zoonotic tuberculosis and food safety · fo o d sa f e t y au t h o r i t y o f ir e l a n d 2....
TRANSCRIPT
Zoonotic Tuberculosis and Food Safety
2nd Edition
Published by:Food Safety Authority of Ireland
Abbey CourtLower Abbey Street
Dublin 1
Advice Line: 1890 33 66 77Telephone: +353 1 817 1300Facsimile: +353 1 817 1301
E-mail: [email protected]: www.fsai.ie
©2008
ISBN 1-904465-54-4
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CONTENTS
PREFACE TO THE SECOND EDITION 2 MembersoftheScientificCommittee 3 MembersoftheMicrobiologySub-committee 3
1. SCOPE OF THE DOCUMENT 4
2. INTRODUCTION 5 2.1Tuberculosis–DefiningCharacteristics 5 2.2Microbiology 6 2.3NaturalHistoryofHumanInfection
withtheM. tuberculosisComplex 7 2.4EpidemiologyofHumanTuberculosisinIreland 9
3. ZOONOTIC TUBERCULOSIS 11 3.1NaturalHistoryofTuberculosisinAnimals 11 3.2EpidemiologyofZoonoticTuberculosisinIreland 12
4. LEGISLATION AND CONTROLS GOVERNING USE OF PRODUCTS DERIVED FROM TUBERCULIN REACTOR ANIMALS AS FOOD 14
4.1ZoonoticTuberculosis:MilkandDairyProducts 14 4.2ZoonoticTuberculosis:Meat 15
5. POTENTIAL FOR HUMAN ACQUISITION OF TUBERCULOUS INFECTION FROM ANIMALS THROUGH THE FOOD CHAIN 16
5.1PotentialfortheTransmissionofZoonoticTuberculosisviaMilkandDairyProducts 16
5.2PotentialfortheTransmissionofZoonoticTuberculosisviaMeat 18
6. CONCLUSIONS 20
7. RECOMMENDATIONS 21 7.1ActiontoControlZoonoticTuberculosis 21 7.2PreventionofTransmission
ofZoonoticTuberculosistoHumans 21 7.3ResearchandInformationGathering 22
REFERENCES 23
PREFACE TO THE SECOND EDITION
TheFoodSafetyAuthorityofIreland(FSAI)publishedthefirsteditionofthisdocumentin2003.Since
thedocumentwaspublished ithasbeen thesubjectof somediscussion,particularly inrelation to
thehazardoftransmissionofMycobacterium bovistohumansthroughconsumptionofcheesesmade
fromunpasteurisedmilktakenfrominfectedherds.Indraftingtheoriginalreport,theMicrobiology
Sub-committee/Scientific Committee recognised the hazard associated with the consumption of
cheeseproducedfromunpasteurisedmilkingeneral,andthespecifichazardofhumaninfectionwith
M. bovisifthemilkoriginatedfromanM. bovis-infectedherd.Thereportrecognisedthat,whenaherd
isofficiallyrestrictedduetothediagnosisoftuberculosis,eitheronthebasisofapositivetuberculin
testorforotherreasons,itmustbeacceptedthatsuchaherdhasbeeninfectedwithMycobacterium
bovis for some time prior to the commencement of that restriction. Consequently, the hazard of
contaminationofmilkproducedbysuchaherdexistsfromsometimepriortothecommencement
ofthatrestrictionandadditionally,thehazardalsoexiststhatcheesesmadefromunpasteurisedmilk
producedbysuchaherdduringthisperiodarealsocontaminatedwithM. bovis.
Theoriginaleditionofthisreportsoughttoindicatethatcheesethathadbeenmadefromunpasteurised
milk,collectedfromaherdthatwas“officiallytuberculosisfree”atthetimeofmilking,butwhichis
subsequentlyrestrictedbecauseofdetectionofbovinetuberculosis,shouldnotgenerallyberegarded
assuitableforhumanconsumption.Indraftingthereport,themembersoftheSub-committeewere
consciousof the implicationsof such a recommendation for cheese producers and therefore, the
reportsoughttoidentifycertainverylimitedcircumstancesinwhichexceptionscouldbeconsidered.
It is apparent that thisqualificationhas resulted in ambiguity in the report and that thismayhave
contributedtoaninterpretationofthereportasgenerallyimplyingthatrestrictionofthesaleofsuch
cheesewasnotwarranted.ThiswasnotthemeaningintendedbytheMicrobiologySub-committee
orScientificCommittee.
Inviewofthis,theScientificCommitteerequestedtheMicrobiologySub-committeetoreviewthe
relevantsectionsofthedocumenttodetermineif,inthelightofexperience,modificationofthereport
wasnecessarytoensurethatprioritywasgiventoensuringclearandunambiguousadvicetoprotect
publichealth.
ThisreportwaspreparedbytheMicrobiologySub-committeeandadoptedbytheScientificCommittee
forpresentationtotheFSAI.ItaimstoprovidetheFSAIandotherstakeholderswithanoverviewof
thescienceandrelated issuessurrounding thepotential fortransmissionofzoonotictuberculosis
viafood.
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Members of the Scientific Committee
Prof. Albert Flynn (Chair)UniversityCollege,Cork
Dr Catherine AdleyUniversityofLimerick
Prof. Dan CollinsUniversityCollege,Dublin
Dr Collette BonnerDeptofHealthandChildren
Dr Philip HessMarineInstitute
Prof. Colin HillUniversityCollege,Cork
Mr Cathal KearneyHealthServiceExecutive
Prof. Brian McKennaUniversityCollege,Dublin
Dr Paul McKeownHealthProtectionSurveillanceCentre
Dr Michael O’KeefeNationalFoodCentre
Dr Iona PrattFoodSafetyAuthorityofIreland
Prof. Michael Ryan UniversityCollege,Dublin
Ms Paula Barry Walsh DeptofAgriculture,FisheriesandFood
Prof. Martin Cormican NationalUniversityofIreland,Galway
Members of the Microbiology
Sub-committee
Prof. Martin Cormican (Chair)NationalUniversityofIreland,Galway
Dr Catherine Adley UniversityofLimerick
Ms Paula Barry WalshDeptofAgriculture,FisheriesandFood
Dr Tom BeresfordTeagasc,MooreparkResearchCentre
Dr Cyril CarrollNationalUniversityofIreland,Galway
Prof. Dan CollinsUniversityCollege,Dublin
Ms Helen CowmanHealthServiceExecutive,SouthernRegion
Dr Bill DoréMarineInstitute
Dr Geraldine DuffyTeagasc,AshtownFoodResearchCentre
Dr Michael FallonDeptofAgriculture,FisheriesandFood
Prof. Seamus FanningUniversityCollege,Dublin
Dr Paul McKeownHealthProtectionSurveillanceCentre
Mr David NolanDeptofAgriculture,FisheriesandFood
Mr Ray ParleHealthServiceExecutive,SouthernRegion
Dr Neil RowanAthloneInstituteofTechnology
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1. SCOPE OF THE DOCUMENT
Indraftingthisdocument,theMicrobiologySub-committeeoftheScientificCommitteeoftheFSAI
took, as its task, a consideration of the potential for transmission of zoonotic tuberculosis (i.e.,
tuberculosisfromanimalstohumans)throughthefoodchain.Thedocumentdoesnotseektoaddress
issuesrelatingtothecontroloftransmissionoftuberculosisinanimalsintendedforfoodproduction,
occupationalrisksoftuberculosisrelatedtoanimalhusbandryorslaughter,orcontroloftuberculosis
transmissionfrompersontoperson,exceptinsofarasisnecessarytoprovidebackgroundforthe
foodsafetyissues.
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2. INTRODUCTION
2.1 Tuberculosis - Defining Characteristics
Tuberculosis is an infectiousdiseasewithdistinctiveclinical andpathological features. Tuberculosis
occursinhumansandmanyanimalspeciesincludingspeciesofanimalsusedforproductionoffood
(milkormeat)forhumanconsumption(cattle,sheep,goatsanddeer).Theprincipalmicroorganism
associatedwithhumantuberculosisisMycobacterium tuberculosis.Mycobacterium bovisisthecausative
agent of tuberculosis in animals used for production of food and accounts for a relatively small
proportionofhumancasesoftuberculosisreportedinIreland.Infectionwiththesemicroorganismsis
chronicandtheinfectedhumanhostmayremainentirelyasymptomaticormayhavemildtomoderate
illnessthatdoesnotcometomedicalattentionforlongperiods.Inaproportionofhumanoranimal
hosts infectedwiththesemicroorganisms,the infectionmayultimatelyprogresstoseveresystemic
illness. Pulmonarydisease istheclassical featureandultimatelythediseasemayprogresstodeath
ofthehostifuntreated.Theclassicalpathologicalfeatureofthediseaseinhumansisthecaseating
granuloma.Thisisanorganisedaggregationofmacrophagessurroundinganareaofcaseousnecrosis.
Classically,tuberculosisissuspectedinhumansbecauseofclinicalfeaturesofchroniccough,weightloss
andsignsdetectedonclinicalexaminationofthechest.Inhumanmedicine,characteristicradiological
featuresmaysupportaclinicalsuspicionoftuberculosis,orradiologicalfeaturesmayraisethepossibility
oftuberculosisinapersoninwhomitwasnotsuspectedpriortoradiologicalexamination.Tuberculosis
mayalsoberecognisedinhumansoranimalsbyobservationofcharacteristicmacroscopicfindings
onpost-mortemexaminationandbymicroscopicfeaturesofgranulomatousinflammatorychangesin
tissuesorlymphnodesonhistopathologicalexaminationofspecimensobtainedante-mortemorpost-
mortem. Mycobacteria may be observed on histopathological examination of appropriately stained
tissuesections,butthespecificspeciesofMycobacteriumpresentcannotbedefinitivelyidentifiedby
thismeans.
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2.2 Microbiology
ThegenusMycobacteriumcomprisesmorethan70species.Manyspeciesofmycobacteriaoccurin
theenvironmentandarerarelyassociatedwithdiseaseinhumansoranimals.Anumberofspeciesof
mycobacteriaareimportantpathogensofanimalsorhumans.Humantuberculosisischieflyassociated
with infectionwiththespeciesMycobacterium tuberculosis,althoughM. africanum isalso important
in some regions. Tuberculosis in bovines and many other animal species is primarily associated
with infectionwithMycobacterium bovis. M. tuberculosis,M. bovis andM. africanum togetherwith
Mycobacterium microti(associatedwithinfectionofrodents)formaverycloselyrelatedphylogenetic
groupandmaybereferredtocollectivelyastheM. tuberculosiscomplex(MTBC).Humaninfection
withmembersoftheMTBCproducesanindistinguishableclinicalpictureandtheindividualspecies
cannot be distinguished from each other based on microscopic examination of stained tissues or
otherclinicalspecimens.Determinationofwhichspeciesisresponsibleforinfectioninaparticular
case normally requires culture of the microorganism in the laboratory. Culture of the infecting
microorganism remains the gold standard for diagnosis of infection with the MTBC; however, the
processmaytakeweeks,asthemicroorganismsgrowslowly in vitro. Inasignificantproportionof
casesofhumantuberculosis,althoughthereissufficientclinicalandradiologicalevidencetoestablish
adiagnosisoftuberculosis,itisnotpossibletoculturethepathogenfromanyclinicalspecimenand
microbiologicalconfirmationofthediagnosisisnotachieved.Identificationoftheparticularspecies
involvedmaynowalsobeaccomplishedbymolecularmethods.Sub-typingofmembersofaparticular
speciesisalsopossibleusingmolecularmethodsandsuchtechniquesmayassistinthedetectionof
relationshipsbetweenmicroorganismsisolatedfromdifferentsources.
Well-standardisedmethodsforexaminationofspecificfoodsforthepresenceofM. bovishavenot
beendeveloped.Whilethereisnoreasoninprinciplewhythemethodsusedforcultureormolecular
detectionofM. bovisfromclinicalspecimensmightnotbeadaptedforapplicationtofoods,atpresent
there is not an accepted laboratory process thatwould permit certificationof a foodproduct as
“M. bovis–free”,oras“freefromriskoftransmissionofzoonotictuberculosis”.
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2.3 Natural History of Human Infection with the M. tuberculosis Complex
When bacteria of the MTBC gain access to tissues they proliferate locally. Local proliferation of
microorganisms at the site of access to the tissues is associated with an inflammatory response
characterised by infiltration of tissue with macrophages and other cells of the immune system.
Macrophagesphagocytosethebacteria.Followingphagocytosis,macrophagespresentMTBCantigens
toT-lymphocytes,which stimulate thedevelopmentof an adaptiveT-lymphocyte immune response
overthesubsequentweeks.
Intheearlystagesofinfection,beforetheadaptiveimmuneresponseisfullydeveloped,themacrophages
arenotcapableofpreventingproliferationofthemicroorganismswithinthemacrophage.Duringthe
periodwhentheadaptiveimmuneresponseisdeveloping,themacrophagescontainingproliferating
MTBCmicroorganismsmigratetothelymphnodesthatdrainthesiteofinitialinfection.Fromthere
theyarecarriedtotheregionallymphnodes.Forexample,initialinfectionofthetonsilswillresult
indrainageofMTBCmicroorganismstothecervical lymphnodes inthefirst instance,while initial
infectionofthelungresultsindrainageofmicroorganismswithininfectedmacrophagestothelymph
nodesatthehilumofthelung.Fromtheregionallymphnodesthemicroorganismsmaygainaccessto
thebloodandcandisseminatewidelythroughoutthebody.
Astheadaptiveimmuneresponsedevelops,thestimulatedT-lymphocytesinteractwiththemacrophages
to enhance the ability of macrophages to inactivate the microorganisms. As the cellular adaptive
immuneresponsedevelops, thecells involved formthecharacteristichistopathological feature, the
granuloma.
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ArisingfromthecomplexinteractionbetweentheMTBCbacteriaandthedevelopingimmunological
response,thereareanumberofpossibleclinico-pathologicaloutcomesforthehost:
• inasmallproportionofinfectedpeople(usuallytheveryyounginfantorthosewithprofound
impairmentofthecellularimmunesystem),thereisnoeffectiveimmuneresponseandthe
microorganismscontinuetoproliferatethroughoutthebody,resultinginrelativelyrapid
deteriorationanddeath.Thisrapidlyprogressivedisseminatedinfectioniscalled“miliary
tuberculosis”
• inasmallproportionofpeople,alocalised,self-limitingdiseasedevelopswithinweeksofinitial
infection.Theclassicalexampleofaself-limitingprimaryinfectionistuberculousinflammation
ofthepleura(pleurisy).Theprogressionoftheinfectionisarrestedbythedevelopment
withinaboutsixweeksofinfectionofaspecificcellularimmuneresponse.Thisactivatesthe
macrophagestopreventfurtherproliferationofthemycobacteriaandresolutionoftheclinical
illnessfollows
• inthemajorityofthoseinfectedwithbacteriaoftheMTBC,thespecificimmuneresponse,
oncedeveloped,effectivelycontrolsproliferationofthebacteriabeforeanyfeaturesofclinical
illnessdevelop.Thisisasymptomaticprimaryinfection.Inthoseinwhomprimaryinfectionis
asymptomatic,themicroorganismmaynotbecompletelyeradicatedbutmayremainviablein
thetissuesformanyyears.Thisisreferredtoas“latent”infection
• inaminority(perhaps5to10%)ofinfectedpeopleinwhomthecellularimmuneresponse
initiallysucceedsincontainingtheinfection,theimmunologicaldefencesfailafteraperiodof
monthsoryears.Thebacteriathenrecommenceproliferation.Ingeneral,immunologicalfailure
isnottotal.Theresultingprocessisoneofchronictissuedestruction,wastinganddeclining
healthovermonthsoryears.Thischronicprogressiveformoftuberculosisisreferredtoas
“secondarytuberculosis”.Thelung(pulmonarytuberculosis)istheorganmostcommonly
affected(approximately2/3ofsuchcases).Clinicalfeaturesincludepersistentcough,weight
loss,fever,andnightsweats.Ultimately,secondarytuberculosisprogressestodeathinmost
casesintheabsenceofeffectiveanti-tuberculosischemotherapy.
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Insummary,mostpeople(possibly90%)infectedwithMTBCmicroorganismsneverdevelopanyclinical
illnessrelatedtothe infection. Asmallproportionof those infecteddeveloparapidlyprogressive
disease(miliarytuberculosis)withinweeksormonthsofinfectionandafurtherproportiondevelop
chronicprogressivediseasemonthsoryearsafteran initial infection. Those inwhomthechronic
progressiveformoftuberculouspneumoniadevelopsaretheprincipalsourceofinfectionforhumans
astheymayshedlargenumbersofmicroorganismsintotheenvironmentininfectiousaerosols.
2.4 Epidemiology of Human Tuberculosis in Ireland
HumantuberculosishadbeensteadilydeclininginIrelandoverthelast20yearsbutinrecentyearsthe
declineinnotificationshasstopped(seeFigure1).
Figure 1. Notification of Tuberculosis, Ireland 1991-2004
Fromatroughin2001of381cases(representinganincidencerateof9.7casesper100,000population)
there has since been a slight increase with 408 cases reported (or 10.4/100,000) in 2002, 407
(or10.4/100,000)in2003and432(or11/100,000)in2004(HPSC,2006).
0
100
200
300
400
500
600
700
800
20042003200220012000199919981997199619951994199319921991
0100200300400500600700800
NMLKJIHGFEDCBA
NUMBER OF CASES
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M. bovisisnotacommoncauseoftuberculosisinhumansinIreland.Between2000and2004,55%
to65%ofallcasesoftuberculosiswereconfirmedbycultureoftheinfectingmicroorganisminthe
laboratory.Onaverage,between1and4%oftheseculturedisolatesoftheMTBCareidentifiedas
beingM. bovis(seeTable1)(HPSC,2006).
Table 1. Cases of Human Tuberculosis Confirmed on Culture as Due to M. bovis, 2000-2004
Year CasesPercentage of culture positive isolates of MTBC
2000 2 0.9
2001 7 3.3
2002 5 2.9
2003 5 2.0
2004 5 1.8
HPSC (2006)
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3. ZOONOTIC TUBERCULOSIS
3.1 Natural History of Tuberculosis in Animals
Thenaturalhistoryofzoonotictuberculosishasbeenbeststudiedincattle,althoughtheprogression
andoutcomeofinfectionsareprobablysimilarinmostspeciesofanimalusedforfoodproductioninthis
country.Aswithhumaninfection,accessofMycobacterium bovistothetissuesisfollowedbyaninitial
macrophageresponsethat isnot,however,sufficienttopreventproliferationofthemicroorganism.
Disseminationofthemycobacteriumtolocalandregionallymphnodesmaybefollowedinrarecases
bybloodbornespreadtootherorgans.
Inanimalswithclinicalmanifestationsoftuberculosis,therespiratorytractanddraininglymphnodes
aretheprincipalfociofdisease.Clinicalmanifestationsandpathologicallesionsmayalsobeobserved
inotherorgans(liver,spleen,kidney,mammaryglandandbonemarrow)andtheirassociatedlymph
nodes,particularlyinadvanceddisease.
Therouteofinfectioninmostanimalsisviatherespiratorytract.Lesscommonly,M. bovismayalso
gainentryviathepharynxorgastrointestinaltract.Theprincipalsourceofinfectionissheddingof
M. bovisbyinfectedanimals.M. bovisisexcretedintermittentlythroughoutallstagesofthediseaseand
inparticularduringitsadvancedstages,whenpulmonarylesionsdischargeM. bovisintothebronchi
andtheupperrespiratorytractinconsiderablenumbers.Exhalationofthebacillusfollows.Likewise,
after infective sputum is swallowed, M. bovis is excreted in the faeces and, with some reduction
in numbers, persists in the excreta and in the contaminated slurry and environment for 330days
andlonger.
Inanimals,asinhumans,pre-clinicalinfectionmayberecognisedbyuseofthetuberculintest.Thistest
isbasedondetectionofthespecificimmunologicalresponsetoMTBCinfection.Thetestinvolves
intradermalinjectionofproteinantigensderivedfromM. bovis(purifiedproteinderivative,PPD)and
inspectionthreedays later forevidenceofa local inflammatoryreactionatthesiteof injection. In
cattle,PPDisadministeredinparallelwithadministrationatanadjacentsiteofproteinderivedfrom
anotherspeciesofmycobacteriumthatiscommonlypresentintheenvironment(viz.Mycobacterium
avium).Incattle,interpretationofthetuberculintestisbasedonmeasurementofanyalterationin
skinfoldthicknessatthesiteofadministrationofM. bovisPPDandatthesiteofadministrationofthe
comparatorantigen,threedaysafteradministrationofPPDs.Comparisonofanyincreaseintheskin
foldthicknessattheM. bovisPPDsitewiththatatthesiteofadministrationoftheM. aviumantigen,
relative to the initialmeasurements, is thebasisof interpretation. Apositive reaction is indicative
of infectionwithM. bovis.Animalswithapositivetuberculintestarereferredtoas“reactors”. All
herdsarerequiredtohaveanannualtestfortuberculosiscarriedoutonalltheanimalswithinthe
herd–eachyearapproximatelytenmillionanimaltestsarecarriedout.Thisleveloftestingensures
thatthereislittleopportunityforthedevelopmentofadvancedcasesoftuberculosisincattle,thus
minimising this possible sourceof infection for humans. The tuberculin test has some limitations.
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Very recent infection (during theweeks immediatelypreceding the test)maynothave resulted in
thedevelopmentofthespecificimmuneresponsetoadetectablelevelatthetimeoftesting(false
negatives).Inpractice,eachyearanumberofcattlepresentedforslaughterthatwerenegativeattheir
most recentprevious tuberculin test, showevidenceof tuberculosisonpost-mortem inspection. In
1997,1,700non-tuberculinreactorcattlewerefoundtohavetuberculosisatpost-morteminspection;
thisnumberhadincreasedto2,264intheyear2005.Thisrepresentsaverysmallpercentage(lessthan
0.002%)ofcattleslaughteredeachyear.
Conversely, not all reactor animals have tuberculous lesions detected on routine post-mortem
examination.Aproportionoftheseanimalsmayrepresentfalsepositivetuberculintests;however,itis
acknowledgedthattheroutinepost-mortemexaminationisnotaperfectinstrumentandthatdiscrete
tuberculouslesionsmaygoundetectedinupto60%ofreactors.ItisalsorecognisedthatM. bovismay
beisolatedonculturefromlymphnodesthatappearnormalongrosspathologicalinspection.
Thetuberculintestisvaluableinthecontrolofzoonotictuberculosisbecauseearlyrecognitionofpre-
clinicalinfectioninanimalsintendedforfoodproductionandearlyremovalofinfectedanimalsfrom
theherdeliminatesafuturesourceofinfectionforotheranimalsandforhumans.
3.2 Epidemiology of Zoonotic Tuberculosis in Ireland
TuberculosisremainsamajoranimalhealthprobleminIreland.Mostcontroleffortsarefocusedon
cattle and it is for this species that thebestepidemiological information is available. Dataon the
stockingdensityofstandardbovinereactoranimalsandofanimalswithvisiblelesionsperkm2indicate
thattheoccurrenceoftuberculosisincattleinIrelandishighlylocalised.In2005,aparticularfocuswas
evidentbothinthewesterncentralandsouthwesterncounties(Figure2).
In each year since1997, approximately10,000herdshavebeen restricteddue to thediagnosisof
tuberculosisincattle.Tuberculosisinherdsmaybeidentified(i)bydetectionofreactoranimalsatthe
annualtuberculintest,conductedoneveryherdintheState,(ii)attestsonherdscurrentlyconsidered
tobeatparticularrisk,or(iii)asaresultofmeatplantsurveillance.In2006,some24,200cattlewere
removedastuberculinreactors.
Althoughthereismuchlesscomplete informationavailableforotheranimalspecies, infectionwith
M. bovisdoesoccurinotherdomesticandwildanimalsincludinggoats,sheep,badgersanddeer.
Considerationoftheroutesoftransmissionofzoonotictuberculosistocattle,ofpoliciesrelatingto
thecontrolofbovinetuberculosisandofreasonsforthedifficultiesincontrollingtuberculosisincattle
inIreland,isoutsidethescopeofthisdocument.
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Figure 2. Density of Tuberculosis Incidence in Cattle per Square Kilometre During 2005
(Kernel Density with Search Radius at 10 km)
Source:CVERA,UCD
<0.0050.005 - 0.0090.01 - 0.0140.015 - 0.0190.02 - 0.0240.025 - 0.0290.03 - 0.0340.035 - 0.0390.04+Non-agricultural Land
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4. LEGISLATION AND CONTROLS GOVERNING USE OF PRODUCTS DERIVED FROM
TUBERCULIN REACTOR ANIMALS AS FOOD
4.1 Zoonotic Tuberculosis: Milk and Dairy Products
There is general agreement that the most critical and most effective control measure to prevent
transmissionofzoonotictuberculosisthroughmilkispasteurisationorothereffectiveheattreatment
ofmilkpriortohumanconsumptionorfurtherprocessing.Currently,asmallnumberofIrishherds
supplymilktocheesemakerswhoproducecheesefromunpasteurisedmilk.
Regulation(EC)No853/2004oftheEuropeanParliamentandoftheCouncilof29April2004laying
downspecifichygienerulesforfoodofanimalorigin1prohibitsmilkofreactoranimalsfromentering
thefoodchainfromthetimetuberculosishasbeendiagnosed.However,milkfromnon-reactoranimals
inthesameherdcanbeusedforconsumptionorthemanufactureofdairyproductsonconditionthat
thismilkisfirstheattreated.Therefore,thislegislationprohibitstheuseofmilkintheunpasteurised
statefromanofficiallypositivebovinetuberculosisherdforthemanufactureofmilkordairyproducts
suchascheese.Asanadditionalriskcommunicationdevice,Regulation(EC)No853/2004alsorequires
thatunpasteuriseddairyproducts,likecheeses,arelabelled‘madewithrawmilk’sothattheconsumer
canseethatthemilkusedtomaketheproducthasnotbeenheattreated.
ProgrammesfortheearlydetectionandeliminationofM. bovis-infectedcattlerepresentasafeguard
againstmilkbornetransmissionofM. bovis,byensuringthatinfectedanimalsareremovedfrommilk-
producingherdsoncetheyarediagnosed.Goatherdskept formilkproduction,whicharekepton
holdingswhichalsocontaincattle,arelegallyrequiredtobeinspectedandtestedforbovinetuberculosis.
Inaddition,consequentialtestingofgoatsisnormallyperformedifthegoatsareincontactwithacattle
herdknowntobeinfectedwithM. bovis.Inothercaseswheregoats,sheeporotherspeciesarekept
formilkproductiononholdingsonwhichcattlearenotkept,Regulation853/2004requiresthatraw
milkmustcomefromaherdorflockthatisregularlycheckedfortuberculosisunderacontrolplan
thatthecompetentauthorityhasapproved.
1EnactedinIrishlawbyS.I.No.910of2005asamended.
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4.2 Zoonotic Tuberculosis: Meat
Allanimalsenteringthefoodchainaresubjectedtoante-mortemandpost-morteminspection.Inthe
caseofcattle,atuberculintestmusthavebeenperformedinthecourseofthe12monthspriorto
presentationforslaughter.Intheabsenceofsucharecenttuberculintest,thecattlearerejectedfor
slaughterandreturnedtothefarmoforigin.Asreactorcattleareconsideredlikelytobeinfected,
theyareslaughteredseparatelyattheendofeachdaytofacilitateamoredetailedinspectionofthe
carcassforevidenceoftuberculosis.
Ifananimal isclinicallyhealthyatante-mortem inspectionandhasnovisibletuberculouslesionson
post-mortemexamination,thecarcassispassedasfitforhumanconsumptionirrespectiveofwhether
ornotitisatuberculinreactor.TherearenobarrierstotradeinthismeatwithinIrelandorwithin
theEuropeanUnion.Intheeventthattuberculouslesionsaredetectedinalymphnodedrainingone
organorpartofthecarcassonly(forexample,aforequarter),thatpartofthecarcassisdeclared
unfit for human consumption. In the event that tuberculous lesions are detected on post-mortem
examination in two or more organs or regions, the entire carcass is considered unfit for human
consumptionandissentfordestruction.
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5. POTENTIAL FOR HUMAN ACQUISITION OF TUBERCULOUS INFECTION FROM ANIMALS THROUGH THE FOOD CHAIN
5.1 Potential for the Transmission of Zoonotic Tuberculosis via Milk and Dairy Products
Asoutlinedearlier,infectionofthemammaryglandmayoccurandmayoccasionallyresultintuberculous
mastitis leadingtocontaminationofmilkwithinthemammarygland. SheddingofM. bovis inoral/
respiratorysecretionsandinfaecesmayoccurearlierinthecourseofinfectionandbeforeaclinical
diagnosisoftuberculosisissuspected.ExpressedmilkmaybecomecontaminatedwithM. bovisfrom
faecesorsecretions.Inthepast,theprincipalrouteofhumaninfectionwithM. bovisinthegeneral
populationwasviaingestionofrawcow’smilkcontaminatedwithM. bovis,ratherthanbyinhalation.
HumaninfectionwithM. bovisbythealimentaryrouteisnowveryuncommoninIreland.
Properlycontrolledheattreatmentofmilk,e.g.pasteurisation,inactivatesM. bovisandthistreatment
hashadamajorimpactonreducingtheimportanceofmilkasavehicleoftransmissionofM. bovis.
Programmes for screening of cattle (and goats in contact with cattle) for M. bovis infection by
tuberculintesting,aswellasregularchecksonregisteredsheepflocksandothergoatherdskeptfor
milkproductionfortuberculosisunderacontrolplanapprovedbythecompetentauthority,provide
additionalsafeguardsastheyfacilitateearlydetectionandremovalofinfectedanimals.Asmentioned
earlier, under existingpolicies, reactor animals are removed and slaughtered, thereby reducing any
likelihoodofcontaminationofmilkatsource.
TherearetwoprincipalconcernswithrespecttothepotentialtransferofM. bovisviamilk.Theseare
theconsumptionofcontaminated,unpasteurisedmilkandconsumptionofdairyproductsmadefrom
contaminated,unpasteurisedmilk.
1. ConsumptionofunpasteurisedmilkonthefarmrepresentsahazardinrelationtoM. bovis2.
Pasteurisationofmilkisawell-establishedandreadilycontrolledinterventiontoprevent
transmissionofthisandotherinfectionsbymilkanddairyproducts.Wherepeoplewishto
consumemilkproducedontheirownfarm,theuseofsmall-scaledomesticpasteurisationunits
canreducetheriskofmilkborneinfectionwithM. bovis.Itisimportantthatsuchpasteurisation
unitsbeproperlyoperatedandmaintained.
2. Consumptionofdairyproductsmadefromunpasteurisedmilkrepresentsahazardinrelation
toM. bovistoapotentiallywiderpopulation.Themostcommondairyproductmadefrom
unpasteurisedmilkischeese.However,theeffectofthecheeseproductionprocessonthe
viabilityofM. bovisisnotwelldefined.Validatedlaboratorymethodsforthedetectionofviable
M. bovisinmilkordairyproductsarenotroutinelyavailable.Therefore,thereisnopracticalway
toassurethatcheesemadefromunpasteurisedmilkcanbeconsidered“freeofM. bovis”.
2 ConsumptionofunpasteurisedmilkonthefarmrepresentsahazardnotonlyinrelationtoM. bovis,butalsoinrelationto
otherpathogenicbacteria,e.g.,Campylobacterspp.andverotoxigenicE. coli.
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IntheeventthatM. bovisinfectionisdetectedinaherd,itisnotpossibletodeterminepreciselyatwhat
pointintimeinfectionwasintroducedintotheherd.Theinfectionmayhaveoccurredatanytimesince
theprevioustuberculintest.Indeed,theinfectionmayhaveoccurredduringtheweeksimmediately
priortothemostrecentnegativetuberculintest.Asoutlinedpreviously,aperiodofweeksmayhave
elapsedbetweenthetimeofinfectionandthetimetodevelopmentofpositivereactorstatus.
Whenatuberculintest,conductedonaherdthathad,untilrecently,beenclassifiedasan“officially
tuberculosisfreeherd”3disclosesanewpositivetuberculintestresultonananimaloranimals,the
herdisthen“restricted”4.Itisclearthatsucharestrictedherdisnotasuitablesourceofmilkforthe
productionofcheesefromunpasteurisedmilk.
Incases inwhichaherdpreviouslyusedasasourceofmilk fortheproductionofcheesewithout
priorpasteurisationofthemilkisnewly“restricted”,theremaybeanamountofcheeseinstorage
thatwasmadefrommilkcollectedatatimewhentheherdwas“officiallytuberculosisfree”.Similar
situationsarisewhentuberculosisisdiagnosedinagoatherdorsheepflockwhosemilkisusedinthe
rawstatefortheproductionofcheese.Decisionsastothemanagementofsuchcheesehavebeen
controversial.
Argumentsinfavourof“withdrawalfromtrade”ofsuchcheeseincludethefollowing:
1. itisnotpossibletoestimatepreciselyatwhatpointintimemilkfromtheherdorflockin
questionbecameatriskofcontaminationwithM. bovis
2. intheabsenceofpasteurisation,therearenotsufficientdataavailabletobeconfidentthatthe
cheesemakingprocessaffordssufficientprotectiontotheconsumer
3. thereisnoreadilyavailablelaboratorymethodologytocertifytheproductas“freeofviable
M. bovis”.
3 OfficiallyTuberculosisfreebovineherdisdefinedinArticle2(d)ofCouncilDirective64/432/EEConanimalhealthproblems
affectingintra-Communitytradeinbovineanimalsandswine,asamended.ThisdefinitionrequiresherdstocomplywithAnnexA
IParagraphs1and2ofthatDirective,asregardstestingandfreedomfromTBofallanimalsinthatherd.
4 RestrictedholdingisdefinedinArticle2oftheBovineTuberculosis(AttestationoftheStateandGeneralProvisions)Order,
1989(S.I.No.308of1989)asamended.ThisdefinitionreferstoArticle12ofthatOrderregardingholdingsinwhichbovine
tuberculosisispresent,withconsequentrestrictionsonmovementofbovineanimalsortheirproductsfromthatholding.
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Ontheotherhand,itisacknowledgedthat:
1. ifanyM. bovisarepresentincheesemadefromunpasteurisedmilk,theconcentrationislikelyto
belowprovidedtheherdhasbeensubjectedtofrequenttuberculintestingandthatnoanimals
intheherdshowanyclinicalorpost-mortemevidenceoftuberculosis
2. availableevidencesupportstheviewthatzoonotictuberculosisisnowuncommoninIreland.
5.2 Potential for the Transmission of Zoonotic Tuberculosis via Meat5
Thedistributionoftuberculouslesionsincattleatslaughter,andintheotherfoodanimalssuchas
pigs,sheepgoatsanddeer, is ingeneral,confinedtothe lymphaticnodesassociatedwiththehead,
thoraxand,lesscommonly,abdomen.Oneorseveralorgans,suchasthelungs,liver,spleen,kidneys
andmammaryglandalongwiththeassociatedlymphnodesandrelatedseroussurfaces(pleuraand
peritoneum)areotherlesscommonsitesofinfection(Corner,1994,2006).Involvementofthemuscle
massisrareandismostlyencounteredonlyintheadvancedstagesofthediseaseatatimewhenother
tissuesshowovertsignsoftuberculosis(Drieux,1957).
Specifictissues(namely, lymphnode, liver,spleen,kidneyandmammarygland)whichdonotdisplay
visible lesions of tuberculosis at post-mortem inspection may nevertheless carry M. bovis. Drieux
(1957) reviewed studies of the isolation of M. bovis from skeletal muscle in cattle with advanced
tuberculosis.Most,butnotalloftheinvestigatorscitedbyDrieuxfailedtoisolateM. bovisfrommuscle
orwereabletoisolateitbyguineapiginoculationonly,orinfrequentlybyculture.Thissuggeststhat
M. boviswaspresentonlyinlownumbers.However,intwoofthereportscitedbyDrieux,M. bovis
wasrecoveredfrommuscleinahighproportionofcasesstudied.
TheAdvisoryCommitteeontheMicrobiologicalSafetyofFood,initsreportonMycobacterium bovis
totheFoodSafetyAgency(UK),followingaqualitativeriskassessment,consideredthat“therisk,ifany,
fromtheconsumptionofmeatsoldasfreshmeatforhumanconsumptionfollowingassessmentand
actionbytheMHSstaffinUKabattoirsisverylow”(FoodStandardsAgency,2003).
5 ThelegaldefinitionofmeatinPoint1.1,Annex1,Regulation(EC)853/2004,referstoallediblepartsoftheanimalincluding
blood.Themorecommonmeaningofthewordmeatiswithreferencetopartsoftheanimalharvestedforhumanconsumption,
primarilycomprisedofskeletalmuscle,butoftencontainingsmallerquantitiesofothertissuetypes,suchasconnective,neural,
lymphatic,orvasculartissue.Thislattercontextisusedforthepurposesofthisreport.
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Onthebasisofavailableevidence,itisreasonabletoconcludethattheoccurrenceofviableM. bovis
inthemusclemassofcattle,andofotherfood-producinganimalsinfectedwithM. bovis,isuncommon.
RecoveryofM. bovisfromorganssuchasthelungs,liver,spleen,kidneysandmammaryglandismore
common; inthesecases,however,otherevidenceof infectionis likelytobepresent intheformof
visibletuberculousgranulomatainthelymphnodesdrainingtheseorgans.
ThescientificinformationavailabledoesnotpermitaquantitativeriskassessmentregardingM. bovis
in meat. In these circumstances, the Microbiology Sub-committee considers, that given historical
experience,andtakingintoaccountthenatureanddistributionoftuberculouslesionsandofM. bovis
ininfectedcattle(Cassidyet al.,1998),deer(GriffinandBuchan,1994),andotherfoodanimals,the
existing safeguards (describedearlier in this report andwhich are subject toperiodic review) are
adequatetoprotectpublichealth.However,thismattercontinuestobethesubjectofreview.
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6. CONCLUSIONS
1. CurrentinformationshowsthathumanzoonotictuberculosisisuncommoninIreland.
2. Transmissionofzoonotictuberculosisthroughmilkderivedfrominfectedherdshas,inthe
past,beenamajorpublichealthproblemthatwaslargelysolvedbytheintroductionofmilk
pasteurisationandtheprogrammefortheeradicationoftuberculosisincattle.Therefore,there
aregroundsforconcernregardingthecontinuingconsumptionofunpasteurisedmilkanddairy
productsderivedfromunpasteurisedmilk.
3. TransmissionofM. bovistohumansthroughtheconsumptionofmeathasnotbeen
documentedasapublichealthconcernduringsurveillancefortuberculosisinmanycountries
overanumberofdecades.Therisk,ifany,fromtheconsumptionofmeatsoldasmeatfor
humanconsumptionfollowingofficialcontrolsconductedbythecompetentauthorityin
abattoirsinIrelandisverylow.
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7.1 Action to Control Zoonotic Tuberculosis
1. Effortsshouldcontinuetocontroloreliminatetuberculosisincattleandotheranimals
usedforfoodproductionasthismaybeexpectedtoreduceoreliminatetheultimatesource
ofM. bovisinfection.
7.2 Prevention of Transmission of Zoonotic Tuberculosis to Humans
1. Thecriticalroleofeffective,well-controlledpasteurisationinensuringthesafetyofmilkand
dairyproductsmustbecontinuallyemphasisedandtheeffectivenessofthepasteurisation
processinindividualplantsshouldbecloselymonitored.
2. Milkintendedtobeconsumed,ortobefurtherprocessed,withoutpriorheattreatment,i.e.
pasteurisationorequivalentheattreatment,shouldcomefromregisteredherdsorflocksthat
aresubjecttoanofficialtuberculosiscontrolplan.Inthecaseofcattle,thecontrolplanshould
includeherdinspectionandherdtestingfortuberculosiseverysixmonthstominimisethe
riskofdelayindetectinginfectedanimals.Likewise,goatherdsandsheepflockskeptformilk
productionshouldbesubjecttoanofficialtuberculosiscontrolplanthataddressespublichealth
concernsintermsoffoodsafety.
3. Cheesemanufacturersproducingcheesefromunpasteurisedmilkshouldberequiredtosource
milkonlyfromregisteredherdsorflocksthataresubjecttoanofficialtuberculosiscontrolplan.
4. Upondetectionoftuberculosisinaherdorflock,allcheesemadefromunpasteurisedmilk
originatingfromthatherdorflocksincethemostrecentherdorflockinspectionornegative
herdtuberculintestshouldberegardedasunsuitableforhumanconsumption.
5. Thepracticeofinformingfarmersandfarmfamiliesoftheparticularrisksassociatedwiththe
consumptionofmilkfromtuberculosis-positiveherdsshouldcontinue.
6. Whenprivatedomesticconsumptionofmilk,producedonthefarmispractisedby
farmfamilies,theuseofeffectiveandwell-maintained,small-scalepasteurisationunits
isrecommended.
7. Dairyfarmers,cheesemakers,theirfamiliesandvisitorstotheirpremisesshouldbeadvised
abouttherisksassociatedwiththeconsumptionofunpasteurisedmilkfromanyanimalspecies.
8. Atriskpopulationgroupsshouldbealertedtotherisksassociatedwithdrinkingunpasteurised
milkandconsumingdairyproductsmadefromunpasteurisedmilk.
7. RECOMMENDATIONS
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9. Thesaleofunpasteurisedmilkintendedforhumanconsumption,originatingfromallfarm
animals,shouldbeprohibited.
10. Thecurrentpolicywithrespecttothecontrolsontheuseofbeeffromtuberculinreactor
cattleshouldcontinue.
11. Auditingoftheante-andpost-morteminspectionofcarcassesatabattoirssoastoverify
compliancewithEUlegislationregardingthecontrolandremoval,fromthefoodchain,
ofcarcassesorpartsthereof,consideredunfitforhumanconsumptionbecauseofthe
presenceoftuberculosis,orforotherreasons,isrecommended.
7.3 Research and Information Gathering
1. Nationally,55-65%ofhumancasesoftuberculosisareconfirmedbyculture.M. tuberculosis
complexbacilliisolatedfromhumansareidentifiedtospeciesleveltodifferentiateM. bovisfrom
M. tuberculosis.Thisdegreeofidentificationisveryvaluable.Itwouldbeofadditionalbenefit
ifallisolatesofM. bovisculturedfromhumansweresubjectedtodetailedmoleculartypingto
determinewhat,ifany,relationshipsexistbetweenstrainsofM. boviscurrentlycirculatingin
cattleandotheranimalspecies(goats,badgersanddeer)andthosestrainsinfectinghumans.
2. DetailedinvestigationofalllaboratoryconfirmedcasesofhumaninfectionwithM. bovis,for
evidenceofahistoryofconsumptionofunpasteurisedmilkordairyproductsmadefrom
unpasteurisedmilk,andresidenceonfarmsatanypointintheirlives,isimportantandshould
continuetobeperformed.Continued,timelyavailabilityofthisinformationatanationallevel
(asprovidedbyrecentHealthProtectionSurveillanceCentrereports)isrecommendedsoasto
ensureabetterunderstandingoftheepidemiologyofhumaninfectionwithM. bovisinIreland.
3. Developmentofvalidatedlaboratorymethodsforroutineexaminationofvariousfoodmatrices,
e.g.milk,dairyproductsandmeat,forM. bovisisrecommended.
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Advice Line: 1890 33 66 77Telephone: +353 1 817 1300Facsimile: +353 1 817 1301
E-mail: [email protected]: www.fsai.ie
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Food Safety Authority of IrelandAbbey Court, Lower Abbey Street,
Dublin 1
Údarás Sábháilteachta Bia na hÉireannCúirt na Mainistreach, Sráid na Mainistreach Íocht.,
Baile Átha Cliath 1