 Pos 13 58 3b 002 002
Female 55 KY 3442 Pos 1440 1400
na 1103 gt15
Prior published US study (Stramer et al Transfusion 2016)2 positives18829 valid results19500 (95CI 12580-156180)
66 yo Male IA (na IUmL Ab pos)71 yo Male IL (14 IUmL Ab neg)
11
HEV RNA Positive Donations
By Donor Residence
N=3 pos50724 (this study)
N=2 pos18829 (prior study)
12
Site Sex Age Province
cobasregHEV Test(Ct value max
= 50)
Viral load(IUmL)
IgM(SCO)
IgG(SCO)
IgM(SCO)
IgG(SCO)
HQ M 34 Quebec 3686 68 004 028 005 1355
HQ M 60 Quebec 3892 lt10 005 121 01 414
HQ M 59 Quebec 3889 55 001 004 025 1462
HQ M 70 Quebec 3889 lt10 047 gt15 005 276
HQ F 21 Quebec 3455 151 221 587 217 311
HQ M 39 Quebec 4041 28 933 1498 091 878
HQ F 41 Quebec 3829 20 001 026 202 924
CBS M 62 NS 3794 32 002 003 233 1473
CBS M 56 Alberta 3897 43 038 002 076 504
CBS M 17 Alberta 3235 3080 001 0 056 1491
CBS M 53 Ontario 3941 lt10 0 002 01 263
Genotype 3 (unique)
Canadian Results11 positives50765 valid results
Total 14615 (95 CI 12579-19244)HQ 12920 (95 CI 11417-17262)
CBS 17582 (95 CI 12961-127825)
13
Follow-up
2
1
7
1
Subset of 5040 RNA-negative samples tested for IgMIgG by 3 Commercial HEV antibody assays (CDC submitted)
Prevalence increases with age
114 prevalence(range 1065-1228)84 agreement between assays
18 prevalence(range 067-29)22 agreementbetween assays
15
Summary
bull HEV RNA is present in US and Canadian donors
ndash Frequency of all ID-NAT studies (RocheGrifols)
ndash 16 pos120318 tested or 17500
bull Wide 95 CIs no statistical difference amongst studies
bull Highest viral load = 3080 IUmL most too low to genotype lt 100 IUmL (all gt 3)
bull Most males (1316)
bull High performance of ID-NAT assays
ndash Ab positivity suggests higher frequencies of infection
bull IgM = 18 vs IgG = 118 =gt this study
bull IgM = 058 vs IgG = 77 =gt prior study
bull IgG = 59 Fearon et al Canada all significantly different
16
Summary
bull Absence of TT HEV in USCanada but clinical disease occurs -magnitude not well understood
ndash Kamar et al-chronic HEV after SOT 17-center survey 2011 Drobeniuc et al-CDC surveillance 2005-2012
ldquoHEV infection causes chronic hepatitis in gt60
recipients of solid organ transplantsrdquo
ndash Hewitt et al-UK mean viral load
bull TT = 453 log10 IUmL vs
bull non-TT = 257 log10 IUmL 95 CIs
overlap
bull Decision making underway in Canadandash RBDM
bull Should screened blood be used for ndash Solid organ stem cell transplant recipients
17
Clinical Presentation
Most cases asymptomatic
bull Acute hepatitis ndash more common in males gt 65 yrs and in pregnant women
ndash Incubation period 2 weeks ndash 2 months
ndash Jaundice fever malaise anorexia
ndash Viremia is transitory ndash disappears with symptom onset
bull Chronic hepatitisndash Chronic HEV infection reported in liver and kidney transplant recipients
(SOT) those with non-Hodgkins lymphoma in HIVAIDS patients stem-cell transplant (SCT) patients (all immunosuppressed patients)
ndash Almost all cases represent autochthonous HEV gt3
ndash Persistent viremia with titers 10^5-10^7 IUmL
ndash Evolution to cirrhosis occurs in up to 50 liver failure
5
Risk Profile of Hepatitis E Virus from Pigs or
Pork in CanadaWilhelm B1 Fazil A2 Rajić A1 Houde A3 McEwen SA1Send toTransbound Emerg Dis 2017 Dec64(6)1694-1708 doi 101111tbed12582 Epub 2016 Oct7
Survey of Canadian retail pork chops and
pork livers for detection of hepatitis E virus
norovirus and rotavirus using real time RT-
PCRWilhelm B1 Leblanc D2 Houde A2 Brassard J2 Gagneacute
MJ2 Plante D3 Bellon-Gagnon P3 Jones
TH4 Muehlhauser V4 Janecko N5 Avery B6 Rajić
A7 McEwen SA7
Int J Food Microbiol 2014 Aug 1818533-40 doi 101016jijfoodmicro201405006 Epub 2014 May 14
PIGS PEOPLE AND
HEPATITIS EResidue Chemistry and Predictive Microbiology Research Wyndmoor PA
Hepatitis E and Transfusion Transmission
bull Over 30 cases of reported cases of transfusion transmission
bull Cases reported in Japan UK France Saudi Arabia
bull To date no reported cases of TT HEV in North America
7
North American Donor Prevalence Studies 1
In 2013 CBS and Hema Quebec in collaboration with the National Microbiology Lab carried out a geographically limited HEV prevalence study on approximately 14000Canadian blood donors
ndash Antibody prevalence of 58
ndash 0 HEV NAT positive donors (pooled testing 48-100)
Fearon M OrsquoBrien S et al Hepatitis E in Canadian Blood Donors Transfusion 2017571420-142
Also in 2013 the American Red Cross surveyed approximately 19000 US blood donors
ndash 2 HEV NAT positive donors out of 18829 tested (ID NAT)
ndash Antibody prevalence of 77 of 4499 tested donors
Stramer S Moritz Eet al Hepatitis E virusseroprevalence and frequency of viral RNA detection among US blood donors Transfusion 201656481-488
8
North American Donor Prevalence Studies 2
bull Two independent RNA prevalence studies ndash target 100000 donations total
ndash US ndash between Feb 2015 - Feb 2016
ndash Canadian - between October 2016 - June 2017
bull 50000 US (ARC) donations throughout US but focus in Midwestndash Unlinked
bull 50000 (30000 CBS and 20000 HQ) donations from every province ndash Linked tested following product release
bull Donations tested for HEV RNA by ID-NAT at the ARC using the Roche cobasreg HEV test and the cobasreg 68008800 System (assay not approved for use in the US or Canada)
ndash Hemi-nested PCR from ampdetection plates at Roche
bull Additional testing on reactive samples performed at Sanquin and included
ndash HEV RNA quantitative PCR (74 bp ORF-3 LOD 103 IUmL)
ndash HEV genotyping (ORF-1 ORF-2)
ndash HEV antibody testing (Wantai)
bull Comparative antibody studies done on a subset of US samples at CDC9
10
Testing System
HEV Analytic Sensitivity
50 LOD (IUmL) (95 CI) 39 (34 - 43)
95 LOD (IUmL) (95 CI) 186 (159 ndash 226)
The cobasreg HEV test is not approved in the US or Canada but is available in countries that accept the CE mark
US Results3 positives50724 valid results
116908 (95 CI 15786-181987)
Sex Age State cobasregHEV Test(Ct valuemax = 50)
hn-PCR(Roche)
ViralLoad
(IUmL)2 reps
Geno-type
IgM (SCO)
IgG (SCO)
Male 65 IN 3854 Pos 15 30 3a 002 002
Male 21 CA 3738 Pos 13 58 3b 002 002
Female 55 KY 3442 Pos 1440 1400
na 1103 gt15
Prior published US study (Stramer et al Transfusion 2016)2 positives18829 valid results19500 (95CI 12580-156180)
66 yo Male IA (na IUmL Ab pos)71 yo Male IL (14 IUmL Ab neg)
11
HEV RNA Positive Donations
By Donor Residence
N=3 pos50724 (this study)
N=2 pos18829 (prior study)
12
Site Sex Age Province
cobasregHEV Test(Ct value max
= 50)
Viral load(IUmL)
IgM(SCO)
IgG(SCO)
IgM(SCO)
IgG(SCO)
HQ M 34 Quebec 3686 68 004 028 005 1355
HQ M 60 Quebec 3892 lt10 005 121 01 414
HQ M 59 Quebec 3889 55 001 004 025 1462
HQ M 70 Quebec 3889 lt10 047 gt15 005 276
HQ F 21 Quebec 3455 151 221 587 217 311
HQ M 39 Quebec 4041 28 933 1498 091 878
HQ F 41 Quebec 3829 20 001 026 202 924
CBS M 62 NS 3794 32 002 003 233 1473
CBS M 56 Alberta 3897 43 038 002 076 504
CBS M 17 Alberta 3235 3080 001 0 056 1491
CBS M 53 Ontario 3941 lt10 0 002 01 263
Genotype 3 (unique)
Canadian Results11 positives50765 valid results
Total 14615 (95 CI 12579-19244)HQ 12920 (95 CI 11417-17262)
CBS 17582 (95 CI 12961-127825)
13
Follow-up
2
1
7
1
Subset of 5040 RNA-negative samples tested for IgMIgG by 3 Commercial HEV antibody assays (CDC submitted)
Prevalence increases with age
114 prevalence(range 1065-1228)84 agreement between assays
18 prevalence(range 067-29)22 agreementbetween assays
15
Summary
bull HEV RNA is present in US and Canadian donors
ndash Frequency of all ID-NAT studies (RocheGrifols)
ndash 16 pos120318 tested or 17500
bull Wide 95 CIs no statistical difference amongst studies
bull Highest viral load = 3080 IUmL most too low to genotype lt 100 IUmL (all gt 3)
bull Most males (1316)
bull High performance of ID-NAT assays
ndash Ab positivity suggests higher frequencies of infection
bull IgM = 18 vs IgG = 118 =gt this study
bull IgM = 058 vs IgG = 77 =gt prior study
bull IgG = 59 Fearon et al Canada all significantly different
16
Summary
bull Absence of TT HEV in USCanada but clinical disease occurs -magnitude not well understood
ndash Kamar et al-chronic HEV after SOT 17-center survey 2011 Drobeniuc et al-CDC surveillance 2005-2012
ldquoHEV infection causes chronic hepatitis in gt60
recipients of solid organ transplantsrdquo
ndash Hewitt et al-UK mean viral load
bull TT = 453 log10 IUmL vs
bull non-TT = 257 log10 IUmL 95 CIs
overlap
bull Decision making underway in Canadandash RBDM
bull Should screened blood be used for ndash Solid organ stem cell transplant recipients
17
Risk Profile of Hepatitis E Virus from Pigs or
Pork in CanadaWilhelm B1 Fazil A2 Rajić A1 Houde A3 McEwen SA1Send toTransbound Emerg Dis 2017 Dec64(6)1694-1708 doi 101111tbed12582 Epub 2016 Oct7
Survey of Canadian retail pork chops and
pork livers for detection of hepatitis E virus
norovirus and rotavirus using real time RT-
PCRWilhelm B1 Leblanc D2 Houde A2 Brassard J2 Gagneacute
MJ2 Plante D3 Bellon-Gagnon P3 Jones
TH4 Muehlhauser V4 Janecko N5 Avery B6 Rajić
A7 McEwen SA7
Int J Food Microbiol 2014 Aug 1818533-40 doi 101016jijfoodmicro201405006 Epub 2014 May 14
PIGS PEOPLE AND
HEPATITIS EResidue Chemistry and Predictive Microbiology Research Wyndmoor PA
Hepatitis E and Transfusion Transmission
bull Over 30 cases of reported cases of transfusion transmission
bull Cases reported in Japan UK France Saudi Arabia
bull To date no reported cases of TT HEV in North America
7
North American Donor Prevalence Studies 1
In 2013 CBS and Hema Quebec in collaboration with the National Microbiology Lab carried out a geographically limited HEV prevalence study on approximately 14000Canadian blood donors
ndash Antibody prevalence of 58
ndash 0 HEV NAT positive donors (pooled testing 48-100)
Fearon M OrsquoBrien S et al Hepatitis E in Canadian Blood Donors Transfusion 2017571420-142
Also in 2013 the American Red Cross surveyed approximately 19000 US blood donors
ndash 2 HEV NAT positive donors out of 18829 tested (ID NAT)
ndash Antibody prevalence of 77 of 4499 tested donors
Stramer S Moritz Eet al Hepatitis E virusseroprevalence and frequency of viral RNA detection among US blood donors Transfusion 201656481-488
8
North American Donor Prevalence Studies 2
bull Two independent RNA prevalence studies ndash target 100000 donations total
ndash US ndash between Feb 2015 - Feb 2016
ndash Canadian - between October 2016 - June 2017
bull 50000 US (ARC) donations throughout US but focus in Midwestndash Unlinked
bull 50000 (30000 CBS and 20000 HQ) donations from every province ndash Linked tested following product release
bull Donations tested for HEV RNA by ID-NAT at the ARC using the Roche cobasreg HEV test and the cobasreg 68008800 System (assay not approved for use in the US or Canada)
ndash Hemi-nested PCR from ampdetection plates at Roche
bull Additional testing on reactive samples performed at Sanquin and included
ndash HEV RNA quantitative PCR (74 bp ORF-3 LOD 103 IUmL)
ndash HEV genotyping (ORF-1 ORF-2)
ndash HEV antibody testing (Wantai)
bull Comparative antibody studies done on a subset of US samples at CDC9
10
Testing System
HEV Analytic Sensitivity
50 LOD (IUmL) (95 CI) 39 (34 - 43)
95 LOD (IUmL) (95 CI) 186 (159 ndash 226)
The cobasreg HEV test is not approved in the US or Canada but is available in countries that accept the CE mark
US Results3 positives50724 valid results
116908 (95 CI 15786-181987)
Sex Age State cobasregHEV Test(Ct valuemax = 50)
hn-PCR(Roche)
ViralLoad
(IUmL)2 reps
Geno-type
IgM (SCO)
IgG (SCO)
Male 65 IN 3854 Pos 15 30 3a 002 002
Male 21 CA 3738 Pos 13 58 3b 002 002
Female 55 KY 3442 Pos 1440 1400
na 1103 gt15
Prior published US study (Stramer et al Transfusion 2016)2 positives18829 valid results19500 (95CI 12580-156180)
66 yo Male IA (na IUmL Ab pos)71 yo Male IL (14 IUmL Ab neg)
11
HEV RNA Positive Donations
By Donor Residence
N=3 pos50724 (this study)
N=2 pos18829 (prior study)
12
Site Sex Age Province
cobasregHEV Test(Ct value max
= 50)
Viral load(IUmL)
IgM(SCO)
IgG(SCO)
IgM(SCO)
IgG(SCO)
HQ M 34 Quebec 3686 68 004 028 005 1355
HQ M 60 Quebec 3892 lt10 005 121 01 414
HQ M 59 Quebec 3889 55 001 004 025 1462
HQ M 70 Quebec 3889 lt10 047 gt15 005 276
HQ F 21 Quebec 3455 151 221 587 217 311
HQ M 39 Quebec 4041 28 933 1498 091 878
HQ F 41 Quebec 3829 20 001 026 202 924
CBS M 62 NS 3794 32 002 003 233 1473
CBS M 56 Alberta 3897 43 038 002 076 504
CBS M 17 Alberta 3235 3080 001 0 056 1491
CBS M 53 Ontario 3941 lt10 0 002 01 263
Genotype 3 (unique)
Canadian Results11 positives50765 valid results
Total 14615 (95 CI 12579-19244)HQ 12920 (95 CI 11417-17262)
CBS 17582 (95 CI 12961-127825)
13
Follow-up
2
1
7
1
Subset of 5040 RNA-negative samples tested for IgMIgG by 3 Commercial HEV antibody assays (CDC submitted)
Prevalence increases with age
114 prevalence(range 1065-1228)84 agreement between assays
18 prevalence(range 067-29)22 agreementbetween assays
15
Summary
bull HEV RNA is present in US and Canadian donors
ndash Frequency of all ID-NAT studies (RocheGrifols)
ndash 16 pos120318 tested or 17500
bull Wide 95 CIs no statistical difference amongst studies
bull Highest viral load = 3080 IUmL most too low to genotype lt 100 IUmL (all gt 3)
bull Most males (1316)
bull High performance of ID-NAT assays
ndash Ab positivity suggests higher frequencies of infection
bull IgM = 18 vs IgG = 118 =gt this study
bull IgM = 058 vs IgG = 77 =gt prior study
bull IgG = 59 Fearon et al Canada all significantly different
16
Summary
bull Absence of TT HEV in USCanada but clinical disease occurs -magnitude not well understood
ndash Kamar et al-chronic HEV after SOT 17-center survey 2011 Drobeniuc et al-CDC surveillance 2005-2012
ldquoHEV infection causes chronic hepatitis in gt60
recipients of solid organ transplantsrdquo
ndash Hewitt et al-UK mean viral load
bull TT = 453 log10 IUmL vs
bull non-TT = 257 log10 IUmL 95 CIs
overlap
bull Decision making underway in Canadandash RBDM
bull Should screened blood be used for ndash Solid organ stem cell transplant recipients
17
Hepatitis E and Transfusion Transmission
bull Over 30 cases of reported cases of transfusion transmission
bull Cases reported in Japan UK France Saudi Arabia
bull To date no reported cases of TT HEV in North America
7
North American Donor Prevalence Studies 1
In 2013 CBS and Hema Quebec in collaboration with the National Microbiology Lab carried out a geographically limited HEV prevalence study on approximately 14000Canadian blood donors
ndash Antibody prevalence of 58
ndash 0 HEV NAT positive donors (pooled testing 48-100)
Fearon M OrsquoBrien S et al Hepatitis E in Canadian Blood Donors Transfusion 2017571420-142
Also in 2013 the American Red Cross surveyed approximately 19000 US blood donors
ndash 2 HEV NAT positive donors out of 18829 tested (ID NAT)
ndash Antibody prevalence of 77 of 4499 tested donors
Stramer S Moritz Eet al Hepatitis E virusseroprevalence and frequency of viral RNA detection among US blood donors Transfusion 201656481-488
8
North American Donor Prevalence Studies 2
bull Two independent RNA prevalence studies ndash target 100000 donations total
ndash US ndash between Feb 2015 - Feb 2016
ndash Canadian - between October 2016 - June 2017
bull 50000 US (ARC) donations throughout US but focus in Midwestndash Unlinked
bull 50000 (30000 CBS and 20000 HQ) donations from every province ndash Linked tested following product release
bull Donations tested for HEV RNA by ID-NAT at the ARC using the Roche cobasreg HEV test and the cobasreg 68008800 System (assay not approved for use in the US or Canada)
ndash Hemi-nested PCR from ampdetection plates at Roche
bull Additional testing on reactive samples performed at Sanquin and included
ndash HEV RNA quantitative PCR (74 bp ORF-3 LOD 103 IUmL)
ndash HEV genotyping (ORF-1 ORF-2)
ndash HEV antibody testing (Wantai)
bull Comparative antibody studies done on a subset of US samples at CDC9
10
Testing System
HEV Analytic Sensitivity
50 LOD (IUmL) (95 CI) 39 (34 - 43)
95 LOD (IUmL) (95 CI) 186 (159 ndash 226)
The cobasreg HEV test is not approved in the US or Canada but is available in countries that accept the CE mark
US Results3 positives50724 valid results
116908 (95 CI 15786-181987)
Sex Age State cobasregHEV Test(Ct valuemax = 50)
hn-PCR(Roche)
ViralLoad
(IUmL)2 reps
Geno-type
IgM (SCO)
IgG (SCO)
Male 65 IN 3854 Pos 15 30 3a 002 002
Male 21 CA 3738 Pos 13 58 3b 002 002
Female 55 KY 3442 Pos 1440 1400
na 1103 gt15
Prior published US study (Stramer et al Transfusion 2016)2 positives18829 valid results19500 (95CI 12580-156180)
66 yo Male IA (na IUmL Ab pos)71 yo Male IL (14 IUmL Ab neg)
11
HEV RNA Positive Donations
By Donor Residence
N=3 pos50724 (this study)
N=2 pos18829 (prior study)
12
Site Sex Age Province
cobasregHEV Test(Ct value max
= 50)
Viral load(IUmL)
IgM(SCO)
IgG(SCO)
IgM(SCO)
IgG(SCO)
HQ M 34 Quebec 3686 68 004 028 005 1355
HQ M 60 Quebec 3892 lt10 005 121 01 414
HQ M 59 Quebec 3889 55 001 004 025 1462
HQ M 70 Quebec 3889 lt10 047 gt15 005 276
HQ F 21 Quebec 3455 151 221 587 217 311
HQ M 39 Quebec 4041 28 933 1498 091 878
HQ F 41 Quebec 3829 20 001 026 202 924
CBS M 62 NS 3794 32 002 003 233 1473
CBS M 56 Alberta 3897 43 038 002 076 504
CBS M 17 Alberta 3235 3080 001 0 056 1491
CBS M 53 Ontario 3941 lt10 0 002 01 263
Genotype 3 (unique)
Canadian Results11 positives50765 valid results
Total 14615 (95 CI 12579-19244)HQ 12920 (95 CI 11417-17262)
CBS 17582 (95 CI 12961-127825)
13
Follow-up
2
1
7
1
Subset of 5040 RNA-negative samples tested for IgMIgG by 3 Commercial HEV antibody assays (CDC submitted)
Prevalence increases with age
114 prevalence(range 1065-1228)84 agreement between assays
18 prevalence(range 067-29)22 agreementbetween assays
15
Summary
bull HEV RNA is present in US and Canadian donors
ndash Frequency of all ID-NAT studies (RocheGrifols)
ndash 16 pos120318 tested or 17500
bull Wide 95 CIs no statistical difference amongst studies
bull Highest viral load = 3080 IUmL most too low to genotype lt 100 IUmL (all gt 3)
bull Most males (1316)
bull High performance of ID-NAT assays
ndash Ab positivity suggests higher frequencies of infection
bull IgM = 18 vs IgG = 118 =gt this study
bull IgM = 058 vs IgG = 77 =gt prior study
bull IgG = 59 Fearon et al Canada all significantly different
16
Summary
bull Absence of TT HEV in USCanada but clinical disease occurs -magnitude not well understood
ndash Kamar et al-chronic HEV after SOT 17-center survey 2011 Drobeniuc et al-CDC surveillance 2005-2012
ldquoHEV infection causes chronic hepatitis in gt60
recipients of solid organ transplantsrdquo
ndash Hewitt et al-UK mean viral load
bull TT = 453 log10 IUmL vs
bull non-TT = 257 log10 IUmL 95 CIs
overlap
bull Decision making underway in Canadandash RBDM
bull Should screened blood be used for ndash Solid organ stem cell transplant recipients
17
North American Donor Prevalence Studies 1
In 2013 CBS and Hema Quebec in collaboration with the National Microbiology Lab carried out a geographically limited HEV prevalence study on approximately 14000Canadian blood donors
ndash Antibody prevalence of 58
ndash 0 HEV NAT positive donors (pooled testing 48-100)
Fearon M OrsquoBrien S et al Hepatitis E in Canadian Blood Donors Transfusion 2017571420-142
Also in 2013 the American Red Cross surveyed approximately 19000 US blood donors
ndash 2 HEV NAT positive donors out of 18829 tested (ID NAT)
ndash Antibody prevalence of 77 of 4499 tested donors
Stramer S Moritz Eet al Hepatitis E virusseroprevalence and frequency of viral RNA detection among US blood donors Transfusion 201656481-488
8
North American Donor Prevalence Studies 2
bull Two independent RNA prevalence studies ndash target 100000 donations total
ndash US ndash between Feb 2015 - Feb 2016
ndash Canadian - between October 2016 - June 2017
bull 50000 US (ARC) donations throughout US but focus in Midwestndash Unlinked
bull 50000 (30000 CBS and 20000 HQ) donations from every province ndash Linked tested following product release
bull Donations tested for HEV RNA by ID-NAT at the ARC using the Roche cobasreg HEV test and the cobasreg 68008800 System (assay not approved for use in the US or Canada)
ndash Hemi-nested PCR from ampdetection plates at Roche
bull Additional testing on reactive samples performed at Sanquin and included
ndash HEV RNA quantitative PCR (74 bp ORF-3 LOD 103 IUmL)
ndash HEV genotyping (ORF-1 ORF-2)
ndash HEV antibody testing (Wantai)
bull Comparative antibody studies done on a subset of US samples at CDC9
10
Testing System
HEV Analytic Sensitivity
50 LOD (IUmL) (95 CI) 39 (34 - 43)
95 LOD (IUmL) (95 CI) 186 (159 ndash 226)
The cobasreg HEV test is not approved in the US or Canada but is available in countries that accept the CE mark
US Results3 positives50724 valid results
116908 (95 CI 15786-181987)
Sex Age State cobasregHEV Test(Ct valuemax = 50)
hn-PCR(Roche)
ViralLoad
(IUmL)2 reps
Geno-type
IgM (SCO)
IgG (SCO)
Male 65 IN 3854 Pos 15 30 3a 002 002
Male 21 CA 3738 Pos 13 58 3b 002 002
Female 55 KY 3442 Pos 1440 1400
na 1103 gt15
Prior published US study (Stramer et al Transfusion 2016)2 positives18829 valid results19500 (95CI 12580-156180)
66 yo Male IA (na IUmL Ab pos)71 yo Male IL (14 IUmL Ab neg)
11
HEV RNA Positive Donations
By Donor Residence
N=3 pos50724 (this study)
N=2 pos18829 (prior study)
12
Site Sex Age Province
cobasregHEV Test(Ct value max
= 50)
Viral load(IUmL)
IgM(SCO)
IgG(SCO)
IgM(SCO)
IgG(SCO)
HQ M 34 Quebec 3686 68 004 028 005 1355
HQ M 60 Quebec 3892 lt10 005 121 01 414
HQ M 59 Quebec 3889 55 001 004 025 1462
HQ M 70 Quebec 3889 lt10 047 gt15 005 276
HQ F 21 Quebec 3455 151 221 587 217 311
HQ M 39 Quebec 4041 28 933 1498 091 878
HQ F 41 Quebec 3829 20 001 026 202 924
CBS M 62 NS 3794 32 002 003 233 1473
CBS M 56 Alberta 3897 43 038 002 076 504
CBS M 17 Alberta 3235 3080 001 0 056 1491
CBS M 53 Ontario 3941 lt10 0 002 01 263
Genotype 3 (unique)
Canadian Results11 positives50765 valid results
Total 14615 (95 CI 12579-19244)HQ 12920 (95 CI 11417-17262)
CBS 17582 (95 CI 12961-127825)
13
Follow-up
2
1
7
1
Subset of 5040 RNA-negative samples tested for IgMIgG by 3 Commercial HEV antibody assays (CDC submitted)
Prevalence increases with age
114 prevalence(range 1065-1228)84 agreement between assays
18 prevalence(range 067-29)22 agreementbetween assays
15
Summary
bull HEV RNA is present in US and Canadian donors
ndash Frequency of all ID-NAT studies (RocheGrifols)
ndash 16 pos120318 tested or 17500
bull Wide 95 CIs no statistical difference amongst studies
bull Highest viral load = 3080 IUmL most too low to genotype lt 100 IUmL (all gt 3)
bull Most males (1316)
bull High performance of ID-NAT assays
ndash Ab positivity suggests higher frequencies of infection
bull IgM = 18 vs IgG = 118 =gt this study
bull IgM = 058 vs IgG = 77 =gt prior study
bull IgG = 59 Fearon et al Canada all significantly different
16
Summary
bull Absence of TT HEV in USCanada but clinical disease occurs -magnitude not well understood
ndash Kamar et al-chronic HEV after SOT 17-center survey 2011 Drobeniuc et al-CDC surveillance 2005-2012
ldquoHEV infection causes chronic hepatitis in gt60
recipients of solid organ transplantsrdquo
ndash Hewitt et al-UK mean viral load
bull TT = 453 log10 IUmL vs
bull non-TT = 257 log10 IUmL 95 CIs
overlap
bull Decision making underway in Canadandash RBDM
bull Should screened blood be used for ndash Solid organ stem cell transplant recipients
17
North American Donor Prevalence Studies 2
bull Two independent RNA prevalence studies ndash target 100000 donations total
ndash US ndash between Feb 2015 - Feb 2016
ndash Canadian - between October 2016 - June 2017
bull 50000 US (ARC) donations throughout US but focus in Midwestndash Unlinked
bull 50000 (30000 CBS and 20000 HQ) donations from every province ndash Linked tested following product release
bull Donations tested for HEV RNA by ID-NAT at the ARC using the Roche cobasreg HEV test and the cobasreg 68008800 System (assay not approved for use in the US or Canada)
ndash Hemi-nested PCR from ampdetection plates at Roche
bull Additional testing on reactive samples performed at Sanquin and included
ndash HEV RNA quantitative PCR (74 bp ORF-3 LOD 103 IUmL)
ndash HEV genotyping (ORF-1 ORF-2)
ndash HEV antibody testing (Wantai)
bull Comparative antibody studies done on a subset of US samples at CDC9
10
Testing System
HEV Analytic Sensitivity
50 LOD (IUmL) (95 CI) 39 (34 - 43)
95 LOD (IUmL) (95 CI) 186 (159 ndash 226)
The cobasreg HEV test is not approved in the US or Canada but is available in countries that accept the CE mark
US Results3 positives50724 valid results
116908 (95 CI 15786-181987)
Sex Age State cobasregHEV Test(Ct valuemax = 50)
hn-PCR(Roche)
ViralLoad
(IUmL)2 reps
Geno-type
IgM (SCO)
IgG (SCO)
Male 65 IN 3854 Pos 15 30 3a 002 002
Male 21 CA 3738 Pos 13 58 3b 002 002
Female 55 KY 3442 Pos 1440 1400
na 1103 gt15
Prior published US study (Stramer et al Transfusion 2016)2 positives18829 valid results19500 (95CI 12580-156180)
66 yo Male IA (na IUmL Ab pos)71 yo Male IL (14 IUmL Ab neg)
11
HEV RNA Positive Donations
By Donor Residence
N=3 pos50724 (this study)
N=2 pos18829 (prior study)
12
Site Sex Age Province
cobasregHEV Test(Ct value max
= 50)
Viral load(IUmL)
IgM(SCO)
IgG(SCO)
IgM(SCO)
IgG(SCO)
HQ M 34 Quebec 3686 68 004 028 005 1355
HQ M 60 Quebec 3892 lt10 005 121 01 414
HQ M 59 Quebec 3889 55 001 004 025 1462
HQ M 70 Quebec 3889 lt10 047 gt15 005 276
HQ F 21 Quebec 3455 151 221 587 217 311
HQ M 39 Quebec 4041 28 933 1498 091 878
HQ F 41 Quebec 3829 20 001 026 202 924
CBS M 62 NS 3794 32 002 003 233 1473
CBS M 56 Alberta 3897 43 038 002 076 504
CBS M 17 Alberta 3235 3080 001 0 056 1491
CBS M 53 Ontario 3941 lt10 0 002 01 263
Genotype 3 (unique)
Canadian Results11 positives50765 valid results
Total 14615 (95 CI 12579-19244)HQ 12920 (95 CI 11417-17262)
CBS 17582 (95 CI 12961-127825)
13
Follow-up
2
1
7
1
Subset of 5040 RNA-negative samples tested for IgMIgG by 3 Commercial HEV antibody assays (CDC submitted)
Prevalence increases with age
114 prevalence(range 1065-1228)84 agreement between assays
18 prevalence(range 067-29)22 agreementbetween assays
15
Summary
bull HEV RNA is present in US and Canadian donors
ndash Frequency of all ID-NAT studies (RocheGrifols)
ndash 16 pos120318 tested or 17500
bull Wide 95 CIs no statistical difference amongst studies
bull Highest viral load = 3080 IUmL most too low to genotype lt 100 IUmL (all gt 3)
bull Most males (1316)
bull High performance of ID-NAT assays
ndash Ab positivity suggests higher frequencies of infection
bull IgM = 18 vs IgG = 118 =gt this study
bull IgM = 058 vs IgG = 77 =gt prior study
bull IgG = 59 Fearon et al Canada all significantly different
16
Summary
bull Absence of TT HEV in USCanada but clinical disease occurs -magnitude not well understood
ndash Kamar et al-chronic HEV after SOT 17-center survey 2011 Drobeniuc et al-CDC surveillance 2005-2012
ldquoHEV infection causes chronic hepatitis in gt60
recipients of solid organ transplantsrdquo
ndash Hewitt et al-UK mean viral load
bull TT = 453 log10 IUmL vs
bull non-TT = 257 log10 IUmL 95 CIs
overlap
bull Decision making underway in Canadandash RBDM
bull Should screened blood be used for ndash Solid organ stem cell transplant recipients
17
10
Testing System
HEV Analytic Sensitivity
50 LOD (IUmL) (95 CI) 39 (34 - 43)
95 LOD (IUmL) (95 CI) 186 (159 ndash 226)
The cobasreg HEV test is not approved in the US or Canada but is available in countries that accept the CE mark
US Results3 positives50724 valid results
116908 (95 CI 15786-181987)
Sex Age State cobasregHEV Test(Ct valuemax = 50)
hn-PCR(Roche)
ViralLoad
(IUmL)2 reps
Geno-type
IgM (SCO)
IgG (SCO)
Male 65 IN 3854 Pos 15 30 3a 002 002
Male 21 CA 3738 Pos 13 58 3b 002 002
Female 55 KY 3442 Pos 1440 1400
na 1103 gt15
Prior published US study (Stramer et al Transfusion 2016)2 positives18829 valid results19500 (95CI 12580-156180)
66 yo Male IA (na IUmL Ab pos)71 yo Male IL (14 IUmL Ab neg)
11
HEV RNA Positive Donations
By Donor Residence
N=3 pos50724 (this study)
N=2 pos18829 (prior study)
12
Site Sex Age Province
cobasregHEV Test(Ct value max
= 50)
Viral load(IUmL)
IgM(SCO)
IgG(SCO)
IgM(SCO)
IgG(SCO)
HQ M 34 Quebec 3686 68 004 028 005 1355
HQ M 60 Quebec 3892 lt10 005 121 01 414
HQ M 59 Quebec 3889 55 001 004 025 1462
HQ M 70 Quebec 3889 lt10 047 gt15 005 276
HQ F 21 Quebec 3455 151 221 587 217 311
HQ M 39 Quebec 4041 28 933 1498 091 878
HQ F 41 Quebec 3829 20 001 026 202 924
CBS M 62 NS 3794 32 002 003 233 1473
CBS M 56 Alberta 3897 43 038 002 076 504
CBS M 17 Alberta 3235 3080 001 0 056 1491
CBS M 53 Ontario 3941 lt10 0 002 01 263
Genotype 3 (unique)
Canadian Results11 positives50765 valid results
Total 14615 (95 CI 12579-19244)HQ 12920 (95 CI 11417-17262)
CBS 17582 (95 CI 12961-127825)
13
Follow-up
2
1
7
1
Subset of 5040 RNA-negative samples tested for IgMIgG by 3 Commercial HEV antibody assays (CDC submitted)
Prevalence increases with age
114 prevalence(range 1065-1228)84 agreement between assays
18 prevalence(range 067-29)22 agreementbetween assays
15
Summary
bull HEV RNA is present in US and Canadian donors
ndash Frequency of all ID-NAT studies (RocheGrifols)
ndash 16 pos120318 tested or 17500
bull Wide 95 CIs no statistical difference amongst studies
bull Highest viral load = 3080 IUmL most too low to genotype lt 100 IUmL (all gt 3)
bull Most males (1316)
bull High performance of ID-NAT assays
ndash Ab positivity suggests higher frequencies of infection
bull IgM = 18 vs IgG = 118 =gt this study
bull IgM = 058 vs IgG = 77 =gt prior study
bull IgG = 59 Fearon et al Canada all significantly different
16
Summary
bull Absence of TT HEV in USCanada but clinical disease occurs -magnitude not well understood
ndash Kamar et al-chronic HEV after SOT 17-center survey 2011 Drobeniuc et al-CDC surveillance 2005-2012
ldquoHEV infection causes chronic hepatitis in gt60
recipients of solid organ transplantsrdquo
ndash Hewitt et al-UK mean viral load
bull TT = 453 log10 IUmL vs
bull non-TT = 257 log10 IUmL 95 CIs
overlap
bull Decision making underway in Canadandash RBDM
bull Should screened blood be used for ndash Solid organ stem cell transplant recipients
17
US Results3 positives50724 valid results
116908 (95 CI 15786-181987)
Sex Age State cobasregHEV Test(Ct valuemax = 50)
hn-PCR(Roche)
ViralLoad
(IUmL)2 reps
Geno-type
IgM (SCO)
IgG (SCO)
Male 65 IN 3854 Pos 15 30 3a 002 002
Male 21 CA 3738 Pos 13 58 3b 002 002
Female 55 KY 3442 Pos 1440 1400
na 1103 gt15
Prior published US study (Stramer et al Transfusion 2016)2 positives18829 valid results19500 (95CI 12580-156180)
66 yo Male IA (na IUmL Ab pos)71 yo Male IL (14 IUmL Ab neg)
11
HEV RNA Positive Donations
By Donor Residence
N=3 pos50724 (this study)
N=2 pos18829 (prior study)
12
Site Sex Age Province
cobasregHEV Test(Ct value max
= 50)
Viral load(IUmL)
IgM(SCO)
IgG(SCO)
IgM(SCO)
IgG(SCO)
HQ M 34 Quebec 3686 68 004 028 005 1355
HQ M 60 Quebec 3892 lt10 005 121 01 414
HQ M 59 Quebec 3889 55 001 004 025 1462
HQ M 70 Quebec 3889 lt10 047 gt15 005 276
HQ F 21 Quebec 3455 151 221 587 217 311
HQ M 39 Quebec 4041 28 933 1498 091 878
HQ F 41 Quebec 3829 20 001 026 202 924
CBS M 62 NS 3794 32 002 003 233 1473
CBS M 56 Alberta 3897 43 038 002 076 504
CBS M 17 Alberta 3235 3080 001 0 056 1491
CBS M 53 Ontario 3941 lt10 0 002 01 263
Genotype 3 (unique)
Canadian Results11 positives50765 valid results
Total 14615 (95 CI 12579-19244)HQ 12920 (95 CI 11417-17262)
CBS 17582 (95 CI 12961-127825)
13
Follow-up
2
1
7
1
Subset of 5040 RNA-negative samples tested for IgMIgG by 3 Commercial HEV antibody assays (CDC submitted)
Prevalence increases with age
114 prevalence(range 1065-1228)84 agreement between assays
18 prevalence(range 067-29)22 agreementbetween assays
15
Summary
bull HEV RNA is present in US and Canadian donors
ndash Frequency of all ID-NAT studies (RocheGrifols)
ndash 16 pos120318 tested or 17500
bull Wide 95 CIs no statistical difference amongst studies
bull Highest viral load = 3080 IUmL most too low to genotype lt 100 IUmL (all gt 3)
bull Most males (1316)
bull High performance of ID-NAT assays
ndash Ab positivity suggests higher frequencies of infection
bull IgM = 18 vs IgG = 118 =gt this study
bull IgM = 058 vs IgG = 77 =gt prior study
bull IgG = 59 Fearon et al Canada all significantly different
16
Summary
bull Absence of TT HEV in USCanada but clinical disease occurs -magnitude not well understood
ndash Kamar et al-chronic HEV after SOT 17-center survey 2011 Drobeniuc et al-CDC surveillance 2005-2012
ldquoHEV infection causes chronic hepatitis in gt60
recipients of solid organ transplantsrdquo
ndash Hewitt et al-UK mean viral load
bull TT = 453 log10 IUmL vs
bull non-TT = 257 log10 IUmL 95 CIs
overlap
bull Decision making underway in Canadandash RBDM
bull Should screened blood be used for ndash Solid organ stem cell transplant recipients
17
HEV RNA Positive Donations
By Donor Residence
N=3 pos50724 (this study)
N=2 pos18829 (prior study)
12
Site Sex Age Province
cobasregHEV Test(Ct value max
= 50)
Viral load(IUmL)
IgM(SCO)
IgG(SCO)
IgM(SCO)
IgG(SCO)
HQ M 34 Quebec 3686 68 004 028 005 1355
HQ M 60 Quebec 3892 lt10 005 121 01 414
HQ M 59 Quebec 3889 55 001 004 025 1462
HQ M 70 Quebec 3889 lt10 047 gt15 005 276
HQ F 21 Quebec 3455 151 221 587 217 311
HQ M 39 Quebec 4041 28 933 1498 091 878
HQ F 41 Quebec 3829 20 001 026 202 924
CBS M 62 NS 3794 32 002 003 233 1473
CBS M 56 Alberta 3897 43 038 002 076 504
CBS M 17 Alberta 3235 3080 001 0 056 1491
CBS M 53 Ontario 3941 lt10 0 002 01 263
Genotype 3 (unique)
Canadian Results11 positives50765 valid results
Total 14615 (95 CI 12579-19244)HQ 12920 (95 CI 11417-17262)
CBS 17582 (95 CI 12961-127825)
13
Follow-up
2
1
7
1
Subset of 5040 RNA-negative samples tested for IgMIgG by 3 Commercial HEV antibody assays (CDC submitted)
Prevalence increases with age
114 prevalence(range 1065-1228)84 agreement between assays
18 prevalence(range 067-29)22 agreementbetween assays
15
Summary
bull HEV RNA is present in US and Canadian donors
ndash Frequency of all ID-NAT studies (RocheGrifols)
ndash 16 pos120318 tested or 17500
bull Wide 95 CIs no statistical difference amongst studies
bull Highest viral load = 3080 IUmL most too low to genotype lt 100 IUmL (all gt 3)
bull Most males (1316)
bull High performance of ID-NAT assays
ndash Ab positivity suggests higher frequencies of infection
bull IgM = 18 vs IgG = 118 =gt this study
bull IgM = 058 vs IgG = 77 =gt prior study
bull IgG = 59 Fearon et al Canada all significantly different
16
Summary
bull Absence of TT HEV in USCanada but clinical disease occurs -magnitude not well understood
ndash Kamar et al-chronic HEV after SOT 17-center survey 2011 Drobeniuc et al-CDC surveillance 2005-2012
ldquoHEV infection causes chronic hepatitis in gt60
recipients of solid organ transplantsrdquo
ndash Hewitt et al-UK mean viral load
bull TT = 453 log10 IUmL vs
bull non-TT = 257 log10 IUmL 95 CIs
overlap
bull Decision making underway in Canadandash RBDM
bull Should screened blood be used for ndash Solid organ stem cell transplant recipients
17
Site Sex Age Province
cobasregHEV Test(Ct value max
= 50)
Viral load(IUmL)
IgM(SCO)
IgG(SCO)
IgM(SCO)
IgG(SCO)
HQ M 34 Quebec 3686 68 004 028 005 1355
HQ M 60 Quebec 3892 lt10 005 121 01 414
HQ M 59 Quebec 3889 55 001 004 025 1462
HQ M 70 Quebec 3889 lt10 047 gt15 005 276
HQ F 21 Quebec 3455 151 221 587 217 311
HQ M 39 Quebec 4041 28 933 1498 091 878
HQ F 41 Quebec 3829 20 001 026 202 924
CBS M 62 NS 3794 32 002 003 233 1473
CBS M 56 Alberta 3897 43 038 002 076 504
CBS M 17 Alberta 3235 3080 001 0 056 1491
CBS M 53 Ontario 3941 lt10 0 002 01 263
Genotype 3 (unique)
Canadian Results11 positives50765 valid results
Total 14615 (95 CI 12579-19244)HQ 12920 (95 CI 11417-17262)
CBS 17582 (95 CI 12961-127825)
13
Follow-up
2
1
7
1
Subset of 5040 RNA-negative samples tested for IgMIgG by 3 Commercial HEV antibody assays (CDC submitted)
Prevalence increases with age
114 prevalence(range 1065-1228)84 agreement between assays
18 prevalence(range 067-29)22 agreementbetween assays
15
Summary
bull HEV RNA is present in US and Canadian donors
ndash Frequency of all ID-NAT studies (RocheGrifols)
ndash 16 pos120318 tested or 17500
bull Wide 95 CIs no statistical difference amongst studies
bull Highest viral load = 3080 IUmL most too low to genotype lt 100 IUmL (all gt 3)
bull Most males (1316)
bull High performance of ID-NAT assays
ndash Ab positivity suggests higher frequencies of infection
bull IgM = 18 vs IgG = 118 =gt this study
bull IgM = 058 vs IgG = 77 =gt prior study
bull IgG = 59 Fearon et al Canada all significantly different
16
Summary
bull Absence of TT HEV in USCanada but clinical disease occurs -magnitude not well understood
ndash Kamar et al-chronic HEV after SOT 17-center survey 2011 Drobeniuc et al-CDC surveillance 2005-2012
ldquoHEV infection causes chronic hepatitis in gt60
recipients of solid organ transplantsrdquo
ndash Hewitt et al-UK mean viral load
bull TT = 453 log10 IUmL vs
bull non-TT = 257 log10 IUmL 95 CIs
overlap
bull Decision making underway in Canadandash RBDM
bull Should screened blood be used for ndash Solid organ stem cell transplant recipients
17
2
1
7
1
Subset of 5040 RNA-negative samples tested for IgMIgG by 3 Commercial HEV antibody assays (CDC submitted)
Prevalence increases with age
114 prevalence(range 1065-1228)84 agreement between assays
18 prevalence(range 067-29)22 agreementbetween assays
15
Summary
bull HEV RNA is present in US and Canadian donors
ndash Frequency of all ID-NAT studies (RocheGrifols)
ndash 16 pos120318 tested or 17500
bull Wide 95 CIs no statistical difference amongst studies
bull Highest viral load = 3080 IUmL most too low to genotype lt 100 IUmL (all gt 3)
bull Most males (1316)
bull High performance of ID-NAT assays
ndash Ab positivity suggests higher frequencies of infection
bull IgM = 18 vs IgG = 118 =gt this study
bull IgM = 058 vs IgG = 77 =gt prior study
bull IgG = 59 Fearon et al Canada all significantly different
16
Summary
bull Absence of TT HEV in USCanada but clinical disease occurs -magnitude not well understood
ndash Kamar et al-chronic HEV after SOT 17-center survey 2011 Drobeniuc et al-CDC surveillance 2005-2012
ldquoHEV infection causes chronic hepatitis in gt60
recipients of solid organ transplantsrdquo
ndash Hewitt et al-UK mean viral load
bull TT = 453 log10 IUmL vs
bull non-TT = 257 log10 IUmL 95 CIs
overlap
bull Decision making underway in Canadandash RBDM
bull Should screened blood be used for ndash Solid organ stem cell transplant recipients
17
Subset of 5040 RNA-negative samples tested for IgMIgG by 3 Commercial HEV antibody assays (CDC submitted)
Prevalence increases with age
114 prevalence(range 1065-1228)84 agreement between assays
18 prevalence(range 067-29)22 agreementbetween assays
15
Summary
bull HEV RNA is present in US and Canadian donors
ndash Frequency of all ID-NAT studies (RocheGrifols)
ndash 16 pos120318 tested or 17500
bull Wide 95 CIs no statistical difference amongst studies
bull Highest viral load = 3080 IUmL most too low to genotype lt 100 IUmL (all gt 3)
bull Most males (1316)
bull High performance of ID-NAT assays
ndash Ab positivity suggests higher frequencies of infection
bull IgM = 18 vs IgG = 118 =gt this study
bull IgM = 058 vs IgG = 77 =gt prior study
bull IgG = 59 Fearon et al Canada all significantly different
16
Summary
bull Absence of TT HEV in USCanada but clinical disease occurs -magnitude not well understood
ndash Kamar et al-chronic HEV after SOT 17-center survey 2011 Drobeniuc et al-CDC surveillance 2005-2012
ldquoHEV infection causes chronic hepatitis in gt60
recipients of solid organ transplantsrdquo
ndash Hewitt et al-UK mean viral load
bull TT = 453 log10 IUmL vs
bull non-TT = 257 log10 IUmL 95 CIs
overlap
bull Decision making underway in Canadandash RBDM
bull Should screened blood be used for ndash Solid organ stem cell transplant recipients
17
Summary
bull HEV RNA is present in US and Canadian donors
ndash Frequency of all ID-NAT studies (RocheGrifols)
ndash 16 pos120318 tested or 17500
bull Wide 95 CIs no statistical difference amongst studies
bull Highest viral load = 3080 IUmL most too low to genotype lt 100 IUmL (all gt 3)
bull Most males (1316)
bull High performance of ID-NAT assays
ndash Ab positivity suggests higher frequencies of infection
bull IgM = 18 vs IgG = 118 =gt this study
bull IgM = 058 vs IgG = 77 =gt prior study
bull IgG = 59 Fearon et al Canada all significantly different
16
Summary
bull Absence of TT HEV in USCanada but clinical disease occurs -magnitude not well understood
ndash Kamar et al-chronic HEV after SOT 17-center survey 2011 Drobeniuc et al-CDC surveillance 2005-2012
ldquoHEV infection causes chronic hepatitis in gt60
recipients of solid organ transplantsrdquo
ndash Hewitt et al-UK mean viral load
bull TT = 453 log10 IUmL vs
bull non-TT = 257 log10 IUmL 95 CIs
overlap
bull Decision making underway in Canadandash RBDM
bull Should screened blood be used for ndash Solid organ stem cell transplant recipients
17
Summary
bull Absence of TT HEV in USCanada but clinical disease occurs -magnitude not well understood
ndash Kamar et al-chronic HEV after SOT 17-center survey 2011 Drobeniuc et al-CDC surveillance 2005-2012
ldquoHEV infection causes chronic hepatitis in gt60
recipients of solid organ transplantsrdquo
ndash Hewitt et al-UK mean viral load
bull TT = 453 log10 IUmL vs
bull non-TT = 257 log10 IUmL 95 CIs
overlap
bull Decision making underway in Canadandash RBDM
bull Should screened blood be used for ndash Solid organ stem cell transplant recipients
17
![Hepatitis screening Chinese [Kompatibilitetstilstand] 2014/Oral presentations...collaboration with the Chinese community High prevalence of hepatitis B infections (6%) Low prevalence](https://static.fdocuments.us/doc/165x107/5e175694a1c2c52b8c4f477f/hepatitis-screening-chinese-kompatibilitetstilstand-2014oral-presentationscollaboration.jpg)
