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Sent to warmwell.com November 7 2007

Bluetongue serotype 8 vaccination policy for England and Wales

By Dr Ruth Watkins 5 11 2007 - second draft

The restriction zone is presently at the Welsh border but is almost certain to come into Wales before the end of 2007. Thus the policy is for England and Wales.

Rationale for vaccination: is it necessary and should it be voluntary or compulsory?

Vaccination is necessary

If we don’t vaccinate we will have a hyper-endemic area of infection with BTV-8 in East Anglia and Kent next year as it has been in Holland, Belgium, Luxembourg, Northern France and North West Germany in the summer of 2007, and infection will surely spread into the North of England, Wales and the South West of England like it has spread in Europe in 2007. The animal welfare problem created by this relatively pathogenic bluetongue virus strain especially in regard to sheep, and the serious economic loss make control and eradication of BTV-8 necessary.

Britain is not as cold as continental Europe yet the infection re-emerged there in 2007 in all the places where it had been recorded in 2006 so it will definitely come back in 2008 in South East England.

Control of livestock movement alone will not prevent spread of the disease because no-one can control the movement of midges as they have discovered in Northern Europe. Infected plumes of midges can be blown for short and long distances, up to 150 km in the direction of the wind when conditions are suitable. The female midge must secure blood meals to mature and lay her eggs and she will fly 2 km to find them.

The midge and the bluetongue virus

The two species of midge implicated in transmission in Northern Europe are Culicoides obsoletus and Culicoides dewulfi. The virus, the bluetongue serotype 8 virus is genetically most closely matched to BTV-8 viruses from Nigeria where it is of course transmitted by C imicola which is not present in N Europe. How this virus reached N Europe is a mystery as it is too far for a midge plume to travel on the wind over the Sahara and the Mediterranean basin and come to land near Maastricht.

It is not certain if there may not be other species (such as C pulicaris) that will spread infection in N Europe from one ruminant to another, species in which the females also take multiple blood meals. The virus can only be spread by an infected female midge (or by contaminated needles and syringes), it is not spread by carcasses as these are not bitten by midges. Though dogs can become infected, humans and other animals like pigs and horses cannot be infected.

Once the sexually mature and mated female midge has taken an infected blood meal in order to mature and lay her eggs she herself can become infected from the ingested blood if it contains BTV. It may take 10 days in warm conditions, or longer if cooler, for her to become infectious. The virus must pass through her midgut to her haemocoel and then to her salivary glands in which it gives rise to a chronic infection and from whence it is shed in her saliva for the rest of her life. Once BTV is shed in her saliva she is infectious to any subsequent non-immune ruminant that she bites.

C dewulfi is associated with farm buildings and lays her eggs in animal dung. C obsoletus is very much more widespread and is associated with woodland but will lay her eggs in damp hay as well as leaves. The midge C obsoletus may be distributed over much of the palaearctic, the largest ecozone on earth. The farmland of N Europe provides a favourable faunal home for the midge species C obsoletus and C dewulfi with its hedges and trees surrounding the fields with a large population of domestic ruminants, and barns where animals are kept in winter. The midge follows the cattle inside in the winter. Ewes are folded on the fields near the farm for lambing in the spring, if they are not also put inside for lambing in January through April.

The midge will bite during the day (blood engorged female C dewulfi have been caught from the back of cows during the day) as well as at dusk and during the night. They will follow animals into buildings. Small numbers of young female C obsoletus (not mature females that have taken a blood meal) have been caught every week throughout the winter of 2007 in 20 sampling sites inside buildings on farms in the Netherlands.

Repellents have not been found to save the animals in N Europe from infection, nor applied treatments such as ivermectin or doramectin. An insecticide spray may have a local effect, in a confined space, but in the farm yard or in the fields it has no significant effect. I cannot find any information on the effect of sheep dip (organophosphate or cis-pyrethroids) on midge biting and protection from infection. Work has not been commissioned to study the usefulness of any of these putative anti-midge treatments for C obsoletus or C dewulfi in Europe

The numbers of these 2 species of midge are legion. The population is high from July through October, rising in May and June and falling in November and December. Whether there is a truly midge free time when female midges are not biting to secure blood meals and breeding inside buildings where ruminants are housed during January through April is not known. There was a 4 month period when there were no new infections in the sentinel ruminants in Europe, but this was a small sample. The infection re-emerged in early summer of 2007 in N Europe in all the areas it had been present in 2006, and BTV-8 infection has been very intense in these areas and spread in an unprecedented manner for BTV infection in Europe during 2007.

The number of infected females of the transmitting midge species was about 1 in a 1000 in 2006, but I don’t have a figure for 2007 except that 10 fold greater numbers of midge were present in 2007 and the relative frequency of the species changed in Southern Netherlands when C dewulfi exceeded C obsoletus in 2007. Wet weather favours the midge.

The only way to prevent the infection of ruminants is to prevent BTV-8 infection in the midge by vaccination of the ruminants. The midge can take her blood meals but not become infected if there is no infectious virus in the bloodstream of the ruminant to infect her.

The vaccine

The vaccine to be used in N Europe will be an inactivated vaccine. BTV-8 is grown in tissue culture, partially purified and concentrated and then chemically treated to render the virus non-infectious. Merial, Intervet and possibly Fort Dodge are in various stages of development and readiness to manufacture. The vaccine product must undergo batch testing for immunogenicity and safety checks i.e. no residual live virus. Inactivated BTV vaccines have been used in Europe before for serotypes 2, 4 and 16.

Normally 2 doses of inactivated vaccine are required unless the antigen is highly potent with an adjuvant when one dose may be all that is required to raise solid immunity in sheep, as for FMD vaccines where one dose is effective. Inactivated vaccines will require booster doses probably at annual intervals. Larger animals require a greater quantity of antigen in the vaccine to elicit the immune response. The vaccine manufacturer would supply guidance on the interval between two doses and the time it takes to attain a protective immunity (for example 2 weeks between the 2 doses and then one further week before the immune response in the form of protective antibody is high enough to be considered immune- thus 3 weeks from the first dose of vaccine upon completing the course).

Any vaccine programme would have to assume immunity upon completion of proper vaccination. Also it should be made clear that the vaccine protects the ruminant against BTV infection and has no effect on the midge at all. One is vaccinating against BTV-8 and not against the midge.

The EU and payment for vaccine and vaccination

The EU will pay for the vaccine and half the costs of vaccination in addition during the first year to support a control and eradication policy for BTV-8. If the CVOs order vaccine to carry out a control and eradication vaccination programme they can expect the monies promised.

If the vaccination programme is voluntary then the country must pay all expenses, which in the UK will mean the farmer. This could be not only for the vaccine itself, but for a vet and individual tagging such as electronic tagging of sheep if this is made a rule by DEFRA. Pre movement testing may also be required in circumstances set out by DEFRA and have to be paid for by the farmer.

Is it beyond the wit and wealth of N Europe to halt the spread of BTV-8? In fact if we ordered 75 million sheep, alpaca, goat and domestic deer courses and 25 million cattle courses for England and Wales to vaccinate all domestic ruminants they very likely could all be made in 2008 though delivery is only likely to start in June or July.

The neighbouring countries as yet uninfected in N Europe do not wish to also become infected in 2008 and when vaccine is available next year they will expect its efficient use so that plumes of infected midges do not blow into their regions.

The vaccination rules for control and eradication that the EU has so far set out allow vaccination in the control zone and the protection zone (but not in the surveillance zone in DEFRA bluetongue policy). These may well be changed so that vaccination is extended to uninfected areas such as the South of France to prevent spread to the Mediterranean basin. Sensible well reasoned policies with the intention of controlling spread would be accepted with discretion by the EU (as the EU applied to the UK after it first declared itself FMD free in September 2007).

Compulsory vaccination is needed

The vaccine would have to be compulsory because unvaccinated susceptible domestic ruminants can be infected and being infected will serve to amplify the virus through the infection of the female midge. Infection could not be controlled unless virtually all ruminants were vaccinated, and so made immune and not susceptible to infection.

There will be a number of wild ruminants in different parts of England and Wales that of course cannot be vaccinated; a number of wild deer infected with BTV-8 have been recorded in Germany. Also there will be some ruminants who will not respond to the inactivated vaccine, there always are such, and it is hoped these will be very few. If these animals altogether are a very low total percentage of the total ruminant population the number of infected midges that could be generated should be very low because the vast majority of the ruminants they bite are not infectious nor able to be infected because immune. The infection may not be spread and may not be sustained if above 80% are immune.

As domestic cattle are bitten most frequently by midges, if these were all vaccinated this would have the most substantial impact on the total numbers of infected female midge. To rephrase this, the best insurance policy to prevent amplification of the virus by preventing infection of the female midge is to render all cattle immune by vaccination. I would like to know the number of midge bites an individual receives but this is not known- would proteomics help here to identify midge saliva protein in the blood to estimate the number of bites a cow or sheep receives in 24 hours?

Similar to that observed in N Europe in 2006 from a small epidemiological sample, the survey in England in 2007 showed the infection rate in infected sheep flocks is very low and that in infected cattle herds not more than about 15%. Thus it would be best to vaccinate the whole herd or flock in any mass vaccination in 2008. Prior testing would not be cost effective and result in unnecessary delay.

Each susceptible ruminant of any age can be infected and serve to infect many female midges. If the cow or ewe has not been vaccinated (or infected) prior to calving or lambing then the newborn is susceptible from birth, there are no antibodies in the colostrum. If in July the adults are vaccinated but not the young, then at least 50% of the ruminant population will be susceptible to infection and this would be sufficient to sustain and amplify BTV infection to very high levels. Thus vaccination in the summer of 2008 must include the newborn and any young animals as well as the adults.

It has been found in N Europe in the hyperendemic area that anywhere spared BTV-8 infection in 2006 when infection was at a low level was infected in 2007, the infection ‘back-filled’. It is probable that no herd or flock has been spared infection in 2007. The intensity of infection in these areas is such that the prevalence of infection in 2007 is at least 80%. However next year the population will be at least 50% non-immune because of all the newborn animals who will become susceptible when their maternal immunity imbibed with colostrum has worn off. Infection in 2008 will be just as intense as 2007 in N Europe because of this fact unless these animals are vaccinated.

If vaccination was voluntary so that the farmer had to pay all expenses, some would elect not to vaccinate at all, others would vaccinate their most valuable animals. Few would choose to vaccinate all the newborn as well as the adults, especially lambs. They might reason that if they were lucky only a small percentage of the lambs would die and their disposal on the national fallen stock scheme is cheaper than ewes and probably less than vaccinating the entire lamb flock especially if they were obliged to pay for electronic tagging of every lamb as well as vaccination and veterinary fees. Farmers may not be able to justify another big expense like vaccination against BTV-8 until the virus has reached the farm gate.

This would ensure that the virus had a free rein in 2008 so that there would be amplification and intense infection in East Anglia and Kent, and spread gradually to all other parts of the UK even if movement restrictions were kept in place.

The only control and eradication policy is a compulsory universal vaccination policy.

If England had delivery of sufficient vaccine and applied it efficiently to all domestic ruminants in the Midlands and East Anglia before the beginning of June 2008, the virus may not reach Wales in 2008. Unfortunately I think this is very unlikely so Wales should also have an control and eradication vaccination policy.

How should vaccination be done?

Vaccination should begin where the infection will first emerge in 2008 and be most intense, that is in the control zone (now called the protection zone).

The availability of vaccine and its effective use will be well after the emergence of mature female midges (those taking blood meals in order to lay their eggs) and the commencement of spread of infection amongst ruminants will already be established. But vaccination will enormously reduce the "amplification" of the virus, at least by October, because it will then have reduced the number of infected female midges by reducing the infectious ruminants available to them for blood meals. There will be a considerable lag time as the average infectious period of an infected ruminant is about 21 days, and this is about the same as the life of an infected female midge.

The BTV-8 epidemic in SE England in 2008 will eventually be damped down by compulsory universal vaccination in the control zone. There is bound to be some further spread before this occurs unless vaccination is also initially applied much more widely outside the 2007 control zone.

If ring vaccination was to be done from outside in then infected female midges could circumvent the ring of vaccination in a wind borne plume coming from the unvaccinated control zone. The vaccination ring would likely have to be more than 150 km deep from the edge of the 2008 control zone.

Initially upon vaccinating all ruminants in the control zone in 2008, my thought was to vaccinate all cattle outside the control zone first over a very large are all of England and Wales and come back later as vaccine permitted to vaccinate sheep and all other ruminants.

However this would be complicated to achieve, in coming back later to vaccinate the sheep. Better perhaps to do all the ruminants holding by holding. In fact if we order sufficient vaccine we should not be so short of the huge number of doses required to vaccinate a much greater proportion of our livestock in the summer of 2008 than I first thought.

If complicated tagging rules are made for vaccinated sheep such as electronic tagging this may make it more efficient to control infection by vaccinating the cattle first as all cattle have passports and their numbers and whereabouts are known.

However compared to N Europe where BTV-8 has circulated we have many more sheep. The ratio of sheep to cattle is reversed compared to N Europe, and in the uplands may be as high as 20:1 sheep:cattle or after lambing 40:1, so the female midges may take their blood meal more frequently from sheep especially where there are few cattle and they must fly more than 2 km to find a bovine. The vaccination of cattle without vaccinating sheep may not be an effective control policy in the UK.

Possible eradication of BTV-8

The virus will re-emerge next spring 2008. But if every domestic ruminant was vaccinated in the spring of 2009 and immune, then re-emergence of the BTV-8 infection in 2009 might be prevented.

If BTV-8 over-winters either in the female midge (perhaps longer lived in lower temperatures not low enough to kill them) in the barns and sheds, or ruminants with an exceptionally long period of infectivity (such as 60 – 90 days), then it should be possible to eliminate the infection in 2009.

There are fears that BTV-8 may be very difficult to eradicate: if the virus overwinters by giving rise to a vertical infection in the midge, via her egg, or if infection is persistent in ruminants for their lifetime (both hypotheses without firm proof in the field as yet, certainly not in the case of BTV-8 in C obsoletus and C dewulfi, nor the postulated persistent infection of gamma/delta T-cells of ruminants). Equally if large populations of wild ruminants were able to sustain infection.

It would be unfortunate if we did not eradicate BTV-8 when we might in N Europe before it spreads widely to poorer countries in Eastern Europe and the Mediterranean basin and beyond in the palaearctic. If BTV-8 is allowed to infect millions of ruminants and gazillions of midges, strains of the virus might be selected that spread vertically in the midge, from generation to generation via infected eggs, or strains that give rise to persistent infection in ruminants, viruses that are therefore most successful at surviving the winter period and many years beyond.

Preserving important genetic stock

There appear to be problems with long term fertility even in the case of unapparent infection in males, quite apart from infectivity of semen or sterility during the period of acute infection. Vaccination of breeding males (bulls, rams, etc) and of rare breeds would be a priority for 2008.

Trading in England and Wales- both countries within one zone

Bearing in mind new infections of ruminants will be infrequent before June 2008, after the first season of infection ends in January 2008 when there is a period of very little midge activity and no transmission, normal trading could be carried from January to the end of May 2008 (one may think it would be safer to make this the end of April 2008). The risk of spreading infection if an infected animal was inadvertently traded would be small and there is vaccination available in summer 2008.

There will be an interim period during 2008 whilst vaccination is proceeding during the summer, gradually to be extended to universal vaccination in England and Wales before the Spring of 2009.

The Autumn sales should be allowed to proceed next year, 2008, without the constraints of restriction zones in England and Wales otherwise livestock farming and the markets and other businesses will not be viable.

On the other hand as we have pre-movement bTB testing for cattle perhaps pre-movement vaccination for any sheep or cattle to be sold other than straight for slaughter from as yet unvaccinated areas could be done to ensure that unvaccinated animals did not appear in vaccinated areas. This could be instituted for 2008 prior to the universal vaccination planned for 2009.

Vaccinated animals can be traded from East to West and unvaccinated animals can be vaccinated before trading from as yet unvaccinated areas in the West.

If there is a universal compulsory ruminant vaccination policy to be completed for England and Wales for Summer and Autumn 2008 and Winter 2009 then there is no real need for testing prior to movement in the one zone created to include all England and Wales.

Voluntary vaccination and the testing that would be required to maintain the different zones would be expensive for farmers. As I have outlined above it would also make little difference to the evolution of the epidemic of BTV-8 in the UK if vaccination was voluntary. However the latter policy would make a vaccinated animal more valuable than an unvaccinated one.

How will we know where infection has spread in 2008?

Surveillance by bloods can be done on the herds & flocks taken as vaccination is proceeding to see if there is spread of infection to holdings other than those investigated because of illness. Such surveillance would be handled by epidemiologists guided by sampling statistics.

How will we know that BTV-8 has been eliminated in 2009?

Surveillance can be done to look for virus, the RT-PCR test on blood.

During the summer of 2009 young ruminants could be selected to forego vaccination, such as summer born calves to act as sentinels to test for virus transmission by infected midges. I think it would be important to make sure that all domestic ruminants were vaccinated at the time of virus re-emergence in the Spring and early summer so that this might be prevented. The test using sentinel calves could be planned for the peak midge month of October to assess whether circulation of the virus had ceased.

The goals of a universal and compulsory vaccination policy are:

Damp down and confine the re-emergence of BTV-8 disease in 2008.

Protect our East and South coasts from new plumes of infected midges in 2009.

Allow trading to proceed during 2008, as near normal as possible.

The main sheep trade is from September through October when ewes and rams are traded. There is a complex series of movements in the main the upland breeds tending to move to the lowland.

The main cattle sales are in May and again in Autumn particularly for pedigree cattle. Cattle sales of stores and dairy cows occur all summer.

Trade of fertile male stock as well as females are essential to the genetic health of Britain’s livestock.

Protect fertile breeding male ruminants against infection (the bulls, rams etc).

Protect and preserve rare breed ruminants.

Prevent any circulation of the virus BTV-8 in 2009- try to eradicate the infection.

ACTION to carry out the vaccination policy for control and eradication of BTV-8

Order BTV-8 vaccine sufficient million doses as set out below NOW.

Relicense Merial at Pirbright to manufacture BTV-8 vaccine only (this is no longer a containment level 3 veterinary virus in the British Isles)

Do not wait to see which way different countries in Europe will jump- they will be vaccinating and our nearest neighbours have a hyperendemic BTV-8 infection this summer and should follow a plan close to that set out in my vaccination policy of 14 10 2007 for zone A.

Prepare our own policy for BTV-8 vaccination with veterinary surgeons - private or SVS, supervising farmers doing the vaccinating, so government vaccine is properly given. (farmers can form bands and so help each other in the parish)

Expect first millions of vaccine doses (at least 20 million courses) to be delivered in June 2008.

Each vaccinated animal should receive the doses (2) of the vaccine to produce primary immunity at the times stated by the manufacturer, and immunity should be presumed at the prescribed time after the vaccination is completed, without testing.

The local SVS will have a complete register of holdings. The BCMS holds all details of cattle. Thus a systematic vaccination campaign can be organised with the help of farmers and their vets, the mechanism of this would have to be arranged. The vaccination would be compulsory.

In July 2008 vaccinate all the domestic ruminants in the protection (previously called the control) zone as it has been applied in January 2008 or expanded in 2008 early summer whilst waiting for the vaccine. Vaccination should be holding by holding of all susceptible animals there. This means vaccinating all bovines, sheep, goats, camelids and domestic deer, of any age old, adults, young and the newborn.

Expect further delivery of vaccine by the end of July 2008, the next millions (20 million courses at least).

Vaccinate all designated breeding rams, camelids and domestic stags intended for breeding stock- 2009 in the case of sheep - the 2008 rut for deer and - ?year for camelids before the end of July if possible.

Vaccinate all rare breed ruminants.

Vaccinate in August 2008 all the other domestic ruminants within about 50 miles of the East coast and South coast where midge plumes may land in 2008. Unfortunately unless our neighbours vaccinate all their young non-immune ruminants there will be considerable infection again in NW Europe in 2008. However most of this coastal area of England will be in the protection or surveillance zone and already be vaccinated.

From August 2008 vaccinate all domestic ruminants in the surveillance (previously called the protection) zone. As in 6. above, vaccinate every single one, of whatever age or sex or neutered holding by holding.

There is an alternative to 11. the strategy of vaccinating all cattle in August in both the surveillance zone and over the whole of the rest of England and Wales. The sheep flock vaccination can be done throughout the winter. This would have the advantage that most lambs especially hill lambs had already been moved, mostly to slaughter.

Vaccinate ruminants for sale as breeding animals in the as yet unvaccinated areas so that they will not be sold to mingle with already vaccinated flocks and herds (as is done for TB skin testing before sale at present).

Winter 2008 / 2009 vaccinate all the other ruminants as above in England (the North-West and South-West) and Wales. Include all young to be kept into the summer of 2009 such as calves.

During the summer of 2009 all young ruminants such as lambs will have to be vaccinated at such time as their maternal antibody permits vaccination and before it has waned to loose all protective value.

A booster will be due a year after initial vaccination during 2009.

Sentinel animals can be left unvaccinated such as summer born calves to be susceptible sentinel animals in October.

 

The whole point of the policy is to allow trade to resume to near normality in a controlled way without introducing the BTV-8 virus chaotically to areas of the SW and NW of England and Wales where it is unlikely to be established during 2007 or early in 2008. Otherwise the whole livestock business and all the other subsidiary businesses will grind to a halt.

 

The vaccine order should be something like:

*40 million doses (20 million courses) by June 2008

*40 million doses (20 million courses) by the end of July 2008

*sufficient to vaccinate the rest of the national flock autumn winter of 2008 / 2009

*sufficient to vaccinate all young-stock by summer 2009

*sufficient to re-vaccinate all adult stock (one dose per ruminant) in 2009

The vaccines will be funded by the EU if there is a policy to control BTV-8 in England and Wales by compulsory vaccination. If eradication be possible in 2009 this will be achieved by universal compulsory vaccination before April 2009. The EU will also fund half the cost of vaccination during this first twelve months of compulsory vaccination.

 

Sources of information

EU commission Bluetongue regulation, including updated regulation in November 2007.

EU Animal Health policy presentation in the parliament Brussels 17th October 2007.

EU EFSA epidemiological report on BTV-8 in N Europe of April 2007.

ELA and FMD and CSF group meeting in Brussels 17th and 18th October 2007.

Personal information from Professor Rudi Meiswinkel.

‘Climate change and the recent emergence of bluetongue in Europe’, Nature vol 3 Feb 2005 pp171 – 181 by Purse et al.

‘Bluetongue: pathogenesis and duration of viraemia’, Veterinaria Italiana, vol 40 (4) 2004 pp 462 – 467 by MacLachlan

PROMED email programme of the International Society for Infectious Diseases, animal health email series on ‘Bluetongue-Europe’