"Open" letter to Dr. Alex Donaldson

Head Pirbright Laboratories, Institute of Animal Health, U.K.

From: Dr. Simon J. Barteling, Amsterdam, The Netherlands

Subject: EU Inquiry

Dear Alex,

Alicia Eykyn and Jon Dobson, both directors of the FMD FORUM, attended your speech to the Inquiry Committee of the EU Parliament on the 17th of June in Brussels. As you are probably aware, the FMD FORUM is strongly against the large-scale killing of animals, when it comes to control and eradication of FMD and I feel the same way, too. There must be other means and Paul Sutmoller and I, as well as other colleagues who have specialised in this field, are convinced of this.

These days you hear "we must look to the future and not to the past", but I disagree, because we must learn from the past in order to build a better future. Lessons must be learned, before we draw the line and start moving on.

The Pirbright Laboratory houses the World Reference Laboratory on FMD. You the Head of it, are considered a key person in FMD policy making – in fact, on a global level – so your talk was followed with great interest. It has even been taped, typed out, and sent to me for what might be termed ‘technical adjustments’. This I have done, together with some minor editing and you find the result, as an annex to this letter. I was also asked to comment your speech, with the intention of forwarding these comments to the Inquiry Committee of the EU Parliament.

It has to be said that I started that task with some trepidation, as we have always had a very good personal relationship and get on together very well. For years we were co-operating in the FMD-subgroup of the (EU) Veterinary Scientific Committee and during the (FAO) Research Group Meetings. In fact I remember the two of us consulting the Taiwanese government at the start of the terrible outbreaks of FMD in Taiwan, as they did not know what to do. There were also so many other occasions where we both tried to make contributions in controlling FMD – each with his own speciality. Also many of your studies, such as those on the spread of FMD by aerosols in particular, I appreciated very much.

That now I disagree with many of your statements may have more to do with our different backgrounds than anything else.

When I started in 1966 to work at the Amsterdam Branch of the Central Veterinary Institute (Frenkel’s institute dedicated to the control of FMD), there were ongoing problems with FMD in pigs. The cattle were vaccinated and well protected. But as you know, the classical Frenkel-type vaccine was not protecting pigs very well. In fact it was only when concentrated vaccines were used, that the pigs turned out to be sufficiently protected to bring the outbreaks under control. In other words, for the control of outbreaks, the Dutch – like other countries of mainland Europe – were relying on good quality vaccines.

The British history is different. Since the FMD Act of 1892, FMD is controlled by "stamping-out" with financial compensation to the farmers. This strategy was successful with one exception during the 1927- 28 outbreaks, when funds became limited and diseased farms at isolated locations were only quarantined (without slaughter and without compensation). When in 1967 outbreaks started in the UK, I asked my boss Professor Jacque van Bekkum (you, of course, know him very well) "Why don’t they vaccinate?" He answered "British vets don’t want to vaccinate. They have always managed FMD by stamping-out and you will see, this time they will manage it in the same way". Well, you know the history and the horrendous costs involved, when deep into 1968 the outbreak was finally brought under control. I honestly thought that lessons from that appalling outbreak had been learned.

Although Pirbright has made very important and essential contributions in the development of FMD vaccines, I always tasted an (Anglo-Saxon?) attitude that stamping-out was the best solution and the applications of vaccines was something for others. Where the UK, with its World Reference Laboratory for FMD, had the greatest "critical scientific mass", and the greatest influence, this attitude finally overruled other views inside the EU and inside other international institutions like the OIE. The risks that amongst vaccinated cattle some carriers may remain, was strongly emphasised. Risks of spreading disease by large scale stamping out and of leaving (silently infected) carriers after stamping-out, as were found in Britain after the ‘67-68 outbreaks, were not taken into account. Even more importantly, the deteriorating, destructive effects that the latter policy might have on great parts of the rural society were not considered either.

 


 

Let me now come to the contents of your speech. Forgive me if my reasoning contains elements that are familiar to you, because I want my arguments also to be clear for non-FMD specialists, who will read them. Let me first discuss your (the British) arguments (p.4) why emergency vaccination or barrier vaccination was not used in the U.K.:

1. "We weren’t expecting the disease".

I find it hard to believe. Great Britain is a country with the largest FMD Laboratory in the World, with a World Reference Laboratory, where daily packages arrive with live virus from all over the world, and with the largest FMD vaccine production plant of Europe. Great Britain not prepared to handle outbreaks of FMD?

Also, what has un-preparedness to do with not using vaccination for controlling outbreaks? Or do you mean: "If we had been better prepared, we probably would have used vaccination"? Allowing un-preparedness of Veterinary Services is certainly one of the major weaknesses in the OIE/WTO regulations. A country can have a status "Free of FMD without vaccination" and still have an un-prepared Veterinary Service, creating time bombs not only for the country itself, but also for trading partners. If anything can be learnt from the British outbreak it is that under the current regulations and practice the (highest) status "Free without vaccination" does not at all mean "risk-free" for trade partners. Argentina is another country where the veterinary Service was not prepared and extended outbreaks were going on before the disease was notified. Argentina is also another example that a country with the highest OIE status of freedom of FMD is not "risk-free" for trade partners. FMD spread into Uruguay and the South of Brazil (Rio Grande do Sul). I think that for countries wanting this highest status, the OIE should create a system of regular and serious inspection of Veterinary Services and of their surveillance system and alertness for FMD. Countries with this profitable status should pay for the costs of such inspections.

2. "When we recognised it, it was widely distributed throughout the country".

I would say that statement was an argument in favour of vaccination. You can cheaply and quickly go for wider rings or areas where you expect the disease to be present and then wait and see where the disease pops up further and focus on that. It was exactly the "out of control" argument that made the Dutch decide to vaccinate all susceptible animals in a whole area including many farms outside 3 km zones Unfortunately, these animals had – for economical (export) reasons - later to be slaughtered. This contributed to the so often misused argument that in The Netherlands the ratio of the number of killed animals to the number of outbreaks is much higher than in the U.K. For reasons of trade the Dutch also started trying to control the outbreaks by (circle) culling. The outbreak curves showed exactly the same increase of outbreaks as in the U.K., meaning that the used policy was not effective. If vaccination had not been applied the dimensions of the catastrophe might well have approached that of the British. By stopping the outbreaks by vaccinating a whole area, the total number of killed animals remained limited to 260.000 (still an awful number).

3. "Prof. Brown has indicated that sheep were extensively involved and identifying whether sheep are infected or not or have mild disease or not is a major problem. So it was very hard to identify which areas were already infected and, therefore, which areas could or could not be vaccinated".

Also here I would say that vaccination of all susceptible animals around spots where there were indications of presence of the disease would have been the solution to get rid of the disease quickly, with least amount of effort and cost. Using the potent vaccine bank vaccines (6 PD50 or more) it would have stopped outbreaks in 4 – 5 days while within the vaccination zone social community life could gradually take its course after 1 to 3 weeks.

4. "In a practical sense though at the start of the epidemic we didn’t have enough vaccine to apply mass vaccination. That changed later as vaccine stocks were built up. However, there was an other important issue. Had we changed and brought in vaccination in addition to all the other control measures which were going on - for which we had inadequate resource at the beginning - it would have diverted our personnel away from what I regard as more important activities of stamping out infected premises. Then, of course – and I can’t really go into it now - we did consider what the extra strategy would be. This of course is complicated. It is easy to start a vaccination programme but it is very difficult to get out of it".

I can hardly believe that the first statement is still made. You know very well that in Europe large amounts of very potent (> 6 PD50, see also below) emergency vaccines are and were available. Although the "International Vaccine Bank" at Pirbright contains rather limited quantities (0.5 million doses per type), the "European Vaccine Banks" contain 10 times as much. As you know, sheep can be vaccinated with 1/3 of a cattle dose. In addition there are the European producers that also have stocks of vaccine available – and which were available at the time. All one had to do was accept that vaccination was the proper policy and ask for fast supply.

In the past, the European Union has helped out Balkan countries, North Africa, and even Korea when they had outbreaks of FMD by sending quantities of vaccine from their stocks. Therefore, I cannot imagine that the EU would have refused to send vaccine to one of its own member states, if it had asked. Also, because vaccination would have quickly reduced the risks of FMD entering into mainland Europe. According to the contracts with the producer, vaccines can be ready for shipment within 4 days, a good time to prepare the vaccination campaigns. It just required the competence and the will to see the right decision taken.

In the 4th sentence you come, in fact, to your basic (British) attitude "the more important activities of stamping-out infected premises". (Circle) culling and "culling on suspicion" takes a lot more from the veterinary staff than vaccination. Not only the shot or (deadly) injection must be given, but also vets must spend time in preparing and conducting the whole operation. Also, you do not talk of the considerable risks of spread of disease that are connected to large-scale culling, in particular, when farms with pre-clinical disease are involved and the people that carry out the cull are not aware of this.

Finally you argue: "It is easy to start a vaccination programme but it is very difficult to get out of it". I do not see that point. When vaccination of all susceptible animals is done within the vaccination zone, the disease has gone within a few days, like in The Netherlands. That international trade nowadays asks additional activities is quite another matter.

 

The points above seem to be the British arguments why vaccination was not used.

The role of epidemiologists is not described. Their approach is that you must make fire-break zones by killing all the animals around outbreak farms, the width of the fire-break  circle and the required speed being calculated on the bases of spread of FMD under British field conditions. I miss the argument that epidemiologists like Woolhouse and Anderson came to the conclusion that in their models it was shown that the disease spread too rapidly to be stopped by (ring-) vaccination and that therefore vaccination was no option. It is an argument that was also used by British officials. However, in my opinion those modellers started from the wrong assumption. They forget that under British field conditions outbreaks were controlled by (circle) culling. They do not pay attention to the fact that culling of (pre-clinically) diseased farms cannot be carried out without a considerable risk of spreading disease and that the speed of spread might well largely be due to the culling practice.

I hope to say more about that, in some detail, during the EU-FMD Research Group Meeting at Izmir in September.

In the rest of your speech you more or less disqualify existing FMD vaccines and their use and finally come to the conclusion that they must be improved first, which I don’t agree.

On page 1 (end of 2nd paragraph) you say; "A high potency vaccine will protect the animals in 4 days. That would be a vaccine of 6 PD50 or more but, the shelf life of that vaccine is quite short, possibly because there are concentrated amounts of enzymes that may break down the protein". This was indeed found for the antigens/vaccines of IVB that were purchased in the eighties when vaccine producers were not (yet) familiar with routine concentration (and purification) of the antigen. In itself the potency of a vaccine has nothing to do with the stability of the antigen. It depends on the grade of purification of the antigen. The (concentrated) antigens/vaccines of the European Vaccine Banks, produced during the nineties, were sufficiently stable. We (at the Community Co-ordinating Institute; CCI) found such vaccines that were tested 3 months after their preparation fully protective (as reported during the EU-FMD Research Group meeting in Brasov, Romania in1997 (p.68). Also Merial, the producer of the antigen (and the vaccines) declared, that the vaccines should have a normal shelf live of one year and longer because these were produced according to standard procedures.

In the many discussions in the U.K. that Paul Sutmoller and I attended often the statement was made – and you conclude with that as well – that we need better vaccines. I disagree with that. For example, the vaccines of the European Vaccine Banks when tested at CCI protected all cattle vaccinated with a full dose. Even 80 % of the cattle vaccinated with a quarter of a dose was protected against injection with virus on the tongue, a level that is generally considered to give sufficient herd protection. Most of the vaccines had PD50s of above 20. Also, with the current purification and concentration methods and by increasing the payload of the vaccines, we can make vaccines almost as potent as we want. You may remember that about 10 years ago your co-workers Frieda Davidson and John Crowther were asking me for a high payload vaccine to raise high levels of antibodies in pigs (they wanted to do some studies with antibodies). We (at CCI) prepared an (O1 BFS) double-oil emulsion vaccine with approximately 10 times the normal quantity of purified inactivated virus antigen. The antigen had been produced according to routine procedures at Lelystad. At Pirbright the vaccine indeed induced high (hyper-immune) levels of antibodies that remained constant during the whole further lives (2= years) of the 2 pigs. Unfortunately, CCI was discontinued and we have not given this study a follow-up. It anyhow demonstrated that – if producers really want to – vaccines can be improved further even with existing methods. The price of such a vaccine that may possibly induce lifelong protection does not need to be exorbitant (I guess between  2 and 3 €uros for a mono-valent dose).

On page 1, 2nd paragraph, 3rd sentence you state: "Generally, routine mass-vaccination has the objective of reducing the prevalence of disease to a level where it becomes financially acceptable to bring in the additional measures. These are essential and would be disease control by stamping out to eliminate the virus, because vaccination itself will not eradicate – eliminate the virus. You need additional measures".

In a general sense this is not true. In several South-American countries FMD has been eradicated by vaccination of the cattle population only, in many cases even without the killing of diseased animals. It has been done in Uruguay in the past and also last year when they had outbreaks as severe as in the U.K. (up to about 50 cases per day). I will come back to that in a moment.

On p.3 you say that in Europe vaccination did not eradicate the virus. I do not understand that. How could we in 1991 stop vaccination and demonstrate freedom of FMD? After that we only had a few (minor) outbreaks at the south-east borders of Europe originating from the Middle East. Or are you referring to outbreaks in Portugal (Spain) and Italy and the few cases in France, The Netherlands and Germany. The latter outbreaks were due to poorly inactivated vaccines – methods of inactivation were not as safe as to day – or escapes from laboratories and vaccine plants and had nothing to do with insufficient protection by vaccination or with ongoing disease. The outbreaks during the 1980’s in Portugal (Spain) and Italy, countries where (officially) general vaccination was applied were more serious. I don’t know the situation in Portugal, how well systematic vaccination of all cattle was carried out and whether the quality of the vaccines that were used was of sufficient potency. I know quite well what happened in Italy where I went twice with Dr. Evans Dexter of DG VI on a fact-finding mission for the EC.

In Italy, because of a change in the governmental organisation, animal health had been brought under the wings of the Ministry of Hygiene. As a consequence, in many districts the (elected) authorities responsible for the FMD vaccination were physicians or had another background in human health. Many of them were not realising the importance of FMD and vaccination was no longer carried out consistently. In some districts only 40% of the cattle had been vaccinated. Therefore, it was not amazing that 2 successive FMD outbreaks near Modena (where all Italian import by train of cattle and pigs was centralised) could spread not only in the non-vaccinated pigs and sheep but also in insufficiently protected cattle herds. This fact may also be used as an argument against re-introduction of general vaccination. After years of freedom of disease, the (costly) vaccination might no longer be supported by farmers and by local authorities. Even a system of independent (international) control cannot guarantee consistent vaccination.

Argentina (p.2 last paragraph) is not a very good example of failure of complete eradication of FMD by vaccination. In the past they were successful in eradicating the disease by vaccination of their cattle only and were factually free of FMD for several years. After that they lost their alertness and were – like the U.K. (?) - not very well prepared. They had very extended outbreaks when disease was reported and (finally) action was taken by re-introduction of general (cattle) vaccination. Last January they reported freedom of disease. Argentina is a very large country, about 5 times the size of the UK (if not more) with a complex infrastructure of livestock breeding. That they do not trust the situation for the full 100 % and continue vaccination for a while, is therefore understandable. Uruguay, in size and livestock population comparable with the U.K., is a better example of how vaccination can work. As you know they had extended outbreaks that started at the end of April. Already the beginning of July, when all cattle had been vaccinated, the standstill of transport of animals was lifted and a second (booster) vaccination was started. The vaccination (of cattle only) was carried out - as usual - by the farmers and farmers hands. In Uruguay they had their last case by the end of August. Uruguay discontinued vaccination and will go for the complete freedom status again (information Dr. Raul Casas). It is however dependent on the freedom of FMD in neighbouring countries and the vaccination shield that is build up there. In Uruguay the costs (about 20 million dollar) were several magnitudes lower than those in the U.K. while the suffering in rural communities was minimal.

From Uruguay (but also from Argentina and Europe in the past) there are also lessons to be learnt from the fact that sheep were left unvaccinated and millions of those sheep are grazing the same pampas as the vaccinated cattle. It demonstrates that:

1. Sheep - like wildlife - are a "dead-end host" (as has been demonstrated in the past in Europe as well), at least, when you don’t move them around or bring them frequently to markets like in the Middle East or in the U.K.

2. Vaccinated carriers do not further spread disease. As in the past, vaccinated carriers must have been around in large numbers because diseased farms were not slaughtered. These carriers are grazing the same grounds as the non-vaccinated sheep (and young not yet vaccinated cattle) without causing continuation of disease.

Point 2 justifies asking the question: Are there anyhow documented cases of animals vaccinated with a qualified vaccine causing new outbreaks? To my knowledge (and to the knowledge of many of our colleagues) there are not. I am realising that this touches an almost central dogma in (FMD) veterinary science that carriers are by definition dangerous. But we have to face it, unless you know of any case. It means that vaccinated carriers do not excrete sufficient virus to cause further outbreaks. It has probably to do with "minimal infectious doses" of virus that are required to infect an animal, of which you know all about.

Therefore, both scientists and makers of rules and legislation in the international community should ask themselves whether (in comparison with stamping-out) the punishment on vaccination – longer exclusion from export trade in animals and animal products – can be justified. For countries relying on export, this punishment makes the use of vaccination for controlling FMD outbreaks, unacceptable. One could (should) also ask oneself whether man-made rules - on the basis of a hypothetical non-demonstrated risk - in their consequences may cause the destruction of millions of cattle, sheep, and pigs and injuring the economy and the (mental) health of so many in our farming societies.

Also, in their considerations the international trading community should take into account that ongoing disease - like in the UK – creates a significant risk of spreading disease to other countries. Therefore, control of outbreaks by "stamping-out" and by (limited) vaccination should have the same consequences for export. Then the best means for eradicating the disease - with minimal disruption of the rural societies – can be applied without prior debate and disputes. Crucially, after any outbreak, the veterinary services shows by serological testing – to the satisfaction of the international trading community - the absence of FMD before normal export could be resumed. This should be required whether stamping-out, stamping-out plus ring vaccination, or vaccination only was used to control an outbreak: The demonstration that serological surveys are carried out rapidly and efficiently will reassure the international community that the eradication of FMD is taken seriously.

With such regulations, awareness of veterinary services, proper emergency plans – including "fire alarm" exercises and with the rapid availability of quantities of vaccine from vaccine banks, FMD does not need to be the disease causing national catastrophes like in the UK. Also, terrorists, purposely spreading FMD, will not necessarily create a disaster of the British dimensions.

Many of your points against the use of vaccination and the disqualification of existing vaccines can, I suggest, only be explained as "Freudian" arguments in the context of the described anti-vaccination attitude, creating a "common truth". Also, when in your conclusion (last paragraph) you state that "we do need better vaccines". I think that above I have given sufficient evidence that this is not the issue. Of course FMD vaccines can be further improved. However, existing vaccines are of sufficient quality to control and eradicate FMD.

I hope that in an "open" debate FMD scientists can find each other on how to go on. What effect it might have on politics is than another matter.

I am looking forward to your reaction.

Best regards,

Simon

 

 

Response from A I Donaldson to Simon Barteling’s "Open Letter"

Dear Simon

In the preamble of your letter you state that the FMD Forum and you are against the large-scale killing of animals and that we should learn from the past in order to build a better future. I would like to emphasise that I, too, am against the unnecessary killing of animals. I have always considered the consequences for animals when I have been involved in influencing disease control policy. Nevertheless, I recognise that the eradication of certain diseases and their causal organisms sometimes requires the slaughter of animals. In my opinion, however, this should always be supported by scientific evidence. I agree with your statement that we should learn from the past, indeed if we don’t we will surely repeat our mistakes.

You refer to the UK "1927-28" outbreaks (actually the years were 1922-2) and point out that the "stamping out" policy was suspended during the epidemic because the funds for compensating farmers for the slaughter of their animals became exhausted and as a result infected premises were only quarantined. I would like to point out that this is only part of the story because 8 months and 15 months after the epidemic was over outbreaks occurred in Lancashire and Yorkshire. These were subsequently traced back to premises infected during the epidemic. It was concluded that the outbreaks in Lancashire and Yorkshire were due to the movement of recovered ("carrier") animals from premises not "stamped out" during the epidemic. The lesson learned by the British authorities was that "stamping out" of infected premises was necessary and should be implemented in all future outbreaks. This view has been endorsed by the Royal Society Committee of Inquiry into Infectious Diseases of Livestock (Report 2002 para 31: www.royalsoc.ac.uk).

I dispute your view that the UK is against FMD vaccination. This flies in the face of your acknowledgement that research at Pirbright has made many significant contributions to the development and improvement of FMD vaccines. Why would we have bothered to undertake vaccine-related research if we didn’t see a role for vaccination? Why would the UK have been the first country to establish an FMD vaccine bank if it did not recognise that vaccination could have a role in FMD control? Perhaps you are not aware that during the 1967-68 epidemic large supplies of vaccine were imported into the UK from Uruguay and the Government was actually on the point of implementing a programme of emergency vaccination when the epidemic started to decline. Only then was it decided not to proceed with a programme of vaccination.

On many occasions, outbreaks in the UK and other FMD-free, non-vaccinating countries, have been quickly eliminated and have not reached epidemic proportions. The critical elements for success are rapid reaction and a well coordinated response. Therefore the British stance has been to use "stamping out" as the first line of response and to keep the possibility of vaccination in reserve as a possible adjunct to "stamping out". A rush into vaccination is not always either necessary or the best approach.

The fact that vaccination has never been used in the UK does not mean that we are totally opposed to the policy. During my presentation in Brussels I underlined the fact that throughout the UK 2001 epidemic the possibility of employing vaccination was considered. Indeed from an early stage the emergency stock of O Manisa antigen was formulated into vaccine and held ready for use. The Chief Scientist’s FMD Group debated different vaccination strategies throughout the crisis and, with one exception, rejected them all. The exception was the vaccination of cattle in sheds in Cumbria and Devon before turning them out to spring grazing. The Science Group was unanimously in favour of that policy but it did not have the support of the National Farmers Union nor a significant segment of the farming community and so it was dropped (see page 125 of the Anderson Report "Lessons to be Learned Inquiry" www.tso.co.uk/bookshop).

Following are my replies to the queries you raised about the presentation I gave in Brussels.

1. "We weren’t expecting the disease".

Your comments about the World Reference Laboratory are correct. On a daily basis we receive suspected FMD samples from all over the world. We provide a 24-hour, 7-day-a-week, 365-day-a-year emergency diagnostic service for the UK. The International Vaccine Bank (IVB) at Pirbright can quickly provide an emergency supply of 500,000 doses of each of 7 strains of high potency FMD vaccine. That said, when FMD occurred in February 2001 neither Pirbright nor the UK State Veterinary Service was prepared to deal with an epidemic on the scale and complexity of that which was encountered and it inevitably took time to recruit additional personnel. This view is supported by the findings (page 124) of the Anderson Report "Lessons to be Learned Inquiry" which records in a reply from the Chief Veterinary Officer, on 28 March 2002, that "No estimate has been made of the human resource requirements for a vaccination programme. For the purpose of this paper the assumption is made that a stamping out policy would be operated first and that, if sufficient trained resources were immediately available as outlined, vaccination could be avoided" (www.tso.co.uk/bookshop).

2. "When we recognised it, it was widely distributed throughout the country".

In my view the use of ring vaccination around the first recorded focus in Essex in the south east would have exhausted the IVB stock of emergency vaccine and diverted scarce resources of personnel away from the top priority tasks of culling animals on infected and dangerous premises. In fact, the lesson that can be learned from the Essex experience is that the traditional "stamping out" method worked and successfully eradicated the virus. Furthermore, a lesson to be learned is that the novel 3 km and contiguous culling methods were not used in Essex.

Details about the early widespread distribution of FMD in the UK in February 2001 can be found on page 30 of the Anderson Report.

3. "Prof Brown has indicated that sheep were extensively involved and identifying whether sheep are infected or not or have mild disease or not is a major problem. So it was very hard to identify which areas were already infected and, therefore, which areas could or could not be vaccinated".

I agree that for a ring of emergency vaccination to be effective it is essential that all the cloven-hoofed animals in the ring are vaccinated. Ideally, the immune belt should be established beyond the infected area so that one avoids vaccinating infected animals. The point I was making is that when sheep predominate in an infected area it is not an easy task to define the outer limits of the infected area i.e. where to start the inner boundary of the zone of ring vaccination.

I do not agree with your statement that "within the vaccination zone social community life could gradually take its course after 1 to 3 weeks". It would have been very unlikely in the circumstances of the UK 2001 epidemic that vaccination in and around "hot spots" would have been 100% effective, almost certainly there would have been outbreaks in the areas where vaccine was used. Your statement overlooks the need to deal with these. Also, it overlooks the many difficulties associated with the restrictions on the movement of vaccinated animals and their products within and from vaccinated zones. These are complex issues and have major consequences for the livestock industry and animal welfare. I’m sure I don’t need to remind you that as a result of the restrictions on animal movement during the classical swine fever epidemic in Holland in 1997 around 9 million pigs were killed on welfare grounds rather than for reasons of direct disease control!

4. "In a practical sense though at the start of the epidemic we didn’t have enough vaccine to apply mass vaccination. That changed later as vaccine stocks were built up. However, there was an other important issue. Had we changed and brought in vaccination in addition to all the other control measures which were going on - for which we had inadequate resource at the beginning - it would have diverted our personnel away from what I regard as more important activities of stamping out infected premises. Then, of course – and I can’t really go into it now - we did consider what the extra strategy would be. This of course is complicated. It is easy to start a vaccination programme but it is very difficult to get out of it".

Within the first week of the epidemic there were outbreaks in the southeast, northeast, northwest, west and southwest of Great Britain. With the exception of the southeast region the other regions have high densities of animals, especially sheep. Defining zones of vaccination could not be done easily due to the problems of identifying the disease in sheep, as stated previously. Therefore, consideration of the possibility of using ring vaccination quickly moved on to a consideration of regional and, in effect, mass vaccination. Mass vaccination would have required the vaccination of tens of millions of animals. The Royal Society of Edinburgh in its Inquiry into Foot-and-Mouth Disease in Scotland (http://www.ma.hw.ac.uk/RSE/enquiries/footandmouth/fm_mw.pdf) examined the availability of vaccine stocks in 2001 and concluded from various submissions (page 24) that at the time of the outbreaks some 3 million doses of vaccine of the appropriate serotype were available.

While I agree that a programme of mass vaccination could have been started piece-meal with the supplies available, the main argument against this was that the mathematical modellers were of the opinion that culling would be more efficient in eliminating the virus. I agree with your comment that large-scale culling carries with it the increased risk of spreading disease. Since the topic for my presentation in Brussels was FMD vaccination, for which I was allocated 15 minutes, I didn’t have time to deal with the topics of mathematical modeling or the role of epidemiologists in influencing strategy. I’m sure you would accept, however, that large-scale vaccination, like any other policy that requires increased movement of vehicles and personnel in an infected or potentially infected area, also carries with it the risk of increased spread of disease.

The point I was making about the difficulty of getting out of a vaccination programme relates to the following considerations: restrictions on the movement of livestock and animal products from vaccinated zones; prolonged export restrictions; loss of clinical surveillance capability and therefore the need to rely on large-scale serological testing to demonstrate that virus is no longer circulating.

I think you have mis-understood my views about current FMD vaccines and the need for further research. I acknowledge that there have been great improvements in both the quality and safety of FMD vaccines. This is fortunate since, as you know, faulty FMD vaccines, i.e. those containing live virus, were responsible for many outbreaks in Europe in the past. For example, France and the UK in 1981, Portugal, Spain and Morocco in 1983-84 and Italy in 1984-5 and 1986. While I accept that improvement have been made there is still the problem of the delay until protection and the fact that animals exposed to virus during this time can transmit infection. Also, compared to several other vaccines the duration of protection following FMD vaccination is relatively short. The public at large generally assume that FMD vaccines give full protection which is long-lasting. In fact, tests are rarely done to determine the duration of protection which FMD vaccines give against challenge with field isolates, normally the homologous vaccine strain is used and this can give an over-optimistic result. My main point is that if vaccines could be developed that would produce a sterilising immunity and give longer protection then the argument for using them as a first response in an emergency would be stronger.

The topic of vaccination is discussed at length in the report of the Royal Society (Chapter 8) and the recommendation is made (Para 50) that an international research programme should be initiated which is aimed at an improved vaccine that would permit routine and global vaccination of livestock against FMD.

I refute the statement that vaccination eradicated FMD virus from Europe or for that matter from anywhere else. The value of FMD vaccination is that it will control disease and protect animals against productivity losses such as the loss of meat and milk production and fatal infection in young animals. However, to eradicate virus, additional actions, including zoo-sanitary measures and movement control are essential. Before vaccination ceased on continental Europe during 1990-91 outbreaks were dealt with by ring vaccination around infected premises, movement control in the surrounding area, as well as total "stamping out" and decontamination of infected premises. Experience showed that all of those elements – not just vaccination – were essential. You may remember from your visits to Italy in the 1980’s that the authorities there used partial instead of total "stamping out" of infected premises and found that it didn’t work. This was mainly because it generally isn’t possible to disinfect an infected premises which contains livestock (whether vaccinated or not) and so further cases can be expected in and around the area.

I agree that the experience of Uruguay would tend to indicate that sheep do not need to be included in mass prophylactic FMD vaccination programmes. However, I disagree with your statement "this demonstrates that sheep - like wildlife - are dead-end hosts". This may be so under certain systems of management, and with some strains of FMD, but is not always the case. For example, in North Africa between 1989 and 1992, following the introduction of virus with sheep imported from the Middle East, infection continued to circulate in the sheep population and spread from Libya westwards to Morocco. In Tunisia in the autumn of 1989 the epidemic caused the death of more than 50,000 lambs. Similarly, in Italy when vaccination was employed, FMD had a seasonal trend and outbreaks often occurred in cattle in the autumn when sheep were brought down from mountain grazing areas and housed with them. This was attributed to the maintenance of infection in the sheep flocks during the summer months and transmission of virus to the cattle when the two species were brought into closer contact. Therefore, one cannot presume that FMD will always die out in sheep populations.

You ask whether there are any documented cases of animals vaccinated with a qualified vaccine causing new outbreaks. Firstly, as you are aware, the evidence that convalescent carrier animals have caused outbreaks is circumstantial and, if it has occurred, is a rare event. However, the fact that carrier animals do occur, irrespective of their immune status i.e. they can occur after recovery from infection or when vaccinated animals are exposed to virus, means that the risk of spread from carriers is not zero. Secondly, if spread occurs from vaccinated carrier animals it is more likely that this will be seen when vaccinated carriers are moved into a susceptible population since the ratio of carriers to susceptibles will then be high. By contrast, if vaccinated carriers remain in a vaccinated population the ratio will be much lower and so any outbreaks due to carriers will be an extremely rare. Even if they were to occur they would probably be attributed to the continued circulation of virus rather than to carriers. Consequently, it is not surprising that evidence for spread by carriers has been associated with the movement of animals from an area where vaccination has been employed to a non-vaccinated area. These circumstances have been reported at least twice in Zimbabwe and were supported by laboratory results showing that the virus isolates from the new outbreaks were closely related to those that had occurred previously.

I would like to point to the experience of Argentina as an example of the risk which FMD vaccination potentially poses for FMD-free countries. As you are no doubt aware, Argentina ceased vaccination in 1999 but in 2000 it suffered epidemics caused by type O and A viruses. Outbreaks continued into 2001 caused by another type A virus. The source of infection for these three different viruses is believed to be Paraguay which continues to vaccinate but has not reported outbreaks. If this is so then three strains of FMD virus must have been circulating unrecognised in Paraguay. These events make me very wary of accepting the claim that vaccination will eliminate FMD virus. In my view, as I underlined in Para 4 previously, vaccination will control disease but does not, by itself, eradicate virus. Therefore, I support the view of OIE that populations in which vaccine has been used should be regarded as posing a greater risk than those in which it has not been employed. For this reason I also believe that animal populations that have been vaccinated during outbreaks should be subjected to longer-term restrictions than those where "stamping out" without vaccination has been employed.

If you have further comments and queries I would be pleased to discuss them with you when we meet at the Session of the Research Group in Turkey.

Kind regards.

Alex I Donaldson

 

 

Second "open" letter to Dr. A. Donaldson

Dear Alex

I am very glad that you responded to my "open" letter and, in addition to your speech, further clarified your views. Again, I considered whether I should continue the dispute. Why not - as you suggested - close the door and discuss the matter further during the Research Group Meeting in Turkey? In conclusion, I realized that these discussions might not be attended by the EU Parliament Inquiry Committee (EUPIC). Where the outcome of these discussions may influence a future policy, I think the matter is too important to leave essential questions unanswered.

Also, at the end of your letter you come to the central element in the discussion for a future policy and thus of significant importance for EUPIC. You point to risks of (vaccinated) carriers and use the Zimbabwe outbreaks in the eighties and early nineties and the situation in Paraguay and Argentina and then conclude:

"These events make me very wary of accepting the claim that vaccination will eliminate FMD virus. In my view, as I underlined in Para 4 previously, vaccination will control disease but does not, by itself, eradicate virus. Therefore, I support the view of OIE that populations in which vaccine has been used should be regarded as posing a greater risk than those in which it has not been employed. For this reason I also believe that animal populations that have been vaccinated during outbreaks should be subjected to longer-term restrictions than those where "stamping out" without vaccination has been employed".

 

Do you realize the consequences of that belief? Do you realize that as long as vaccination is punished by longer bans on export and other related problems (as you explain in relation to "getting out of a vaccination program") responsible authorities will first try to cover the situation by using stamping-out and large-scale culling? Also, after having taken that approach, it becomes more and more difficult to change to vaccination? First of all –as you describe – because you have to attract your human resources away from the tracing and the culling but, also, it becomes more and more difficult because of "losing face". How to justify the large scale killing and, in connection, the large offers that were asked, when, successively, it is demonstrated that vaccination works?

When you use the word "believe" we come to the heart of the dispute. Until November 2000 I was pretty neutral to that belief. Then, in South Africa I became involved in discussions on how to control an outbreak (also of the pandemic O-strain) that had entered a black rural community, approximately 1000 farmers and 5000 cattle and sheep. The question was whether to vaccinate the livestock of that community or to kill the whole lot. Considering all the circumstances – e.g. villagers trying to bring their livestock to safer areas – in my opinion vaccination was the only option, but epidemiologists / modellers and the meat industry (for reasons of export) wanted to cull all the livestock. My arguments were taken seriously and the applied vaccination brought - as usual - the outbreak to an end.

Confronted with the dramatic consequences of believing that vaccinated carriers are a significant risk for causing new outbreaks, I wondered whether our scientific and practical experiences justify this belief and its consequences. I discussed this with Dr. Paul Sutmoller, who as you know has enormous field experience with FMD in South America and practically spent his whole scientific career studying the carrier phenomenon. We came to the conclusion that any hard evidence of vaccinated animals causing new outbreaks did not exist.

I will return later to the arguments (the Zimbabwe outbreak and the situation in Paraguay and Argentina) that you use to justify that countries suffering from outbreaks of FMD are additionally punished if vaccination is used to control these outbreaks. I first want to discuss some of the other points in your response which are probably of interest to the members of EUPIC.

First of all, knowing you quite well, I have never doubted that you are also against the unnecessary killing of animals. However, the anti-vaccination attitude and the acceptance of the approach of the epidemiologists / modellers have led to the large-scale killing of the 2001 epidemic. Not only that so many million animals were killed also lives of farmers - many dairy farmers and hobby farmers in particular – were damaged not to speak about the reported suicides. Many of the farmers still suffer from the traumatic experiences.

This also brings me to other ethical questions:

- Is any method allowed to control a contagious animal disease?

- Do scientists have a responsibility to judge methods of eradicating a contagious disease also on their effects with respect to number of animals to be killed, personal harm, and harm to rural societies as a whole? In other words, can the approach of modellers – killing of all susceptible animals in the direct environment of an outbreak - in an ethical sense be justified?

- Are international trade organizations allowed – without a proper risk analysis - to reject trade in animals from countries where there is an assumed, however, non-proven risk?

- Are such organizations also responsible for the effects of their legislation? In other words if vaccination is more "punished" in terms of export trade than slaughter, vaccination will often not be used with consequences like in the U.K.

I realize that these are complex, rather political issues as well.

I understood from your reaction that you also had great difficulty with the approach of the modellers and I saw that Paul Kitching greatly criticized them as well for a number of wrong input parameters. Again, their argument that vaccination would not work was based on data obtained after large scale culling not even discussing the fact that this culling also may (considerably) contribute to spreading of the disease.

You must forgive me if I was wrong about the exact years of the UK outbreaks in the twenties. When I wrote my reaction I was at - what one could call - my "holiday resort", an old farmhouse in central France. I collected the data from Fogedby’s review that he wrote upon his retirement (in 1961) as the first secretary of the European (FAO) Commission for the Control of FMD. Unfortunately, I did not bring this documentation with me to verify the exact years but this is not so essential, is it? The Lancashire and Yorkshire outbreaks were also mentioned by Fogedby together with the (few) other cases where there was circumstantial evidence that (recovered) carriers where involved. It strikes me that in all those cases (including those in Yorkshire and Lancashire) bulls were involved. Sexual transmission of FMD? It might fit in the context of the Bastos’ paper where she found evidence that carrier buffalo bulls might transfer disease by mating with cows. Also, I agree with you when you state the cases in Yorkshire and Lancashire, that – with our current knowledge - under European conditions, stamping out of infected premises is necessary.

When you dispute my view that the UK - at least its veterinary society – is/was against FMD vaccination this has nothing to do with my recognition of Pirbright’s important contributions in FMD vaccinology and the many fundamental contributions on how FMD-vaccines work. I know all the names by heart and I feel fortunate that practically all of them I know personally as well.

I don’t think that the presence of a relatively small vaccine bank – that is shared with a number of other countries - does in itself tell much about a pro- or contra-vaccination attitude.

What is the use of a vaccine bank if a Veterinary Service in its contingency planning has not prepared itself to organize the required vaccination teams? Doesn’t that have more significance?

It is the attitude of the (official) British veterinary society – certainly not all the vets - that I indicated and that I encountered the past 1= year at seminars in the U.K. and at discussions in The House of Lords. Practically all the false arguments that were used to justify the anti-vaccination attitude I found back in a letter that Dr. Roger Green wrote to the FMD Forum (Alicia Eykyn). He wrote this letter in his position as President of the Royal Veterinary College and as a consultant for DEFRA in developing a new FMD policy. I did send this letter and my reaction – to which he did not respond – to you. I have attached it (again), since I understood that you missed it.

With my statements on the British anti-vaccination attitude I am in the rather good company of Mr. Morley, the Under- Secretary of State of DEFRA. I quote from his reaction in The Times of July 6th on Mr. Magnus Linklater's view of the foot-and-mouth (FMD) outbreak (Commentary, June 29):

"I don't see how a future vaccination policy would be seen as "a slap in the face for Defra", when it is Defra itself that is promoting the debate and science on vaccine use that could overcome deep-seated objections".

It was these "deep-seated objections" that played a crucial role. It is not essential that vaccination was discussed 10 or 20 times. It is crucial that vaccination was not used where – certainly for the main outbreak areas - it was clear from the rising outbreak numbers, that the culling practice was not proving effective and that vaccination was the only tool left. Because officials very consistently declared that "vaccination was no option", I explained my views in a letter/paper that I sent in the beginning of March to Paul Kitching (no response, probably too busy) and in another version to The Times, The Financial Times, and The Guardian. The F.T. judged it "interesting, but outside the (economic) scope of their journal". The Guardian (Paul Brown) was "very interested" and "certainly would do something with the paper" but never published it, probably because of the objections of my views by British officials.

The anti-vaccination attitude also penetrated into the rest of the EU when the commissioners Fischler and Byrne and also the Dutch prime-minister and minister of agriculture declared that "vaccination was not a solution because it keeps the disease amongst us". It penetrated into the public opinion to the extent that one of our leading morning journals "De Volkskrant", headed an interview with me as: "Dutch virologist knows for sure: vaccination against FMD works!". The day when it was published my telephone didn’t stop and that day and the days following I was interviewed by practically all the Dutch radio and TV actuality programs and journals. This was news!  Vaccination protects against FMD!

I was disappointed when I did not hear strong opposition from Pirbright against these "deep-seated objections", in particular, when it came to the ridiculous "consumers’ argument" against products from vaccinated animals. I don’t need to tell you that for almost half an age inhabitants of mainland Europe were only eating meat and dairy products from vaccinated cattle. Also, that many million kilograms of high-quality "vaccinated meat" are imported into Europe annually from South-America and that supermarkets are eager to sell that meat for good prices. Even EU commissioner Byrne was very poorly informed on this subject when he followed the British "consumers’ argument".

The anti-vaccination attitude also crept into the farmers association. In a discussion in The House of Lords I was confronted with the (anti-vaccination) views of a farmers’ leader. About the same arguments as those of Dr. Roger Green were used. When I explained why his arguments were false, he got red in the face and discontinued the discussion. That is how people react when you attack "belief systems".

What happened in the U.K. was understandable.

Once rural communities are so much damaged by a stamping-out and a (circle) culling policy, it becomes all the time more difficult to recognize (and demonstrate) that vaccination works. One wants to demonstrate that proper choices were made (not "losing face") and wishful thinking makes the authorities declare "It is all under control" and, "we are on the right track". In the meantime the nightmare continues because FMD does not listen to what authorities declare or "modellers" predict.

What can I further add to my previous comments on your arguments why vaccination was not used? Again, if vaccine had been really required, it would have been available in sufficient quantities either from the EU banks or on the international market. If necessary, O1 Campos vaccine could have been imported from GMP-operating plants in South America. As you may remember, the vaccine worked quite well against the pandemic O1 strain in Taiwan.

Certainly where sheep were so extensively involved and where diagnosis in sheep is difficult (your point 3) vaccination of all susceptible animals (including sheep) would have been the only solution. It is the only way to make sure that in any area with a suspicion of the presence of FMD, virus spread from non-clinically diseased sheep will stop and that virus that is already spread will "fall into non-fertile grounds".

I do not agree that, ideally, the immune belt should be established beyond the infected area. Because we enter a more technical discussion here, which we could elaborate on in Izmir I would just like to offer this short version. In my view - which is shared with Paul Sutmoller and was also practiced by the Dutch – all endangered animals should be vaccinated. Vaccination should be carried out both from the outer circle inwards (to build up a protective belt) and from the outbreak farm (s) outwards to protect the most endangered farms. One never knows for sure where the infection has gone. Therefore, vaccination teams have to act very carefully following rules for containment of disease. In The Netherlands the vaccination teams were well instructed and did a proper job because there was no indication that virus was spread from the already infected premises.

When I stated that "within the vaccination zone social community life could gradually take its course after 1 to 3 weeks", I do not mean to say that within that period all problems are solved.

If there is still disease in the area it will – like in The Netherlands – demonstrate itself within a week. As you stated in your lecture, the protection by vaccination is effective within a week. This means that virus spread will stop because the virus can no longer multiply in sufficient quantity and virus that is still spread into the environment will fall into "dead grounds". This means that within the vaccination zone the "social quarantine" of the farming communities can gradually be relaxed.

In Uruguay – without stamping-out of infected premises - within one month after the last vaccination, restrictions on the movement of vaccinated animals and their products were discontinued. A second round of vaccination finished the (few) further outbreaks.

Restrictions are "man-made" and, as stated before, not based on proper risk analysis. Some risks are blown-up and one goes for a zero-risk which, for FMD, does not exist. Other risks are neglected. While – maybe with the exception of the Zimbabwe case (see below) – there are no indications that animals vaccinated with a qualified vaccine ever caused new outbreaks, the presence of vaccinated animals is punished. The possible presence of carriers left from sub-clinical or non-notified disease, after the disease has been controlled by stamping-out, is not punished. I may refer to the carriers that were detected in the UK, quite long after the ‘67-’68 outbreaks had been brought under control by stamping-out. Other risks are also not sufficiently considered or are not really checked and regularly controlled by the OIE when it comes to an FMD-free status (without vaccination).

Let me list them:

1. Lacking surveillance systems and/or lacking alertness for FMD (contingency plans) of veterinary services. In fact some European countries (like The Netherlands) and some South-American countries (like Uruguay) were "punished" by lacking systems in a neighbouring country (see my previous comments).

2. Allowing swill processing on farms. Many outbreaks (e.g. South Africa 2000, U.K. 2001) are associated with the feeding of kitchen offal (swill) that is processed on the farm. In my view allowing swill-feeding on farms is not compatible with the FMD-free status unless the swill is processed in approved plants.

3. The presence of FMD-laboratories and FMD vaccine plants. During the past 20 years there were 4 escapes from such institutions (South America not included). The OIE does not verify whether in the context of an FMD-free status such institutions are really safe, which, for justification of the FMD-free status and for the safety of trade, should be thoroughly checked on a regular basis.

4. Tourism, of the farming community in particular. These days international tourism - by farmers and their families as well – becomes more and more popular. There are many countries where you can find FMD along the streets and in market places like in Hong Kong (pigs), India (cows), and the Middle East (sheep and goat). Although so far there are no known cases of tourists bringing in FMD, there certainly is a (not yet evaluated) risk. The OIE could ask from countries with an FMD-free-status awareness of tourists coming back from countries with active FMD.

The EU could also play an active role in paying attention to these risks. These days there is also the risk of terrorist spreading FMD which should be dealt with in the contingency plans. In my view the FMD-free status - with an associated control-free trade of animals - is only justified if the OIE or another international organization continuously pays serious attention to these points. The countries that profit from this status, could pay for the costs (e.g. in relation to the value of their export).

When you discuss the quality of existing vaccines I agree that there is room for improvement. I disagree, however, that existing vaccines cannot do the job of eradicating FMD and then "what the public at large assumes" is not so important, is it? In South America vaccine producers have to demonstrate that their (oil emulsion) vaccines protect for at least 3 months and batch control is at 6 weeks. The potent EU vaccine bank O1 BFS vaccine raised neutralizing antibody levels that remained constantly high until 6 months when we finished the experiment. I think this is long enough for controlling an outbreak. Neutralizing titres were also high for non-homologous O strains from the Middle East, which indicates that there will be sufficient cross-protection. These data were reported during the Research Group meeting in Israel.

When you write: "I refute the statement that vaccination eradicated FMD virus from Europe or for that matter from anywhere else". Here you are well in the company of Defra’s Mr. Morley - who I quoted above for the "deep-seated objections" - when he continues: "However, it is worth remembering that whilst vaccination is a useful control tool it will not on its own eradicate FMD".

How can you maintain that vaccination did not eradicate FMD when you consider experiences both in Europe, in South America, and in South Africa that you – I am sure – are familiar with as well? Or are you simply referring to what has become a veterinary dogma: "Vaccination against FMD prevents the symptoms but does not eradicate the disease".

Of the many examples that I can give that FMD has been eradicated by consistent vaccination with a qualified vaccine the following:

1. In the sixties The Netherlands suffered from large-scale outbreaks in the non-vaccinated pigs first of type C and later of type O. The virus entered from Germany where general vaccination was not yet applied. The routine Frenkel-type vaccine that was used for cattle did not sufficiently protect the pigs. On the (mixed) outbreak farms the vaccinated cattle were well protected and were left alive, and many of them became carriers (see publications of van Bekkum c.s.). When the outbreaks were under control, by the application of (expensive) concentrated Frenkel-type vaccine - restrictions on transports and markets were lifted. Also, the vaccination of the pigs (in the outbreak area) was - because of the costs – discontinued. Because of their high turn-over rate, the pig population soon became fully susceptible again. Although at the time there were many mixed farms (with cattle and pigs) no further outbreaks occurred neither of "pig-o-phylic" type C nor of type O strain.

2. You refer to the Italian outbreaks of 1985-’86 and of 1987 of type C and type A respectively. I also mentioned them in my previous reaction. The last outbreak occurred in a large pig holding (approximately 15.000 pigs). Because of limited rendering capacity the authorities decided to vaccinate the whole lot with a potent aluminium hydroxide vaccine emulsified in oil. Until 5 days after the vaccination a few more pans became infected that were slaughtered. After that in Italy neither type C nor type A ever occurred.

3. A similar approach as described above was followed in a very large cattle holding (about 18.000 cattle, but don’t hold me to the exact numbers). Also there, vaccination worked very well and disease in this case of the SAT-type did not re-occur.

4. Israel completely relies on (consistent) vaccination only. Cattle are vaccinated twice a year, sheep once a year (the latter species only against type O). At their borders sometimes they have FMD in their (nomadic) sheep and sometimes also in the outbreed meat cattle, in the not yet or once vaccinated calves. The infected animals are left alive and in the outbreak area the Israelis simply apply an additional round of vaccination. There are no indications that outbreak strains re-occur.

5. I can refer to many more examples of recent outbreaks controlled by vaccination without re-occurrence of the disease, that – I am sure – you know as well: Russia 1995, Albania and Macedonia 1996, South Africa 2000 and 2001, Turkey (Thrace) 2001 and as it seems Uruguay 2001.

I hope that above examples can convince you that consistent vaccination – no holes in the vaccination blanket - with a qualified vaccine can eradicate FMD. Also, that products from the vaccinated animals do not represent a risk, or at least that this risk is an acceptable, "near to zero" risk.

Paul Sutmoller and I and a number of other senior colleagues (FMD specialists) consider the (possible) presence of vaccinated carrier cattle also an acceptable "near to zero" risk. We base that on the fact that there is no evidence that the millions of vaccinated (A, O, and C-type) carriers that in the past must have been around in Europe and in South America ever caused new outbreaks.

You use the outbreaks in Zimbabwe (in the late eighties and early nineties) of SAT-type virus - ascribed to vaccinated carriers – to justify "punishment" on trade if vaccination is used to control outbreaks. I am certainly intrigued by those outbreaks; however, how hard is that evidence?

In the first place you must recognize that the SAT-type viruses occurring in southern Africa have a special survival mechanism via wild-life carriers – buffalo’s in particular – that is not known for other FMD sero-types.

In addition, I have my questions whether it really was the vaccinated carriers that caused the outbreaks on farms in the northern districts of SAT strains occurring in central Zimbabwe.

The vaccinated carriers were moved around from central Zimbabwe to farms in the northern districts (sometimes backwards as well) and they certainly were not the only animals that were moved around. The presence of carriers is for the officials an easy argument to explain the outbreaks and the fact that the strains were related to a strain occurring in central Zimbabwe, gave additional evidence. However, was introduction of sub-clinically infected animals excluded? Were all the Lorries that bridged the central and northern districts well disinfected? Were there no other contacts between the central districts and the Northern provinces that excluded transmission of disease? In his paper Gavin Thomson also suggests the possibility that "sexual transmission" from carrier bulls to cows might be involved, certainly something for further study.

In addition to the Zimbabwe story, you use the situation in Paraguay and Argentina to justify the "punishment" on the use of vaccination.

Do we really know in sufficient detail what is going on in Argentina and/or in Paraguay? I visited both countries in 1988 in the context of a fact-finding mission on FMD organized by the European Commission.

In my previous reaction I have already mentioned the complexity of animal husbandry in Argentina, an enormous country with areas that are not quite easily accessible. One might call it a miracle that by vaccination of their cattle only they became free of outbreaks for a number of years. Paraguay (about 400.000 km2) also has many difficult accessible areas in between broad meandering rivers. At the time, I was not very impressed by the efficiency of their veterinary service. For an efficient control manpower and means were lacking. In certain districts, for religious reasons farmers didn’t want to vaccinate. In the neighbourhood of Asuncion, the capital, a Frenkel-type vaccine production plant had open windows in rooms where they splashed around with the cultured virus. Although the situation might have been improved by now, my impression was that official "freedom of outbreaks" did not say too much about the real situation.

How can you use the situation in countries like Argentina and Paraguay to justify that countries like the U.K. (your letter) will tend to stick to a slaughter policy of catastrophic dimensions or, like The Netherlands, have to slaughter all the vaccinated animals?

If you can agree that the risk of vaccinated carriers causing new outbreaks is very small or may be even a "near to zero" risk, together with our colleagues in veterinary science, we can try to evaluate the size of that risk. Accordingly, that risk can even further be reduced by NSP testing of vaccinated cattle herds (and testing for antibodies in the surveillance zone). Then, the presence of vaccinated cattle does no longer need to hit export in a general sense and (dairy and hobby) farmers can have their valuable livestock protected by vaccination whenever appropriate.

To protect trade partners from "hidden disease" (e.g. in sheep flocks) in regions where outbreaks occurred, it is anyhow desirable that for some time after outbreaks – whether controlled by stamping-out or by vaccination - exported animals are quarantined and screened for freedom of antibodies.

I hope that our discussions help the EUPIC in their task to sort out all complicated matter.

Also, I hope to see you in Izmir, to discuss new approaches in the eradication of FMD that really spare the lives of animals and prevent the deeply traumatic experiences of so many in our farming societies.

Kind regards,

Simon

Amsterdam, 27-08-‘02

 
 
 

This correspondence followed the  speech by Dr. Alex Donaldson for the European Inquiry Committee on Foot-and-Mouth Disease at Brussels on 17-06-‘02

 

Thank you Madam Chairman.

 

I don’t need to turn this into a lecture so I will go through this quite quickly but it is by way general information. There are 7 serotypes of FMD they are called O, A, C, A 1,Sat 1,2, 3 there are also strains within serotypes. The importance of this is that animals vaccinated with one type or indeed in some cases with one strain are susceptible to the other 6. Now this causes problems in some parts of the world because several serotypes or strains can co-circulate. Foot and Mouth disease vaccine is relatively expensive in many parts of the world. It sells at about a dollar a dose approximately, so as a result, many developing countries in which the disease is endemic or sporadic, use it selectively and generally, if they do that it is used on high producing dairy cattle. The main immunogen for foot and mouth disease virus resides on the virus capsid and I will show you a cartoon of that in a moment. But in essence there are copies of the VP1 on the protein outside of the vaccine. Generally speaking, FMD vaccines strains are grown in suspension cultures of baby hamster kidney cells (BHK21 cells) and then, after that, the live virus is inactivated by treatment with chemicals. Binary ethylene immine is the most common one. Then, after that, to the concentrate of the virus antigen is added an adjuvant which improves the immune response. That is generally either an alhydrogel saponin or oil. This is just a cartoon showing the way the virus is put together, but, essentially, the RNA core codes for structural proteins which are then assembled into the outside of the virus. It is on the outside of the virus that there are the main epitopes or the components that stimulate an immune response. Then within the core of the virus there is the viral RNA which is the replicative material and it is that which is inactivated by chemical treatment so that the virus in the vaccine does not replicate when it is inoculated into animals.

 

Generally speaking, in the past and by tradition, the alhydrogel saponin vaccines were used to vaccinate ruminant animals, that is cattle, sheep and goats, whereas oil vaccines were used for both ruminants and pigs. More recently there has been a trend towards oil vaccines because they can be used in all species. Now the potency of the Foot and Mouth vaccine can be expressed in what are called PD50 units, for example if a vaccine has 3 PD50, what that means is one can dilute the vaccine a threefold and then it should still protect 50% of the animals. A high potency vaccine - say 6PD50 can for example be diluted 1 in 6 and that should produce protection in 50% of the animals. Now the standard routine commercial vaccine should protect animals in about nine days after primary immunisation and that immunity should last for about 6 or 7 months. Now this of course is not a very long term protection particularly when you compare it with some vaccines, particularly live vaccines which give immunity for life in some cases after one shot of the vaccine. And that would be for example, say measles or rinderpest. A high potency vaccine on the other hand will protect animals in about 4 days. Now that would be a vaccine with 6 PD50 or more but, the shelf life of that vaccine is quite short, possibly because there are concentrated amounts of enzymes that may break down the protein.

 

Now the different strategies of using vaccination. Unfortunately these became mixed up when people argue about the use of vaccination. There is what is called routine mass vaccination and Professor Brown has referred to its use in Europe. Generally, routine mass-vaccination has the objective of reducing the prevalence of disease to a level where it becomes financially acceptable to bring in the additional measures. These are essential and would be disease control by stamping out to eliminate the virus, because vaccination itself will not eradicate – eliminate the virus. You need additional measures.

Then there is buffer or barrier vaccination. That can be used as a sort of an immune wall to protect the free area from the threat of a non vaccinated country or zone, which is geographically nearby. So the immune belt separates the free area from the infected area and protects the free area.

Then there is ring vaccination. Although, it can also be used for barrier vaccination, that is used to create a ring of immunity around the focus of infection to prevent further spread. The strategy there is to apply the vaccine outside the infected area and sometimes that presents problems because in this one you do not want to vaccinate animals that are incubating but delineating, defining which animals are not infected can be a problem.

Then there is what we call suppressive vaccination. It is a type of ring vaccination but in addition to creating the immune belt around the focus one goes right into the area which is infected and you accept that you are going to vaccinate animals that may already be incubating - so it is a mixture.

Around the world there are a whole series of FMD vaccine banks which have been set up as a contingency, to allow countries to use vaccination as an adjunct to stamping out in the event of an outbreak. I have listed them here and I won’t go into details.

There is an international vaccine bank at Pirbright in the UK. The European Community has vaccine banks which are located in Italy and France, then there are many Western European Countries have individual vaccine banks, as indeed do also countries in Central Europe and in South America. Then, separately, there is a North American vaccine bank.

Now Prof. Brown has mentioned that there are consequences, trade consequences, economic consequences to the use of vaccination by a country that is normally free and doesn’t practise vaccination. Now I have listed here the rules according to OIE which were in force last year when there was the massive epidemic in the United Kingdom which then spread into other countries. And according to the rules at that time as written in red here, there was a waiting period of three months after the slaughter - and I must emphasise slaughter - of the last vaccinated animal where emergency vaccination, stamping out and serological surveillance had been applied. Now that is what we were faced with in the UK when considering whether or not to vaccinate. On the other hand there is a period of twelve months after the last case where vaccination has been practised with stamping out. The period extends to two years after the last case when vaccination has been practised without stamping out. Now, just recently, at the last general session of the OIE, the rules have been changed. It has been decided that there is a 6 months period without slaughter of the vaccinated animals, provided that a serological survey -using an accepted NSP test - has shown no evidence of infection, then the country can resume its non vaccinating FMD free status. So this is a more liberal attitude.

Just to give you some background information and I wont lengthen this, to show you the dramatic improvement produced by the implementation of vaccination in Europe. You can see that in the 1960’s there were hundreds and thousands of cases of FMD in Europe the introduction by the Netherlands first and then other countries of mass vaccination of the cattle had a dramatic effect in bringing down the prevalence of disease. Now this sub cartoon here shows you the scale in a different way and you can see that the numbers of outbreaks on a yearly basis was down in many years around 100 or less. But I would make a point that vaccination in Europe stopped during a period from 1990, 1991, to allow free movement from 1st January 1993. But, there was the situation that in the 1980’s there were more than 2000 outbreaks of FMD. Vaccination did not in Europe – I repeat, did not eradicate the virus. There were 2000 outbreaks in the 1980’s most of them in Italy and in Portugal . Then the vaccination policy was stopped in 1990, 1991. Then there were a number of outbreaks before we got into the really bad one in the UK last year.

Now just another example. Argentina stopped vaccination in 1999 and it then had an outbreak starting in the year 2000. In fact it had three epidemics, one due to Type 01, and then two due to type A and this shows you the epidemic profile. Now Argentina reverted to its policy of mass vaccination of cattle because it didn’t manage to control the disease by any other means. And using mass vaccination it did bring the epidemic under control, but it is continuing to vaccinate. That has not eradicated the virus and so the trading positions on Argentina still remain in regard to live animals. It can export its de-boned beef but is still regarded by international authorities as potentially infected. Argentina spread virus into Uruguay. Uruguay had stopped vaccination in 1994, it had one single outbreak in the year 2000 which it eliminated by stamping out, but then in the year 2001 it had a massive epidemic with more than 2000 outbreaks and it is continuing to vaccinate.

Some countries have used emergency vaccination, these are countries which would normally be free and they have used it and I have given examples here (on screen) but one has to point out that in some of them vaccination continued after the disease was brought under control, such as Algeria.

Now during the UK epidemic various vaccination scenarios were considered. In fact we considered all of them and these are the ones that were listed.

The epidemic was first recognised at an abattoir in Essex on the 20th February. But in the first week, at the start of the epidemic there were outbreaks around the country as shown here (on screen). Then it was quite quickly realised, that there had been very extensive spread. Because from the first confirmed case it was recognised, that there was a link to an abattoir in Northumberland and there had been spread from that abattoir in Northumberland – sorry that pig farm in Northumberland - to a nearby mixed cattle and sheep farm. Sheep from that farm went through a local market - the yellow here is a market [pointing to screen] - they went through a local market and then they went through a local market in the North West and there was very extensive movement through the country. Now ring vaccination around the primary focus or indeed the second one recognised would not have worked. Now we believe this is the pattern of spread that occurred to involve neighbouring countries – but I won’t go into this. But the important example I would like you to look at is the Netherlands.  I am sure colleagues here will give more detail on that, but the Dutch in their decision to vaccinate, had advance warning about the presence of infection in the United Kingdom, in fact they had about a month in which to prepare. I understand that they used vaccination really, in order to buy time, because they had limited rendering capacity. Then they decided to use suppressive vaccination because they wanted to regain their export status as quickly as possible – and I sure we will hear in detail and I wont go into it now as to what strategy they followed. Now, the reasons why emergency vaccination or barrier vaccination was not used in the UK are listed here and I have mentioned some of these already.

  1. We weren’t expecting the disease;
  2. When we recognised it, it was widely distributed throughout the country;
  3. Prof. Brown has indicated that sheep were extensively involved and identifying whether sheep are infected or not or have mild disease or not is a major problem. So it was very hard to identify which areas were already infected and, therefore, which areas could or could not be vaccinated;
  4. In a practical sense though at the start of the epidemic we didn’t have enough vaccine to apply mass vaccination. That changed later as vaccine stocks were built up. However, there was an other important issue. Had we changed and brought in vaccination in addition to all the other control measures which were going on - for which we had inadequate resource at the beginning - it would have diverted our personnel away from  what I regard as more important activities of stamping out infected premises. Then, of course – and I can’t really go into it now - we did consider what the extra strategy would be. This of course is complicated. It is easy to start a vaccination programme but it is very difficult to get out of it.

 

What was considered - and indeed what was approved by the Government - was the vaccination of cattle in sheds in Cumbria and Devon, before turning them out to Spring pasture. The specific objectives of that was to save the lives of those animals – which would have totalled about 200,000 - plus to reduce the burden on corpse disposal. Because that was one of the big issues for us, in getting rid of animals, disposing of them as fast as possible. We didn’t want additional cattle added to that if we could avoid it. Now the areas where the vaccination of cattle were considered were Cumbria and the Lake District and then Devon and the South West. However when this policy was muted or stated there was a significant resistance from a proportion of farmers and also the NFU and in addition the British Cattle Veterinary Association. Their main concerns related to economic issues – how would the public react to Supermarkets labelling the products from vaccinated animals. Now this was stated as being a possibility. Of course we have been consuming meat from vaccinated meat for decades but there was the concern about the public perception, there was also concern about the anticipated loss of the export trade vis a vis OIE rules and regulations.

Just finally I would like to say Madame Chairman and Prof. Brown has already stated we do need better vaccines – hopefully those that would block transmission and prevent the establishment of the carrier-state. If we could stop the carrier-state, this would remove a lot of the difficulty of FMD vaccination. And, as he has already stated, we do need to validate the tests - which are already in an advanced state in development - which can differentiate infected from vaccinated animals. We also need the application of mathematical modellers so that very quickly we can look at the consequences of different vaccination strategies and do so objectively and as quickly as possible because with FMD if one doesn’t act quickly then ones options become less and less open. Thank you.

 

 

 

   

 

 

 

 

      

          

 

            

 

 

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