Import Risk Analysis Report on the Revision of Import Policy Related to Scrapie

Attachment A

FINAL REPORT

August 2000

Australian Quarantine and Inspection Service

GPO Box 858

Canberra ACT 2601

AUSTRALIA

TABLE OF CONTENTS

EXECUTIVE SUMMARY3

ABBREVIATIONS AND ACRONYMS4

1.INTRODUCTION5

2.HAZARD IDENTIFICATION AND EXPOSURE PATHWAYS6

3.RISK ASSESSMENT7

4.RISK MANAGEMENT - OVINE SEMEN AND EMBRYOS 10

5.RISK MANAGEMENT - CAPRINE SEMEN AND EMBRYOS24

6.REFERENCES 33

EXECUTIVE SUMMARY

The Australian Quarantine and Inspection Service (AQIS) has assessed the probability of introducing scrapie via the importation of live sheep and goats from Canada, the United States of America and Member States of the European Union as high. However the probability of introducing scrapie via ovine and caprine embryos and semen has been assessed as low.

The risks associated with importing scrapie via sheep and goats were considered to be unmanageable and AQIS does not propose to establish conditions for importation at this time. Risk management options for the importation of ovine and caprine genetic material are assessed and measures recommended. The risk management measures recommended for ovine embryos and semen include:

• donors must be 5 years of age and older before export of genetic material;
• donors must be genetically susceptible to scrapie;
• donors must be from breeds in which PrP genotypes and their susceptibility to scrapie have been studied sufficiently to permit the accurate selection of scrapie susceptible donors;
• country of export restrictions;
• flock of origin restrictions;
• autopsy of semen donors and female embryo donors and negative immunohistochemical testing for scrapie before export of genetic material;
• embryos collected, stored and handled in accordance with OIE and IETS recommendations;
• semen collected, stored and handled in accordance with OIE recommendations for small ruminants.

The risk management measures recommended for caprine semen and embryos are similar but do not include restrictions based on PrP genotype or breed.

Import requirements relating to scrapie are included in the attached conditions for ovine embryos and semen and caprine embryos and semen from Canada, the United States of America and Member States of the European Union.

ABBREVIATIONS AND ACRONYMS

APHISAnimal and Plant Health Inspection Service

AQISAustralian Quarantine and Inspection Service

AQPMAnimal Quarantine Policy Memorandum

BSEbovine spongiform encephalopathy

CFIACanadian Food Inspection Agency

CMPComplete Monitored Program

CNScentral nervous system

CodeOIE International Animal Health Code

DNAdeoxyribonucleic acid

EUMember States of the European Union

nvCJDnew variant Creutzfeldt-Jacob disease

NZNew Zealand

OIEOffice International des Epizooties

PCRpolymerase chain reaction

PrPprion protein

PrPscinfective prion protein

RFLPrestriction fragment length polymorphism

RSARepublic of South Africa

SIAscrapie infective agent

SFAP Scrapie Freedom Assurance Program

TSEtransmissible spongiform encephalopathy

UKUnited Kingdom

USAUnited States of America

USDAUnited States Department of Agriculture

1INTRODUCTION

Scrapie is a progressive and invariably fatal transmissible spongiform encephalopathy (TSE) affecting sheep and goats. Scrapie has been known to occur in the United Kingdom (UK) and Germany since the eighteenth century and is now present in many of the sheep raising countries of the world. Scrapie has been diagnosed in Australia on one occasion - on a single property in Victoria in 1952. Four of a group of 10 Suffolk sheep imported from the UK were affected and the disease was eradicated by slaughter and quarantine.

Since 1952, the importation of sheep and goats into Australia has been prohibited from all countries except New Zealand (NZ). Ovine and caprine genetic material has been imported from NZ and ovine and caprine embryos from the Republic of South Africa (RSA). Both NZ and RSA are considered by Australian Quarantine and Inspection Service (AQIS) to be free from scrapie. There have been three importations of washed ovine and caprine embryos from countries where scrapie is endemic.

The imported embryos were subjected to a Scrapie Freedom Assurance Program (SFAP). SFAPs were comprehensive post-arrival quarantine programs which took at least three and a half years to complete and were designed to ensure detection of the scrapie agent if present in the imported embryos. The animals produced from imported embryos and sentinel animals were held on quarantine premises that met strict design, security and management requirements, and were subject to AQIS supervision. The quarantine program involved control over the movement of personnel, equipment, animal products, live animals, embryos and semen. Surveillance for scrapie included the collection and inoculation of mesenteric lymph node material into sentinel sheep or goats and systematic performance of autopsies on all sentinels and sick or dead animals on the quarantine station. The animals produced from the imported embryos, sentinels and embryo recipients were slaughtered, autopsied and tested for scrapie before the second, and subsequent, generations were released from quarantine.

AQIS required health certification stating that scrapie was notifiable in the country of export and the flock of origin had remained free from scrapie during the 10 year period immediately prior to export of the embryos.

There was one importation of ovine and caprine embryos from the United States of America [USA] (in this instance live animals were imported to the Cocos Island Animal Quarantine Station and their progeny subjected to a SFAP on the mainland), one importation of goat embryos from Zimbabwe and one importation of ovine embryos from Cyprus. Each of these importations were subjected to a SFAP carried out in animal quarantine stations at Torrens Island, Kirra and Terraweena in South Australia; Kununurra and Wongan Hills in Western Australia; and Glendook in Victoria.

There is a growing demand for the importation of ovine and caprine genetic material from North America and the European Union (EU). Importers are hesitant about becoming involved in expensive SFAPs and have hoped that recent developments in the study of prion protein (PrP) genotypes, and the diagnosis of scrapie, would lead to the adoption of simpler import requirements.

AQIS proposed that the quarantine risk associated with sheep and goats in respect of scrapie be the subject of a routine risk analysis in Animal Quarantine Policy Memorandum (AQPM) 1997/67, circulated 17 September 1997. AQIS received comments from 10 respondents; all supported the proposal. One of the respondents stressed that careful consideration should be given to policy relating to biologicals, particularly those intended for in vivo use. Two other respondents questioned the use of a routine risk analysis process stating that significant uncertainties still existed about the quarantine risks associated with scrapie.

Current quarantine policy and practice

Scrapie is listed in Schedule 3 Diseases affecting animals of Quarantine Proclamation 1998 and as such is a quarantinable disease. Animal semen, embryos or ova are listed in Table 11 of Part 4, Section 27 as prohibited biological materials. Section 28 Importation of biological materials states that importation is not prohibited if the Director of Quarantine has granted a permit. Division 2 of Part 6 of the Proclamation deals with the importation of animals, animal parts and animal products into Australia. Section 37 of Division 2 addresses the importation of live animals which are prohibited unless a permit to import has been issued. Section 38 (4) prohibits the importation of animal parts (including animal reproductive material) except by permit.

Importation of sheep and goats is currently prohibited from all countries except NZ. The importation of ovine and caprine semen is permitted only from NZ and ovine and caprine embryos only from NZ and the RSA.

2HAZARD IDENTIFICATION AND EXPOSURE PATHWAYS

2.1 HAZARD IDENTIFICATION

Scrapie is an Office International des Epizooties (OIE) list B disease that is not present in Australia.

Australia is free from scrapie and the introduction of scrapie infective agent (SIA) is considered to be a hazard in the importation of sheep, goats and ovine and caprine genetic material from countries affected by scrapie.

2.2 EXPOSURE PATHWAYS

SIA could be introduced to Australia in live sheep or goats imported from scrapie endemic countries. The 1952 outbreak of scrapie occurred in sheep imported from the UK.

Despite the efforts of research groups in the USA and Scotland it is still unclear whether scrapie can be transmitted via washed ovine embryos. The most recent publications present conflicting conclusions. Until the situation is elucidated by further research it must be presumed that there is a risk that scrapie can be transmitted by ovine embryo transfer.

The limited amount of published work available on the transmission of scrapie via caprine embryos suggests that transmission does not occur.

Attempts to isolate SIA from ovine semen, seminal vesicles and testes have not been successful and limited research and observations indicate that scrapie is not transmitted in semen. However further research is required to confirm this.

AQIS is not aware of any published information on the transmission of scrapie in caprine semen.

3RISK ASSESSMENT

Scrapie is a progressive and invariably fatal degenerative disease of the central nervous system of sheep and goats.

The precise molecular nature of the SIA has not been determined. Like a virus it can be transmitted from one host to another but biochemically it does not resemble a virus as it is extremely resistant to heat, irradiation and most disinfectants known to inactivate viruses. When SIA reaches the central nervous system it produces a change of the natural, soluble cell membrane protein PrP into an abnormal, insoluble and protease resistant form - PrPsc . It is the accumulation of PrPsc in the neurones that leads to brain degeneration with the characteristic spongiform changes which are seen histologically in all TSEs (Wrathall 1997).

3.1 PROBABILITY OF SIA BEING PRESENT IN SHEEP AND GOATS

The distribution of SIA within infected sheep has been the subject of much research the results of which are summarised by Wrathall (1997). In an infected, clinically normal 25 month old sheep SIA was found in lymphatic tissue, spleen, ileum and proximal colon and parts of the brain. In naturally infected adult sheep showing clinical signs of scrapie, SIA was found at high levels in the brain and spinal cord; at moderate levels in the spleen, tonsil, ileum, proximal colon and lymph nodes; and at low levels in the cerebrospinal fluid, pituitary gland, distal colon, adrenal cortex and sciatic nerve and occasionally traces were also detected in the nasal mucosa, pancreas, liver, bone marrow and thymus.

The probability of transmission of SIA via placentae is unclear, as there is conflicting evidence regarding the infectivity of placentae from infected ewes (Race et al 1998). SIA has not been detected in testes or semen.

Scrapie is endemic and compulsorily notifiable in Canada (from 1945) and the USA (from 1952). The prevalence of the disease is very low in both North American countries with 74 cases reported in Canada and 63 cases in the USA during 1998 (OIE). However, the health status of a flock or herd with respect to scrapie can be difficult to determine. Within flock/herd prevalence varies and is difficult to assess as few tests currently available detect subclinical cases of infection.

There are more than 13 000 flocks in Canada and 90 000 flocks in the USA. On 7 December 1998 there were 63 known infected flocks in the USA, 40 of which were Suffolk sheep (USDA). Scrapie has not been diagnosed in goats in Canada since 1973. At 20 May 1997 only 5 natural cases of scrapie had been diagnosed in goats in the USA (USDA).

Scrapie has been compulsorily notifiable in Member States of the EU since 1993 (Council Directive 91/68/EEC of 28/1/91). Scrapie has been reported in sheep and goats in the UK (465 cases in 1998) and Italy (9 outbreaks in 1998); and sheep only in France (52 outbreaks in 1997), Greece (6 outbreaks in 1998), Germany (2 outbreaks in 1998), Ireland (9 outbreaks in 1998), the Netherlands (16 outbreaks in 1998), Norway (3 outbreaks in 1998), Switzerland (no outbreaks since 1995), Sweden (no outbreaks reported since 1986) and Austria (1 outbreak April 2000).. Scrapie has not been reported from Denmark, Finland, Luxembourg, Portugal or Spain.

There is no test for scrapie that will detect early infection. The incubation period varies from 6 months to 8 years in sheep and 8 months to 2 years in goats. In endemic countries the prevalence in goats is far less than in sheep and scrapie has been reported in goats only in the UK, Italy, Canada (not since 1973) and the USA. There is no evidence that maternal transmission occurs in goats and it appears that goats become infected either by close association with sheep or from eating contaminated meat-and-bone meal.

Recently developed tests will detect scrapie infection at least 12 months before clinical evidence of infection. These tests involve the use of immunohistochemistry to detect PrPsc in lymphatic tissue obtained by biopsy from either the tonsil (Schreuder et al 1998) or, the more accessible, nictitating membrane (O’Rourke et al 1998).

3.2 PROBABILITY OF SIA BEING IN OVINE AND CAPRINE EMBRYOS

The interpretation of results of research to determine if scrapie can be transmitted via ovine embryo transfer has been complicated by low numbers of susceptible control sheep (Foote et al 1993), the use of unwashed embryos and possibly sub-clinically infected recipients (Foster et al 1992) and possible exposure of trial sheep to SIA in the environment (Foster et al 1996). Despite the considerable amount of research in both Scotland and the USA the probability that scrapie is transmitted by ovine embryo transfer is unknown.

Published information on scrapie transmission by embryo transfer in goats is limited but indicates that scrapie is probably not transmitted via caprine embryos (Wrathall 1997). Foster et al 1999 showed that experimentally induced BSE did not transmit via caprine embryos or by maternal transmission to offspring born to infected donors.

3.3 PROBABILITY THAT SIA IS PRESENT IN OVINE AND CAPRINE SEMEN

The limited observations on the transmission of scrapie in ovine semen indicate that scrapie is probably not transmitted in ovine semen (Wrathall 1997). There is no evidence that scrapie is transmitted in caprine semen. There is strong evidence that Bovine Spongiform Encephalopathy (BSE) is not transmitted by bovine semen and this is reflected in the OIE Code Chapter 3.2.13. on BSE. Foster et al 1999 found no indication that experimental BSE in goats could be spread by venereal infection to males mated with infected does.

3.4 CONSEQUENCES OF SIA INTRODUCTION

Australia’s strategy for control and eradication of scrapie, an assessment of social and economic effects, funding and compensation and strategy if the disease becomes established are detailed in AUSTVETPLAN 2nd Edition 1996.

Biological consequences

If infected sheep or goats were introduced it could be several years before the disease became evident. The length of this period would depend on the age and the genotypes of the imported infected animals. If import conditions restricted the numbers imported to small consignments of breeding animals eradication would not be difficult as the animals could easily be traced and imported animals, offspring and in-contact animals destroyed. However if large numbers of animals of various breeds were imported eradication may be difficult.

The consequences of the introduction into Australia of SIA in genetic material would depend on several variables:

. The number of recipients

. The genotype of the recipients

. The management of the recipients

If ewes could be infected by insemination the worst case scenario could be the importation of infective semen from one or more donors. This semen could be used to impregnate and infect females in many flocks in many parts of the continent. The introduction may not become apparent for many years, depending on the PrP genotype of the infected sheep and it would be unlikely that clinical disease would be seen before 2 or 3 years after importation. If the animals produced were keenly sought by studs and breeders as superior genetic stock, infected offspring could be numerous and widespread by the time scrapie was diagnosed. However even in this worst case scenario the eradication of the disease would be simplified by the fact that the breeds of sheep affected would be known and the tracing of the imported infected semen and the offspring not unduly difficult.

Environmental consequences

Australia has no native sheep or goats and the environmental impact of the introduction of scrapie would be negligible. Large populations of feral goats do occur in some areas of Australia. However it would be most unlikely that scrapie would be maintained in these populations.

Economic consequences

If scrapie was to become established in commercial flocks, it is unlikely that the disease would have a significant economic impact on Australia’s livestock industries. Scrapie is endemic in the flocks of our main trading partners and only scrapie free countries such as New Zealand, the RSA and South American countries – which are all exporters, not importers, of sheep and ovine products – would be likely to apply any trade restrictions. The most significant effect of the establishment of scrapie would be the implications for Australia’s TSE-free status, and possible effects on exports of some ruminant products, such as ovine pharmaceutical products for in vivo use. Exports of such products could be greatly reduced at least until the extent of the outbreak was determined and regionalisation applied, if possible.

The establishment of scrapie would be unlikely to have significant impact on production, as even in countries where the prevalence of scrapie is high, production is not greatly affected. If the disease were to become established, transmission would probably be strictly limited due to factors associated with Australia’s pastoral management system. The prevalence of infection would be expected to remain extremely low and infection could well be confined to certain geographic areas.

The most significant economic effect of the establishment of scrapie would probably be the cost of eradication (see AUSTVETPLAN 2nd Edition 1996).

3.5 CONCLUSIONS

Scientific evidence indicates that the probability of importing scrapie via live sheep and goats is far greater than that associated with the importation of embryos or semen. Factors contributing to the higher probability associated with live animals include the lack of a test to detect animals incubating the disease until 12 – 18 months prior to the development of clinical signs, and the difficulty of accurately ascertaining flock or herd status for this pathogen. Until these problems are solved, it is not possible to develop conditions that would achieve Australia’s appropriate level of protection for the importation of live sheep and goats from countries/zones affected by scrapie.