Schmallenberg Syndrome: Contrasting Approaches to an

Emerging DiseasePeter L. Merrill, DVM

Director, Animal ImportsNational Import Export ServicesUSDA APHIS Veterinary Services

NIAA ConferenceOmaha, NE April 1, 2014

Learning ObjectivesQuick review of relevant Precautionary

Principle issues, as well as APHIS’ missionsSBV: What, Who, Where, When, HowEU and US positions (past and current)What’s at stake?

Salient PP Issues

KNYK, NKWYN, KWYDK, NKWYDK‘Better safe than sorry’‘First, do no harm’‘The absence of evidence is not evidence of absence’Proving the negativeIf an action or policy has a suspected risk of causing

harm to animal [public, environmental, etc.] health in the absence of scientific consensus that the action or policy is harmful, the burden of proof that it is NOT harmful falls on those taking an action

Problematic consensus regarding ‘suspected’, ‘risk’, ‘harm’, ‘science’

Zero-Risk Tolerance

Salient Missions: USDA/APHIS/VS/NIES

Protecting American agriculture while facilitating (safe) tradeGaining, expanding, or retaining (safe) market

access for animals and animal products/byproducts Prevent the introduction of dangerous and costly

pests and diseases (vs. mitigating/eradicating post-entry)

Domestic animal health and export status linked

What is Schmallenberg syndrome?Disease caused by infection with

Schmallenberg virus (SBV), named after region in North Rhine-Westphalia, Germany where virus was first isolated

Group V: enveloped, (-) sense, segmented, ssRNA

Family Bunyavirudae: Genus Orthobunyavirus: Simbu serogroup (e.g. Aino, Akabane, Shamonda viruses)

Closest relatives: Douglas/Sathuperi virusesCauses a form of arthrogryposis-

hydranencephaly syndrome (AHS)

Who is affected?Ruminants (cattle, sheep, goats, bison, water

buffalo, camels, llamas, alpacas, mouflon, roe/red/fallow deer. moose)…others?

HorsesWild boarDogs?Not presumed zoonoticFarmers, regulators

Where did SBV come from, and where is it now?Origin uncertain/unknown; first Simbu virus in Europe19 EU Member States (Austria, Belgium, Czech Republic,

Denmark, Estonia, Finland, France, Hungary, Germany, Ireland, Italy, Latvia, Luxembourg, Netherlands, Poland, Slovenia, Spain, Sweden and United Kingdom)

3 other European countries (Switzerland, Norway, Croatia)

Many thousands of farms/holdings affected in EuropeNOT in North America

When did SBV appear?Probably Summer 2011 (first cases reported November) in

The Netherlands, Belgium and GermanyContinuous temporal distribution since 2011 has resulted

in steady progression north and east

Sept 2011--Apr 2012

Sept 2012--Oct 2012

Nov 2012--Apr 2013

May 2012--Aug 2012

When did SBV appear?

SBV (2011-13) BTV(2003-13)

How is SBV transmitted?Biting midges (Culicoides spp.); other

insects?Transdermal; secretions? Viral incubation/replicationInfective virus shed in

bovine/ovine/caprine semenTrans-placental transmission to

embryo/fetus

How is SBV transmitted?Wildlife reservoirs?Vector over-winteringFomitesOther pathways?Virulence factors; temporal evolutionMaterial found to be positive by virus isolation (up to

October 2013): Blood and semen from affected adults; and brain from

infected fetusMaterial found PCR-positive (up to October 2013):

Organs and blood of infected fetus, placenta, amniotic fluid, meconium

Following an acute infection, SBV RNA can be detected up to several weeks in different tissues like semen, lymphatic organs (esp. mesenteric lymph nodes), and spleen

How is SBV detected?Clinical signs (not pathognomonic); abortions;

stillbirths; AHSViral culture: insect cells (KC); hamster cells (BHK),

monkey kidney cells (VERO)Serology: virus neutralization; serum neutralization, IFA, ELISAMolecular: RT-PCR (blood, not semen), rRT-PCR, EM Samples for pathogen detection in acute infection:

serum or EDTA blood samples when clinical signs are observed (fever, drop in milk yield, diarrhea).

Samples for pathogen detection in fetuses, abortions, stillbirths and malformed ruminants: brain (cerebrum and brainstem), amniotic fluid and placenta.

K

How is SBV neutralized*?Temperature: Infectivity lost (or

significantly reduced) at 50–60°C for at least 30 minutes.

Chemicals/Disinfectants: Susceptible to common disinfectants (1 % sodium hypochlorite, 2% glutaraldehyde, 70 % ethanol, formaldehyde)

Survival: Does not survive outside the host or vector for long periods

*extrapolated from other Orthobunyaviruses

How is disease* caused?Incubation period 1-4 days; viremia lasts for 1 -

5 daysAB response; avg. seroconversion by 14-28 dpiMorbidity/mortality*: up to 100%/<1% respectively

in adultsIn adult animals that are NOT pregnant:

infection leads to variably transient/relatively brief clinical symptoms including: inappetance fever diarrhea loss in milk production (up to 50% in dairy animals)* More studied in cattle than sheep/goats

How is disease caused?In pregnant females, infection also leads to

variable levels of increased birth defects (species-dependent, but avg. ~4%?)

Critical gestational susceptibility: d. 40-150 (bovines);

d. 20-80 (S/G)Abortions; stillbirths

Arthrogryposis/ HydranencephalyBrachygnathia inferiorAnkylosis; torticollis; scoliosisHypoplasia of the central nervous systemPorencephalySubcutaneous edema (calves)

How can SBV be prevented/treated?No treatment once infected/clinicalLocation in non-vector areasRe-synchronization of breeding seasonVector-proofing breeding facilitiesTest/remove/cullingDeliberate exposure (duration of immunity uncertain,

or whether cross-protective against new serotypes)Passive immunity via colostrum Killed vaccine commercially available; 2 doses 4 wks

apart (cattle); 1 dose S/G; cost variable but can be >$10/head; efficacy unknown

Passive immunity may interfere w/vaccine-stimulated ABs

Genetic resistance?

European Approach (SBV)

Research (FLI, others) EFSA reportsImpact AnalysisEC web portalsOIE Technical Fact Sheet

Intra-European Trade (SBV)The European Commission (EC) has not applied

any specified trade restrictions due to SBV; Not a reportable condition; some individual

Member States require donor testing and certifications (Intra-Community movement eligibility similar to US interstate requirements)

The EC does not consider that live animals, meat, milk or animal by-products to pose a risk of transmission

The EC considers restrictive trade measures for SBV taken by trading partners against exports of ruminants and their products are not justified

Similar to position for Aino/Akabane/BT (retrospectively)

OIE Technical Fact Sheet/EFSA correlations

EU Inventories and Statistics*Bovines: ~115 million domestic head (2012)Imports: none (from non-EU sources)Exports: ~500,000/yr. (to non-EU countries)S/G: (avg. annual 2007-11): ~90 million

domestic sheep; ~13 million goats~1.9 million sheep exports/yr. to non-EU

countries (zero imports)Economic values: well over $100 billionOverall impacts from SBV losses unknown,

but substantial* Various sources

APHIS approach for SBV as an emerging diseaseSBV technically meets criteria for FADAPHIS considered (and considers) SBV as a

significant emerging disease not known to be present in the United States

Canadian import requirements generally similarMexico import requirements: none?Questions remain about the transmission risks

associated with SBV; more research and information is considered necessary in order to determine an appropriate level of trade restrictions to prevent the introduction or spread of the disease

APHIS approach for SBV as an emerging diseasePathways analysisCulicoides vectors: C. obsoletus, C. dewulfi;

others?Case definitionPassive surveillance; AOSAPHIS fact sheets/outreach to industryLaboratory collaborationsScientific/trade information monitoringModified risk assessment through extensive

literature reviewDiscussions with Canada and other trade

partners/industryProactive import restrictions for ruminant

germplasm

APHIS approach for SBV as an emerging diseaseNIES Import Alerts: first in Mar. 2012

Applicable to EU and countries following EU legislation (exc. Iceland)

Only allowed bovine S/E collected prior to June 1, 2011Oct. 2012-- additional criteria:

Donors can be tested twice for SBV by a serum neutralization assay, with negative results (using a 1:8 cutoff titer). The first SBV test must be performed within 30 days prior to collection, and the second between 28 and 60 days after collection. Tests must be performed at a laboratory approved by the country’s competent authority for animal health. Any serologically positive resident donors were re-tested negative by real-time RT-PCR or virus isolation within 4 days after additional collection(s) for export to the United States

May 2013-- further revision of that last sentence above: Until additional information is available, semen and embryos collected

from bovines that are seropositive for SBV are not eligible for importation to the United States

2014: Comprehensive Systematic Review (KNYK, etc)O/C semen still not eligible for importation

Inventories and financial stats*: Ovines/Caprines~77,000 sheep farms in the U.S~138,000 goat farms in the U.S.~5.5 million domestic sheep; ~2.5 million goats<10,000 live sheep/goats imported/yr.

(Can/Aus/NZ)Avg. U.S. annual economic importance: live

S/G imports value of ~$300,000 ; germplasm much less

U.S. exports of live S/G: ~$5 millionDomestic market value: ~$500 million sheep;

goats?*various sources

Inventories and financial stats*: Bovines

~750,000 beef cattle farms in the U.S.~50,000 dairy cattle farms in the U.S.US (2014): 87.7 million domestic head (lowest

since 1951) Imports: ~2 million/yr. Exports: ~100,000/yr.Avg. U.S. annual economic importance: live

bovine/germplasm import value of ~$4 billionU.S. exports of live bovines/germplasm: ~$300

millionDomestic market value: ~$50 billion beef; ~$45

billion dairy* various sources

Industry and other perspectivesReported morbidity/mortality provided by EU

farmers differ widely from EFSA estimates and conclusions

Many S/G farms experience between 20-50% birth defects

Actual economic consequences can be catastrophic depending on many exposure factors

US ruminant producers have generally been supportive of APHIS’s position/approaches

US germplasm industry also generally supportive to date

European Commission has been highly critical of APHIS and other countries’ risk-aversion positions to date

‘Right’ vs. ‘wrong’ approaches?Systematic Review results will help clarify the

risk picture

Questions?