Download Bluetongue virus serotype 8 in Northern Europe

Bluetongue virus serotype 8 in
Northern Europe
Talk by Dr Ruth Watkins to Pedigree Beef Society Group
on 24 10 2007 at the Emergency Bluetongue Meeting
held at Stoneleigh National Agricultural Centre
First found near Maastricht in the Netherlands
in July 2006
Documented in >35,000 holdings in 2007
Netherlands, Belgium, Luxemburg, Germany,
France, England, Denmark
Could spread over the whole palaearctic
Infection of ruminants by infected female
midge; insect animal cycle
Bluetongue infection of a
ruminant
• Inoculation of virus into blood from saliva of
biting midge (or needle)
• Viraemia within a few days
• Infectious day ~3 to day ~21, occ. up to 60 or even
70+ days
• Cells of the immune system infected, RBCs,
platelets and endothelial cells lining small blood
vessels
• Vasculitis, leukopaenia, D.I.C.
Test for the presence of virus
• RT-PCR (Reverse Transcriptase Polymerase Chain
Reaction)
• This test detects the RNA genome of the virus
• Blood sample required for lab.
Immune response to infection
• Within first week T-cell specific immune
response
• Then virus specific antibody formed from
B-cells within 14 days, tested for by ELISA
• Antibody is serotype specific – BTV-8
• Neutralizes virus
• Protects against reinfection
• Immunity for life
Meaning of test results
• Antibody –ve, PCR –ve
• Antibody –ve, PCR +ve
• Never been infected
= susceptible, or
within first few days
of infection after
inoculation
• Infected within last 2
to 14 days,
infectious to female
midges
Meaning of test results
• Antibody +ve, PCR +ve
• Antibody +ve, PCR -ve
• Infected within last 14 to
180 days – may or may
not be infectious to
midges (red blood cell
half life is 180 days; virus
sequestered in RBCs until
end of their life and not
infectious to midges)
• Infected more than 6
months ago, or
vaccinated
Disease
• There may be no disease “inapparent
infection” cattle > sheep
• 1ary viral disease, high temp, no appetite,
nasal discharge, swollen face & conjunctivitis,
excoriation of mucosa, frothy saliva, bloody
nasal discharge and pneumonitis, laminitis &
coronitis, muscle stiffness, ulceration of udder,
diarrhoea, loss of fleece, long illness, abortion
and sterility
• 2ary bacterial infection
Treatment of ill animals
• Get animal in shade
• Supportive treatment, fluid and electrolyte
replacement, soft food (cut grass)
• Anti-inflammatory – flunixin
• ? Dexamethasone
• Antibiotics for secondary infection which
follows 1ary viral infection
Morbidity and mortality
No European breed exempt from illness,
figures below approximate
• Cattle
• 10 – 15% ill
• <1 – 3% die
• Sheep
• Up to 50% ill
• 10 - 40% die
The virus
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Orbivirus family
Capsid encloses double stranded RNA genome
10 segments encode at least 10 proteins
At least 25 serotypes, each serotype only gives
protective immunity against itself
• Only serotype in N Europe is BTV-8
• Btv-8 Originates south of the Sahara, virus from
Nigeria best RNA match
• Introduction unknown – infected animal, midge
(lab escapee? Too far for Nigerian midge)
The midge
• The female midge is the vector – nuliparous (immature), parous
(mature egg laying)
• The vector midge must take several blood meals, one to infect her,
subsequent meals to infect susceptible ruminants
• Implicated species are Culicoides obsoletus complex and
Culicoides dewulfi
• C obsoletus @woodland, eggs in leaf litter, damp hay
• C dewulfi @ farms, eggs in dung, horse & cow
• Females must secure blood meal, will fly 2 km
• Attracted to ruminants by CO2
• Prefer to feed on bovines- cattle bitten more than sheep
• Follow animals into housing
• Bite most at dusk and at night but also during daylight
• Midge is tiny, prefers wet warm climate, ‘faunal’ home
Cycle of virus infection between midge
and ruminant
 Parous infected female midge bites a susceptible ruminant
 Period of infectivity of ruminant for midge about 21 to 60 days
after 3 day ‘gap’ (incubation)
 Uninfected female midges (1000s) bite an infected ruminant
 She ingests a blood meal (lays some eggs) and virus infects her
midgut, haemocoel and then the salivary glands
 It takes 7 or more days depending on the ambient temperature for
the newly infected female midge to shed virus in the saliva (called
the extrinsic incubation period EIP). She sheds virus for life.
 About 1 in a 1000 parous females are infected.
 She lives for several weeks and takes several more blood meals
injecting virus with her saliva
 She dies
 Her eggs become larvae then nuliparous females (or males) but are
not infected (no vertical infection).
The winter midge free or not?
Cold kills midges = midge free season = no transmission of BTV between
ruminants
2006 in N Europe new cases in December, restart in May 2007
infection rate highest July through October
BTV-8 overwintered in N Europe 2006/2007
*Importance of housed animals and associated midges*
A few animals infectious for 4 months?
Infected female parous midges ‘slow down’, life is prolonged until spring?
A few nuliparous females of C obsoletus were trapped throughout winter,
Low level of continuous breeding?
Or
Immune reservoir of gamma delta cells in infected animal activated next year
or vertical infection of midges (these last 2 possibilities not proven)
The summer of 2007 in Europe
• Spread of BTV-8 despite
movement restrictions by
the midge flying, ~2km a
day
• Spread by plume of
midges on suitable winds
– some distance within
Europe and across the sea
to England; “midge
tsunami”
• Prevalence of
infection in 2007 very
high in areas infected
in 2006. Average 80%
(30 – 96%)? No
premises uninfected.
‘Infill’ of areas that
escaped last year
• No re-infections
proven
Prevention of infection
• Cannot eliminate midges
• Repel or control midges?
Ivermectin or Doramectin
in blood or dung (killing) or affecting attractants on sheep wool
Deltamethrin or OP or CP sheep dip or shower (repellent)
*No studies on N European midges
*Probably made no difference in experience of EU farmers
Vaccination
 Used for a century in S Africa
 Prevents disease and infection against serotypes in vaccine
 Either MLV (modified live virus) using attenuated virus
 Or inactivated whole virus vaccine
 Could vaccination eliminate BTV-8 infection?
Inactivated vaccine for BTV-8
CVO must order
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Technology proven and available (conditional license)
1ary course 2 doses, annual booster
Safe for very young and pregnant animals
One circulating serotype = monovalent vaccine
Experience of using it in Europe, BTV-2, -4 and -16
Merial vaccine BTV-2 in Balearic Islands led to
elimination of BTV-2. Could BTV-8 be eliminated?
• Animals could be screened before vaccination for previous
infection in hyperendemic areas
• Infection of vaccinated animals could be detected by
testing for RNA (infection within last 6 months)
Live attenuated vaccine (MLV)
• Not available as a monovalent vaccine for BTV-8 from
S. Africa, would take long period to attenuate and prepare
Advantage
Life long immunity
Disadvantages
Spread to susceptible animals via infection of vector
May recombine with other BTV if co-circulating
Vertical infection of ruminants, infection of newborn
Can go ‘off’ if not stored or made up correctly
Therefore not an option for Europe