Opinion of the Scientific Panel on Biological Hazards of the European Food Safety Authority on:

Opinion of the Scientific Panel on Biological Hazards of the European Food Safety Authority on: A quantitative assessment of risk posed to humans by tissues of small ruminants in case BSE is present in these EFSA-Q-2004-170 Opinion adopted on 8 June 2005 SUMMARY Following the confirmation of BSE in a goat in France on 28 January 2005, the European Commission (EC) (DG Sanco) invited the European Food Safety Authority (EFSA) and its Scientific Panel on Biological Hazards (BIOHAZ) to carry out a quantitative assessment of risk posed to humans by tissues of small ruminants in case BSE is present in these The mandate requests a quantitative assessment of the risk posed by human consumption of meat derived from goats and sheep of different ages and genotypes in case BSE is confirmed. It should take account of studies of the tissue distribution of the agent, prevalence evaluations and any other relevant data and, if possible, should consider different scenarios. In addition to current legislative measures the EC also stepped up its surveillance programme in sheep and goat. These new measures became mandatory in early 2005 and include a three step testing strategy in order to differentiate between scrapie and BSE for all confirmed positive scrapie cases in both sheep and goats and an increase in surveillance focusing on increased testing of goats for both healthy and fallen stock. In carrying out this risk assessment, the BIOHAZ panel and its Working Group (WG) considered the available data on epidemiology and scientific reports on studies concerning the pathogenesis of BSE in sheep and goats as the basis for their assessment. Additional data gathered from the EC, individual Member States and EFSA and its Advisory Forum (AF) were also taken into account. The BIOHAZ Panel WG concluded that there are currently not enough data on BSE in goats to allow a quantitative assessment of risk posed to humans by consumption of meat and meat products derived from goats infected with BSE. The WG accepted that there were more experimental research data available for sheep both related to the pathogenesis of BSE in sheep and surveillance in the sheep population. Therefore, at this time, a risk assessment directed specifically at goat meat would necessarily be based on data from sheep. Such an approach would neither provide a proportionate response to the EC nor a science-based assessment of public health risks from goat meat and goat meat products. Although data are still lacking at present, the prospect of further information, including information related to exposure and other epidemiological factors, may allow a comprehensive and reliable quantitative risk assessment (QRA) for BSE in sheep in the future. 1

In considering all of the required data for a QRA of goat meat it was concluded that the most significant data to be obtained relate to the current prevalence of BSE in goats. It was acknowledged that steps had been taken to acquire this data but that complete results from recently initiated surveillance including discriminatory testing of goats for BSE will not become available before end 2005. The WG concluded that a qualitative RA on goat meat could be made considering the existing risk management (RM) measures in place since 2001 and the results of the recently increased level of surveillance in goats and the discriminatory testing. For such a qualitative RA on goat meat, account is taken of a number of facts including that the goat found positive was born before the feed ban in 2001, and that currently, goats slaughtered for human consumption at a young age and born after the introduction of the feed ban, would present a lower risk than the adult population. Also other risk management measures in place (e.g. Specified Risk Material (SRM) list, rendering) contribute to the further reduction of the risk to the consumer. Moreover, the initial results of increased testing and discriminatory testing have not indicated any additional suspect BSE cases in goats or sheep. Therefore, the current risk in terms of BSE, related to the consumption of goat meat and goat meat products is considered at this time to be small for goats born after the feed ban, i.e. in 2001 and later. The BIOHAZ panel recommended collecting additional data which would make a QRA possible in the future. In addition to the increased surveillance already initiated, it is also recommended to initiate as soon as possible additional research focusing on the experimental induction of BSE infection in goats. This would allow evaluation of the pathogenesis of the disease after oral exposure, including the tissue distribution and infectivity relative to age and incubation period, and thereby to determine the tissues most at risk as well as their infectivity load. Key words : BSE, scrapie, goat, sheep, meat, testing, surveillance. BACKGROUND 1. Suspicion of Bovine Spongiform Encephalopathy (BSE) in a goat The French authorities announced the suspicion of BSE in a goat on 28 October 2004. A panel of experts at the Community Reference Laboratory (CRL) at Weybridge evaluated a first set of French data on 25 November 2004 but indicated that additional data were needed for a final decision. These additional data became available soon after and during a second evaluation round, the experts confirmed Bovine Spongiform Encephalopathy (BSE) in the goat on 28 January 2005 1. Following this confirmation the European Food Safety Authority (EFSA) prepared a statement and a press release and also the European Commission (EC) and its Directorate General for Health and Consumer Protection (DG Sanco) prepared a press release 2. 1 http://europa.eu.int/comm/food/food/biosafety/bse/crl_statement_tse_goats_28-01-05_en.pdf 2 http://www.efsa.eu.int/science/biohaz/biohaz_documents/787_en.html 2

2. Existing community legislation on BSE in small ruminants Existing community legislation requires that Member States (MS) shall draw up guidelines specifying the national measures to be implemented in relation to culling, removal of Specified Risk Material (SRM) and testing of animals where cases of TSE are confirmed in accordance with Article 14 of Regulation (EC) No 999/2001 of the European Parliament and of the Council laying down rules for the prevention, control and eradication of certain transmissible spongiform encephalopathies (TSE) 3, as last amended by Commission Regulation (EC) No 1993/2004 4. The EC has requested the MS to draft a contingency plan in case BSE is detected in small ruminants based on the opinion on safe sourcing of small ruminant materials adopted by the Scientific Steering Committee (SSC) in April 2002. Regulation 999/2001 also lays down rules for eradication measures to be applied to TSE infected flocks, for monitoring and for the removal of SRM. The current SRM list consists of skull, brain, eyes, tonsils and spinal cord of sheep and goats over 12 months and the spleen and ileum of sheep and goats of all ages. Commission Decision 2003/100/EC introduced breeding programmes for resistance to TSEs in sheep. 3. Updated Community legislation following confirmation of BSE in a goat. Following the confirmation of BSE in a goat, DG Sanco proposed new measures to the MS which were discussed and agreed at their last meeting (November 2004) and which were put into force in early 2005 and which will initially run for a period of 6-8 months. These include: A three step mandatory strategy for differential testing between scrapie and BSE for all confirmed positive scrapie cases in both sheep and goats. Steps include the discriminatory rapid testing, molecular testing and the mouse bioassay (strain typing) and became mandatory in January 2005 (EC regulation 36/2005 as from 12 January 2005). This increases the likelihood that BSE, if present, is found in small ruminants. An increase in surveillance (EC regulation 214/2005 entering into force 9 February 2005) concentrating on an increase in testing of goats of both healthy and fallen stock. http://www.efsa.eu.int/press_room/press_release/790/pr_biohaz_goat_2005_en1.pdf http://europa.eu.int/rapid/pressreleasesaction.do?reference=ip/05/105&format=html&aged=0&language=en&guilanguage= en 3 4 OJ L 147, 31.5.2001, p.1. OJ L 344, 20.11.2004, p. 12 3

MANDATE The European Food Safety Authority (EFSA) is invited to carry out A quantitative assessment of risk posed to humans by tissues of small ruminants in case BSE is present in these The mandate requests assessment of the risk posed by human consumption of meat derived from goats and sheep of different ages and genotypes in case BSE is confirmed. The assessment should be quantitative, taking into account studies of the tissue distribution of agent, prevalence evaluations and any other relevant data. If possible, different scenarios should be considered, including: effect of SRM removal, in particular the effect of removing collected blood, dorsal root ganglia, peripheral nervous tissues and lymph nodes not associated with the alimentary tract; possible inactivation by processing of intestines for use in the preparation of sausages; monitoring programmes (full monitoring of healthy slaughtered animals or not); age of the animals (< 6 months, 6-18 months, > 18 months); genotype. The estimations should be compared with an estimation of the risk posed by the consumption of beef taking into account the current legislation (as at January 2005). ASSESSMENT The Scientific Panel on Biological Hazards refers to the report in annex of the Working Group (WG) on BSE in Goats for full details on the assessment: http://www.efsa.eu.int/science/biohaz/biohaz_opinions/opinion_annexes/987_en.html 1. The scope of the mandate The intention of the current mandate is clearly to receive a Quantitative Risk Assessment (QRA) rather than a qualitative assessment and to concentrate on meat and meat products of goats and possibly sheep. This QRA is needed to assist the EC in their risk management decisions in order to take proportionate actions and not to over react at any time. In order to be prepared to answer possible questions relating to both species, EC would like to see the opinion cover both sheep and goats but, if 4

appropriate for EFSA, the opinion may be limited to goat meat and goat meat products as a first stage. 2. Feasibility of a QRA confined to goat meat The WG considered a feasibility study, previously commissioned by EFSA, on the availability and usefulness of existing scientific data and other information as the basis for a quantitative assessment of the risks involved in the consumption of goat meat products, together with additional data gathered from the EC, individual MS and EFSA and its advisory forum. Previous assessments which have included consideration of the potential for the occurrence of BSE in sheep and goats have discussed goats together with sheep under the common heading of small ruminants (SMRU). This has not been a reflection of any disregard for possible differences between sheep and goats regarding the risks that their products might pose, but because of the paucity of data relating specifically to goats and, indeed, the degree of agreement between the relevant information on goats and that available on sheep, suggesting that goats may be regarded for practical purposes in many respects, as being equivalent to sheep. Clearly, the potential for BSE to be detected in sheep, based on surveillance in the EU, might be considered greater than for detection in goats. However, given that BSE has been confirmed initially and solely, among small ruminants, in goats, then the WG considered that it would be prudent to review possible variance in BSE in goats compared to BSE in sheep. It considered also, that irrespective of the outcome of this exercise it was inevitable that broader aspects of the safety of small ruminant products should be addressed since any measures announced to increase the safety of goat meat and meat products would unavoidably raise questions on the safety of sheep meat and meat products. However, the extent and complexity of the wider task and the fact that currently the evidence suggests that the occurrence of BSE in SMRU species is confined to the goat, argue strongly for an initial exploration of an approach to the conduct of a quantitative risk assessment on the safety of goat meat and meat products. A major difficulty in this respect is that most, if not all, recent research and new scientific information that might be relevant concerns experiments in sheep rather than in goats. Since almost all experimental data on BSE in small ruminants are with respect to sheep and given the outcome of the limited data on goats, goats could be considered as highly susceptible sheep in terms of BSE. In this case, data available on sheep would allow extrapolations to goats. Another factor to be taken into account would be the geographical risk since there is marked variation in the distribution of sheep and goats over the different MS. 3. Consideration of the estimation of a risk posed by consumption of goat products compared with an estimation of the risk posed by consumption of beef. 5

To make a comparison between a QRA for SMRU products and that for beef would require not only the QRA for SMRU products but also a prospective QRA for beef to calculate a current risk, rather than a historical risk, of BSE agent in beef, specifically taking account of current controls. However, the anticipated lack of quantitative data on SMRU and the absence also of a quantitative risk assessment in relation to human consumption of beef would not allow the direct comparison requested. The report in annex provides full details of the assessment. CONCLUSIONS The Scientific Panel on Biological Hazards concludes: 1. Currently there are not enough data (particularly in terms of pathogenesis and epidemiology) on BSE in goats to allow a quantitative assessment of risk posed to humans by consumption of meat and meat products derived from goats infected with BSE. Consequently, none of the specific scenarios that EFSA was requested to consider in the mandate, including the effects of SRM removal and the removal of collected blood, inactivation through processing of intestines, the extent of monitoring programmes (testing at slaughter) or the age of animals or genotype, can be examined in anything other than qualitative terms. It follows also that no current estimation of risk from consumption of goat meat can be compared with a risk of consumption of beef. 2. In considering all of the required data for a QRA of goat meat: the species barrier, the infectious load, the prevalence of BSE positive animals that become slaughtered for food and the effects of processing, to determine whether or not any of the risks present are reduced significantly and estimation of human risk/exposure patterns, it is concluded that the most significant data to be obtained related to the current prevalence of BSE in goats. It was acknowledged that steps had been taken to acquire such data but that results from recently initiated surveillance, including discriminatory testing of goats for BSE, will not become available until late 2005. 3. Past assumptions used in examining risk assessment for SMRU, by regarding sheep and goats similarly, may be inappropriate and the relevance of data on experimental BSE in sheep and/or data on scrapie to the risks for goats may be questionable. At this time, a risk assessment directed specifically at goat meat would be based on data from sheep. This approach would not provide a proportional response or a science-based assessment of public health risks from goat meat and goat meat products. 4. It is considered appropriate and proportionate, at present, to limit the RA to goats and not to expand it to a detailed consideration of the risks from BSE in sheep. It is, however, accepted that there were more experimental research data available on the pathogenesis (infectious load) of BSE in sheep and on 6

surveillance for BSE in sheep. Although data are lacking at present, the prospect of further information, including information related to exposure and other epidemiological factors, may allow a comprehensive and reliable QRA for BSE in sheep in the future. Therefore, the BioHaz panel considers that the feasibility of a QRA - sheep will require collection of more data and will require more time for the analysis of existing research and analysis of data still to be collected. 5. It is thought that a QRA-sheep was more feasible than a QRA-goat because more information was available about the phenotype and case definition, genotype effects, infectious load and prevalence of BSE in sheep than BSE in goat. However, even in this more favourable case, the paucity of quantitative data on titres of BSE agent in sheep tissues and the lack of a methodology for the geographical BSE risk assessment for sheep (GBR-S) precluded a worthwhile QRA-sheep at this time. The discrepancies between the data available for these two species would probably require separate QRA analyses to be done prior to a generalised QRA-SMRU. 6. A qualitative RA on goat meat can be made considering the existing Risk Management measures in place since 2001, the results of the recently increased level of testing in goats and the discriminatory testing. Although not quantifiable, account is taken of a number of facts: The goat found positive and which died in 2002, was born before the feed ban in 2001. Goats slaughtered for human consumption at a young age and born after the introduction of the feed ban, would now present a lower risk than the adult population. Other RM measures in place (SRM list, rendering) contribute further to a reduction of the risk to the consumer. Initial results of increased testing and discriminatory testing have not indicated any additional suspect BSE cases in goats or sheep based on the results of tests on approximately 125.000 sheep and 93.000 goats (as of 24.06.2005). Therefore, the current risk in terms of BSE, related to the consumption of goat meat and goat meat products is considered at this time to be small for goats born in 2001 after the feed ban and later. RECOMMENDATIONS 1. Future approach to a QRA-goat Results of surveillance and discriminatory testing for BSE in goats have been enhanced and cumulative results are expected late 2005. This will make available data for further epidemiological analyses to assess the current prevalence of BSE in goats. Of the data required for a QRA-goat, this is the principal input obtainable in the short to medium term. Further data on tissue infectivity relative to pathogenesis of BSE in goats can only be obtained by the initiation of prospective studies requiring a period of several years to 7

complete. If testing for BSE in goats within all MS s fails to reveal any further positive cases, providing that the TSE surveillance is conducted as described in the EFSA opinion of Nov 2003, for all categories for a sufficient long time (at least one year) this factor will be overriding in the calculation of a QRA-goat, even if inputs for other factors have to be based on hypothetical scenarios. Discriminatory testing should be applied on all primary TSE cases detected during this enhanced surveillance and thereafter to further confirm the data obtained. With respect to phenotype and case definition of goat BSE, special attention should be given to ensure appropriate ways to collect and store samples and to standardise conduct of discriminatory testing. Therefore, clear definitions of the tissue samples and the different tests to be applied, are needed. 2. Requirements for additional research Any remaining archival material of positive TSE cases in both sheep and goats available for further testing in MS could contribute to establishing information on the respective phenotypes and retrospective occurrence. This is particularly important in countries with historically high BSE prevalence. Additional research should focus on experimental BSE infection in goat to allow study of the pathogenesis of the disease after oral exposure including the tissue distribution and infectivity relative to age/incubation period and thereby to determine the tissues most at risk and their infectivity load. In conjunction with this aspect further anatomical data are needed on the distribution of lymphatic tissue, particularly regional carcass lymph nodes in goats, and how these might differ from the distribution in sheep. Such studies are also required to assist in the phenotypic definition of BSE in the goat, including the characterization of clinical signs. Co-infection studies of goats using ratios of scrapie and BSE would improve understanding of relative pathogenicity and resultant phenotypes and assist the development of better diagnostic tools to distinguish BSE from goat scrapie. The risk posed by goat BSE for human infection should be investigated by inoculation of goat BSE into humanized PrP transgenic mice. With the establishment of an appropriately infected herd the potential for horizontal transmission of BSE in the goat should be researched. Further research on goat PrP genetics is required. Since the infection in goats could represent a source of infection for sheep, or because it could herald similar common source infection for sheep, there would be no scientific basis on which to restrict risk management measures to goats alone. It is recommended to EFSA to immediately commission a research group to inoculate goats intra-cerebrally with BSE. This would ensure that material is quickly generated for further studies on the passage of the BSE agent in goats by more natural routes of exposure, enabling description of the pathology and infectivity distribution/load BSE in the goat, immunological testing and assay development and inoculation of various PrP transgenic mouse models. These funds could cover a bridging period pending the availability of funds through 8

DG RTD in the next Framework call for proposals. If material is available from the original French goat positively identified for BSE or from future cases, it is recommended to study secondary passage characteristics in goats. 3. Requirements for collection of additional information by EC Continue to secure data from MS s on number of samples that have or are undergoing discriminatory testing Obtain more data from MS s on goat meat consumption and specifically on differences in preferences among MS s. Collect data on age structure of goat populations and age of goats at slaughter. Request data on export of goat meat between countries. Establish the end use of all organs/tissues from slaughtered goats, including the frequency with which intestines are used for the production of casings. It is recommended for surveillance purpose to follow guidelines as prepared and published by the SSC (EC, 2001e) and EFSA (EFSA, 2003). Maintain the level of discriminatory testing of goats for BSE for an indefinite period, after the first six months are completed, to increase the confidence in the low level of risk indicated in this Opinion. 4. Requirements for collection of additional information by EFSA With respect to phenotype and case definition of BSE in the goat, there is a need to consult all companies involved in TSE testing (and with tests on the market or currently under evaluation), to request information whether or not the test used was developed and evaluated using caprine samples. If such data are available, there is a need to establish whether the evaluation was carried out on brain and/or lymphoid material and the numbers tested. As a preliminary step, it is acknowledged that the TSE testing report on scrapie tests for small ruminants (mainly sheep) has been adopted and was published (EFSA, 2005). To ascertain overview and tabulate the different mouse strains and Tg models used in the strain typing bio-assay and the related incubation times. To request the GBR WG of EFSA to consider a possible update of the SSCopinion on GBR-S for the information of the WG experts to provide an initial review to indicate where the conclusions and/or recommendations could/should be changed. DOCUMENTATION PROVIDED TO EFSA The formal mandate received from DG SANCO (D(2004) DS/cm/421319) of the European Commission requests EFSA s Scientific Panel on Biological Hazards for an opinion On a quantitative assessment of risk posed to humans by tissues of small ruminants (SMRU) in case BSE is present in these 9

Supporting Documents Opinion on safe sourcing of small ruminant materials adopted by the Scientific Steering Committee (SSC) during its meeting of 4-5 April 2002. Opinion of the Scientific Panel on Biological Hazards of the European Food Safety Authority on the interpretation of results of EU surveillance of transmissible spongiform encephalopathies (TSEs) in ovine and caprine animals, culling strategies for TSEs in small ruminants and the TSE-related safety of certain small ruminant products, adopted on 26 November 2003. VLA manuscript on tissue distribution of BSE infectivity in sheep following oral challenge. Report of the CRL expert group on strains addressing the relevance of atypical scrapie, in particular with regard to the presence of BSE in sheep. Paper of the VLA on interpreting the results of retrospective and prospective testing of sheep TSE cases. Commission report on the monitoring and testing of ruminants for the presence of TSE in the EU in 2003. The report gives an overview of the TSE prevalence in sheep and the reported genotypes of confirmed cases. Oral communication of Member States on the number of tests differentiating between BSE and scrapie in small ruminants. Paper forwarded by O. Andreoletti (UMR INRA-ENVT, Physiopathologie Infectieuse et Parasitaire des Ruminants, Ecole Nationale Vétérinaire, Toulouse, France) entitled : Données disponibles en matières de tremblante caprine. Report on the histological research on the cleaning efficacy of mechanically versus manually processed sheep intestines. (Koolmees and others). Report on the risk assessment of the use of sheep natural casings and legs of lambs (Koolmees and others). Other references to scientific publications and other documents are listed in the report in annex. SCIENTIFIC PANEL MEMBERS Herbert Budka, Sava Buncic, Pierre Colin, John D Collins, Christian Ducrot, James Hope, Mac Johnston, Günter Klein, Hilde Kruse, Ernst Lücker, Simone Magnino, Riitta Liisa Maijala, Antonio Martínez López, Christophe Nguyen-The, Birgit Noerrung, Servé Notermans, George-John E Nychas, Maurice Pensaert, Terence Roberts, Ivar Vågsholm, Emmanuel Vanopdenbosch. 10

ACKNOWLEDGEMENT The Chairman, rapporteur and members of the working group are acknowledged for their valuable contribution to this mandate. The members of the working group are: Olivier Andreoletti, Thierry Baron, Chris Bostock, Herbert Budka, Maria Caramelli, John Collins, Christian Ducrot, James Hope (Chairman), Ernst Lücker, Marion Simmons, Christina Sigurdson, Emmanuel Vanopdenbosch, Gerald Wells (rapporteur), Robert Will and John Wilesmith. ANNEX Report of the Working Group (WG) which deals in detail with the assessment: http://www.efsa.eu.int/science/biohaz/biohaz_opinions/opinion_annexes/987_en.html 11