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Vaccination against bluetongue serotype 8:
a proposal for discussion
(prepared 14 Oct 2007)
Dr Ruth Watkins
Hill Sheep Farmer, Wales
Formerly, Consultant Clinical Virologist, St Mary's Hospital, London
Filed 01 Nov 07
©Ruth Watkins
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. Cattle will need
a bigger anitgen 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 = Hyperendemic 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 unrecognised 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.
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.
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 tham against infection
in the 2007 season so that all susceptible young are rendered immune.
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 reinfection, or any significant reinfection, 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 hyperendemic 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 overwintered
by a low level female midge breeding programme and the availablility
of susceptible ruminants (see MacLachlan slide show, overwintering).
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 outwintered 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 overwintering
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:
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.
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,
according to current scientific opinion.
Goal for 2009- Eradication of BTV-8 infection
In the first 3 months of 2009
(1) All ruminats vaccinated during the first
6 months of 2008 will need to have a booster dose of vaccine.
(2) All outwintered 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, Cand D.
In the months
April, May and June of 2009
Continue to vaccinate all newborn calves, lambs
and kids.
In the second half of 2009
Continue to vaccinate all newborn calves
(lambs and kids if any born).
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 overwintering.
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 programme unsuccessful at elimination
of BTV-8. Surveillance can be done by laboratory testing so it is
preferrable 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 proove 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 proove
non-infection.
©Rruth Watkins |
