Streptococcus suis Meningitis- Epidemiology,Clinical Presentation and Treatment原版完整文件VIP

VECTOR-BORNEANDZOONOTICDISEASES

VolumeXX,NumberXX,2019

ªMaryAnnLiebert,Inc.

DOI:10.1089/vbz.2018.2399

StreptococcussuisMeningitis:Epidemiology,ClinicalPresentationandTreatment

MariaHlebowicz,PawełJakubowski,andTomaszSmiatacz

Abstract

Streptococcussuis,aprevalentporcinepathogen,maysporadicallycauseinfectionsinhumans,andhasrecentlyemergedasacauseofzoonosesinsomeprofessionals.Theaimofthisarticlewastoreviewavailabledataonepidemiology,etiopathogenesis,diagnostics,andmanagementofthemostcommonformofS.suisinfection,purulentmeningitis.LiteraturedatashowthatS.suisisanimportantetiologicalfactorofpurulentmeningitis,especiallyinsubjectsbeingoccupationallyexposedtocontactwithpigsand/orporkmeat.OwingtogrowingincidenceofS.suismeningitis,ahistoryofsuchexposureshouldbeverifiedineachpatientpresentingwithtypicalmeningealsymptoms.WheneverS.suiswasconfirmedastheetiologicalfactorofpurulentmeningitis,therapeuticprotocolshouldbeadjustedappropriately,toavoidpatient’sexposuretopotentiallyototoxicantimicrobialagentsandcorticosteroids.ConsideringthebiphasiccharacterofS.suismeningitisanditsfrequentlyatypicaloutcome,allindividualswiththisconditionshouldbeoptimallysupervisedbyamulti-disciplinaryteam,includinganENTspecialist.

Keywords:Streptococcussuis,meningitis,therapy,diagnostics,occupationaldisease

Introduction

S

treptococcussuis,aprevalentporcinepathogen,maysporadicallycauseinfectionsinhumans,andhasrecently

emergedasacauseofzoonosesinsomeprofessionals.Pa-tientsinfectedwithS.suistypicallypresentwithmeningitis,arthritis,and/orsepsis.MainriskgroupsforS.suisinfectionaresubjectsbeingoccupationallyexposedtopigsand/orpork,forexample,farmers,butchers,meatsellers,foresters,andhunters.

Theaimofthisarticlewastoreviewavailabledataonepidemiology,etiopathogenesis,diagnostics,andmanage-mentofthemostcommonformofS.suisinfection,purulentmeningitis.

MicrobiologyofS.suis

S.suisisaheterogeneousGram-positivebacterium.Thisfacultativeanaerobe,sphericalorovoidinshape,typicallypresentsinpairsorasshortchains.Anotherspecificfeatureof

S.suisisthepresenceofalphahemolysisonselectivemediaenrichedwithhorseblood(Staatsetal.1997,Fengetal.2014).Thelackofgrowthin6.5%NaClagar,negativeresultofVoges-Proskauertest,andsynthesisofacidfromtrehalose

orsalicinaresufficienttoconsideranalpha-hemolyticGram-positivecoccusasaS.suisisolate(Goyette-Desjardinsetal.2014,Okuraetal.2016).However,moreaccurateidentifi-cationrequiresadditionalbiochemicaltests:forargininedihydrolase(positiveresult),productionofacidfromlac-tose,sucrose,andinulin(positiveresult)andsynthesisofacidfromglycerol,mannitol,andsorbitol(negativeresult)(Goyette-Desjardinsetal.2014,Okuraetal.2016).

S.suisisaverycommonswinepathogen,isolatedfromupperairways(predominantlytonsilsandnasalcavity),gas-trointestinaltract,andgenitalsofpigs.Markedlylessoften,

S.suismaybealsoisolatedfromotherspecieslikehorses,dogs,andcats.Apparently,someporcinestrainsofS.suishaveevolvedandbecomepotenthumanpathogens,aswell(Staatsetal.1997,GottschalkandSegura2000,Huangetal.2005).Althoughtothisdate,atotalof35variousserotypesof

S.suishavebeenidentifiedbasedontheheterogeneityoftheircapsularantigens,itisserotype2(SS2)thatplaysacrucialroleinthepathogenesisofhumaninfections(Gottschalketal.2007,Wertheimetal.2009).Otherserotypes,lessoftenisolatedfromhumans,areSS1,SS4,SS5,SS14,SS16,andSS24(ArendsandZanen1988,Maietal.2008,Nghiaetal.2008,Haleisetal.2009,Kerdsinetal.2009,2011,Gus-tavssonandRamussen2014).However,thisserotype-based

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DepartmentofInfectiousDiseases,MedicalUniversityofGdansk,Gdansk,Poland.

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classificationraisessomecontroversies.Someauthorswhodocumentedthepresenceof‘‘S.suis-likestrains,’’whichalthoughsatisfiedthepreviouslymentionedbiochemicaltaxonomiccriteria,wereshowntobegeneticallydistinctentities(Hilletal.2005,Tienleetal.2013,Ishidaetal.2014,Baigetal.2015,Nomotoetal.2015,Okuraetal.2016).Hence,molecularmethodshavebeenusedincreasinglytoultimatelyconfirmtheidentityofpresumableS.suisisolates(see,Okuraetal.2016).Usingamolecularapproach,namelymultilocussequencetyping,SS2,themostcommoncauseofhumaninfectionsamongS.suisserotypes,hasbeenclassifiedintoatleast16sequencetypes(STs),someofwhichformclonalcomplexes(Kingetal.2002,Goyette-Desjardinsetal.2014).

AnumberofS.suisvirulencefactorshavebeenidentifiedtodate.Theycanbeclassifiedintofourmaincategories:(1)surface/secretedelements,(2)enzymes/proteases,(3)tran-scriptionfactors/regulatorysystems,and(4)transporters/se-cretionsystems(Fengetal.2014).Basedontheprofileoftheirvirulencefactors,S.suisstrainsareclassifiedashighlypathogenic,weaklypathogenic(hypovirulent),andnon-pathogenic(avirulent)(Fengetal.2014).Themostpromi-nentandbestcharacterizedvirulencefactorsofS.suisaresurfaceandsecretedelements:capsularpolysaccharides,muramidase-releasedprotein,anda38kDasurfaceprotein,suilysin(SLY)(Wilsonetal.2007).Althoughthelistofconfirmedandputativevirulencefactorsisextensive(see,Fittipaldietal.2012,Seguraetal.2017)andatleast37ofthemareclaimedtobe‘‘critical,’’theroleofmanystillhasnotbeenverifiedappropriately.

EpidemiologyofS.suisInfections

S.suiswasfirstidentifiedasanetiologicalfactorofhumaninfectionsin1968(Wertheimetal.2009),andsincethenatotalof*1600casesofzoonosescausedbythispathogenhavebeenreportedin*30countriesinEurope(Austria,Belgium,Croatia,Denmark,France,Germany,Greece,Hungary,Ireland,Italy,theNetherlands,Poland,Portugal,Spain,Sweden,andUnitedKingdom),Asia(China,HongKong,India,Japan,Korea,Laos,Philippines,Singapore,Taiwan,Thailand,andVietnam),NorthAmerica(CanadaandUnitedStates),SouthAmerica(Argentina,Chile,andFrenchGuiana),Australia,andNewZealand(Shneersonetal.1980,Robertson1986,Yenetal.1994,Kayetal.1995,Michaudetal.1996,Staatsetal.1997,Spissetal.1999,GeffnerSclarskyetal.2001,Kopic´etal.2002,Ibarakietal.2003,Rosenkranzetal.2003,TeekakirikulandWiwanitkit2003,Suankratayetal.2004,Huangetal.2005,Huietal.2005,Lopretoetal.2005,Willenburgetal.2006,Yuetal.2006,Gottschalketal.2007,Camporeseetal.2007,Lunetal.2007,Leeetal.2008,Maetal.2008,Maietal.2008,Manzinetal.2008,vandeBeeketal.2008,Fittipaldietal.2009,Wertheimetal.2009a,2009b,Fengetal.2010,Huhetal.2011,Nghiaetal.2011,Demaretal.2013,Kochetal.2013,Zalas-Wieceketal.2013).Althoughamajorityofthesecasesweresporadicinfections,twooutbreaksofS.suisSS2epidemicswerereportedfromChina(Huangetal.2005,Yeetal.2006,Yuetal.2006,Lunetal.2007,Fengetal.2009,2010,Maetal.2009),andthisbacteriumwasshowntooccurendemicallyinThailandandVietnam(TeekakirikulandWiwanitkit2003,Suankratayetal.2004,Maietal.2008,

Wertheimetal.2009a,2009b,Kerdsinetal.2009,2011,Nghiaetal.2011,Ngoetal.2011).AllthispointstoS.suisasapotentialpublichealththreat.

RelativelymorefrequentoccurrenceofhumanS.suisin-fectionsinAsiancountriespointstoapotentialgeographicaltropismofthispathogenthatprobablyshouldbeattributednotonlytothespecificclimatebutalsototheleadingroleofporkindustryandpopularityofporkdishesinthisarea(seeRiskFactors,RiskGroups,andRoutesofInfectionsection)(Fengetal.2014).MostEuropeancasesofS.suisinfectionsinhumanswerereportedfromtheNetherlands(n=41),theUnitedKingdom(n=15),andDenmark(n=12),andzoo-nosescausedbythispathogenoccurredonlysporadicallyintheremainingcountries(Wertheimetal.2009a).OnespecificfeatureoftheEuropeanisolatesofS.suisistheirpredilectiontothemeningesandfrequentinvolvementintheetiologyofpurulentmeningitis(Fengetal.2014).S.suisinfectionshavebeenrelativelyrarelydocumentedintheUnitedStatesandCanada,twopotentplayersintheglobalswinemarket(Donsakuletal.2003,Heidtetal.2005,Gottschalketal.2007).RecentevidencesuggeststhatthelatterphenomenonmaybeatleastpartiallyexplainedbydifferentstructureoftheNorthernAmericanS.suisSTs.AlthoughmostS.suisfoundinAsiaandEuropewerehighlyvirulentST1isolates,theintermediate-virulenceST25andST28strainsseemtoprevailintheUnitedStatesandCanada(Goyette-Desjardinsetal.2014,Atheyetal.2015).

RiskFactors,RiskGroups,andRoutesofInfection

LiteratureevidencesuggeststhattheprincipalriskgroupforS.suisinfectionareindividualsexposedtopigsandporkmeat,usuallyinanoccupationalsetting.ThefollowinggroupscanbeidentifiedasparticularlypredisposedtoS.suisinfection:farmers,slaughterhouseworkers,butchers,andmeatsellers(Dupasetal.1992,Staatsetal.1997,Charlandetal.2000,Lalondeetal.2000).However,thereisalsoev-idenceofoccupationalS.suisinfectioninwhichwildboarswerethesourceofthepathogen,forexample,forforestersandhunters(Rosenkranzetal.2003).Thesusceptibilitytoinfectiondoesnotseemtobeageandsexspecific,aszoo-nosescausedbyS.suiswerereportedin30-to70-year-oldsubjects,bothmenandwomen(Fengetal.2014).

Theaimofacase–controlstudyconductedinVietnam(Nghiaetal.2011)wastoidentifytheriskfactorsforS.suismeningitisusingasubsetof100patientswiththistypeofinfectionandagroupofmatchedhospital(n=303)andcommunitycontrols(n=300).Thestudyidentifiedcon-sumptionofdishescontainingundercooked,rawpork,swineintestines,andporcineblood,occupationalexposuretopigsandpork,andpresenceofskininjurieswhiledealingwithpigsandpigmeatasindependentriskfactorsforS.suisin-fection(Nghiaetal.2011).Accordingtosomeauthors,theincidenceofS.suiszoonosesishigherinsummer(Maetal.2008).Othersshowedthatswineindustryworkersconstituteupto60%ofpatientsinfectedwiththispathogen(Huietal.2005),andresearchersfromtheNetherlandsdemonstratedthatoccupationalexposuretopigsisassociatedwithupto1000-foldincreaseintheriskforS.suisinfection(Halabyetal.2000).However,therearealsopublishedreportsontheoccurrenceofS.suisinfectionsinsubjectswhohaveneverhadanycontactwithswineorconsumedthe‘‘high-risk’’raw

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porkdishes(Kopic´etal.2002,Manzinetal.2008,vandeBeeketal.2008,Fittipaldietal.2009).

Nevertheless,theabovementionedfindings,aswellastheevidencefrommanypublishedcasereports,implythattyp-icallyS.suiszoonosesresultfromawoundinfectionorin-gestionofporkcontaminatedwiththispathogen.Thiswasalsoconfirmedinarecentmeta-analysisbasedonthreestudieswithatotalof1454casesreported,whichidentifiedrawporkconsumption,exposuretopigsorpork,pig-relatedoccupation,andmalesexassignificantriskfactorsforS.suisinfection(Rayanakornetal.2018).

Regardingtherouteoftransmission,agrowingbodyofevidencesuggeststhatS.suiscanbeanairbornepathogen.

S.suiswasshowntosurviveinfecesforupto104days(Clifton-HadleyandEnright1984),andanairbornetrans-missionofthispathogenhasbeendemonstratedinexperi-mentalstudiesinpigs(Berthelot-Heraultetal.2001,Madsenetal.2001).ThosefindingsweremorerecentlyconfirmedbyBonifaitetal.(2014),whodetectedS.suisintheaerosolfromtheswineconfinementbuildingsandinthenasalswabsfrom58%ofporkproducers,takenbeforetheworkshift.

PurulentMeningitisastheMostCommonFormofS.suisInfectioninHumans

Accordingtoliterature,themostcommonformsofzoo-noticS.suisinfectionsaremeningitisandsepsis(Suankratayetal.2004,Wertheimetal.2009b).Thefirstreportedcaseof

S.suismeningitiswasdiagnosedinDenmarkin1968(Staatsetal.1997).Sincethen,meningitiswasshowntobethemostcommonpresentationofthisinfectioninbothEuropeandAsia(84.6%and75.2%,respectively),andsepsisturnedouttobethesecondmostcommonofS.suis-relatedzoonoses(15.4%and18.6%,respectively)(Huangetal.2005).Other,lessoftenreportedclinicalformsofS.suisinfectionincludeenteritis,arthritis,endocarditis,pneumonia(predominantlyanopportunisticone),spondylodiscitis,endophthalmitis,uveitis,andperitonitis(Huangetal.2005).AlsoinalargeretrospectiveanalysisofpatientsfromHongKonghospital-izedowingtoS.suisinfection,primaryclinicalmanifesta-tionsweremeningitis(48%),sepsis(38%),andendocarditis(14%)(Maetal.2008).

S.suiscanbealsoanetiologicalfactorofstreptococcaltoxicshock-likesyndrome(STSLS).AfewcasesofSTSLScausedbyS.suishavebeendescribedinvariouscountriesthusfar,primarilyinpigfarmers(Gomezetal.2014,Ya-manakaetal.2015,Mancinietal.2016,Kimetal.2018).Accordingtoliterature,thiscondition,characterizedbyshock,multiorganfailure,rapidlyprogressivesoft-tissuein-fection,andhighfatality,maybecausedbysomeS.suisisolatesthatreleasemoreproinflammatorycytokinesthanothers(Yeetal.2009).

Usually,S.suisinfectionstartswiththetypicalmeningealsigns,suchasfever,headache,nausea,andvomiting,andneurologicalsymptoms,suchasdizziness,balancedisorders,andlimbtrembling.Theresultsofcentralnervoussystemimagingarenormalinmostcases.Thediagnosisofpurulentmeningitiscanbeconfirmedbasedoncerebrospinalfluid(CSF)examinationandCSFandbloodculturing.Mostpa-tientsrespondwelltobroad-spectrumintravenousantibioticssuchaspenicillin,ampicillin,amikacin,orcefotaxime.Usuallyaspectacularimprovementofgeneralandneuro-

logicalstatusisobservedwithinafewdays/weekofsuchtreatment.Howevercontrarytopurulentmeningitisofotheretiologies,infectionscausedbyS.suisshowatendencytorelapse(Dupasetal.1992,Bronsteinetal.1995,Grebeetal.1997).

LiteraturedataimplythatS.suismeningitisischaracter-izedbyprolonged,biphasiccoursewithfrequentincidenceofcerebellarataxiaanddeafness(sometimesirreversible)(Dupasetal.1992,Bronsteinetal.1995,Grebeetal.1997).Exacerbationofthesymptomsisusuallyobservedafter2–3weeksoffirst-lineantibiotictherapy.ClinicalmanifestationofrelapsingS.suismeningitisvaries.Accordingtotheau-thorsofonereviewarticle,aconsiderableproportionofpa-tientswithS.suismeningitis(50.5%fromEuropeand51.9%fromAsia)developdeafnessafteratemporaryimprovementoftheirclinicalstatus(Huangetal.2005),anddatafromothercentersimplythattheprevalenceofsecondarydeafnessinsubjectswithS.suismeningitismaybeevenhigher,upto80%(Kayetal.1995,Maietal.2008,Wertheimetal.2009a).TheauthorsofanotherreviewarticleshowedthathearinglossinS.suismeningitisissensorineural,involveshigh-frequencyrange,andcanbeprofound(>80dB)(Wertheimetal.2009a).Eitheroneorbothearscanbeaffected.Al-thoughitmaysometimesresolveovertime,typicallythehearinglossispermanent.InastudyconductedinVietnam,66.4%ofadultpatientswithS.suismeningitispresentedwithmild-to-severehearinglossatthetimeofhospitaldischarge,ascomparedwith47.7%sixmonthsthereafter(Fengetal.2014).Sometimes,hearinglossmaybeassociatedwithvestibulardysfunction,forexample,ataxia(Fengetal.2014).Despiteconsiderableprevalence,stilllittleisknownontheetiopathogenesisofhearingimpairmentobservedatlaterstagesofS.suismeningitis.Accordingtoonetheory,thelossofhearingisassociatedwithpurulentinternalotitis,resultingfromdamageofcochleartissuesbySLY,apreviouslymentionedtoxinofS.suis(Kay1991).However,thistheoryhasnotbeenconfirmedinhumansthusfar(Spissetal.1999).TheauthorsofaVietnamesestudy(Maietal.2008)identi-fiedindependentriskfactorsforhearingimpairmentduringthecourseofS.suismeningitisbasedontheretrospectiveanalysisof151patientswiththiscondition.Severedeafnessathospitaldischargewasassociatedwithpatients>50yearsofage,infectionwithastraincarryingtheepfgeneanddexamethasonetherapy,butnotwithbacterialDNAloadin

theCSF(Maietal.2008).

TherapeuticImplicationsandPreventiveMeasures

Someauthorsclaimedonefficientcontrolofthefirst-phaseinfectionwithbroad-spectrumantimicrobials,suchaspeni-cillin,ampicillin,andceftriaxone(Huangetal.2005,Maetal.2008,Huhetal.2011).However,frequentoccurrenceofhearingimpairmentinsubjectswithS.suismeningitisim-pliesthatpotentiallyototoxicagents,suchasaminoglycosideantibiotics,shouldbeusedwithextremecautioninthisgroup.Moreover,someevidencesuggeststhatagrowingproportionofS.suisstrainsinvolvedinpurulentmeningitismayshowmultidrugresistance(Hoaetal.2011).Althoughthisseemstobeanissuemainlyincountrieswithhighin-cidenceofS.suisinfections,itshouldnotbeneglected,es-peciallyafterastudyconductedinNewZealandshowedhighratiooflocalfarmersandmeatinspectorsbeingseropositive

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toS.suisSS2(Dickieetal.1987,Coolenetal.1989),whichpointstothelikelypresenceofsubclinicalinfections.

Finally,steroiduserequirescarefulanalysis;whilester-oidsareanimportantelementofsuccessfultherapyofbac-terialmeningitis,theyarealsoariskfactorforsecondaryhearingloss.

ApartfromthecontrolofS.suisinfection,equallyim-portantisprimaryprevention,specificallyuseofappropriateprotectivedevices(e.g.,gloves)bypersonnelexposedtocontactwithpigsandpork,especiallywhentheskininteg-rityisbreached,andalsoathoroughveterinarycontrolofslaughteredanimalsandadherencetoallgeneralsanitaryandhygienicstandardsarefollowed.

Conclusion

LiteraturedatashowthatS.suisisanimportantetiologicalfactorofpurulentmeningitis,especiallyinsubjectsbeingoccupationallyexposedtocontactwithpigsand/orporkmeat.OwingtogrowingincidenceofS.suismeningitis,ahistoryofsuchexposureshouldbeverifiedineachpatientpresentingwithtypicalmeningealsymptoms.Whenever,

S.suiswasconfirmedastheetiologicalfactorofpurulentmeningitis,therapeuticprotocolshouldbeadjustedappro-priatelytoavoidpatient’sexposuretopotentiallyototoxicantimicrobialagentsandcorticosteroids.ConsideringthebiphasiccharacterofS.suismeningitisanditsfrequentlyatypicaloutcome,allindividualswiththisconditionshouldbeoptimallysupervisedbyamultidisciplinaryteam,in-cludinganENTspecialist.

AuthorDisclosureStatement

Nocompetingfinancialinterestsexist.

References

ArendsJP,ZanenHC.MeningitiscausedbyStreptococcussuis

inhumans.RevInfectDis1988;10:131–137.

AtheyTB,AugerJP,TeateroS,DumesnilA,etal.Complexpopulationstructureandvirulencedifferencesamongsero-type2Streptococcussuisstrainsbelongingtosequencetype28.PLoSOne2015;10:e0137760.

BaigA,WeinertLA,PetersSE,HowellKJ,etal.Wholege-nomeinvestigationofadivergentcladeofthepathogenStreptococcussuis.FrontMicrobiol2015;6:1191.

Berthelot-He´raultF,GottschalkM,Labbe´A,CarioletR,etal.ExperimentalairbornetransmissionofStreptococcussuiscapsulartype2inpigs.VetMicrobiol2001;82:69–80.

BonifaitL,VeilletteM,Le´tourneauV,GrenierD,etal.De-tectionofStreptococcussuisinbioaerosolsofswinecon-finementbuildings.ApplEnvironMicrobiol2014;80:3296–3304.

BronsteinAM,MorlandAB,RuddockKH,GrestyMA.Re-coveryfrombilateralvestibularfailure:Implicationsforvi-sualandcervico-ocularfunction.ActaOtolaryngolSuppl1995;520:405–407.

CamporeseA,TizianelG,BruschettaG,CruciattiB,etal.HumanmeningitiscausedbyStreptococcussuis:Thefirstcasereportfromnorth-easternItaly.InfezMed2007;15:111–114.

CharlandN,NizetV,RubensCE,SikKimK,etal.Strepto-coccussuisserotype2interactionswithhumanbrainmicro-vascularendothelialcells.InfectImmun2000;68:637–643.

Clifton-HadleyFA,EnrightMR.FactorsaffectingthesurvivalofStreptococcussuistype2.VetRec1984;114:584–586.

CoolenL,DensJ,BaeckE,ClaesC,etal.Streptococcussuismeningitis,permanentperceptivedeafnessanden-dophthalmitis.IntensiveCareMed1989;15:545.

DemarM,BelzunceC,SimonnetC,RenauxA,etal.Strepto-coccussuismeningitisandbacteremiainman,FrenchGui-ana.EmergInfectDis2013;19:1545–1546.

DickieAS,BremnerDA,WongPY,etal.Streptococcussuis

bacteraemia.NZMedJ1987;100:677–678.

DonsakulK,DejthevapornC,WitoonpanichR.Streptococcussuisinfection:Clinicalfeaturesanddiagnosticpitfalls.SoutheastAsianJTropMedPublicHealth2003;34:154–158.

DupasD,VignonM,GerautC.Streptococcussuismeningitis.Aseverenoncompensatedoccupationaldisease.JOccupMed1992;34:1102–1105.

FengY,ShiX,ZhangH,ZhangS,etal.RecurrenceofhumanStreptococcussuisinfectionsin2007:Threecasesofmen-ingitisandimplicationsthatheterogeneousS.suis2circulatesinChina.ZoonosesPublicHealth2009;56:506–514.

FengY,ZhangH,MaY,GaoGF.UncoveringnewlyemergingvariantsofStreptococcussuis,animportantzoonoticagent.TrendsMicrobiol2010;18:124–131.

FengY,ZhangH,WuZ,WangS,etal.Streptococcussuisinfection:Anemerging/reemergingchallengeofbacterialinfectiousdiseases?Virulence2014;5:477–497.

FittipaldiN,CollisT,ProtheroB,GottschalkM.Streptococcussuismeningitis,Hawaii.EmergInfectDis2009;15:2067–2069.

FittipaldiN,SeguraM,GrenierD,GottschalkM.VirulencefactorsinvolvedinthepathogenesisoftheinfectioncausedbytheswinepathogenandzoonoticagentStreptococcussuis.FutureMicrobiol2012;7:259–279.

GeffnerSclarskyDE,MorenoMun˜ozR,CampilloAlperaMS,PardoSerranoFJ.Streptococcussuismeningitis.AnnMedIntern2001;18:317–318.

GomezE,KennedyCC,GottschalkM,CunninghamSA,etal.Streptococcussuis-relatedprostheticjointinfectionandstreptococcaltoxicshock-likesyndromeinapigfarmerintheUnitedStates.JClinMicrobiol2014;52:2254–2258.

GottschalkM,SeguraM.ThepathogenesisofthemeningitiscausedbyStreptococcussuis:Theunresolvedquestions.VetMicrobiol2000;76:259–272.

GottschalkM,SeguraM,XuJ.Streptococcussuisinfectionsinhumans:TheChineseexperienceandthesituationinNorthAmerica.AnimHealthResRev2007;8:29–45.

Goyette-DesjardinsG,AugerJP,XuJ,SeguraM,etal.Strep-tococcussuis,animportantpigpathogenandemergingzoo-noticagent-anupdateontheworldwidedistributionbasedonserotypingandsequencetyping.EmergMicrobesInfect2014;3:e45.

GrebeT,BergenthalD,FahrAM,SchejaHW.MeningitiscausedbyStreptococcussuistype2inanadult.DtschMedWochenschr1997;122:1244–1247.

GustavssonC,RamussenM.SepticarthritiscausedbyStrep-tococcussuisserotype5inpigfarmer.EmergInfectDis2014;20:489–491.

HalabyT,HoitsmaE,HuppertsR,SpanjaardL,etal.Strep-tococcussuismeningitis,apoacher’srisk.EurJClinMi-crobiolInfectDis2000;19:943–945.

HaleisA,AlfaM,GottschalkM,BernardK,etal.MeningitiscausedbyStreptococcussuisserotype14,NorthAmerica.EmergInfectDis2009;15:350–352.

DownloadedbyEastCarolinaUniversityfrom

at03/13/19.Forpersonaluseonly.

HeidtMC,MohamedW,HainT,VogtPR,etal.Humanin-fectiveendocarditiscausedbyStreptococcussuisserotype2.JClinMicrobiol2005;43:4898–4901.

HillJE,GottschalkM,BrousseauR,HarelJ,etal.Biochemicalanalysis,cpn60and16SrDNAsequencedataindicatethatStreptococcussuisserotypes32and34,isolatedfrompigs,areStreptococcusorisratti.VetMicrobiol2005;107:63–69.

HoaNT,ChieuTT,NghiaHD,MaiNT,etal.TheantimicrobialresistancepatternsandassociateddeterminantsinStrepto-coccussuisisolatedfromhumansinsouthernVietnam,1997–2008.BMCInfectDis2011;11:6.

HuangYT,TengLJ,HoSW,HsuehPR.Streptococcussuis

infection.JMicrobiolImmunolInfect2005;38:306–313.

HuhHJ,ParkKJ,JangJH,LeeM,etal.Streptococcussuismeningitiswithbilateralsensorineuralhearingloss.KoreanJLabMed2011;31:205–211.

HuiAC,NgKC,TongPY,MokV,etal.BacterialmeningitisinHongKong:10-years’experience.ClinNeurolNeurosurg2005;107:366–370.

IbarakiM,FujitaN,TadaM,OhtakiO,etal.AJapanesecaseofStreptococcussuismeningitisassociatedwithlumbarepidu-ralabscess.RinshoShinkeigaku2003;43:176–179.

IshidaS,TienleHT,OsawaR,TohyaM,etal.DevelopmentofanappropriatePCRsystemforthereclassificationofStrep-tococcussuis.JMicrobiolMethods2014;107:66–70.

KayR.Thesiteofthelesioncausinghearinglossinbacterialmeningitis:Astudyofexperimentalstreptococcalmeningitisinguinea-pigs.NeuropatholApplNeurobiol1991;17:485–493.

KayR,ChengAF,TseCY.StreptococcussuisinfectioninHongKong.QJM1995;88:39–47.

KerdsinA,DejsirilertS,SawanpanyalertP,BoonnarkA,etal.SepsisandspontaneousbacterialperitonitisinThailand.Lancet2011;378:960.

KerdsinA,OishiK,SripakdeeS,BoonkerdN,etal.ClonaldisseminationofhumanisolatesofStreptococcussuissero-type14inThailand.JMedMicrobiol2009;58:1508–1513.

KimHS,LeeMH,KimYS,ChoiJK,etal.Acaseoflife-threatingStreptococcussuisinfectionpresentedassepticshockandmultipleabscesses.InfectChemot