EUFMD 

33rd Session

Report

Appendix 01

Appendix 02

Appendix 03

Appendix 04

Appendix 05

Appendix 06

Appendix 07

Appendix 09

Appendix 10

Appendix 11

Appendix 12

Appendix 13

Appendix 14

Appendix 15

Appendix 16

Appendix 17

Appendix 18

Appendix 19

Appendix 20

Appendix 21

Appendix 14 - Conclusions and Recommendations of the 1997 and 1998 Sessions of the Research Group of the Standing Technical Committeee

Session held in Poiana-Brasov, Romania

23-27 September 1997

Items referred to the Group by the Executive Committee: proposals for better interaction between the Research Group and the Members of the European Pharmacopoeia.

The Group highlighted the deficiencies in the current FMD Monograph and the absence of information in certain key areas. For example, he pointed to the developments which have occurred in FMD vaccines for emergency use yet there is an absence of protocols for assuring their potency. The EP specifies that FMD vaccines for routine prophylactic use should have a minimum potency of 3PD₅₀ yet experts in FMD are of the opinion that that value is too low and no longer acceptable. Furthermore, protocols are lacking for vaccines for certain species, for examples sheep and pigs. The absence of the latter is seen as a particularly important deficiency.

These points and additional areas of deficiency and lack of specification were discussed by the Group which concluded that:

1. there is an urgent need for the Research Group to re-establish contact with the EP Committee so that it can participate in its deliberations, identify the deficiencies in the current edition of the FMD Monograph and the need for revisions and ensure that the Committee is aware of any new developments in FMD vaccinology which have relevance to the FMD Monograph.

The Group recommended that:

1. the Executive Committee should be made aware of the need for the Research Group to establish closer links with the EP Committee so that it can have an input in their deliberations.

2. the Executive Committee should make contact with members of the EP Committee requesting that steps be taken to ensure closer links between the EP Committee and the Research Group.

3. there should be a call for papers for the next Session of the Research Group which identify and discuss the deficiencies in the current version of the FMD Monograph of the EP.

Potency testing of FMD vaccine, alternative tests to cattle challenge

The Group discussed the advantages of reducing the number of cattle challenge experiments in terms of animal welfare, cost and biosecurity, and the difficulties of assessing the results of animal challenge due to the variability of individual animal response.

Conclusions

1. The Group concluded that there is now sufficient data available to show that cattle potency tests could in most cases be replaced by serological tests.

2. The Group recognised that with the procedure currently prescribed for potency testing (reduced dose application) the vaccine must contain at least 6 PD50 per dose for cattle.

Recommendations

1. Discussion should be initiated with the objective of replacing cattle potency tests by serological tests for the assessment of conventional (prophylactic and emergency) FMD vaccines.
2. A new independent FMD vaccine control laboratory supported by international organizations (EU, FAO) should be established in Turkey.

Persistence of FMD virus in ruminants

Conclusions

• Small ruminants play an important role in the spread of FMD outbreaks as infection is often subclinical.
• The presence of virus could be confirmed only with a very sensitive test in serologically positive, but clinically negative, contact sheep.
• Different kinds of relevant samples from several animals have to be taken. Mouth swabs are a good alternative to probang samples in subclinical cases.
• There was evidence of transmission of virus from contact sheep to sentinel animals.
• Contact sheep could present a source for the transmission of FMDV. It has to be stressed that these animals could easily be considered as FMDV-free animals after examination by classical laboratory methods.

Recommendations

1. The transmission of FMD infection in small ruminants should be studied under field conditions.
2. Subclinically infected sheep should be considered as important hosts in the epidemiology of FMD.
3. These experimental results provide the possibility of clarifying the status of seropositive, clinically negative, animals. Further work should be undertaken to adapt the test for large-scale application.
4. Further work should be done to compare mouth swabs as an alternative to OP samples for detecting subclinically infected sheep.

Differentiation of antibodies induced by vaccination and by infection

It was recommended that:

1. assays which measure antibody to 3 ABC be used to:

detect viral activity in vaccinated populations

assist risk assessment in animals found sero-positive for antibody to structural proteins

2. assays which measure antibody to non-structural proteins be combined with other assays to identify the infectious state of an animal, such as the measurement of specific IgA in saliva, and PCR using probang or nasal and/or mouth swab samples.

3. additional funds be sought from the EU to continue the Concerted Action programme overseeing the collaboration between European laboratories examining improved diagnostic techniques for identifying animals carrying FMD virus.

4. in order to detect low sero-prevalence in an area whole herds must be tested. This would only be possible if test kits incorporating 3ABC reagents were available to allow the participation of regional laboratories. Funds should be allocated for the development and manufacture of a stock of complete test kits.

Species adaptation of different strains of FMDV: field and experimental findings

The Group discussed the results and circumstantial evidence of species adaptation of FMD during epidemics. Examples quoted were the spread of FMD in sheep in the 1989 Tunisian and 1994 Greek epidemics but its failure to cause disease in pigs which were at risk. Similarly, the occurrence of FMD in sheep, but not in pigs, was reported during outbreaks in Bulgaria and Israel.

The Group concluded that:

1. The 1997 Taiwan epidemic is a salutary lesson for FMD-free countries and especially those with high stocking densities of animals.

2. The episode highlights the necessity for countries to establish National Contingency Plans for FMD and to test and evaluate them periodically. National Contingency Plans for FMD should include a capability to diagnose FMD or else alternative plans for submission of suspected material to a national, or regional laboratory or to the WRL.

The Group recommended that:

1. FMD diagnostic laboratories should employ tissue culture systems originating from different species for the attempted isolation of virus from clinical specimens suspected to contain FMD virus.

2. Further investigations should be carried out to determine the basis of species adaptation in FMD. In support of this objective FMD laboratories which have species adapted strains in their collections and which isolate them during outbreaks should send samples of the original field material to the WRL.

Development of test using milk from sheep

The group discussed the use of a milk test for FMD virus antibody and recommended

1. further development of the test using samples collected in countries with endemic FMD.

2. use of the test to assess FMD immunity levels in vaccinated populations.

3. combining the test for FMD antibody in other programmes in which milk samples are collected.

Serosurveillance

The Group recommended that

1. more relevant strains should be used for serological testing in Europe, especially for import testing. A₂₂ and O₁ Middle East should replace the A₅ and O₁ Europe strains which are still used in most laboratories.
2. an international standardised surveillance system for FMD in the Balkan countries is needed to reduce to a minimum the risk from spread of FMD. The following steps should be taken:

1. the Veterinary Services should agree on the objectives and apply the same procedures for FMD surveillance.
2. FAO, OIE, EEC should coordinate the use of the same methods for detecting viruses and antibodies.
3. the laboratories most advanced in diagnosis and epidemiological surveillance of FMD should pass the benefits of their experience on to other countries by means of meetings of specialists and exchanges of protocols, materials and reagents.

Quality assurance in FMD national laboratories

The Group agreed the following conclusions:

1. Confidence in the QA programmes used by different countries and in the procedures used for compliance monitoring will increase as those procedures are better known and understood.

2. There is a need for an international organization to disseminate information about programmes for QA and compliance monitoring and to take the lead in developing a system for harmonising standards between countries.

3. The Organization for Economic Co-operation and Development (OECD) has gained the relevant organizational experience through its standardisation activities in the field of chemicals and would be a suitable organization to promote the development of a similar system for veterinary diagnostic laboratories, especially those involved in international trade.

4. The strategy adopted by the IAEA/FAO Joint Division and OECD to formulate proposals for the accreditation and compliance of laboratories in developing countries and Eastern Europe could be applied in parallel for laboratories in Western Europe and developed countries.

5. Financial support will be required to develop and sustain a system for QA and compliance monitoring.

6. The procedures for implementing compliance monitoring will need to be considered, in particular the identification of organizational responsibility.

The Group recommended that:

1. The conclusions above should be referred to the Executive Committee for their endorsement.

2. The agreement of the Executive Committee should be sought for the Group to make contact with and representation to the IAEA/OECD through the attendance of its Chairman, Dr. De Clercq, at a workshop to be held at IAEA, Vienna in February 1998 at which it is planned to discuss the development of a scheme for laboratory accreditation and compliance for veterinary diagnostic laboratories.

3. In anticipation of the adoption of this Scheme National FMD laboratories should adopt progressive measures to implement a programme of Quality Assurance.

Emergency vaccination policy in Europe

The Group concluded that:

1. Emergency vaccination is an important and valuable adjunct to the policy of stamping out.

2. In applying emergency vaccination it is a prerequisite that the principle of regionalisation be accepted at the international level.

3. In the light of the availability of improved diagnostic methods which will in the future be applied to larger scale surveillance there are opportunities for reducing, both in extent and time, the restrictions which are applied to emergency vaccination zones.

4. To be able to make more accurate predictions of the epidemic potential of outbreaks and to assess whether or not to use emergency vaccination, there is a need to further refine decision support systems, taking into account of different animal husbandry systems, animal densities, virus strain characteristics, etc.

5. A decision to apply emergency vaccination will also be influenced by other considerations such as the availability of the food supply for human beings, welfare and ethical considerations, acceptance by public opinion and environmental impact.

6. A national authority which is considering the implementation of emergency vaccination will need to inform and co-ordinate its actions with neighbouring countries.

The Group recommended:

1. That all aspects of emergency vaccination shall be considered by the appropriate national and international animal health organisations so that the zoo-sanitary rules relating to it are clearly established.

2. That procedures relating to emergency vaccination developed and agreed by the Group are recognized at the international level.

Session held in Aldershot and Pirbright , UK

14-18 September 1998

Conclusions & Recommendations

Species adaptation of different strains of FMDV: field and experimental findings - New variants of FMD virus.

1. Rapid recognition of new variants, with more attention on the 'index case', and an effective response is important for control. Submission of material to the world reference laboratory is therefore essential.

2. Molecular epidemiological studies have identified the emergence of several new strains of FMDV type A in recent years, each with a defined geographical distribution.

3. Further research is required into how new variants of FMDV can best be controlled by vaccination. The relative merits of adapting new variants to derive new vaccine strains, altering the antigenic payload, and the use of more potent vaccines with novel adjuvants, should all be evaluated.

4. FMDV strain A Iran 96 causes disease predominantly in cattle. Experimental data supports the observation from the field that FMDV isolates from Greece in 1996 are particularly virulent for sheep. Subclinical infection with FMDV can occur in pigs.

Research is required to identify the host, viral and transmission factors that are responsible for adaptation of FMDV to a particular species.

Adaptation to a particular species can result in either a reduced ability to infect or cause disease in another species or both of these.

Changes in control strategy due to identification of a species adapted variant are rarely indicated.

Developments in diagnostic techniques - Persistence of FMD virus in ruminants.

1. RT-PCR is a useful adjunct to conventional diagnostic techniques, but should be used in combination with other assays, and/or clinical signs of infection.

The results presented provide further evidence for the important role of subclinically infected sheep in the epidemiology of FMD. Whenever possible, new diagnostic methods should also be validated on small ruminants. The reduction of virus replication and excretion as well as the number of sub-clinically infected sheep was reported after the use of emergency vaccine.

2. In order to get proper insight into the antigenic profile of new field isolates, antigenic relationships using either monoclonal or polyclonal antibodies should be studied.

3. There is a need to improve diagnostic methods in terms of sensitivity, speed and simplicity and to investigate the diagnostic potential of newly developed physicochemical assays such as electrochemiluminescence, surface plasmon resonance, atomic force microscopy and biosensors.

4. Collaboration on the development and validation of diagnostic methods should be continued and colleagues from non-EU member states should be invited to participate.

Standardisation of FMD Diagnosis (Phase XV).

1. Primary reference sera for FMDV types O1 (Middle East), A22 (Middle East), and C1 (Europe) have been selected. The WRL for FMD should make available the selected reference sera - negative/weak positive/cut-off sera - to National FMD laboratories.

Laboratories are encouraged to evaluate these reference sera as controls in use in routine testing and report results as part of Phase XVI.

2. National Laboratories should use these sera as primary reference. Laboratories should create their own secondary and tertiary standards using strong positive sera. Advice should be given by the WRL as to how laboratories should generate their own standards.

3. Laboratories wishing to participate in the FAO Phase XVI study should make contact with the Secretary of the EUFMD Commission or the WRL for FMD.

Serology (NSP), serosurveillance, persistence of antibody induced by vaccination.

1. Detection of antibody to NS proteins can be used to identify infected animals, with any of the seven serotypes, whether vaccinated or not and regardless of the clinical outcome.

2. Field validation in the Balkans showed that measurement of antibody to NS proteins was useful at detecting unrecognised, subclinical spread of infection either geographically or between species, even 18-20 months after an outbreak.

Measurement of antibody to NS proteins should form part of any serological survey intended to detect past or present infection of animals vaccinated against FMD.

The assays should be used on a herd or group basis. Investigations in the field are necessary to determine the sampling rate.

Results of individual animals should be interpreted with care as not all vaccinated, infected animals seroconvert to NSP.

The tests cannot be used to determine the carrier status.

3. Measurement of antibody to several NS proteins at the same time can give a more reliable indication of the infection status of an animal.

4. No single ELISA format has yet been shown to be definitively superior to all others. The development of fully validated tests in a form suitable for supply to laboratories involved in diagnosis and control of FMD should be a priority.

Quality assurance.

The meeting was informed that the OIE agreed to create an ad hoc group to study the proposals of the Vienna meeting. The chairman was asked to follow the progress of the ad hoc group.

National laboratories are encouraged to proceed with the implementation of a Quality Assurance Programme. They are advised to approach their National Accreditation Bodies.

In the future the FAO Collaborative Studies should comply with OIE Guidelines for Proficiency Testing.

The investment required for QA/QC activities at laboratories is high. A study should be conducted to compare the investments made by laboratories and those of private industry. In this way laboratories can justify adjustments to their future budgets.

Inactivation of FMD virus.

Results were presented on the failure of dry heat to inactivate air-dried FMD virus. It was concluded that this method which is in the present FAO security standards for FMD laboratories in Europe should be changed. FMD laboratories and Institutes are requested to review their current inactivation procedures by taking this information into account.

Further research combining different treatments and risk analysis should be carried out.

Vaccine and proposals for amendments of the FMD Monograph of the European Pharmacopoeia.

Based on a proposal from the Research Group, the Executive Committee had decided to invite representatives of European vaccine producers to present their view for amendment of the FMD vaccine Monograph of the European Pharmacopoeia. It is generally accepted that the EP Monographs are designed to be appropriate to the needs of Regulatory Authorities, persons involved in the control of product quality as well as manufacturers of starting materials and medicinal products.

In particular two areas of concern were identified:

The replacement of the in-vivo safety test by more sensitive and statistically valid in-vitro tests. Results of safety testing of FMD vaccine batches were presented. Out of 253 batches only one failed the in-vivo test whereas 17 failed to pass the in-vitro safety test, clearly indicating that the in-vivo test does not really contribute to safety control of the vaccine.

The need to evaluate the PD50 and alternative methods for potency testing in other target species with a view to future inclusion in the European Pharmacopoeia.

The Chairman of the Research Group suggested to establish an ad hoc Working Group to be appointed by the Executive Committee. Dr Amadori, Dr Barteling and Dr Haas could be members of the Group together with representatives of producers, vaccine banks and of the EC Scientific Committee. Other experts of control authorities, EMEA (European Agency for the Evaluation of Medicinal Products) and specialists in statistics and quality assurance could be invited to participate in certain meetings in accordance with the Agenda.

Closed Session.

Vaccination against A/Iran and type A vaccines.

Considering the field information already available on this subject and the possibility to get sera from vaccine producers and from Turkey for additional serological testing, the Group agreed that there was no need for organising a trial on large animals to verify the protection of the existing vaccines against the new strain.

The Group is of the opinion that there is a need to make a reassessment of the appropriate A vaccine to be used in Turkey.

The question of the appropriate antigen and sera to be used for the detection of the new type A virus and antibodies in national laboratories was raised and it was agreed that sera against the new A/Iran strain should be provided to laboratories.

Development of kits for the non-structural protein

As a start a double blind collaborative study should be organised under the next phase of the EU concerted action coordinated by the national laboratory of Germany.

Serosurveillance in Bulgaria

The Group agreed that the serosurveillance in small ruminants should be continued on the border with Turkey.

The collection of samples reinforces the clinical surveillance and the testing of sera maintains the activity in the national laboratory.

Testing against the 3D non-structural protein has been suggested.

Bulgaria shall provide a protocol and an annual report to EUFMD when the Commission supports the cost of reagents.

Provision of vaccine strains by the WRL and focus on index case

The Group agreed that the provision of viral strains adapted for vaccine production is beyond the responsibility of the WRL.

The Group agreed on the need to define the index case and that procedures for early detection and investigation should be foreseen in the Contingency Plans.

Other items

The Group was informed that Professor Schüller had taken up new duties in Brussels and therefore had resigned as a member.

The Group expressed regret that one of the members was unable to attend the two successive Sessions in 1997 and 1998 and suggested that this could be avoided for the next Group to be designated in 1999.

The participant from France extended an informal invitation to the Group to hold their next Session at Maisons Alfort in France in 1999, and the participant from Bulgaria proposed to organise the next open Session in Sofia in 2000.

© European Commission for the Control of Foot-and-Mouth Disease

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