Isabel Esteves Unidade de Infecciologia Pediátrica

Departamento de Pediatria, Hospital de Santa Maria – CHLN, EPE Directora: Maria do Céu Machado

Lisbon, Portugal

VACCINE-PREVENTABLE OUTBREAKS IN PORTUGAL:

HEPATITIS A AND MEASLES

May 12-13th, 2017 EAP SPRING MEETING

FARO, PORTUGAL

OUTBREAKS IN PORTUGAL

HEPATITISA§ Introduc*on–thevirusandthedisease§ Na*onalandeuropeanprevalencedata§ OutbreakinPortugalandEUcountries2016-2017§ ManagementbyNa*onalHealthAuthori*es

§ DiscussionMEASLES§ Introduc*on–thevirusandthedisease§ Na*onalandeuropeanprevalencedata§ OutbreakinPortugal§ ManagementbyNa*onalHealthAuthori*es

§ Discussion

hGp://wwwnc.cdc.gov/travel/yellowbook/2012/

HEPATITIS A – GLOBAL SEROPREVALENCE

HEPATITIS A

§  Non-envelopedRNAhepatovirus(Picornaviridae)-1975§  1serotype,severalgenotypes§  Resistanttoinac*va*on(Temp.60°cor≤4°c,eter,acid,anionic

substances)

VaughanGetal,InfectGenetEvol2014,227-43PintoRM,FutureMicrobiol2012,331-46

HEPATITIS A

GENOTYPES I a VI (I - III – human infection)

SUBTYPES A e B

CLUSTERS Variable

IA:worldwide80%ofhumaninfec*onsIIIA:Asia

VaughanGetal,InfectGenetEvol2014,227-43PintoRM,FutureMicrobiol2012,331-46

Transmissionroute

Fecal-oral:-Water/foodcontaminated-InterpersonalcontactParenteral

Incuba;onInfec;ousperiod

30days(15-50days)incuba*on(2Wks)è1Wka^ersymptomsbegin

Presenta;on Asymptoma*c(children)Fever,vomi*ng,abdominalpain,astenia,jaundice,choluria

Agevaria;on Adolescentandadult:ésymptoms(70%Vs30%by6yrs)andcomplica*ons;émortality(>50A:1,8%)

Complica;ons RecurrentHepa**s,prolongedFulminantHepa**s<1%,Mortality(0,1-0,6%)

Diagnosis IgMan*-HAV;RNAHAV(PCR:clusters)

Treatment Suppor*ve;!toxicdrugsandalcohol

ChristensonJC,PediatrRev2016,426-438hGp://www.uptodate.com

HEPATITIS A PRESENTATION

HEPATITIS A PRESENTATION

FecalHAV

Symptomsjaundice

0 1 2 3 4 5 6 12 24

IgGan*-HAV

ALT

IgMan*-HAV

Monthsa^erexposure

Viraemia

Diagnosis

ChristensonJC,PediatrRev2016,426-438hGp://www.uptodate.com

§  Availablesince1998(extra-Na*onalImmunisa*onProgramme)§  Inac*vatedvaccines§  Imunogenic,safe,effec*ve(comparable),interchangeable

HAVRIX®(Glaxo) VAQTA®(Merck)

Type adsorved,inac*vated adsorved,inac*vated

Presenta*on ped®720EL.U/0,5mLadult®1440EL.U/1mL

25U/0,5mL50U/1mL

Age 1yrto15yr(<18A)>16yr

1yra18yr>18yr

Dosis 2dosis(0,6a12M) 2dosis(0,6a18M)

Seroconversion 1dose:88%(2Wks)96-100%(4-6wks)�2dosis:>95%a^er25yrs

1dose:88%(2Wks)96-100%(4-6wks)�2dosis:>95%a^er25yrs

Immunisa*on,VaccinesandBiologicals.WHO,IIseries,2011*RCMVaqta:99%às4sem;�RCMHavrix:99%às4sem

HEPATITIS A PREVENTION: VACCINES

hGp://ecdc.europa.eu/en/publica*ons/Publica*ons/hepa**s-a-virus-EU-EEA-1975-2014.pdf

HEPATITIS A SEROPREVALENCE: EU (2000-13)

hGp://ecdc.europa.eu/EU-EEA-1975-2014

Incidence-0.5cases:100.000

Seroprevalence2000-2013:93%,≥55yrs

Seroprevalence2016,Lx*:30%,20-29A88%aos≥55A

*PalminhaPetal,JClinVirol2016(82),S79-80

HEPATITIS A IN PORTUGAL: LOW ENDEMICITY

hGp://ecdc.europa.eu/EU-EEA-1975-2014

HEPATITIS A: CURRENT EU OUTBREAK (JUL/16 – FEV/17)

§  Reportedcasesin13EUcountries(287*)

§  AffectMSM-Sexualtransmission(analandoro-analroute)-Highlocalandregionalinterconec*vity(MSM)

Riskfactors–epidemiologicalques;onnaires

ü UK:-ac*vi*esingroup(saunas,clubs),useofmee*ngapps(LGBT)-mul*plesexualpartners,anonimouscontacts-sexualac*vityassubsistenceü Germany:-travelling(na*onalandinterna*onal)andgroupevents

RIVM-HAV16-090 (Japan and China; Europride)

VRD_521_2016 (Central and South America)

V16-25801 (Frankfurt e Munich)

HEPATITIS A: CLUSTERS IN EU OUTBREAK

SouthandcentralAmerica(UK/Spain)Asia(JapanandChina)EuroprideinAmsterdam(Jul-Ago/17)Munich/Frankfurt

ECDC.Hepa**sAoutbreaksintheEU/EEA–firstupdate,23February2017.Stockholm:ECDC;2017

§  3clustersofHAVsubgenotypeIA§  Independenttransmissionchains

HEPATITIS A: CLUSTER VRD_521_2016 (Portugal)

§  1/Janthrough24/Apr/2017:242cases*no*fied§  93%areyoungadultmen°

§  79%liveinLisbon°§  50%admiGedtohospital°

Na*onalGuidelinesforOutbreakControl-DGS(09-04-17)OutbreakinPortugal/EU

Globalvaccinerestric*ons(EU)

°Source:Hepa**sA,Na*onalGuidelines,08/05/2017,Na*onalHealthDirec*on*Source:DGS

§  ControlofvaccinesbyNa*onalHealthAuthori*es§  Specificloca*onsforvaccineadministra*on

Hepa*teA,Normano003/2017de09/04/2017,DireçãoGeraldeSaúde

§  OUTBREAKCONTROL:-  IMMUNISATIONisthemaincontrolmeasure-  Alertabouthygieneandsanitarypreven*vemeasures-  Educa*onandcommunica*on(LGBTcommunity)

HEPATITIS A OUTBREAK: MANAGEMENT IN PORTUGAL

§  Vaccina*on:preandpost-exposurecondi*onsü Target:MSM;iden*fica*onofcontactsü 1doseofan;-HAVvaccine:freeofchargeü Thosewhohave1doseofvaccineareconsideredprotected

Travelers???

HEPATITIS A PREVENTION: IMMUNOGLOBULIN

§  Immunoglobulin:post-exposure(2wks)ü  IGIM0,02mL/kg;protec*onin80-90%through3M

-  Immunodeficiencywithvaccinefailure-  Children<12Mofage-  Chronichepa*cdisease-  Vaccinecontraindica*ons

Hepa*teA,Normano003/2017de09/04/2017,DireçãoGeraldeSaúde

§  IGIMpre-exposure:0,02mL/KgIM(dura*on<3M)

0,06mL/KgIM(dura*on3-5M)

HEPATITIS A OUTBREAK: DISCUSSION

§  ControversiesaboutNa*onalHealthAuthorithiesguidelines:ü Travelersandotherriskgroupsneglectedü Efficacyofhealtheduca*onefforts?ü Pediatricvaccineinpre-exposureprophylaxis?Evidence?

§  Outbreakac*vity:ü Numberofcases/week?Severity?

§  Managementguidelines:ü  Nºofadministeredvaccinesin1month?(1149)ü  Nºofsecondarycases/contacts?Pediatriccases?ü  Nºofavailablevaccines?

MEASLES

MEASLES VIRUS (MeV)

§  RNAvirus,morbilivirus,paramyxoviridae

§  1serotype,24genotypescompiledin8clades(A-H)andclusters

MossWJ,GriffinDE.Lancet,2012GriffinDE(2013)Measles,inFieldsVirology.WoltersKluwer/LippincoG,Williams&Wilkins,Philadelphia

FeiginandCherry’s.TEXTBOOKOFPEDIATRICINFECTIOUSDISEASES.SeventhEdi*on

§  Humanreservoir

§  Transmission:dropletsandairborne

§  Highlyinfec*ous(Ro12-18)

§  Infec*veperiod:4dbefore/4da^erexanthem

TYPICAL MEASLES - PRESENTATION

COMPLICATIONS Source: DGS, WHO

CONTAGIOUNESS

RISK FACTORS FOR SEVERE MEASLES

•  Pregnancy

•  Imunodeficiency

•  Poor nutrition

•  Vit. A deficiency

•  Infants / Adults

Measles keratitis + Vit A deficiency: blindness

MEASLES COMPLICATIONS

§  ≈30%ofmeaslescases

§  InducesTimunosupression:>riskofsecondaryinfec*on

Persistentfever>3daysa^erthebeginingoftheexanthem:alertsign

Bester JC .JAMA Pediatr, 2016

MEASLES – WORLDWIDE PREVALENCE

SOURCE: WHO 2017

§  134.200deaths/2016

MeV GENOTYPE GEOGRAPHICAL DISTRIBUTION 2016-2017

. www.who-measles.org

EUROPEAN PREVALENCE 2016-2017

SOURCE: WHO 2017

Measlesno;fica;onrate:Apr2016–Mar2017

§  EU:6597cases/yr–30countries(1stApr/2016è31stMar/2017)

4793cases1739cases

EUROPEAN VACCINATION COVERAGE

ECDC; WHO 2017

Measlesvaccina;oncoverage(2nddose)Jan2014April2017

NATIONAL IMMUNISATION SCHEDULE 1965-2017

1965 1973/4 1980 1984 1987 1990 1993/5 2000 2006 2008/9 2012 2015 2017

smallpox smallpox

Diphteria Diphteria

Diphteria

Diphteria

Diphteria

Diphteria

Diphteria

Diphteria

Diphteria

Diphteria

Diphteria

Diphteria

Diphteria

Tetanus Tetanus Tetanus

Tetanus

Tetanus

Tetanus

Tetanus

Tetanus

Tetanus

Tetanus

Tetanus

Tetanus

Tetanus

pertussis pertussis pertussis

pertussis

pertussis

pertussis

pertussis

pertussis

pertussis

pertussis

pertussis

pertussis.

pertussispregnant

BCG BCG BCG BCG BCG BCG BCG BCG BCG BCG BCG BCG Riskgroups

Polio Polio Polio Polio Polio Polio Polio Polio Polio Polio Polio Polio Polio

Measles Measles Measles

MeaslesAdol.F

MeaslesAdol.F

MMR15M

MMR15M

11-13A

MMR15M11-13A

MMR15M5–6A

MMR15M5–6A

MMR15M5–6A

MMR12M5–6A

MMR12M5–6A

MMR12M5A

HepB HepB HepB HepB HepB HepB HepB

Hib Hib Hib Hib Hib Hib

MenC MenC MenC MenC MenC

HPV HPV HPV HPV

PCV13 PCV13

Campaign VAS 1973-77

Children 1–4 A

MEASLES PREVALENCE - PORTUGAL

1974 Measles vaccine

1990 2ªdose: 11-13yrs 2000

2ªdose: 5-6 yrs

Source: DGS/ DDO

2012 1ªdose: 12 M

1987 – Epidemics Insufficient vaccine coverage: ± 12.000 cases and 30 deaths

1993/4 – Epidemics Good general coverage but assimetric: ± 3000 cases

YEAR NºOFCASES

CONFIRMEDCASES DATA

2004 1 0

2005 7 6 -1casefromRomenia+5secondarycases(migrantcommunity)

2006 0 0

2007 0 0

2008 1 1 -1casefromUK

2009 3 3 -Outbreak2cases:1casefromE*opia+1secondary-1casefromFrance

2010 5 5 -Outbreak4cases:1fromÁfricadoSul+3secondary(healthcareworker)-1casefromUK

2011 7 2 -1casefromFrance(genotypeD4)-1casefromAngola(genotypeB3.1)

2012 21 5 -Outbreakof4cases:1fromChina+2secondary+1terciary(genH1)-1casefromUK(genotypeD4)-1casefromAngola(genotype?)

2013 6 1 -1casefromGermany(genotypeD8)

2014 ? 0

2015 ? 0

2016 ? 0

SOURCE: DGS Palminha P et al. Diagnóstico laboratorial do sarampo em Portugal, 2011-2013. Observações_ Boletim Epidemiológico

MEASLES CASES IN PORTUGAL – 2004/16

MEASLES CASES IN PORTUGAL – 2017 Caseson2ndmay/2017:week18(1–6thmay/2017)

ECDC; WHO 2017

Confirmed cases by week of

symptoms

Confirmed cases by age

D8

B3

B3

Cases by Region 114 notifications since 1st jan/2017 27 confirmed cases

64% age ≥18yrs 60% non-vaccinated 48% in healthcareworkers 1 death

Age

MMR VACCINE COVERAGE IN PORTUGAL

IMPORTANT TO CONSIDER:

• Seroprevalence–na;onaldata

• Vaccinecoverage–localandregional

• Immunisa;ondelay

• VaccinefailureSOURCE: DGS

VACCINE COVERAGE BY BIRTH DATE

VACCINE COVERAGE MMR2 BY BIRTH DATE

MMR VACCINE FAILURE – TYPE I AND II

Haralambieva IH et al..Trends Mol Med, 2015

MEASLES OUTBREAK – CASE DEFINITION

§  Possiblecase(clinicalcriteria)§  Probablecase(clinicalandepidemiologicalcriteria)

§  Confirmedcase(clinicalandlabcriteria)

DGS 2017. Norma SARAMPO: Procedimentos em unidades de saúde - Programa Nacional Eliminação Sarampo

CLINICALCRITERIA

LABCRITERIA

EPIDEMIOLOGICALCRITERIA

FeverandExanthemand

1of:CoughRhini*sConjunc*vi*s

Atleastoneof:-MeVisola*on(sample)-MeVRNAdetec*on(sample)-SpecificserumIgMdetected-Seroconversionin2samples

Epidemiologicallink

iden*fied

MEASLES OUTBREAK – LAB DIAGNOSIS

SOURCE: www.who.int/immunization_monitoring/LabManualFinal.pdf

1.  Serology

2.  RT-PCR

3.  Viral isolation

Genetic analysis

Exanthem < 3 wks

Exanthem > 3 wks

Blood Oral fluids / Oropharynx exudate

Urine

Blood

National reference laboratory – INSA

Samples sent free of charge

MEASLES OUTBREAK: MANAGEMENT IN PORTUGAL

1.  Isolation of suspected cases 2.  Identification and follow-up of contacts 3.  Post-exposure vaccination (<72h) and IG

CONTACT: Any person who has shared the same space for any period of time, or being in the same location 30 mins after the patient has exited the location (during the infectious period) •  Cohabitants •  Healthworkers •  Patients in the same space •  Working or school colleagues •  Contacts during trips / transportation

DGS 2017. Norma SARAMPO: Procedimentos em unidades de saúde. Programa Nacional Eliminação Sarampo

*National Serological Inquiry 2001-2002, >97% of protection DGS 2017. Norma SARAMPO: Procedimentos em unidades de saúde. Programa Nacional Eliminação Sarampo

1.  Isolation 2.  Identification and follow-up of contacts 3.  Post-exposure vaccination (<72h) and IG

AGE/CONDITION REQUIREDMMRDOSIS

≥6Mand<12M 1dose(“zerodose”)

≥12Mand<18yrs 2dosis

≥18yrsandbornt≥1970 2dosis

≥18yrsandbornt<1970* 1dose

Healthcareworkers 2dosis

HIVinfec*onwithoutimmunosupression

Inaccordancewithageandcondi*on

Others Inaccordancewithage/condi*on

MEASLES OUTBREAK: MANAGEMENT IN PORTUGAL

DGS 2017. Norma SARAMPO: Procedimentos em unidades de saúde. Programa Nacional Eliminação Sarampo

1.  Isolation 2.  Identification and contacts follow-up 3.  Post-exposure vaccination (<72h) and IG

INDICATIONSFORPOST-EXPOSUREIGADMINISTRATION

Un*l6dayspost-exposure,whenMMRiscontraindicatedorhasriskofcomplica*ons

Children<6MoldPregnantwomenHIVinfec*onwithimmunosupressionSevereImunosupression

Un*l6dayspost-exposure,whenMMRperiodofadministra*onwasovercomed

Childrenaged6M–12M,withoutvaccineHIVinfec*onwithoutimmunosupressionOthers

MEASLES OUTBREAK: MANAGEMENT IN PORTUGAL

ERADICATION OF MEASLES: REMAINING CHALLENGES

Unmask

FEAR FEAR

Vaccine Disease

MYTHS Disease

Vaccine

§  Fightvaccinecoverageasymmetries§  Vaccinedelayandfalsecontraindica*ons§  An*-vaccinemovements

§  Elimina*on/Eradica*onispossible

ü Exclusivehumantransmission

ü Effec*vevaccine

§  Managementplan:transmissioninterrupted(south)andê(Lisbon)in2months

§  Fightvaccinehesitancy:teaching(notcoercion/obliga*on)

ERADICATION OF MEASLES: REMAINING CHALLENGES

ThankyouJ!

isabel.castro.menezes@gmail.comAcknowledgmentsfordataandpptonMeaslesoutbreak:DrDianaMoreira

HEPATITIS A NAD MEASLES OUTBREAK: DISCUSSION