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RedBookUpdate:2018
MichaelT.Brady,MD
ProfessorofPediatricsTheOhioStateUniversityAssociateMedicalDirectorNationwideChildren’sHospital
RedBookUpdate:2018MichaelT.BradyMD NeitherInormyspouse/partnerhaveanyrelevantfinancialrelationshipswiththemanufacturer(s)oranycommercialproduct(s)and/orproviderofcommercialproductsorservicesdiscussedinthisCMEactivity.Idonotintendtodiscussunapproved/investigativeuseofcommercialproduct(s)/device(s)inmypresentation.
Author: Committee on Infectious Diseases David W. Kimberlin, MD, FAAP, Editor
Michael T. Brady, MD, FAAP, Associate
Editor Mary Anne Jackson, MD, FAAP, Associate
Editor Sarah S. Long, MD, FAAP, Associate Editor Hard copy is once again an AAP member benefit. Members need to go online to order their complimentary copy. Limited “life span” : 2018-2021 2018 Red Book
- Distribution starts May 1, 2018 - Available at PAS
HPVVaccine
AdolescentHPVVaccineCoverage:StillNeedToDoBetter
3dosefemale
3dosemale
HumanPapillomavirusVaccines
Characteristicsofthethreehumanpapillomavirus(HPV)vaccineslicensedforuseintheUnitedStates.
Characteristic Bivalent(2vHPV) Quadrivalent(4vHPV) 9-valent(9vHPV)
Brandname Cervarix** Gardasil** Gardasil9
VLPs* 16,18 6,11,16,18 6,11,16,18,31,33,45,52,58
*Virus-likeparticles **NolongeravailableinUS
RelativeContributionofHPVTypesin9vHPVtoCervicalCancersWorldwide
LancetOncol2010;11:1048-1056InfectAgentCancer2012;7:38
8
HPV-AssociatedCancersTrends—UnitedStates,1999–2014
Rateswereconsideredtoincreaseifannualaveragepercentagechange(AAPC)>0(p<0.05)andtodecreaseifAAPC<0(p<0.05);otherwiserateswereconsideredstable.*=p<0.05
[CELLRANGE]
[CELLRANGE]
[CELLRANGE]
[CELLRANGE]
[CELLRANGE][CELLRANGE]
[CELLRANGE]
[CELLRANGE]
0
1
2
3
4
5
6
7
8
9
10
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
Rate(casesper100,000)
Yearofdiagnosis
Vagina Vulva
Penis Anus-Female
Anus-Male Oropharynx-Female
Cervix Oropharynx-Male
AAPModificationofTimeofInitiationofHPVVaccine
ACIP2018and2015RedBookWording:“…recommendsstartingtheseriesatage11or12yearsofageandstatesthatvaccinationcanbeadministeredstartingatage9years.WhenHPVvaccineisbegunat9or10yearsofage,otheradolescentvaccines(e.g.,MenACWYandTdap)arestillrecommendedtobeadministeredonlyat11to12yearsofage.2018RedBookWording:TheAAPrecommendsstartingtheseriesbetween9and12years,atanagethattheproviderdeemsoptimalforacceptanceandcompletionofthevaccinationseries.
HumanPapillomavirusVaccine2Dosesvs.3Doses
• AAPrecommendsstartingvaccinationseriesbetween9and12yearsofage
• Forpersonsinitiatingvaccinationbeforethe15thbirthday,therecommendedimmunizationscheduleis2dosesofHPVvaccine(0,6-12monthschedule)
• Forpersonsinitiationvaccinationonorafterthe15thbirthday,therecommendedimmunizationscheduleis3dosesofHPVvaccine(0,1-2,6monthschedule)
AgeatInitiationofHPVVaccinationandCompletionofVaccineSeries
Characteristic AgeatInitiationofHPVVaccinationSeries
P-value
9-10years 11-12yearsCompleted3dosesofvaccineby13.5yearsofage
707/725(97.5%) 1258/1613(78.0%) <0.001
Completed3dosesofvaccineby15yearsofage
722/725(99.6%) 1517/1613(94%) <0.001
Completed2dosesofvaccineby13.5yearsofage
946/951(99.5%) 2071/2259(91.7%) <0.001
Completed2dosesofvaccineby15yearsofage
950/951(99.9%) 2210/2259(97.8%) <0.001
PreventiveMedicine2016;89:327-333
HumanPapillomavirusVaccineImmunocompromisedPatients
• Immunocompromisedfemalesandmalesaged9through26yearsshouldreceive3dosesofHPVvaccine(0,1-2,6month)
• Personswhoshouldreceive3doses:– Primaryorsecondaryimmunocompromisingconditionsthat
mightreducecell-mediatedorhumoralimmunity.– HIVinfection.– Malignantneoplasmortransplantation.– Autoimmunediseaseorimmunosuppressiontherapy.
• Recommendationfora3-dosescheduledoesnotapplytochildrenaged<15yearswithasplenia,asthma,chronicgranulomatousdisease,chronicheart/liver/lung/renaldisease,CNSanatomicbarrierdefects(e.g.cochlearimplant),complementdeficiency,diabetes,orsicklecelldisease.
HumanPapillomavirusVaccineAdditionalInformation
• 9vHPVmaybeusedtocontinueorcompleteaseriesstartedwith4vHPVor2vHPV.
• Forpersonswhohavebeenadequatelyvaccinatedwith2vHPVor4vHPV.Therearenocurrentrecommendationsforanyadditionalimmunizationswith9vHPV.(9vHPVmaybeconsideredifrequestedforadditionalHPVstrainprotection.However,insurancereimbursementcouldbeanissue.Giving9vHPVtoadolescentimmunizedwith2vHPVor4vHPVwouldpreventmorediseasethanprovidingMenBvaccinetoadolescents).
• Ifthevaccinescheduleisinterruptedforanyduration,thevaccinationseriesdoesnotneedtoberestarted.
Question
Whichvaccine-preventableinfectionismostlikelytocausethedeathofoneofyourpatients
in2018.
Influenza
PediatricDeaths
InfluenzaSeason PredominantStrain
PediatricDeaths
Hospitalizations(0-4yearsold)
per100,000
Hospitalizations(5-17yearsold)
per100,000
2017-2018(upto:4/15/2018) H3N2 156 47.1 12.3
2016-2017 H3N2 98 44.1 16.7
2015-2016 pH1N1 85 42.5 9.6
2014-2015* H3N2 148 57.3 16.6
2013-2014 pH1N1 111 47.3 9.4
2012-2013 H3N2 171 67 14.6
2011-2012* H3N2 37 16 4
2010-2011 H3N2 123 49.5 9.1
2009-2010 pH1N1 288 77.4 27.2
2008-2009 H1N1 137 28 5
2007-2008 H3N2 88 40.3 5.5
2006-2007 H1N1 77 34.6 2.3
PediatricDeathsByHighRiskMedicalConditions
2017-18LanguageinAAPPolicyAnnualuniversalinfluenzaimmunizationisindicatedwitheitheratrivalentorquadrivalent(nopreference)inactivatedvaccine.Quadrivalentliveattenuatedinfluenzavaccine(LAIV4)isnotrecommendedforuseinanysettingintheUnitedStatesduringthe2017–2018influenzaseason.Thisinterimrecommendation,originallymadein2016,followedobservationaldatafromtheUSInfluenzaVaccineEffectivenessNetworkrevealingthatLAIV4performedpoorlyagainstinfluenzaA(H1N1)pdm09virusesinrecentinfluenzaseasons;
InfluenzaVaccinationCoveragebyAgeGroup,Children6months–17years,NIS-Flu,UnitedStates,2016–17Season
Age Group Unweighted Sample Size
%* ±95% CI†
Difference from the 2015−16 Season ±95%
CI 6 months−17 years 143,169 59.0 ± 0.7 -0.3 ± 1.1 6 months−4 years 44,094 70.0 ± 1.3 0.0 ± 1.9
6−23 months 16,374 76.3 ± 2.0 1.0 ± 2.6
2−4 years 27,720 66.2 ± 1.6 -0.6 ± 2.4
5−17 years 99,075 55.6 ± 0.8 -0.3 ± 1.2
5−12 years 63,130 59.9 ± 1.0 -1.9 ± 1.6‡
13−17 years 35,945 48.8 ± 1.3 2.0 ± 1.9‡
* Percentage vaccinated. † Confidence interval half-widths. ‡ Statistically significant difference between the 2016–17 season and the 2015–16 season by t-test (P<0.05).
PossibleReasonsforLowVaccineEfficacy(VE)ofLAIVtoA/
H1N1pdm09
• DifferencesinviralreplicationandinfectivityaffectVE.• Duringandafter2009,pre-pandemicA/H1N1inLAIVwasreplaced
withA/H1N1pdm09HAandNAproteinsàpoorerreplicationandshedding.
• AnaminoacidsequencewasidentifiedintheHAstalkregionofwild-typeA/California/7/2009H1N1pdm09virusthatreducedthermalstabilityandinfectivityoftheLAIVvaccineviruscontainingtheHAgene.Likelynottheproblem.
• Changeinstrainin2015-16toA/Bolivia/559/2013/H1N1pdm09for2015-16didNOTimprovevaccineefficacy.
• ChangefromLAIV3toLAIV4withoutdosechange.• Effectofrepeatedvaccinationsinchildren.• Otherunknownimmunologiceffects.
ChungJR,FlanneryB,ThompsonMG,etal.SeasonalEffectivenessofLiveAttenuatedandInactivatedInfluenzaVaccine.Pediatrics.2016;137(2):e20153279
VEMeta-Analysis(2011-2016seasons)Summary
A(H1/N1)pdm09• LAIVwasbetterthannovaccinefor2-17yearoldsinUS-IPD;but
notinothersurveillancesystems.• IIVbetterthanLAIVforallagegroupsintheUS.• A/SloveniawasinLAIV4for2017-18season(usedinUK,Finland,
Canada).• NoUSVEdataforLAIVsince2015,orwithA/Sloveniainother
countries.H3N2• LAIV=IIV,exceptfor2-4yearoldswhereIIVwasbetter.Bstrains• LAIVmightbebetterthanIIV(notstatisticallysignificant).Thereare13licensedinfluenzavaccines.Recommendationsforindividualinfluenzavaccinesarenotgenerallybaseduponcomparativeeffectivenessdata.
ACIPVoteFebruary2018“Forthe2018-19season,immunizationprovidersmaychoosetoadministeranylicensed,ageappropriate,influenzavaccine(includingLAIV,IIV,andRIV).LAIV4isanoptionforinfluenzavaccinationforpersonsforwhomitisotherwiseappropriate.”ThisadditionallanguagewillbeintheBackgroundInformationintheInfluenzaStatement:“AlthoughtheeffectivenessofthenewformulationofLAIV4againstH1N1pdm09virusesisnotyetknown,availabledatasuggeststhatthenewLAIV4containingA/Sloveniamayprovideprotectionmorecomparabletothatobservedwithpre-2009[LAIV]influenzavaccines.”SuggestionforpreferentialrecommendationforIIVwasvoteddown.
DiscussionofCOID4/12/2018• MostCOIDmemberswouldnot“recommend”LAIV4based
onnewavailabledata.• COIDneedstocommentonACIP’srecommendationon
LAIV4.• Mustprovideguidancetoproviders.
• However,reviewofoldandnewdatashowsthatthereispotentialprotectionagainstinfluenzastrainsH3N2andBbyuseofLAIVevenifVEforH1N1isunknown.
• PolicystatementwillbepublishedinSeptemberwithonlineavailabilityinAugust.AAPNewsarticlewillbepublishedassoonasAAPBoardapproves.
Language“approvedbyCOID”April2018• AAPrecommendsinfluenzavaccinationforallchildren>6
months.• ACIPapprovednewformulationofLAIV4asanoptionforthe
2018-2019season.• TheeffectivenessofthenewLAIV4formulationforprotection
againstA/H1N1for2018-2019isunknown.• TheAAP“prefers”IIV(trivalentorquadrivalent)for
influenzavaccinationinchildrenbecauseeffectivenessofquadrivalentliveattenuatedinfluenzavaccine(LAIV4)againstA/H1N1wasinferiorinpriorseasons.
• LAIV4maybeusedforchildrenwhowouldnototherwisereceiveinfluenzavaccineandforwhomitisappropriate.
• FinalwordingofthepolicywillbecontingentuponreviewsfrommultipleAAPCommittees/Sections/CouncilsandapprovalbytheAAPBoard.
InfluenzaVaccineStrains2018-2019
TRIVALENT• A/Michigan/45/2015(H1N1)pdm09-likevirus(sameas
2017-2018)• A/Singapore/INFIMH-16-0019/2016(H3N2)-likevirus(NEW)• B/Colorado/06/2017-likevirus(B/Victoria/2/87lineage)
(NEW)
QUADRIVALENT• B/Phuket/3073/2013-likevirus(B/Yamagata/16/88lineage)
VaccinesforYoungTravelers
ImmunizationsforYoungTravelers(6monthsto12monthsofage)
Previous
• MMR(offlabel)isrecommendedforinfants6to12monthsofageiftravellingtoacountrywithendemicmeasles.Thisdosedoesnotcounttowardsrequirementforthefirstdoseofthe2doseseriestobegivenatorafter12monthsofage.
• Immuneglobulin(IGIM)isrecommendedforinfants6to12monthsofageiftravellingtoacountrywithendemichepatitisA.
ImmunizationsforYoungTravelers(6monthsto12monthsofage)
New• SincemanycountriesmayhavebothendemicmeaslesandendemichepatitisA,prophylaxisforbothinfectionsneedstobeadministered.
• SinceMMRcannotbegivensimultaneouslywithIGIMandifIGIMisgiven,thereneedstobea3monthtimeperiodafterIGIMbeforeMMRcanbegiven,thereare3options:– GiveMMRandgiveIGIMatleastonemonthlater.– GiveIGIMandgiveMMR3monthslater.– GiveMMRandhepatitisAvaccine(offlabel).LiketheMMR,theofflabelhepatitisAvaccinedoesnotcountasthefirstdoseofthe2doseseries.
Mumps
Year
1966
1969
1972
1975
1978
1981
1984
1987
1990
1993
1996
1999
2002
2005
2008
2011
2014
2017
Numb
er of
repo
rted c
ases
100
1000
10000
100000
35
MumpsCasesintheU.S.1966–Present
Schoolimmunizationlaws
Licensureofmonovalentvaccine(1967)
LicensureofMMR(1971)
1-doseMMRprogram(1977)
2-doseMMRprogram(1989)
• Highestincidence:18-22years• Age:Median–21years• Vaccinationstatus:75%>2MMRdoses
RecentMumpsCases
• Majorityof“identified”mumpscasesareassociatedwithoutbreaks.
• Youngadultsareathighestrisk.• Halfofalloutbreaksoccurredinuniversity
setting.• 80%ofcasesoccurredinoutbreaksof>50
cases.
MMRVaccine(2Dose)Effectiveness
• Median2-dosemumpsvaccineeffectivenessis88%(20estimates:range31-95%).
• MosteffectivenessstudiesincludedindividualswhohadreceivedMMR2<10yearsprior.
• Increasedriskofmumpsanddecreasedmumpseffectiveness(waningimmunity)isrelatedtotimesinceMMR2(meanof27yearsforlossofimmunitywithwidevariability).
• 2DoseMMRhasnotbeenefficientinpreventingmumpsoutbreaks.
Lewnard,GSciTranslMedePubMarch21,2018doi:10..1126/scitranslmed.aao594
MolecularEpidemiologyofWild-typeVirus• MumpsvaccineisgenotypeA(JerylLynnstrain).
• RecentcirculatingmumpsstrainshavebeengenotypeG.
• NeutralizingantibodiesfollowingmumpsimmunizationsneutralizebothgenotypeAandgenotypeG;higherlevelsofantibodiesarerequiredtoneutralizegenotypeGascomparedtogenotypeA.
• RelevanceofhigherantibodylevelstoneutralizegenotypeGisunclearbecauselevelsneededtoprotectagainstmumpshasnotbeenestablished.
• Ifmis-matchedgenotype(Gvs.A)wasresponsibleforlackofprotectionagainstmumpsthenmorechildrenshouldbeaffectedduringoutbreaks.
Lewnard,GSciTranslMedePubMarch21,2018doi:10..1126/scitranslmed.aao594
NewACIPMumpsRecommendations
Anyonepreviouslyvaccinatedwithtwodosesofmump-containingvaccinewhoareidentifiedbypublichealthatincreasedriskformumpsbecauseofanoutbreakshouldreceiveathirddoseofamump-containingvaccinetoimproveprotectionagainstmumpsdiseaseandrelatedcompilations.
MeningococcalBVaccine
MeningococcalSerogroupBVaccines
• MenB-FHbp(Trumenba®,Pfizer),licensedonOctober29,2014– 3-dose(increasedrisk)or2-dose(notincreasedrisk)series
• MenB-4C(Bexsero®,Novartis/GSK),licensedonJanuary23,2015– 2-doseseries
• Bothlicensedfor10through25yearolds• Protectionbasedondevelopingimmunitytobacterialproteinsratherthancapsularpolysaccharides(aswithMenACWY)
Pediatrics138(3);September2016
MeningococcalSerogroupBVaccinesRecommendations
• Whenused,MenB-4Cshouldbeadministeredasa2-doseseries,withseconddosegivenatleastonemonthfollowingthefirst.
• Whenused,MenB-FHbpshouldbeadministeredasa3-doseseriesinhighriskpatients(0-,1-to2-,and6months),andasa2-doseseriesinnon-highriskpatients(withseconddosegivenatleast6monthsfollowingthefirst).
Pediatrics138(3);September2016
MeningococcalSerogroupBVaccinesRecommendations
• Persons≥10yearsofageatincreasedriskofmeningococcalBdiseaseshouldreceiveaMenBvaccineroutinely(CategoryA)
• AMenBvaccineseriesisnotroutinelyrecommendedbutmaybeadministeredtoadolescentsandyoungadults16through23yearsofagetoprovideshort-termprotectionagainstdiversestrainsofmeningococcalBdisease(CategoryB)
Pediatrics138(3);September2016
CurrentACIPvaccinationrecommendationsforpersonsatincreasedriskformeningococcaldiseasePopulation MenACWY(aged≥2
months)MenB(aged≥10
years)
Persistentcomplementcomponentdeficiencies(includingeculizumab)
X X
Functionaloranatomicasplenia(includingsicklecelldisease)
X X
HIVinfection X
Unvaccinatedfirstyearcollegestudentslivingindorms
X
Militaryrecruits X
MicrobiologistsroutinelyexposedtoN.meningitidis
X X
Traveltoendemicorhyperendemiccountries
X
Personsatriskduetoanoutbreak X X
UncertaintiesRegardingMeningococcalSerogroupBVaccines
• Bothvaccineslicensedunderacceleratedapprovalpathways.
• Durationofimmunogenicityuncertain;antibodylevelsdecreaseby50%by1-2years–variesbyantigen.
• BreadthofcoverageacrossMenBstrainsindifferentgeographicregionsuncertain.
• Long-termsafetyuncertain:– TheoreticalconcernsregardingautoimmunediseasewithMenB-FHbpvaccine.
Pediatrics138(3);September2016
MenBVaccine:What’sNext• BothmanufacturersareplanningstudiesinordertogetFDA
approvalforMenBVaccinesdowntoage1year.
• ACIPisdiscussing:– WhattodowithpersonsalreadyimmunizedwithMenBduringanoutbreakduetoconcernforAbwaning?
– WillMenBvaccineboostersbeneededtoprotectadolescents/youngadultsthroughoutcollegeyearsduetoAbwaning?
– IfMenBvaccinesareapprovedforages1through9years,whatrecommendationswouldbeappropriate?
52
Estimatedincidenceofmeningococcaldiseaseamongpersonsaged18-24yearsbyserogroupandyearoflife–UnitedStates,2014-2016
SerogroupB SerogroupsC,W,Y
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
18 19 20 21 22 23 24
Casesp
er100,000
Age(years)
College
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
18 19 20 21 22 23 24
Casesp
er100,000
Age(years)
College
54
Trendsinincidenceofmeningococcaldiseaseamongchildrenaged<10yearsbyagegroup–UnitedStates,
2010-2016
0.0
0.5
1.0
1.5
2.0
2.5
3.0
2010 2011 2012 2013 2014 2015 2016
Casesp
er100,000
Year
<1year 1year 2-4years 5-9years
Source:NationalNotifiableDiseasesSurveillanceSystem(NNDSS)data
Reportedmeningococcaldiseasecasesinpersonsatincreasedriskformeningococcaldisease1
Population Complementdeficiency2
/eculizumabuse3
Asplenia,includingsicklecelldisease4
SerogroupBcases
Age<10years 0 0
Age≥10years 0 3
SerogroupA,C,W,Ycases
Age<10years 0 0
Age≥10years 6 141Source:ActiveBacterialCoresurveillance(ABCs)Since22005,32017,41995
Cost-per-QALYinadolescentvaccinesintheUSBase-caseComparisons
Vaccine Targetgroup CostperQALYgained(comparedtonovaccination)
HepatitisB Collegefreshmen <$0(cost-saving)to≈$10,000
HepatitisA Collegefreshmen <$0(cost-saving)to≈$15,000
HPV 12-year-oldfemales ≈$4,000to$46,000
Influenza(LAIV) 12-to17-yearolds,highrisk ≈$11,000
HPV 12-year-oldmales(+lowfemalecoverage) ≈20,000to$40,000
TDaP All11-year-olds ≈$26,000
HPV 12-year-oldmales(+highfemalecoverage) ≈75,000to>$250,000
Meningococcal(MCV4)* All11-to17-year-olds ≈$97,000
Influenza 12-to17-yearolds,healthy ≈$133,000
Meningococcal(MCV4) 2-dose,all11&16-year-olds $230,000
Meningococcal(MenB) Series,allfreshmancollegein4yrand2yr $9.6Million
Meningococcal(MenB) Series,all11-year-olds+booster $10.8Million
Meningococcal(MenB) Series,all18-year-olds $11.2Million
Meningococcal(MenB) Series,all16-year-olds $12.7Million
Source:Ortega-Sanchezetal.Pediatrics(2008),HPV(MMWR,Dic2011)andnewMeningRecom(MMWR,March2013)*includesHerdImmunity&duration10years(Ortega-Sanchezetal.,CID2008)AllfigureswereadjustedtoDecember2016US$
HepatitisBvaccine
HepatitisBvaccine:BirthDose
MaternalHBsAgStatus Birthweight Timing(Ageinhours)Positive >2000gm <12hrs*Unknown >2000gm <12hrs**Negative >2000gm <24hrs
Positive <2000gm*** <12hrs*Unknown <2000gm*** <12hrs**Negative <2000gm*** 1monthofageor
hospitaldischarge,whicheverissooner
*HBIG<12hrsofage **HBIG<12hrsofage,ifSTATHBsAgispositiveorHBsAgisnotavailableby2hrsofage***IfHepBvaccineisgivenatbirth,3additionaldoseswouldbeneededtocompleteseries
HBsAg+-exposedInfants
• Serologictestingfollowing3or4doseseriesat9-12monthsofageor1-2monthsfollowinglastdoseifcompletionofHepB vaccineseriesisdelayed:
• – anti-HBs->10mIU/mL-immune/protected
– anti-HBs-<10mIU/mL-needadditionalHepB
vaccinedose(s)
HBsAg+-exposedInfantsOptionAforInfantswithanti-HBs<10mIU/mLatage9-12monthsofageorafter1-2monthsafterlastdose
• GiveasingledoseofHepBvaccineandrepeatanti-HBs1-2monthslater:– anti-HBs->10mIU/mL-immune/protected– anti-HBs-<10mIU/mL-give2additionaldosesofHepBvaccineandrepeatanti-HBs1-2monthsafterlastdose
• Ifanti-HBs<10mIU/mLafter6dosesofHepBvaccine,nomoredosesshouldbegivenathistime.
HBsAg+-exposedInfantsOptionBforInfantswithanti-HBs<10mIU/mLatage9-12monthsofageorafter1-2monthsafterlastdose
• Giveanadditional3dosesofHepBvaccine
andrepeatanti-HBs1-2monthslater• Ifanti-HBs<10mIU/mLafter6dosesofHepB
vaccine,nomoredosesshouldbegivenatthistime.
Doxycycline
PreferredTherapiesforRickettsialInfectionsDisease Treatment
RockyMountainspottedfever Doxycycline Rickettsialpox Doxycycline Murine(endemic)typhus Doxycycline Epidemictyphus Doxycycline Scrubtyphus Doxycycline Humanmonocyticehrlichiosis Doxycycline Anaplasmosis Doxycycline Q-fever Doxycycline Mediterraneantickfever Doxycycline Africantickfever Doxycycline
2018ReportoftheCommitteeonInfectiousDiseases
DoxycyclineandToothStaining• RetrospectivecohortstudyofNativeAmericanreservationinArizona.
• 58childrenexposedtodoxycycline:– 107totalcoursesofdoxycyclinebeforetheageof8yearsold
– Averageduration7.3days(range1-10,SD=2.8)– Averageageofdoxycyclineadministration4.5yearsold(range0.2-7.9,SD2.4)
– Averageof1.8coursesperchild– Meanageattimeofdentalexam9.8yearsold(range8.1-15.6,SD1.7)
• 213childrenwhoneverreceiveddoxycycline– Meanageattimeofdentalexam11.8yearsold(range8.0-16.9,SD2.2)
JPediatr2015;166:1246-51
DoxycyclineandToothStaining• Novisibletetracycline-likestainingpatternswereseenonanyteethfromeithergroup(95%CI:0%to5%)
Doxycycline<8y,N(%)
NoDoxycycline,N(%)
Age-AdjustedPrevalenceRatio(95%CI)
Age-AdjustedPrevalenceRatio,Pvalue
Enamelhypoplasia
2(4) 8(4) 1.6(0.2-13.5) 0.65
Fluorosis 5(9) 28(13) 0.86(0.4-2.0) 0.72
JPediatr2015;166:1246-51
DoxycyclineandToothStaining
• Blind,randomized,controlledstudyofchildrentreatedwithdoxycyclineforcontrollingasthma.
• 4mg/kgBIDonDay1,then2mg/kgQDonDays2-10.
• 31treatedvs.30controlnon-doxycyclineexposed.
• Notoothstainingdetectedinanyofthechildrenineithergroup
ClinPediatr(Phila)2007;46:121-6
LiberalizationofDoxycyclineRecommendations
Doxycyclinebindslessreadilytocalciumcomparedwithothermembersofthetetracyclineclass,butbecauseofconcernforadrugclasseffectwithtetracyclines,itsusepreviouslyhasbeenlimitedlargelytopatients8yearsandolder,andtheseolderchildrenhavebeenstudiedmorethoroughlythanyoungerchildren.Recentcomparativedatainyoungerchildren,however,suggestthatdoxycyclineisnotlikelytocausevisibleteethstainingorenamelhypoplasiainchildrenyoungerthan8years.ThesereassuringdatasupporttherevisedrecommendationbytheAmericanAcademyofPediatrics,reflectedthroughoutthe2018RedBook,thatdoxycyclinecanbeadministeredforshortdurations(i.e.,21daysorless)withoutregardtothepatient’sage.Whenused,patientsshouldbecarefultoavoidexcesssunexposureduetothephotosensitivityassociatedwithdoxycycline.
2018ReportoftheCommitteeonInfectiousDiseases.RickettsialDiseases