BrazJOtorhinolaryngol.2017;83(3):241---242
www.bjorl.org
Brazilian
Journal
of
OTORHINOLARYNGOLOGY
EDITORIAL
Acute
otitis
media
in
children:
a
vaccine-preventable
disease?
夽
Otite
média
aguda
na
infância:
uma
doenc
¸a
prevenível
por
vacinas?
Acute otitis media (AOM) is one of the most common childhood diseases, being the main cause of medical consultationsandantimicrobialprescriptionsindeveloped countries,where infantsreceive an average ofmore than 40daysofantimicrobialsperyear.Priortotheintroduction ofpneumococcalconjugatevaccines,itwasestimatedthat fourof fiveinfants would have an episodeof AOMbefore theywerethreeyearsold,withthepeakincidence occur-ringatsixto18monthsofage.40%ofthemwouldhaveat leastsixrecurrentepisodesbeforetheageofsevenyears.
Anothercruciallyimportantpublichealthaspectisthat the disease burden and its complications have a much moresignificantimpactondevelopingcountries,with esti-mates by the World Health Organization (WHO) showing that approximately 51,000 deaths occur annually in chil-drenyoungerthanfiveyears,attributabletocomplications ofAOM,suchasintracranialinfections.Additionally, approx-imately60%ofthehundredsofmillionsofindividualswho developchronicsuppurativeotitismanifesthearing impair-mentandbehavioralchanges.1
These AOM characteristics make thepossibility of pre-ventingit,throughvaccines,themainandmostattractive option for its management. Several studies have shown that themost common bacterialpathogens to causeAOM areStreptococcus pneumoniaetogether withnontypeable
Haemophilus influenzae (NTHi) and Moraxella catarrhalis
andtoalesserextent,Streptococcuspyogenesand Staphy-lococcusaureus.Finally,viralagents[influenza,respiratory syncytialvirus(RSV),adenovirus,parainfluenza,andother viruses] account for approximately 30% of the cases and, togetherwith bacteria,accountfor approximately 15%of casesofAOM.2
夽
Pleasecitethisarticleas:SáfadiMA,JarovskyD.Acuteotitis
mediainchildren:avaccine-preventabledisease?BrazJ
Otorhino-laryngol.2017;83:241---2.
The incorporationof pneumococcal conjugatevaccines intoroutineinfantimmunizationprogramsinanincreasing numberof countries worldwide,as well asthe expansion ofinfluenzavaccinerecommendationsforseveralpediatric age groups, has created an expectation of a decrease in AOM-relatedmorbidityinthesepopulations.Theexperience gainedfromtheconsolidationoftheseprogramsworldwide hastaughtusimportantlessonsthatdeservetobeanalyzed inthiseditorial.
The evaluation of the influenzavaccine impactonthe reductionof AOMepisodesin randomizedcontrolledtrials hasshownconflictingresultsregardingtheinfluenzavaccine efficacyinpreventingAOMepisodesinchildren.The pres-enceofabroadspectrumofrespiratoryvirusespotentially implicatedinAOMinchildren,aswellasthelowerefficacy ofinfluenzavaccine ininfants---theagegroupmostoften affected by otitis --- arethe main reasons for the limited effectiveness of influenza vaccines in preventing AOM in children.3
Althoughtheyweredevelopedessentiallyaimingat pre-ventinginvasivepneumococcaldiseases(meningitis,sepsis, and bacteremic pneumonia), the contribution of pneu-mococcal conjugate vaccines (PCVs) to the reduction of mucosal infections (especially otitis) has always been a matter of debate. The results of the pre-licensing stud-iesof thesevaccines indicated apotential reductionof a maximumof 10% ofAOMepisodes amongvaccinated chil-dren.Amongthemainreasonsforthelimitedperformance of PCVs in the prevention of AOM, we highlight the fact thattheserotypesincludedintheseveralexistingvaccines (CPV7,CPV10andCPV13)areresponsibleforalimited pro-portion of these cases, considering the total number of circulatingpneumococcalserotypes(atleast98havebeen identifiedtodate).Additionally,studieshaveshownatrend towardreplacementofthepathogenscausingAOMin vac-cinatedpopulations,withanincreasedprevalenceofother otopathogensandpneumococcalserotypes notincludedin
http://dx.doi.org/10.1016/j.bjorl.2017.02.004
1808-8694/©2017Associac¸˜aoBrasileiradeOtorrinolaringologiaeCirurgiaC´ervico-Facial.PublishedbyElsevierEditoraLtda.Thisisanopen
242 EDITORIAL
the vaccines (the replacement phenomenon).4 Moreover,
thesestudies have showna greater efficacy for outcomes considered more severe, associated with complex otitis, tympanostomytubeplacement,andrecurrentotitismedia. TheseresultssuggestedthattheuseofPCVsinyounginfants wouldbemoreeffectiveforthepreventionofcomplex oti-tisandchronic otitis witheffusion thanfor prevention of episodesofsimpleacuteotitismedia.
S. pneumoniaeisrecognizedasapathogenresponsible for early infections and can act as a trigger for mid-dle ear lesions, generating a cascade of events that will resultin subsequent polymicrobial infections, more often related to NTHi strains and biofilm formation. Infections causedbyNTHishowgreaterrisk oftreatmentfailureand complications,suchasrecurrenceandchronicity.5
Anotherimportantfindingofthesestudieswasthatthe lateadministration of PCVs in toddlers older than 1 year of age wasnot aseffective in preventing complexcases, when compared to the administration of PCVs in young infants.The probable interpretationof thisfindingisthat immunizing older children that have already experienced aninitialepisodeofpneumococcalotitiscannotexerta pro-tectiveeffectinpreventingtheeventsthatwillleadtothe formation of complexand chronic otitis media, sincethe pathogenicalterationsthatpredisposethesechildrento sub-sequentepisodeshavealreadybeen triggeredand,atthis stage,theserotypesincludedinthePCVsarenotarelevant causeofinfection.5
After the inclusion of PCVs into infant immunization programs,real-world observational studiesfound a signif-icant reduction not only in AOM episodes, but mainly in the incidence and prevalence of complex cases. Overall, the magnitude of the reduction substantially exceeded thepredictions basedon theresults obtained in the pre-licensingstudies.Forinstance,intheUnitedStates,afew yearsaftertheintroductionofPCV7,therewasareduction of up to 28% in frequent otitis media, 23% in ventilation tube placement rates, 42% in antimicrobial prescriptions and43% in the rates of outpatient visits related tootitis media in children younger than 2 years. In the United Kingdom,therewasa22%reductionintheincidencerates of otitis media in children younger than 10 years of age followingtheintroductionofPCV7,withanadditional19% reductionafter PCV7 wasreplacedby PCV13.4,5 Similarly,
inBrazil,theratesofoutpatientvisitsrelatedtoall-cause otitis AOM decreased 44% in children aged 2---23 months aftertheintroductionofPCV10.6 Alsoworthmentioningis
thereductionintheincidencerates ofpenicillin-resistant pneumococci, both among invasive disease isolates and middleearandnasopharyngealisolates.4,5
The licensingofthe10-valentconjugatepneumococcal vaccine(PCV10), whichutilizesH.influenzae Dproteinas carrierin8ofits10serotypes,broughttheperspectiveofa potentialadditionalbenefitofprotectionagainstinfections causedbyNTHi.However,todateithasnotbeenpossible
toconvincinglydemonstrate,intheseveralcountrieswhere thisvaccinewasintroduced,thatthiseffectcanbeattained inchildrenvaccinatedwithPCV10.
Therefore, despite the promising data regarding the impactofPCVsontheburdenofAOManditscomplications, it is important to note that the main benefit of these vaccines remains the prevention of invasive pneumococ-caldiseasesinchildhood.Thedevelopment,inthecoming decades,of more effective vaccinesagainst theinfluenza virus, of vaccinesagainst other clinicallyrelevant viruses such as RSV, adenovirus and parainfluenza virus, of pro-teinvaccinesthatcanprovideuniversalprotectionagainst all pneumococcal serotypes, as well as effective vac-cines against NTHi infections, usually associated with recurrent and complex otitis, will be of crucial impor-tanceinultimatelyconsideringotitisavaccine-preventable disease.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
References
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3.NorhayatiMN,HoJJ,AzmanMY.Influenzavaccinesforpreventing acuteotitismediaininfantsand children.CochraneDatabase SystRev.2015;24:CD010089.
4.Fortanier AC, VenekampRP, BoonackerCWB, Hak E, Schilder AGM, Sanders EAM, et al. Pneumococcal conjugate vaccines for preventing otitis media. Cochrane Database Syst Rev. 2014;4:CD001480.
5.Dagan R, PeltonS, Bakaletz L, Cohen R. Prevention of early episodes of otitis media by pneumococcal vaccines might reduce progression to complex disease. Lancet Infect Dis. 2016;16:480---92.
6.SartoriAL, MinamisavaR,AfonsoET,AntunesJLF,Bierrenbach AL,Morais-NetoOL,etal.Reductioninall-causeotitis-related outpatientvisitsinchildrenafterPCV10introductioninBrazil.In: 9thInternationalsymposiumonpneumococciandpneumococcal diseases.2014.
MarcoAurélioPalazziSáfadia,b,∗, DanielJarovskya,b aSantaCasadeSãoPaulo,FaculdadedeCiênciasMédicas,
DepartamentodePediatria,SãoPaulo,SP,Brazil
bHospitalInfantilSabará,Servic¸odeInfectologia
Pediátrica,SãoPaulo,SP,Brazil
∗Correspondingauthor.
