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The Farm - Bluetongue 
Vaccination against Bluetongue Serotype 8 – A proposal for discussion  
by Dr. Ruth Watkins BSc Hons, BFA Oxon, MBBS, MSc, MRCP, MRCPath - 22nd October 2007

The Bluetongue Vaccine
The manufacturers, Merial and Intervet have stated that the Bluetongue vaccine (BTv8) could be available by May 2008 if they receive orders for it.

Other European countries have already done so but DEFRA is dithering! 
The vaccine is urgently needed!
JB. Ed

INTRODUCTION

The ideal would be to have limitless supplies of vaccine so that all domestic ruminants in Northern Europe can be vaccinated.

Unfortunately this will not happen until perhaps late 2009 or 2010, when both Merial and Intervet are in full production. It is also likely that 2 doses of an inactivated vaccine will be required to prime immunity and an annual booster, also cattle will need a bigger antigen dose than sheep as they are larger animals.

Until then vaccine will come on line slowly from about Springtime 2008. Merial awaits inspections and the go ahead from DEFRA, and this is not likely before January as inspection is to be made in December. I don’t have a timeline for Intervet.

Vaccination would have to be done by farmers with the help of their vets and a witness method validated.

Goal for 2008- Damp down the BTV-8 infection and disease in the endemic areas of N Europe and prevent further outward spread.

I will divide the infected areas as the French (see page 2 of their most recent report):

A = Hyper endemic area. Almost all holdings have infected ruminants, and most have been infected ( the areas of dense red dots)

B = Recently infected area. Some holdings have infected ruminants and the % infected in each holding is low, below 10 – 20 % (zone ‘jeune pale’ with scattered outbreaks, also as in the eastern fringe of East Anglia at present)

C = The zone where infection is imminent or has occurred but unrecognized as animal disease (the zone ‘bleu’)

D = The zone of surveillance comprising the French zone beyond the zone bleu, in which active surveillance is carried out as shown by numbers of holdings or ‘foyers’ sampled on white county areas.

Demarcate each infected country into these areas at the end of December 2007.

Vaccine starts becoming available during the first half of 2008.

During the first 6 months of 2008

Zone A Vaccinate all calves lambs and kids born after the 1st August 2007 through to July 2008. This should be done promptly as a priority. Each will need two doses of inactivated vaccine about 2 to 4 weeks apart to gain full immunity.

  1. The objective is that >80% of all domestic ruminants in zone A are immune from the 1st July. It is said that >80% vaccination of susceptible domestic animals in the case of BTV-2 and BTV-4 using inactivated vaccine has been sufficient to control infection with the BTV vaccine serotype.
  2. The young each year add almost 50% of new susceptibles to an already immune adult population, quite enough to keep the BTV-8 virus in circulation. By choosing a date such as the 1st of August it is hoped to capture all young animals including those whose maternal antibody might have protected them against infection in the 2007 season so that all susceptible young are rendered immune.
  3. The vaccination course should be given between 2 and 8 weeks old so that there is not a gap where there is no protective immunity.

It is assumed that the greater majority of adult animals have already been infected in the hyper-endemic areas. It would be ideal if there were some antibody sampling to check this is the case. These infected animals that have recovered are immune for life against re-infection, or any significant re-infection, with BTV-8 so will never need vaccination with BTV-8 vaccine. It would be a waste of vaccine to vaccinate them unnecessarily when there is likely to be insufficient vaccine. They will also pass on passive antibody to their offspring. This should not interfere with vaccination, normally neonatal and very young animals (including humans) respond very well to virus antigen vaccines (the presence of maternal antibody does interfere with live vaccines hence the wait until this is lost).

If adult animals are screened for antibody in zone A and found to be seronegative then they too should be vaccinated at this time. Any lacunae of susceptible (uninfected) animals in the hyper endemic area in 2008 will act as amplifiers of infected female midges and it is large numbers of these that the vaccine programme is designed to prohibit. The Authorities should be encouraged to provide such antibody screening tests. Otherwise if laboratory tests are done privately vaccine should be made available to vaccinate the non-immune (the uninfected).

Zones B and C Vaccinate all cattle young and old, of any age, male and female: cows calves heifers steers and bulls.

They will all need two doses of the inactivated vaccine.

When this is completed and there is enough vaccine then vaccinate all cattle as above in zone D.

The purpose of this is

  1. To prevent cattle acting as the amplifiers of infected female midges, as cattle are the most important amplifiers. They seem to be infected first when the virus arrives and they are bitten by more midges than sheep because of their larger surface area.
  2. There are less cattle than sheep, in Wales the ratio is at least 10 :1 sheep:cattle. When the vaccine is in short supply this will give the greatest benefit over the great area in N Europe that needs action to prevent BTV-8 infection.
  3. Sheep flocks will act as sentinels. About 80% of infected sheep will become ill alerting one to confirm the diagnosis in a virology lab, thus continued circulation will be detected.

July August September October 2008

Continue to vaccinate all summer born calves in zones A, B, C and D between 2 and 6 weeks of age. (They will all imbibe passive antibody with their mothers colostrum. If not vaccinate from neonate)

If any sheep flock has so much as one infected sheep confirmed in the diagnostic laboratory in zones B, C, and D then vaccinate the whole flock and the contiguous flocks. This should include all adult and young animals even animals that are shortly to go to slaughter. The vaccine is harmless to consume, likewise an infected animal.

If any sheep flock in zone A has so much as one infected sheep confirmed in the diagnostic laboratory by detection of virus RNA then it would be desirable to do antibody testing on the whole adult flock. All antibody negative adult sheep should be vaccinated (the lambs have already been vaccinated). It is reasonable to assume that vaccination of any sheep incubating the infection is unlikely to make any difference to the outcome.

The end of October.

It is hoped that this strategy applied to the Netherlands, Belgium, Luxembourg, France, Germany, Denmark and England and other neighbouring countries infected in 2007, will prevent the huge amplification of infected female midges as has occurred in 2007.

It is also hoped that the cattle vaccination over a very large area combined with a much smaller incursion of infected female midges will have prevented enlargement of the area infected with BTV-8.

The movement restrictions along the present lines would have to remain in place to prevent infected ruminants from starting distant foci of infection. The next year in 2009 movements can become more relaxed see later. A workable movement to slaughter arrangement should be in place, as in France.

The major midge season is over and most lambs have gone into the food chain.

The opportunity of November and December 2008.

This is the window when much more vaccine is available and an opportunity to eliminate infection arises.

The midges implicated in Northern Europe are associated with animal housing in winter and dung for breeding, namely C dewulfi and C obsoletus complex. They follow the animals indoors in winter, into the barns, and maintain the virus by a low rate of midge reproduction or prolonged survival in a torpid state- thus virus is over wintered by a low level female midge breeding programme and the availability of susceptible ruminants (see MacLachlan slide show, over wintering). This is likely to occur in and around barns in the case of BTV-8 in Northern Europe.

The proposal therefore is to ensure that all animals housed in barns on any farm in zones A, B, C and D are immune to BTV-8. Also all ruminants grazing on surrounding fields within 2 Km also need to be immune.

It is possible that sheep out wintered on the hill far from housed animals in barns and dung heaps do not require to be immune as they are unlikely to play any part in the over wintering of BTV-8 in Northern Europe (see caveat).

Wild ruminants in other countries are both at a lower latitude and have different Culicoides species, implicated in the spread of many serotypes of BTV, with different biological niches for example C imicola.

Action to be taken:

  1. Vaccinate all unvaccinated domestic ruminants that fall into the housed and surrounding flocks or herds in zones B, C, and D. In the case of domestic ruminants in Zone A it would be desirable to do an antibody test on all non-vaccinated animals, with the view of vaccinating only those without antibody. This would ensure that all domestic ruminants in zones A, B, C, and D were immune in the barns and on the surrounding fields.
  2. The reason for ensuring immunity by the end of December 2008 is that a few infected animals may remain infectious for some 20 days to female midges that themselves can live at least 3 weeks (may be longer in the cool weather). In order to break the cycle before a mild spring or summer all infected female midges should have died with no newly infected female midges generated. The virus is not transmitted vertically in ruminants or in the midge. (current scientific opinion)

Goal for 2009- Eradication of BTV-8 infection

In the first 3 months of 2009

  1. All ruminantes vaccinated during the first 6 months of 2008 will need to have a booster dose of vaccine.
  2. All out wintered sheep flocks or other animals in zones B, C and D that have not been vaccinated will need to be vaccinated either when they are brought in or before lambing or calving on the hill. This should be within the first 3 months of 2009. Those in Zone A should have antibody screening if not vaccinated and vaccination of all non-immune or susceptible animals.
  3. Vaccinate all newborn calves, lambs and kids in zones A, B, C and D.

In the months April, May and June of 2009

  1. Continue to vaccinate all newborn calves, lambs and kids.

In the second half of 2009

  1. Continue to vaccinate all newborn calves (lambs and kids if any born).
  1. Carry out the booster vaccination programme in all the vaccinees.

It is hoped there will not be a season of BTV-8 disease from July onwards in 2009.

There will be no susceptible domestic ruminants in zones A, B, C, and D from July onwards in 2009.

Caveat: There is a hypothesis of persistence of bluetongue virus in gamma/delta cells of the immune system but it has not yet been proven that this does account for over wintering. If true a female midge in the next season would be infected from a ruminant infected during the previous season and who has cleared viraemia and infectivity via blood months previously. The inflammation from midge bites is hypothesized to facilitate reactivation of the virus in the gamma/delta cells attracted to the inflamed skin and so infect further biting midges. If this hypothesis is true then the virus cannot be eliminated until new infections are terminated and all those previously infected have died.

Monitoring for infection

Those few that have been missed somehow or who have not responded to the vaccine (which will happen in a small proportion of vaccinees) will be insufficient, < 20% of the entire ruminant population, to maintain circulation of the virus (it is hoped wild ruminants will not be great enough in number). The reason every effort must be made not to exclude flocks or herds is that the proportion of non-responders and wild ruminants if too great may make the vaccine program unsuccessful at elimination of BTV-8. Surveillance can be done by laboratory testing so it is preferable not to have unvaccinated sentinel farms etc within the vaccinated area.

The inactivated vaccine is not a DIVA vaccine. Thus infection will have to be confirmed by RT-PCR for the virus RNA in whole blood, (usually an EDTA blood sample) in a vaccinated animal. In an unvaccinated animal either antibody or/ and the more expensive RT-PCR can be done.

Confirmation of infection by the virology lab should be done in all herds or flocks suspected of disease. Also surveillance should be carried out outside zone D.

There should be sufficient vaccine in 2009 to give it routinely to all domestic ruminants in the affected and surrounding countries over the winter period to ensure that re-emergence does not occur in summer 2010.

Movement restrictions

These can be relaxed in 2010 and may be relaxed in 2009 in the affected countries. Movement out of a vaccination zone and into a non-vaccination zone or country may require an RT-PCR in a vaccinated animal to prove non-infection., instead of serology as now. Alternatively a DIVA vaccine may come into use in 2009 or 2010 so that the cheaper test for antibody can be done to prove non-infection.

Ruth Watkins - 22nd October 2007



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