* a vaccine will only give effective protection if it has been tailor-made for a particular strain as immunity is virus type-specific.
This statement assumes that vaccines are either "fully effective" or "not at all effective". In practice, the 1967 O type vaccine, produced at Merial in July, has been used and is still being used in Turkey to vaccinate against the newest strain of type 'O' The vaccine may not be a perfect match but it offers a degree of protection.The EU now has an FMD vaccine bank with vaccines offering at least some protection against all FMD type and is regularly updated, thanks to intelligence coming in from countries around the world.
In this FMD outbreak, the vaccine of the appropriate strain ( ironically) is available just down the road.
* Current vaccines only provide 6 months protection at best
For cattle, two shots are needed when the animal has no immunity at all, as in the UK. In the past, when vaccination was allowed in Europe, cattle older than 6 months were vaccinated only once a year. This did the job.All the same, this point is irrelevant to a successful use of emergency ring vaccination used to stop the cycle of infection in the UK.
We only need to vaccinate in response to an FMD outbreak. Therefore vaccine is needed only to the one infecting strain of virus, the one serotype. Vaccine works well, the high potency killed vaccine inducing a good immunity within 10 days of vaccination, thus preventing onward spread of the virus because there are no new susceptible animals to infect. It is unlikely the whole country would need to be covered by vaccination, but a zone round each infected premise (or in the Pirbright outbreak, round Pirbright and the 2 infected farms would be all that is required). The more infection spreads and proceeds - perhaps unremarked in the case of sheep flocks for instance - the greater the likelihood of further spread into domesitc and wild animals.
* the danger that vaccinated animals, although protected against developing the disease, may become carriers if exposed to new infections of the virus
If they run into infection with the very first days after vaccination it is possible for cattle, sheep and goats to become sub-clinically infected. (Pigs have never been found to become carriers once vaccinated) In such cases, where infection was caught in the first hours following vaccination and before it could take effect, cattle may remain sub-clinically infected "carriers" for some years. Sheep and goats for 3-9 months. The vital point is that after DECADES OF EXTENSIVE SCIENTIFIC RESEARCH, CARRIERS HAVE NEVER BEEN FOUND TO BE ABLE TO SPREAD FMD.With any sort of vaccination, if any host is successfully vaccinated , they may boost their antibody and white cell immunity by exposure to wild type virus but they will not become "carriers" in the sense implied by the argument above. Nor will they excrete virus in to the environment. The whole basis of vaccination is to reduce virus within the environment and therefore host to host infection.
*A policy of prophylactic vaccination would also make it impossible under current EU and OIE regulations to maintain the export trade in meat and livestock.
This is the crux of the matter for big producers - the cutting off of its European and other markets. The current EU trade rules are based on the assumption above - that "Carriers are a Danger" - and this is a misconception that must be examined and put right. In any case, discriminatory tests have been developed, described by the OIE, and successfully used in practice by countries such as Uruguay to demonstrate freedom from infection.- ( Note: Although DEFRA would appear to be relying on Merial, the marker-test principle is helpfully explained in this pdf file from Intervet about its ready to use Chekit-FMD-3ABC marker vaccine. Merial's differentiating marker vaccine would seem to be developed along the same lines. As Intervet says, (page 10 of its 11 page pdf file)
- "...Regional vaccination: if FMD is established in a certain area and the rest of the
country is still free, it may be decided to vaccinate all susceptible animals in the
region. The use of the 3ABC test still enables authorities to monitor the spread of
disease. Slaughter and consumption of vaccinated animals (provided they are
from 3ABC-negative farms) is still possible without the risk on further spread."
This antibody is a signature of virus infection. Surveillance is done 3 weeks after the last case and before the lifting of restrictions. The time scale given for this surveillance is exactly the same whether vaccination is used or not before export as an FMD free country can be resumed.)
That the legislation is still arranged to make vaccination the poor relation in disease control - and for such erroneous reasons - is surely an indication that the industry needs to lobby to change this, rather than fight vaccination itself.
Legislation must take account of the natural history and science behind infection and vaccine induced immunity . Vaccinated meat is perfectly safe. (The UK was always said 'to run its army on Brazilian and Argentinian meat'. Are we to assume that the army is fed substandard produce?)
At present in the UK, no one is arguing for the use of prophylactic vaccination, but pointing out that since
emergency vaccination to live is now part of EU and UK policy the public need to be given some good reasons not to use it. No good scientific or veterinary reasons have been given.
* It is estimated* that the capitalised cost of prophylactic vaccination in the 34 years between the 1967 and 2001 outbreaks would have been £5 billion, at current prices.
It is difficult to comment on these figures. All British cattle ever might have been used for this calculation - but one would need to start with the cost of one vaccination shot and the cost of the person administering it. But the cost of not vaccinating in 2001- the cost of that outbreak still exceeds 12 BILLION EUROS. The risks of new outbreaks are increasing because of globalisation, open borders and the increased mobility of people, animals and the products.While even the 2001 outbreak of FMD cost more than the 5 billion suggested above, the human costs and trauma involved are - as this website aims to show - beyond financial calculation
* under a policy of prophylactic vaccination, there would be periodic vaccine breakdowns, leading to eruptions of disease, with all of their associated costs. And after each breakdown, a new vaccine would need to be developed, and flocks and herds re-vaccinated.
Annual vaccination comes with an annual update of the vaccine - just like that for influenza - based on analysis of samples coming in from around the world.Any Animal Health policy needs constant monitoring of diseases, not just on one's own country but also abroad. Bluetongue gives us a good example: It is possible that BTV-8 is endemic in Turkey but we just don't know. As for FMD however, we do have a good system of collecting data so we know, for example, that a new 'O' type has developed and is spreading in Southern Asia. (NB see also the new Bio Portal)
The arrangements that the observation addresses are not clear. Vaccine should be used as a ring outside an infected area to limit virus replication and should be used in conjunction with restriction on animal movements and, if necessary, limited culling. No one is advocating random vaccination with no other containment measures. The idea is to preserve stocks, limit infection and use all the recourses mentioned to contain disease.
* it would not be practically possible to vaccinate wildlife, a reservoir of infection would almost certainly develop in the deer population, making FMD outbreaks a constant threat.
As long as a certain minimum percentage of susceptible animals is vaccinated, the disease (if present) cannot spread. In the example of the Netherlands and many other European countries, they usually only vaccinated cattle. Sheep, pigs, goats and deer were not vaccinated (see also Uruguay in 2001) - and FMD was got rid of.In all of South America, as a rule only cattle were vaccinated. This an important argument why "carriers" are not important. There were always sufficient susceptible sheep around in close contact with vaccinated cattle. It caused no problem.
It is possible that wild mammals are infected, the odd deer for instance. However deer are extensive and the infection probably keeps coming to a dead end; that is one infected animals does not infect another. In extensively grazing sheep the infection will peter out (as it was left to do in sheep in 1967).
This is in contrast to on-farm stock when a flock or herd is penned into a field or enclosed in a shed.
A correspondent adds:
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On the issue of distinguishing vaccinated, healthy animals from vaccinated carrier animals, I would like to make a few points. The debate about the so-called discriminatory tests has been going on since 2001 and as it shows, there are still many scientists who believe:
- vaccinated carrier animals are a potential problem
- available discriminatory tests are not reliable enough
Now, if we just concentrate for a while on the second argument, there are a number of discriminatory tests in use. I believe Uruguay used one of them (the Panaftosa test) to demonstrate freedom of FMD infection with vaccination which was internationally accepted in 2001, helping Uruguay to start exporting beef (from vaccinated cattle) to the EU again. I mentioned this fact in an article which was published by the OIE in 2001 (page 12 of the enclosed article 'LTO OIE contribution 2002').
The OIE refers to this test in its manual of diagnostics:
-
"Nonstructural protein antibody tests
Antibody to expressed recombinant FMD virus NSPs (e.g. 3A, 3B, 2B, 2C, 3ABC) can be measured by different ELISA formats or immunoblotting. These ELISAs either use purified antigens absorbed directly to microplates or use polyclonal or monoclonal antibodies to trap specific antigens from semi-purified preparations (14, 20, 41, 58). The index screening method used in Panaftosa is described in detail below. Other indirect and competitive ELISAs detecting bovine antibodies to 3ABC have been shown to have equivalent diagnostic performance characteristics (17). This same study corroborates preliminary data from Panaftosa that suggests that the diagnostic performance characteristics of these tests are similar in cattle, sheep and pigs."
Of course, none of these tests give 100% guarantee. The EU has funded research into improvement of these tests and results were satisfactory for herd testing. That is why herd testing is often carried out, allowing for the use of statistics.
The Netherlands, certainly, would after an emergency vaccination, probably test all vaccinated animals. There might be a number of false positives and, in the very unlikely case of virus circulation, there would be a number of false negatives. Because this is what statistics command.
But of course, vaccinating all susceptible animals in an area means that the virus will stop circulating in that area. Yes, some vaccinated animals might catch the virus during the days immediately after vaccination and these animals might become silent carriers (remark: in the case of pigs, carriers have never been found!). The point we have been trying to make over and over again is that, in many trials, these animals have never been shown to spread virus.
This is supported by the fact that the Netherlands got rid of FMD in the 1960s thanks to annual vaccination of only cattle over 6 months. Pigs, sheep and goats were not annually vaccinated as far as we are aware. Some cattle carriers must have been around in the Netherlands (and elsewhere in Europe) but these animals have never caused outbreaks. When Europe ceased annual vaccination in 1991, there must still have been some carrier cattle around for some years. These animals never caused outbreaks, although the live stock cattle population gradually lost its immunity.
At present in the UK, very few are arguing for the use of prophylactic vaccination - that is, wholescale vaccination throughout the country.
(See NFMG letter August 14 2007 )
And another expert adds:
-
I think it is about time that veterinarians had higher specialist training in infection and became practising experts. They should continue to keep up to date with their infection knowledge on an international stage.
There is no equivalent in veterinary medicine to the expertise in human medicine - and it shows. The only qualification for vets at the Royal College of Pathologists is one in General Pathology. In human medicine this was superseded 40 years ago with specialist qualifications in the different subjects - ever growing as understanding and refinement of diagnosis and management takes place.
Virology has more recently split from microbiology. We do not wheel research scientists out from their labs when there is an outbreak of infection in humans. Their knowledge and development of diagnosis and vaccines may be essential in the control by a team of medical infection experts - and these are peer reviewed and up to date with their knowledge. They have a clearly explained policy on the international stage. Experts in human medicine moreover are also not hidebound by rules - usually out of date and made by large groups of civil servants.
There has not been an "objective truthfulness" in veterinary medicine. That is improving perhaps since at least, in this outbreak, a farm is not being called an Infected Premise unless the laboratory confirms this - based on the diagnostic specimens sent to them.
In 2001 the laboratory results were disregarded. In fact in 2001 there were about 1029 farms with confirmed infection and some 1000 so-called IPs were not infected; the laboratory diagnosis was negative.
Again, the outbreak in 2001 was very different. There was no focus of infection and it was later learned that FMD had been present in sheep flocks in Northumbria before it was recognised on the pig farm.
Even if movements had been stopped the day the first outbreak was recognised there would still have been some considerable spread already.
The 2 infected farms in this outbreak have not had movements off the farm (nor within the incubation period of the disease observed on the farms onto the farm, I believe.) The imposition of the severe movement restrictions still in place over the whole of England and to some extent is still present in Wales and Scotland.
This is looking disproportionately harsh, with animals suffering and farmers losing money and being pursued for minor infringements.
Farming outside the South East and the favoured arable areas is often hard. Farmers are struggling to survive at all.
Apart from that given to farmers in the designated zone in Surrey and those whose animals have been culled, there will be no compensation.
In 2001 there was no compensation except for farms that were culled.
Rural tourism and business could also be less severely affected if vaccination within a designated zone was carried out. After 10 days there is no reason for footpaths to remain closed.
Article written for Mary Critchley and Jane Barribal. Dr Ruth Watkins 11th August 2007
Arguments for why DEFRA should have vaccinated as soon as they had the information that the virus at the first farm in Normandy near Pirbright was the historic strain, O1 BFS 67.
This would have entailed a delay of 2 days while the vaccine is prepared for delivery from storage in highly concentrated form, and vaccination teams are readied.- The working hypothesis must be that the virus causing this outbreak derives from Pirbright because it is a historic strain.
- They have the vaccine that is the perfect match for this virus originally derived from the 1967 epidemic of FMD in the UK it being the vaccine strain that 'escaped' from Pirbright.
- They had an area near Pirbright which would have been appropriate to identify as a vaccination zone.
- They could have had the "rose" of the prevailing wind for the dates that they have defined in July when the exposure of the first infected farm was deemed likely to have occurred in case of airborne spread.
- They should know that it would take some time to establish what had happened namely if it was a viral 'plume' of aerosolised virus, or other exposure such as a contact; the latter a point source of contamination rather than contamination spread over a wider area by a plume.
- They should also know that it may not be possible to demonstrate the route of escape from Pirbright. Investigation of possible sabotage or bioterrorist activity would also be very time consuming. Vaccination cannot wait upon these results.
- The biological characteristics of the O1 virus must be known to them, and they should have considered spread by the very many possible routes including water and wildlife such as deer- these could create a problem in control.
- They should be able to explain to us how the excellent killed FMD vaccine works and lay to rest the fears of the unions such as the myth of perpetuating infection by vaccination or the belief that it is necessary to cull uninfected animals just because they have been vaccinated. Also the manner in which vaccinated and infected animals are distinguished on serology testing. The science backing the policy should be clearly articulated.
- The legislation which they, DEFRA, are responsible for both at EU level and within the UK should not give vaccination a penalty over culling, and indeed does not anymore by the EU.
- The supermarkets should state publicly and categorically that vaccinated meat is safe to eat and therefore they will not label vaccinated meat as such nor make any price differential to the producer or consumer.
We are also very lucky that decades of scientific research has provided us with excellent vaccine to all the major serotypes of FMD virus. We are also fortunate that we have these scientific and vaccine establishments in the UK, and we should be ready to take advantage of the benefits they can give us.
- (Whilst we agonise over our FMD outbreak and allow the same arguments for and against vaccine to rage unresolved in the farming community as in 2001, Bluetongue Virus serotype 8 infection, BTV-8, has broken out again this year in Northern Europe - and in Holland alone there have been 125 farms with infected animals in the last 2 weeks.
It first appeared in Holland in July 2006 and came from South Africa by means unknown but most likely in an imported infected ruminant or midges - these can be blown much longer distances than aerosolised FMD virus.
There is no vaccine against disease caused by BTV-8 in ruminants (it does not infect humans but is spread by biting midges so it has spread in Northern Europe inexorably despite control of domestic animal movements) but Merial and Intervet are to undertake development of a killed vaccine.
Whilst such a vaccine may not protect against infection with BTV-8 and therefore not eliminate BTV-8, on the basis of similar vaccines used against other serotypes of BTV, it may protect against disease.
With global warming we may expect the incursion of a number of exotic viruses into the domestic animals of Northern Europe, which if they are insect borne or infect a wildlife reservoir may not be eliminated. May we have diagnostics and vaccines ready to meet them. However fortunately we don't have to live with FMD and vaccination has historically been important in control and elimination of FMD infection from regions or countries. In places like Brazil or Saudi Arabia repeated incursion of FMD cannot be prevented it seems at present from poorer surrounding countries because infected animals are continually imported legally or illegally.
Why does FMD vaccine work so well?
FMD virus belongs to the family of viruses called Piconaviridae. They can be imagined as a box, the capsid, containing and protecting the delicate contents, a nucleic acid genome, an RNA molecule a mere 5000 nucleic acid bases long - as viruses they are simple and minute, much less complicated than bacteria. The function of the box or capsid is to introduce the virus into a cell whereupon it opens to release the genome so it can start to multiply. This gives rise to an infection.
After infection antibody is formed to all the virus proteins, those found in infected cells and those making up the virus itself, including the box , the capsid.
Vaccination is designed to evoke antibody to the outside surface of the box, the virus capsid.
Infection of an animal with FMD virus is distinguished from vaccination by the presence of antibodies to proteins other than those that comprise the virus, those that make up the box, the capsid. In infection antibody is made to all proteins the virus genome encodes. The virus encodes proteins that facilitate its multiplication, many new genome RNA molecules made by copying the infecting genome RNA. The RNA to RNA synthesis this process requires does not occur in any animal cell, so the infecting virus encodes the proteins necessary for this- they are not found in the FMD vaccine.
Viruses in the Picornaviridae family have well conserved neutralisation sites on the surface of their box , the capsid. The neutralisation sites are special antigenic sites that when bound by an antibody that fits perfectly or almost perfectly causes the box to remain closed and therefore the nucleic acid cannot be released even when the virus, or box, enters a cell. The nucleic acid is locked in and eventually the virus particle is harmlessly degraded by the cell. Cells cannot therefore be infected by neutralised virus.
Vaccination is designed to protect against infection by evoking antibodies against the neutralisation site.
These antibodies are present ready to meet a virus and if matched to the neutralisation site on the surface render the virus non-infectious as described above.
There are at least 7 different serotypes of FMD, that is virus types with different neutralisation sites. In order to evoke the protective neutralising antibody the vaccine used must be of the same serotype as the outbreak or epidemic virus. Hence the importance of typing an outbreak virus done most quickly now by sequencing the nucleic acid.
Each different serotype of FMD has been grown up by Merial and inactivated to form the appropriate vaccine to match each and all of the different possible serotypes of FMD. Live attenuated strains of FMD have not been developed for reasons I am not sure of, so the vaccine preparation involves the culture of very large quantities of the wild virus types, the pathogenic or disease causing virus, now historic such as the British Field Strain from the 1967 outbreak for example, before it is inactivated or 'killed' to make up the vaccine.
Though the current circulating strains of FMD, or other Picornaviridae such as polio which has 3 serotypes, do slowly evolve in that changes gradually accrue to the RNA genome the neutralisation site is as a rule highly conserved in this virus family. There must be constraints on its evolution such as any change to the neutralisation site renders the virus incompetent. This is why the laboratory strains of FMD are historic, their genome reflecting a circulating wild type virus of yester year. Historic strains of virus are used in preparation of FMD vaccines as they are in the preparation of polio vaccine.
This is in contrast to influenza virus for example where the vaccine must be updated at least annually to take account of the slow evolution of the neutralisation sites on the heamagglutinin or H molecule on the outside of the influenza virus (if a new H type comes along the vaccine must be reformulated entirely).
All virus families have different characteristics, and to some we may never be able to make protective neutralising antibody at all such as Hepatitis C virus. How lucky we are to have such a good vaccine against FMD - it is theoretically possible to eliminate FMD from the world by vaccination as has nearly been accomplished with poliovirus.
Monday, August 20 2007 ~ "I wouldn't eat vaccinated meat!"
- When someone close to you says such a thing (as happened today) your jaw tends to drop. Have we been so unclear? Do they know no biology at all? And then you realise that in fact people have never been informed. They have a quite reasonable fear of food additives, pesticides and unnecessary chemicals. All one can do is gently point out the following:
- One of the most monstrous pieces of misinformation about vaccination - still going unchallenged and perhaps even encouraged - is that eating vaccinated meat somehow involves 'chemicals'.. No one will tell the truth. The truth is that vaccinated meat has not one trace of "vaccine" in it.
- The immune system, having responded to the jab, destroys the natural viral protein by biodegrading it - it can be likened to a wasp sting - the substance injected is biodegradable, indeed it is biodegraded by the very cells that form the immune (antibody) response
- We spend all our lives being exposed to proteins and infections and carry many, even in our clean modern world, all our lives - but we can protect ourselves from many pathogens that would otherwise lead to painful illness and death. Vaccination for us is one of the blessings of being in the civilised world. Would we deny vaccination to our children and pets?
Ignorance about vaccination is precisely what allows the EU trade rules to persist.
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