Hepatitis E virus infection,

France, 2002-2015

Elisabeth Couturier

Institut de Veille Sanitaire

ECDC December 2015

Objectives

To describe main hepatitis E virus infection

surveillance data in France, 2002-2015

Data sources

Surveillance systems

• National Reference Centre (NRC), 2002-2014

• Other sources

Hospital discharge reports (2004-2014)

Reimbursement data of anti-HEV EIA tests (2005-2014)

Investigations and studies

• Outbreak investigations (2005-2015)

• National descriptive study of autochthonous cases (2010)

• Case control study (2015)

• Seroprevalence studies (2003-2012)

National Reference Centre (NRC),

2002-2014

• Diagnostic algorithm

Immunocompetent

IgM(+) = recent infection to confirm by PCR

IgM(-) = no recent infection

Immunocompromised

* IgM(+) and HEV RNA(+) = recent or active infection

Clearance or persistence by testing for HEV RNA

* IgM(-) and HEV RNA(-) = no recent infection

Number of tested persons,

imported and autochthonous hepatitis E cases,

2002-2014, France (source: NRC)

1

10

100

1000

10000

100000

2002 2004 2006 2008 2010 2012 2014

N tested

N autochthonous

N imported

Number of tested persons,

imported and autochthonous hepatitis E cases,

2002-2014, France (source: NRC)

Year Tested persons

(N)

Cases (n) HEV(+) (n/N)

(%)

Imported Autochthonous Total

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

209

155

233

327

583

1 012

1 700

2 150

2 549

3 429

17 566

35 416

44 382

4

11

4

19

14

10

21

23

16

19

9

3

12

9

3

16

20

24

97

159

183

216

249

801

1 848

1 813

13

14

20

39

38

107

180

206

232

266

801

1 851

1 825

6

9

8

12

6

10

10

10

9

8

5

5

4

HEV genotypes, France, 2007-2014 (source: NRC)

0

50

100

150

200

250

300

350

400

450

500

2007 2008 2009 2010 2011 2012 2013 2014

HEV 1

HEV 2

HEV 3

HEV 4

HEV 3 subtypes, France, 2007-2014 (source: NRC)

0

50

100

150

200

250

300

2007 2008 2009 2010 2011 2012 2013 2014

3a

3b

3c

3e

3f

3i

3c

3e

3f

Characteristics of autochthonous hepatitis E cases,

2002-2014, France (source: NRC)

Year M/F sex ratio Mean age (y) Southern

regions*

2002-2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

3

1,8

2,7

2,7

4,6

2,9

2,6

2,5

ND

1,9

45

45,5

56

56

61

55

55

55

ND

55±15

70%

65%

72%

60%

57%

50%

ND

40%

ND

45%

*Aquitaine, Corse, Midi-Pyrénées, Languedoc-Roussillon, Provence-Alpes-Côte d’Azur

Number

Case definition : ICD-10 code B17.2 (acute hepatitis E)

M/F sex ratio = 2.2; mean age = 54.5y

Hospitalisation incidence rate

regional disparity 0.2-1.2/100,000

highest in southern regions

Hospital discharge reports (2004-2014)

0

100

200

300

400

500

600

700

800

2004 2006 2008 2010 2012 2014

Hospitalstay

Case

Year

Year

Number

Reimbursement data of anti-HEV EIA tests,

2005-2007 and 2010-2014

0

5000

10000

15000

20000

25000

30000

2005 2006 2007 2010 2011 2012 2013 2014

HEV EIA

Outbreak investigations (2005-2015)

Year Population Indigenous

cases (N)

Suspected source

2005-2006

2007

2007-2009

2009

2011

2011

2012

2013

2013

2015

ND*

4

18

4

59

ND*

200

15

111

200

6

3

7

1

7

11

4

2

17

7

environment

raw figatelli**

raw figatelli**

raw figatelli**

unknown

raw figatelli**

unknown

raw smoked ham

undercooked pig liver

stuffing

private well connected to

public water supply

*not documented; **pork liver sausage

• National descriptive study of autochthonous cases (2010)

N = 139; sex ratio M/F = 2.9; median age 55 y [18-86]

65% residing southern France

60% jaundice; 6% reported neuralgic amyotrophy at symptom onset

19% immunocompromised

74% subtype 3f

39% consumed raw pig-liver based products

More frequent in SE regions (52%) compared to SW (33%) and North (25%)

raw pork-liver products may be a risk factor

• Case control study (2015): ongoing

To estimate the fraction of cases attributable to consumption of raw pig-liver

products, other risk factors

Frequency and characteristics of neurologic disorders

Studies

HEV seroprevalence studies, 2003-2012, France

Year Regions Population Seroprevalence

2003-2004

2010

2009-2010

2011

2011-2012

2011

2012

1 (SW)

France

5 (East)

6

2 (South)

France

blood donors (n=529)

same blood samples

general (n=5,400)

forestry workers (n=593)

pig farm workers (n=306)

tertiary employees (n=322)

forestry workers (n=231)

blood donors (n=3,353)

blood donors (n=861)

16.6%

52%* [48-57]

4.9% [4.1-5.8]

31%

44%

26%

36%

39.1%* (IgG)

3.3%* (IgM)

23.6%* (IgG)

*Wantai HEV IgG assay

• 1rst published French case of transfusion-associated hepatitis E (Colson et al, Emerg Infect Dis 2007)

• November 2012-December 2013

53,234 blood donations

0.045% [0.043-0.047]

estimated detection rate of HEV RNA in plasma donation

1 HEV(+) sample/2,218 blood donations

2-fold greater in southern France

adjusted on region, age and sex 1/3,800 [1/6,200-1/2,700]

• 2013-2014 : systematic testing for HEV RNA

on plasma processed with solvent-detergent

• Since 2015: testing for HEV RNA

to have in stock 20-30% of plasma VHE free

Blood transmission

• Various sources: NRC, private laboratories, hospital, descriptive study

• HEV cases: male, mid-fifties, southern France

• Since 2002-2004, increasing trends (autochthonous cases, hospitalisation)

due to increasing awareness and tests availability

• Molecular surveillance

• Higher prevalence in southern France

• Small outbreaks

• Foodborne transmission: consumption of raw pork-liver products

• Labelling “Cook thoroughly” on raw pig-liver products (2009)

• Case control study: other risk factors?

Conclusion