RevPaulPediatr.2016;34(3):251---253
REVISTA
PAULISTA
DE
PEDIATRIA
www.rpped.com.br
EDITORIAL
In
time:
the
persistence
of
congenital
syphilis
in
Brazil
---
More
progress
needed!
Em
tempo:
a
persistência
da
sífilis
congênita
no
Brasil
---
Mais
avanc
¸os
são
necessários!
Joshua
M.
Cooper
a,
Ian
C.
Michelow
b,
Phillip
S.
Wozniak
a,
Pablo
J.
Sánchez
a,∗aNationwideChildren’sHospital,TheOhioStateUniversityCollegeofMedicine,Columbus,UnitedStates
bRhodeIslandHospital,AlpertMedicalSchoolofBrownUniversity,Providence,UnitedStates
Despite decades of epidemiologic and clinical experience withmaternal and congenitalsyphilis,both remain major public health problems in Brazil and in the rest of the Americas.In2010andsupportedbytheWorldHealth Organi-zation(WHO),thePanAmericanHealthOrganization(PAHO) Member States approved the Strategy and Plan of Action for theElimination ofMother-to-Child TransmissionofHIV andCongenitalSyphiliswiththegoalofreducingthe inci-dence of congenital syphilis to ≤0.5 cases per 1000 live
birthsby2015.1In2014,17,400cases(1.3/1000livebirths)
of congenitalsyphilis werereportedin the Americas,and 17countriesmayhave eliminatedmaternal-to-child trans-mission ofsyphilis.2 Despite someprogress, Brazildid not
meetthecongenitalsyphiliseliminationgoalbutrather,the epidemicrageson,resultinginsubstantialfetaland neona-tal mortality. In 2010, 6916 cases (2.27/1000 live births) of congenital syphiliswere reported tothe Brazilian Min-istry of Health and PAHO, while in 2013, the number of cases increased to 13,705 (4.70/1000 live births) before decreasingto6793casesin2014.2,3
Congenital syphilis is a preventable disease,and there must be zero tolerance for its occurrence as even one case represents a failure of the public health system. Health care professionals know what must be done to
∗Correspondingauthor.
E-mail:[email protected](P.J.Sánchez).
prevent congenital syphilis and its complications which includestillbirth,prematurity,nonimmunehydropsfetalis, and neonatal mortality.4 The WHO estimates that
glob-ally, 1.5---1.85 million pregnant women are infected with syphilisannuallyandhalfofthemhaveinfantswithadverse outcomes.4IntheUnitedStatesfrom1999to2013,neonatal
mortalitysecondarytocongenitalsyphiliswas12/1000live births,withacasefatalityrateof6.5%.5Ofthe418reported
deaths, 82% were stillbirths and 89% of the mothers had untreatedor inadequately treatedsyphilis. Moreover,less prenatalcarewasassociatedwithincreasedrisk ofdeath, andimportantly,59%ofthedeathsoccurredby31weeksof gestation.
Itisclearthatpregnantwomenmusthaveaccesstoearly prenatalcareandbescreenedserologically for syphilisat thefirstprenatalvisitand,inhighriskareas,againat28---32 weeks’gestationanddelivery.6 AccordingtoPAHO,94%of
pregnantwomenintheAmericasattendedatleastone ante-natal care visit during the pregnancy, and 80% received syphilis testing at some point during the pregnancy.2 In
Brazil,Dominguesetal.7 interviewed23,894 women
post-partumandreportedthat98.7%hadatleastoneantenatal carevisit,89% haddocumentationof atleast onesyphilis testonprenatalrecordcards,butonlyanadditional41%had asecondtestperformed.From2011to2014,PAHOreported anincreasefrom81%to86%insyphilis-infectedwomenwho haddocumentation of appropriate treatment, although it wasstillbelowitsgoalof95%.2Itthereforeisnotsurprising
http://dx.doi.org/10.1016/j.rppede.2016.06.004
2359-3482/©2016SociedadedePediatriadeS˜aoPaulo.PublishedbyElsevierEditoraLtda.ThisisanopenaccessarticleundertheCCBY
252 CooperJMetal.
thatcongenitalsyphilisremains amajorprobleminBrazil andtherestoftheAmericas.
Inadditiontoidentificationofinfectedpregnantwomen, timely treatment is mandatory for prevention of congen-ital syphilis.8,9 In locales where follow-up is uncertain or
difficult,rapidpoint-of-caresyphilistestingshouldbe per-formedsothatwomenaretreatedonsiteandwithoutdelay. Inaddition,serologictestingandpresumptivetreatmentof theirsexualpartnerisessentialtopreventreinfectionand transmissiontothefetus.10InBrazil,ithasbeenestimated
thatonlyabout 12%ofsexualpartnersreceivedtreatment forsyphilis,11certainlyafailureofthepublichealth
infra-structure as contact tracing and treatment is the major methodofcontrollingsyphilistransmissionincommunities. Penicillin G is the only known effective antimicrobial agent for preventing vertical transmission of syphilis and treatingfetalinfection.6Pregnantwomenshouldreceivethe
penicillinregimenappropriateforthestageofinfection,and ifanydoseoftherapyismissedforlatentsyphilis,thefull courseoftherapymustberepeated.Pregnantwomenwho have ahistory of penicillinallergy shouldbe desensitized andtreatedwithpenicillin.
Unfortunately, the diagnosis of congenital syphilis remainsproblematicduetotheinabilitytodetectorculture
Treponema pallidum in clinical specimens, thus necessi-tating reliance on laboratory tests that detect maternal nontreponemalandtreponemal IgGantibodiestransferred transplacentallytothe fetus. Nonetheless,theuse ofIgM immunoblotting,PCR assays,andrabbit infectivitytesting (RIT,inoculationofinfectedpatientfluidintorabbittestes withresultantsyphiliticinfectionoftherabbit)inresearch laboratories hasallowed evidence-basedrationale for the managementofinfantsborntomotherswithreactive sero-logictestsforsyphilis.12---15
Neonates withproven or highly probablysyphilis, that is, those who have an abnormal physical examination, serum quantitative nontreponemal serologic titer that is fourfold or higher than the mother’s titer, or pos-itive darkfield microscopy or PCR of lesions or body fluids/tissues/placenta,16 arediagnosedreadilyandshould
receive10daysofintravenousaqueouscrystallinepenicillin GorintramuscularprocainepenicillinGtherapy.Virtuallyall oftheseinfantshaveapositiveIgMimmunoblot,andatleast 50%ofthemhavespirochetesdetectedincerebrospinalfluid byRIT.17
Thewell-appearinginfantwithanormalphysical exami-nationandborntoamotherwithuntreatedorinadequately treated (<4 weeks before delivery or any nonpenicillin G regimen)syphilisremainsadiagnosticconundrum.However, whileasmany as20% oftheseinfants have apositiveIgM immunoblot indicative of in utero infection, almost none willhavecentralnervoussysteminvasionbyT.pallidumif theircomplete evaluation(complete blood cellcountand platelets, long bone radiographs, and cerebrospinal fluid [CSF] examination) is normal.17 These infants can receive
a single intramuscular injection of benzathine penicillin G (50,000U/kg).6 Finally, normal infants born to mothers
adequately treated during pregnancy and greater than 4 weeks before delivery should be considered as a ‘‘close contact’’ and receive a single intramuscular injection of benzathinepenicillinG,althoughnoevaluationisrequired or recommended.6 Similarly, normal infants who have
a nonreactive serum nontreponemal test result but are born to mothers with untreated or inadequately syphilis can receive a single dose of intramuscular benzathine penicillinG without evaluation --- an increasingly common scenariowiththeuseof treponemaltestssuchasenzyme immunoassays or chemiluminescence immunoassays for syphilisscreening(‘‘reversesequence’’screening).18
Assyphiliscanbeaco-factorforHIVinfection,allwomen and their sexual partner(s) who have syphilis should be testedforHIVinfection.Infantsborntomotherscoinfected withsyphilis and HIV donot requiredifferent evaluation, therapyorfollow-up.
All infants with reactive nontreponemal tests should receive carefulfollow-up examinationsandserologic test-ing (i.e., a nontreponemal test) every 2---3 months until the test becomes nonreactive.A reactive serum trepone-maltestbeyond18monthsofagewhenmaternalantibodies havedisappearedconfirmsadiagnosisofcongenitalsyphilis, althoughasmanyas20%ofinfectedinfantsmayserorevert completelytononreactivesyphilisserologictests.
Recently,apenicillinshortagein Brazilandotherparts of the worldhas posed aserious health threatto fetuses andinfantsofmotherswithsyphilis.Ifpreparationsof peni-cillinare unavailable, a10 day course of ceftriaxone can be considered with careful clinical and serologic follow-up,includingrepeatCSFevaluation.6,19Researcheffortsare
neededtoevaluatewhetherotherantibioticssuchas ampi-cillincantreateffectivelycentralnervoussystemdisease.
Thelackof timelyidentificationandappropriate treat-mentofinfectedinfantscanhaveprofoundconsequencesin laterlife.Manifestationsoflatecongenitalsyphilisinvolve thecentralnervoussystem,bonesandjoints,teeth,eyes, andskinandincludeHutchinson’striad(interstitial kerati-tis,eighthcranialnervedeafness,notchedcentralincisors), named after Sir Jonathan Hutchinson (1828---1913) from England.
Researchandhumanitarianeffortsmustcontinueto con-trol, treat, and eventually eliminate congenital syphilis globally.The publichealthimpactofsyphilisinpregnancy andinfancyremainssubstantial,andonlythroughoptimal prenatal healthcareserviceswill elimination of maternal-to-child transmission of syphilis become a reality in the Americas.
Funding
Thisstudydidnotreceivefunding.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
Acknowledgements
Intime:thepersistenceofcongenitalsyphilisinBrazil---Moreprogressneeded! 253
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