MIC1IEP

Zoonoses &
27th May2016
ANNA MORRIS
ROOM 310
THOMAS CHERRY BUILDING
PH: 9479- 1501
a.morris@latrobe.edu.au

Animaltransmitteddiseases
Zoonoses :animaldiseases
primarilyofanimalstransmittedto
humans
Nonhumanvertebrateisnatural
host
Transmissionviadirectcontact,
aerosolsorbites
Difficulttoeradicateas
numberofanimalreservoirsis
high

Zoonoses
Microorganismfoundinanimals
Mayormaynotcausediseaseinanimal
Maycrossspeciesbarriertocausediseaseinman
Animalhostactsasreservoirofinfection
Spreadtootheranimalsandman
Examples:
Rabies
Arboviruses
Animal&birdreservoirs,transferredto
otheranimalsandmanviainsectbite
Usuallysubclinicalinfectioninanimals&
acuteinfectioninman

Zoonosis example
InfluenzaA
Infectionofpigsandbirds
Crossesspeciesbarriertocausediseaseinmanindirectcontact
Notusuallytransmittedfromhumantohuman

InfluenzatypeA
AvianInfluenzaH5N1
Birds&humans

SwineFluH1N1
Pigs&humans

EmergingInfectiousdiseases
Neworemergingdiseasesareonesthatareon
theriseagainorhaveneverbeenseen
previously
90suchinfections
reportedafter1980
mostarecausedbyviruses
mostzoonoses
Originateinanimals
AIDS,SARS,MERS,Hendra(HeV),Bat
Lyssavirus

HendraVirus
Yearofemergence:1994
OutbreakinBrisbane,Qld,Australia
InitiallynamedEquineMorbillivirus
Acuteequinerespiratorysyndrome
Deathofhorsetrainer
Deathof14racehorses
Encephalitislikesymptoms
Strapperalsohadantibodies
1995deathinMackayofassistanttohorse
autopsy

Hendravirus
Previouslyunknownvirus
Transmissionviabloodornasal&oralsecretions
Hassincecaused3deaths
Crossedspeciesbarrier
Naturalreservoir=fruitbats
Causesinfectionofhorses,cats,dogsandhumans
OnlypresentinAustralia

OnlyfoundinAustralia

HeVepidemiology1994 Sept09
Date

Location

Equinecases

Humancases

Aug1994

Mackay, QLD

Sept1994

Hendra,QLD

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Jan 1999
Oct2004

Cairns,QLD

Dec20014

Townsville,QLD

June2005

Peachester,QLD

Oct2006

Murwillambah,
NSW

June2007

Peachester,QLD

July2007

CliftonBeach,QLD

July2008

Thornlands,QLD

July2008

Proserpine,QLD

Aug2009

Cawarral,QLD

Sept2009

Bowen,QLD

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HendraVirus
Paramyxovirus
GenusHenipavirus
Newgenus
ContainsHendra&Nipahvirus
NamedafterHendra,suburbofBrisbane
Endemicinfruitbats
Antibodiesinupto50%offruitbatsin
mainlandAustralia

HendraVirus:ssRNA,enveloped
GproteinattachestoEFNB2proteinonmammalianhostcell

Transmission
Directtransmissiontohorsesfrombatsrare
Infectionviacontactwithcontaminatedpastures
orhorsefeed
bodyfluids
Excretions
Transmissiontoman
Viaclosecontactwithinfectedhorses
Heavyexposuretoinfected:
respiratorysecretions
Bodyfluids
tissue

Reportedcases,Sept1994
40yearoldstablehand
Contactviarespiratorysecretions
Influenzalikeillness
Recovery
Norelapse
49yearoldtrainer
Contactviarespiratorysecretions
Pneumonia,multiorganfailure
death

Symptoms
Humans
Appearwithin5 16days
Initialsymptoms:
Fever,cough,sorethroat,headache,malaise
Selflimitinginfluenzalikeillness

Furtherprogressofinfection:
Meningitis
Encephalitis
Eitherresultingindeath

Exposure
Novaccineavailableforhumans

Equinecases&symptoms
Courseofillnessforfatallyinfectedhorses:2days
frominitialsignsofinfectiontodeath
HeV excretedinrespiratorysamplesatleast2days
priortosymptoms
Fever,tachycardia
Respiratorymanifestations
Tachypnoea,respiratorydistress,nasaldischarge

Neurologicalmanifestations
Ataxia,headtilt,facialnerveparalysis

Noevidenceforsubclinicalinfectionofhorses

EquivacR HeV

Evolutionofavaccine
Newvirusidentified&placedintonewgenuswithin
Paramyxoviridae family
14clustersofHendravirusinfectioninhorsesbw 1994
2010
2011 18outbreaks,24casesinQLD&NSW
Dogtestspositive
Confirmedoutbreakinhorseswestofdividingrange
Resultedindeathof20horses

Raceforvaccinedevelopment
Vaccinelaunchedin2012
2013vaccineshowntobeprotective6monthsafter
vaccination
VaccinationnowrecommendedbyAustralianVeterinary
Assoc

Aug2015:fearshorsesaredyingduetoover
vaccination

Zoonoses
Domesticanimals:Routinevaccination
ensureshealthofpet&alsopreventsdisease
spreadtohuman
Feralanimals:Nocontrolofdiseasesinthese,
novaccination&noveterinarycare
Mostzoonosesresultfromcontactwithwild
animals

Rabies
ReservoirsinUSA skunks,racoons,coyote,foxes,
bats&somedomesticpets
Endemicindogsindevelopingcountries
Worldwidedeathtoll>50,000annually
1milliontreatedforrabiesbitesperyearworldwide
&20,000intheUSA
3casesreportedinUSAannually

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RabiesVirus
Helicalsymmetry,Enveloped,RNAvirus

Rabiessymptoms
VirusinfectscellsofCNS&braintissue
Symptoms:headache,fever,malaise,excitation,
anxiety,dilationofpupils&excessivesalivation,
delirium,convulsions,
hydrophobia
Deathoccurswithin2 6daysfollowingsymptoms

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CycleofInfectionofRabiesvirus

Rabiesdisease
TransmissionofRhabdovirusviasalivaofinfected
animal
entryintobodyafterbite
Contactwithmucousmembranes

Replicationatinoculationsite&thentravelsto&
infectscellsofthecentralnervoussystem
ProliferatesinThalamus&
Hypothalamus

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Pathogenesis
1.animalisbittenbyrabid
animal
2.Virusentersviasaliva
3.Spreadofvirusthrough
nervestospinalcordand
brain
4.Incubationperiodfor3
12weeks
5.Virusreachesbrain,
multipliesrapidly,passesto
salivaryglands.Animal
showssignofdisease.

Hypothalamuscontrols:
1Autonomiccontrol
2Temperatureregulation
3Thirstandcontrolofbodywater
4Appetitecontrol
5Endocrinecontrol
6Emotionalreactions
7Sleepandwakefulness
8Stressresponse
http://www.neurophysiology.ws/diencephalo
n.htm

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Treatment
Lackoftreatmentresultsinuncontrollablespasmsof
throat&leadstoeventualrespiratoryparalysisand
death
Treatmentbyrabiesvirusantibodies&inactivated
rabiesvaccine
Treatmentiseffectiveduetolongincubationperiod
inman upto9months,(butcanbevariable)
Incubationperiodindogs10 14days

Prevention
Vaccinationofonlyatriskindividuals
Domesticanimalsvaccinatedroutinelyduetorisk
ofcontactwithwildanimals
Oralvaccinationofwildanimalpopulationbyfood
baits

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RabiesinAustralia?
Australiaisrabiesfree
Remotelocationandislandcontinentprevents
diseasesendemictoothercountriesfromspreading
here
Internationaltravel&disregardoflocalcustomslaws
risktheintroductionofinfectiousdiseasesnot
previouslyseenhere
RabiespresenceinneighbouringIndonesiaisa
concern

RabiesinAustralia
3deaths 1867,1987&1990
Causeofdeathestablishedafterdeath
Brisbane:9yearoldmale
monkeybiteoccurredinIndia16monthspriortoillness

Sydney:10yearoldfemale
VietnameseimmigranttravelledviaHongKongfromNorth
Vietnam.
Incubationperiodthoughttobe~least6yearsand3
months

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AustralianBatLyssavirus
Firstidentifiedin1996inQld,NT&NSW
Closelyrelatedtoclassicalrabiesvirus
Widelydistributedintheflyingfoxpopulation&some
insectivorousbatspeciesinAustralia
Veterinarypersonnel&staffandotheratriskgroups
vaccinatedwithrabiesvaccine
Domesticdogsandcatsnotthoughttobenaturally
infectedbyvirus

AustralianBatLyssavirus
ThreeABLfatalitiesreportedinAustralia
bathandler,1996
27yearoldQueenslandfemale,1998,bittenbyflyingfox
twoyearsearlier
Bothlinkedtoscratchesorbitesbybats
8yearoldboyin2013

Bitesandscratchescanresultinviruscarriedinsaliva
makingdirectcontactwithexposedtissueandnerve
endings
Treatbythoroughwashofwoundwithsoapywater
andthenfollowwithvaccineandIg

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AustralianBatLyssavirus
Positivelyisolatedorinfection
demonstrated,inbothinsectivorousand
fruitbats(flyingfoxes)from:
NewSouthWales
NorthernTerritory
Queensland
Victoria
WesternAustralia.

Hostrangeandspecificity
Viruses can infect bacteria, plants, fungi, insects, and
animals including humans
Highlyselective
Hostrange
Withinhostrangewillusuallyonlyinfectonetypeie plant,animal

Celltype
Tissuetype

HOWEVER!Canvary
Widehostrange
Narrowhostrange

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Hostrangeandspecificity
Someabletocrossspeciesbarrier
InfluenzatypeAinfectsbirds,animals,humans
Rabiesvirusinfectsracoons,dogs,humans
Plant viruses some can replicate in plants and insects
plantandanimalvirusesdonotinfectbacteria
bacterial viruses specifically infectbacteria
Bacterialviruses bacteriophageor"phage"

Hostrangeandspecificity
specificreceptorsoncell & virusforattachment
Viralattachmentproteinsonhostcellsurfaceallowattachment
Chemicalgroups(ligands)inspecificviralattachmentproteinson
surfaceofthevirus

Receptorsitesmaybespecific&predetermined
Orthomyxoviruses
Bindtoterminalsialicacidmoleculelocatedonasidechainofamembrane
glycolipidorglycoprotein

HIV
Gp120attachmentproteinofHIVbindstotheCD4receptormoleculeonthe
membraneofT4lymphocytes

Specificitybetweenhostcellreceptorsitesandvirusisnot
absolute

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InfluenzaAvirusbindstosialicacid,asavirus
receptor,locatedintheterminalofglycochain onthe
hostcellsurface

HIVadsorptionreceptorsite
Gp120 attachment protein of HIV binds to the CD4 receptor molecule on
the membrane of T4 lymphocytes

viral protein

cell surface
receptor

cell coreceptor

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Initiatinginfection
Viruses can make initial contact with
- surface associated proteins/glycoproteins
- terminally modified sugars (sialic acid)
- components of the extracellular matrix
eg. heparin sulfate
Bacterial cell wall

Mammalian plasma membrane

Plant cell wall

Hostrangeandspecificity
Specificitybetweenhostcellreceptorsitesandvirusisnot
absolute
Receptorsitemaybeusedbyunrelatedviruses
Resultsinhostcellsbeingsusceptibletorangeofviruses

Similarvirusesmayusedifferentreceptorsites
Somevirusesabletorecognisemorethanonetypeofreceptorsite
Receptorsondifferenttissuetypesresultsinincreasinghostrange

Ie increasestissuetropism
RabiesvirusattachestoAchreceptoraswellassialyted gangliosides
Resultsinexpandingrangeofsusceptiblehostcellsitcaninfectandallowsittocross
speciesbarrier

Themorecommonthereceptorsitethewiderrangeofcellsthe
viruscanattack
Viruseshaveevolvedtomakethemostofglycoproteinreceptor
sitesonhostcells

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Hostrangeandspecificity
Hostcellreceptorsitesdesignedforanotherpurpose
Receptorisusuallypartofthenormalfunctionofhostcell

Presenceofhostcellreceptorisessentialtoallowviral
attack&determinessusceptibilityofhostcell
Poliovirus
Hasspecificitywithreceptorsonprimatecellsonly
Specificitywithneuronalandmusclecells

Resultsindiseasebeingseeninmanandmonkeysbutnotmicefor
instance
Butnotallprimatecellsarenecessarilypermissive

Poliodisease=primatecells+permissivecells

Hostcelladsorptionsites
Specific components on the cell surface act as receptors:
- bacterial viruses: may use cell wall, lipopolysaccharides
or proteins, flagella, pili

- animal viruses: use glycoproteins or proteins on

animal cell surface (e.g. HIV and CD4)

- no specific receptors identified for plant viruses

entry via grafting

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Whatdeterminessuccessful
infection?
Presenceofcellsurfacereceptorsdetermineswhetheracell
issusceptible toavirus
Onlypermissive cellsallowvirusreplication
Forsuccessfulinfection,cellsmustbebothsusceptible and
permissive
determinestropism
Tissuetropism Specificitybetweenvirus(orbacteria)
withaparticularcellortissuewithinanorganism
Virusmayhavebroadornarrowtropism

PortalofEntry

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Virallife
cycle
5definedsteps:
1.
2.
3.
4.
5.

Attachment
Penetration
Synthesis
Assembly
Release

Literature may

list 6 defined
steps as:
-attachment
- penetration
- translation
- replication
- assembly
- maturation

5definedstepsoftheVirallife
cycle
1. Attachment:alsoreferredtoasadsorptionofthevirusto
hostcell
2. Penetration entryorinjectionofvirusnucleicacidinto
thehostcell
3. Synthesis ofviralnucleicacidandproteinbyhostcell
machineryasdirectedbythevirus
4. Assembly ofcapsidsandpackagingofviralgenomesinto
newvirusparticles
5. Release ofnewlyformedvirusparticlesfromhostcell.
:burstsizecanbefewto>1,000virusparticlesperhost
cell,anddependsontheparticularvirusandhostcells
involved.

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Viralattachment

egHIV

In most cases both a primary receptor and a co-receptor are required to facilitate
virus entry

co-receptor

primary
receptor

BacterialVirusentry insertion
Bacterial viruses need to insert their genomes through the tough and complex
bacterial cell wall

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Animal & Human v i ra l d i s e a s e s

influenza
common cold
(rhinovirus)
poliomyelitis
(poliovirus)
measles
mumps
rubella
chicken pox/shingles
(varicella-zoster virus)
infectious
mononucleosis
(glandular fever)
herpes simplex

hepatitis A B C E G (cancer)
encephalitis (insect
transmitted)
yellow fever
dengue
rabies
foot and mouth disease
myxomatosis (myxoma
virus)
rabbit haemorrhagic disease
canine distemper
Porcine parvovirus
AIDS (HIV)
Nipah virus

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LearningObjectives
Atcompletionofthislecturestudentsshouldbefamiliar
with:
Someofthebasiccharacteristics&clinicalfeaturesof
theEquineandHumanHendravirusdisease
Themodeoftransmission,pathogenesis,symptoms,
treatmentandpreventionofinfectioninhorsesand
man
Befamiliarwiththe5definedstepsofthevirallife
cycle

References

BrockBiologyofMicroorganisms,
14th Edition,Chapter30
MicrobiologyandInfectionControlforHealth
professionals,Lee&Bishop,6th Edition2015.
https://health4horses.com.au/Products/Equivac
HeV/
http://www.ncbi.nlm.nih.gov/pubmed/1106195
4
http://www.abc.net.au/news/201508
23/hendravirusvaccinescientistfearshorses
beingovermedicated/6717048
http://www.csiro.au/en/Research/BF/Areas/Pro
tectingAnimalandHumanHealth/Zoonotic
capability/Hendra

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References
http://www.couriermail.com.au/news/queensland/
hendravirusalertafterhorsekilledbydeadly
bugsouthofbrisbane/storye6freoof
1226083788342
http://www.infectionlandscapes.org/2013/05/rabie
s.html

References
http://www.research.pirbright.ac.uk/picornavirusstructure/
https://www.google.com.au/search?q=virus+entry+into+cells&espv=2&biw
=1920&bih=945&source=lnms&tbm=isch&sa=X&ved=0CAYQ_AUoAWoVCh
MIvp2Gr_bZxwIVYZSmCh1iowLn&dpr=1#imgrc=070iSNndaAw8M%3A

file:///C:/Users/Anna9194/Downloads/GRDCFS
BYDV%20pdf.pdf
Chapter8,BrockBiologyofMicroorganisms
MicrobiologyandInfectioncontrolforHealthprofessionals.
Chapter5,Lee&Bishop.

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