Sheep Veterinary Society
Division of the British Veterinary Association

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Royal Veterinary College, North Mymms, Hatfield, Herts AL9 7TA

(published with the agreement of the author,
with acknowledgements to the British Cattle Veterinary Association and the Veterinary Record)

Introduction

There is increasing pressure for a vaccination programme to control the current outbreak of Foot-and-Mouth (FMD) disease. At its simplest, this would appear to be an obvious and supportable request. Vaccines are used to control, if not eradicate, other viral diseases (e.g. the global elimination of smallpox and possibly, in 2010, rinderpest).  However, for some diseases, there are strategic decisions that need to be considered before embarking on national vaccination. Some of those issues relating to FMD are discussed below.

History of FMD

FMD has been recognised for several centuries to be a highly contagious disease of cloven-footed animals; its major clinical signs being vesicular oral or foot lesions. These vesicular lesions are most easily seen in cattle and pigs whereas in sheep and goats they can be less apparent. It is the inapparence of lesions in sheep that has become so pertinent to the current outbreak.

Although the disease usually has a low mortality in adult animals (2%) it does cause severe and painful pathology with unacceptable production losses (>25%) in milk yield and weight gain (Radostits et al, 1994); in those surviving infection, recovery can take several months. In young animals, however, the mortality can be far higher (60 -90%). In the 1997 Taiwan outbreak of FMD (serotype O), there was severe disease in pigs with high mortality in piglets (>70%). More recently, when the FMD virus (O) strain PanAsia swept through the Middle East, lamb mortality was up to 90% (Paul Kitching - pers comm.) Thus, it is likely that a high death rate in lambs born to infected ewes in the current UK outbreak may yet occur.

To say that FMD is no more than ‘flu (Abigail Wood – The Times (2), 1^st March 2001) is to misunderstand the disease and underestimate the welfare implications.

Introduction of FMD vaccines

FMD vaccines have a long history (Kitching 1992); they are still used extensively in countries with endemic disease (e.g. countries in South America, Africa and Asia). They have never been part of any UK FMD control programme. They were used in the mainland European countries until the early 1990’s together with a ‘stamping out’ policy to eradicate FMD.

‘Stamping out’ is the slaughter of all affected and in-contact susceptible animals on the premises, followed by the disposal of carcasses by burial, burning or rendering. The premises are correctly disinfected and not re-stocked with susceptible animals for a defined period (usually 6 months).

Present position of FMD vaccines

There are a number of FMD vaccines that partly reflects the need to provide protection against all serotypes of the virus. There are seven serotypes: A, C, O, Asia1, SAT1, SAT2, SAT3; with viruses within the A, C, & O serotypes having the widest distribution. Within each serotype there are a spectrum of strains that can be grouped together according to their genomic relationship. The virus causing the present UK outbreak has the designation FMD  virus (FMDV) serotype O, PanAsia strain. In a truly remarkable and rapid epidemiological study, researchers at the Pirbright laboratory have established the molecular sequence of this UK strain and its relationship to other world isolates of the PanAsia strain (Knowles et al., 2001). 

FMD vaccines are presently available from major animal health pharmaceutical companies. All vaccines are derived from viruses grown in tissue culture, chemically inactivated and adjuvanted. The adjuvant for ruminants is commonly Al (OH)₃ with or without saponin, whereas pig vaccines require oil adjuvants. The vaccines are usually marketed as monovalent vaccines, e.g. type A or type O, and, in some cases, it is important to known the strain of virus used in the vaccine e.g. Type O Manisa strain. This allows decisions to be made that match the most appropriate vaccine (providing the closest ‘antigenic homology’) to the outbreak strain. However, in countries where more than one serotype circulates, then bi- and tri-valent vaccines are used (e.g. containing inactivated A, C & O viruses).

There is some variation in the reported composition and duration of immunity following vaccination between the commercial vaccines available (Aftovax/Aftopor – Merial;  Bayovac – Bayer;  Decivac - Intervet ). As a generalisation, FMD vaccines require a primary injection with a booster injection after 1 month, followed by booster inoculations every 6 months.  There has been some recent field evidence that partial vaccine breakdowns have occurred even when vaccines containing the appropriate serotype have been used. This has been reported recently in the present FMDV O PanAsia pandemic where cattle in Saudi Arabia had oral FMD erosions even though they had been vaccinated with serotype O vaccines.  However, vaccine failure can be attributable to several causes, not least the level of challenge.

A BCVA member with experience of the disease abroad says  "We fight FMD all the time in this part of the world and despite awesome herd security and what is probably the most vigorous vaccination schedule in the world we have had 2 outbreaks in the three years since I arrived. In 1999 we suffered with type O, (I believe the same strain that the UK has now) and last year with SAT2."

Is there sufficient vaccine available in the event of a national outbreak of FMD?

The European Vaccine Bank was established by the EU and, on 14th January 2000, set out the designated FMDV antigen banks at three sites in Europe (now at two sites). Within this European FMD vaccine bank, there are 5 million doses of type O strain Manisa vaccines. The FMDV type O strain Manisa is a closely related strain antigenically to the present PanAsia strain (Pirbright laboratories – personal communication). These 5 million doses are, then, the quantity of vaccine that can be requested for immediate use for the present outbreak. Clearly this is insufficient for a general vaccination of all susceptible sheep, pigs and cattle, though there would be sufficient for strategic vaccination. It provides us with an invaluable safety net if all else fails.

Presently, there are no new molecular or ‘marker’ vaccines that are licensed in Europe.

Eradication of FMD from UK

FMD was eradicated from the UK in the early 1950’s by ‘stamping out’ without any pre-emptive vaccination programme. Vaccination against FMD has never been used in the UK.

Definition of FMD freedom

There are internationally agreed definitions for the designation of FMD-freedom for countries and zones. They are encapsulated within the Articles of the OFFICE INTERNATIONAL DES EPIZOOTIES (OIE). (Extracts of relevant sections are shown below)

For those countries that have an outbreak, there is a definition for the steps to be taken and successfully completed before it can reclaim its ‘FMD-free’ status.

Thus, the criteria, agreed internationally, clearly state that to achieve “ FMD free country” status, we must await 3 months after the last clinical case where there is a stamping-out policy. However, new proposals currently being considered would extend the time period to 2 years if all vaccinated animals were not slaughtered.

 In “countries where vaccination is regularly practised” (i.e. not relevant to the U.K.), it may take 2 years to re-establish freedom (Paul Kiching - pers. comm.).

It is difficult to imagine how long it would take to clear FMD without a stamping out policy but it would not be unreasonable to predict that FMD, once endemic, would take a decade or longer to eliminate. Vaccination may shorten this period but we would still have to return to 'stamping-out' in order to achieve FMD freedom.

Does vaccination enhance viral persistence or obscure diagnosis?

It is clear from experimental work that ruminants that come into contact with live virus can become 'carriers' of FMD for an extensive period of time; for cattle ithis is for periods up to 3 years and sheep up to 9 months. There is also field evidence, although no experimental studies, to indicate that carriers can precipitate new outbreaks.

Vaccination can reduce this number of carriers by reducing the general level of virus in the field, but vaccinated animals that have contact with live virus are just as likely to become carriers as animals that have recovered from clinical disease. Thus, vaccination can reduce disease but does not prevent infection: this means that the virus can circulate subclinically.

It is possible to distinguish antibodies from animals that have been infected from those that are vaccinated. However, when a vaccinated animal becomes infected, this distinction is usually lost. This becomes a critical issue for epidemiological surveillance and for export. Thus, any animal with antibodies must still be considered as having potentially been infected. Such animals are not acceptable for importation into FMDV- free countries (see table above OIE Section 2.1.1.2 line 3).

The 1967 outbreak of FMD in the UK

The occurrence of outbreaks on that occasion and the pattern seen in the current outbreak are illustrated in Figure 1.

DAILY OUTBREAKS OF FOOT AND MOUTH
1967 vs 2001  

In the 1967/68 outbreak a total of 432,268 animals were slaughtered between October 1967 and June 1968, whilst in the current outbreak approx 300,000 animals were slaughter or due to be slaughtered in the first 4 weeks. Furthermore, in the current outbreak, it is the rapidly increasing total number of animals involved which is increasing the pressure.  In this outbreak many more sheep are involved.  In 1967, there were about 80 new cases per day and considerable pressure for vaccination. At that time, the majority of new infections were in cattle herds.  Vaccination was, however, resisted and this was documented in the Northumberland Report.

The Northumberland Report

In 1968, the Northumberland committee was commissioned to review the conduct of the 1967 outbreak and make recommendations apposite to 'the policy and arrangements for dealing with foot-and-mouth disease in Great Britain'.

In their detailed and considered opinion, they made the following recommendations and comments (again I have selected and highlighted):

At the General Press Conference in 1969, The Duke presented his Report and, when asked about the possibility of general vaccination, answered

"it would be extremely wasteful of veterinary manpower, and would cost about £13,000,000 in the first year and about £5,000,000 a year thereafter." [The equivalent today would be £128M in first year and £65M per year (Bank of England)].

"it would upset farming practice and it had to be remembered that, to be successful, such vaccination should cover between 72 and 80% of the sheep and cattle population." [Pigs would also need to be considered in the present outbreak]

"a problem which would present itself was that in Britain we had very large number of sheep on scattered hill areas." [The extensive transportation of sheep and sheep marketing has been an added problem not encountered in the 1967]

Ring Vaccination for FMD

In any new outbreak, there is always the possibility, if not pressure, for ring vaccination around infected zones to prevent further transmission. This was one of the recommendations made in the Northumberland Report

They have been used before in outbreaks (though never in the UK) and have been considered a successful adjunct to control in local areas. Obviously, it takes 2-3 weeks after the first vaccination to initiate protective immunity. With the use of high potency vaccine, immunity to aerosol challenge can occur within 4 days. This immunity is temporary and needs a booster inoculation at 3-4 weeks to provide a longer term protection. Thus for ring vaccination, a single inoculation may be sufficient.

However, with the present PanAsia FMDV strain, there appears to be very limited aerosol spread (Paul Kitching - pers. comm.). Furthermore, it is not possible to fully protect pigs by vaccination.

It is clear that ring vaccination can only be effective in containing the outbreak if there is no animal movement beyond the area of ring vaccination.  With the present identification of outbreaks in the first 7 days in Essex, Northumberland, Devon, Wiltshire and Anglesey, ring vaccination could not have controlled this national spread of virus; it is already clear from MAFF reporting that widespread sheep movements and marketing have been central to the epidemiology.  That being said, the subsequent two weeks have shown an even greater increase in disease locations across the UK with particular enlargement of the Cumbrian and Devon outbreaks.

In retrospect (of three weeks only!), it would be difficult to see where ring vaccination could have helped in the initial phase of this outbreak. There may still be a case for strategic vaccination of endangered animals (e.g. the Chillingham herd and zoo animals), however; the political consequences may be prohibitive.  The value of selective vaccination around or downwind of large pig units may also be suggested.

Conclusion

The Northumberland Report (1969) considered general FMD vaccination of all susceptible animals in the UK untenable but proposed that, in future, there may be a role for ring vaccination. In the first three weeks of this outbreak, it would appear that any ring vaccination would have had little influence on the extraordinary spread of the virus by the transport and marketing of sheep throughout the UK. Even if ring vaccination were to be introduced now, it would almost certainly be necessary to return to a stamping out policy later to regain FMD-free country status. The use of vaccines extends the interval between the last FMD case and retrieving our precious FMD-free status from 3 to12 months and possibly as long as 2 years.

Thus, it appears once again that the essential elements to control the FMD outbreak are the availability of professionals in the field, the rapidity of diagnosis, informed policy and courage at the top.

The other recommendations of the Northumberland Report deal with the risks of importation of animal products from FMD infected countries – an issue for another time!

Acknowledgements

Informed guidance has been given from my colleagues at Institute for Animal Health - Pirbright laboratories,Veterinary Laboratory Agency, Merial SAS Pirbright, Intervet and Bayer. Particular thanks go to Dr Paul Kitching at the Pirbright Laboratories, IAH and both Mr Keith Baker and Dr Tony Little at the BVA . The article was commisioned by the BCVA and strongly supported by Dick Sibley, their President.

References

Kitching R.P. (1992) The application of biotechnology to the control of foot-and-mouth disease virus.British Veterinary Journal: 148: 375-388.

Knowles N.J, Samuel A.R., Davies P.R., Kitching R.P. & Donaldson A (2001) Outbreak of foot-and-mouth disease virus serotype O in the U.K. caused by a pandemic strain.The Veterinary Record: 148: 258 - 259.

Mackay D.K.J (1998) Differentiating infection from vaccination in Foot-and-Mouth disease.The Veterinary Quarterly 20: suppl 2 2-5

Radostits O.M., Blood D.C. &  Gay C.C. (1994)  Veterinary Medicine, 8^th Edition pubBailliere Tindall.