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Zoonotic Tuberculosis and Food Safety

2nd Edition

Microbiology

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

F o o d S a F e t y a u t h o r i t y o F i r e l a n d

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.

F o o d S a F e t y a u t h o r i t y o F i r e l a n d

F o o d S a F e t y a u t h o r i t y o F i r e l a n d

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

F o o d S a F e t y a u t h o r i t y o F i r e l a n d

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.

F o o d S a F e t y a u t h o r i t y o F i r e l a n d

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.

F o o d S a F e t y a u t h o r i t y o F i r e l a n d

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”.

F o o d S a F e t y a u t h o r i t y o F i r e l a n d

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.

F o o d S a F e t y a u t h o r i t y o F i r e l a n d

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.

F o o d S a F e t y a u t h o r i t y o F i r e l a n d

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

F o o d S a F e t y a u t h o r i t y o F i r e l a n d

�0

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)

F o o d S a F e t y a u t h o r i t y o F i r e l a n d

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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.

F o o d S a F e t y a u t h o r i t y o F i r e l a n d

��

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.

F o o d S a F e t y a u t h o r i t y o F i r e l a n d

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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

F o o d S a F e t y a u t h o r i t y o F i r e l a n d

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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.

F o o d S a F e t y a u t h o r i t y o F i r e l a n d

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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.

F o o d S a F e t y a u t h o r i t y o F i r e l a n d

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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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Report,2004-05,oftheCentre forVeterinary

EpidemiologyandRiskAnalysis

Cassidy JP, Bryson DG, Pollock JM,

Evans RT, Forster F and Neill SD(1998)

Earlylesionformationincattleexperimentally

infectedwithMycobacterium bovis. Journalof

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Cassidy JP, Bryson DG, Pollock JM,

Evans RT, Forster F, Neill SD (1999)

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Corner LA (1994) Post-mortem diagnosis

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in domestic animals: how to assess the risk.

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genotyping. Revue Scientifique et Technique de

l’Office International des Epizooties,19,675-688

Durr PA, Hewinson RG and Clifton-

Hadley RS (2000b) Molecular epidemiology

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healthriskstoconsumersofmeatfromcattle

withevidenceofMycobacterium bovisinfection.

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Hammond RF (1999)A density analysis of

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lesions in Irish Herds: a focused approach to

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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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