BluetongueBluetongue Arthur Otter, VLA ShrewsburyArthur Otter, VLA Shrewsbury

Epidemiology of BluetongueEpidemiology of Bluetongue

There are There are 24 serotypes24 serotypes of bluetongue virus (BTV)of bluetongue virus (BTV)Primarily a disease of sheep and cattle > goats and wild Primarily a disease of sheep and cattle > goats and wild ungulatesungulatesThe disease is associated with insect vectors (The disease is associated with insect vectors (CulicoidesCulicoidesmidges) in which the virus replicatesmidges) in which the virus replicatesCaused by a reovirus (an arbovirus: group > 400 RNA Caused by a reovirus (an arbovirus: group > 400 RNA viruses spread by variety of arthropod vectors):viruses spread by variety of arthropod vectors):

African horse sickness virus (AHSV) African horse sickness virus (AHSV) -- horses, donkeys, dogshorses, donkeys, dogsEpizootic haemorrhagic disease virus (EHDV) Epizootic haemorrhagic disease virus (EHDV) -- deer, cattle deer, cattle

Virus typesVirus types

SerotypingSerotyping done at done at PirbrightPirbright (EU Reference Laboratory)(EU Reference Laboratory)Serotypes 1, 2, 4, 9 and 16 have been recorded in Serotypes 1, 2, 4, 9 and 16 have been recorded in southern Europesouthern EuropeSerotype 8 has been identified in northern EuropeSerotype 8 has been identified in northern Europe

previously found in subpreviously found in sub--Saharan AfricaSaharan Africa

The virulence of strains varies The virulence of strains varies Other factors influence disease (breed, age, exposure to Other factors influence disease (breed, age, exposure to sunlight, walking on rough ground and stress)sunlight, walking on rough ground and stress)

BT spread from animal BT spread from animal to to animalanimal

Worldwide occurrenceWorldwide occurrence

Globally was Globally was considered to be considered to be restricted between restricted between latitudes 35latitudes 35ooS and S and 4040ooNNIt has never occurred It has never occurred in the UK prior to 22in the UK prior to 22ndnd

September 2007September 2007

40° N

35° S

World distribution of Bluetongue Virus

The vectorThe vectorCulicoides spp.Culicoides spp.are biting midges which carry a are biting midges which carry a range of tropical diseases range of tropical diseases only female only female CulicoidesCulicoides, are involved , are involved in disease transmissionin disease transmissionBTVBTV is entirely dependent on is entirely dependent on CulicoidesCulicoides for its transmission, but for its transmission, but the species of the species of CulicoidesCulicoides involved involved varies in different parts of the varies in different parts of the worldworldVector competence Vector competence determines if determines if BTV transmitted BTV transmitted –– temperature temperature dependentdependentTemperature also affects Temperature also affects survivability of adults though survivability of adults though winter and activity of midgeswinter and activity of midgesAll stages of All stages of CulicoidesCulicoides also also influenced by moisture: semiinfluenced by moisture: semi--aquatic breeding habitatsaquatic breeding habitatsMidges are strong fliers but also Midges are strong fliers but also passively dispersed by windpassively dispersed by windBTV spread more than 300 km to BTV spread more than 300 km to the Balearics from Tunisia or the Balearics from Tunisia or SardiniaSardinia

Vector competenceVector competenceCompetence to spread disease• Temperature dependant• Heritable• Once infected remain so lifelong• Very efficient transmission

– a single bite will infect and can kill a sheep• Virus not transmitted vertically• Virus unable to develop inmidges at temperatures <10oC• Viral development takes 7-10d

CulicoidesCulicoides sppspp.. ‘‘aerial planktonaerial plankton’’

C. obsoletus & C. pulicaris- present in Britain= potential vectors

C. imicola- main vector worldwide- not present in Britain

C. dewulfii identified as thevector in northern Europe

CulicoidesCulicoidesLifespan averages 2Lifespan averages 2--3 weeks3 weeksUp to 3 months in cooler climatesUp to 3 months in cooler climatesFeed on domestic livestockFeed on domestic livestock

Prefer cattlePrefer cattleFewer on hillsides with sheepFewer on hillsides with sheepFew where climatic conditions more Few where climatic conditions more extremeextremeHorses can be targets for feedingHorses can be targets for feedingHorse muck suitable for breeding Horse muck suitable for breeding

Most active dusk to dawnMost active dusk to dawnRarely enter confined spaces such Rarely enter confined spaces such as buildingsas buildings

C. imicola distribution: known northern limits at 1999 & 2003

BTV & C. imicola in the Mediterranean Basin 1998-2003

Previous European BT incursions ( 1998Previous European BT incursions ( 1998--2005)2005)

Pathogenesis of diseasePathogenesis of diseaseBTV first replicates in the local lymph nodes BTV first replicates in the local lymph nodes ViraemiaViraemia seeds other lymph nodes, spleen, lung and seeds other lymph nodes, spleen, lung and vascular vascular endothelium endothelium and replicates and replicates BTV circulates in bloodstream associated with erythrocytes whichBTV circulates in bloodstream associated with erythrocytes whichprotect from protect from humoralhumoral antibodyantibodyViraemiaViraemia usually lasts 3usually lasts 3--5 days but can be up to 30 days in sheep, 5 days but can be up to 30 days in sheep, 60 days in cattle60 days in cattleEndothelial damage and DIC cause clinical signsEndothelial damage and DIC cause clinical signsIncubation period 6Incubation period 6--9 days9 daysAntibody detected from 6 days post infectionAntibody detected from 6 days post infection

Protective against homologous challengeProtective against homologous challenge

Clinical signsClinical signs

Associated with virus replication in endothelial cells Associated with virus replication in endothelial cells which results in:which results in:

HaemorrhageHaemorrhageIschaemiaIschaemiaInflammationInflammationOedemaOedema

Lesions are common in areas subject to mechanical Lesions are common in areas subject to mechanical trauma and abrasion:trauma and abrasion:

Feet, mouth, eyesFeet, mouth, eyes

Clinical signs Clinical signs -- sheepsheepFever Fever –– up to 42up to 42ooCCRespiratory signsRespiratory signsConjunctivitisConjunctivitisMucosal inflammation and oedemaMucosal inflammation and oedemaPetechiaePetechiae, , ecchymosesecchymoses, cracking of lips, cracking of lipsSalivationSalivationCoronitisCoronitis and lamenessand lamenessAbortionAbortionSome cases subSome cases sub--clinicalclinical

‘Monkey face’

‘Sore muzzle’

CoronitisCoronitis

BTV CLINICAL SIGNS - Wool break

Abortions, stillbirths, weak lambs andcongenital defects

Production lossesand poor thrift

Vascular haemorrhageVascular haemorrhage

Clinical signs Clinical signs -- cattlecattle

FeverFeverReduced milk yieldReduced milk yieldLamenessLamenessMouth and muzzle lesionsMouth and muzzle lesionsSalivationSalivationOral ulcerationOral ulcerationConjunctivitis, Conjunctivitis, lacrimationlacrimationTeat lesions Teat lesions ++ vulvavulva++ CutaneousCutaneous lesionslesionsMany cases subMany cases sub--clinicalclinical

‘Burnt muzzle’

Confirmation of diagnosisConfirmation of diagnosisVirus detectionVirus detection

PCR for viral RNAPCR for viral RNADetects all 24 serotypesDetects all 24 serotypes6 hours6 hoursPCRsPCRs for European serotypesfor European serotypesVirus sequencingVirus sequencingVirus isolation in Virus isolation in embryonatedembryonated eggs (5/6 days), then eggs (5/6 days), then grow in tissue culture (CPE in 3grow in tissue culture (CPE in 3--7 days), check using 7 days), check using PCRPCR

SerologySerologycELISAcELISASNT, VNTSNT, VNT

TreatmentTreatment

NursingNursinggentle handlinggentle handlingmove minimallymove minimallysoft foodsoft foodshadeshadewaterwater

AntiAnti--inflammatoriesinflammatoriesAntibioticsAntibiotics

BTV detection in 2006BTV detection in 2006

First outbreak in flock of 90 sheep in Netherlands 17th August 2006

BTV infected area 2006BTV infected area 2006

Disease outbreaks in 2006Disease outbreaks in 2006

Disease restrictionsDisease restrictions

All animals within 20km of infected farms to be housed All animals within 20km of infected farms to be housed immediately (immediately (‘‘infected areainfected area’’))No transport of animals permittedNo transport of animals permittedInsecticides to be used on farms compulsorilyInsecticides to be used on farms compulsorilyExport ban on live cattle, sheep, goats and Export ban on live cattle, sheep, goats and germplasmgermplasm‘‘Protection zoneProtection zone’’ of 100km around infected farmsof 100km around infected farmsFurther 50km zone around protection zone established Further 50km zone around protection zone established as a as a ‘‘surveillance zonesurveillance zone’’

BTV spread by imported cattleBTV spread by imported cattle

Disease features in 2007Disease features in 2007

Clinical disease identified >2 months earlierClinical disease identified >2 months earlierDisease more severe in sheep and cattleDisease more severe in sheep and cattle

more animals dying directly from diseasemore animals dying directly from diseasemore with severe disease, especially more with severe disease, especially coronitiscoronitis, , necessitating cullingnecessitating cullingdisease also reported in goatsdisease also reported in goats

Infection reported in similar but more Infection reported in similar but more extensive areas of Holland, Germany, extensive areas of Holland, Germany, Luxembourg, Belgium and FranceLuxembourg, Belgium and FranceNow also reported in UK and DenmarkNow also reported in UK and Denmark

Disease Status in Northern Disease Status in Northern Europe 2Europe 2ndnd October 2007October 2007

BelgiumBelgium4138 outbreaks4138 outbreaks20002000--3000 sheep dying each week3000 sheep dying each week

GermanyGermany11, 321 outbreaks, 430 cases per week11, 321 outbreaks, 430 cases per weekfirst reported cases in goatsfirst reported cases in goats

HollandHolland5051 infected holdings5051 infected holdings110 in first week in 2006: 789 in first week in 2007110 in first week in 2006: 789 in first week in 2007

LuxembourgLuxembourg940 outbreaks940 outbreaks1/3 in sheep: 2/3 in cattle1/3 in sheep: 2/3 in cattle

FranceFrance2100 cases2100 casesMost in cattle (low sheep density area)Most in cattle (low sheep density area)

What would happen if BTV What would happen if BTV disease occurred in Britain?disease occurred in Britain?

UK sheep population naUK sheep population naïïve ve –– hence very susceptiblehence very susceptibleClinical disease in sheep > cattleClinical disease in sheep > cattleDirect losses could be severe Direct losses could be severe –– up to 70% case fatality in up to 70% case fatality in outbreaks, usually 15outbreaks, usually 15--30%30%Globally it is one of the most economically important Globally it is one of the most economically important diseases of livestockdiseases of livestockBan on exports of live ruminantsBan on exports of live ruminantsDifficult to control once establishedDifficult to control once established

will now

is

Distribution of positive Distribution of positive farms: 5 areasfarms: 5 areas

IpswichIpswichLowestoftLowestoftEssexEssexKent and East SussexKent and East SussexPeterboroughPeterborough

Disease totals @ 2Disease totals @ 2ndnd

November 2007November 2007

216 report cases216 report cases6060 confirmed outbreaksconfirmed outbreaks27 on surveillance bleeds27 on surveillance bleeds5 outstanding5 outstanding

WhatWhat’’s in a name?s in a name?

Control Zone now known Control Zone now known as the as the Protection ZoneProtection Zone

Protection Zone now Protection Zone now known as the known as the Surveillance Surveillance ZoneZone

Surveillance serologySurveillance serologyAll cattle tested within 3km of IPAll cattle tested within 3km of IPAll cattle in herds in area 3All cattle in herds in area 3--5 km 5 km areaareaAll cattle in herds of > 50 cattle in All cattle in herds of > 50 cattle in 55--10 km area10 km area

Objective: to estimate the prevalence of Objective: to estimate the prevalence of infected cattle herds within 10 km of the infected cattle herds within 10 km of the initially observed initially observed IPsIPs, considered with the , considered with the within herd within herd prevalencesprevalences in order to in order to design future surveillance strategiesdesign future surveillance strategies

Prevalence of infection in UKPrevalence of infection in UK

Clinical disease incidence is lowClinical disease incidence is lowMost herds and flocks have had Most herds and flocks have had only 1 affected animalonly 1 affected animal

Prevalence of infection is lowPrevalence of infection is lowAverage c.10% in cattle herdsAverage c.10% in cattle herdsOne herd of 56 cattle 49% +One herd of 56 cattle 49% +veve< 3% in sheep flocks< 3% in sheep flocksOne flock of 79 sheep 13% +One flock of 79 sheep 13% +veve

Source of Source of infection infection to the UKto the UK

Infected plume Infected plume from Belgium from Belgium detected by detected by meteorologists on meteorologists on 44thth August 2007August 2007

Differential diagnosesDifferential diagnoses

CattleCattle BothBoth SheepSheep

FMDFMDMCFMCF PPRPPR

IBRIBR OrfOrf

Facial eczemaFacial eczemaPhotosensitisationPhotosensitisation

FasciolosisFasciolosisHaemonchosisHaemonchosis

Lameness/laminitisLameness/laminitisOestrus Oestrus ovisovis

Similarities and differences between Similarities and differences between BT and FMDBT and FMD

Oral lesions including Oral lesions including vesiclesvesiclesCoronitisCoronitis -- lamenesslamenessSalivationSalivationPyrexiaPyrexiaClinical or subClinical or sub--clinical clinical diseasediseaseAbortionAbortion

FMD low mortality, BT FMD low mortality, BT potentially high mortalitypotentially high mortalityPigs unaffected by BTPigs unaffected by BTFacial swelling with BTFacial swelling with BTVesicles and ulcers Vesicles and ulcers characteristic of FMD but characteristic of FMD but less common in BTless common in BTFMD highly infectious, BT FMD highly infectious, BT requires vectorsrequires vectorsWindborne spread of Windborne spread of FMD, wind can disperse FMD, wind can disperse vectors of BTvectors of BT

Cattle Cattle -- FMDFMD

‘‘Indicators of diseaseIndicators of disease’’

Usually rapid development of Usually rapid development of lesionslesionsLesions are usually more Lesions are usually more severe than in pigs or sheepsevere than in pigs or sheepOn a farm with all 3 species On a farm with all 3 species the disease is most likely to the disease is most likely to be identified in cattlebe identified in cattle

Sheep Sheep -- FMDFMD

‘‘Maintenance hostsMaintenance hosts’’

Disease can take Disease can take longer to be recognised longer to be recognised than in cattlethan in cattleSigns are often mildSigns are often mildBut animals are But animals are infectious during this infectious during this time and can transmit time and can transmit to othersto others

How hasHow has BTBT rere--occurredoccurred inin 2007 ? 2007 ?

Overwintering occurs by:Overwintering occurs by:persistence in ruminants, orpersistence in ruminants, orwhere vectors are present all year ie warmer climateswhere vectors are present all year ie warmer climates

CulicoidesCulicoides eggs eggs and and larvae may overlarvae may over--winter, butwinter, butThere appears to be There appears to be no no ovarian transmissionovarian transmissionEpisodes Episodes of AHS of AHS are terminated by are terminated by frostfrostBTVBTV--9 has 9 has recrudesced annually over recrudesced annually over a 6a 6--year year period period in in the Balkansthe Balkans

International disease controlInternational disease control

All imported animals from countries All imported animals from countries most recently affected by BTV are most recently affected by BTV are tested for the virustested for the virusSentinel cattle are widely used in Sentinel cattle are widely used in southern Europe to detect and monitor southern Europe to detect and monitor DEFRA collects and monitors midge DEFRA collects and monitors midge populationspopulationsHouse ruminants 6pmHouse ruminants 6pm--8am8amVaccination Vaccination –– problems!problems!

VaccinesVaccinesSerotype specific type required as no Serotype specific type required as no heterologousheterologous protectionprotectionInactivatedInactivated

none available commerciallynone available commerciallyIAH IAH PirbrightPirbright developingdeveloping

Attenuated liveAttenuated liveOnderspoortOnderspoort multivalent vaccine in wide use in Africa, Israel and USAmultivalent vaccine in wide use in Africa, Israel and USASeveral Several diadvantagesdiadvantages

RecombinantRecombinantWould be better vaccinesWould be better vaccinesOngoing developmentOngoing development

Vaccines have only been developed for protection against Vaccines have only been developed for protection against disease in sheepdisease in sheep

Disadvantages of live Disadvantages of live attenuated vaccinesattenuated vaccines

Potential of rePotential of re--assortment with field strainassortment with field strainRisk of reversion to virulence after passage in Risk of reversion to virulence after passage in vectorsvectorsCan cross placenta Can cross placenta –– risk of abortion, foetal risk of abortion, foetal abnormalitiesabnormalitiesContamination of semen (rare with field infection)Contamination of semen (rare with field infection)Cause Cause viraemiaviraemia –– potential for transmissionpotential for transmissionThere is circumstantial evidence of reversion of There is circumstantial evidence of reversion of BTV4 vaccine in Greece and vector transmission BTV4 vaccine in Greece and vector transmission

Potential vaccine requirementsPotential vaccine requirements……..

BTV2BTV2

BTV4BTV4

BTV9 BTV9

BTV16BTV16

Is it all because of global warming?Is it all because of global warming?Temperature and moisture changesTemperature and moisture changes1.21.2ooC rise has occurred in last 100 years in Europe (2x C rise has occurred in last 100 years in Europe (2x global rate of increase); further increases predictedglobal rate of increase); further increases predictedNight temperatures have increased Night temperatures have increased –– facilitates facilitates CulicoidesCulicoidesflight timeflight timeWinter temperature increases more than summer increases Winter temperature increases more than summer increases important important –– have facilitated BTV survival (in vectors)have facilitated BTV survival (in vectors)Further temperature increases will:Further temperature increases will:

Increase Increase CulicoidesCulicoides distributiondistributionIncrease number of vectors, longer seasonIncrease number of vectors, longer seasonIncrease the proportion of vectors which can transmit BTIncrease the proportion of vectors which can transmit BT

Resulting in increased prevalence of BTV in EuropeResulting in increased prevalence of BTV in Europe

The ultimate solution???The ultimate solution???Culicoides nubeculosus: Culicoides nubeculosus: sweet itchsweet itch

http://www.defra.gov.uk/animalh/diseases/notifiable/disease/bluetongue.htmhttp://www.efsa.europa.eu/en/in_focus/bluetongue/outbreak_overview.html

AcknowledgementsAcknowledgements

Dr Phillip Mellor, IAH Dr Phillip Mellor, IAH PirbrightPirbrightDr Dr FalkoFalko Steinbach, VLA WeybridgeSteinbach, VLA WeybridgeAmanda Carson, VLA Amanda Carson, VLA PenrithPenrith