2014-2015+AAP儿童流感的预防与控制建议

DOI: 10.1542/peds.2014-2413

; originally published online September 22, 2014;

Pediatrics COMMITTEE ON INFECTIOUS DISEASES

2015

?

Recommendations for Prevention and Control of Influenza in Children, 2014

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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

POLICY STATEMENT

Recommendations for Prevention and Control of In ?uenza in Children,2014–2015

abstract

The purpose of this statement is to update recommendations for rou-tine use of seasonal in ?uenza vaccine and antiviral medications for the prevention and treatment of in ?uenza in children.The American Acad-emy of Pediatrics recommends annual seasonal in ?uenza immuniza-tion for all people 6months and older,including all children and adolescents.Highlights for the upcoming 2014–2015season include the following:

1.The in ?uenza vaccine composition for the 2014–2015season is unchanged from the 2013–2014season.

2.Both trivalent and quadrivalent in ?uenza vaccines are available in the United States for the 2014–2015season.

3.Annual universal in ?uenza immunization is indicated with either a trivalent or quadrivalent vaccine (no preference).

4.Live attenuated in ?uenza vaccine (LAIV)should be considered for healthy children 2through 8years of age who have no contra-indications or precautions to the intranasal vaccine.If LAIV is not readily available,inactivated in ?uenza vaccine (IIV)should be used;vaccination should not be delayed to obtain LAIV.

5.The dosing algorithm for administration of in ?uenza vaccine to children 6months through 8years of age re ?ects that virus strains in the vaccine have not changed from last season.As always,pediatricians,nurses,and all other health care personnel should be immunized themselves and should promote in ?uenza vac-cine use and infection control measures.In addition,pediatricians should promptly identify clinical in ?uenza infections to enable rapid antiviral treatment,when indicated,to reduce morbidity and mortality.Pediatrics 2014;134:1–17

INTRODUCTION

The American Academy of Pediatrics (AAP)recommends annual seasonal in ?uenza immunization for all people 6months and older,including all children and adolescents,during the 2014–2015in ?uenza season.In addition,special effort should be made to vaccinate people in the following groups:

COMMITTEE ON INFECTIOUS DISEASES

KEY WORDS

in ?uenza,immunization,live attenuated in ?uenza vaccine,inactivated in ?uenza vaccine,vaccine,children,pediatrics ABBREVIATIONS

AAP —American Academy of Pediatrics

ccIIV3—trivalent cell culture-based inactivated in ?uenza vaccine CDC —Centers for Disease Control and Prevention FDA —US Food and Drug Administration

GRADE —Grading of Recommendations Assessment,Development,and Evaluation

HCP —health care personnel ID —intradermal

IIV —inactivated in ?uenza vaccine

IIV3—trivalent inactivated in ?uenza vaccine IIV4—quadrivalent inactivated in ?uenza vaccine IM —intramuscular

LAIV —live attenuated in ?uenza vaccine

LAIV4—quadrivalent live attenuated in ?uenza vaccine NAIs —neuraminidase inhibitors PCR —polymerase chain reaction

PCV13—13-valent pneumococcal conjugate vaccine pH1N1—in ?uenza A (H1N1)pandemic virus RIV3—trivalent recombinant in ?uenza vaccine

This document is copyrighted and is property of the American Academy of Pediatrics and its Board of Directors.All authors have ?led con ?ict of interest statements with the American Academy of Pediatrics.Any con ?icts have been resolved through a process approved by the Board of Directors.The American Academy of Pediatrics has neither solicited nor accepted any commercial involvement in the development of the content of this publication.The guidance in this policy statement does not indicate an exclusive course of treatment or serve as a standard of care.Variations,taking into account individual circumstances,may be appropriate.Policy statements from the American Academy of Pediatrics bene ?t from expertise and resources of liaisons and internal (AAP)and external reviewers.However,policy statements from the American Academy of Pediatrics may not re ?ect the views of the liaisons or the organizations or government agencies that they represent.

All policy statements from the American Academy of Pediatrics automatically expire 5years after publication unless reaf ?rmed,revised,or retired at or before that time.

(Continued on last page)

FROM THE AMERICAN ACADEMY OF PEDIATRICS

Organizational Principles to Guide and De ?ne the Child Health Care System and/or Improve the Health of all Children

All children,including infants born preterm,who are6months and older with conditions that increase the risk of complications from in?u-enza(eg,children with chronic med-ical conditions,such as asthma, diabetes mellitus,hemodynamically signi?cant cardiac disease,immuno-suppression,or neurologic and neu-rodevelopmental disorders);

Children of American Indian or Alaska Native heritage

All household contacts and out-of-home care providers of

?Children with high-risk condi-tions

?Children younger than5years, especially infants younger than

6months

All health care personnel(HCP) All child care providers and staff All women who are pregnant,are considering pregnancy,are in the postpartum period,or are breast-feeding during the in?uenza sea-son

KEY POINTS RELEVANT FOR THE 2014–2015INFLUENZA SEASON 1.Annual seasonal in?uenza vac-

cine is recommended for all

people6months and older,in-

cluding all children and adoles-

cents,during the2014–2015

in?uenza season.It is impor-

tant that household contacts and

out-of-home care providers of chil-

dren younger than5years,es-

pecially infants younger than6

months,and children of any age

at high risk of complications

from in?uenza(eg,children with

chronic medical conditions,such

as asthma,diabetes mellitus,he-

modynamically signi?cant cardiac

disease,immunosuppression,or

neurologic and neurodevelopmen-

tal disorders)receive annual in?u-

enza vaccine.In the United States,

more than two-thirds of children

younger than6years and almost

all children6years and older

spend signi?cant time in child

care or school settings outside

the home.Exposure to groups of

children increases the risk of con-

tracting infectious diseases.Chil-

dren younger than2years are at

elevated risk of hospitalization and

complications attributable to in?u-

enza.School-aged children bear

a large in?uenza disease burden

and have a signi?cantly higher

chance of seeking in?uenza-related

medical care compared with

healthy adults.Reducing in?uenza

virus transmission(eg,appropriate

hand hygiene,respiratory hygiene/

cough etiquette)among children

who attend out-of-home child care

or school has been shown to de-

crease the burden of childhood

in?uenza and transmission of in?u-

enza virus to household contacts

and community members of all

ages.

2.The percentage of outpatient visits

for in?uenza-like illness,rates of

hospitalization,and deaths attrib-

uted to pneumonia and in?uenza

were lower during the2013–2014

in?uenza season when compared

with the previous season.As of

August23,2014,107laboratory-

con?rmed in?uenza-associated pe-

diatric deaths were reported to

the Centers for Disease Control

and Prevention(CDC)during the

2013–2014in?uenza season.The

2009in?uenza A(H1N1)pandemic

(pH1N1)viruses predominated,but

in?uenza A(H3N2)and in?uenza B

viruses also were reported in the

United States.Of the107deaths,87

were associated with in?uenza A

viruses,and16deaths were asso-

ciated with in?uenza B viruses.

Two deaths were associated with

an undetermined type of in?uenza

virus,and2deaths were associ-

ated with dual infection with both

in?uenza A and B viruses.Although

children with certain conditions

are at higher risk of complications,

47%of the deaths occurred in chil-

dren with no high-risk underlying

medical condition.Among children

hospitalized with in?uenza and for

whom medical chart data were

available,approximately43%had

no recorded underlying condition,

whereas26%had underlying asthma

or reactive airway disease(Fig1).A

recent preliminary observation of

the2013–2014in?uenza season

noted a high number of healthy peo-

ple(ranging from infants to older

adults)who needed care in the ICU,

91%of whom were not previously

vaccinated.

3.Both trivalent and quadrivalent in-

?uenza vaccines are available in

the United States for the2014–

2015season.Neither vaccine for-

mulation is preferred over the

other.Both vaccines contain an A/

California/7/2009(H1N1)–like vi-

rus,an A/Texas/50/2012(H3N2)vi-

rus,and a B/Massachusetts/2/

2012–like virus(B/Yamagata line-

age).The quadrivalent in?uenza

vaccines include an additional B

virus(B/Brisbane/60/2008–like vi-

rus[B/Victoria lineage]).These

strains are unchanged from those

in the2013–2014seasonal in?u-

enza vaccines.

4.Optimal protection is achieved

through annual immunization.An-

tibody titers wane to50%of their

original levels6to12months af-

ter vaccination.Although the vac-

cine strains for the2014–2015

season are unchanged from last

season,a repeat dose this season

is critical for maintaining protec-

tion in all populations.

https://www.wendangku.net/doc/b07848293.html,ing the Grading of Recommen-

dations Assessment,Development,

and Evaluation(GRADE)frame-work,the CDC Advisory Committee on Immunization Practices(ACIP) systematically reviewed the evi-dence pertaining to the ef?cacy of live attenuated in?uenza vaccine (LAIV)and inactivated in?uenza vaccine(IIV)for healthy children. It concluded that there is greater relative ef?cacy of LAIV as com-age).The risk of adverse events

after immunization,including fe-

ver,wheezing,and serious adverse

events,appears to be similar for

LAIV and IIV.Therefore,LAIV should

be considered for healthy children

2through8years of age who have

no contraindications or precau-

tions to the intranasal vaccine.If

LAIV is not readily available,IIV

tion on the basis of demonstration

of superior ef?cacy of LAIV(ages2

through6years)and for program-

matic consistency(8years is the

upper age limit for receipt of2

doses of in?uenza vaccine in a pre-

viously unvaccinated child).

6.The number of seasonal in?uenza

vaccine doses to be administered

in the2014–2015in?uenza season

FIGURE1

Selected underlying medical conditions in patients hospitalized with laboratory-con?rmed in?uenza,FluSurv-NET2013–2014.Source:Centers for Disease Control and Prevention.FluView2013–2014Preliminary Data as of August23,2014.Available at:https://www.wendangku.net/doc/b07848293.html,/grasp/?uview/FluHospChars.html. Asthma includes a medical diagnosis of asthma or reactive airway disease.Cardiovascular diseases include conditions such as coronary heart disease, cardiac valve disorders,congestive heart failure,pulmonary hypertension,and aortic stenosis;does not include hypertension disease only.Chronic lung diseases include conditions such as chronic obstructive pulmonary disease,bronchiolitis obliterans,chronic aspiration pneumonia,and interstitial lung disease.Immune suppression includes conditions such as immunoglobulin de?ciency,leukemia,lymphoma,HIV/AIDS,and the use of immunosuppressive medications.Metabolic disorders include conditions such as diabetes mellitus,thyroid dysfunction,adrenal insuf?ciency,and liver disease.Neurologic disorders include conditions such as seizure disorders,cerebral palsy,and cognitive dysfunction.Neuromuscular disorders include conditions such as multiple sclerosis and muscular dystrophy.Obesity was assigned if indicated in patient’s medical chart or if BMI>30kg/m2.Pregnancy percentage calculated by using number of female cases aged between15and44years of age as the denominator.Renal diseases include conditions such as acute or chronic renal failure,nephrotic syndrome,glomerulonephritis,and impaired creatinine clearance.No known condition indicates that the case did not have any known underlying medical condition indicated in medical chart at the time of hospitalization.

In?uenza vaccines are not li-censed for administration to

infants younger than6months. Children9years and older need only1dose.

Children6months through8 years of age receiving the sea-

sonal in?uenza vaccine for the

?rst time should receive a sec-

ond dose this season at least4

weeks after the?rst dose. Children6months through8 years of age need only1dose

of vaccine in2014–2015if they

have received it according to

any of the following scenarios:

?At least1dose of2013–

2014seasonal in?uenza

vaccine.

?2or more doses of sea-

sonal vaccine since July1,

2010.

?2or more doses of seasonal

in?uenza vaccine from any

previous season and at least

1clearly documented dose of

a pH1N1-containing vaccine

(ie,any seasonal vaccine

since July1,2010or a mono-

valent pH1N1vaccine during

the2009–2010season).

Children in this age group for

whom one of these conditions

is not met need2doses in

2014–2015to be adequately

primed.Vaccination should

not be delayed to obtain a spe-

ci?c product for either dose.

Any available,age-appropriate

trivalent or quadrivalent vac-

cine can be used;IIV and LAIV

are considered interchange-

able.A child who receives only

1of the2doses as a quadriva-

lent formulation is likely to be

less primed against the addi-

tional B virus.

7.Pediatric of?ces may choose to

serve as an alternative venue for providing in?uenza immunization

for parents and other care pro-

viders of children if the practice

is acceptable to both pediatricians

and the adults who are to be vac-

cinated.1There are important medi-

cal liability issues and medical

record documentation require-

ments that must be addressed

before a pediatrician begins immu-

nizing adults(see details at www.

https://www.wendangku.net/doc/b07848293.html,/implementation).

Pediatricians are reminded to

document the recommendation

for adult immunization in the vul-

nerable child’s medical record.In

addition,adults should still be

encouraged to have a medical

home and communicate their

immunization status to their pri-

mary care provider.Offering im-

munizations in the pediatric

practice setting would not be

intended to undermine the adult

medical home model but could

serve as an additional venue for

parents and other care providers

for children to receive vaccina-

tions.Immunization of close con-

tacts of children at high risk of

in?uenza-related complications

is intended to reduce their risk

of contagion(ie,“cocooning”).

The practice of cocooning may

help protect infants younger than

6months,because they are too

young to be immunized with in-

?uenza vaccine.Infants younger

than6months also can be pro-

tected through vaccination of their

mothers during pregnancy,with

resulting transplacental transfer

of antibodies.The risk of in?uenza-

associated hospitalization in healthy

children younger than24months

has been shown to be greater

than the risk of hospitalization

in previously recognized high-

risk groups,such as older adults,

during in?uenza season.Children

24through59months of age have

shown higher rates of outpatient

visits and antimicrobial use asso-

ciated with in?uenza-like illnesses

than older children.

8.As soon as the seasonal in?uenza

vaccine is available locally,pedia-

tricians or vaccine administra-

tors should immunize HCP,notify

parents and caregivers of vaccine

availability and the importance of

annual vaccination,and immu-

nize children6months and older

per recommendations,especially

those at high risk of complications

from in?uenza.Health care pro-

vider endorsement plays a major

role in vaccine uptake.A strong

correlation exists between health

care provider endorsement of

in?uenza vaccine and patient ac-

ceptance.Prompt initiation of

in?uenza immunization and contin-

uance of immunization throughout

the in?uenza season,whether or

not in?uenza is circulating(or

has circulated)in the community,

are critical components of an ef-

fective immunization strategy.

Administering the vaccine early

during the in?uenza season is

not believed to pose a signi?cant

risk that immunity might wane be-

fore the end of the season.The

seasonal vaccine is not100%effec-

tive,but it still is the best strategy

available for preventing illness

from in?uenza.It is moderately ef-

fective in reducing the risk for out-

patient medical visits caused by

circulating in?uenza viruses by

approximately one-half to three-

quarters in most people.Even

during seasons when the vaccine

is only moderately effective,in?u-

enza vaccine has been shown to

reduce illness,antibiotic use,doc-

tor visits,time lost from work,

hospitalizations,and deaths.

9.Providers should continue to offer

vaccine until the vaccine expiration

date (June 30,marking the end of the in ?uenza season),because in-?uenza is unpredictable.Protec-tive immune responses persist throughout the in ?uenza season,which can have >1disease peak and may extend into March or later.Although the peak of in ?uenza ac-tivity in the United States tends to occur in January through March,in ?uenza activity can occur in early fall (ie,October and November)or late spring (eg,in ?uenza circulated through the end of May during the 2013–2014season).This approach also provides ample opportunity to administer a second dose of vac-cine when indicated,as detailed in Key Point 6above.In addition,international travel may result in potential exposure to in ?uenza throughout the year.

10.HCP,in ?uenza campaign organiz-ers,and public health agencies

should collaborate to develop im-proved strategies for planning,communication,and administra-tion of vaccines.

Plan to make seasonal in ?u-

enza vaccine easily accessi-ble for all children.Examples include alerts to families that vaccine is available (eg,e-mails,texts,and patient por-tals);creating walk-in in ?u-enza clinics;extending hours beyond routine times during peak vaccination periods;ad-ministering in ?uenza vaccine during both well and sick vis-its;considering how to immu-nize parents,adult caregivers,and siblings at the same time in the same of ?ce setting as children 1;and working with other institutions (eg,schools,child care programs,and reli-gious organizations)or alter-

native care sites,such as emergency departments,to ex-pand venues for administering vaccine.If a child or adult re-ceives in ?uenza vaccine out-side his or her medical home,such as at a pharmacy,retail-based clinic,or another practice,appropriate documentation of immunization should be pro-vided to the patient for his or her medical home and entered into the state immunization reg-istry where possible.

Concerted efforts among the

aforementioned groups,plus vaccine manufacturers,distrib-utors,and payers,also are necessary to prioritize distrib-ution appropriately to the pri-mary care of ?ce setting and patient-centered medical home before other venues,especially when vaccine supplies are de-layed or limited.

Vaccine safety,effectiveness,

and indications must be com-municated properly to the pub-lic.Pediatricians and of ?ce staff should explain the importance of annual in ?uenza vaccination for children and emphasize when a second dose of vaccine is indicated.HCP should act as role models by receiving in-?uenza immunization annually and recommending annual im-munizations to both colleagues and patients.In ?uenza immu-nization programs for HCP ben-e ?t the health of employees,their patients,and members of the community.2

11.Antiviral medications also are im-portant in the control of in ?uenza but are not a substitute for in-?uenza immunization.The neur-aminidase inhibitors (NAIs)oral oseltamivir (Tami ?u;Roche Labo-ratories,Nutley,NJ)and inhaled

FIGURE 2

Number of 2014–2015seasonal in ?uenza vaccine doses for children 6months through 8years of age.For simplicity,this algorithm takes into consideration only doses of seasonal in ?uenza vaccine received since July 1,2010.As an alternative approach in settings where vaccination history from before July 1,2010is available,if a child aged 6months through 8years is known to have received 2or more doses of seasonal in ?uenza vaccine from any previous season and at least 1clearly documented dose of a pH1N1-containing vaccine (ie,any seasonal vaccine since July 1,2010or a monovalent pH1N1vaccine during the 2009–2010season),then the child needs only 1dose for 2014–2015.

FROM THE AMERICAN ACADEMY OF PEDIATRICS

zanamivir(Relenza;GlaxoSmithKline,

Research Triangle Park,NC)are

the only antiviral medications rec-

ommended for chemoprophylaxis

or treatment of in?uenza during

the2014–2015season.Intravenous

preparations of oseltamivir,zana-

mivir,and peramivir are not ap-

proved by the US Food and Drug

Administration(FDA).However,in

consultation with infectious dis-

eases specialists,investigational in-

travenous zanamivir should be

considered for critically ill children,

especially those who are immuno-

compromised or cannot tolerate or

absorb oral or enterically admin-

istered oseltamivir.Recent viral

surveillance and resistance data

indicate that the majority of cur-

rently circulating in?uenza viruses

likely to cause2014–2015seasonal

in?uenza in North America con-

tinue to be sensitive to oseltamivir

and zanamivir.In contrast,amanta-

dine and rimantadine should not

be used,because circulating in?u-

enza A viruses currently have levels

of resistance to these drugs,and

they are not effective against in?u-

enza B viruses.Because resistance

characteristics can change rapidly,

pediatricians should verify suscep-

tibility data at the start of the in-

?uenza season and monitor them

throughout the season.Up-to-date

information can be found on the

AAP Web site(https://www.wendangku.net/doc/b07848293.html, or

https://www.wendangku.net/doc/b07848293.html,/?u),through

state-speci?c AAP chapter Web

sites,or on the CDC Web site

(https://www.wendangku.net/doc/b07848293.html,/?u/index.htm).

SEASONAL INFLUENZA VACCINES Before the2013–2014in?uenza sea-son,only trivalent in?uenza vaccines that included a single in?uenza B strain were available.However,since 1985,2antigenically distinct lineages (ie,Victoria or Yamagata)of in?uenza B viruses have circulated globally.Vac-

cination against1B viral lineage con-

fers little cross-protection against the

other B viral lineage.Thus,trivalent

vaccines offer limited immunity against

circulating in?uenza B strains of the

lineage not present in the vaccine.

Furthermore,in recent years it has

proven dif?cult to predict consistently

which B lineage will predominate dur-

ing a given in?uenza season.Therefore,

a quadrivalent in?uenza vaccine with

in?uenza B strains of both lineages

should offer greater protection.Post-

marketing safety and vaccine effec-

tiveness data are not yet available,

precluding a full risk–bene?t analy-

sis of newer versus previously available

products.

For the2014–2015season,IIVs will be

available for intramuscular(IM)in-

jection in both trivalent(IIV3)and

quadrivalent(IIV4)formulations.The

intranasally administered LAIV will be

available only in a quadrivalent formu-

lation(LAIV4).All quadrivalent vaccines

will contain the identical in?uenza

strains anticipated to circulate during

the2014–2015in?uenza season.

IIVs contain no live virus.IIV3for-

mulations are available for IM and

intradermal(ID)use.The IM formula-

tion of IIV3is licensed and recom-

mended for children6months and

older and adults,including people with

and without chronic medical con-

ditions.The most common adverse

events after IIV administration are lo-

cal injection site pain and tenderness.

Fever may occur within24hours after

immunization in approximately10%to

35%of children younger than2years

but rarely in older children and adults.

Mild systemic symptoms,such as

nausea,lethargy,headache,muscle

aches,and chills,may occur after

administration of IIV3.

An ID formulation of IIV3is licensed for

use in people18through64years of

age.ID vaccine administration involves

a microinjection with a shorter needle

than needles used for IM administra-

tion.The most common adverse events

are redness,induration,swelling,pain,

and itching,which occur at the site of

administration;although all adverse

events occur at a slightly higher rate

with the IM formulation of IIV3,the rate

of pain was similar between ID and IM.

Headache,myalgia,and malaise may

occur and tend to occur at the same

rate as that with the IM formulation of

IIV3.There is no preference for IM or

ID immunization with IIV3in people

18years or older.Therefore,pedia-

tricians may choose to use either the

IM or ID product for their young adult

patients and for any adults they are

vaccinating(ie,as part of a cocooning

strategy).

IIV4is available in IM but not ID for-

mulations.One formulation of IIV4is

licensed for use in children as young as

6months of age.In children,the most

common injection site adverse reac-

tions were pain,redness,and swelling.

The most common systemic adverse

events were drowsiness,irritability,

loss of appetite,fatigue,muscle aches,

headache,arthralgia,and gastroin-

testinal tract symptoms.These events

were reported with comparable fre-

quency among participants receiving

the licensed comparator trivalent vac-

cines.IIV4is an acceptable vaccine for

people6months or older when oth-

erwise appropriate and may offer

broader protection than IIV3.The rela-

tive quantity of doses of IIV4that will be

available is not certain and likely to be

limited.

During the2in?uenza seasons span-

ning2010–2012,there were increased

reports of febrile seizures in the

United States in young children who

received IIV and the13-valent pneu-

mococcal conjugate vaccine(PCV13)

concomitantly,but this has not been

observed in more recent seasons.Si-

multaneous administration of IIV and

PCV13for the2014–2015in?uenza season continues to be recommended when both vaccines are indicated. LAIV4is a quadrivalent live attenuated in?uenza vaccine that is administered intranasally.It is licensed by the FDA for previously healthy people2through 49years of age.The most common-ly reported reactions in children were runny nose or nasal congestion, headache,decreased activity or leth-argy,and sore https://www.wendangku.net/doc/b07848293.html,IV4should not be administered to people with notable nasal congestion that would impede vaccine delivery.The safety of LAIV in people with a history of asthma, diabetes mellitus,or other high-risk medical conditions associated with an elevated risk of complications from in?uenza(see Contraindications and Precautions)has not been established. In a postlicensure surveillance of LAIV over7seasons,the Vaccine Adverse Event Reporting System(VAERS),jointly sponsored by the FDA and CDC,did not identify any new or unexpected safety concerns,although there were reports of use of LAIV in people with a contra-indication or precaution.The use of LAIV in young children with chronic medical conditions,including asthma,has been implemented outside the United States, but the vaccine is not licensed for these indications in the United States.

Two trivalent in?uenza vaccines man-ufactured using technologies that do not use eggs will also be available for people18years or older during the 2014–2015season:cell culture–based inactivated in?uenza vaccine(ccIIV3) and recombinant in?uenza vaccine (RIV3).These manufacturing methods would probably permit a more rapid scale-up of vaccine production when needed,such as during a pandemic. ccIIV3is a trivalent cell culture–based inactivated in?uenza vaccine indicated for people18years or older,admin-istered as an IM https://www.wendangku.net/doc/b07848293.html,IIV3has comparable immunogenicity to US-licensed IIV3comparator vaccines.

Although ccIIV3is manufactured from

virus propagated in Madin Darby ca-

nine kidney cells rather than embry-

onated eggs,before production,seed

virus is created from the World Health

Organization reference virus strains,

which have been passaged in eggs.

However,egg protein is not detectable

in the?nal vaccine,and egg allergy is

not mentioned as a contraindication

in the package insert.Other contra-

indications to vaccine delivery are

similar to those for other IIVs.The

most common solicited adverse reac-

tions included injection site pain,er-

ythema at the injection site,headache,

fatigue,myalgia,and malaise.

RIV3is a recombinant baculovirus–

expressed hemagglutinin vaccine pro-

duced in cell culture.It is indicated

for people18through49years of age

and is administered via IM injection.

The most frequently reported adverse

events were pain,headache,myalgia,

and fatigue.There are no egg proteins

in this version of in?uenza vaccine.

Tables1and2summarize information

on the types of2014–2015seasonal

in?uenza vaccines licensed for im-

munization of children and adults.It is

likely that more than1type or brand

of vaccine may be appropriate for

vaccine recipients.However,vaccina-

tion should not be delayed to obtain

a speci?c product.

A large body of scienti?c evidence de-

monstrates that thimerosal-containing

vaccines are not associated with ele-

vated risk of autism spectrum dis-

orders in children.Therefore,the AAP

extends its strongest support to the

recent World Health Organization rec-

ommendations to retain the use of

thimerosal in the global vaccine supply.

Some people may still raise concerns

about the minute amounts of thimer-

osal in IIV vaccines,and in some states

there is a legislated restriction on the

use of thimerosal-containing vaccines.

The bene?ts of protecting children

against the known risks of in?uenza are

clear.Therefore,children should receive

any available formulation of IIV rather

than delaying immunization while wait-

ing for reduced thimerosal-content or

thimerosal-free vaccines.Although some

formulations of IIV contain only a trace

amount of thimerosal,certain types can

be obtained thimerosal https://www.wendangku.net/doc/b07848293.html,IV4does

not contain thimerosal.Vaccine manufac-

turers are delivering increasing amounts

of thimerosal-free in?uenza vaccine each

year.

INFLUENZA VACCINES AND EGG

ALLERGY

Although most IIV and LAIV vaccines

are produced in eggs and contain

measurable amounts of egg protein,

recent data have shown that IIV ad-

ministered in a single,age-appropriate

dose is well tolerated by most recipi-

ents with a history of egg allergy.More

conservative approaches in children

with a history of egg allergy,such as

skin testing or a2-step graded chal-

lenge,no longer are recommended.No

data have been published on the safety

of administering LAIV to egg-allergic

recipients.

As a precaution,pediatricians should

continue to determine whether the

presumed egg allergy is based on

a mild(ie,hives alone)or severe re-

action(ie,anaphylaxis involving car-

diovascular changes,respiratory or

gastrointestinal tract symptoms,or

reactions that necessitate the use of

epinephrine).Pediatricians should

consult with an allergist for children

with a history of severe reaction.Most

vaccine administration to patients with

egg allergy can occur without the need

for referral.Data indicate that only

approximately1%of children have

immunoglobulin E–mediated sensitiv-

ity to egg,and of those,a rare mi-

nority have a severe allergy.The Joint

Task Force on Practice Parameters,

FROM THE AMERICAN ACADEMY OF PEDIATRICS

representing the American Academy of Allergy,Asthma&Immunology(AAAAI) and the American College of Allergy, Asthma&Immunology(ACAAI),recently published an updated recommenda-tion that special precautions regarding medical setting and waiting periods af-ter administration of IIV to egg-allergic recipients beyond those recommended for any vaccine are not warranted.This concept has not been universally ac-cepted by all allergists,so the AAP rec-ommendation has not changed. Standard immunization practice should include the ability to respond to acute hypersensitivity reactions.Therefore, in?uenza vaccine should be given to children with egg allergy with the following preconditions(Fig3): Appropriate resuscitative equip-

ment must be readily available.3

The vaccine recipient should be ob-

served in the of?ce for30minutes

after immunization,the usual observa-

tion time for receiving immunotherapy.

Providers may consider use of ccIIV3

or RIV3vaccines produced via non–

egg-based technologies for patients

18years or older with egg allergy in

settings in which these vaccines are

available and otherwise age appropri-

https://www.wendangku.net/doc/b07848293.html,IIV3,which does contain trace

amounts of ovalbumin,should be ad-

ministered according to the guidance

for other IIVs(Fig3).RIV3,which con-

tains no ovalbumin,may be adminis-

tered to people with egg allergy of any

severity who are18through49years

of age and do not have other contra-

indications.However,vaccination of pa-

tients with mild egg allergy should

not be delayed if RIV3or ccIIV3is not

available.Instead,any licensed,age-

appropriate IIV should be used.

VACCINE STORAGE AND

ADMINISTRATION

The AAP Storage and Handling Tip

Sheet provides resources for practices

to develop comprehensive vaccine

management protocols to keep the

temperature for vaccine storage con-

stant during a power failure or other

disaster(https://www.wendangku.net/doc/b07848293.html,/immunization/

pediatricians/pdf/DisasterPlanning.pdf).

TABLE1Recommended Seasonal In?uenza Vaccines for Different Age Groups:United States,2014–2015In?uenza Season Vaccine Trade Name Manufacturer Presentation Thimerosal Mercury

Content(μg of Hg per

0.5-mL dose)

Age Group

Inactivated

IIV3Fluzone Sano?Pasteur0.25-mL pre?lled syringe06–35mo

0.5-mL pre?lled syringe0≥36mo

0.5-mL vial0≥36mo

5.0-mL multidose vial25≥6mo IIV3Fluzone Intradermal Sano?Pasteur0.1-mL pre?lled microinjection018–64y IIV3Fluzone HD Sano?Pasteur0.5-mL pre?lled syringe0≥65y

IIV3Fluvirin Novartis0.5-mL pre?lled syringe≤1.0≥4y

5.0-mL multidose vial25≥4y

IIV3Fluarix GlaxoSmithKline0.5-mL pre?lled syringe0≥36mo IIV3FluLaval ID Biomedical Corporation of

Quebec(distributed by

GlaxoSmithKline)

5.0-mL multidose vial25≥36mo

IIV3A?uria CSL Biotherapies

(distributed by Merck)

0.5-mL pre?lled syringe0≥9y a

5-mL multidose vial24.5≥9y a ccIIV3Flucelvax Novartis Vaccines0.5-mL pre?lled syringe0≥18y

IIV4Fluzone Quadrivalent Sano?Pasteur0.25-mL pre?lled syringe06–35mo

0.5-mL pre?lled syringe0≥36mo

0.5-mL vial0≥36mo IIV4Fluarix Quadrivalent GlaxoSmithKline0.5-mL pre?lled syringe0≥36mo IIV4FluLaval Quadrivalent ID Biomedical Corporation of

Quebec(distributed by

GlaxoSmithKline)

5.0-mL multidose vial25≥36mo

Recombinant

RIV3FluBlok Protein Sciences0.5-mL vial018–49y Live attenuated

LAIV4FluMist Quadrivalent MedImmune0.2-mL sprayer02–49y Sources:American Academy of Pediatrics,Committee on Infectious Diseases.Recommendations for prevention and control of in?uenza in children,2013–2014.Pediatrics.2013;132(4): e1089–e1104;and Centers for Disease Control and Prevention.Prevention and control of seasonal in?uenza with vaccines:recommendations of the Advisory Committee on Immunization Practices(ACIP)—United States,2014–2015in?uenza season.MMWR Recomm Rep.2014;63(32):691–697.

a Age indication per package insert is≥5y;however,the Advisory Committee on Immunization Practices recommends A?uria not be used in children6mo through8y of age because of febrile reactions reported in this age group.If no other age-appropriate,licensed inactivated seasonal in?uenza vaccine is available for a child5through8y of age who has a medical condition that increases the child’s risk of in?uenza complications,A?uria can be used;however,pediatricians should discuss with the parents or caregivers the bene?ts and risks of in?uenza vaccination with A?uria before administering this vaccine.

Any of the in?uenza vaccines can be administered at the same visit with all other recommended routine vaccines. Intramuscular Vaccine

The IM formulation of IIV is shipped and stored at2°C to8°C(35°F–46°F).It is administered intramuscularly into the anterolateral thigh of infants and young children and into the deltoid muscle of older children and adults. The volume of vaccine is age depen-dent;infants and toddlers6months through35months of age should re-ceive a dose of0.25mL,and all people 3years(36months)and older should receive0.5mL/dose.

Intradermal Vaccine

The ID formulation of IIV also is shipped and stored at2°C to8°C(35°F–46°F).It is administered intradermally only to people18through64years of age,preferably over the deltoid muscle and

only using the device included in the

vaccine package.Vaccine is supplied in

a single-dose,pre?lled microinjection

system(0.1mL)for adults.The pack-

age insert should be reviewed for full

administration details of this product.

Live Attenuated(Intranasal)

Vaccine

The cold-adapted,temperature-sensitive

LAIV4formulation currently licensed in

the United States must be shipped and

stored at2°C to8°C(35°F–46°F)and

administered intranasally in a pre?lled,

single-use sprayer containing0.2mL of

vaccine.A removable dose divider clip

is attached to the sprayer to administer

0.1mL separately into each nostril.Af-

ter administration of any live virus

vaccine,at least4weeks should pass

before another live virus vaccine is ad-

ministered.

CURRENT RECOMMENDATIONS

Seasonal in?uenza immunization is rec-

ommended for all children6months and

https://www.wendangku.net/doc/b07848293.html,IV should be considered for

healthy children2through8years of age

who have no contraindications or pre-

cautions to the intranasal vaccine.This is

based on a GRADE analysis done by the

CDC,which concluded that there is

greater relative ef?cacy of LAIV as

compared with IIV against laboratory-

con?rmed in?uenza among younger

children.If LAIV is not readily available,IIV

should be used;vaccination should not

be delayed to obtain LAIV.Particular fo-

cus should be on the administration of

IIV for all children and adolescents with

underlying medical conditions associated

with an elevated risk of complications

from in?uenza,including the following:

Asthma or other chronic pulmonary

diseases,including cystic?brosis

TABLE2LAIV4Compared With IIV3and IIV4

Vaccine Characteristic LAIV4IIV3IIV4

Route of administration Intranasal spray Intramuscular or

intradermal injection a

Intramuscular injection a Type of vaccine Live virus Killed virus Killed virus

Product Attenuated,cold adapted Inactivated subvirion

or surface antigen Inactivated subvirion or surface antigen

No.of included virus strains4(2in?uenza A,

2in?uenza B)3(2in?uenza A,1in?uenza B)4(2in?uenza A,

2in?uenza B)

Vaccine virus strains updated Annually Annually Annually Frequency of administration b Annually Annually Annually

Approved age groups All healthy people aged

2–49y All people aged≥6mo

(ID18–64y)

All people aged≥6mo

Interval between2doses in children4wk4wk4wk Can be given to people with medical risk factors for in?uenza-

related complications?

Not preferred Yes Yes Can be given to children with asthma or children aged2–4y

with wheezing in the previous year?

No c Yes Yes Can be simultaneously administered with other vaccines?Yes d Yes d Yes d

If not simultaneously administered,can be administered within 4wk of another live vaccine?No,recommended to

space4wk apart

Yes Yes

Can be administered within4wk of an inactivated vaccine?Yes Yes Yes

Sources:American Academy of Pediatrics,Committee on Infectious Diseases.Recommendations for prevention and control of in?uenza in children,2013–2014.Pediatrics.2013;132(4): e1089–e1104;and Centers for Disease Control and Prevention.Prevention and control of seasonal in?uenza with vaccines:recommendations of the Advisory Committee on Immunization Practices(ACIP)—United States,2014–2015in?uenza season.MMWR Recomm Rep.2014;63(32):691–697.

a The preferred site of IIV intramuscular injection for infants and young children is the anterolateral aspect of the thigh.

b See Fig2for decision algorithm to determine number of doses of seasonal in?uenza vaccine recommended for children during the2014–2015in?uenza season.

c LAIV4is not recommende

d for children with a history of asthma.In the2-through4-y ag

e group,there are children who have a history o

f wheezin

g wit

h respiratory illnesses in whom reactive airway disease is diagnosed and in whom asthma may later be diagnosed.Therefore,because of the potential for increased wheezing after immunization,children2through4y of age with recurrent wheezing or a wheezing episode in the previous12mo should not receive LAIV4.When offering LAIV4to children in this age group,a pediatrician should screen those who might be at higher risk of asthma by asking the parents or guardians of2-,3-,and4-y-olds(24-through59-mo-olds)the question,“In the previous12months,has a health care professional ever told you that your child had wheezing?”If the parents answer“yes”to this question,LAIV4is not recommended for these children.

d LAIV4coadministration has been evaluated systematically only among children12–15mo of ag

e with measles–mumps–rubella and varicella vaccines.IIV coadministration has been evaluated systematically only among adults with pneumococcal polysaccharide and zoster vaccines.

FROM THE AMERICAN ACADEMY OF PEDIATRICS

Hemodynamically signi ?cant car-diac disease Immunosuppressive disorders or therapy

HIV infection

Sickle cell anemia and other hemo-globinopathies

Diseases that necessitate long-term aspirin therapy,including ju-venile idiopathic arthritis or Kawasaki disease

Chronic renal dysfunction

Chronic metabolic disease,includ-ing diabetes mellitus

Any condition that can compro-

mise respiratory function or han-dling of secretions or can increase the risk of aspiration,such as neu-rodevelopmental disorders,spinal cord injuries,seizure disorders,or neuromuscular abnormalities Although universal immunization for all people 6months and older is recom-mended for the 2014–2015in ?uenza season,particular immunization ef-forts with either IIV or LAIV should be made for the following groups to pre-vent transmission of in ?uenza to those at risk,unless contraindicated:

Household contacts and out-of-home

care providers of children younger than 5years and at-risk children of all ages (healthy contacts 2through 49years of age can receive either IIV or LAIV).

Any woman who is pregnant or

considering pregnancy (IIV only),

is in the postpartum period,or is breastfeeding during the in ?u-enza season.Studies have shown that infants born to immunized women have better in ?uenza-related health outcomes.However,accord-ing to Internet panel surveys con-ducted by the CDC,only 51%of pregnant women reported receiv-ing an in ?uenza vaccine during the 2012–2013season,even though both pregnant women and their infants are at higher risk of com-plications.In addition,data from some studies suggest that in-?uenza vaccination in pregnancy may decrease the risk of preterm birth and of giving birth to infants who are small for gestational age.Pregnant women can receive

the

FIGURE 3

Precautions for administering IIV to presumed egg-allergic children.

in?uenza vaccine safely during any trimester.

Children and adolescents of Amer-ican Indian or Alaska Native heri-tage.

HCP or health care volunteers.De-spite the AAP recommendation for mandatory in?uenza immunization for all HCP,2many remain unvacci-nated.As of November2013,the CDC estimated that only62.9%of HCP received the seasonal in?u-enza vaccine.The AAP recommends mandatory vaccination of HCP,be-cause HCP frequently come into contact with patients at high risk of in?uenza illness in their clinical settings.

Close contacts of immunosuppressed people. CONTRAINDICATIONS AND PRECAUTIONS

Minor illnesses,with or without fever, are not contraindications to the use of in?uenza vaccines,particularly among children with mild upper respiratory infection symptoms or allergic rhinitis. Children Who Should Not Be Vaccinated With IIV

Infants younger than6months. Children who have a moderate to severe febrile illness,on the basis of clinical judgment of the clini-cian.

Children Who Should Not Be Vaccinated With LAIV

Children younger than2years. Children who have a moderate to severe febrile illness.

Children with an amount of nasal congestion that would notably im-pede vaccine delivery.

Children2through4years of age with a history of recurrent wheezing or a medically attended wheezing

episode in the previous12months

because of the potential for in-

creased wheezing after immuniza-

tion.In this age range,many

children have a history of wheezing

with respiratory tract illnesses and

are eventually diagnosed with

asthma.Therefore,when offering

LAIV to children24through59

months of age,the pediatrician

should screen them by asking the

parent or guardian,“In the previous

12months,has a health care pro-

fessional ever told you that your

child had wheezing?”If a parent

answers“yes”to this question,LAIV

is not recommended for the child.

IIV would be recommended for the

child to whom LAIV is not given.

Children with the diagnosis of

asthma.

Children with a history of egg allergy.

Children who have received other

live virus vaccines within the last4

weeks;however,other live virus

vaccines can be given on the same

day as LAIV.

Children who have known or sus-

pected immunode?ciency disease

or who are receiving immunosup-

pressive or immunomodulatory ther-

apies.

Children who are receiving aspirin

or other salicylates.

Any woman who is pregnant or

considering pregnancy.

Children with any condition that

can compromise respiratory func-

tion or handling of secretions or

can increase the risk for aspira-

tion,such as neurodevelopmental

disorders,spinal cord injuries,sei-

zure disorders,or neuromuscular

abnormalities.

Children taking an in?uenza antivi-

ral medication should not receive

LAIV until48hours after stopping

the in?uenza antiviral therapy.If

a child recently received LAIV but

has an in?uenza illness for which

antiviral agents are appropriate,the

antiviral agents should be given.Re-

immunization may be indicated be-

cause of the potential effects of

antiviral medications on LAIV rep-

lication and immunogenicity.

Children for Whom IIV Is Preferred

Children with chronic underlying

medical conditions,including meta-

bolic disease,diabetes mellitus,

other chronic disorders of the pul-

monary or cardiovascular systems,

renal dysfunction,or hemoglobinop-

athies.The safety of LAIV in these

populations has not been estab-

lished.These conditions are not

contraindications but are listed un-

der the“Warnings and Precautions”

section of the LAIV package insert.A

precaution is a condition in a recip-

ient that might increase the risk or

seriousness of an adverse reaction

or complicate making another diag-

nosis because of a possible vaccine-

related reaction.A precaution also

may exist for conditions that might

compromise the ability of the vac-

cine to produce immunity.Vaccina-

tion may be recommended in the

presence of a precaution if the ben-

e?t of protection from the vaccine

outweighs any risk.

IIV is the vaccine of choice for anyone in

close contact with a subset of severely

immunocompromised people(ie,those

in a protected environment).IIV is

preferred over LAIV for contacts of

severely immunocompromised people

because of the theoretical risk of in-

fection attributable to LAIV strain in an

immunocompromised contact of an

LAIV-immunized person.Available data

indicate a very low risk of transmission

of the virus in both children and adults

vaccinated with LAIV.HCP immunized

with LAIV may continue to work in most

units of a hospital,including the NICU

and general oncology wards,using

FROM THE AMERICAN ACADEMY OF PEDIATRICS

standard infection control techniques. As a precautionary measure,people recently vaccinated with LAIV should restrict contact with severely immu-nocompromised patients for up to28 days after immunization,although there have been no reports of LAIV transmission from a vaccinated person to an immunocompromised person.In the theoretical scenario in which symptomatic LAIV infection develops in an immunocompromised host,oselta-mivir or zanamivir could be prescribed, because LAIV strains are susceptible to these antiviral medications. SURVEILLANCE

Information about in?uenza surveil-lance is available through the CDC Voice Information System(in?uenza update,888-232-3228)or at www.cdc. gov/?u/index.htm.Although current in?uenza season data on circulating strains do not necessarily predict which and in what proportion strains will circulate in the subsequent sea-son,it is instructive to be aware of 2013–2014in?uenza surveillance data and use them as a guide to empirical therapy until current seasonal data are available from the https://www.wendangku.net/doc/b07848293.html,rma-tion is posted weekly on the CDC Web site(https://www.wendangku.net/doc/b07848293.html,/?u/weekly/?uactivity.htm).

VACCINE IMPLEMENTATION

These updated recommendations for prevention and control of in?uenza in children will have operational and ?scal effects on pediatric practice. Therefore,the AAP has developed implementation guidance on supply, payment,coding,and liability issues; these documents can be found at https://www.wendangku.net/doc/b07848293.html,/implementation. In addition,the AAP’s Partnership for Policy Implementation has developed a series of de?nitions using accepted health information technology stand-ards to assist in the implementation of this guideline in computer systems

and quality measurement efforts.This

document is available at www2.aap.

org/informatics/PPI.html.

USE OF ANTIVIRAL MEDICATIONS

Oral oseltamivir remains the antiviral

drug of choice for the management of

in?uenza infections.Inhaled zanamivir

is an equally acceptable alterna-

tive but is more dif?cult to admin-

ister.Antiviral resistance can emerge

quickly between seasons.If local or

national in?uenza surveillance data

indicate a predominance of a partic-

ular in?uenza strain with a known

antiviral susceptibility pro?le,then

empirical treatment can be directed

toward that strain.For example,all

the in?uenza A(H3N2)and in?uenza B

viruses tested since October1,2013

were sensitive to oseltamivir and

zanamivir during the2013–2014in-

?uenza season.Among the pH1N1

viruses tested for resistance,only

1.2%were found to be resistant to

oseltamivir,and none were found to

be resistant to zanamivir.In contrast,

high levels of resistance to amanta-

dine and rimantadine exist,so these

drugs should not be used in the up-

coming season unless resistance

patterns change signi?cantly.

Current treatment guidelines for

antiviral medications(Table3)are

applicable to both infants and chil-

dren with suspected in?uenza when

known virus strains are circulating

in the community or when infants

or children are con?rmed to have

seasonal in?uenza.

Oseltamivir is available in capsule

and oral suspension formulations.

The commercially manufactured liq-

uid formulation has a concentration

of6mg/mL.If the commercially

manufactured oral suspension is

not available,the capsule may be

opened and the contents mixed

with simple syrup or Oral-Sweet

SF(sugar-free)by retail pharma-

cies to a?nal concentration of6

mg/mL(Table3).

Continuous monitoring of the epi-

demiology,change in severity,and

resistance patterns of in?uenza

strains may lead to new guidance.

Treatment should be offered for:

Any child hospitalized with pre-

sumed in?uenza or with severe,

complicated,or progressive illness

attributable to in?uenza,regardless

of in?uenza immunization status or

whether onset of illness occurred

>48hours before admission.

In?uenza infection of any severity in

children at high risk of complica-

tions of in?uenza infection(Table4),

such as children younger than2

years.

Treatment should be considered for:

Any otherwise healthy child with

in?uenza infection for whom a de-

crease in duration of clinical symp-

toms is felt to be warranted by his

or her pediatrician.The greatest

impact on outcome will occur if

treatment can be initiated within

48hours of illness onset but still

should be considered if later in the

course of illness.

Reviews of available studies by the

CDC,the World Health Organization,

and independent investigators have

consistently found that timely oselta-

mivir treatment can reduce the risks

of complications,including those re-

sulting in hospitalization and death.

Although a2012Cochrane review of

studies primarily in outpatient settings

suggested that oseltamivir may not be

effective in preventing complications

or hospitalizations from in?uenza,its

authors correctly pointed out that the

data reviewed were not always com-

plete,were analyzed in a variety of

treated populations,and used a num-

ber of clinical trial designs.In addition,

a recently revised2014Cochrane

review of NAIs for in?uenza further evaluated published and previously unpublished data from randomized clinical trials largely in healthy out-patients with mild illness.Unlike other analyses of the ef?cacy of antiviral drugs,this Cochrane analysis included both in?uenza virus–infected and noninfected people with in?uenza-like illness.Given the speci?c antiviral activity of NAIs against in?uenza viru-ses,this analytic approach under-estimates the treatment ef?cacy of NAIs and their valuable role in helping to lessen complications in those at high risk for them,including hospi-talized patients.Furthermore,this re-view of outpatients was not designed to assess the effect on severe out-

comes such as hospitalizations or

deaths.

Importantly,treatment with oseltamivir

for children with presumed serious,

complicated,or progressive disease,

irrespective of in?uenza immunization

status or even whether illness began

greater than48hours before admis-

sion,continues to be recommended by

the AAP,CDC,and Infectious Diseases

Society of America(IDSA)(http://www.

https://www.wendangku.net/doc/b07848293.html,/In?uenza_Statement.aspx).

Earlier treatment provides better clini-

cal responses.However,treatment after

48hours of symptoms in adults and

children with moderate to severe dis-

ease or with progressive disease has

been shown to provide some bene?t

and should be strongly considered.In

previous years,the use of double-dose

oseltamivir,particularly for those hos-

pitalized with severe illness caused by

pH1N1,was believed to provide better

outcomes.However,recently published

data from a randomized,prospective

trial with75%of subjects younger than

15years documented no bene?t of

double-dose therapy over standard-

dose therapy.

Dosages for antiviral agents for both

treatment and chemoprophylaxis in

children can be found in Table3and

on the CDC Web site(http://www.cdc.

gov/?u/professionals/antivirals/index.

htm).Children younger than2years

TABLE3Recommended Dosage and Schedule of In?uenza Antiviral Medications for Treatment and Chemoprophylaxis for the2014–2015In?uenza Season:United States

Medication Treatment(5d)Chemoprophylaxis(10d)

Oseltamivir a

Adults75mg twice daily75mg once daily

Children≥12mo

Body wt

≤15kg(≤33lb)30mg twice daily30mg once daily

>15–23kg(33–51lb)45mg twice daily45mg once daily

>23–40kg(>51–88lb)60mg twice daily60mg once daily

>40kg(>88lb)75mg twice daily75mg once daily

Infants9–11mo b 3.5mg/kg per dose twice daily 3.5mg/kg per dose once daily

Term infants0–8mo b3mg/kg per dose twice daily3mg/kg per dose once daily for infants3–8mo;not

recommended for infants<3mo,unless situation judged

critical,because of limited safety and ef?cacy data in this

age group

Preterm infants See details in footnote c

Zanamivir d

Adults10mg(two5-mg inhalations)twice daily10mg(two5-mg inhalations)once daily

Children(≥7y for treatment,≥5y for

chemoprophylaxis)

10mg(two5-mg inhalations)twice daily10mg(two5-mg inhalations)once daily

Sources:Centers for Disease Control and Prevention.Antiviral agents for the treatment and chemoprophylaxis of in?uenza:recommendations of the Advisory Committee on Immunization Practices(ACIP).MMWR Recomm Rep.2011;60(RR-1):1–24;Kimberlin DW,Acosta EP,Prichard MN,et al.National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.Oseltamivir pharmacokinetics,dosing,and resistance among children aged<2y with in?uenza.J Infect Dis.2013;207(5):709–720.

a Oseltamivir is administered orally without regard to meals,although administration with meals may improve gastrointestinal tolerability.Oseltamivir is available as Tami?u in30-mg,45-mg,and75-mg capsules and as a powder for oral suspension that is reconstituted to provide a?nal concentration of6mg/mL.For the6-mg/mL suspension,a30-mg dose is given with5 mL of oral suspension,a45-mg dose is given with7.5mL oral suspension,a60-mg dose is given with10mL oral suspension,and a75-mg dose is given with12.5mL oral suspension.If the commercially manufactured oral suspension is not available,a suspension can be compounded by retail pharmacies(?nal concentration also6mg/mL),based on instructions that are present on the package label.In patients with renal insuf?ciency,the dose should be adjusted on the basis of creatinine clearance.For treatment of patients with creatinine clearance10–30mL/min,administer75mg,once daily,for5d.For chemoprophylaxis of patients with creatinine clearance10–30mL/min,administer30mg,once daily,for10d after exposure or75 mg,once every other day,for10d after exposure(5doses).See https://www.wendangku.net/doc/b07848293.html,/?u/professionals/antivirals/antiviral-drug-resistance.htm.

b Approved by the FDA for children as young as2wk of age.Given preliminary pharmacokineti

c data an

d limited safety data,oseltamivir can b

e used to treat in?uenza in both term and preterm infants from birth because bene?ts o

f therapy are likely to outweigh possible risks of treatment.

c Oseltamivir dosing for preterm infants.The weight-base

d dosing recommendation for preterm infants is lower than for term infants.Preterm infants may hav

e lower clearance o

f oseltamivir because of immature renal function,and doses recommended for full-term infants may lead to very high dru

g concentrations in this age group.Limited data from the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group provide the basis for dosing preterm infants using their postmenstrual age(gestational age+chronological age):1.0mg/kg per dose,orally,twice daily,for those<38wk postmenstrual age;1.5mg/kg per dose,orally,twice daily,for those38through40wk postmenstrual age;3.0mg/kg per dose,orally,twice daily,for those>40wk postmenstrual age.For extremely premature infants(<28wk postmenstrual age),consult a pediatric infectious disease physician.

d Zanamivir is administered by inhalation using a proprietary“Diskhaler”devic

e distributed together with the medication.Zanamivir is a dry powder,not an aerosol,and should not be administered with nebulizers,ventilators,or other devices typically used to administer medications in aerosolized solutions.Zanamivir is not recommended for people with chronic respiratory diseases,such as asthma or chronic obstructive pulmonary disease,which increase the risk o

f bronchospasm.

FROM THE AMERICAN ACADEMY OF PEDIATRICS

are at elevated risk of hospitalization and complications attributable to in?u-enza.The FDA has licensed oseltamivir for children as young as2weeks of age.Given preliminary pharmacoki-netic data and limited safety data, oseltamivir can be used to treat in-?uenza in both term and preterm infants from birth because bene?ts of therapy are likely to outweigh pos-sible risks of treatment.

Clinical judgment(on the basis of un-derlying conditions,disease severity, time since symptom onset,and local in?uenza activity)is an important fac-tor in treatment decisions for pediatric patients who present with in?uenza-like illness.Antiviral treatment should be started as soon as possible after illness onset and should not be delayed while waiting for a de?nitive in?uenza test result because early therapy provides the best outcomes.Recently available rapid antigen tests have moderate sensitivity,even for the pH1N1virus strain,but are not as sensitive as nucleic acid–based molecular diag-nostic techniques(eg,polymerase chain reaction[PCR]assay).Decisions on treatment and infection control can be made based on positive rapid anti-gen tests.However,if rapid test results are negative,PCR techniques should be considered,because they have greater sensitivity for in?uenza infection than antigen tests.Positive results are

helpful,because they may reduce ad-

ditional testing to identify the cause of

the child’s in?uenza-like illness.Treat-

ment should not be withheld in high-

risk patients awaiting PCR results.

People with suspected in?uenza who

present with an uncomplicated febrile

illness typically do not need treatment

with antiviral medications unless they

are at higher risk of in?uenza compli-

cations(eg,children with chronic

medical conditions such as asthma,

diabetes mellitus,hemodynamically

signi?cant cardiac disease,immuno-

suppression,or neurologic and neuro-

developmental disorders),especially in

situations with limited antiviral medi-

cation availability.Antiviral treatment

also should be considered for symp-

tomatic siblings of children younger

than6months or with underlying

medical conditions that predispose

them to complications of in?uenza.If

there is a shortage of antiviral medi-

cations,local public health authorities

should provide additional guidance

about testing and treatment.In past

years,local shortages have occurred

based on uneven drug distribution,but

national shortages have not occurred.

Randomized placebo-controlled stud-

ies showed that oseltamivir and

zanamivir were ef?cacious when ad-

ministered as chemoprophylaxis to

household contacts after a family

member had laboratory-con?rmed

in?uenza.During the2009pandemic,

the emergence of oseltamivir resis-

tance was observed among people

receiving postexposure prophylaxis.

Decisions on whether to administer

antiviral chemoprophylaxis should

take into account the exposed person’s

risk of in?uenza complications,vacci-

nation status,the type and duration of

contact,recommendations from local

or public health authorities,and clin-

ical judgment.Optimally,postexposure

chemoprophylaxis should only be

used when antiviral agents can be

started within48hours of exposure.

Early treatment of high-risk patients

without waiting for laboratory con?r-

mation is an alternative strategy.

Although immunization is the pre-

ferred approach to infection pre-

vention,chemoprophylaxis during an

in?uenza outbreak,as de?ned by the

CDC,is recommended

For children at high risk of compli-

cations from in?uenza for whom in-

?uenza vaccine is contraindicated

For children at high risk during the2

weeks after in?uenza immunization

For family members or HCP who

are unimmunized and are likely

to have ongoing,close exposure to

?Unimmunized children at high

risk

?Unimmunized infants and tod-

dlers who are younger than24

months

For control of in?uenza outbreaks

for unimmunized staff and chil-

dren in a closed institutional set-

ting with children at high risk(eg,

extended-care facilities)

As a supplement to immunization

among children at high risk,includ-

ing children who are immunocom-

promised and may not respond to

vaccine

TABLE4People at Higher Risk of In?uenza Complications Recommended for Antiviral Treatment of Suspected or Con?rmed In?uenza

Children<2y

Adults≥65y

People with chronic pulmonary(including asthma),cardiovascular(except hypertension alone),renal, hepatic,hematologic(including sickle cell disease),or metabolic disorders(including diabetes mellitus) or neurologic and neurodevelopment conditions(including disorders of the brain,spinal cord, peripheral nerve,and muscle such as cerebral palsy,epilepsy[seizure disorders],stroke,intellectual disability[mental retardation],moderate to severe developmental delay,muscular dystrophy,or spinal cord injury)

People with immunosuppression,including that caused by medications or by HIV infection

Women who are pregnant or postpartum(within2wk after delivery)

People<19y who are receiving long-term aspirin therapy

American Indian or Alaska Native people

People who are morbidly obese(ie,BMI≥40)

Residents of nursing homes and other chronic care facilities

Source:Centers for Disease Control and Prevention.Antiviral agents for the treatment and chemoprophylaxis of in?uenza: recommendations of the Advisory Committee on Immunization Practices(ACIP).MMWR Recomm Rep.2011;60(RR-1):1–24.

As postexposure prophylaxis for family members and close con-tacts of an infected person if those people are at high risk of compli-cations from in?uenza

For children at high risk and their family members and close con-tacts,as well as HCP,when circu-lating strains of in?uenza virus in the community are not matched with seasonal in?uenza vaccine strains,on the basis of current data from the CDC and local health departments

These recommendations apply to rou-tine circumstances,but it should be noted that guidance may change on the basis of updated recommendations from the CDC in concert with antiviral availability,local resources,clinical judgment,recommendations from local or public health authorities,risk of in?uenza complications,type and du-ration of exposure contact,and change in epidemiology or severity of in?uenza. Chemoprophylaxis is not recommended for infants younger than3months, unless the situation is judged critical, because of limited safety and ef?cacy data in this age group. Chemoprophylaxis Should Not Be Considered a Substitute for Immunization

In?uenza vaccine should always be of-fered when not contraindicated,even after in?uenza virus has been cir-culating in the community.Antiviral medications currently licensed are im-portant adjuncts to in?uenza immuni-zation for control and prevention of in?uenza disease;toxicities associated with antiviral agents or indiscriminate use might limit availability.Pedia-tricians should inform recipients of antiviral chemoprophylaxis that risk of in?uenza is lowered but still remains while they are taking the medica-tion,and susceptibility to in?uenza re-turns when medication is discontinued.Oseltamivir use is not a contraindication

to immunization with IIV(unlike LAIV).

For recommendations about treat-

ment and chemoprophylaxis against

in?uenza,see Table 3.Among some

high-risk people,both vaccination and

antiviral chemoprophylaxis may be

considered.Updates will be available at

https://www.wendangku.net/doc/b07848293.html,/?u and www.cdc.

gov/?u/professionals/antivirals/index.htm.

FUTURE NEEDS

For the2014–2015season,the AAP does

not have a preferential recommenda-

tion for any type or brand of in?uenza

vaccine over another.This is partly be-

cause the supply and distribution of

newer vaccines may be limited during

the2014–2015season.Moreover,post-

marketing safety and vaccine effective-

ness data are limited,precluding a full

risk–bene?t analysis of newer versus

previously available products.However,

such analyses will be performed as

data become available,and in the future

speci?c vaccines may be preferentially

recommended for particular groups.

A large body of evidence indicates that

even children with severe(anaphylac-

tic)allergic reactions to the inges-

tion of eggs tolerate IIV in a single,

age-appropriate dose.If,as expected,

safety monitoring continues to show no

elevated risk for anaphylactic reactions

in egg-allergic recipients of IIV,special

precautions regarding allergy consul-

tation and waiting periods after ad-

ministration to egg-allergic recipients

beyond those recommended for any

vaccine may no longer be recom-

mended.Studies examining the safety

of LAIV in egg-allergic recipients also

are ongoing.

Efforts should be made to create ad-

equate outreach and infrastructure to

facilitate the optimal distribution of

vaccine so that more people are im-

munized.Pediatricians also should

become more involved in pandemic

preparedness or disaster planning

efforts.A bidirectional partner di-

alogue between pediatricians and

public health decision makers assists

efforts to address children’s issues

during the initial state,regional,and

local plan development stages.Ad-

ditional information about disaster

preparedness can be found at www.

https://www.wendangku.net/doc/b07848293.html,/en-us/advocacy-and-policy/aap-

health-initiatives/children-and-disasters/

Pages/Pediatric-Preparedness-Resource-

Kit.aspx.

Health care for children is best pro-

vided in the medical home,which may

have limited capacity to accommodate

all patients(and their families)seek-

ing in?uenza immunization.With the

greater demand for immunization dur-

ing each in?uenza season,the AAP

and the CDC recommend vaccine ad-

ministration at any visit to the medical

home during in?uenza season when it

is not contraindicated,at specially

arranged vaccine-only sessions,and

through cooperation with community

sites,schools,and child care centers

to provide in?uenza vaccine.If alter-

native venues,including pharmacies

and other retail-based clinics,are used

for immunization,a system of patient

record transfer is bene?cial in main-

taining the accuracy of immuniza-

tion records.Immunization information

systems should be used whenever

available.Two-dimensional barcodes

have been used to facilitate more ef-

?cient and accurate documentation of

vaccine administration,with limited

experience to date.Multiple barriers

appear to affect in?uenza vaccination

coverage for children in foster care,

refugee and immigrant children,and

homeless children.Access to care

issues,lack of immunization records,

and questions about who can provide

consent may be addressed by linking

children with a medical home,using all

health care encounters as vaccination

opportunities,and more consistently

using immunization registry data.

FROM THE AMERICAN ACADEMY OF PEDIATRICS

Cost-effectiveness and logistic feasi-bility of vaccinating everyone continue to be concerns.With universal immu-nization,particular attention is being paid to vaccine supply,distribution, implementation,and?nancing.Po-tential bene?ts of more widespread childhood immunization among recip-ients,their contacts,and the commu-nity include fewer in?uenza cases, fewer outpatient visits and hospital-izations for in?uenza infection,and a decrease in the use of antimicrobial agents,absenteeism from school,and lost parent work time.To administer antiviral therapy optimally in hospi-talized patients with in?uenza who cannot tolerate oral or inhaled anti-viral agents,FDA-approved intravenous NAIs for children also are needed. Continued evaluation of the safety,im-munogenicity,and effectiveness of in-?uenza vaccine,especially for children younger than2years,is important.The potential role of previous in?uenza vaccination on overall vaccine effec-tiveness by virus strain and subject age in preventing outpatient medical visits, hospitalizations,and deaths continues to be evaluated.Continued assessment of the safety of LAIV is warranted as more children receive the vaccine an-nually.In addition,the routine use of LAIV in children with certain respiratory and nonrespiratory chronic medical conditions warrants additional consid-eration.There is also a need for more systematic health service research on in?uenza vaccine uptake and refusal as well as identi?cation of methods to increase uptake.In addition,de-velopment of a safe,immunogenic vaccine for infants younger than6 months is essential.Until such a vac-cine is available for infants younger than6months,vaccination of their mothers during pregnancy is the best way to protect these infants.Breast-feeding also is recommended to protect against in?uenza viruses by activating innate antiviral mechanisms,specif-

ically type1interferons.Mandatory

annual in?uenza immunization of all

HCP has been implemented success-

fully at an increasing number of pedi-

atric institutions.Future efforts should

include broader implementation of

mandatory immunization programs.

Optimal prevention of in?uenza in the

health care setting depends on the

vaccination of at least90%of HCP.

Additional studies are needed to in-

vestigate the extent of offering to im-

munize parents and adult child care

providers in the pediatric of?ce setting;

the level of family contact satisfaction

with this practice;how practices handle

the logistic,liability,legal,and?nancial

barriers that limit or complicate this

service;and,most importantly,how this

practice will affect disease rates in

children and adults.In addition,adju-

vants have been shown to increase

immune responses to in?uenza vac-

cines,but certain adjuvants have been

associated with the development of

narcolepsy in some studies.Additional

studies on the effectiveness and safety

of in?uenza vaccines containing adju-

vants are needed.Finally,efforts to

improve the vaccine development pro-

cess to allow a shorter interval be-

tween identi?cation of vaccine strains

and vaccine production continue.

COMMITTEE ON INFECTIOUS

DISEASES,2014–2015

Carrie L.Byington,MD,FAAP,Chairperson

Elizabeth D.Barnett,MD,FAAP

H.Dele Davies,MD,FAAP

Kathryn M.Edwards,MD,FAAP

Mary Anne Jackson,MD,FAAP,Red Book

Associate Editor

Yvonne A.Maldonado,MD,FAAP

Dennis L.Murray,MD,FAAP,FIDSA

Mobeen H.Rathore,MD,FAAP

Mark H.Sawyer,MD,FAAP

Gordon E.Schutze,MD,FAAP

Rodney E.Willoughby,MD,FAAP

Theoklis E.Zaoutis,MD,FAAP

FORMER COMMITTEE MEMBERS

John S.Bradley MD,FAAP

Walter A.Orenstein,MD,FAAP

EX OFFICIO

Henry H.Bernstein,DO,MHCM,FAAP–Red Book

Online Associate Editor

Michael T.Brady,MD,FAAP–Red Book Associate

Editor

David W.Kimberlin,MD,FAAP–Red Book Editor

Sarah S.Long,MD,FAAP–Red Book Associate

Editor

H.Cody Meissner,MD,FAAP–Visual Red Book

Associate Editor

CONTRIBUTORS

Stuart T.Weinberg,MD,FAAP–Partnership for

Policy Implementation

Rebecca J.Schneyer,BA,and Catherina Yang,BA

–Research Assistants,Cohen Children’s Medi-

cal Center of New York

John M.Kelso,MD,FAAP–Division of Allergy,

Asthma and Immunology,Scripps Clinic,San

Diego,CA

LIAISONS

Marc Fischer,MD,FAAP–Centers for Disease

Control and Prevention

Bruce Gellin,MD,MPH–National Vaccine

Program Of?ce

Richard L.Gorman,MD,FAAP–National Institutes

of Health

Lucia H.Lee,MD,FAAP–Food and Drug

Administration

R.Douglas Pratt,MD–Food and Drug

Administration

Joan Robinson,MD–Canadian Pediatric

Society

Marco Aurelio Palazzi Safadi,MD–Sociedad

Latinoamericana de Infectologia Pediatrica

Jane Seward,MBBS,MPH,FAAP–Centers for

Disease Control and Prevention

Geoffrey Simon,MD,FAAP–Committee on

Practice Ambulatory Medicine

Jeffrey R.Starke,MD,FAAP–American Thoracic

Society

Tina Q.Tan,MD,FAAP–Pediatric Infectious

Diseases Society

STAFF

Jennifer Frantz,MPH

ACKNOWLEDGMENTS

This AAP policy statement was pre-

pared in parallel with CDC recom-

mendations and reports.Much of

this statement is based on literature

reviews,analyses of unpublished data,

and deliberations of CDC staff in collab-

orations with the Advisory Committee

on Immunization Practices In?uenza

Working Group,with liaison from the

AAP.

DOI: 10.1542/peds.2014-2413

; originally published online September 22, 2014;

Pediatrics COMMITTEE ON INFECTIOUS DISEASES

2015

?

Recommendations for Prevention and Control of Influenza in Children, 2014

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