Investigating the transmission of Hepatitis E virus on a ... · infections • All indigenously acquired infections between 2003-2012 due to G3 viruses • Emergence of group 2 since

Investigating the transmission of Hepatitis E virus on a UK pig farm

Susan Withenshaw

Department of Epidemiological Sciences

Animal and Plant Health Agency

United Kingdom

Overview• Hepatitis E in the UK

• Human population

• Pig population

• UK abattoir study

• Current APHA study• Prospective study of single batch on farrow-to-finish farm

• Investigating trends in on-farm persistence of HEV

• Future work

On-farm study of HEV epidemiology in UK pigs 2

Hepatitis E in the UK: Human population

• PHE enhanced surveillance since 2003

• Increase in number of cases• Driven by increase in number of indigenously acquired

infections

• All indigenously acquired infections between 2003-2012 due to G3 viruses

• Emergence of group 2 since 2008 and now the dominant phylotype

• Infection in England and Wales associated with consumption of processed pork products

3On-farm study of HEV epidemiology in UK pigs

From Ijaz et al. 2014

From Adlhoch et al. 2016

From Ijaz et al. 2014

Hepatitis E in the UK: Pig population

4

• HEV is believed to be widespread on farms

• Found on most farms where investigated so far

• Has been present since at least 1991 (Banks et al. 2004)

• HEV-antibody testing of historical serum samples from VLA (APHA)

• But what about at point of slaughter?

On-farm study of HEV epidemiology in UK pigs

Banks et al. 2004Bedfordshire, England

Farm 1: 9/40 (22.5%)Farm 2: 2/2 (100%)

HEV RNA in faeces

McCreary et al. 2008Yorkshire Humberside, England

9 farms, 20 samples eachAll farms at least 1 positive sampleRange 5-35% sample prevalence

HEV RNA in faeces

Crossan et al. 2015Scotland

23 farms in 6 regions in ScotlandAll regions positiveRange 4-21% sample prevalence

HEV RNA in serum

UK pig production

10,000 pig farms

1600 farms 92% of production

Geographically widespread

High densities NE England, East Anglia, NE Scotland

APHA LDDG Pig Population Report Nov 2017

Multi-agency project resourced by multiple funders

Initiated by Defra, led by AHVLA (APHA)

AHVLA, VMD, FSA, PHE, British Pig Executive

1st UK-wide prevalence estimates for a number of important pathogens incl. HEV


2013 UK Abattoir Study

STUDY DESIGN

Cross-sectional study of slaughter pigs

• 14 abattoirs

• Process 80% of UK pigs

• 439 farms (1-10 pigs / farm)

• Weighted and stratified sampling across abattoirs

• Random selection of pigs at each abattoir on the sampling day

Caecal content samplesPlasma samples

HEV RNA(active infection)

HEV-specific antibodies(Wanti Total HEV antibody assay)

(prior exposure)

Paired samples for 629 pigs

Text in footer 6

Exposure to infection common


RNA prevalence =Detectable active infection rarer

High-level viraemia very rare

Antibody prevalence =

5.7%95% C.I. 3.9 - 7.6%

1%6 / 629

92.8%95%C.I. 90.7 - 95.0%

20.5%95%C.I 17.2 - 23.8%

In plasma and/orcecal content

in plasma in cecal content17.0%

95% C. I. 14.0 - 20.0%

% of plasma samples with viral load > 102 IU/mL

=

Text in footer 7

From Grierson et al. 2015

VIRAL SEQUENCES

• 27 RNA samples sequenced at 348-bp fragment of ORF2

• 23 unique sequences

• All G3, most (22/23) clustered with human “group 1”

• Most viruses from UK patients cluster with “group 2”


• Viruses involved in most human cases in the UK are unlikely to come from UK-bred pigs

• Infections in UK-bred pigs not the source of recent increase in indigenous human cases

• But potential for emergence

• Strategy across pig-producing countries needed to tackle problem


Reducing prevalence of active infection in pigs at slaughter is key to reducing risk of food-borne human HEV infections

Reducing risk of viraemia at slaughter

• Infection at some point during production is common

• Abattoir study – high seroprevalence at slaughter

• Age-related differences in risk

• Studies from several countries

• Function of:

• susceptibility (e.g. maternal Ab, endocrinology, coinfections, …)

• exposure (opportunities for transmission).


From McCreary et al. 2008

Control when pigs are infected rather than aiming

to eradicate

Managing opportunities for HEV transmission

• Groups of pigs may be mixed together at different stages in production

• The timing of group mixing may affect the risk of active infection being present at slaughter

• Opportunities for transmission at an early age

• Infected pigs recover and develop immunity before slaughter age

• Also greater herd immunity reduces risk of infection in naïve older pigs


CURRENT EVIDENCE

AnecdotalUK abattoir data

Based on retrospective analysisWalachowski et al. 2014

Mathematical modellingCrotts et al. 2018

Prospective studies designed to investigate the role of herd

management strategies on risk of HEV infection at slaughter are

currently lacking

Current APHA study

1. Track infection in batch of pigs from pre-weaning to slaughter age

• How does presence of HEV infection change as the batch progresses through different stages of production?

• How is this affected by group mixing?

2. Investigate trends in persistence of HEV in the herd more broadly

• Relate to any on-farm changes over time

3. Investigate environmental sources of HEV on farm


0

20

40

60

Time

• Single farm

• Indoor

• Farrow-to-finish

• Closed herd

• All production stages on same site

• Weekly farrowing

• Batch of piglets produced each week

• Batch divided across multiple pens (“groups”) at each production stage

• Pigs from different groups are mixed at different stages

• Timing and frequency of mixing varies across groups within the same batch

AIMS


Tracking HEV infection in batch of pigs

x 18 in a weekly farrowing batch

Piglets tagged to identify litter of origin

Litters mixed into larger weaner

groups

Weaners mixed into larger grower groups

Using the ear tags we will keep track of how groups are mixed at each stage

Groups may be mixed “early” or

“late”

Tracking HEV infection in batch of pigs


Pre-farrowing Pre-weaning Weaners Growers Finishers

Cohort age4 weeks 12 weeks 18 weeks 22 weeks

30 pigs/pen 30 or 60 pigs/pen 60 pigs/pen 10 or 20 pigs/pen

1 pig/pen18 sows per weekly

farrowing

1 sow + litter/pen

Mixing Event #1 Mixing Event #2

EARLY LATE

What is the HEV shedding status of each sow?

What is the HEV shedding status within each group of the batch? (shedding or not)

How do these compare?

Viral shedding in faeces used as an

indirect measure of HEV infection status

What is the HEV shedding prevalence across the entire batch?

How does this change over time?

Is this related to status of group previously?

Future work• Faecal shedding of HEV indirect measure of infection

• Blood sampling – viraemia, Ab prevalence

• Oral fluids – alternative to blood sampling for Ab

• Abattoir sampling – direct measure of status at slaughter

• Susceptibility as well as exposure infection risk

• Maternal antibodies, re-infection, coinfections …

• Other risk factors must be considered:

• Herd size

• Open vs closed herds

• Farm type (single vs multiple production stages on site)

• Source of pigs coming into the herd

• Seasonal affects

• Coinfections

• PRRSV


Acknowledgements• APHA colleagues:

• Richard Smith (Dept. of Epidemiological Sciences)

• Sylvia Grierson, Bhudipa Choudhury, Falko Steinbach (Dept. of Virology)

• Farmer

• DEFRA funding

• Med-Vet-Net funding to attend workshop


Documents

Investigating the transmission of Hepatitis E virus on a ... · infections • All indigenously acquired infections between 2003-2012 due to G3 viruses • Emergence of group 2 since