Seronegativity to polio viruses among previously immunized adult candidates to solid organ transplantation

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brazjinfectdis2018;22(2):150–152

w w w . e l s e v ie r . c o m / l o c a t e / b j i d

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

Brief

communication

Seronegativity

to

polio

viruses

among

previously

immunized

adult

candidates

to

solid

organ

transplantation

Luciana

Gomes

Pedro

Brandão

a,∗

_,

_Pedro

_Emmanuel

_Alvarenga

_Americano

_do

_Brasil

b

_,

Silas

de

Souza

Oliveira

c

_,

_Edson

_Elias

_da

_Silva

c

_,

_Guilherme

_Santoro

_Lopes

d

a_Instituto_Nacional_de_Infectologia_Evandro_Chagas_(Fiocruz),_Laboratório_de_Pesquisa_em_{Imunizac¸ões}_e_Vigilância_em_Saúde_(LIVS),

CentrodeReferênciaparaImunobiológicosEspeciais,RiodeJaneiro,RJ,Brazil

b_Instituto_Nacional_de_Infectologia_Evandro_Chagas,_Laboratório_de_Pesquisa_em_{Imunizac¸ões}_e_Vigilância_em_Saúde_(LIVS),_Rio_de

Janeiro,RJ,Brazil

c_Instituto_Oswaldo_Cruz_(Fiocruz),_Laboratório_de_{Enterovírus,}_Rio_de_Janeiro,_RJ,_Brazil

d_Universidade_Federal_do_Rio_de_Janeiro,_Departamento_de_Medicina_Preventiva,_Rio_de_Janeiro,_RJ,_Brazil

a

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t

i

c

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Articlehistory:

Received24October2017

Accepted9February2018

Availableonline1March2018

Keywords:

Poliomyelitis Immunity

Solidorgantransplantation

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b

s

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t

Inthecurrentefforttoeliminatepoliofromtheworld,itisimportanttorecognizeand

vacci-natesusceptiblegroups,especiallyimmunocompromisedpatientslivingincountrieswhere

attenuatedpoliovaccineisstillused.Inthisreport,wedescribethefrequencyofprotective

antibodiesinasmallsampleofadultSOTcandidatesinwhompreviousvaccinationcould

beascertained.Patientsincludedinthisreportwereselectedamongtheparticipantsofan

ongoingprospectivestudycarriedoutattheReferenceCenterforSpecial

Immunobiologi-calsoftheEvandroChagasNationalInstituteofInfectiousDiseasesinRiodeJaneiro,Brazil.

Amongtheﬁrst100patientsenrolledinthisstudy,onlysevenadultSOTcandidateshad

provenpoliovaccinationatchildhood.Threeofthesesevenpatients(43%)hadno

protec-tiveantibodytiterstooneormorepoliovirussubtypebeforesolidorgantransplant.Proven

childhoodvaccinationagainstpoliodoesnotreliablyprovidelifelongprotectiveantibody

titersforadultSOTcandidatesandshouldnotbeusedasacriteriontoanalyzetheneedfor

vaccinationinthispopulation.

openaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/

by-nc-nd/4.0/).

Intheearlytwentiethcentury,poliowasanepidemicdisease,

whichcausedparalysisinthousandsofchildren,resultingin

apublichealthproblemwithenormouspsychosocialimpact.

∗ _{Corresponding}_author.

E-mailaddress:luciana.pedro@ini.ﬁocruz.br(L.G.Brandão).

Aftertheadventofspeciﬁcvaccines,inactivated(in1955)and

attenuated(in1961),thediseasehasbeeneliminatedinmost

countries.

Despite the current progress toward eradication of the

disease,in2014,the spread ofwildpoliovirus topolio-free

countries was recognized asa Public Health Emergency of

https://doi.org/10.1016/j.bjid.2018.02.003

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brazj infect dis.2018;22(2):150–152

151

InternationalConcern,1 _and_there_was_a_recent

demonstra-tionofsilentcirculationofwildpoliovirus1inIsrael.2These

arealertsthatreintroductionofwildpoliovirusinareaswhere

thediseasehadbeeneradicatedmaystillbethreatening,

espe-ciallyforgroupsofunderimmunizedpeople.Inaddition,in

countriessuchasBrazil,whereoralliveattenuatedpoliovirus

vaccine(OPV)isstillused,infectioncausedbyvaccinederived

poliovirusesremainspossible,especiallyin

immunocompro-misedindividuals.3

Intheﬁnalstepofpolioeradication,seroprevalence

stud-ieshaveincreasedinimportanceandcanpointtoimmune

gapsinspeciﬁcpopulations.4–6_Serum_neutralizing_antibody

titers,thetraditionalmeasureofvaccine-inducedimmunity,

haveareliablecorrelationwithprotectionagainstparalytic

poliomyelitis. However,it isalimited determinantofvirus

replicationintheintestinaltract.Mucosalimmunityis

pre-sumedtohaveakeyrole inprotectingagainstentericand

pharyngealinfectionwithpoliovirus,and henceitcould be

crucialindiminishingtheefﬁciencyoftransmission.7

Inrecentdecades,solidorgan transplantation(SOT) has

becomeatherapeuticalternativeformanyirreversible

con-ditions such as chronic renal failure and liver cirrhosis.

The success of SOT, however, depends on lifelong use of

immunosuppressivedrugs,whichmakestheindividual

sus-ceptible tovarious infectious diseases.Vaccination pre- or

post-transplantationis a recommended strategy to reduce

vaccine-preventable diseases.8 _Although _a _previous _study

has demonstrated very low seroprevalence of protective

antibodies topoliovirus inpatients who received a kidney

transplantation,9_{recommendations}_regarding_polio

vaccina-tionforadultSOTcandidatesandrecipientsarenotuniform

andinsomecountries(includingBrazil)vaccinationisonly

indicated for adult patients who had not been previously

immunizedorforthoseplanningtotraveltoriskareas.8,10–13

In this report, we describe the frequency of protective

antibodies in a small sample of SOT candidates in whom

previousvaccinationcouldbeascertained.Patientsincluded

inthisreportwereselectedamongparticipantsofan

ongo-ingprospectivestudycarriedoutattheReferenceCenterfor

SpecialImmunobiologicalsofthe EvandroChagas National

InstituteofInfectiousDiseases(INI-Fiocruz)inRiodeJaneiro,

Brazil.ThisstudyincludescandidatesforanytypeofSOT,aged

18 yearsor older who had no contraindication to

vaccina-tionwithinactivatedpoliovaccine(IPV)andgaveawritten

informed consent to participate in the study. This report

includesonlythesubsetofpatientsinwhomprevious

vac-cinationcouldbeconﬁrmedbycheckingthevaccinationcard.

Datacollectedfromeachpatientintheﬁrstvisitincludedage,

sex,underlyingorgandisease,comorbiditiessuchas

hepati-tisCinfection,HIVinfection,diabetesmellitus,currentuse

ofimmunosuppressivedrug, andpreviousOPVvaccination.

Abloodsamplewascollectedintheﬁrstvisitfor

determina-tionofantibodytitersagainstpoliovirus1,2and3.Thiswas

performed by microneutralization test, according to World

Health Organization protocol,14 _at _the _Enterovirus

Labora-tory(WHORegionalReferenceLaboratory),ofOswaldoCruz

Institute(Fiocruz,RiodeJaneiro,Brazil).Titers≥1:8were

con-sideredprotective.Patientswithtitersbelow1:8receivedone

doseofIPV(SanoﬁPasteur).Asecondbloodsamplewas

col-lectedafter30daystoevaluatetheimmunogenicresponseto

vaccination.ThisstudywasapprovedbytheEthicsResearch

CommitteeofINI(12718913.0.0000.5262).

Amongtheﬁrst100patientsenrolled inthis study,only

sevenSOTcandidateshadprovenpoliovaccinationat

child-hood,allwerekidneytransplantcandidates.Threeofthese

seven patients had no protectiveantibody titers toone or

morepoliovirussubtype.Theﬁrstpatientwasa30-year-old

malepatient,withchronicrenalinsufﬁciencycausedbyAlport

Syndrome,inconservativetreatment.Hehadreceivednine

OPVdoses.Thelast dosewas in1987.Samplecollected in

2013forpoliovirusserologyrevealedtiters<1:8forallthree

subtypes ofpoliovirus. Thesecond casewas a 37-year-old

female, withchronicrenalfailurecausedbyarterial

hyper-tension, onhemodialysis sinceJuly2012.Shehad received

threeOPVdoses,lastdosein1980.Samplecollectedin2013

forpoliovirusserologyrevealedtiters<1:8forpoliovirus2and

1:16 forpoliovirus1and 3.Thelastpatient wasa

25-year-oldfemale,withchronicrenalinsufﬁciencycausedbyarterial

hypertension, onconservative treatment. Shehad received

sevendosesofOPV,lastdosein1993.Samplecollectedin2014

forpoliovirusserologyrevealedtiters<1:8forpoliovirus1and

3,1:8forpoliovirus2.Noneofthesepatientswereon

immuno-suppressivetherapy,andHCVandHIVserologywerenegative

inallofthem.Thethreepatientsdevelopedprotectivetiters

ofantibodiestoallpoliovirusaftervaccinationwithonedose

ofIPV.

Brazil maintains high immunization coverage for

poliomyelitis.Itisestimatedthat>93%ofthechildpopulation

receives polio vaccine. The current national immunization

schedule forpoliomyelitisconsistsofthreedoses ofIPV in

theﬁrstyearoflife(at2,4and6months),followedbytwo

boosters(at15 monthsand betweenthe2ndand 4thyear)

using OPV. Additionally, thereare annual massivenational

campaignswithtwodosesoforalvaccine,onemonthapart,

for all children (twomonths toﬁve years old). Until 2012,

only OPV was used in the national vaccination program.

Thereafter,IPVprogressivelyreplacedOPVintheﬁrstthree

vaccinedoses,butOPVisstillusedasboosterdosesandin

annualcampaigns.

The transmission of OPV viruses from a recently

vac-cinated child to a non-immunized immunocompromised

individualinthecommunityisassociatedwithtwopotential

hazards.Immunocompromised hostshave higher

probabil-itytodevelopﬂaccidparalysisafterbeingexposedtoOPV.15

Inaddition,prolongedviralreplicationinimmunedeﬁcient

hostscould increase theprobability ofOPVviruses

regain-ing ﬁtness and neurovirulence.3 To reducethese risks, the

BrazilianSocietyofOrganTransplantationrecommendsthat

adultSOTcandidatesandrecipientswhohadnotbeen

previ-ouslyimmunizedshouldbevaccinatedwithIPV.However,the

BrazilianMinistryofHealthinlinewiththenational

guide-linesofothercountriesrecommendsthatIPVshouldbeused

onlybychildrenandtravelerstopolioriskareas.8,10–13

The identiﬁcation of three adult SOT candidates who

did not have protective levels of neutralizing antibodies

despite proven immunization at childhood suggests that

childhood immunization isnot a reliable predictor of

pro-tectionagainstpoliovirusinfectionforadultSOTcandidates.

Naturalorvaccine-inducedpolioimmunitymay wanewith

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152

braz j infect dis.2018;22(2):150–152

dysfunction, the immune response to vaccines can be

compromised.17_Although,_immune_memory_seems_to_prevent

clinicaldisease,itmaynotbecapableofpreventinginfection

andviralsheddinginfeces.16_This_ﬁnding_lends_support_to

theapproachrecommendedbytheAmericanSocietyof

Trans-plantationwhichistoroutinelyvaccinateSOTcandidatesand

recipientswithIPV,althoughrecognizingthatthis

interven-tionisnotbasedonhigh-qualityevidence.8

In conclusion, in the current effort to eliminate polio

from the world,it isimportant torecognize and vaccinate

susceptiblegroups,includingimmunocompromisedpatients,

especiallyinthelargenumberofcountriesinwhich

circula-tionofattenuatedpoliovaccinevirusstilloccurs.Ourﬁndings

suggestthatprovenchildhoodvaccinationagainstpoliodoes

notreliablypredictlifelongprotectionamongadultSOT

can-didates even in a context of large scale attenuated virus

circulation.Therefore,furtherstudiesarenecessaryto

eluci-datethebeststrategytopreventpoliovirusinfectioninthis

population.

Funding

support

ThisstudywaspartlysupportedbyTEIASProject(Territórios

Integrados de Atenc¸ão à Saúde), Enterovirus Laboratory

(OswaldoCruzInstitute)andEvandroChagasNational

Insti-tuteofInfectiousDiseases(INI-Fiocruz).

Conﬂicts

of

interest

Theauthorsdeclarenoconﬂictsofinterest.

Acknowledgement

WeacknowledgeDanielMarinhodaCostaforhisparticipation

inthecareofthepatients.

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