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Measles(Rubeola)DiseaseReport By:JeannaReed EtiologicalAgent ! MeaslesVirus:Measlesvirus(MeV)isamemberofthegenusMorbillivirusofthefamilyParamyxoviridae.(1) Transmission • DirectContact/Airborne:Measlesiswellknownasacontagious,infectiousdisease;90%ofsusceptiblepersons withclosecontacttoameaslespatienttypicallydevelopmeaslesinfection.Thevirusistransmittedbydirectcontact withinfectiousdropletsbutcanalsoinfectvianondirectcontact.MeVcanalsobespreadthroughtheairwhenan infectedpersonbreathes,coughs,orsneezes.Airborne,themeaslesvirusiscapableofinfectionforuptotwohours afteraninfectedpersonexitsthearea.(2) Reservoirs • Humans:Measlesisahumandisease.Thereisnoknownanimalreservoir.(3) MicroorganismGeneralCharacteristics • SinglestrandedRNAvirus:“Measlesvirusisanegative-sense,singlestrandedRNAvirus.Itconsistsofahelical nucleocapsid,100-300nmindiameter,surroundedbyanenvelope.Theenvelopeislinedbymatrixproteinsand carriestransmembranehemagglutininandfusionglycoproteinswhicharethevirulencefactors.”(4) IdentificationKeyTests • LaboratoryConfirmation: Measles-specificIgMantibodyandmeaslesRNAdetectionbyreal-timepolymerase • • • • chainreaction(RT-PCR)aretypicalmethodsusedtoconfirmmeaslesinfection.Insuspectedpatients,serumsamples andthroatswab(ornasopharyngealswab)shouldbecollectedatfirstcontact.(2) TheCDCusesassaysintheirreferencelabspecificformeaslesserologictestingofIgMandIgG.Theassaysusea recombinantmeaslesnucleoprotein(NP)antigenintheEIA(enzymeimmunoassay).(5) Urinesamplesmayalsodetectthemeaslesvirus.(2) MolecularAnalysiscanalsobecompleted.Genotypingisusedtomapthetransmissionpathwaysofmeaslesviruses. Thegeneticdatacanhelptolinkorunlinkcasesandcansuggestasourceforimportedcases.“Genotypingistheonly waytodistinguishbetweenwild-typemeaslesvirusinfectionandarashcausedbyarecentmeaslesvaccination.”(2) OccasionallyfalsepositiveIgMresultsareproduced.Noassayis100%specific.Whenwarranted,theCDCprovides additionalserologicaltestingtoaidinconfirmationofdiagnosis.(5) SignsandSymptomsofDisease • • • • • • • • • Prodromalfever.Canbeashighas105°Fahrenheit.(1) Cough.(6)(1) Coryza(runnynose).(1) Conjunctivitis(redeyes).(6) Sorethroat.(1) Redorreddishbrownrash.(7)(8) Koplikspots.(7)(8) 1to2dayspriortotherashdevelopment,Koplikspotsmayappear.Theyaretypicallywhiteincolorandasandtype appearance.Thespotscanbefoundintheliningofthecheeks,roofofmouthandinsidethelips.(9) 3to5daysfollowingsymptoms,arashtypicallydevelops.Flatredspotsaloneorwithsmallraisedbumpsontop becomevisibleonthefaceatthehairlineandspreaddownwardtowardsthefeet.Thespotsmayspreadandjoin together.Inaddition,whentherashappears,aperson’sfevercanrisetomorethan104°Fahrenheit.Afterafew days,therashwillfadeoncethefeversubsides.(8) HistoricalInformation • 900CE:APersianphysiciandescribedsmallpoxandmeaslesinawrittenpublicationtryingtodifferentiatebetween thetwodiseases.(10) 1657-1757:Duringthisperiod,measlesisnotedtomakeanappearanceincoloniesoftheU.Swithdeaths reported.(10) 1757:AScottishphysicianshowedmeaslescanbecausedbyaninfectiousagentinthebloodofhumans.(11) 1861:TheCivilWarsawitsfairshareofmeaslesoutbreaksandsecondaryinfectionsresultingincasualtiesonboth sidesofthewar.(10) 1912:Measles(ifcontractedintheUS)mustnowbereportedbyhealthcareprovidersandlaboratories.(11) 1920:PerMMWR(MorbidityandMortalityWeeklyReport)thisyear469,924measlescaseswerereported,and 7575patientsdied.(13) 1954:JohnEndersandDrThomasPeeblesweresuccessfulinisolatingmeaslesvirusfromaninfectedthirteenyear oldpatientnamedDavidEdmonston.(11) 1958-1962:503,282measlescasesand432measles-associateddeathswerereportedonaverageoverthisfive yearperiod.(13) 1963:“Edmonston-Bstrain”oftheMeaslesvirusisdevelopedbyJohnEndersandteamtobecomeavaccineandis licensedwithintheUnitedStates.(11) 1968:MauriceHillemanPhDandhisteamdevelopandimprovethecurrentmeaslesvaccinebymakingaweaker, • moreattenuatedstrainrenamed“Moraten”.Thisvaccinewaswidelydistributedandcontinuestobetheonly measlesvaccineusedwithintheUnitedStatessince1968.(11) 1971:FirstMMR(MeaslesMumpsRubella)combinationtrivalentvaccineislicensedintheUS.(10) • • • • • • • • • • • • 1978:CenterforDiseaseControldeclaresgoalstoeliminatemeaslesintheUSby1982.(11) 1981:ReportedUSmeaslescaseswerenoteliminatedcompletely,butgreatlyreduced(80%)comparedto1980. Vaccinecoverageiscreditedforthisachievement.(11) 1986:NCVIA(NationalChildhoodVaccineInjuryAct)ispassedbyUSCongresstoaddressgrowingpublicconcernsof • adversereactionsfollowingvaccineadministration.NVICP(NationalVaccineInjuryCompensationProgram)wasalso includedintheNCVIAtoallowcompensationtoindividualsfortableinjuryandnon-tableinjuryclaims.Measles (MMR),Mumps(MMR,MR,M)islistedasacompensablevaccine.(14)(15) 1988:Measles,mumps,rubellaoranyofitscomponentsarelistedontheVaccineInjuryTablewithillness,injury, disability,andconditionscoveredincludingdeath.Thetimeframeinwhichthesymptom,significantaggravation,or manifestationofonsetmayoccurisalsoestablished.(16) 1989:“Measlesoutbreaksamongvaccinatedschool-agedchildrenpromptedtheAdvisoryCommitteeon ImmunizationPractices(ACIP),theAmericanAcademyofPediatrics(AAP),andtheAmericanAcademyofFamily Physicians(AAFP)torecommendaseconddoseofMMRvaccineforallchildren.Followingwidespread implementationofthisrecommendationandimprovementsinfirst-doseMMRvaccinecoverage,reportedmeasles casesdeclinedfurther.”(11) 2000:Measlesconfirmed“eliminated”pertheUS.Nocasesreportedwithinoneyear.(11) • 2005:MMRV(Measles,Mumps,Rubella,Varicella/ProQuad)vaccineapprovedbyFDAandmarketedasan • • • alternativetomonovalentvaccinesandMMRalone.(17) 2007:WHO/UNICEFreportsthateffortstoachieveareductioninmeaslesmortalitywereverysuccessfulandhad reducedmeaslesmortalityby60%,fromanestimated873,000deathsin1999to345,000deathsin2005.(18) 2010:ApaperpublishedinajournalcalledVirologyinvestigateddivergencetimessuggestingMeVpossiblycame th th fromanonhumanspeciesandwasresponsiblefortheinfectiousdiseasearoundthe11 to12 century.(12) 2011-2013:PertheCDC,collectively464measlescaseswerereportedintheUS.(19) • 2014-2016:AccordingtotheCentersforDiseaseControl,2014sawthebiggestincreaseinmultiplestatesof • • measlescases(667confirmed)reportedsincetheCDCdeclaredmeasleseliminatedin2000fromtheUS.Multiple outbreakshaveoccurredworldwideduringthistime.(20) VirulenceFactors • • Portalofentry=Respiratorymucousmembranes.(21) Attachment=Humagglutinin(H)proteinfoundonthesurfaceofthevirusandFusion(F)protein.Bothinteractin ordertoestablishattachmentandfusionoftheviralenvelopewiththehostcellularreceptors.(M)proteinisalso involvedinviralassembly.(21) • • • MeVquicklyspreadstothelymphsystemandentersthebloodstreamwheremultipleorgansystemscanthenbe infected.ComplicationsfrommeaslesvirushasbeenreportedineveryorganincludingRespiratory,Gastrointestinal, Neurological(includingCentralNervousSystem),andOcularsystems.Themostcommoncauseoflongtermsequelae isencephalitis.(22) Immunesuppressionoccurslongenoughtoevadeimmunedefensesallowingmeaslesvirustoestablishitself.Asthe diseaseprogresses,destructionoftissuecancausesignificantneutropeniaandsecondarybacterialinfectionswhich canalsobedeadly.(21)(22) Agecanaffecttherateofcomplicationsandunderlyingconditionsresultinginmild,modifiedandatypicalMeV.(21) ControlandTreatment • • • • 4daysbeforeto4daysafterthemeaslesrashappearspatientsareconsideredtobeinfectious.Onceconfirmed, promptisolationishighlyrecommendedandtreatmentforMeVismainlysupportive.(23) Postexposureprophylaxisisavailable(typicallybestifgivenwithin72hours)tothoseexposedtoMeVbutcannot showimmunitytomeaslesintheformofMMRvaccination.Immunoglobulin(IG)administeredviaIMorIVcanalso begivenwithin6daysofexposuretoselectpatients.(2) WHO(WorldHealthOrganization)recommendssupplementingVitaminA(dosingagedependent)tohelpreduce complications.Alsoantibiotictherapiesforsecondaryinfectionscanhelpwithreductioninmeaslesassociateddeaths indevelopingcountries.(22) Factorsthataffectmeaslesmorbidityandmortalityincludesex,age,crowding,immunosuppression,malnutritionand VitaminAdeficiency.(22) PreventionandVaccines • • • Preventionofmeaslesvirusinfectionispossiblewithameasles-containingvaccine.IntheUnitedStates,theCenters forDiseaseControlareadvisedbyACIP(AdvisoryCommitteeonImmunizationPractices)andarecommendedvaccine scheduleispublishedannually.(24) MonovalentmeaslesvaccineisnolongeravailableintheUSandhasbeenreplacedwithtwocombinationvaccines. CurrentlyMMR(MeaslesMumpsRubellaIIbyMerckandCo.,Inc.)andquadrivalentvaccineProQuad(Measles, Mumps,Rubella,VaricellabyMerckandCo.,Inc.)arerecommendedtopreventmeaslesinfection.Bothare administeredsubcutaneouslyandareindicatedforpatientstwelvemonthsorolder.However,certaincircumstances mayallowforearlieradministrationofthevaccinedependingonthechoiceofcombinationvaccineselectedandthe conditionofthepatient.(24) Forpreventionofmeaslesinfection,onedoseofeitherMMRorMMRVisrecommendedforpreschoolagedchildren (12-15monthsold)andadultsnotathighriskforexposureandtransmission.Twodosesarerecommendedfor schoolagechildren(Kindergartenthrough12 years)andadultsinahighrisksetting.MMRV(ProQuad)isnotlicensed foranyoneundertheageof12months.(24)(17) LocalCurrentOutbreaks/Cases • • In1958measlesincidencepeakedat85,862casesinthestateofTexas.Asmeaslesvaccineswereintroduced,these casesdroppedconsiderablyto99.9%.MeaslesexposureresultinginoutbreaksintheUSandTexassince2000have primarilyoccurredduetopeopleexposedduringtraveltocountrieswheremeaslesisconsideredendemic.(25) 2013recordsindicate27casesofmeaslesinfectionwerereportedstatewidewithadecreasein2014to10cases.No deathshavebeenreportedsince2000pertheTexasDepartmentofStateHealthServicesdatabaseforMeasles.(25) GlobalCurrentOutbreaks/Cases • • In2015theUnitedStatesreportedalargemeaslesoutbreakovermultiplestatesthatweretracedbacktoan amusementparkinCalifornia.Furtherinvestigationsuggestedoneofthecaseshadrecentlytraveledinternationally andbecameinfectedwiththemeaslesvirus.Detectionofthemeaslesviruswasimplementedimmediatelybut identificationofthesourceisstillunknown.However,“AnalysisbytheCentersforDiseaseControlshowedthatthe measlesvirustypeinthisoutbreak(B3)wasidenticaltothevirustypethatcausedthelargemeaslesoutbreakinthe Philippinesin2014.”(20) WhilemeaslescaseshavedeclinedconsiderablyintheUnitedStates,measlesanddeathsgloballyarestillreported. Measlesoutbreakscanoccurespeciallywheregapsinvaccinationprogramsexist.WHO(theWorldHealth Organization)supportschangesinpoliciesandpracticesinordertoensurehighaccessandcoverageoflifesaving vaccines.In2001multipleorganizationsjoinedtogethertoformtheMeaslesandRubellaInitiative.Aprogram creditedwithpreventing17.1millionmeaslescases.(26) • • In2014,theAmericasandWesternPacificregionssawincreasednumbersofreportedcasesdueinparttolarge outbreaksinChina,thePhilippinesandVietNam.InAngola,Ethiopia,India,theRussianFederationandSomalialarge outbreaksalsooccurredalthoughtheoverallnumberofcasesdeclinedinsomeregions.PerWHOin2014, approximately114,900peoplediedgloballyfrommeaslesandthemajorityofthecaseswerechildrenundertheage offive.(26)(27) “Despitethewelcomereductioninmeaslesdeaths,thishighly-infectiousdiseasecontinuestotakeaterribletollon thelivesofchildrenaroundtheworld,”saidDrSethBerkley,CEOofGavi,theVaccineAlliance.“Acoordinated approachthatputsstrongerroutineimmunizationatitscorewillbecentraltogettingmeaslesundercontroland securingfurtherreductionsinmortalityfromthisvaccine-preventabledisease.”(27) References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 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