Immunization of high-riskpaediatric populations:Central European VaccinationAwareness Group (CEVAG)recommendationsExpert Rev. Vaccines Early online, 1–15 (2014)

Darko Richter*,Ioana Anca,Francis E Andre,Mustafa Bakir,Roman Chlibek,Milan Cizman,Atanas Mangarov,Zsofia Meszner,Marko Pokorn,Roman Prymula,Nuran Salman,Pavol Simurka,Eda Tamm,Goran Tesovic,Ingrid Urbancıkova,Vytautas Usonis,Jacek Wysocki andDace Zavadska

*Author for correspondence:

Tel.: +385 1237 6521

Fax: +385 1237 6573

darko.richter@zg.t-com.hr

For a full list of author affiliations,

please see page 15.

Over the last decade, childhood immunization has substantially reduced morbidity andmortality from vaccine-preventable diseases. However, particular paediatric risk groups, suchas those with comorbidities, may not be adequately vaccinated despite being moresusceptible to complications and death from certain infectious diseases. This may be due tolack of immunization recommendations, lack of awareness, or incomplete adherence toexisting guidelines. Furthermore, recommendations for immunization can be inconsistentacross Europe. An expanded initiative from the Central European Vaccination AwarenessGroup aims to raise awareness of the different high-risk paediatric groups, differentiate themaccording to their specific risk, and formalise a guidance statement for the immunization ofeach population.

KEYWORDS: Central Europe • high-risk • immunization • paediatric • recommendations

Immunization programs represent one of themost impactful advances in medicine [1]. Uni-versal immunization schedules are primarilyaimed at infants and young children becausethey suffer the highest incidence of disease andrisk of complications and death. From 1900to 1998, US childhood immunization pro-grams dramatically reduced pediatric mortalityfrom infectious diseases from 62 to 2% [1]. In2011, the CDC listed the worldwide preven-tion of an estimated 2.5 million deaths in chil-dren aged <5 years annually as one of the top10 public health achievements in the lastdecade [2].

Pediatric subgroups at raised risk of severedisease and mortality from vaccine-preventableinfections, such as influenza [3], may not becovered by universal national immunizationprograms (NIPs) or country-specific high-riskrecommendations. Although herd immunitymay effectively prevent the microbial circula-tion in the population, individual risks andcircumstances should also be considered [1]. Anexpanded initiative to target specific high-risk

pediatric populations could provide furtherprotection from particular infections. Immuni-zation recommendations for high-risk groupsvary between European countries, and theadoption of standardized recommendationscould encourage the dissemination of appro-priate information about pediatric subgroupsthat are most at risk.

This paper has therefore collated for the firsttime all recommendations for high-risk pediat-ric populations in Central European Vaccina-tion Awareness Group (CEVAG) countries tocreate an immunization guidance statement foradaptation to individual country needs.

About CEVAGCEVAG comprises regional experts from12 Central European countries: Bulgaria, Cro-atia, the Czech Republic, Estonia, Hungary,Latvia, Lithuania, Poland, Romania, Slovakia,Slovenia and Turkey [4]. The aim of CEVAGis to encourage the efficient and safe use ofvaccines to prevent, control and, if possible,eliminate infectious diseases by raising

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awareness of immunization and compiling and distributingappropriate information. CEVAG is an established voluntaryassociation of national representatives and legal entities inter-ested in promoting immunization in Central Europe. CEVAGis organizationally independent of state administration and self-administration bodies, political parties and other civil associa-tions and initiatives. The association does, however, cooperatewith these groups to realize and promote common plansand interests.

What is a high-risk group?

A high-risk group includes individuals who are at a higher thanaverage risk of acquiring infection or those at higher risk ofhaving adverse outcomes [3]. In epidemiology, it is ‘a group ofpeople in the community with a higher-than-expected risk fordeveloping a particular disease, which may be defined on ameasurable parameter, for example, an inherited genetic defect,physical attribute, lifestyle, habit, socioeconomic and/or educa-tional feature, as well as environment’ [5]. This paper definesindividuals as ‘high risk’ when their physiological, medical,social, ethnic, occupational, environmental or economic condi-tions result in a higher than average risk of acquiring certaininfectious diseases. These groups are also at increased risk ofhospitalization, complications, severe disease progressionor death.

Why vaccinate high-risk groups?

Mortality from vaccine-preventable disease is sometimes higherin children with pre-existing disorders than in healthy children.

In 2009–2010, children with moderate and severe pre-existing conditions accounted for 11 and 64% of the 70 pediat-ric pandemic influenza (H1N1)-related deaths in England andWales, respectively, with most deaths (87%) among those<2 years [6]. A German observational study reported comorbid-ities (e.g., chronic respiratory or cardiac disease; neurodevelop-mental disorder) in 75% of intensive care unit pediatricadmissions due to pandemic influenza (H1N1) [7]. In a Belgianmulticenter survey, 47% of children hospitalized with pan-demic influenza had similar comorbidities [8].

In 2009, due to the ongoing burden of influenza, theEuropean Council of ministers recommended that EU MemberStates implement national action plans to achieve an influenzaimmunization coverage rate of 75% in high-risk groups by thewinter season of 2014/2015 [9]. This includes all individualswith the following comorbidities: chronic respiratory and car-diovascular diseases, chronic metabolic disorders, chronic renaland hepatic diseases and congenital or acquired immune systemdisorders [9].

Who vaccinates high-risk groups?

Overall, the CEVAG countries practice the system of manda-tory NIPs with full financial coverage by the state. In mostCEVAG countries, immunizations are implemented by primarycare pediatricians/general practitioners. In some countries(e.g., Hungary, Slovakia), a ‘Special Immunization Services’

network provides individual immunization plans for high-riskpatients. Current mandatory NIPs of CEVAG countries aresummarized in TABLE 1. USA recommendations issued annuallyby the Advisory Committee on Immunization Practices (ACIP)are included for comparison. Exceptions to the mandatory orfully reimbursed immunizations are given in the footnotes (6,22, 23, 26, 31, 33) to TABLE 1.

High-risk group categoriesNeonates, infants & very young children

The initial protection provided by maternal antibodies ininfants eventually wanes, and their immature or naıve immunesystems leave them vulnerable to infection [1]. Consequently,neonates, infants and very young children are the principalrecipients of most universally recommended or mandatory vac-cinations (TABLE 1).

WHO recommends annual influenza vaccination or revacci-nation, particularly for high-risk groups (i.e., children aged6–59 months and individuals with defined comorbidities) [10].Children aged 6–23 months have a high burden of severe dis-ease from influenza, and the WHO recommends targeting thisgroup when sufficient resources are available. Children aged2–5 years have a lower burden of disease than those aged<2 years and respond better to vaccination, resulting in broaderand higher levels of protection [10].

Premature & low birth-weight infants

Preterm babies (<37 weeks’ gestation) are at increased risk ofcomplications and morbidity from vaccine-preventable diseases,but are less likely to receive timely immunizations [11,12]. Thisis partially due to high rates of medical complications andphysicians’ concerns regarding fragility and impaired vaccineimmune responses in preterm babies [12]. All vaccines routinelyrecommended for full-term infants are safe to use in preterm,low birthweight (<2500 g) and even very low birthweightinfants (<1500 g) [12,13]. Medically stable preterm and lowbirthweight infants are recommended to receive full doses ofpneumococcal conjugate vaccine (PCV), Haemophilus influenzaetype b (Hib), diphtheria, tetanus and pertussis (DTaP), hepatitisB (HepB), rotavirus and poliovirus vaccines at a chronologicalage consistent with the standard schedules for full-terminfants [12]. Larger premature infants have similar immuneresponses to full-term infants although responses may bereduced in very premature infants (<28–32 weeks’ gestation atbirth) [14]. Surprisingly, antibody titers with the inactivated tri-valent influenza vaccine in extremely low birthweight infants(birthweight <1000 g) vaccinated at 6–17 months of age weretiters or more in matched full-term infants [15]. The traditionalexception to this practice of early immunization regardless ofgestational age is the Bacillus Calmette–Guerin (BCG) vaccineagainst tuberculosis (TB). If recommended at birth, then BCGis usually given to infants weighing ‡2000 g or 34–35 weekspostmenstrual age, despite recent data that preterm (31–34weeks) and full-term infants have a similar response to thetuberculin test post-BCG vaccination [16]. BCG is universally

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Table

1.Pediatric

nationalim

munizationprogrammeschedulesin

CentralEuropeanVaccinationAwareness

Groupco

untriesandUSA

Advisory

CommitteeonIm

munizationPracticesreco

mmendations(upto

date

2014).

Vaccine

BG

HR

CZE

EE

HU

LVLT

PO

RO

SK

SI

TR

USA35

BCG

0d1

0d,13y2

1–5

d0d

2–5

d2–3

d0d

2–7

d0d3

2m

DTaP

2m,3m,

4m,

16m

4,6y

2m,4m,

6m,1y,

5y

9w,13w,

17w

11–18m,

5–6

y

3m,4.5

m,

6m,2y,

6–7

y

2m,3m,

4m,18m,

6y,

2m,4m,

6m,12–

15m,7y

2m,4m,

6m,18m,

6–7

y

2m,4m,

6m,16m

5

5y

2m,4m,

6m,12m,

4y,

6y

2m,4m,

10–11m,

5y

3m,

4–5

m,

6m,

12–24m

2m,

4m,

6m,

18m,6y

2m,4m,

6m,

15–18m,

4–6

y

dT/DTaP

12y,

17y6

dT:

14y,

18y

10–11y7

17y8

11y9

14y1

015–16y

14y,

19y1

1

14y1

212y1

38–9

y,

16–18y1

4

14y

11–12y

HepatitisB

0d,1m,

6m

0d,2m,

6m,12y1

5

9w,13w,

17w

11–18m

16

0d,1m,

6m,12y1

7

0d18,14y

0d19,2m,

4m,6m,

12–15m,

14y1

5

0d,1m,

6m

0d,2m,

7m

0d,2m,

6m

0d20,2m,

4m,10–

11m

0d21,

5–6

y

0d,1m,

6m

0d,

1–2

m,

6–1

8m

HepatitisA

2y2

218m,

24m

12–23m

Hib

2m,3m,

4m,16m

4

2m,4m,

6m,1y

9w,13w,

17w

11–18m

3m,4.5

m,

6m,2y

2m,3m,

4m,18m

2m,4m,

6m,12–

15m

2m,4m,

6m,18m

2m,4m,

6m,16m,

2m,4m,

6m,12m

2m,4m,

10–11m

3m,

4–5

m,

6m,

12–24m

2m,

4m,

6m,

18m

2m,4m,

6m,

12–15m

HPV

12y2

313y

12y2

412y2

512y2

611–12y

11–12y

MMR

13m,12y

1y,

6y

15m,21–

25m

1y,

13y

15m,11y

12–15m,

7y,

12y2

7

15–16m,

6–7

y,

12y2

8

13m,10y

12m,7y

14–17m,

10y

12–18m,

5–6

y

12m,6y

12–18m,

4–6

y

Pneu

mococcal

(PCV)

2m,3m,

4m,

12m

29

9w,13w,

17w

12–15m

2m

30,

4m

30,

15m

30

2m,4m,

12–15m

2m,4m,

10–11m

2m,

4m,

6m,

12m

2m,4m,

6m,

12–15m

Polio

(IPV)

2m,3m,

4m,

16m

4,6y

2m,4m,

6m,1y,

6y,

14y

9w,13w,

17w

11–18m

10–11y

3m,4.5

m,

6m,2y,

6–7

y

2m,3m,

4m,18m,

6y

2m,4m,

6m,12–

15m,7y,

14y

2m,4m,

6m,18m,

6–7

y

2m,4m,

6,16m

31

5y3

2

2m,4m,

6m,12m,

6y,

9y

2m,4m,

10–11m,

5y,

12y

3m,

4–5

m,

6m,

12–24m

2m,

4m,

6m

32,

18m

32,

6y

2m,4m,

6–1

8m,

4–6

y

Rotavirus

6–2

4w

33

2m,4m

or

2m,4m,

6m

34

2m,4m,

or2m,

4m,

6m

34

Varicella

12–15m,

7y

12m

12–15m,

4–6

y

Influenza

annually

6–2

3m

(IIV)

2–1

8y(IIV

andLA

IV)

Men

ingococcal

11–12y,

16y

Immunization of high-risk pediatric populations Review

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given in most CEVAG countries (except inthe Czech Republic and Slovakia). The ratio-nale for this practice is difficult to referenceappropriately. The BCG has an accepted rolein the prevention of disseminated tuberculosisinfection in children born in populationswith general annual TB incidence >40/100,000 [17]. Only Latvia (42 in 2011), Lith-uania (58.2 in 2011) and Romania (90.5 in2010) of the CEVAG countries have a higherincidence (data communicated by theCEVAG panel members). In the USA, onlychildren known to be exposed to persons withpulmonary TB are recommended to get BCG.It is not recommended for any particular med-ical condition including HIV infection [18]. Allpreterm and low birthweight infants shouldreceive the influenza vaccine at 6 months ofage preferably prior to, but also at any timeduring the influenza season [12]. The infantshould receive a second vaccine dose at aninterval of ‡4 weeks. Preterm infants are par-ticularly susceptible to respiratory syncytialvirus (RSV) due to their immature and vulner-able airways, immature immune system andthe incomplete transfer of maternal antibod-ies [19]. Since there is no available vaccine,passive immunization with monoclonalhumanized anti-RSV antibodies (palivizumab)is recommended. However, the gestation cut-off varies between countries. Being born pre-maturely or having a low birthweight is a riskfactor for severe rotavirus gastroenteritis [20],and the ACIP supports vaccination of preterminfants (<37 weeks’ gestation) with the sameschedule and precautions as full-terminfants [21]. Immunization recommendationsin CEVAG countries are summarizedin TABLE 2 and APPENDIX A (supplementary mate-rial can be found online at www.informa-healthcare.com/suppl/10.1586/14760584.2014.897615). US recommendations issued annu-ally by ACIP are included for comparison.

Children with chronic medicalconditionsChronic lung/pulmonary disease

Chronic lung disease in children is a risk fac-tor for severe influenza and pneumococcaldisease [22,23]. Lung diseases warrantingadministration of pneumococcal and influ-enza vaccines include bronchopulmonary dys-plasia (chronic lung disease of prematurity),cystic fibrosis and allergic asthma, especiallyif high dose inhaled corticosteroids or oral1

Rep

eatvaccinationto

bead

ministeredat7monthsifnoscar

andtuberculin

neg

ative;repeatvaccinationto

beadministeredat

7,11an

d17years

iftuberculin

neg

ative.

2Revaccinationin

tuberculin-neg

ativechildren.

3Recommen

ded

tonew

born

infants

ofim

migrantfamiliesin

last

5years

from

countrieswithahighprevalence

oftuberculosisandwhen

mothersare

treatedfortuberculosis.

4Minim

um

1yearafterthirddose.

5At2,4,6and16months–DTPw.

6dTvaccination(reduceddiphtheria

dose)recommendedat25years

ofageandthen

every

10years

thereafter;

dTis

usedroutinelyan

dreim

bursed

while

DTaPhas

beenrecommended

since

October2012,butis

notreim

bursed.

7DTaP-IPVadministered.

8DTaPisadministered.

9DTaPisadministered(reduceddiphtheria

andpertussisdose).

10Recommen

ded

every10years

thereafter;dTadministered.

11At14and19years

–dT.

12Recommen

ded

every10years

thereafter;dTfrom

14yearson,DTaPat

2,4,6,12months,4years

and6years.

13DTap+IPVadministeredat12years

ofage,dTvaccinationrecommen

dedevery

15years

thereafter.

146–1

8yearoldsreceiveDTaPandadultsreceivedT;

revaccinationgivenevery

10years.

15Onlyifunvaccinatedpreviously(catch-up);three-dose

sched

ule

(at0,1and6months).

16Hexavalentvaccine;

secondandthirddosesadministered‡1

month

afterprecedingdose

butwithin

firstyearoflife;

fourthdose

administered6monthsafterthirddose

andbefore

18monthsofage.

17Administeredat12years

ifchild

born

between1995an

d2003andnotpreviouslyvaccinated(catch-up).

18Administeredto

infants

ofHBsA

g-positive

mothersandto

motherswithunknownHBsA

gstatus:threedosesstartingwithin

12hpostpartum,seconddose

1month

laterandthirddose

6monthsafterfirstdose.

19Administeredasamonovaccineat

0–1

2hafterbirth

onlyto

new

bornsofHBsA

g-positive

mothersorto

motherswithanunknownHBsA

gstatus.

20Administeredto

infants

born

toHBsA

g-positive

mothers;athree-dose

primary

courseofhep

atitisBvaccinationisgivenat

birth

(upto

24hafterbirth),at3–5

weeksandat5–9

months.

21Obligatory

fornew

born

infants

ofHBsA

g-positive

mothers;administeredin

fourdoses(at0,1,2an

d12monthsofagesched

ule)startingwithin

12hpostpartum.

22Recommen

ded

(notman

datory)for2-year-old

childrenwholivein

poorsocialconditions.

23Recommen

ded

since

October2012(National

program

forcervicalcarcinomaprevention);im

munizationisonvoluntary

basisandfully

reim

bursed

;three-dose

sched

ule.

24Three-dose

sched

ule.

25Notyetincluded

intheNIP,buttheRomanianMoHwillbeg

inasecondcampaignforvaccinationofschoolgirls(>12years,threedoses).

26Recommen

ded

(notman

datory)for12-year-old

girls,partially

reim

bursed.

27Administeredto

allunvaccinatedgirls,an

dgirlsonlyvaccinatedonce

previously.

28Notrequirediftw

opreviousdosesadministered.

29Minim

um

6monthsafterthirddose.

30Nonmandatory.

31Recommen

ded

inthefirstandsecondyearoflife–IPV,attheageof5years

oralpolio

vaccine,notreim

bursed.

32Oralpolio

vaccinead

ministeredconcomitantlywithDTaP.

33Recommen

ded

butnotreim

bursed.

34Two-orthree-dose

seriesdep

endingonwhichvaccineisused(RV1orRV5).

35Advisory

CommitteeonIm

munizationPracticesrecommendations[79].

Countries–BG:Bulgaria;HR:Croatia;CZE:

Czech

Rep

ublic;EE:Estonia;HU:Hungary;

LV:Latvia;LT:Lithuan

ia;PO:Poland;RO:Romania;SK

:Slovakia;SI:Slovenia;TR

:Tu

rkey(Advisory

CommitteeonIm

munization

PracticesRecommen

dations).

BCG:BacillusCalm

ette–Guerin;d:Days;DTaP:Diphtheria,tetanusan

dacellularpertussis;dT:

Diphtheria

andtetanus;

HBsA

g:HepatitisBsurface

antigen

;Hib:Haem

ophilusinfluenzaetypeb;IPV:Inactivatedpoliovirus

vaccine;

m:Months;MMR:Measles,mumpsandrubella;PCV:Pneumococcalconjugate

vaccine;T:

Tetanus;Empty

field:Norecommen

dation;w:Weeks;y:

Years.

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Table

2.CentralEuropeanVaccinationAwareness

Groupco

untry-specificandUSA

(Advisory

CommitteeonIm

munizationPractices)

reco

mmendationsforhigh-riskgroups.

High-risk

group

CentralEuropeanVaccinationAwareness

Groupco

untry

BG

HR

CZE

EE

HU

LVLT

PO

RO

SK

SI

TR

USA§§

Premature/LBW

Inf,

RSV

Inf,RSV,

Rot

Inf,

RSV,

Rot

Pn,

RSV

Inf,RSV

Inf,RSV,Rot

RSV

Pn,RSV†

Inf

Inf,RSV‡

RSV

Inf,RSV

Chroniclung

disease

Inf,Pn

Inf,Pn

Inf,Pn

Inf,Pn

Inf,Pn

Inf,Pn

Inf

Inf,Pn

Inf

Inf,Pn

Inf,Pn

Inf,Pn

Pn

Chronicheart

disease

Inf,Pn

Inf,Pn,

Rot

Inf,Pn

Inf,

Pn,

RSV

Inf,Pn,

RSV

Inf,Pn

,Rot

Inf

Inf,Pn

Inf

Inf,Pn,

RSV

Inf,Pn,

RSV

Inf,Pn,

RSV

Pn

Neu

rological

and

neuromuscular

diseases

Inf,Pn

Inf,Pn,

Rot

Inf,Pn

Inf,Pn

Inf,Pn

,Rot

Inf

Inf

Inf,Pn

Inf

Chronicrenal

disease

Inf,Pn

Inf,Pn,

Rot,

HepB§

Inf,Pn

Inf,

Pn,

HepB

Inf,Pn

Inf,Pn

,Rot,

HepB

Inf

Inf,Pn

Inf

Inf,Pn,

HepB

Inf,Pn,

HepB

Inf,Pn

Pn

Chronic

metabolic

disease

Inf,Pn

Inf,Pn,

Rot

Inf,Pn

Inf,Pn

Inf,Pn

Inf,Pn

,Rot

Inf,Pn

Inf,Pn

Inf

Inf,

HepB‡

Inf,Pn

Inf,Pn{

Pn

Asplenia

Pn,

Inf,

Men,

Hib

Pn,Men,

Hib

Pn,

Men,

Hib,

Inf

Pn,

Men

,

Hib

Pn,Men

,

Hib

Pn,Men,Hib

Pn,Men,

Hib

Pn,Men,

Hib

Pn,Men,

Hib

Pn,Men,

Hib

Pn,Men,

Hib

Pn,Men,

Hib

Pn,Hib,

Men

†Notincluded

inNIP,butrecommended

inspecialprophylacticprogramsforLBW.

‡Nospecificrecommen

dations;vaccinationisthesameas

infull-term

infants

(included

inNIP).

§Atdouble

dosageforhem

odialysispatients.

{ Diabetes

only.

#Nolivevaccinesrecommended

.††Allvaccines,excep

tBCG,are

recommended.

‡‡Alsofornonim

munehousehold

contacts<12years

ofage.

§§Advisory

CommitteeonIm

munizationPracticesrecommen

dations[79].Since

allofthelistedvaccines

are

included

intheroutinerecommendedim

munizationsched

ule

intheUSA,thehigh-riskgrouprecommendations

referto

previouslyunim

munized,notfully

immunized,requiringanprotectionearlierthan

routinelyrecommen

ded

orlast

dose

less

than

14daysprecedingim

munosuppression(see

details

onCDCwebsite).

Countries–BG:Bulgaria;HR:Croatia;CZE:

Czech

Rep

ublic;EE:Estonia;HU:Hungary;

LV:Latvia;LT:Lithuan

ia;PO:Poland;RO:Romania;SK

:Slovakia;SI:Slovenia;TR

:Tu

rkey(Advisory

CommitteeonIm

munization

PracticesRecommen

dations).

Immunization

key

–HepB:Hepatitis

B;Hep

A:HepatitisA;Hib:Haemophilusinfluenzae

type

B;Inf:

Influenza;Men

:Men

ingococcal;

MMR:Measles,

mumps,

and

rubella;Pn:Pneumococcal;

Rot:

Rotavirus;

RSV

:Respiratory

syncytial

virus;TDP:Tetan

us,diphtheria,andpertussis;Var:Varicella;Empty

field:Norecommendation.

CV:Cardiovascular;HBsA

g:hep

atitisBsurface

antigen;HBIG:HepBim

muneglobulin;LBW:Low

birthweight;NNMD:Neurologicalandneu

romusculardisorders;TB

E:Tick-borneencephalitis.

Recommen

dationsources–EE:EstonianHealthBoard

[80];HU:Recommendationofim

munizationfor2012,National

Cen

treforEpidem

iology[81];LV

:Latvianjournalofthelegislationforums[82]

andseverallocal

recommen

dationsfrom

ProfessionalSo

cieties;RO:Influenza

[83];RSV

[84];HepB[85];HepA,Hib

[86];HBIG

[87]:CDCMan

ualfortheSu

rveillance

ofVaccine-Preventable

Diseases,4th

Edition,2008–2009;SK

:Ministry

ofHealthDecreeNo.585/2008,establishingdetails

ofpreventionandcontrolofcommunicable

diseases[88].

Immunization of high-risk pediatric populations Review

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Table

2.CentralEuropeanVaccinationAwareness

Groupco

untry-specificandUSA

(Advisory

CommitteeonIm

munizationPractices)

reco

mmendationsforhigh-riskgroups(cont.).

High-risk

group

CentralEuropeanVaccinationAwareness

Groupco

untry

BG

HR

CZE

EE

HU

LVLT

PO

RO

SK

SI

TR

USA§§

Complement

deficien

cy

see#

Pn,Men

,

Hib

Pn,

Men,

Hib

Pn,Men,

Hib

Men

Pn

Men

Pn,Hib,

Men

HIV

infection

Inf,

Pn,

Men

,

Hib

††

Inf,Pn

Inf,Pn

Hep

B,

PnInf

Referral

to vaccine

centers

Inf

Pn

Inf

Inf,Pn

Inf,Pn

,

Hib,

HepA,

HepB

Inf,Pn

Hib

Organ

transplantation

Inf

Pn,

Hib,

Men

Hep

B,

PnInf

Referral

to vaccine

centers

Inf,HepA,

Men,Pn

Pn

Inf

Hep

BInf,Pn

Pn

Malignan

t

disease

Inf,

Pn,

HepB

Pn

Inf,

Pn,

Hep

B

Inf,Pn,

HepB

Pn,HepB

Inf,HepB

Pn,Var‡‡

Inf

Pn

Inf

Inf,Pn

Pn,Hib

Freq

uen

tblood

transfusions/

haemophilia

Inf,

HepB,

HepA

Inf,HepB

Inf,

HepB

Inf,

Hep

B

Inf,HepB

Inf,HepB

Inf,Hep

Pn

Inf,HepB

Inf,HepB

Inf,HepB,

HepA

Inf,HepB

HBsA

g-positive

mothers

HepB

HBIG

HepB

HBIG

HepB

HBIG

HepB

HBIG

HepB

HBIG

HepB

HBIG

Hep

B

HBIG

HepB,

HBIG

Hep

B

HBIG

Long-term

aspirin

therapy

Inf

Inf

Inf

Inf

Inf

Inf

Inf

Inf

Inf

Inf

Cochlear

implants

Pn

Pn

Pn

Pn

PnPn,Inf

Pn

Pn

Pn

Pn

†Notincludedin

NIP,butrecommendedin

specialprophylacticprogramsforLBW.

‡Nospecificrecommendations;vaccinationisthesameas

infull-term

infants

(included

inNIP).

§Atdouble

dosageforhem

odialysispatients.

{ Diabetesonly.

#Nolivevaccinesrecommended.

††Allvaccines,exceptBCG,are

recommen

ded

.‡‡Alsofornonim

munehousehold

contacts<12years

ofag

e.§§Advisory

CommitteeonIm

munizationPracticesrecommendations[79].Since

allofthelistedvaccines

are

includedin

theroutinerecommen

ded

immunizationsched

ule

intheUSA,thehigh-riskgrouprecommen

dations

referto

previouslyunim

munized,notfully

immunized,requiringan

protectionearlierthan

routinelyrecommended

orlast

dose

less

than

14daysprecedingim

munosuppression(seedetailsonCDCweb

site).

Countries–BG:Bulgaria;HR:Croatia;CZE:Czech

Rep

ublic;EE:

Estonia;HU:Hungary;

LV:Latvia;LT:Lithuania;PO:Po

land;RO:Roman

ia;SK:Slovakia;SI:Slovenia;TR:Turkey(Advisory

CommitteeonIm

munization

PracticesRecommendations).

Immunization

key

–HepB:Hep

atitis

B;HepA:Hepatitis

A;Hib:Haem

ophilusinfluenzae

type

B;Inf:

Influenza;Men

:Men

ingococcal;

MMR:Measles,

mumps,

and

rubella;Pn:Pneumococcal;Rot:

Rotavirus;

RSV

:Respiratory

syncytialvirus;TDP:Tetanus,diphtheria,andpertussis;Var:Varicella;Empty

field:Norecommendation.

CV:Cardiovascular;HBsA

g:hep

atitisBsurface

antigen

;HBIG:Hep

Bim

muneglobulin;LBW:Low

birthweight;NNMD:Neurologicalan

dneu

romusculardisorders;TBE:Tick-borneencephalitis.

Recommendationsources–EE:EstonianHealth

Board

[80];HU:Recommendationofim

munizationfor2012,National

CentreforEpidemiology[81];LV

:Latvianjournal

ofthelegislationforums[82]

andseverallocal

recommen

dationsfrom

ProfessionalSocieties;RO:Influenza

[83];RSV

[84];Hep

B[85];HepA,Hib

[86];HBIG

[87]:CDCMan

ual

fortheSurveillance

ofVaccine-Preventable

Diseases,4th

Edition,2008–2

009;SK

:Ministry

ofHealthDecreeNo.585/2008,establishingdetails

ofpreventionan

dcontrolofcommunicab

lediseases[88].

Review Richter, Anca, Andre et al.

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corticosteroid therapy are required [24]. The ACIP recommendsroutine pneumococcal vaccination of all children from 2 to59 months and an additional dose for immunocompetent chil-dren aged up to 71 months with comorbidities includingchronic lung disease [23]. Additionally, children in this groupaged ‡2 years are recommended to receive one dose ofPPSV23 ‡8 weeks after the last PCV dose [23]. The ACIP alsorecommends that vaccine efforts should focus on individuals athigher risk of influenza-related complications including thosewith chronic lung disease. However, they should not receivethe live attenuated influenza vaccine [22]. Most European coun-tries (all CEVAG countries) identify high-risk groups, regard-less of age, as primary influenza vaccination targets [25].

Chronic heart/cardiovascular disease

Children with significant chronic heart disease are at increased riskof infections, complications and death from influenza and pneu-mococcal disease [22,23]. Specific cardiovascular conditions that maybe indications for immunization include congenital heart diseasewith significant shunting, cyanosis, valvular disease, cardiomyopa-thy and congestive heart failure. The ACIP classifies children withchronic heart disease as having an underlying comorbidity that isan indication for pneumococcal vaccination [23] and children<18 years with heart disease as a high-risk group for influenza [22].Rotavirus immunization is recommended in some countries dueto frequent hospitalization and increased exposure to nosocomialgastroenteritis [26]. Additionally, infants with symptomatic cardiacdisease are at increased risk of complicated RSV bronchiolitis [19,27].Passive immunization with palivizumab can reduce the number ofRSV hospitalizations [27] and is usually recommended in infantswith hemodynamically significant congenital heart disease duringthe first year of life and second RSV season [28].

Children with neurological & neuromuscular diseases

Individuals with neurological and neuromuscular disease(NNMD) are at higher risk of developing influenza-related com-plications [6,29]. These conditions include disorders of the brain,spinal cord, peripheral nerve and muscle, such as cerebral palsy,congenital brain and/or spinal cord malformations, ischemic andhemorrhagic brain injury, epilepsy, intellectual disability, moder-ate-to-severe developmental delay, muscular dystrophy or spinalcord injury. Children with these conditions often have compro-mised respiratory function, frequent pulmonary aspirations andthe inability to handle secretions, which are further exacerbatedby influenza infection and resulting pneumonia [28]. However,during 2005, the ACIP updated its recommendation to includechildren with NNMD (cognitive dysfunction; spinal cordpathology; seizure disorder) [30]. In a study evaluating childrenhospitalized with community-acquired influenza, those withNNMD had the highest risk of respiratory failure [31].

Chronic kidney disease/renal failure & nephrotic syndrome

Children with chronic kidney disease (e.g., glomerular disorders,especially with significant proteinuria; on chronic immunosup-pressants; end-stage renal disease; dialysis and renal transplant

patients) are at increased risk of infection from vaccine-preventable diseases, but also have reduced immunologicalresponsiveness to certain vaccines [32]. These patients shouldreceive all routine immunizations, except for those on immuno-suppressants who should not receive live vaccines (rotavirus;MMR; varicella; live attenuated influenza vaccine) [32,33]. There-fore, MMR and varicella vaccines should ideally be administeredbefore immunosuppressants. In the USA, in children with end-stage renal disease, only 32% received influenza vaccine and 13%received pneumococcal vaccine [34]. This population shouldreceive pneumococcal, influenza and HepB vaccines [32,34].Patients with chronic renal failure are at particular risk of HepBinfection [35]; therefore, antibody levels should be monitoredannually and additional doses given if anti-HBs antibody levelsare <10 mIU/ml after a three-dose schedule [31,32].

Chronic metabolic diseases (including diabetes & obesity)

Insulin-dependent diabetes mellitus can increase vulnerability toinfections, including influenza and pneumonia, which tend tobe more severe than in the general population [36]. Diabeticpatients are three-times more likely to be hospitalized or diefrom influenza-related complications [37]. The main immuniza-tions recommended for diabetic patients include those againstinfluenza, pneumococcal disease and HepB [38].

In adults, obesity (BMI ‡30) and morbid obesity (BMI‡40) are independently associated with an increased risk ofrespiratory hospitalizations, intensive care admission and deathfrom influenza [39,40]. Annual influenza vaccinations are recom-mended [40,41]. Data in the pediatric age group are missing.

Children with inherited metabolic disease also have a high-risk of infection [41,42]. Glycogen storage disease type IB isregularly associated with neutropenia, predisposing patients topurulent skin and respiratory infections including pneumococ-cal disease.

Immunocompromised childrenImmunocompromised patients are a heterogeneous populationwith special immunization requirements. Immunocompromis-ing conditions are divided into two groups: primary (congeni-tal) or secondary (due to comorbidity, immunosuppressants orHIV infection).

Immunocompromised children are at increased risk of infec-tion, for example, pneumococcal [23], influenza [22]. Vaccine rec-ommendations depend on the degree of immunosuppression andsusceptibility to infection [43]. In general, live vaccines are contra-indicated in immunocompromised patients in which replicationof vaccine strains can be enhanced and induce serious disease [44].However, all asplenic, neutropenic and complement-deficientpatients can receive live attenuated vaccines. Inactivated or com-ponent vaccines pose no risk to immunocompromised popula-tions although they may be unable to mount a protectiveimmune response. Nevertheless, immunocompromised patientsshould be differentiated according to their specific risk and thenature of their immune defect and immunized appropriately togain at least partial immunity.

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Whenever possible, patients from these groups should havetheir protection tested by a surrogate marker, typically serumantibody titer to the vaccinal pathogen. The correlation maynot always be perfect. In some instances, for example asplenia,titers against Streptococcus pneumoniae sertoypes and Hib mayhave to be higher than in healthy population for adequate pro-tection [45]. Some of the cutoffs proposed for protective anti-body thresholds are: Hib 1.0 mg/ml 3–4 weeks followingthe initial series, S. pneumoniae 1.3 mg/ml at 3–4 weeks, Neisse-ria meningitidis 2.0 mg/ml at 3–4 weeks, tetanus 0.15 IU/ml3–4 weeks following initial series [46]. Polio neutralizing anti-bodies, influenza hemagglutinin inhibition, hepatitis A andHepB antibodies have also been utilized [47]. Response to vacci-nation may also be used in order to assess a child’simmunocompetence [45,46].

Asplenia

Children with anatomical or functional asplenia are at increasedrisk of bacterial sepsis (overwhelming postsplenectomy infec-tion) [48,49]. People without a functional spleen are particularlysusceptible to infection with encapsulated bacteria (e.g., N.meningitidis, Hib and particularly S. pneumoniae) due to loss ofsplenic phagocytic function [50]. Vaccination against pneumo-coccal, meningococcal, Hib and influenza vaccinations isrecommended [49].

Children with complement deficiency

Classical and alternative complement pathway defects renderthe patient exceptionally prone to infection due to encapsulatedbacteria, primarily S. pneumoniae, H. influenzae, N. meningitidisand Enterobacteriaceae [51]. Children with defects in properdinor membrane attack complex are highly susceptible to infec-tions by N. meningitidis. Although very rare, patients with thesedefects are universally recommended to receive the widest possi-ble coverage against pneumococcal, Hib and meningococcaldisease.

HIV infection

Although pediatric HIV infection can be managed withHAART, vaccine-preventable diseases still cause significantmorbidity and mortality in this population [52]. Despite theHIV-associated immune system impairment, vaccinationagainst infectious diseases remains one of the most effectivepreventive strategies. HIV-infected children should receivepneumococcal, Hib, meningococcal, influenza and MMR vac-cines [53]. Children on HAART respond to revaccination eventhough some may not achieve long-term immunity [54]. S.pneumoniae is the most common invasive bacterial pathogen inHIV-infected children [53], who have a 40-fold increased risk ofIPD. Consequently, despite <1% of children under 5 years ofage being HIV positive, they constitute approximately 10% ofall annual deaths from S. pneumoniae [53,55,56]. HIV-positivechildren are also at a higher risk for varicella, Herpes zoster andmeasles complications [53]. Due to the limited safety, immuno-genicity and efficacy data in these individuals, varicella and

MMR vaccination should only be considered if the child is notseverely immunocompromised (i.e., CD4+ T-lymphocyte count‡15%) [53]. Postvaccination testing for HepB is recommendeddue to the potentially impaired humoral response; if anti-HBslevels are <10 mIU/ml, then revaccination with a second three-dose series is recommended [53]. All HIV-positive childrenshould have individually tailored immunizations, adjusted fordisease stage, HIV viral load and CD4+ count.

Organ transplantation

Infectious diseases, including vaccine-preventable infections, arethe leading cause of morbidity and mortality in bone marrowand solid-organ transplant recipients [57]. Post-transplant immu-nosuppression and decreased antibody production increase sus-ceptibility to infectious diseases and associated life-threateningcomplications in transplant recipients, regardless of prior vacci-nation status [57]. Once stabilized, transplant patients should, inprinciple, continue to receive routine inactivated vaccinesaccording to local NIPs [58]. Hematopoietic stem cell transplant(HSCT) recipients are at increased risk of vaccine-preventablediseases because antibody titers decline 1–4 years post-trans-plant, if they are not revaccinated [59]. All HSCT recipients arerecommended to receive pneumococcal, Hib, meningococcalconjugate, DTaP, inactivated influenza and inactivated poliovaccines post-transplant [60]. PCV and influenza vaccines can begiven 3–6 and 4–6 months post-HSCT, respectively [60]. Othernonlive vaccines can be started 6–12 months post-transplant.Live vaccines, such as MMR and varicella, should be adminis-tered 2 years post-transplantation, if the patient is adequatelyimmunocompetent [59]. Therefore, when possible, a childshould receive all possible missed or indicated vaccinations pre-transplantation and <3 weeks prior to immunosuppression [58].Following solid-organ transplantation, live vaccines remaincontraindicated including MMR. Starting at 2–6 months post-transplant, the child should be evaluated for booster and addi-tional inactivated vaccines (commonly influenza, pneumococcaland meningococcal) [45].

Malignant disease

Children with malignant disease have a higher risk of acquir-ing vaccine-preventable diseases and developing complica-tions. Immunosuppressive treatment and the malignantdisease itself adversely affect the immunity established byprior vaccination. Children who receive immunosuppressivecancer therapy will benefit from immunization; however,safety and reduced vaccine responsiveness should be takeninto consideration [61]. As a general rule, these children cancontinue to receive routine inactivated vaccines according tolocal NIPs during the stable phases of disease, but shouldnot receive live vaccines [58]. After completing their treat-ment, these children should be re-evaluated for booster dosesof previously administered vaccines [62] and additional pro-tection starting ‡3 months postchemotherapy and ‡6months post-anti-B-cell monoclonal antibodies for inacti-vated vaccines [45].

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Children on medical immunosuppression

This group includes children with chronic inflammatory diseasesof various organs receiving systemic corticosteroids, cytostaticagents (e.g., methotrexate, cyclophosphamide), biologic therapy(e.g., anti-TNF therapy) and monoclonal antibodies (e.g., rituxi-mab). In the CEVAG countries, it has not been singled out as aspecific high-risk group, perhaps due to lack of centralized care (asopposed to the organ transplant and cancer group). Additionally,the immunization problems are compounded by the fear of puta-tive flare-ups of the underlying disease related to vaccines [63]. Thevaccination problems in these children are left to individual incen-tives of the subspecialist and/or primary care physicians. Thesepatients, especially the ones on anti-TNF therapy, are inordinatelysusceptible to pneumococcal, influenza and human papillomavi-rus infections [64]. They should receive all the inactivated vaccineslisted in the NIPs plus conjugated pneumococcal and meningo-coccal, inactivated influenza and hepatitis A no less than 4 weeksprior to the planned immunosuppression. If vaccines are givenduring the period of treatment, then they should be delivered dur-ing remission. Live vaccines should not be given during any lowor high level of active immunosuppresion [45]. Immunization willhave no effect if given during treatment with drugs that selectivelyeliminate B cells (rituximab). BCG in general should not begiven, and Kawasaki disease is a strict contraindication to BCGbecause of a high rate (50%) of severe local reactions [65].

Children who require frequent blood transfusions

Patients with bleeding disorders have an increased risk of infec-tion due to previous and potential exposure to blood prod-ucts [66]. The WHO states that individuals who frequentlyrequire blood or blood products are possible targets for HepBcatch-up vaccination [35]. Children with bleeding disordersshould also receive subcutaneously administered vaccines due tothe risk of hematoma formation [66].

Other risk groupsInfants born to HepB surface antigen-positive mothers

These infants are universally recognized as high risk due to ver-tical transmission from mother to child (70–90%, if themother is HepB surface antigen [HBsAg] and HBeAg positive)and associated high likelihood of chronic infection (90% ofthose infected) [67]. Whether HepB vaccination is universal atbirth, or later, all infants of HBsAg-positive mothers shouldalso receive HepB immune globulin within 12 h postpartum.The administration of HepB immune globulin is particularlyimportant in this high-risk group as the timing of the nextHepB dose in the NIP varies between countries. HBsAg shouldbe tested on umbilical cord blood, and infants should also betested for HBsAg and antibody to HBsAg (anti-HBs) 1 monthafter completion of at least three doses of HepB series andagain at 9–18 months [57].

Long-term aspirin (salicylates) therapy

Reye’s syndrome is a very rare but potentially fatal disease inchildren that causes encephalopathy and fatty degeneration of

the liver. It affects children who are on long-term aspirin ther-apy and have a varicella or influenza virus infection [68]. Reye’ssyndrome is now particularly rare since aspirin is no longerroutinely given to children and due to the availability of diag-nostic tools to detect congenital errors of mitochondrial fattyacid oxidation. Children aged 0.5–18 years on long-term aspi-rin should receive the influenza vaccine [22]. Furthermore, theunderlying cardiovascular condition for which aspirin is pre-scribed is also an indication for influenza vaccination. Varicellavaccination should also be recommended.

Children with cochlear implants

Children with cochlear implants are at greater risk of bacterialmeningitis and have a >30-fold higher incidence of pneumo-coccal meningitis than the general population [69]. Infants andchildren who are candidates for cochlear implants shouldreceive pneumococcal and Hib conjugate vaccines and annualinfluenza immunization [70]. Children should receive PCV orPPSV23 at least 2 weeks before surgery [23]. Physicians shouldbe aware that, despite available recommendations, this pediatricgroup may not be optimally protected as pneumococcal guide-lines for high-risk children are regarded as complicated and dif-ficult to interpret [71]. For example, in the UK, 54% ofchildren with cochlear implants are not optimally immunizedbefore surgery and 75% require further immunizations [71].

Children living in endemic TBE areas

Tick-borne encephalitis (TBE) is a viral zoonotic disease trans-mitted to humans via ticks or unpasteurized dairy products.Most cases present with influenza-like symptoms, while 10% canlead to inflammation of the meninges, brain or spinal cord [72].The incidence of TBE varies considerably between countries andregions. In areas that are highly endemic (‡5 cases/100,000 popu-lation), the WHO recommends that immunization be offered toall age groups including children [73]. TBE is highly endemic insome Central European countries, and CEVAG strongly recom-mends universal TBE vaccination in children >1 year of age insuch areas [66]. For countries with a low risk of TBE, the vaccineshould be offered to children >10 years of age and to those travel-ling to endemic areas [74].

Current immunization recommendations for all high-riskgroups in each CEVAG country are presented in TABLE 2 andAPPENDIX A.

CEVAG guidance statementPhysicians, healthcare workers and families of infants and chil-dren need to be made aware of the infectious diseases relevantto each high-risk category. Physicians should take a broad andrational approach to immunization, as delineated in this paper,when advising patients on their exposure risks and the need toget vaccinated. In particular, for immunocompromised chil-dren, the extent of immunosuppression should be consideredand recommendations should be made on an individual basis.This can best be achieved through multidisciplinary approachinvolving the primary care physician, treating subspecialist,

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clinical immunologist and vaccine expert. Every effort shouldbe made to administer vaccines prior to immunosuppressivetreatment. Details concerning the immunization of individualpatients in this group are beyond the scope of this paper; theyare amply discussed elsewhere [45].

The risks need to be better defined by the epidemiologicservices of each country. CEVAG suggests adopting mandatorydisease reporting of vaccine-preventable diseases and broadeningthe case definition to include all relevant cases, regardless ofclinical presentation.

The CEVAG group high-risk immunization recommendationsare summarized in TABLE 3. Influenza and pneumococcal vaccinesshould be recommended for most high-risk groups includingthose with chronic lung, heart, metabolic and renal diseases. Allvaccines routinely recommended for full-term infants should begiven to premature and low birthweight infants; this includesinfluenza, pneumococcal conjugate, Hib, DTaP, HepB, rotavirusand poliovirus vaccines. This risk group should additionallyreceive RSV prophylaxis. Children who are immunocompromisedare also recommended to receive immunization for most infec-tious diseases, unless the specific vaccine is contraindicated.Human papillomavirus is not specifically recommended for anyof the high-risk groups in the CEVAG countries.

The CEVAG panel strongly feels thatall high-risk children should receive fullmandatory NIP vaccinations unless medi-cally contraindicated. Reliance on herdimmunity due to high NIP coverage acrossmost CEVAG countries should not be theargument to avoid NIP vaccines.

Expert commentaryWith an increasing number of vaccinesgaining approval in Europe, immunizationschedules are becoming more complex. Anin-depth understanding of both vaccinesand associated infectious diseases is impor-tant to ensure that the right people receivethe right vaccines. To allow this, there aretwo general approaches to immunization:universal administration of all vaccines toa predefined age group and target high-risk populations. Although universalimmunization is effective in reducing dis-ease burden and can result in herd immu-nity, individual risks and circumstancesshould also be considered.

Evaluation of current high-risk recom-mendations in CEVAG countries hasrevealed a broad consensus as to whichhigh-risk groups should receive particularvaccinations. In most CEVAG countries,influenza vaccination is broadly recom-mended across all pediatric risk groupsincluding children with malignancy or

immunodeficiency. Recommendations for other vaccines, suchas those against pneumococcal and meningococcal disease, areless consistent although there is general agreement on whichgroups are at high risk from these infections. The availability ofconjugate vaccines has extended the indications for pneumococ-cal disease prevention beyond the time-honored conditions ofasplenia and complement deficiencies; however, these stillremain the principal indications for meningococcal vaccination.

Immunization recommendations for risk groups with definedcomorbidities are fairly consistent across CEVAG countries.However, recommendations for conditions with heterogeneouspopulations, such as immunocompromised children, are lessconsistent. The heterogeneity of this population means that theexisting guidelines may not be applicable to all conditions [61].Furthermore, immunocompromised children may not receiveroutine immunizations as a result of lack of efficacy and safetydata in this group [75]. However, all killed vaccines are generallysafe and live vaccines can be given depending on the extent ofthe suppression and time elapsed since therapy [45]. Indirectprotection of high-risk children should be secured by increasingimmunity in household and other close contacts of the child,especially healthcare workers. These should be up to date withall mandatory vaccines and additionally receive inactivated

Table 3. Central European Vaccination Awareness Group consensusof recommended immunizations for high-risk groups.

High-risk group Recommended immunizations

Premature and low birthweight babies All routine immunizations plus RSV, Rot, Inf

Chronic lung disease Pn, Inf, RSV (<1–2 years old)

Chronic heart disease Pn, RSV (<1–2 years old), Inf

NNMD Inf

Chronic renal disease Pn, Inf, HepB

Chronic metabolic disease Pn, Inf, TD, HepB

Immunocompromised (general) Pn, Inf, Men

Asplenia Pn, Men, Hib, Inf

Complement deficiency Pn, Hib, Men

HIV infection Pn, Men, Hib, Inf, MMR, Var

Organ transplantation Inf, Pn, MMR†, Var†, HepA (prior to liver

transplantation)

Frequent blood transfusions HepB, HepA, Inf

Malignant disease Pn, Inf

Long-term aspirin therapy Inf, Var (before aspirin is started)

Cochlear implants Pn, Hib, Inf

Newborns of HBsAg-positive mothers HepB, HBIG

†Live vaccines should be taken before immunosuppressive treatment.Immunization key:HepB: Hepatitis B; HepA: Hepatitis A; Hib: Haemophilus influenzae type b; Inf: Influenza; Men: Meningococcal;MMR: Measles, mumps, and rubella; Pn: Pneumococcal; Rot: Rotavirus; RSV: Respiratory syncytial virus;TBE: Tick-borne encephalitis; TDP: Tetanus, diphtheria and pertussis; Var: Varicella.HBsAg: Hepatitis B surface antigen; HBIG: HepB immune globulin; NNMD: Neurological and neuromuscular disorders.

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influenza, pneumococcal, inactivated polio, MMR, varicellaand rotavirus vaccines if needed/indicated. MMR strains arenot transmitted in human contact. Rotavrius may be excretedin stools, but transmission to contacts has not been reported.For varicella, no specific precautions are needed unless the vac-cine recipient develops a rash, in which case, direct contactshould be avoided until the rash resolves. Attenuated oral poliovaccine should not be given to contacts of immunocompro-mised children [45,76].

Children with neurological conditions are one of the threegroups (the others being chronic heart and lung disease) thatare particularly at risk of severe influenza [77,78]. Children withNNMDs are overlooked in some CEVAG countries as thereare recommendations for influenza and pneumococcal immuni-zation in eight and six of CEVAG countries, respectively. Evenwhen such recommendations exist for a particular risk group,they may be overlooked due to the complexity of care for thesechildren and a lack of understanding of the vaccine contraindi-cations. Furthermore, frequent hospitalization may result inmissed doses.

There have been several published studies highlighting thegeneral lack of optimal immunization of these high-riskgroups [32,71]. Reasons for this may include the lack of efficacyand safety data, in particular for immunocompromised popula-tions [65]. Inadequate vaccination of solid-organ transplantpatients is a common problem worldwide, and a standardizedapproach to vaccination of solid-organ transplant patients istherefore required.

It is also apparent that the supporting evidence for vaccina-tion of individual high-risk groups with comorbidities is lim-ited. This is due in part to the lack of epidemiological data forcertain conditions [3]. As a general rule, high-risk patientsemerge as candidate groups for immunization from retrospec-tive analyses unless the condition is very common, such as dia-betes [3], or the association of an underlying condition andadverse outcome of an infection is difficult to oversee (e.g.,obesity, neurological disorder and influenza) [78]. There alsoappears to be a lack of European morbidity and mortality datafor individual high-risk groups. Such data are available for theUSA but not for most of Europe. As a result, the burden ofpreventable infectious diseases in these risk groups may beunderestimated leading to a lack of awareness. Discussing theaffected risk groups should in turn help raise awareness andincrease reporting of infectious diseases in children at high risk.

Adherence to the recommendations presented in this papermay help raise awareness among physicians of the infectious dis-eases relevant to their subspecialty and ensure that their patientsreceive all appropriate immunizations. However, cost remains anissue. Although the CEVAG countries reimburse the cost of vac-cinations included in the NIP, additional immunization mustoften be paid for by parents who in many cases cannot afford it.Detailed knowledge of the rationale for delivering specific vacci-nations is required for high-risk groups, but clear and transparentguidelines for each individual condition would ensure that thesepopulations receive the appropriate vaccines.

Five-year viewIn many countries with moderate or modest Gross NationalProduct, high-risk groups are targeted for vaccination to avoidlarge scale, universal immunization costs. In some cases, placingvaccines on the list for high-risk groups allow for future intro-duction into the NIP. This is likely to be the case with immu-nization against pneumococcal disease, and it is foreseeable thatthis vaccine will be included in the NIP soon after it has beenintroduced for high-risk groups. However, even if vaccines dobecome included in the NIP, CEVAG recommendationsshould remain in place as it is unlikely that universal immuni-zation will cover all age groups and circumstances includingthose who become severely immunocompromised and requirerevaccination. With improved disease monitoring and reportingthroughout Europe, it is likely that the risk factors involved foreach infectious disease will be increasingly understood and therecommendations can be refined and revised accordingly.

Acknowledgements

All authors were actively involved in the selection and review of all con-

tent and had full editorial control during the writing of the manuscript.

Financial & competing interests disclosure

D Richter has received honoraria for lectures on vaccines and respiratory

drugs from GlaxoSmithKline (GSK) Croatia, MSD Idea Inc. Croatia,

Pfizer and Medoka (representing Sanofi Pasteur). I Anca has been the

principal investigator in clinical studies supported by GSK, Apogepha and

Ferring. The author has also been a scientific consultant to GSK, Wyeth

Lederle, Teva, AstraZeneca and Nestle and has received sponsorship from

GSK, Pfizer and Nestle to attend scientific meetings. M Bakir has received

sponsorship for scientific meetings from GSK, Wyeth Lederle, sanofi aventis

and Merck Sharp & Dohme (MSD). R Chlibek has received lecture fees

and sponsorship to attend scientific meetings from GSK, Sanofi Pasteur

and Pfizer and has been principal investigator in clinical trials sponsored

by GSK. M Cizman has received honoraria for lectures on vaccine use

from GSK, Pfizer and MSD. A Mangarov has been a scientific consultant

to GSK, Aventis Pasteur, Pfizer, Danone and Solvay Pharma and has

received sponsorship from these companies to attend scientific meetings. Z

Meszner is a consultant to Pfizer, GSK, MSD, Sanofi Pasteur, Novartis

and Baxter on vaccination issues and has also received travel grants. M

Pokorn has received lecture fees from GSK Slovenia, speaker fees from

GSK and has received sponsorship from GSK and PharmaSwiss Slovenia

to attend scientific meetings. R Prymula is a member of advisory boards

for GSK, MSD, Pfizer, Baxter and Aventis Pasteur and has received

research grants and honoraria from GSK, Pfizer, Baxter, Aventis Pasteur

and Novartis. P Simurka has received consulting fees and lecture fees from

GSK, Pfizer and MSD. E Tamm has received sponsorship from GSK and

PharmaSwiss to attend scientific meetings. G Tesovic has received sponsor-

ship from GSK, MSD, PharmaSwiss, and Pfizer to attend scientific meet-

ings. I Urbancıkova has been a scientific consultant to GSK and Pfizer

and has received lecture fees from GSK, Pfizer, MSD and Novartis and

sponsorship from GSK, Pfizer and Sanofi Pasteur to attend scientific meet-

ings. V Usonis has been the principal investigator in clinical studies sup-

ported by GSK, Novartis and Pfizer. The author has also been a scientific

consultant to Aventis Pasteur, Baxter, GSK, Merck and Pfizer and has

Immunization of high-risk pediatric populations Review

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received sponsorship from these companies to attend scientific meetings. J

Wysocki has been principal investigator in clinical trials sponsored by

GSK, Wyeth, Pfizer and Novartis. The author has also received sponsor-

ship from GSK, Pfizer and Wyeth to attend scientific congresses. D Zavad-

ska has received lecture fees from GSK, Sanofi Pasteur and Abbott and

has received sponsorship from GSK and Baxter to attend scientific meet-

ings. F Andre and N Salman have no competing interests. The authors

have no other relevant affiliations or financial involvement with any

organization or entity with a financial interest in or financial conflict

with the subject matter or materials discussed in the manuscript apart

from those disclosed.

Preparation of this report was supported by an educational grant from

GlaxoSmithKline, Novartis and Pfizer.

Writing assistance was utilized in the production of this manuscript.

Editorial assistance was provided by C Combs and Wells Healthcare Com-

munications Ltd.

Key issues

• High-risk groups are defined as those who are more susceptible to vaccine-preventable diseases and their complications, and include

those with underlying chronic diseases or comorbidities and those at increased risk of exposure to vaccine-preventable diseases.

• High-risk groups therefore require additional immunization recommendations and strategies to ensure maximum protection.

• Physicians, healthcare workers and families of infants and children need to be made aware of the infectious diseases relevant to each

high-risk category.

• Neonates, infants and very young children remain the principal targets of most universal national immunization programmes (NIPs)

because of the high risk of morbidity and mortality at this young age.

• Preterm and low birthweight babies are at even higher risk of complications and morbidity from vaccine-preventable diseases and

should receive all routine vaccines including rotavirus and influenza, as well as respiratory syncytial virus prophylaxis.

• Vaccines against influenza, pneumococcus and rotavirus are currently the most commonly recommended for pediatric high-risk groups

across Central European Vaccination Awareness Group countries.

• Children with cochlear implants are at increased risk of bacterial meningitis (pneumococcal in particular) and should receive

pneumococcal, Haemophilus influenzae type b and influenza vaccines.

• Immunizations for immunocompromised children should be individually tailored according to their specific condition, disease stage and

level of immunosuppression.

• Limited financial resources and lack of consistent surveillance systems may explain the practice of limited targeting of high-risk groups

with vaccines that are included in NIPs in many countries.

• The decision to include a vaccine-preventable disease in the NIP could be greatly facilitated by making the disease notifiable and

gathering sound evidence from surveillance.

• Expanded immunization initiatives should help prevent the disproportionate morbidity and mortality that can occur when high-risk

pediatric populations contract vaccine-preventable diseases.

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Affiliations

Darko RichterDepartment of Paediatrics, University Hospital Centre, Zagreb, Croatia

Ioana AncaUniversity of Medicine and Pharmacy ‘Carol Davila’ Bucharest – Institute for Motherand Child Care, Bucharest, Romania

Francis E AndreChaussee de Huy, 136, 1325-Chaumont-Gistoux, Belgium

Mustafa BakirDepartment of Pediatrics, Division of Pediatric Infectious Diseases, MarmaraUniversity School of Medicine, Istanbul, Turkey

Roman ChlibekFaculty of Military Health Sciences, University of Defence, Hradec Kralove, CzechRepublic

Milan CizmanDepartment of Infectious Diseases, University Medical Centre, Ljubljana, Slovenia

Atanas MangarovInfectious Diseases Hospital, Sofia, Bulgaria

Zsofia MesznerNational Institute of Child Health, Budapest, Hungary

Marko PokornDepartment of Infectious Diseases, University Medical Centre, Ljubljana, Slovenia

Roman PrymulaFaculty of Military Health Sciences, University of Defence, Hradec Kralove, CzechRepublicandUniversity Hospital, Hradec Kralove, Czech Republic

Nuran SalmanDivision of Infectious Disease and Clinical Microbiology, University of Istanbul,Istanbul, Turkey

Pavol SimurkaUniversity of Trencin, Pediatric Clinic, Faculty Hospital, Trencın, Slovakia

Eda TammChildren’s Clinic of Tartu University Hospital, Tartu, Estonia

Goran TesovicPaediatric Infectious Diseases Department, University of Zagreb, School of Medicine,Zagreb, Croatia

Ingrid UrbancıkovaDepartment of Paediatric Infectious Diseases, Children’s Faculty Hospital, Kosice,Slovakia

Vytautas UsonisFaculty of Medicine, Clinic of Children’s Diseases, Vilnius University, Vilnius,Lithuania

Jacek WysockiDepartment of Preventive Medicine, Poznan University School of Medical Sciences,Poznan, Poland

Dace ZavadskaDepartment of Pediatrics, Riga Stradins University, Riga, Latvia

Immunization of high-risk pediatric populations Review

informahealthcare.com doi: 10.1586/14760584.2014.897615

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