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