REVISTA
PAULISTA
DE
PEDIATRIA
www.rpped.com.br
REVIEW
ARTICLE
The
impact
of
varicella
vaccination
on
varicella-related
hospitalization
rates:
global
data
review
Maki
Hirose
∗,
Alfredo
Elias
Gilio,
Angela
Esposito
Ferronato,
Selma
Lopes
Betta
Ragazzi
HospitalUniversitáriodaUniversidadedeSãoPaulo,SãoPaulo,SP,Brazil
Received28July2015;accepted1December2015 Availableonline10May2016
KEYWORDS
Varicella/chicken pox;
Hospitalization; Varicellavaccination; Vaccine
Abstract
Objective: Todescribetheimpactofvaricellavaccinationonvaricella-relatedhospitalization ratesincountriesthatimplementeduniversalvaccinationagainstthedisease.
Datasource:Weidentifiedcountriesthatimplementeduniversalvaccinationagainstvaricella at the http://apps.who.int/immunizationmonitoring/globalsummary/schedules site of the WorldHealthOrganizationandselectedarticlesinPubmeddescribingthechanges (pre/post-vaccination)inthevaricella-relatedhospitalizationratesinthesecountries,usingtheKeywords ‘‘varicella’’, ‘‘vaccination/vaccine’’ and‘‘children’’ (or) ‘‘hospitalization’’.Publications in EnglishpublishedbetweenJanuary1995andMay2015wereincluded.
Datasynthesis: 24countrieswithuniversalvaccinationagainstvaricellaand28articles describ-ingtheimpactofthevaccineonvaricella-associatedhospitalizationsratesinsevencountries wereidentified.TheUShad81.4%---99.2%reductioninhospitalizationratesinchildrenyounger thanfouryears,6---14yearsaftertheonsetofuniversalvaccination(1995),withvaccination coverage of90%;Uruguay: 94%decrease(childrenaged1---4 years)insixyears,vaccination coverageof90%;Canada:93%decrease(age1---4years)in10years,coverageof93%;Germany: 62.4%decrease(age1---4years)in8years,coverageof78.2%;Australia:76.8%decrease(age 1---4years)in5years,coverageof90%;Spain:83.5%decrease(age<5 years)infour years, coverageof77.2%andItaly69.7%---73.8%decrease(generalpopulation),coverageof60%---95%.
Conclusions: The publicationsshowed variationsinthe percentageofdecreasein varicella-relatedhospitalizationratesafteruniversalvaccinationintheassessedcountries;theresults probablydependonthetimesincetheimplementationofuniversalvaccination,differences inthestudiedagegroup,hospitaladmissioncriteria,vaccinationcoverageandstrategy,which doesnotallowdirectcomparisonbetweendata.
©2016SociedadedePediatriadeS˜aoPaulo.PublishedbyElsevierEditoraLtda.Thisisanopen accessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).
∗Correspondingauthor.
E-mail:[email protected](M.Hirose).
http://dx.doi.org/10.1016/j.rppede.2016.03.001
2359-3482/©2016SociedadedePediatriadeS˜aoPaulo.PublishedbyElsevierEditoraLtda.ThisisanopenaccessarticleundertheCCBY
PALAVRAS-CHAVE
Varicela/catapora; Internac¸ão hospitalar; Vacinacontra varicela; Vacina
Impactodavacinavaricelanastaxasdeinternac¸õesrelacionadasàvaricela:revisão dedadosmundiais
Resumo
Objetivo: Descreveroimpactodavacinavaricelanastaxasdeinternac¸õeshospitalares associ-adasàvaricelanospaísesqueadotaramavacinac¸ãouniversalcontraadoenc¸a.
Fontesdedados: Identificaram-se países que adotaram a vacinac¸ão universal contra varicelapelositehttp://apps.who.int/immunizationmonitoring/globalsummary/schedulesda Organizac¸ão Mundial de Saúde e selecionaram-se os artigos no Pubmed que descrevem a variac¸ão (pré/pós-vacinal) nas taxas de internac¸ões relacionadas à varicela desses países, com auxílio das palavras chaves: ‘‘varicella’’, ‘‘vaccination/vaccine’’ e ‘‘children’’ (ou) ‘‘hospitalization’’.Incluíram-sepublicac¸õeseminglêsentrejaneirode1995emaiode2015.
Síntesedosdados: Foramidentificados24paísescomvacinac¸ãouniversalcontraavaricelae 28artigosquedescrevemoimpactodavacinanasinternac¸õesassociadasàvaricelaemsete países.OsEUAtiveram81,4%-99,2%dereduc¸ãonataxadeinternac¸ãoemcrianc¸asmenores dequatroanos,após6-14anosdoiníciodavacinac¸ãouniversal(1995),comcoberturavacinal de90%;Uruguai:94%dequeda(crianc¸asde1-4anos)em 6anos,coberturavacinalde90%; Canadá:93%dereduc¸ão(1-4anos)em10anos,coberturade93%;Alemanha:62,4%dereduc¸ão (1-4anos)em 8anos, coberturade78,2%;Austrália:quedade76,8%(1-4anos)em 5anos, coberturade90%;Espanha:83,5%dequeda(<5anos)em4anos,coberturade77,2%;eItália: quedaentre69,7%-73,8%(populac¸ãogeral),coberturade60%-95%.
Conclusões: Aspublicac¸õesrevelaramvariac¸ãonopercentualdequedanahospitalizac¸ãopor varicelaapósavacinac¸ãouniversalnospaísespesquisados;osresultadosprovavelmente depen-demdotempodecorridoapósintroduc¸ãodavacinac¸ãouniversal,diferenc¸asnafaixaetária estudada,critérios deinternac¸ão, coberturavacinal eestratégiade vacina,nãopermitindo comparac¸ãodiretaentreosdados.
©2016SociedadedePediatriadeS˜aoPaulo.PublicadoporElsevierEditoraLtda.Este ´eum artigoOpenAccesssobumalicenc¸aCCBY(http://creativecommons.org/licenses/by/4.0/).
Introduction
Varicella is caused by a DNA virus of the Herpesviridae
family. It is highly contagious, with an annual incidence of 26---61 casesper 1000 unvaccinated individuals; it usu-allyhasabenigncourse,butcanevolvewithcomplications fromthevirusitselforfromsecondarybacterialinfections in both immunodeficient patients and immunocompetent individuals.1---4
Complications from varicella virus itself are
pneumo-nia, acute obstructive respiratory disease, cerebellitis,
encephalitis, meningitis, and other rarer conditions such
asneutropenia,thrombocytopenia,Henoch---Schonlein,
syn-ovitis, and Reye’s syndrome.5,6 The complications from
secondarybacterialinfectioninclude impetigo,abscesses,
cellulitis,necrotizingfasciitis,pneumonia,toxicshock
syn-drome,andsepsis.7,8Mortalitybyvaricellaisconsideredlow
(6.7/100,000infected),butthediseasemayhavetemporary
orpermanentsequelae.9
Thevaricellavaccine(VV)withliveattenuatedvirus(Oka
strain)wasdevelopedinJapanin1974andits
commercial-ization started in 1987. In 1995, the United States (USA)
becamethefirstcountrytoincludeitinthenational
immu-nizationschedule.10Thelocalepidemiologicalscenariowas
characterizedbyanincidenceoffourmillioncases,11,000
hospitalizations,and100deathsyearlyduetovaricella.5In
2006,thecountryintroducedtheseconddoseofvaccinefor
childrenbetween4and6years,inordertoreduce
commu-nityoutbreaks.Overthepast20years,othercountrieshave
implemented universal vaccination against this disease in
oneortwodoses,accordingtothecriteriaofeachcountry
or region,andseveralstudiesanalyzingtheimpactofthis
measurehavebeenpublished.
InBrazil,varicella isnot acompulsory notification
dis-ease,anditsepidemiologicaldataarerestrictedtoschools
andkindergardensoutbreakreports,andDATASUS(Ministry
of Health) information generated by Hospital Admissions
Authorizations(Autorizac¸õesdeInternac¸ãoHospitalar[AIH])
fromtheNationalUnifiedHealthcareSystem(SistemaÚnico
de Saúde [SUS]).11 According to DATASUS, the number of
hospitalizations for varicella in Brazil hasvaried between
4200 and 7800 cases yearly, but this number accounts
only for the hospitalizations in the public healthcare
system.
Following the global trend of universal
implementa-tion of VV, the Brazilian Ministry of Health announced,
in September 2013, the inclusion of this vaccine in the
NationalImmunizationProgramforchildrenbornfromJune
2012 onwards.The onedose scheduleassociatedwiththe
measles,mumps,andrubella(MMR)vaccineat15months,
without a booster dose; varicella-related hospitalizations
are expected to decrease by 80%.12 Two years after the
implementation of this vaccine, the impact of this
mea-sure on varicella-related hospitalizations in Brazil is still
undetermined.
This study aimed to describe the impact of VV in
varicella-relatedhospitalizationratesincountriesthathave
topredicttheimpactofthisstrategyinBrazilforthecoming years.
Method
Usingthevaccine-preventablediseasesmonitoringsystemof theWorldHealthOrganization(WHO;http://apps.who.int/ immunizationmonitoring/globalsummary/schedules), the
countriesthathavealreadyimplementeduniversalVVwere
identified and the immunization schedule adopted was
verified.
At the same time, a literature search was conducted
atPubMed,usingthekeywords‘‘varicella’’+‘‘vaccination/
vaccine’’+‘‘children’’ and ‘‘varicella’’+‘‘vaccination/
vaccine’’+‘‘hospitalization.’’Articlespublishedafter1995
(theyearofintroductionofVVintheUSA)thatpresented
the impact of universal VV in varicella-related
hospital-ization rates in the previously identified countries were
selected.ThesearchincludedarticlespublishedinEnglish;
studiesthatevaluatedcountries/regionswherethevaccine
was implemented only in the private healthcare system
wereexcluded.
Toobservepossiblesimilaritiesamongthedatapublished
bydifferentcountries,dataontheimpactofVVinchildren
aged1---4yearswerepreferentially soughtafter,asthisis
usually theage group with thehighest rates of
varicella-related hospitalization.The epidemiological situation five
yearsaftertheintroductionofuniversalvaccinationinthese
countrieswasassessed.Theimmunizationcoverageandthe
vaccinationschedule(oneortwodoses)adopted bythese
countries were considered. In addition, varicella-related
hospitalizationwasdefinedascasesinwhichvaricellawas
themaindiagnosisorpartofthehospitalizationdiagnoses.
Results
In a search conducted in May 2015 on the WHO website (whichstillpresenteddataonvaccineschedulesfrom2014), itwasobservedthat24countrieshadadoptedtheVV univer-sally(Table1):eightinEurope,tenintheAmericas,fourin
the Eastern Mediterranean, and twoin the East Pacific.13
Furthermore, another 12 countries --- Argentina, Bahrain,
Slovenia,France, Grenada,Iran, Iceland,Kuwait,Mexico,
United Kingdom, Saint Lucia, and Trinidad and Tobago
---indicated the vaccine to specific populations: healthcare
workers, children with cancer (and their contacts), and
groupswithriskof severediseaseprogression. Halfof the
countriesadopted the single-dose scheduleand theother
half,two-doses.Mostcountrieschoseimmunizeinfantsaged
12---18months,withabooster(whenthetwo-doseschedule
waschosen)after afew monthsor at 4---6years;
Switzer-land,Barbados,andsomeautonomousregionsofSpainhave
chosentovaccinatesusceptibleadolescentsonly.
InasearchconductedatPubMed(May2015),2059results
wereretrieved,1683of whichwerepublishedafter1995;
of these, 28 showed the impact of the VV in
varicella-relatedhospitalization(Fig.1)insevencountriesthathave
universallyadoptedthevaccine.Furthermore,areviewby
Helmutetal.withrecentdataonincidence,hospitalization,
andmortalityrelatedtovaricellainEuropewasretrieved,
Table1 Countriesthathaveadoptedthevaricellavaccine, numberofdoses,andvaccinationscheduleadopted.
Country Dose Vaccinationschedule
EasternMediterranean
Oman 1 12months
Qatar 2 12monthsand4---6years
SaudiArabia 2 12monthsand6years UnitedArabEmirates 1 12months
Europe
Germany 2 11---14monthsand15---23 months
Greece 2 12---15monthsand4---6 years
Israela 2 12monthsand6years Italy 2 13---15monthsand5---6
years
Latvia 1 12---15months
Spain 2 10---14years(2nddose afteronemonth) Switzerland 2 11---15years(2nddose
afteronemonth)
Turkey 1 12months
WesternPacific
Australia 2 18monthsand10---15 years
Korea 1 12---15months
Americas
Bahamas 2 1year4---5years Barbados 1 After18yearsofage
Brazil 1 15months
Canada 2 12monthsand18months
CostaRica 1 15months
Ecuador 1 12---23monthsor6---10 years
Panama 1 15---18months
Paraguay 1 15months
UnitedStates 2 12---15monthsand4---6 years
Uruguay 1 1year
The continents were divided in accordance withthe United Nations(UN)standard.
Source: World Health Organization [http://apps.who.int/ immunizationmonitoring/globalsummary/schedules 6] (May/
2015).13
a InaccordancewiththeWorldHealthOrganization,Israelwas
includedinthegroupofEuropeancountries.
including some countries that have already implemented
universalVV.14
Table2showsthecountrieswiththegreatestimpactin
reducingvaccine-relatedhospitalizationsaftertheinclusion
ofVVintheroutinevaccinationschedule.
USA
Table2 Impactofvaricellavaccineinhospitalizationratesintheanalyzedcountries.
Country Reductioninhospitalization rate(%)a
Agerange (year)
Yearsof observationb
Vaccination coverage(%)
USA2 >99.2 0---1 15 90
Spain(Navarra)38 95.2 <15 5 >89
Uruguay26 94.0 1---4 6 96
Canada29 93.0 1---4 10 93
Italy(Puglia)33 84.0 1---4 7 91.1
Germany(Bavaria)30 77.6 <5 5 52.7
Australia37 76.8 1---4 5 90
aComparingthepre-vaccineperiodwiththepost-vaccineuniversalizationperiod.
b Aftervaccineuniversalization.Thehighestvalueobservedintheanalyzedstudieswasconsidered(includingregionalstudies).
andcomparedvaricella-relatedhospitalizationratesinthe pre-vaccineperiodwiththoseat2---4yearsafterthe intro-duction of the vaccine, and found an increased vaccine coverage:43.2%in1998and59%in1999.5,15,16 Infirsttwo
yearsperiodstudy,therewasnodecreaseinthe
varicella-relatedhospitalization rates, and the results for the first
fouryearsindicatedareductionof23.5%.15,16In2004,Davis,
Patel,andGebremarian publishedasurveybythe
Nation-wideInpatientSample,withvaricellarelatedhospitalization
databetween 1993and 2001, andassessedthe impactof
theVVoverthefirstsixyearsafteritsintroduction:therate
between1993 and1995 was5/100,000 population, andit
wasreducedto1.3/100,000in2001,resultinginadecrease
of74%. Considering onlythe age groupof 0---4 years,this
28 articles 1683 articles 2059 articles PubMed (search performed on
May 2015)
Articles on the impact of the vaccine in one of the 24
countries selected Publications after 1995
(year of universal varicella vaccination
onset – USA) Keywords: “varicella”+ “vaccination/vaccine”+
“children”+
Figure1 SearchperformedinPubMed.
reduction wasevengreater: 81.8% (29.2to 5.3/100,000), with vaccine coverage of 76.3% at the end of the study period.Thestudyalsoindicatedadecreaseintheestimated cost of varicella-related hospitalizations, from US$ 161.1 millionin 1993toUS$66.3million in2001(areductionof 58.8%).17 In the following 17 years, studies with
observa-tionperiods ranging seventoten yearsafter introduction
of the vaccine have been published, observing reductions
thatrangedfrom59.1%and92.5%inhospitalizationrates,
according to the assessed age, with a vaccine coverage
that reached 90%.18---22 In 2006,the USAintroduced a
sec-onddoseofVVforchildrenbetween4and5years,andthe
mostrecentstudiespresentdataontheimpactofVVover
the15yearsofitsimplementation,includingthreetofour
yearsfromtheintroductionoftheseconddose.Therewas
75.6%reductioninvaricella-relatedhospitalizationratesin
the general population between 1994 and 2006 (2.13 to
0.52/100,000)andof88.3%between1994and2009(2.13to
0.25/100,000). Consideringonly theimpactof thesecond
dose, 51% reduction in admissions was observed between
2006 and 2009.2 When the impactof the vaccine in
chil-drenaged0---4yearswasassessed,hospitalizationrateswere
reduced by 90.6% between 1994 and2006 and by >99.2%
between1994and2009.Otherarticleshavedescribedthe
impactoftheseconddoseofthevaccinenotonlyin
hospital-izationrates,butalsointhereductionofvaricellaincidence
andoutbreaks.23---25
Uruguay
UruguaywasthesecondcountrytoincludeVVinthe immu-nization schedule (1999), in a single-dose regimen at 12 months;sincethebeginningofuniversal vaccination, vac-cine coverage between 88% and 96% (depending on the region)has been reached. As aconsequence, the country achievedareductionof81%inthevaricella-related hospi-talizationrateinthegeneralpopulation,and94%decrease inchildrenaged1---4yearsfrom1999to2005.26
Canada
of vaccination coverage, which in 2013 ranged between 67.0% and 97.2%. One dose schedule between 12 and 18 months (with a booster after 2010) wassupplemented in some territorial units with a two-dose schedule for sus-ceptible adolescents (>12 years). The first study of the impactof the vaccine on varicella-related hospitalization ratesobserveda48%reductionintheAlbertaprovinceafter oneyear(2001---2002)ofVVuniversalization.27Areduction
of90.1%(172to17hospitalizations/100,000childrenaged
1---4 years) was described by Tan etal., when comparing
themeanadmissionsperyearin 2000---2002withthe2008
result,includingregionstwotoeightyearsafteruniversal
vaccinationonset.28AnotherCanadianstudyreporteda
fur-therreductionof70%onadmissionofindividualsbelow40
years,and of 65%---93% in children aged between 1 and 4
years,includingregions threetotenyearsafteruniversal
vaccinationonset.29
Germany
Thecountryinitiallyadoptedasingledoseregimento chil-drenaged11---14monthsin2004;fiveyearslater,thesecond dose was implemented for children aged 15---23 months. The results achieved were described in twoarticles. One describedtheimpactofthevaccinespecificallyinthestate of Bavaria. In that state, five years after the implemen-tation of universal vaccination (53% coverage), therewas a 77.6% decrease (from 21 to 4.7/100,000) in varicella-related hospitalizations in children under5 years of age. Anotherstudy, conductedat the national level by Siedler andDettmannbetween1995and2012,indicated a reduc-tioninvaricella-relatedhospitalizationratesof62.4%(from 21.8to8.2/100,000)inchildrenbetween1and4years,with avaccinecoverageof78.2%foronedoseand67.6%fortwo doses.30,31
Italy
According to the WHO, Italy is among the countries that alreadyofferVVuniversally;however,fourstudiesretrieved ontheimpactofthevaccineinItalyindicatedthat,ofthe 21 Italianregions, only eight(Puglia, Basilicata,Calabria, Friuli-VeneziaGiulia,Sardinia, Sicily,Tuscany,andVeneto) adoptedthevaccine(firstdosebetween13and15months ofage andseconddose between5 and6years).The vac-cinewasimplementedbetween2003and2013,depending ontheregion,andresultedinameandecreaseof70%---75% inthehospitalizationrateinthegeneralpopulation,witha vaccinationcoveragerangingbetween60%and95%.32Other
publicationspresentedlocaldata:thevaricella-related
hos-pitalization rates in the Veneto region decreased 73.6%
(from44.3to11.7/100,000childrenaged1---4years)three
yearsafter the onsetof universal vaccination against the
disease, with a vaccination coverage of 78.6%; in Puglia,
an84% reduction(from35.1 to5.6/100,000 childrenaged
1---4 years) in varicella-related hospitalization rates was
observed after seven years, with a vaccination coverage
above 90%; finally, in Sicily, a reduction of 83.3% (from
4.8to0.8/100,000)invaricella-relatedhospitalizationswas
observedtenyearsafteruniversalvaccinationonset,witha
vaccinecoverageof84.7%.1,33,34
Australia
VVwasuniversallyintroduced inAustralia’spublic health-careservicein 2005,withthefirstdose at18monthsand thesecond between 10and 15 years.Threearticles have describedtheimpactofthisvaccineinvaricella-related hos-pitalizationrates.Thefirst,from2010,referstothedataof theStateofVictoria,whichpresentedarateof38.6/100,000 childrenunder4yearsbetween1995and1999(theperiod priortothevaccinelicensinginthecountry)andobserved areductionto19.4/100,000 (<4years)between 2006and 2007--- adecreaseof49.7%,witha78%vaccinecoverage.35
After three years, Marshall et al. assessed the rate of
varicella-related hospitalizations in fourtertiary hospitals
inAustraliaandfoundareductionof73.2%when
compar-ingaperiodpriortoVV(1999---2001)withalatersampling
(2007---2010).36Finally,in2014,Heywoodpublisheda
nation-widestudyinwhichthepre-vaccineperiod(1998---2000)was
comparedwiththepost-vaccine (2006---2010),observing a
decreaseof57.3%invaricella-relatedhospitalizationinthe
generalpopulation,morepronounced(76.8%,from83.3to
29.3/100,000) in children aged1---4 years,with a vaccine
coverageof82%---90%.37
Spain
In Spain, universal VV has been implemented from 2006 onwards,withdifferent strategiesby region,asthese are defined by the regional governments. Some regions have chosen tovaccinateinfants at 15months, witha booster atage3 years,andothershave decidedtoimmunize sus-ceptibleadolescentswithoneortwodosesofthevaccine. Navarraadoptedthe firstoptionin 2007;after fiveyears, a95.2%reductioninvaricella-relatedhospitalizationrates (from20.9to1.0/100,000)wasobservedinchildrenunder 15years,withvaccine coveragegreater than89% for two doses.38 In2014,Gil-Prietopresentednationalstatisticson
theimpactofVV andrevealed adecreaseof 83.5% (from
42.7 to 7.04/100,000) in children under 5 years in the
regionswhereinfantswerevaccinated,anda35.8%
reduc-tion(from 46.4 to29.8/100,000) for the same age group
in areas where susceptible adolescents were vaccinated.
Thesameauthordescribedsignificant regionaldifferences
invaricella-relatedhospitalizationrates,withdataranging
from12.08 to51.55 hospitalizations per 100,000 children
under5 years, with clear advantage for the regions with
greatercoveragevaccine.39,40
Table2showsthecountrieswiththegreatestreductions
ofvaricella-related hospitalizations after the vaccine was
includedintheroutineschedule.
Brazil
InBrazil,thefirstpublicationincludingdataontheimpact oftheVVwasastudycomparingtheincidenceofvaricellain childrenfromFlorianópolis---acitythatimplementedVVin thepopulationunder2yearsoldin2002---andtheremainder ofthestateofSantaCatarina.41Thestudyobserveda75.5%
decreaseintheincidencerateofthecapital,comparedwith
therestofstate,inchildrenaged1---4years,andcompared
presentdataonhospitalizationrates.Atthe2015meeting
ofthe European Society of PaediatricInfectious Diseases,
Andradeetal.presentedacase---controlstudyonthe
effec-tivenessofthevaccineintroduced inBrazilin2013intwo
Braziliancities,GoiâniaandSãoPaulo,withvaccination
cov-erageof74%and78%,respectively.42Theseauthorsshowed
that,duringthefirstyearofVVimplementation,thegroup
ofchildrenwithvaricellahadasmallerproportion(18.8%)
ofvaccineeswhencomparedwiththecontrolgroup(54%).
Theeffectivenessofthevaccinewas86.5%(95%confidence
interval:70.2%---94.1%)formoderateandsevereformsofthe
disease.
Discussion
AlthoughthefirstthreeAmericanpublicationsontheimpact ofuniversal VVdid notdemonstrate a statistically signifi-cantreductioninvaricella-relatedhospitalizationrates,or observed only a modest reduction,this can be explained bytheshortobservationperiodaftervaccine implementa-tion(2---4years)andlowvaccinationcoverage(<60%)inthe earlyyearsofVVintroduction.Allsubsequentpublications evaluatedinthisreview,bothfromtheUSAandtheother countries,demonstrated thatVV universalization resulted insignificantreductionsinhospitalizationrates.Theresults arehighlyvariable;thesmallestdecreaseinthedescribed hospitalizationratewas30.9%forthegeneralpopulationof theStateofVictoria(Australia)andthehighest,99.2%,in childrenaged0---4yearsintheUSA.2,35 Thislarge
discrep-ancyinvaluesisunderstandablewhenconsideringthatfirst
resultreportedonlytwoyearsperiodafteruniversalvaccine
onset,includedthehospitalizationrateoftheentire
popu-lation,withaone-dosevaccinationscheduleforinfants,and
vaccinationcoverageof78%,whilethesecondassessedthe
situationafter14yearsofvaccineintroduction,considered
thespecificagegroupofchildrenupto4years,witha
two-dosevaccinationscheduleandvaccinationcoverageof90%.
Greater decrease in varicella-related hospitalization
rates is expected when considering a longer period of
timeaftertheadoptionofuniversalvaccination,whenthe
statisticreferstoinfants andpreschoolers(the agegroup
generallymostaffectedbythedisease),andwhenvaccine
coverageishigher.Thus,although Table2liststheresults
ofhospitalizationreductionincountriesthathaveadopted
thevaccine,adirectcomparisonofthedataisunworkable.
Thereareimportantdifferencesinstudiedagegroups(0---4
years,1---4years,<15years),intimeperiodanalyzedafter
VVintroduction(1---15years),invaccinationschedule(some
countrieswithonedose,otherswithtwo),andinstrategies
regardingvaccination age. Furthermore,a highly variable
vaccine coverage was observed among the studies: from
12.9%to96%. WhileUS publications showthe importance
oftheseconddoseofthevaccine,itisdifficulttosaythat
countriesthat haveadopted two doseshad betterresults
thanthosewhoadoptedasingledosewithhighvaccination
coverage,asshownintheUruguayanexperience,which
pro-videdexcellentresultsfromthe useof asingledose with
highvaccinationcoverage.2,23,26
Anotherissuethatcouldexplainthedifferenceinresults
isthewidevariationinvaricella-relatedratesof
hospitaliza-tionsinthepre-vaccineperiod(USA:29/100,000;Australia:
24/100,000; Spain: 21/100,000; and Italy: 44/100,000),
which created different pre-vaccine baselines among the
various locations.Those with thehighest rates beforeVV
implementationtendtodemonstrateagreaterimpactfrom
vaccine.Oneofpublicationsindicatedspecificpopulations
ofnativeAmericansandAlaskans,whopresented
varicella-related hospitalization rates three times higher than the
American average in pre-vaccine period, had one of the
largest reductions in this statistic (greater than 95%) in
the post-vaccine period.25 Likewise, some countries had
hadareasonable vaccinationcoverageagainstvaricellain
privatehealthcaresystem whenuniversal vaccinationwas
introduced.SomeCanadianagegroupreached 28%inthat
kindofcoverage,whileinVenetothisratewasestimatedat
6.8%.Theimpactofthevaccinetendstobehigherinareas
withlowervaccinationcoverage(bytheprivatehealthcare
system) inthe periodpriortovaccine universalization.1,43
The admissioncriteriaandtheadmissionsnotification
sys-tems also differ from one country to another, hindering
comparativeanalysis.
Several studies indicate that, after VV
universaliza-tion, reductions in varicella-related hospitalizations were
observed in non-vaccinated age groups, such as children
under1yearandteenagers,demonstratingtheindirect
ben-efitofuniversalvaricellavaccinationonthepopulationasa
whole,aneffectknownasherdimmunity.1,25,28,29,39
Conclusions
Inadditiontooutliningcountriesthathavealready imple-mented VV this review showed that, 20 years after the introductionofVVinAmericanvaccinationcalendar(1995), therehasbeenagrowinginterest byscientificcommunity in monitoring the impact of this measure on the reduc-tionofincidence,hospitalization,andmortalityrelatedto the disease, which is reflected by significant increase of publications onthesubject from1995 onwards.Observed reductionsinhospitalizationratesbetween62.4%and99.2% cannotbedirectlycomparedduetolackofuniformityinthe agegroupstudied,timefromvaccinationonset,vaccination schedulevaccinationcoverage,andhospitalizationcriteria, amongotherfactors.
Afterinclusion ofVVintheNational Immunization Pro-graminBrazilin2013,theannualratesofvaricella-related hospitalization are expected to reduce. Although these results may be scarcely evident in the early years, as occurredintheUSA,thehighvaccinationcoverageobserved in Brazil may promote a faster, sharper reduction in this statistic. Itis criticaltostudy thepre-vaccinationdata in Brazil in order tomeasure real impactof introduction of VVin coming years,aswell astoassessthe need for the implementationofseconddosevaccineinthefuture.
Funding
Thisstudydidnotreceivefunding.
Conflicts
of
interest
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