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Hadeel Abdullah

Abdulrhman Al-Jashaam

Abdulrhman Al-Jashaam

Nader Al-Aridah

4

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It’sbeenawhilehasn’tit?Let’srun-throughsomepoints;

TheEnterobacteriaceae(coliforms)arealarge,heterogeneousgroup

ofgram-negativerodswhosenaturalhabitatistheintestinaltractof

humansandanimals.Somearepartofthenormalmicrobiota(e.g.E.

coli)andincidentallycausedisease,butothers(e.g.Salmonellae

andShigellae)areregularlypathogenicforhumans.Theyare

facultative anaerobes oraerobes,possessacomplexantigenic

structure,andproduceavarietyoftoxinsandothervirulence

factors.

Salmonellaeareoftenpathogenicforhumansoranimals

whenacquiredbytheoralroute.Theyaretransmittedfromanimals

andanimalproductstohumans,wheretheycausegastroenteritis,

systemicinfection,andentericfever(infectionsmightoverlap).

Mostisolatesaremotilewithperitrichousflagella,sotheyhave

Hantigens(antigenslocatedonflagella).

Theyaregram-negativebacilli,

sotheypossessOantigens.

Theyhavethevirulent

capsularViantigens.

Theygrowreadilyonsimple

media,buttheyalmostnever

fermentlactoseorsucrose.

Theyfermentglucoseand

mannosetoformacidandsometimesgas(theyfermentrather

thanoxidizeglucose;theyareoxidasenegative).

- Non-lactosefermenters=theygivecolorlesscoloniesin

EosinmethyleneblueEMBorMacConkeyagarplates.

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TheyusuallyproduceH₂S(extrainfo:theyreducecompounds

thatpossesssulfurinordertoobtainenergy).

- RecallthatShigellaedon’tproduceH₂S(differential

test).

Theysurvivefreezinginwaterforlongperiods.

Theyareresistanttocertainchemicals(e.g.brilliant green,

sodiumtetrathionate,sodiumdeoxycholate)thatinhibitother

entericbacteria;suchcompoundsarethereforeusefulfor

inclusioninmediatoisolateSalmonellaefromfeces.

CLASSIFICATION

Theclassificationofsalmonellaeiscomplex and controversial.

Regardlessofhow,Salmonellaisdividedintotwospecieseach

withmultiplesubspecies and serotypes.Thetwospeciesare

Salmonella enterica (causeshumanillness) andSalmonella

bongori(associatedwithcold-bloodedanimals).

Sixserovars(serotypes) ofsalmonellaeofmedicalimportance:

1. S.entericasubsp.typhi(causestyphoidfever).

2. S.entericasubsp.enteritidis(causesgastroenteritis).

3. S.entericasubsp.typhimurium.

4. S.entericasubsp.choleraesuis(causesbacteremiaand

focallesions).

5. S.entericasubsp.paratyphi.

6. S.entericasubsp.dublin.

Salmonella entericaserotypescanbedividedintotwomain

groups;typhoidal(causetyphoidfeverthatwillbediscussed)

andnon-typhoidal.

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Fourtyphoidalserotypescanbeidentifiedintheclinical

laboratorybybiochemicalandserologictests.Theseserotypes

shouldberoutinelyidentifiedbecauseoftheirclinical

significance.Theyareasfollows:

1. SalmonellaparatyphiA(serogroupA).

2. SalmonellaparatyphiB(serogroupB).

3. Salmonellaparatyohi C (serogroupC).

4. Salmonellatyphi

Non-typhoidalSalmonellaserotypes(NTS)primarilycause

gastroenteritis,bacteremia,andfocalinfections.Manyofthese

non-typhoidalinfectionsarecausedby₁S.enteritidisand₂ S.

typhimuriumthatcausegastroenteritis,₃S.choleraesuis thatcauses

bacteremiaandfocal infections.

- EnteritidisandTyphimuriumarethetwomost

commonserotypesreportedinthedevelopedworld.

- Imadethischartformoreclarification,youwon’tfindit

intheslides.

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HumansaretheonlyreservoirforSalmonella typhi,theycan

carrythebacteriainthebiliary tractforverylongtimes(chronic

asymptomaticcarriers,notnormalflora),andtransmitthe

bacteriatootherpersons(eitherdirectly₁orindirectly₂via

foodorwatercontaminationbytheirfeces).Theseindividualsare

amoreimportantsourceofcontaminationthanfrankclinical

cases (symptomatic)thatarepromptlyisolated,suchaswhen

carriersworkingasfoodhandlersare“shedding”organisms.

However,thevastmajorityofSalmonellae (otherthanS.typhi)are

chieflypathogenicinanimalsthatconstitutethereservoirfor

humaninfectionastheycarrythebacteriaintheirtissues,

excreta,oreggs(e.g.cattle,rodents,andfowl).

- Recall:

Shigella, Salmonella, and Yersiniaarenotnormallypartofthe

humanmicrobiomeandarealwaysconsideredpathogenicif

foundthere.

THE “ENTERIC FEVERS” (TYPHOID FEVER)

TyphoidisaseveresystemicdiseasecausedbyS. typhi, S. paratyphi

A, B, and C.Itisthemostseverepresentationofsalmonellosis(a

majorcauseofmorbidityandmortalityworldwide).

Thecharacteristicfeatureoftyphoidisthatitisamonth-long

fever.

Asmentionedabove,Salmonellatyphicancolonizethe

gallbladderandpersistinanasymptomaticcarrierstate

thatisfrequentlyassociatedwiththepresenceofgallstones.

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- Therefore,itisstrictlyahumandiseaseandmustbe

tracedbacktoahumanreservoir.

Itsincidencedifferssignificantlydevelopingvs.developed

counties0.2-4casestoupto500/10⁵population.

PATHOGENESIS

Theorganismsalmostalwaysenterviatheoralroute -vertical

transmission(trans-placental)ispossible-,usuallywith

contaminatedfoodordrink,andamongthehostfactorsthat

contributetoresistancetosalmonellainfectionaregastric acidity₁,

normal intestinal microbiota₂,andlocalintestinalimmunity₃ (in

otherwords,stomachacidityandnormalintestinalmicrobiotaare

importantdeterminantsofsusceptibility;acidityandintestinal

bacteriacankilltheSalmonellabeforeithastheopportunityto

invadecellsandreplicate).Therefore,themeaninfectivedoseto

produceclinicalorsubclinicalinfectioninhumansishigh(10⁵to

10⁸),i.e.lowdosesarenotsufficienttocausethedisease.Thank

god.

Afteringestion,infectionwithSalmonellaeischaracterizedby

attachmentofthebacteriatocellsliningtheintestinallumen.

Salmonellaeselectivelyattachtospecializedepithelialcells(M

ormicrofoldcells)ofthePeyer’spatches(justlikeShigellae).

Thebacteriaaretheninternalizedbyendocytosis(within

vacuolesorphagosomes)andtransportedtothelamina

propria,wheretheyarereleased intothelymphatic

circulation.

Oncethebacteriareachintestinallymphnodes,theymultiply

inmononuclearcells tomesentericlymphnodestoblood

throughthoracicduct(transientbacteremia).

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Alongtheirjourneythroughthemesentericlymphnodestothe

thoracicduct,theyinvadethereticuloendothelial tissuesof

theliver,spleen,andbonemarrow.

Circulatingendotoxincauseprolongedfever(endotoxinisa

componentoftheexteriorcellwallofgram-negativebacteria).

Inflamedmucosaandlymphatics,necrosisandsloughingof

overlayingepithelium.

Producingulcerthatmaybleed,however,theseulcersheal

withoutscarring.

Cellmediatedimmunityisimportant(it’sanintracellular

pathogen).

Extra:recallthatShigellaeescapefromtheirvacuolesandarenot

transportedwithinphagosomesintothelaminapropriatobe

releasedintothecirculation.Instead,theybecomefreeandinvade

adjacentepithelialcells.

CLINICAL MANIFESTATIONS

Theincubationperiodranges

from7-14days.

Onsetisinsidious.

Duringthe1stweek(theweek

aftertheincubationperiod):

Fever,malaise,anorexia,

myalgia,headache,abdominal

pain,diarrhea(early),and

constipation(later)occur.

Theincreaseintemperaturein

astepwisefashionbecomeunremittingandhigh (i.e.thefever

risesgraduallytoahighplateau(becomesconstant)).

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Inthe2ndweek:

Highfever,fatigue,cough,epistaxis,abdominalsymptoms

moreseverandrosespotsareseen(skinrashormaculeson

chestandback).

Inthe3rd- 4thweek:

Ifnocomplicationsarise,symptomsandsignsgradually

resolveontheirown.

Inthepre-antibioticera,thechiefcomplicationsofenteric

feverwereintestinalhemorrhageandperforation,andthe

mortalityratewas10–15%.Now,afterantibiotics,mortality

decreases↘tolessthan1%.

Theprimarydiagnosticmethodisbloodculturing.

ENTEROCOLITIS

Thisisthemost commonmanifestation(CLINICAL)of

Salmonellainfection(typhoidfeveristhemostserious

manifestation).

IntheUnitedStates,S.typhimuriumandS.enteritidisare

prominent,butenterocolitiscanbecausedby anyofthemore

than1400groupIserotypes(subs.enterica)ofSalmonellae.

Aswesaid,thereservoirsareinfectedanimals and their

productsspecificallypoultry,eggs,anddairy.

CLINICAL MANIFESTATIONS

Eightto48hoursafteringestionofsalmonellae,thereis

nausea,headache,vomiting,andnon-bloodydiarrhea,with

fewleukocytesinthestools.Low-gradefeveriscommon,but

theepisodeusuallyresolvesin2–3 days.

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Inflammatorylesionsofthesmallandlargeintestineare

present.However,bacteremiaisrare(2–4%)exceptin

immune-deficient persons.

- Intestinallesions>positive.

- Bacteremia>negative.

Bloodcultureresultsareusuallynegative (no bacteremia),

butstoolcultureresultsarepositiveforSalmonellae andmay

remainpositiveforseveralweeksafterclinicalrecovery.

- Blood>negative.

- Stool>positive.

BACTERAEMIA WITH FOCAL LESIONS

ItisassociatedcommonlywithS. Choleraesuisbutyouhavetoknow

thatall Salmonellae can cause bacteremia.

Afteroralinfection,thereisearlyinvasionofthebloodstream

withpossiblefocallesionsinlungs,bones,meninges,andso

on…butintestinalmanifestationsareoftenabsent.

Itisnowonderthatbloodculturesarepositive(bacteremia).

Bacteremiaisassociatedwithlocalsuppurativeinfections

seedingfromanorgan,usuallythebonecausingosteomyelitis

orthejointsintheformofarthritisinmorethan10%ofthe

patients.

Bacteremiadependsontheserotypeandthepatients’health

state.

- Sicklecellanemiapatients(sicklers)aremorelikely

todevelopSalmonellaebacteremia.

Theprimarydiagnosticmethodisblood culturing.

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DIAGNOSTIC LABORATORY TESTS (FOR ALL SALMONELLA INFECTIONS) (I - III)

I) SPECIMENS:

-Bloodforculturemustbetakenrepeatedly.

Inenteric feversandsepticemias (bacteremia),blood

cultureresultsareoftenpositiveinthefirstweekofthe

disease.Bonemarrowculturesmaybeuseful.

-Urinecultureresultsmaybepositiveafterthesecondweek.

-Stoolspecimensalsomustbetakenrepeatedly.Inenteric

fevers,thestoolsyieldpositiveresultsfromthesecondor

thirdweekon,whileinenterocolitis,thestoolsyieldpositive

resultsduringthefirstweek(early).

-Apositivecultureofduodenaldrainageestablishesthe

presenceofsalmonellaeinthebiliary tractincarriers

(asymptomatic).

II) BACTERIOLOGIC METHODS FOR ISOLATION OF SALMONELLAE

1. Enrichmentcultures:thespecimen(usuallystool)isputinto

“seleniteF”or“tetrathionatebroth”,bothofwhich inhibit

replication of normal intestinal bacteria₁andpermit

multiplication of salmonellae₂.

2. DifferentialandSelectivemediumcultures:

A) Differentialmediumculture:EMB, MacConkey,or

deoxycholatemediumpermitsrapiddetectionof

lactosenon-fermenters(notonlysalmonellae).

Gram-positiveorganismsaresomewhatinhibited.

Bismuthsulfitemediumpermitsrapid detectionof

Salmonellae,whichformblackcoloniesbecauseofH₂S

production.

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B) Selectivemediumculture:

Thespecimenisplatedon

salmonella-shigella(SS)agar,

Hektoenentericagar,xylose-

lysinedecarboxylase(XLD)

agar.

3. Finalidentification:Suspectcoloniesfromsolidmediaare

identifiedbybiochemicalreaction(e.g.H₂Sproduction)

patternsandslideagglutination(serological)testswith

specificsera.

III) SEROLOGIC METHODS

1. Agglutinationtest:inthistest,knownsera(containantibodies

specificforSalmonellae antigens)andunknown(suspectedto

carrySalmonellaecolonies)culturearemixedonaslide.

- Clumping (positive),canbeobservedwithinafew

minutes.Thistestisparticularlyusefulforrapid

preliminaryidentificationofcultures.Thereare

commercialkitsavailabletoagglutinateandsero-

groupSalmonellaebytheirOantigens:A,B,C1,C2,

D,andE.

2. Tubedilutionagglutinationtest(Widaltest):

InthistestwelookforSalmonellaeantibodiesinthepatient’s

serumusingantigensthatarespecificforSalmonellae(from

thelaboratory).

Serumagglutinins(antibodies)risesharplyduringthe

secondandthirdweeksofS.typhiinfection(inthepatient’s

serum).TheWidaltestdetectstheseantibodiesagainstthe

OandHantigens.

** EMB and MacConkey agar

plates promote the growth of

Enterobacteriaceae family

and differentiate between

them in lactose fermentation.

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Serialdilutionsofunknownsera(here,theseraare

unknown;becausewedon’tknowwhetherthereare

Salmonella-specificantibodiesornot)aretestedagainst

antigensfromrepresentativeSalmonellae.

- False-positiveandfalse-negativeresultsoccur.

Theinterpretivecriteriawhensingleserumspecimensare

testedvary,butatiteragainsttheOantigenofgreater

than 1:320andagainsttheH antigenofgreaterthan

1:640isconsideredpositive.

- Oantigen>greaterthanoneover320titer

- Hantigen>greaterthanoneover640titer

ResultsofserologictestsforSalmonellainfectioncannotbe

reliedupontoestablishadefinitivediagnosisbecauseof

thecrossreactivitybetweenantigensthatmayoccurdueto

immunization(againsttyphoidforexample)orprevious

intestinalinfectionsotherthanSalmonellainfections.

**HightiterofantibodytotheViantigenoccursinsomecarriers

(notmentioned).

**Atleasttwoserumspecimens,obtainedatintervalsof7–10days,

areneededtoproveariseinantibodytiter(notmentioned).

**AlternativestotheWidaltestincluderapidcolorimetricandEIA

methods(notmentioned).

IMMUNITY

InfectionswithSserotypeTyphiorParatyphiusuallyconfer

acertaindegreeofimmunity.However, reinfection may

occurbutisoftenmilderthanthefirstinfection.

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CirculatingantibodiestoOandViarerelatedtoresistance

toinfectionanddisease.However, relapses may occurin

2–3weeksafterrecoverydespiteantibodies.

SecretoryIgAantibodiesmaypreventattachmentof

Salmonellaetointestinalepithelium(IgAantibodiesarethe

cornerstoneofimmunityinSalmonellainfections)

Aswementionedbefore,personswithS/S hemoglobin

(sicklecelldisease)areexceedinglysusceptibleto

Salmonellainfections,particularlyosteomyelitis.Persons

withA/Shemoglobin(sicklecelltrait)maybemore

susceptiblethannormalindividuals(thosewithA/A

hemoglobin).

Extrainfo:hemoglobinS(HgbS)isanabnormaltypeof

hemoglobinthatyoucaninheritfromyourparents.While

hemoglobinA(HgbA)isthenormaltypeofhemoglobininthered

bloodcells.

TREATMENT

Althoughentericfeversandbacteremiawithfocallesions

require antimicrobialtreatment(usuallyciprofloxacinor

cephalosporin),thevastmajorityofcasesofenterocolitisdo

not.AntimicrobialtreatmentofSalmonellaenteritisin

neonatesisimportant.

o Inenterocolitis,clinicalsymptomsandexcretionofthe

Salmonellaemaybeprolongedbyantimicrobialtherapy.

Inseverediarrhea,replacementoffluidsandelectrolytes

isessential.

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AntimicrobialtherapyofinvasiveSalmonellainfectionsis

withampicillin,fluoroquinolones,trimethoprim–

sulfamethoxazole,orathird-generationcephalosporin

Multipledrugresistancetransmittedgeneticallybyplasmids

amongentericbacteriaisaprobleminSalmonellainfections.

Susceptibilitytestingisanimportantadjuncttoselectinga

properantibiotic.

Inmostcarriers,theorganismspersistinthegallbladder

(particularlyifgallstonesarepresent)andinthebiliarytract.

Somechroniccarriershavebeencuredbyampicillinalone,

butinmostcasescholecystectomy(removalofgallbladder)

mustbecombinedwithdrugtreatmenthenceitisthemost

commonsiteofcolonization.

PREVENTION AND CONTROL

Threepercentofsurvivorsoftyphoidbecomehealthy

permanentcarriers,harboringtheorganismsinthe

gallbladder,biliarytract,or–rarely-theintestineorurinary

tract.

Sanitary measuresmustbetakentopreventcontamination

offoodandwaterbyrodentsorotheranimalsthatexcrete

salmonellae.

Infectedpoultry,meats,andeggsmustbethoroughly

cooked.

Carriersmustnotbeallowedtoworkasfood handlersand

shouldobservestricthygienicprecautions.

Twotyphoid*symptomatic form*vaccinesarecurrently

available:anorallive,attenuatedvaccineandaVicapsular

polysaccharidevaccineforintramuscularuse.Vaccinationis

recommendedfortravelerstoendemicregions,especiallyif

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thetravelervisitsruralareasorsmallvillageswherefood

choicesarelimited,efficacyof50–80%(notthatmuch;it

givesshort-lived immunity).

Salmonellae √

Yersiniacomprisesgram-negativebacteriaofthefamily

Enterobacteriaceae(gammaproteobacteria←theclassname)

Yersiniaeareshort,pleomorphic(cocco-bacilli)rodsthatcan

exhibitbipolarstaining(i.e.theendsofthebacillistainmore

intenselythanthemiddle).

Mosthaveanimalsastheir

naturalhosts,buttheycan

produceseriousdiseasein

humans–occasionally-.

Theygrowbest(optimally)at

25°Candaremotileat25°C

butnon-motileat37°C (body

temperature).

Y.pestis–thecauseofplague(blackdeath)-istransmittedto

humansusuallythroughthebiteofaninfectedflea,although

inhalationisanotherpotentialroute.

Yersiniosisisazoonoticinfectionwithanenteropathogenic

Yersiniaspecies,usuallyY. enterocoliticaorY.

pseudotuberculosis.

Y. enterocoliticaexistsinmorethan70serotypes;most

isolatesfromhumandiseasebelongtoserotypesO:3,O:5,

O:8,andO:9.

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Y. enterocoliticahasbeenassociatedwithtransfusionrelated

infectionscausedbycontaminatedredbloodcells.Thisisa

consequenceoftheabilityoftheorganism,transmittedbyan

asymptomaticdonor,tomultiplyatrefrigeration

temperatures.

**Y.enterocoliticaisfoundworldwideandhasbeenisolatedfroma

widevarietyofwildanddomesticanimalsandenvironmental

samples,includingsamplesoffoodandwater(notmentioned).

**Mostclinicalinfectionsareassociatedwithsero-groupsO:3,O:9,

andO:5,27,withadecliningnumberofO:8infections(not

mentioned).

**Consumptionorpreparationofrawmeat,productsmilk

(pasteurized,unpasteurized,andchocolate-flavored)andvarious

foodscontaminatedwithspringwaterproductsarelinkedwith

infection(notmentioned).

**Y.pseudotuberculosisislessfrequentlyreportedasacauseof

humandiseasethanY.enterocolitica(notmentioned).

PATHOGENESIS

Transmissiontohumansprobablyoccursbycontaminationof

food,drink,orfomites(transmittedorally).

Initialreplicationinthesmallintestineisfollowedbyinvasion

ofPeyer’spatchesofthedistalileumviaM cells,withonward

spreadtomesenteric lymph nodes (rememberSalmonellae?).

Theliverandspleencanalsobeinvolvedafteroralinfection.

Thecharacteristichistologicappearanceofentero-pathogenic

Yersiniaeafterinvasionofhosttissuesisasextracellularmicro-

abscessessurroundedbyanepithelioidgranulomatouslesion.

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Y. enterocoliticacanproduceaheat-stable enterotoxin₁,but

theroleofthistoxinindiarrheaassociatedwithinfectionisnot

welldefined.

AllYersiniaepossesslipopolysaccharides(gram-negative)that

haveendotoxicactivity₂whenreleased.

Theyhavetype III secretion systems ₃thatconsistofa

membrane-spanningcomplexthatallowsthebacteriatoinject

proteinsdirectlyintocytoplasmofthehostcells.

ThepathogenicYersiniaehavea pathogenicity island (PAI)₄

thatencodesforanironscavengingsiderophore.

CLINICAL MANIFESTATIONS

Y.enterocoliticaismorecloselyassociatedwithterminalileitis

andY.pseudotuberculosiswithmesenteric adenitis,but both

organisms maycausemesenteric adenitisandsymptomsof

abdominal pain, fever, and tendernessthatresultin

pseudo-appendicitis,withthesurgicalremovalofanormal

appendix.(i.e.Y.enterocoliticaandY. pseudotuberculosisare

possibleinfectiousagentsinpseudo-appendicitis).

Yersinia gastroenteritisisthemostcommonreported

presentationininfectionwithpathogenicY.enterocolitica,

especiallyinchildrenundertheageof4,whoformthesingle

largestgroupinmostcaseseries.Itischaracterizedbyaself-

limitingdiarrhea,fever,andabdominalpain.

Post-infectivephenomenaofreactive arthritismightbe

developingwithin2–4weeksofaprecedinginfection.

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- Bloodmaybedetectedindiarrhealstool.

- Olderchildren(>4y/o)andadultsaremorelikely

thanyoungerchildrentopresentwithabdominal

pain,whichcanbelocalizedtotherightiliacfossa

(appendixsite),asituationthatoftenleadsto

laparotomyforpresumedappendicitis(pseudo-

appendicitis).

Gastrointestinalcomplicationsincludegranulomatous

appendicitis,achronicinflammatoryconditionaffectingthe

appendix.

LABORATORY DIAGNOSIS

1. Specimens:

Specimensmaybestool₁,

blood₂,ormaterialobtainedat

surgicalexploration₃.

2. Culture:

ThenumberofYersiniaeinstool

maybesmallandcanbe

increasedby“cold enrichment”

(why cold? because it grows

optimally at 25 C ⁰) wheremanyfecalorganismsdonot

survive,butY. enterocolitica multiplies.

Then,subculturesmadeatintervalsonMacConkeyagarmay

yieldYersiniae.Alternatively,mostclinicallaboratoriesusea

Yersiniaselectiveagarsuchascefsulodin-Irgasan-

novobiocin (CIN) agarincubatedatroom temperaturefor

severaldays.

Y.enterocoliticacolonieshaveabull’seyeappearancewitha

redcenteronCINagar.

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Extrainfo:Subculturesaremadebytransferringsomeorallcells

fromapreviousculturetofreshgrowthmedium,inordertoprolong

thelifeorexpandthenumberofcellsandmicroorganismsinthe

culture.

3. Serology

Serumspecimenstaken2ormoreweeksapart,arisein

agglutinatingantibodiescanbeshown;however,cross-

reactionsbetweenYersiniaeandotherorganisms(Vibrios,

Salmonellae,andBrucellae)mayconfusetheresults.

Therefore,resultsarenotreliable.

TREATMENT

Mostcasesofdiarrheacausedbyentero-pathogenicYersinia

areself-limiting.Datafromclinicaltrialsdo not support

antimicrobialtreatmentforadultsorchildrenwithY.

enterocoliticadiarrhea.- Sidenote:Y.enterocoliticaandY.pseudotuberculosisarethe

twoentero-pathogenicYersiniae.

Y. enterocoliticaistypicallyresistanttoampicillin₁ and to

first-generation cephalosporin₂.Ontheotherhand,Y.

pseudotuberculosishasshownsusceptibilitytoampicillin₁,

cephalosporin₂,andaminoglycosides₃.

**Systemicinfectionswithbacteremiaorfocalinfectionsoutside

thegastrointestinaltractgenerallyrequireantimicrobialtherapy

(notmentioned).

**Fluoroquinolonetherapyiseffectiveforbacteremiainadults,

suchasciprofloxacin,athird-generationcephalosporinisan

alternative(notmentioned).

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PREVENTION AND CONTROL

1. Safehandlingandprocessingoffood.

2. Novaccineiseffectiveinpreventingintestinalcolonizationof

foodanimalsbyentero-pathogenicYersinia.

3. Consumptionoffoodmadefromrawmeatshouldbe

discouragedatpresentbecauseitisnotpossibletoeliminate

contaminationwiththeentero-pathogenicYersiniastrains

foundworldwide.

Yersinia √