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"Schmallenberg" virus: State of Art

Assessment Methodology (AMU) and Animal and Plant Health (AHAW) unit

OUTLINE

• Context of the report

• SBV current knowledge

• Assessment based on modelling predictions:

–Serological surveys

–Spread Models

• Assessment of Impact

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Research initiatives in Member States should be followed up, producing a comprehensive report on the state of art of the scientific knowledge on SBV

The report should summarize the latest scientific findings on SBV, especially co-financed studies by the EU

An update of the overall assessment of the impact to allow for complementing previous report produced by EFSA

Term of Reference

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SBV – Genetic Analysis

• More than 170 named virus isolates comprise the genus Orthobunyavirus in the family Bunyaviridae.

• The identification of SBV was based on metagenomic analysis indicating that the closest relatives were viruses in the Simbu serogroup (Hoffmann et. al, 2012).

• Detection, isolation and characterization of Simbu serogroup viruses in Africa are needed to determine whether a virus closely related to SBV circulates in this region.

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SBV – Simbu Serogroup

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Species Virus Distribution Clinical Signs Principal Arthropod Vector

Akabane

Akabane Africa, Asia, Australia + Mosquitoes, Culicoides spp.Sabo Africa Culicoides spp.Tinaroo Australia Culicoides spp.Yaba-7 Africa ?

Manzanilla

Manzanilla S America ?Buttonwillow N America Culicoides spp.Ingwavuma Africa, Asia + mosquitoesInini S America ?Mermet N America mosquitoes

Oropouche

Oropouche S America Culicoides spp, mosquitoesFacey’s Paddock Australia ?Utinga S America ?Utive S America ?

SathuperiSathuperi Africa, Asia + Culicoides spp, mosquitoesDouglas Australia Culicoides spp.

Simbu Simbu Africa mosquitoes

ShamondaShamonda Africa, Asia + Culicoides spp.Peaton Australia + Culicoides spp.Sango Africa + Culicoides spp, mosquitoes

ShuniShuni Africa Culicoides spp. mosquitoesAino Asia, Australia + Mosquitoes, Culicoides spp.Kaikalur Asia, Australia mosquitoes

Thimiri Thimiri Africa, Asia ?

SBV – Evolution

• Bunyaviruses can evolve through two mechanisms: - Accumulation of mutations - Genome segment re-assortment

• High levels of variability, especially in the M segment• Two studies (Coupeau et. al, 2013, Fischer et. al, 2013)

reported a hypervariable of mutation within the coding sequence for the N-terminus of Gc glycoprotein, suggesting that this may play a role in immune evasion

• Two inactivated SBV vaccines- Bovilis SBV (MSD Animal Health) - SBVvax (Merial)

• Impact of genetic variation within SBV isolates on protection by these two vaccines requires assessment.

• The lack of other Simbu serogroup viruses in Europe suggests that reassortment might NOT be a concern.

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SBV – Susceptible species

• Animal species where SBV and clinical expression (either in adult animals or their offspring) of the disease have been demonstrated:– Animal species infected naturally: Domestic Cattle, Sheep, Goats

– Animal species infected experimentally: Domestic Cattle, Sheep, Goats

• Animal species with direct detection of SBV: Dog

• Animal species with indirect detection of SBV: Alpacas, Anatolian water buffalo, Elk, Bison, deers (Red, Fallow, Sika and Roe), Muntjac, Chamois, Wild boar and Dogs

• Zoo species with indirect detection of SBV: Bongo, Babirusa, Banteng, Congo buffalo, European bison, Gaur, Gemsbok, Greater kudu, Grevy's zebra, Moose, Nile lechwe, Nubian goat, Onager, P.S. deer, Reindeer, Roan antelope, Scimitar-horned oryx, Sitatunga and Yak

• Horses, poultry and pigs NOT susceptible

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SBV – Pathogenesis

• Viraemic Period:– Positive PCR from 2-6 days post inoculation from experimental studies– Similar results in cattle and sheep– No dose difference in length and height of RNAemia after

experimental infections in sheep– Viral RNA detected up to 44 days post inoculations

• Susceptible Period during gestation:– SBV infection leads to infection of the placenta and umbilical cord– In ewes the proportion of positive placentas is higher when inoculation

at 45 days than for 38 days– More positive samples found in lambs were infected at day 60

compared to day 45– One malformed fetus observed in cattle experiment from total of 24

corresponding to infection carried out at gestation day 90.– Very limited number of malformations induced 8

SBV – Vector Transmission

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• Formal criteria to recognize a species as a vector:– Recovery of virus from wild-caught specimens free from visible blood– Demonstration of ability to become infected by feeding on a viraemic

vertebrate host or an artificial substitute– Demonstration of the ability to transmit biologically by bite– Field evidence confirming association of the vector with the appropriate

vertebrate population in which disease or infection is occurring

• Studies confirmed that several Culicoides species are likely to be capable of transmitting SBV

• Studies on mosquitoes’ competence provide preliminary evidence that they may not play a substantial role in transmission of SBV in the field

SBV – Semen Results

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Country Tested SBV RNA PositiveBatches Bulls Batches % Bulls %

Germany 766 95 29 3.8 11 11.6Netherlands 55 8 3 5.5 2 25Austria 164 7 7 4.3 1 14.3France 904 160 26 2.9 2 1.3Total 1889 270 65 3.4 16 5.9

• Studies on risk of transmission via semen and embryos are limited• Low frequency of SBV detection in semen samples• No evidence yet of transmission through insemination, only

experimental infection demonstrated via subcutaneous injection of positive semen batches in calves

SBV – Vertical Transmission

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• Vertical Transmission:– Passage of an infection from mother to her embryo or fetus which persist the

point of birth

– For SBV could be considered either for vectors and/or ruminant hosts

• Evidence for vertical transmission by Culicoides remain very

slight

• SBV has been detected in certain tissues, but neither SBV

virus nor RNA has been documented in blood

• No evidence yet that vertical transmission is a major route of

transmission

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• Overwintering:– Ability of the virus to survive for prolonged periods during which vectors are

absent and no new hosts appear to be infected

• Ways the virus can persist:– In the vector population

– In the host population

– A cycle involving one or more novel vector or host populations

• SBV has successfully overwintered despite lengthy period of minimal vector activity

• Mechanism of overwintering is still unknown, however vertical transmission may play a role

• No evidence of persistent infection in the host

SBV – Overwintering

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• Limited information regarding duration of immunity:– Experimental and field settings for Cattle– No information yet published on Sheep

• Experimental study indicates duration of immunity in cattle for at least 56 days

• Surveillance in Belgium indicates that animals in the same cohort when followed over time present similar seroprevalence levels, implying potential immunity duration of at least one year

• Sampling scheme were similar, but the animals were not followed up over time, thus findings should be interpreted with caution

SBV – Duration of Immunity

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SBV – Seroprevalence Studies

0 20 40 60 80 100

Prevalence Regional and Animal Level

0 10 20 30 40 50 60 70 80 90

Turkey, 2006 - 2013 (Ref. ID 1)

Greece, Mar 2013 (Ref. ID 2)

Netherlands, Nov 2011 - Jan 2012 (Ref. ID 3)


France, Winter 2011 - 2012 (Ref. ID 4)

Belgium, Feb - Apr 2012 (Ref. ID 5)

Turkey, 2006 - 2013 (Ref. ID 1)

Poland, Jul 2012 (Ref. ID 7)

Germany, Jan - Jun 2012 (Ref. ID 6)

Turkey, 2006 - 2013 (Ref. ID 1)

Greece, Mar 2013 (Ref. ID 2)




UK, Dec 2012 - Jan 2013 (Ref. ID 9)

CattleGoatsSheep

0 20 40 60 80 100

Prevalence Regional and Herd Level

0 10 20 30 40 50 60 70 80 90 100

Belgium, Feb - Apr 2012 (Ref. ID 5)

Germany, Jan - Jun 2012 (Ref. ID 6)


UK, Dec 2012 - Jan 2013 (Ref. ID 9)

CattleGoatsSheep

Regional Level Summary Results

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SBV – Seroprevalence Studies

National Level Summary Results

0 20 40 60 80 100

Prevalence National and Animal Level

0 10 20 30 40 50 60 70 80 90

Belgium, Jan - Mar 2012 (Ref. ID 8b)

Belgium, Jan - Feb 2013 (Ref. ID 8c)

Netherlands, Nov 2011 - Mar 2012 (Ref. ID 10)



Belgium, Nov 2011 - Apr 2012 (Ref. ID 8a)




CattleGoatsSheep

0 20 40 60 80 100

Prevalence National and Herd Level

0 10 20 30 40 50 60 70 80 90

Belgium, Jan - Mar 2012 (Ref. ID 8b)







CattleGoatsSheep

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SBV – Geographical and Temporal Spread

Within Herd Transmission R0

Basic reproduction number (R0) for Schmallenberg virus in (a) cattle and (b) sheep and its dependence on temperature. Posterior median (circles) and 95% credible intervals (error bars) for R0. The black dashed line indicates the threshold at R0=1. The grey diamonds indicate the median R0 for Bluetongue

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Regional Spread: A Network approach

Spread from farm-to-farm by three routes:

•Movement of cattle– Cattle Tracing Scheme, 2006

•Movement of sheep– Animal Movement Licensing Scheme, 2006

•Dispersal of vectors– Non-directional (and follows a kernel!)

r

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Regional Spread: Results

Scenario Description

Movement restrictionsRelative reduction

No Yes

Farms Radius Farms Radius Farms Radius

BTV All estimates for BTV 166 23.1 109 9.4 34.3 59.3

SBV All estimates for SBV 3281 50.9 3148 49.1 4.1 3.5

• Rapid spread of infection across study region• Changes to four epidemiological parameters (latent period, duration of

viraemia, probability of transmission from host to vector and virus replication) are sufficient to account for the rapid SBV spread within and between farms relative to that seen for BTV-8.

• Alternative transmission mechanism (direct transmission or additional vector species) not necessary to explain the observed patterns of spread of SBV

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• Under-ascertainment might influence infection impact

• Direct impact on adult animals: fever, diarrhoea and decreased milk production in low proportion of infected animals

• Direct impact on fetuses/newborn animals: offspring of animals infected with SBV during certain stages of pregnancy are at risk of complications including deformation and abortion

• Indirect impacts: trade restrictions and costs related with treatments (e.g. complications at calving and lambing)

SBV – Impact

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• Impact on dairy farms: – Probable effect of SBV infection on abortion, short gestation, non-return and

the number of artificial inseminations required per animal– Drop in milk production– Very limited impact on cow and calf mortality rates

• Impact on beef farms: – No data available

• Impact on sheep farms: – France:

• 85% of ewes in France (34,470) gave birth at full term to only healthy lambs• 11% of ewes gave birth at full term but at least one of their lambs was stillborn, born deformed

or died within 12 hours of birth and 4% of ewes aborted

– Netherlands:• Significantly higher mortality rates before weaning in Netherlands• Clinical signs reported as limited in adult animals• The impact for the entire sheep industry reported to be very limited

SBV – Impact

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• Estimation of indirect impact:– Principal economic impact felt via international trade restrictions– Most of EU semen trade happens within EU (2010: 73.4% and 2011: 82.8%)– 15.1% and 10.9% of the total EU semen trade for 2010 and 2011 happen with

countries imposing restrictions– Pure-bred breeding animals exports show a 20% decline in 2012 with respect

to 2011

• Expected future impact:– Impact observed in 2012 likely to represent a worst case scenario, unlikely to

be repeated if SBV remains endemic in Europe– Incidence of SBV in Europe may vary between years– Duration and amplitude of interannual epidemic cycles will depend on the rate

at which susceptible hosts enter the population– If Europe becomes SBV free, subsequent reintroduction of SBV could result in

an outbreak of similar magnitude to that seen in 2012

SBV – Impact

Acknowledgements

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EFSA Animal Health Network

EFSA WG: Simon Gubbins, Anthony Wilson, Matthew Baylis, Thomas Balenghien, Richard Elliott, Claire Ponsart, Antoine Poskin, Stefan Zientara and Brigitte Cay

EFSA STAFF: José Cortiñas Abrahantes, Anna Zuliani, Ana Afonso, Jane Richardson, Andrea Bau, Didier Verloo and Franck Berthe

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For further information or any additional questions,

[email protected]

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