Brucellosis is a public health problem in southern Italy: Burden and epidemiological trend of human and animal disease

ContentslistsavailableatScienceDirect

Journal

of

Infection

and

Public

Health

j o u r n al ho me p ag e :h t t p : / / w w w . e l s e v i e r . c o m / l oc a t e / j i p h

Brucellosis

is

a

public

health

problem

in

southern

Italy:

Burden

and

epidemiological

trend

of

human

and

animal

disease

Alessio

Facciolà

_,

_Maria

_A.R.

_Palamara

_,

_Giuseppa

_D’Andrea

_,

_Fernanda

_Marano

_,

Domenico

Magliarditi

_,

_Giovanni

_Puglisi

_,

_Isa

_Picerno

_,

_Angela

_Di

_Pietro

_,

Giuseppa

Visalli

a_{DepartmentofClinicalandExperimentalMedicine,UniversityofMessina,Italy}

b_{DepartmentofBiomedicalandDentalSciencesandMorphofunctionalImaging,UniversityofMessina,Italy}

c_{EpidemiologyOperativeUnit,DepartmentofPrevention,SanitaryProvincialAgency,Messina,Italy}

d_{VeterinaryEpidemiologyOperativeUnit,VeterinaryPreventionDepartment,SanitaryProvincialAgency,Messina,Italy}

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r

t

i

c

l

e

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n

f

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Articlehistory:

Received7May2018

Receivedinrevisedform6July2018

Accepted15July2018 Keywords: Brucellosis Zoonosis Epidemiology PublicHealth

a

b

s

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Background:Brucellosisisthemostcommonglobalbacterialzoonoticdisease.Italianannual2015report onanimalbrucellosiscontrolthatwassubmittedtotheIntegratedNationalPlanoftheItalianHealth MinistryshowedthattheItalianregionwiththehighestprevalenceandincidenceofbrucellosiswas Sicily(3.3%).Thisstudyaimstodemonstratetheburdenofdiseaseandtheepidemiologicaltrendof humanandanimalbrucellosisinMessina,Sicily,from1997to2016.

Methods:Theanalysiswasconductedinthetwenty-years1997–2016.Weexaminedthecomputerised andpaperregistersoftheMessinaProvincialHealthAgencyn.5toevaluatehumanandanimalbrucellosis reports.

Results:1462casesofhumanbrucellosiswerereportedwithanimportantoutbreakin2016inwhich werereported137caseswhiletheprevalenceofinfectedcattleandsheep/goatsdecreasedfrom3.8% and8%,respectively,in1997to1.7%forbothin2016.Astatisticallysignificantcorrelationwasobserved betweenthedecreaseofbothanimalandhumancasesduringtheconsideredperiod.

Conclusions:OurstudydemonstratethatbrucellosisisstillpresentinSicilywithanumberofcases iden-tifiedinbothanimalsandhumansandithypothesisesalargenumberofprobableunderreportedcases. Ourfindingsconfirmtheneedtoimproveknowledgeoftherisksassociatedwithconsumingrawmilk anditsderivatives,mainlyfromsheepandgoats,anddemonstratesthatpublichealthwouldbenefitfrom cooperationbetweenhumanandveterinaryhealthservices.

©2018 TheAuthors.PublishedbyElsevierLimitedonbehalfofKingSaudBinAbdulazizUniversity forHealthSciences.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http:// creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

Zoonosesarediseasestransmissiblefromanimalstohumans throughdirectcontactorthrough food,waterand environment andrepresentanimportantpublichealthproblem[1–3]. Brucel-losisisthemostcommonglobalbacterialzoonoticdisease[4–6]. Ruminantbrucellosisisgenerallytransmittedtohumansthrough theingestionofunpasteurisedmilkderivedfrominfectedanimals (usuallycattle,goatsandsheep),contaminatedundercookedfood orthroughanoccupationalexposure.However,thehigh temper-aturesduringcookingandpasteurisationrapidlykillBrucellaspp.

[7–9].Incountrieswhereitiscommonpracticetopasteurisemilk,

∗ Correspondingauthor.

E-mailaddress:gvisalli@unime.it(G.Visalli).

brucellosishasbecomemoreofoccupationaldisease,especiallyin thoseworkingwithinfectedanimalsortheirtissues(i.e.farmers, livestockbreeders,veterinariansandlaboratoryworkers)[10–12]. However, brucellosisremains an important zoonotic diseasein areaswhereBrucellaspp.isendemicinsheepandgoats,suchas theMediterraneanbasin,SouthwestAsiaandpartsofLatinAmerica

[13].

In2015,27countriesintheEuropeanUnionreportedatotal of437confirmedcasesofhumanbrucellosis,withanotification rateof0.09/100,000individuals.Asinpreviousyears,the coun-triesthatreportedthehighestratesofbrucellosiswereGreece(109 confirmedcaseswithanotificationrateof1/100,000individuals), Italy(105confirmedcaseswithanotificationrateof0.17/100,000 individuals)andPortugal(46confirmedcaseswithanotification rateof0.44/100,000individuals),whichcollectivelyaccountedfor 59.5%stronglyofallconfirmedcasesthatyear.Spainwasfourth,

https://doi.org/10.1016/j.jiph.2018.07.007

1876-0341/©2018TheAuthors.PublishedbyElsevierLimitedonbehalfofKingSaudBinAbdulazizUniversityforHealthSciences.Thisisanopenaccessarticleunderthe

evenwiththewell-knownproblemofunderreporting[16,17]. Italyissuedlawstoeliminatebovine,sheepandgoatbrucellosis, whichhaveledtoasubstantialdeclineofbrucellosisandtothe eradicationofthediseaseinthenorthernItalianregions.In2002, Sicilyissuedthedecree519/2002entitled“Implementationofthe extraordinaryplansforthecontrolofbovine,ovineandcaprine brucellosis”.Moreover,inNovember2006,theMinistryofHealth issuedthe‘Extraordinaryveterinarypolicemeasureson tuberculo-sis,bovineandbuffalobrucellosis,ovo-caprinebrucellosis,bovine leukosisinCalabria,Campania,PugliaandSicily’,whichwas mod-ifiedandupdatedin2012and2015[18–20].However,eradication programmesin thesouthofItaly, especiallyinSicily,were hin-deredbytheincompletecontrolofmovement,theidentification ofanimals,thelackofputtingdownofinfectedanimalsandthe traditionalbreedingpracticesdescribedabove.

In2014,inSicilyandPugliawerepositiveforbrucellosis1519 cattleonatotalof1723animalsculledduringtheyear.Atotalof 13,529sheepandgoatwerepositiveinCalabriaandSicilyin2015 and16,170wereculled[21].

AccordingtotheRegionalVeterinaryEpidemiologicalBulletin (whichispublishedbytheRegionalExperimentalZooprophylactic Institute) in December 2016, of the total official regionally-controlledinfectedcattle/sheepandgoatfarms,76.3%and69.1%, respectively,wereinMessina[22].

Thisdescriptivestudyaimstodemonstratetheepidemiological trendofhumanandanimalbrucellosisinMessina,Sicily,from1997 to2016,showingthepersistenceofthisinfectionandthenecessity ofincreasingtheofficialcontroltoimprovethehealthconditionof breedinganimalsandhumansafety.

Materialandmethods

Datacollection

Theanalysiswasconductedinthetwenty-years1997–2016.In theseyears,thepopulationresidentintheentireMessinaprovince, from1997/12/31 to2016/12/31 decreasedof3.1%rangingfrom 656,646to636,653inthetwoyearsrespectively.37.3%of inhab-itantsliveinMessinatown.Theentireprovincialterritoryisthe ProvincialHealthAgencyn.5(ASP 5)of theSicilian Region.The allAgencyissubdividedin8districts,oneoftheseincludesthe Messinatown.ThecomputerisedandpaperregistersofthePublic Health,EpidemiologyandPreventiveMedicineUnitoftheMessina ASP5 Prevention Department collectallthehumanbrucellosis reports fromall districts.These registers were usedtoidentify humancases,whichweresubsequentlysubdividedbygender,age andthemonthofoccurrence.

Similarly, the computerised and paper registers of the Vet-erinary Epidemiology Unit of the Messina ASP 5 Prevention Department collectallcases of animal brucellosisof theentire provincialterritoryandwereusedtoidentifyallanimalcases.

between1997and2016.Interestingly,thefirst7years(1997–2003) werecharacterisedbymoreintensepeaksthantherestofthe con-sideredperiod,whichcanbeattributedtotheincreasinglevelsof officialcontrolsaftertheemanationofdecree519/2002.Despite thedecreasingnumbersof notifiedcases duringtheconsidered period,theinfectionpersistsinourterritorieswithanumberof casesthat,in2016,resultedinanimportantoutbreaktotalling137 notifiedcases.Theoutbreakthen endedasevidencedbyonly8 expectedcasesreportedbetweenJanuaryandAugust2017(data notshown).Thenumbersofcasesreportedperyearandthe inci-dencesareshowninFig.1A.

During1997–2015,malesaccountedfor60%ofallcasesand females accountedfor40%.The 25–64agegroupwasthemost affected,accountedfor58%ofallcases,andwasfollowedbythe ≥65(15%),15–24(14%)and0–14(13%)agegroups.The hospitali-sationratewas82%andonly6%wasaccountedforbyworkerswho wereatriskofcontractingbrucellosis(i.e.veterinaries,breeders, farmersandbutchers).Concerningthe2016outbreak,therewas nosignificantdifferencebetweenaffectedmalesandfemales.The agegroupspercentagesduringthistimewereverysimilartothose oftheentireperiod.Thehospitalisationratewas46%andonly2% wereat-riskworkers.Themonthlyreportingtrendduringthe2016 outbreakisshowninFig.1B.

Thepeaknumberofreportsoccurredinthefirstpartoftheyear, fromFebruarytoJuly.Thistrendwasconsequenttotheoriginofthe outbreak.Sevendifferentsourcesoftheoutbreakwereidentified, ofwhich40caseswererelatedtothedistributionofalocalcheese (‘tuma’)duringthelivingnativitysceneatChristmas2015ina vil-lageinthesouthernsuburbsofthecity.Therestofthereported caseswereallconcentratedinthesouthernpartofthecityand wererelatedtotheconsumptionoffreshcheesesboughtinshops suppliedbysmalllocalretailers.

Analysingthereportedandthehospitalizedhumancases,we observedaratheroverlapduringtheyearsexceptinthe2016 out-breakinwhichthehospitalizationratewas46%comparedtoan 81%averagehospitalizationrateofallpreviousyears(Fig.2).

Animalcases

Duringtheconsideredperiod,thenumberofcontrolledfarms forcattleandsheep/goatshasincreasedconsiderablyfrom44%and 37%,respectively,in1997to100%forbothin2016.Thenumberof controlledcattleandsheep/goatsalsoincreasedduringthisperiod from36.2%and30.1%,respectively,in1997to100%forbothin2016 (Fig.3A–B).Theincreasewasconsequenttotheimplementationof decree519/2002,whichledtoanoverlapbetweencontrollableand controlledfarms(Fig.3C–D).

Inaddition,theprevalenceofinfectedcattleandsheep/goats decreased from3.85% and 8%,respectively, in 1997to1.7% for bothin2016(Fig.3E–F).Asimilardecreasewasalsoobservedfor thenumberofinfectedanimalsthatwereculledordied(datanot shown).

Fig.1.Epidemiologicaltrendofreportedhumancasesduringthetwentyyears1997–2016(A)andmonthlytrendofreportedcasesduringthe2016outbreak(B).

Fig.2.Comparisonbetweennumberofreportedandhospitalizedhumancases.

Astatisticallysignificantcorrelationwasobservedbetween ani-maland humancasesduringtheconsideredperiod (r0.461for cattleandr0.426forsheep/goats)(Fig.4A–B).Particularly,theslope wassignificantbothforcattleandsheep/goats(P<0.01forboth). Analysingthesteepnessoftheslopeweobservedthata5% reduc-tionofseropostivityincattleandsheep/goatsleadstoadecreaseof 208(95%CI:184.21–288.37)and62(95%CI:56.72–81.51)human casesrespectively.

Discussion

Brucellosisis stillone of themostcommonzoonosesinthe world. Brucella melitensis is known to be the most pathogenic species of the Brucellaceae family, producing the most intense symptoms,thegreatesttissuedamageandthehighestincidence oflocalisationinbodyorgans,systemsortissues[23].However,a separatestudyreportedthattherewasnoevidencethatB. meliten-siswasmorevirulentthanBrucellaabortusorthatinfectionsdueto B.abortuswerelessseverethaninfectionswithB.melitensis,despite thehigherprevalenceofB.melitensisinhumans[24].Bovine bru-cellosisismainlysustainedbyB.abortus,ascattlearethenatural hostandreservoirofthismicroorganism;secondaryhostsinclude bison,buffalo,camelandmoose,whilecasualhostsincludepigs, horsesanddogs.B.melitensisistheprimaryetiologicagentofsheep andgoatbrucellosis.

BrucellosishasbeenacompulsorynotificationdiseaseinItaly since1934andreacheditshighestincidenceinhumansinthelate 1940safterWorldWarII(20casesper100,000inhabitants). Start-ingfromthesecondhalfofthe1950s,followingtheadoptionof

nationalandregionalcontrolplans,adecreaseintheincidenceof thediseaseinhumansandanimalswasobserved[25].Duetothese efforts,themajorityofItalianprovincesarenowclassifiedas “offi-ciallyundamagedterritories”;however,brucellosiscontinuestobe animportantdiseaseinmanyareasoftheMediterraneanregion

[26].

Indeed,brucellosisisstillpresentinSicilywithanumberofcases identifiedinbothanimalsandhumans.Thissituationisstrongly linkedtothepersistenceof alargenumberof infectedanimals inthis territory,especially inthesheepand goatpopulation.In fact, sheepand goatbreeding is themain zootechnical activity oftheregionandisoneofthemostimportantresourcesforthe regionaleconomy.Theproductionoflocalcheeseby smallhold-ersandsmall-scalefarmersisfrequentinthisregion.Inaddition, thepromiscuityofthedifferentanimals(sheep,goatsandcattle) is verycommonand increasesthepossibilityof contamination, transmissionandthespreadofinfections[27].

Theannual2015reportonbrucellosiscontrolthatwas submit-tedtotheIntegratedNationalPlanoftheItalianHealthMinistry showedthat99.6%ofcompaniescoveredbytheprogrammefor theeliminationofbovinebrucellosiswerecheckedandthatthe regionwiththehighestprevalenceandincidencewasSicily(3.3%). Thesamereportalsoshowedthat97.4% ofthecompanies cov-eredbytheeradicationprogrammeofsheepandgoatbrucellosis werecheckedandthattheregionswiththehighestprevalenceand incidencewereSicily(3.7%)andCalabria(1.1%).

Sheep,goats,andtheirproductsappeartobethemajorsources ofinfection,asdemonstratedbytheelevatednumberof brucel-losiscasesintheseanimalscomparedtocattle;theprevalenceof

Fig.3.Comparisonbetweencontrolledfarmsandanimalsforcattle(A)andsheep/goats(B).GraphicsCandDshowtheoverlapbetweencontrolledandcontrollablefarms

forcattleandsheep/goatsrespectively.Prevalenceofcattle(E)andsheep/goats(F)brucellosisintheconsideredperiod.

Fig.4.Correlationbetweenhumanandanimalcasesincattle(A)andsheep/goats(B).

BrucellainfectioninsheepandgoatsinMessinaisthehighestin Italy.Moreover,sheepandgoatsplayakeyroleinthespreadof brucellosisincattleandinhumans;infact,cattlearenottheusual reservoirofBrucellaspp.[23].Theincidenceratesofanimal

bucel-losisarevariableindifferentcountries.InArgentinatheaverage incidencerateis1.7[28],inNigeriarangesfrom9.9to15%incattle

[29],inLibyatheprevalenceofthediseaseis0.2%incattle,8.3%in sheep,and14.8%ingoats[30].

Epidemiologicaldataontheincidenceofhumanbrucellosisare mostlikelyunderestimated,asthediseasehasnonspecificsigns andsymptoms[9,31].

Duringtheperiodconsideredinthisstudy,theaffectedsubjects werecommonlyyoungadultmalesandtherewasnocorrelation betweeninfectionandworkingrisk,asthepercentageofat-risk workerswasverylowduringallperiods,probablybecausethe out-breaksdidnotoriginatefromcontrolledfarmsbutfromunofficial farmingfamilies.Thisfindingisnotinagreementwithother stud-ies[12].Becausethedifferencebetweenthesexesisnotlinked tooccupationalrisks,probablymalesarelesscarefulabout drink-ingunpasteurisedorrawmilkoreatinguncontrolledcheesethan females.

Thisstudyalsoshowedthatofficialcontrolsefficientlyreduced theincidenceofthediseaseinanimalsandhumans,witha sig-nificantdecrement of infected compared to controlledanimals followingtheenactmentofdecree519/2002.Thisfindingwasin linewiththoseseeninotherstudies[32].Thestatistically signifi-cantcorrelationbetweenanimalandhumaninfectionmeansthat veterinarysurveillancecouldeliminatehumanbrucellosis,aswas seeninthenorthernregions[33].

However,theinfectionpersistenceindicatesthatsmall breed-ers, often in the form of farming families who produce and distributehomemadecheese,couldevadetheofficialcontrolsand beamajorcauseofthecurrentsituation.Particularly,thehabitof addingrawmilktofinishedcheesetoimproveitstasteisoneof theprinciplecausesoftheinfection.Infact,whenitwaspossible toidentifythecauseoftheinfection,themajorimplicatedfoods werealwayslocalcheeses(“primosale”,“tuma”and“ricotta”).

Moreover,thedifferenceinthehospitalisationrate between 1997–2015andthe2016outbreakrevealsaprobableand signifi-cantunderreportingrate.Indeed,inlightofthehighhospitalisation rateregisteredinthefirstperiod, itis verylikely thatonlythe hospitalisedcaseswerereportedandnotthosetreatedathome. Probably, themediaattention focusedonthe mostrecent out-breakhaspromptedphysicianstoalsoreportthecasestreatedat home.Probably,alargenumberofnon-hospitalizedcaseswerenot reportedbyfamilyphysicians,thusescapingofficialsurveillance.

Conclusions

Brucellosisremainanimportantpublichealthproblem world-wide. Our findings, although related to a local area, are surely overlappingtotheepidemiologicalsituationofendemic Mediter-ranean countries. The main public health goal is to decrease theprevalenceofbrucellosisamonghumansbyeliminatingthe infectionsources.Preventionshouldincludeimplementingofthe governmental surveillance programme to collect all suspected casesofbrucellosisandfighttheunderreportingwhichisstillmuch probableinthestudiedarea;creatingasmoothandfastflowofdata reportingfromperipherallaboratoriestothespecificnational cen-treandendowingperipheralcentreswiththequalifiedlaboratory personnelandequipment.Moreover,itisalsonecessarytoenforce animalcontrols,vaccinateallsusceptibleanimalsandincreasethe levelofeducationandawarenessamongpeople,especially regard-ingtheconsumptionofnotcontrolledmilkandderivatives.Finally, theconstantprevalenceoftheinfectionin animals,particularly sheepand goats,suggeststheneedtoimprovetheofficial con-trolmeasuresanderadicationefforts,especiallyinbreedsthatare currentlynotcontrolledandinwhich ahighprevalenceof ani-malbrucellosisisoftenpresent.Thisconfirmstheneedtoimprove knowledgeoftherisksassociatedwithconsumingrawmilkandits derivatives,mainlyfromsheepandgoats,anddemonstratesthat publichealthwouldbenefitfromcooperationbetweenhumanand veterinaryhealthservices.

Limitofthestudy

This research focused the attention on a problem that has presentinmanypartsofworldbutthathasbecomeuncommon in high-income countries suchas Northern Europeand United States.Forthisreason,thefindingscouldnotinterestthepublic healthactionsinthelatters.Moreover,wehypothesisean impor-tantunder-notificationrateofthediseasebutwearenotableto demonstrateorquantifyit.

Funding Nofundingsources. Competinginterests Nonedeclared. Ethicalapproval Notrequired. References

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