Peter L. Merrill, DVMDirector, Animal Imports

National Import Export Services

USDA APHIS Veterinary Services

NIAA ConferenceOmaha, NE April 1, 2014

Learning Objectives

Quick review of relevant Precautionary Principle issues, as well as APHIS’ missions

SBV: What, Who, Where, When, How

EU 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 negative If 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) trade

Gaining, 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: Simbuserogroup (e.g. Aino, Akabane, Shamonda viruses)

Closest relatives: Douglas/Sathuperi viruses

Causes a form of arthrogryposis-hydranencephalysyndrome (AHS)

Who is affected?

Ruminants (cattle, sheep, goats, bison, water buffalo, camels, llamas, alpacas, mouflon, roe/red/fallow deer. moose)…others?

Horses

Wild boar

Dogs?

Not presumed zoonotic

Farmers, regulators

Where did SBV come from, and where is it now? Origin uncertain/unknown; first Simbu virus in Europe

19 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 Europe

NOT in North America

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

Netherlands, Belgium and Germany

Continuous 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/replication

Infective virus shed in bovine/ovine/caprinesemen

Trans-placental transmission to embryo/fetus

How is SBV transmitted? Wildlife reservoirs? Vector over-wintering Fomites Other pathways? Virulence factors; temporal evolution Material found to be positive by virus isolation (up to October

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

fetus

Material 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;

AHS

Viral culture: insect cells (KC); hamster cells (BHK), monkey kidney cells (VERO)

Serology: virus neutralization; serum neutralization,

IFA, ELISA

Molecular: 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.

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 days

AB response; avg. seroconversion by 14-28 dpi

Morbidity/mortality*: up to 100%/<1% respectively in adults

In 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/ Hydranencephaly

Brachygnathia inferior

Ankylosis; torticollis; scoliosis

Hypoplasia of the central nervous system

Porencephaly

Subcutaneous edema (calves)

How can SBV be prevented/treated? No treatment once infected/clinical Location in non-vector areas Re-synchronization of breeding season Vector-proofing breeding facilities Test/remove/culling Deliberate 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 reports

Impact Analysis

EC web portals

OIE 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 billion

Overall impacts from SBV losses unknown, but substantial

* Various sources

APHIS approach for SBV as an emerging disease

SBV technically meets criteria for FAD

APHIS considered (and considers) SBV as a significant emerging disease not known to be present in the United States

Canadian import requirements generally similar

Mexico 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 disease

Pathways analysis

Culicoides vectors: C. obsoletus, C. dewulfi; others?

Case definition

Passive surveillance; AOS

APHIS fact sheets/outreach to industry

Laboratory collaborations

Scientific/trade information monitoring

Modified risk assessment through extensive literature review

Discussions with Canada and other trade partners/industry

Proactive import restrictions for ruminant germplasm

APHIS approach for SBV as an emerging disease

NIES 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, 2011

Oct. 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 million

Domestic 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 billion

U.S. exports of live bovines/germplasm: ~$300 million

Domestic market value: ~$50 billion beef; ~$45 billion dairy

* various sources

Industry and other perspectives Reported 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?