Recommendations for Prevention and Control of Influenza in Children, 2014-2015

 
Recommendations for Prevention and Control of Influenza in Children, 2014-2015
FROM THE AMERICAN ACADEMY OF PEDIATRICS
                                                                                                Organizational Principles to Guide and Define the Child
                                                                                          Health Care System and/or Improve the Health of all Children

POLICY STATEMENT

Recommendations for Prevention and Control of
Influenza in Children, 2014–2015
COMMITTEE ON INFECTIOUS DISEASES
KEY WORDS
                                                                       abstract
influenza, immunization, live attenuated influenza vaccine,              The purpose of this statement is to update recommendations for rou-
inactivated influenza vaccine, vaccine, children, pediatrics
                                                                       tine use of seasonal influenza vaccine and antiviral medications for the
ABBREVIATIONS                                                          prevention and treatment of influenza in children. The American Acad-
AAP—American Academy of Pediatrics                                     emy of Pediatrics recommends annual seasonal influenza immuniza-
ccIIV3—trivalent cell culture-based inactivated influenza vaccine
CDC—Centers for Disease Control and Prevention                         tion for all people 6 months and older, including all children and
FDA—US Food and Drug Administration                                    adolescents. Highlights for the upcoming 2014–2015 season include
GRADE—Grading of Recommendations Assessment, Development,              the following:
and Evaluation
HCP—health care personnel                                              1. The influenza vaccine composition for the 2014–2015 season is
ID—intradermal                                                            unchanged from the 2013–2014 season.
IIV—inactivated influenza vaccine
IIV3—trivalent inactivated influenza vaccine                            2. Both trivalent and quadrivalent influenza vaccines are available in
IIV4—quadrivalent inactivated influenza vaccine                            the United States for the 2014–2015 season.
IM—intramuscular
LAIV—live attenuated influenza vaccine
                                                                       3. Annual universal influenza immunization is indicated with either
LAIV4—quadrivalent live attenuated influenza vaccine                       a trivalent or quadrivalent vaccine (no preference).
NAIs—neuraminidase inhibitors
                                                                       4. Live attenuated influenza vaccine (LAIV) should be considered for
PCR—polymerase chain reaction
PCV13—13-valent pneumococcal conjugate vaccine                            healthy children 2 through 8 years of age who have no contra-
pH1N1—influenza A (H1N1) pandemic virus                                    indications or precautions to the intranasal vaccine. If LAIV is not
RIV3—trivalent recombinant influenza vaccine                               readily available, inactivated influenza vaccine (IIV) should be used;
This document is copyrighted and is property of the American              vaccination should not be delayed to obtain LAIV.
Academy of Pediatrics and its Board of Directors. All authors have
filed conflict of interest statements with the American Academy of       5. The dosing algorithm for administration of influenza vaccine to
Pediatrics. Any conflicts have been resolved through a process             children 6 months through 8 years of age reflects that virus
approved by the Board of Directors. The American Academy of
                                                                          strains in the vaccine have not changed from last season.
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   As always, pediatricians, nurses, and all other health care personnel
course of treatment or serve as a standard of care. Variations,
taking into account individual circumstances, may be appropriate.
                                                                       should be immunized themselves and should promote influenza vac-
                                                                       cine use and infection control measures. In addition, pediatricians
Policy statements from the American Academy of Pediatrics
benefit from expertise and resources of liaisons and internal           should promptly identify clinical influenza infections to enable rapid
(AAP) and external reviewers. However, policy statements from          antiviral treatment, when indicated, to reduce morbidity and mortality.
the American Academy of Pediatrics may not reflect the views of         Pediatrics 2014;134:1–17
the liaisons or the organizations or government agencies that
they represent.
All policy statements from the American Academy of Pediatrics
automatically expire 5 years after publication unless reaffirmed,       INTRODUCTION
revised, or retired at or before that time.
                                                                       The American Academy of Pediatrics (AAP) recommends annual
                                          (Continued on last page)
                                                                       seasonal influenza immunization for all people 6 months and
                                                                       older, including all children and adolescents, during the 2014–
                                                                       2015 influenza season. In addition, special effort should be made to
                                                                       vaccinate people in the following groups:

PEDIATRICS Volume 134, Number 5, November 2014                                                                                                      1
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Recommendations for Prevention and Control of Influenza in Children, 2014-2015
 All children, including infants born              more than two-thirds of children             virus, and 2 deaths were associ-
      preterm, who are 6 months and                 younger than 6 years and almost              ated with dual infection with both
      older with conditions that increase           all children 6 years and older               influenza A and B viruses. Although
      the risk of complications from influ-          spend significant time in child               children with certain conditions
      enza (eg, children with chronic med-          care or school settings outside              are at higher risk of complications,
      ical conditions, such as asthma,              the home. Exposure to groups of              47% of the deaths occurred in chil-
      diabetes mellitus, hemodynamically            children increases the risk of con-          dren with no high-risk underlying
      significant cardiac disease, immuno-           tracting infectious diseases. Chil-          medical condition. Among children
      suppression, or neurologic and neu-           dren younger than 2 years are at             hospitalized with influenza and for
      rodevelopmental disorders);                   elevated risk of hospitalization and         whom medical chart data were
 Children of American Indian or                    complications attributable to influ-          available, approximately 43% had
      Alaska Native heritage                        enza. School-aged children bear              no recorded underlying condition,
                                                    a large influenza disease burden              whereas 26% had underlying asthma
 All household contacts and out-of-                                                             or reactive airway disease (Fig 1). A
                                                    and have a significantly higher
      home care providers of
                                                    chance of seeking influenza-related           recent preliminary observation of
 Ø Children with high-risk condi-                   medical care compared with                   the 2013–2014 influenza season
     tions                                          healthy adults. Reducing influenza            noted a high number of healthy peo-
 Ø Children younger than 5 years,                   virus transmission (eg, appropriate          ple (ranging from infants to older
     especially infants younger than                                                             adults) who needed care in the ICU,
                                                    hand hygiene, respiratory hygiene/
     6 months                                                                                    91% of whom were not previously
                                                    cough etiquette) among children
 All health care personnel (HCP)                   who attend out-of-home child care            vaccinated.
 All child care providers and staff                or school has been shown to de-           3. Both trivalent and quadrivalent in-
 All women who are pregnant, are                   crease the burden of childhood               fluenza vaccines are available in
      considering pregnancy, are in the             influenza and transmission of influ-           the United States for the 2014–
      postpartum period, or are breast-             enza virus to household contacts             2015 season. Neither vaccine for-
      feeding during the influenza sea-              and community members of all                 mulation is preferred over the
      son                                           ages.                                        other. Both vaccines contain an A/
                                                 2. The percentage of outpatient visits          California/7/2009 (H1N1)–like vi-
KEY POINTS RELEVANT FOR THE                         for influenza-like illness, rates of          rus, an A/Texas/50/2012 (H3N2) vi-
2014–2015 INFLUENZA SEASON                          hospitalization, and deaths attrib-          rus, and a B/Massachusetts/2/
                                                    uted to pneumonia and influenza               2012–like virus (B/Yamagata line-
    1. Annual seasonal influenza vac-
                                                                                                 age). The quadrivalent influenza
       cine is recommended for all                  were lower during the 2013–2014
                                                    influenza season when compared                vaccines include an additional B
       people 6 months and older, in-
                                                    with the previous season. As of              virus (B/Brisbane/60/2008–like vi-
       cluding all children and adoles-
                                                    August 23, 2014, 107 laboratory-             rus [B/Victoria lineage]). These
       cents, during the 2014–2015
                                                    confirmed influenza-associated pe-             strains are unchanged from those
       influenza season. It is impor-
                                                    diatric deaths were reported to              in the 2013–2014 seasonal influ-
       tant that household contacts and
                                                    the Centers for Disease Control              enza vaccines.
       out-of-home care providers of chil-
       dren younger than 5 years, es-               and Prevention (CDC) during the           4. Optimal protection is achieved
       pecially infants younger than 6              2013–2014 influenza season. The               through annual immunization. An-
       months, and children of any age              2009 influenza A (H1N1) pandemic              tibody titers wane to 50% of their
       at high risk of complications                (pH1N1) viruses predominated, but            original levels 6 to 12 months af-
       from influenza (eg, children with             influenza A (H3N2) and influenza B             ter vaccination. Although the vac-
       chronic medical conditions, such             viruses also were reported in the            cine strains for the 2014–2015
       as asthma, diabetes mellitus, he-            United States. Of the 107 deaths, 87         season are unchanged from last
       modynamically significant cardiac             were associated with influenza A              season, a repeat dose this season
       disease, immunosuppression, or               viruses, and 16 deaths were asso-            is critical for maintaining protec-
       neurologic and neurodevelopmen-              ciated with influenza B viruses.              tion in all populations.
       tal disorders) receive annual influ-          Two deaths were associated with           5. Using the Grading of Recommen-
       enza vaccine. In the United States,          an undetermined type of influenza             dations Assessment, Development,

2      FROM THE AMERICAN ACADEMY OF PEDIATRICS
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Recommendations for Prevention and Control of Influenza in Children, 2014-2015
FROM THE AMERICAN ACADEMY OF PEDIATRICS

FIGURE 1
Selected underlying medical conditions in patients hospitalized with laboratory-confirmed influenza, FluSurv-NET 2013–2014. Source: Centers for Disease
Control and Prevention. FluView 2013–2014 Preliminary Data as of August 23, 2014. Available at: http://gis.cdc.gov/grasp/fluview/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 deficiency, leukemia, lymphoma, HIV/AIDS, and the use of immunosuppressive
medications. Metabolic disorders include conditions such as diabetes mellitus, thyroid dysfunction, adrenal insufficiency, 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 >30 kg/m2. Pregnancy percentage
calculated by using number of female cases aged between 15 and 44 years 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.

     and Evaluation (GRADE) frame-                       age). The risk of adverse events                     tion on the basis of demonstration
     work, the CDC Advisory Committee                    after immunization, including fe-                    of superior efficacy of LAIV (ages 2
     on Immunization Practices (ACIP)                    ver, wheezing, and serious adverse                   through 6 years) and for program-
     systematically reviewed the evi-                    events, appears to be similar for                    matic consistency (8 years is the
     dence pertaining to the efficacy                     LAIV and IIV. Therefore, LAIV should                 upper age limit for receipt of 2
     of live attenuated influenza vaccine                 be considered for healthy children                   doses of influenza vaccine in a pre-
     (LAIV) and inactivated influenza                     2 through 8 years of age who have                    viously unvaccinated child).
     vaccine (IIV) for healthy children.                 no contraindications or precau-                  6. The number of seasonal influenza
     It concluded that there is greater                  tions to the intranasal vaccine. If                 vaccine doses to be administered
     relative efficacy of LAIV as com-                    LAIV is not readily available, IIV                  in the 2014–2015 influenza season
     pared with IIV against laboratory-                  should be used; vaccination should                  depends on the child’s age at the
     confirmed influenza among younger                     not be delayed to obtain LAIV. The                  time of the first administered
     children (based on 2 studies in-                    age of 8 years is selected as the                   dose and his or her vaccine his-
     cluding children up to 6 years of                   upper limit for this recommenda-                    tory (Fig 2):

PEDIATRICS Volume 134, Number 5, November 2014                                                                                                        3
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 Influenza vaccines are not li-               providing influenza immunization              shown higher rates of outpatient
          censed for administration to              for parents and other care pro-              visits and antimicrobial use asso-
          infants younger than 6 months.            viders of children if the practice           ciated with influenza-like illnesses
       Children 9 years and older                  is acceptable to both pediatricians          than older children.
          need only 1 dose.                         and the adults who are to be vac-         8. As soon as the seasonal influenza
                                                    cinated.1 There are important medi-
       Children 6 months through 8                 cal liability issues and medical
                                                                                                 vaccine is available locally, pedia-
          years of age receiving the sea-                                                        tricians or vaccine administra-
                                                    record documentation require-                tors should immunize HCP, notify
          sonal influenza vaccine for the
                                                    ments that must be addressed                 parents and caregivers of vaccine
          first time should receive a sec-
                                                    before a pediatrician begins immu-           availability and the importance of
          ond dose this season at least 4           nizing adults (see details at www.
          weeks after the first dose.                                                             annual vaccination, and immu-
                                                    aapredbook.org/implementation).              nize children 6 months and older
       Children 6 months through 8                 Pediatricians are reminded to                per recommendations, especially
          years of age need only 1 dose             document the recommendation                  those at high risk of complications
          of vaccine in 2014–2015 if they           for adult immunization in the vul-           from influenza. Health care pro-
          have received it according to             nerable child’s medical record. In           vider endorsement plays a major
          any of the following scenarios:           addition, adults should still be             role in vaccine uptake. A strong
          ✓ At least 1 dose of 2013–                encouraged to have a medical
                                                                                                 correlation exists between health
            2014 seasonal influenza                  home and communicate their
                                                                                                 care provider endorsement of
            vaccine.                                immunization status to their pri-
                                                                                                 influenza vaccine and patient ac-
          ✓ 2 or more doses of sea-                 mary care provider. Offering im-
                                                                                                 ceptance. Prompt initiation of
            sonal vaccine since July 1,             munizations in the pediatric
                                                                                                 influenza immunization and contin-
            2010.                                   practice setting would not be
                                                                                                 uance of immunization throughout
                                                    intended to undermine the adult
          ✓ 2 or more doses of seasonal                                                          the influenza season, whether or
                                                    medical home model but could
            influenza vaccine from any                                                            not influenza is circulating (or
                                                    serve as an additional venue for
            previous season and at least                                                         has circulated) in the community,
                                                    parents and other care providers
            1 clearly documented dose of                                                         are critical components of an ef-
                                                    for children to receive vaccina-
            a pH1N1-containing vaccine                                                           fective immunization strategy.
                                                    tions. Immunization of close con-
            (ie, any seasonal vaccine                                                            Administering the vaccine early
                                                    tacts of children at high risk of
            since July 1, 2010 or a mono-                                                        during the influenza season is
                                                    influenza-related complications
            valent pH1N1 vaccine during                                                          not believed to pose a significant
                                                    is intended to reduce their risk
            the 2009–2010 season).                                                               risk that immunity might wane be-
                                                    of contagion (ie, “cocooning”).
           Children in this age group for                                                        fore the end of the season. The
                                                    The practice of cocooning may
           whom one of these conditions             help protect infants younger than            seasonal vaccine is not 100% effec-
           is not met need 2 doses in               6 months, because they are too               tive, but it still is the best strategy
           2014–2015 to be adequately               young to be immunized with in-               available for preventing illness
           primed. Vaccination should               fluenza vaccine. Infants younger              from influenza. It is moderately ef-
           not be delayed to obtain a spe-          than 6 months also can be pro-               fective in reducing the risk for out-
           cific product for either dose.            tected through vaccination of their          patient medical visits caused by
           Any available, age-appropriate           mothers during pregnancy, with               circulating influenza viruses by
           trivalent or quadrivalent vac-           resulting transplacental transfer            approximately one-half to three-
           cine can be used; IIV and LAIV           of antibodies. The risk of influenza-         quarters in most people. Even
           are considered interchange-              associated hospitalization in healthy        during seasons when the vaccine
           able. A child who receives only          children younger than 24 months              is only moderately effective, influ-
           1 of the 2 doses as a quadriva-          has been shown to be greater                 enza vaccine has been shown to
           lent formulation is likely to be         than the risk of hospitalization             reduce illness, antibiotic use, doc-
           less primed against the addi-            in previously recognized high-               tor visits, time lost from work,
           tional B virus.                          risk groups, such as older adults,           hospitalizations, and deaths.
    7. Pediatric offices may choose to               during influenza season. Children          9. Providers should continue to offer
       serve as an alternative venue for            24 through 59 months of age have             vaccine until the vaccine expiration

4      FROM THE AMERICAN ACADEMY OF PEDIATRICS
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                                                                                                                  native care sites, such as
                                                                                                                  emergency departments, to ex-
                                                                                                                  pand venues for administering
                                                                                                                  vaccine. If a child or adult re-
                                                                                                                  ceives influenza 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-
FIGURE 2
Number of 2014–2015 seasonal influenza vaccine doses for children 6 months through 8 years of age.
                                                                                                                  ution appropriately to the pri-
For simplicity, this algorithm takes into consideration only doses of seasonal influenza vaccine received          mary care office setting and
since July 1, 2010. As an alternative approach in settings where vaccination history from before July 1,          patient-centered medical home
2010 is available, if a child aged 6 months through 8 years is known to have received 2 or more doses
of seasonal influenza vaccine from any previous season and at least 1 clearly documented dose of                   before other venues, especially
a pH1N1-containing vaccine (ie, any seasonal vaccine since July 1, 2010 or a monovalent pH1N1 vaccine             when vaccine supplies are de-
during the 2009–2010 season), then the child needs only 1 dose for 2014–2015.                                     layed or limited.
                                                                                                                Vaccine safety, effectiveness,
     date (June 30, marking the end of                      should collaborate to develop im-                     and indications must be com-
     the influenza season), because in-                      proved strategies for planning,                       municated properly to the pub-
     fluenza is unpredictable. Protec-                       communication, and administra-                        lic. Pediatricians and office staff
     tive immune responses persist                          tion of vaccines.                                     should explain the importance
     throughout the influenza season,                         Plan to make seasonal influ-                         of annual influenza vaccination
     which can have >1 disease peak                             enza vaccine easily accessi-                      for children and emphasize
     and may extend into March or later.                        ble for all children. Examples                    when a second dose of vaccine
     Although the peak of influenza ac-                          include alerts to families                        is indicated. HCP should act as
     tivity in the United States tends to                       that vaccine is available (eg,                    role models by receiving in-
     occur in January through March,                            e-mails, texts, and patient por-                  fluenza immunization annually
     influenza activity can occur in early                       tals); creating walk-in influ-                     and recommending annual im-
     fall (ie, October and November) or                         enza clinics; extending hours                     munizations to both colleagues
     late spring (eg, influenza circulated                       beyond routine times during                       and patients. Influenza immu-
     through the end of May during the                          peak vaccination periods; ad-                     nization programs for HCP ben-
     2013–2014 season). This approach                           ministering influenza vaccine                      efit the health of employees,
     also provides ample opportunity to                         during both well and sick vis-                    their patients, and members
     administer a second dose of vac-                           its; considering how to immu-                     of the community.2
     cine when indicated, as detailed                           nize parents, adult caregivers,            11. Antiviral medications also are im-
     in Key Point 6 above. In addition,                         and siblings at the same time                  portant in the control of influenza
     international travel may result in                         in the same office setting as                   but are not a substitute for in-
     potential exposure to influenza                             children1; and working with                    fluenza immunization. The neur-
     throughout the year.                                       other institutions (eg, schools,               aminidase inhibitors (NAIs) oral
10. HCP, influenza campaign organiz-                             child care programs, and reli-                 oseltamivir (Tamiflu; Roche Labo-
    ers, and public health agencies                             gious organizations) or alter-                 ratories, Nutley, NJ) and inhaled

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zanamivir (Relenza; GlaxoSmithKline,      B viruses have circulated globally. Vac-     a microinjection with a shorter needle
    Research Triangle Park, NC) are           cination against 1 B viral lineage con-      than needles used for IM administra-
    the only antiviral medications rec-       fers little cross-protection against the     tion. The most common adverse events
    ommended for chemoprophylaxis             other B viral lineage. Thus, trivalent       are redness, induration, swelling, pain,
    or treatment of influenza during           vaccines offer limited immunity against      and itching, which occur at the site of
    the 2014–2015 season. Intravenous         circulating influenza B strains of the        administration; although all adverse
    preparations of oseltamivir, zana-        lineage not present in the vaccine.          events occur at a slightly higher rate
    mivir, and peramivir are not ap-          Furthermore, in recent years it has          with the IM formulation of IIV3, the rate
    proved by the US Food and Drug            proven difficult to predict consistently      of pain was similar between ID and IM.
    Administration (FDA). However, in         which B lineage will predominate dur-        Headache, myalgia, and malaise may
    consultation with infectious dis-         ing a given influenza season. Therefore,      occur and tend to occur at the same
    eases specialists, investigational in-    a quadrivalent influenza vaccine with         rate as that with the IM formulation of
    travenous zanamivir should be             influenza B strains of both lineages          IIV3. There is no preference for IM or
    considered for critically ill children,   should offer greater protection. Post-       ID immunization with IIV3 in people
    especially those who are immuno-          marketing safety and vaccine effec-          18 years or older. Therefore, pedia-
    compromised or cannot tolerate or         tiveness data are not yet available,         tricians may choose to use either the
    absorb oral or enterically admin-         precluding a full risk–benefit analy-         IM or ID product for their young adult
    istered oseltamivir. Recent viral         sis of newer versus previously available     patients and for any adults they are
    surveillance and resistance data          products.                                    vaccinating (ie, as part of a cocooning
    indicate that the majority of cur-        For the 2014–2015 season, IIVs will be       strategy).
    rently circulating influenza viruses       available for intramuscular (IM) in-         IIV4 is available in IM but not ID for-
    likely to cause 2014–2015 seasonal        jection in both trivalent (IIV3) and         mulations. One formulation of IIV4 is
    influenza in North America con-            quadrivalent (IIV4) formulations. The        licensed for use in children as young as
    tinue to be sensitive to oseltamivir      intranasally administered LAIV will be       6 months of age. In children, the most
    and zanamivir. In contrast, amanta-       available only in a quadrivalent formu-      common injection site adverse reac-
    dine and rimantadine should not           lation (LAIV4). All quadrivalent vaccines    tions were pain, redness, and swelling.
    be used, because circulating influ-        will contain the identical influenza          The most common systemic adverse
    enza A viruses currently have levels      strains anticipated to circulate during      events were drowsiness, irritability,
    of resistance to these drugs, and         the 2014–2015 influenza season.               loss of appetite, fatigue, muscle aches,
    they are not effective against influ-      IIVs contain no live virus. IIV3 for-        headache, arthralgia, and gastroin-
    enza B viruses. Because resistance        mulations are available for IM and           testinal tract symptoms. These events
    characteristics can change rapidly,       intradermal (ID) use. The IM formula-        were reported with comparable fre-
    pediatricians should verify suscep-       tion of IIV3 is licensed and recom-          quency among participants receiving
    tibility data at the start of the in-     mended for children 6 months and             the licensed comparator trivalent vac-
    fluenza season and monitor them            older and adults, including people with      cines. IIV4 is an acceptable vaccine for
    throughout the season. Up-to-date         and without chronic medical con-             people 6 months or older when oth-
    information can be found on the           ditions. The most common adverse             erwise appropriate and may offer
    AAP Web site (www.aap.org or              events after IIV administration are lo-      broader protection than IIV3. The rela-
    www.aapredbook.org/flu), through           cal injection site pain and tenderness.      tive quantity of doses of IIV4 that will be
    state-specific AAP chapter Web             Fever may occur within 24 hours after        available is not certain and likely to be
    sites, or on the CDC Web site             immunization in approximately 10% to         limited.
    (www.cdc.gov/flu/index.htm).               35% of children younger than 2 years         During the 2 influenza seasons span-
                                              but rarely in older children and adults.     ning 2010–2012, there were increased
SEASONAL INFLUENZA VACCINES                   Mild systemic symptoms, such as              reports of febrile seizures in the
Before the 2013–2014 influenza sea-            nausea, lethargy, headache, muscle           United States in young children who
son, only trivalent influenza vaccines         aches, and chills, may occur after           received IIV and the 13-valent pneu-
that included a single influenza B             administration of IIV3.                      mococcal conjugate vaccine (PCV13)
strain were available. However, since         An ID formulation of IIV3 is licensed for    concomitantly, but this has not been
1985, 2 antigenically distinct lineages       use in people 18 through 64 years of         observed in more recent seasons. Si-
(ie, Victoria or Yamagata) of influenza        age. ID vaccine administration involves      multaneous administration of IIV and

6   FROM THE AMERICAN ACADEMY OF PEDIATRICS
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PCV13 for the 2014–2015 influenza                 licensed IIV3 comparator vaccines.         The benefits of protecting children
season continues to be recommended               Although ccIIV3 is manufactured from       against the known risks of influenza are
when both vaccines are indicated.                virus propagated in Madin Darby ca-        clear. Therefore, children should receive
LAIV4 is a quadrivalent live attenuated          nine kidney cells rather than embry-       any available formulation of IIV rather
influenza vaccine that is administered            onated eggs, before production, seed       than delaying immunization while wait-
intranasally. It is licensed by the FDA for      virus is created from the World Health     ing for reduced thimerosal-content or
previously healthy people 2 through              Organization reference virus strains,      thimerosal-free vaccines. Although some
49 years of age. The most common-                which have been passaged in eggs.          formulations of IIV contain only a trace
ly reported reactions in children                However, egg protein is not detectable     amount of thimerosal, certain types can
were runny nose or nasal congestion,             in the final vaccine, and egg allergy is    be obtained thimerosal free. LAIV4 does
headache, decreased activity or leth-            not mentioned as a contraindication        not contain thimerosal. Vaccine manufac-
argy, and sore throat. LAIV4 should not          in the package insert. Other contra-       turers are delivering increasing amounts
be administered to people with notable           indications to vaccine delivery are        of thimerosal-free influenza vaccine each
nasal congestion that would impede               similar to those for other IIVs. The       year.
vaccine delivery. The safety of LAIV in          most common solicited adverse reac-
people with a history of asthma,                 tions included injection site pain, er-    INFLUENZA VACCINES AND EGG
diabetes mellitus, or other high-risk            ythema at the injection site, headache,    ALLERGY
medical conditions associated with an            fatigue, myalgia, and malaise.
                                                                                            Although most IIV and LAIV vaccines
elevated risk of complications from              RIV3 is a recombinant baculovirus–         are produced in eggs and contain
influenza (see Contraindications and              expressed hemagglutinin vaccine pro-       measurable amounts of egg protein,
Precautions) has not been established.           duced in cell culture. It is indicated     recent data have shown that IIV ad-
In a postlicensure surveillance of LAIV          for people 18 through 49 years of age      ministered in a single, age-appropriate
over 7 seasons, the Vaccine Adverse              and is administered via IM injection.      dose is well tolerated by most recipi-
Event Reporting System (VAERS), jointly          The most frequently reported adverse       ents with a history of egg allergy. More
sponsored by the FDA and CDC, did not            events were pain, headache, myalgia,       conservative approaches in children
identify any new or unexpected safety            and fatigue. There are no egg proteins     with a history of egg allergy, such as
concerns, although there were reports            in this version of influenza vaccine.       skin testing or a 2-step graded chal-
of use of LAIV in people with a contra-          Tables 1 and 2 summarize information       lenge, no longer are recommended. No
indication or precaution. The use of LAIV        on the types of 2014–2015 seasonal         data have been published on the safety
in young children with chronic medical           influenza vaccines licensed for im-         of administering LAIV to egg-allergic
conditions, including asthma, has been           munization of children and adults. It is   recipients.
implemented outside the United States,           likely that more than 1 type or brand      As a precaution, pediatricians should
but the vaccine is not licensed for these        of vaccine may be appropriate for          continue to determine whether the
indications in the United States.                vaccine recipients. However, vaccina-      presumed egg allergy is based on
Two trivalent influenza vaccines man-             tion should not be delayed to obtain       a mild (ie, hives alone) or severe re-
ufactured using technologies that do             a specific product.                         action (ie, anaphylaxis involving car-
not use eggs will also be available for          A large body of scientific evidence de-     diovascular changes, respiratory or
people 18 years or older during the              monstrates that thimerosal-containing      gastrointestinal tract symptoms, or
2014–2015 season: cell culture–based             vaccines are not associated with ele-      reactions that necessitate the use of
inactivated influenza vaccine (ccIIV3)            vated risk of autism spectrum dis-         epinephrine). Pediatricians should
and recombinant influenza vaccine                 orders in children. Therefore, the AAP     consult with an allergist for children
(RIV3). These manufacturing methods              extends its strongest support to the       with a history of severe reaction. Most
would probably permit a more rapid               recent World Health Organization rec-      vaccine administration to patients with
scale-up of vaccine production when              ommendations to retain the use of          egg allergy can occur without the need
needed, such as during a pandemic.               thimerosal in the global vaccine supply.   for referral. Data indicate that only
ccIIV3 is a trivalent cell culture–based         Some people may still raise concerns       approximately 1% of children have
inactivated influenza vaccine indicated           about the minute amounts of thimer-        immunoglobulin E–mediated sensitiv-
for people 18 years or older, admin-             osal in IIV vaccines, and in some states   ity to egg, and of those, a rare mi-
istered as an IM injection. ccIIV3 has           there is a legislated restriction on the   nority have a severe allergy. The Joint
comparable immunogenicity to US-                 use of thimerosal-containing vaccines.     Task Force on Practice Parameters,

PEDIATRICS Volume 134, Number 5, November 2014                                                                                     7
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TABLE 1 Recommended Seasonal Influenza Vaccines for Different Age Groups: United States, 2014–2015 Influenza Season
     Vaccine                  Trade Name                         Manufacturer                              Presentation                      Thimerosal Mercury              Age Group
                                                                                                                                            Content (μg of Hg per
                                                                                                                                                0.5-mL dose)
Inactivated
   IIV3                  Fluzone                        Sanofi Pasteur                            0.25-mL prefilled syringe                              0                     6–35 mo
                                                                                                 0.5-mL prefilled syringe                               0                     ≥36 mo
                                                                                                 0.5-mL vial                                           0                     ≥36 mo
                                                                                                 5.0-mL multidose vial                                25                     ≥6 mo
    IIV3                 Fluzone Intradermal            Sanofi Pasteur                            0.1-mL prefilled microinjection                        0                     18–64 y
    IIV3                 Fluzone HD                     Sanofi Pasteur                            0.5-mL prefilled syringe                               0                     ≥65 y
    IIV3                 Fluvirin                       Novartis                                 0.5-mL prefilled syringe                              ≤1.0                   ≥4 y
                                                                                                 5.0-mL multidose vial                                25                     ≥4 y
    IIV3                 Fluarix                        GlaxoSmithKline                          0.5-mL prefilled syringe                               0                     ≥36 mo
    IIV3                 FluLaval                       ID Biomedical Corporation of             5.0-mL multidose vial                                25                     ≥36 mo
                                                           Quebec (distributed by
                                                           GlaxoSmithKline)
    IIV3                 Afluria                         CSL Biotherapies                         0.5-mL prefilled syringe                                0                    ≥9 ya
                                                           (distributed by Merck)
                                                                                                 5-mL multidose vial                                  24.5                   ≥9 ya
    ccIIV3               Flucelvax                      Novartis Vaccines                        0.5-mL prefilled syringe                               0                     ≥18 y
    IIV4                 Fluzone Quadrivalent           Sanofi Pasteur                            0.25-mL prefilled syringe                              0                     6–35 mo
                                                                                                 0.5-mL prefilled syringe                               0                     ≥36 mo
                                                                                                 0.5-mL vial                                           0                     ≥36 mo
    IIV4                 Fluarix Quadrivalent           GlaxoSmithKline                          0.5-mL prefilled syringe                               0                     ≥36 mo
    IIV4                 FluLaval Quadrivalent          ID Biomedical Corporation of             5.0-mL multidose vial                                25                     ≥36 mo
                                                           Quebec (distributed by
                                                           GlaxoSmithKline)
Recombinant
   RIV3                  FluBlok                        Protein Sciences                         0.5-mL vial                                            0                    18–49y
Live attenuated
   LAIV4                 FluMist Quadrivalent           MedImmune                                0.2-mL sprayer                                         0                    2–49 y
Sources: American Academy of Pediatrics, Committee on Infectious Diseases. Recommendations for prevention and control of influenza in children, 2013–2014. Pediatrics. 2013;132(4):
e1089–e1104; and Centers for Disease Control and Prevention. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization
Practices (ACIP)—United States, 2014–2015 influenza season. MMWR Recomm Rep. 2014;63(32):691–697.
a
  Age indication per package insert is ≥5 y; however, the Advisory Committee on Immunization Practices recommends Afluria not be used in children 6 mo through 8 y of age because of
febrile reactions reported in this age group. If no other age-appropriate, licensed inactivated seasonal influenza vaccine is available for a child 5 through 8 y of age who has a medical
condition that increases the child’s risk of influenza complications, Afluria can be used; however, pediatricians should discuss with the parents or caregivers the benefits and risks of
influenza vaccination with Afluria before administering this vaccine.

representing the American Academy of                            Appropriate resuscitative equip-                              severity who are 18 through 49 years
Allergy, Asthma & Immunology (AAAAI)                                ment must be readily available.                 3          of age and do not have other contra-
and the American College of Allergy,                            The vaccine recipient should be ob-                           indications. However, vaccination of pa-
Asthma & Immunology (ACAAI), recently                               served in the office for 30 minutes                         tients with mild egg allergy should
published an updated recommenda-                                                                                               not be delayed if RIV3 or ccIIV3 is not
                                                                    after immunization, the usual observa-
tion that special precautions regarding                                                                                        available. Instead, any licensed, age-
                                                                    tion time for receiving immunotherapy.
medical setting and waiting periods af-                                                                                        appropriate IIV should be used.
ter administration of IIV to egg-allergic                      Providers may consider use of ccIIV3
recipients beyond those recommended                            or RIV3 vaccines produced via non–
                                                               egg-based technologies for patients                             VACCINE STORAGE AND
for any vaccine are not warranted. This
                                                               18 years or older with egg allergy in                           ADMINISTRATION
concept has not been universally ac-
cepted by all allergists, so the AAP rec-                      settings in which these vaccines are                            The AAP Storage and Handling Tip
ommendation has not changed.                                   available and otherwise age appropri-                           Sheet provides resources for practices
Standard immunization practice should                          ate. ccIIV3, which does contain trace                           to develop comprehensive vaccine
include the ability to respond to acute                        amounts of ovalbumin, should be ad-                             management protocols to keep the
hypersensitivity reactions. Therefore,                         ministered according to the guidance                            temperature for vaccine storage con-
influenza vaccine should be given to                            for other IIVs (Fig 3). RIV3, which con-                        stant during a power failure or other
children with egg allergy with the                             tains no ovalbumin, may be adminis-                             disaster (www2.aap.org/immunization/
following preconditions (Fig 3):                               tered to people with egg allergy of any                         pediatricians/pdf/DisasterPlanning.pdf).

8          FROM THE AMERICAN ACADEMY OF PEDIATRICS
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FROM THE AMERICAN ACADEMY OF PEDIATRICS

TABLE 2 LAIV4 Compared With IIV3 and IIV4
                       Vaccine Characteristic                                             LAIV4                                    IIV3                                   IIV4
Route of administration                                                        Intranasal spray                    Intramuscular or                           Intramuscular injectiona
                                                                                                                      intradermal injectiona
Type of vaccine                                                                Live virus                          Killed virus                               Killed virus
Product                                                                        Attenuated, cold adapted            Inactivated subvirion                      Inactivated subvirion or
                                                                                                                      or surface antigen                         surface antigen
No. of included virus strains                                                  4 (2 influenza A,                    3 (2 influenza A, 1 influenza B)             4 (2 influenza A,
                                                                                  2 influenza B)                                                                  2 influenza B)
Vaccine virus strains updated                                                  Annually                            Annually                                   Annually
Frequency of administrationb                                                   Annually                            Annually                                   Annually
Approved age groups                                                            All healthy people aged             All people aged ≥6 mo                      All people aged ≥6 mo
                                                                                  2–49 y                              (ID 18–64 y)
Interval between 2 doses in children                                           4 wk                                4 wk                                       4 wk
Can be given to people with medical risk factors for influenza-                 Not preferred                       Yes                                        Yes
   related complications?
Can be given to children with asthma or children aged 2–4 y                    Noc                                 Yes                                        Yes
   with wheezing in the previous year?
Can be simultaneously administered with other vaccines?                        Yesd                                Yesd                                       Yesd
   If not simultaneously administered, can be administered within              No, recommended to                  Yes                                        Yes
       4 wk of another live vaccine?                                             space 4 wk apart
Can be administered within 4 wk of an inactivated vaccine?                     Yes                                 Yes                                        Yes
Sources: American Academy of Pediatrics, Committee on Infectious Diseases. Recommendations for prevention and control of influenza in children, 2013–2014. Pediatrics. 2013;132(4):
e1089–e1104; and Centers for Disease Control and Prevention. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization
Practices (ACIP)—United States, 2014–2015 influenza 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 Fig 2 for decision algorithm to determine number of doses of seasonal influenza vaccine recommended for children during the 2014–2015 influenza season.
c
  LAIV4 is not recommended for children with a history of asthma. In the 2- through 4-y age group, there are children who have a history of wheezing with 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, children 2 through 4 y
of age with recurrent wheezing or a wheezing episode in the previous 12 mo should not receive LAIV4. When offering LAIV4 to children in this age group, a pediatrician should screen those
who might be at higher risk of asthma by asking the parents or guardians of 2-, 3-, and 4-y-olds (24- through 59-mo-olds) the question, “In the previous 12 months, has a health care
professional ever told you that your child had wheezing?” If the parents answer “yes” to this question, LAIV4 is not recommended for these children.
d
  LAIV4 coadministration has been evaluated systematically only among children 12–15 mo of age with measles–mumps–rubella and varicella vaccines. IIV coadministration has been
evaluated systematically only among adults with pneumococcal polysaccharide and zoster vaccines.

Any of the influenza vaccines can be                             preferably over the deltoid muscle and                          CURRENT RECOMMENDATIONS
administered at the same visit with all                         only using the device included in the                           Seasonal influenza immunization is rec-
other recommended routine vaccines.                             vaccine package. Vaccine is supplied in
                                                                                                                                ommended for all children 6 months and
                                                                a single-dose, prefilled microinjection
                                                                                                                                older. LAIV should be considered for
Intramuscular Vaccine                                           system (0.1 mL) for adults. The pack-
                                                                                                                                healthy children 2 through 8 years of age
The IM formulation of IIV is shipped                            age insert should be reviewed for full
                                                                                                                                who have no contraindications or pre-
and stored at 2°C to 8°C (35°F–46°F). It                        administration details of this product.
                                                                                                                                cautions to the intranasal vaccine. This is
is administered intramuscularly into
                                                                Live Attenuated (Intranasal)                                    based on a GRADE analysis done by the
the anterolateral thigh of infants and
                                                                Vaccine                                                         CDC, which concluded that there is
young children and into the deltoid
                                                                                                                                greater relative efficacy of LAIV as
muscle of older children and adults.                            The cold-adapted, temperature-sensitive
                                                                                                                                compared with IIV against laboratory-
The volume of vaccine is age depen-                             LAIV4 formulation currently licensed in
dent; infants and toddlers 6 months                                                                                             confirmed influenza among younger
                                                                the United States must be shipped and
through 35 months of age should re-                                                                                             children. If LAIV is not readily available, IIV
                                                                stored at 2°C to 8°C (35°F–46°F) and
ceive a dose of 0.25 mL, and all people                         administered intranasally in a prefilled,                        should be used; vaccination should not
3 years (36 months) and older should                            single-use sprayer containing 0.2 mL of                         be delayed to obtain LAIV. Particular fo-
receive 0.5 mL/dose.                                            vaccine. A removable dose divider clip                          cus should be on the administration of
                                                                is attached to the sprayer to administer                        IIV for all children and adolescents with
Intradermal Vaccine                                             0.1 mL separately into each nostril. Af-                        underlying medical conditions associated
The ID formulation of IIV also is shipped                       ter administration of any live virus                            with an elevated risk of complications
and stored at 2°C to 8°C (35°F–46°F). It                        vaccine, at least 4 weeks should pass                           from influenza, including the following:
is administered intradermally only to                           before another live virus vaccine is ad-                         Asthma or other chronic pulmonary
people 18 through 64 years of age,                              ministered.                                                          diseases, including cystic fibrosis

PEDIATRICS Volume 134, Number 5, November 2014                                                                                                                                          9
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FIGURE 3
Precautions for administering IIV to presumed egg-allergic children.

 Hemodynamically significant car-                      rodevelopmental disorders, spinal        is in the postpartum period, or is
     diac disease                                      cord injuries, seizure disorders, or     breastfeeding during the influ-
 Immunosuppressive disorders or                       neuromuscular abnormalities              enza season. Studies have shown
     therapy                                       Although universal immunization for all      that infants born to immunized
                                                                                                women have better influenza-related
 HIV infection                                    people 6 months and older is recom-
                                                                                                health outcomes. However, accord-
                                                   mended for the 2014–2015 influenza
 Sickle cell anemia and other hemo-                                                            ing to Internet panel surveys con-
                                                   season, particular immunization ef-
     globinopathies                                                                             ducted by the CDC, only 51% of
                                                   forts with either IIV or LAIV should be
 Diseases that necessitate long-                  made for the following groups to pre-        pregnant women reported receiv-
     term aspirin therapy, including ju-                                                        ing an influenza vaccine during the
                                                   vent transmission of influenza to those
     venile idiopathic arthritis or Kawasaki                                                    2012–2013 season, even though
                                                   at risk, unless contraindicated:
     disease                                                                                    both pregnant women and their
                                                    Household contacts and out-of-home
 Chronic renal dysfunction                            care providers of children younger
                                                                                                infants are at higher risk of com-
                                                                                                plications. In addition, data from
 Chronic metabolic disease, includ-                   than 5 years and at-risk children of     some studies suggest that in-
     ing diabetes mellitus                             all ages (healthy contacts 2 through     fluenza vaccination in pregnancy
 Any condition that can compro-                       49 years of age can receive either IIV   may decrease the risk of preterm
     mise respiratory function or han-                 or LAIV).                                birth and of giving birth to infants
     dling of secretions or can increase            Any woman who is pregnant or               who are small for gestational age.
     the risk of aspiration, such as neu-              considering pregnancy (IIV only),        Pregnant women can receive the

10     FROM THE AMERICAN ACADEMY OF PEDIATRICS
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FROM THE AMERICAN ACADEMY OF PEDIATRICS

   influenza vaccine safely during                   episode in the previous 12 months           has an influenza illness for which
   any trimester.                                   because of the potential for in-            antiviral agents are appropriate, the
 Children and adolescents of Amer-                 creased wheezing after immuniza-            antiviral agents should be given. Re-
   ican Indian or Alaska Native heri-               tion. In this age range, many               immunization may be indicated be-
   tage.                                            children have a history of wheezing         cause of the potential effects of
                                                    with respiratory tract illnesses and        antiviral medications on LAIV rep-
 HCP or health care volunteers. De-
                                                    are eventually diagnosed with               lication and immunogenicity.
   spite the AAP recommendation for
                                                    asthma. Therefore, when offering
   mandatory influenza immunization
                                                    LAIV to children 24 through 59           Children for Whom IIV Is Preferred
   for all HCP,2 many remain unvacci-
   nated. As of November 2013, the
                                                    months of age, the pediatrician           Children with chronic underlying
                                                    should screen them by asking the            medical conditions, including meta-
   CDC estimated that only 62.9% of
                                                    parent or guardian, “In the previous        bolic disease, diabetes mellitus,
   HCP received the seasonal influ-
                                                    12 months, has a health care pro-           other chronic disorders of the pul-
   enza vaccine. The AAP recommends
                                                    fessional ever told you that your           monary or cardiovascular systems,
   mandatory vaccination of HCP, be-
                                                    child had wheezing?” If a parent            renal dysfunction, or hemoglobinop-
   cause HCP frequently come into
                                                    answers “yes” to this question, LAIV        athies. The safety of LAIV in these
   contact with patients at high risk
                                                    is not recommended for the child.           populations has not been estab-
   of influenza illness in their clinical            IIV would be recommended for the
   settings.                                                                                    lished. These conditions are not
                                                    child to whom LAIV is not given.            contraindications but are listed un-
 Close contacts of immunosuppressed              Children with the diagnosis of               der the “Warnings and Precautions”
   people.                                          asthma.                                     section of the LAIV package insert. A
                                                  Children with a history of egg allergy.      precaution is a condition in a recip-
CONTRAINDICATIONS AND
PRECAUTIONS                                       Children who have received other             ient that might increase the risk or
                                                    live virus vaccines within the last 4       seriousness of an adverse reaction
Minor illnesses, with or without fever,             weeks; however, other live virus            or complicate making another diag-
are not contraindications to the use of             vaccines can be given on the same           nosis because of a possible vaccine-
influenza vaccines, particularly among               day as LAIV.                                related reaction. A precaution also
children with mild upper respiratory                                                            may exist for conditions that might
                                                  Children who have known or sus-
infection symptoms or allergic rhinitis.                                                        compromise the ability of the vac-
                                                    pected immunodeficiency disease
                                                                                                cine to produce immunity. Vaccina-
                                                    or who are receiving immunosup-
Children Who Should Not Be                                                                      tion may be recommended in the
                                                    pressive or immunomodulatory ther-
Vaccinated With IIV                                                                             presence of a precaution if the ben-
                                                    apies.
 Infants younger than 6 months.                  Children who are receiving aspirin
                                                                                                efit of protection from the vaccine
 Children who have a moderate to                   or other salicylates.
                                                                                                outweighs any risk.
   severe febrile illness, on the basis                                                      IIV is the vaccine of choice for anyone in
                                                  Any woman who is pregnant or              close contact with a subset of severely
   of clinical judgment of the clini-
                                                    considering pregnancy.                   immunocompromised people (ie, those
   cian.
                                                  Children with any condition that          in a protected environment). IIV is
Children Who Should Not Be                          can compromise respiratory func-         preferred over LAIV for contacts of
Vaccinated With LAIV                                tion or handling of secretions or        severely immunocompromised people
                                                    can increase the risk for aspira-
 Children younger than 2 years.                    tion, such as neurodevelopmental
                                                                                             because of the theoretical risk of in-
                                                                                             fection attributable to LAIV strain in an
 Children who have a moderate to                   disorders, spinal cord injuries, sei-    immunocompromised contact of an
   severe febrile illness.                          zure disorders, or neuromuscular         LAIV-immunized person. Available data
 Children with an amount of nasal                  abnormalities.                           indicate a very low risk of transmission
   congestion that would notably im-              Children taking an influenza antivi-       of the virus in both children and adults
   pede vaccine delivery.                           ral medication should not receive        vaccinated with LAIV. HCP immunized
 Children 2 through 4 years of age                 LAIV until 48 hours after stopping       with LAIV may continue to work in most
   with a history of recurrent wheezing             the influenza antiviral therapy. If       units of a hospital, including the NICU
   or a medically attended wheezing                 a child recently received LAIV but       and general oncology wards, using

PEDIATRICS Volume 134, Number 5, November 2014                                                                                      11
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standard infection control techniques.         of this guideline in computer systems         SF (sugar-free) by retail pharma-
As a precautionary measure, people             and quality measurement efforts. This         cies to a final concentration of 6
recently vaccinated with LAIV should           document is available at www2.aap.            mg/mL (Table 3).
restrict contact with severely immu-           org/informatics/PPI.html.                   Continuous monitoring of the epi-
nocompromised patients for up to 28                                                          demiology, change in severity, and
days after immunization, although              USE OF ANTIVIRAL MEDICATIONS                  resistance patterns of influenza
there have been no reports of LAIV                                                           strains may lead to new guidance.
                                               Oral oseltamivir remains the antiviral
transmission from a vaccinated person
                                               drug of choice for the management of       Treatment should be offered for:
to an immunocompromised person. In
the theoretical scenario in which
                                               influenza infections. Inhaled zanamivir      Any child hospitalized with pre-
                                               is an equally acceptable alterna-             sumed influenza or with severe,
symptomatic LAIV infection develops in
                                               tive but is more difficult to admin-           complicated, or progressive illness
an immunocompromised host, oselta-
                                               ister. Antiviral resistance can emerge        attributable to influenza, regardless
mivir or zanamivir could be prescribed,
                                               quickly between seasons. If local or          of influenza immunization status or
because LAIV strains are susceptible to
                                               national influenza surveillance data           whether onset of illness occurred
these antiviral medications.
                                               indicate a predominance of a partic-          >48 hours before admission.
                                               ular influenza strain with a known
SURVEILLANCE                                                                               Influenza infection of any severity in
                                               antiviral susceptibility profile, then
                                                                                             children at high risk of complica-
Information about influenza surveil-            empirical treatment can be directed
                                                                                             tions of influenza infection (Table 4),
lance is available through the CDC             toward that strain. For example, all
                                                                                             such as children younger than 2
Voice Information System (influenza             the influenza A (H3N2) and influenza B
                                                                                             years.
update, 888-232-3228) or at www.cdc.           viruses tested since October 1, 2013
gov/flu/index.htm. Although current             were sensitive to oseltamivir and          Treatment should be considered for:
influenza season data on circulating            zanamivir during the 2013–2014 in-          Any otherwise healthy child with
strains do not necessarily predict             fluenza season. Among the pH1N1                influenza infection for whom a de-
which and in what proportion strains           viruses tested for resistance, only           crease in duration of clinical symp-
will circulate in the subsequent sea-          1.2% were found to be resistant to            toms is felt to be warranted by his
son, it is instructive to be aware of          oseltamivir, and none were found to           or her pediatrician. The greatest
2013–2014 influenza surveillance data           be resistant to zanamivir. In contrast,       impact on outcome will occur if
and use them as a guide to empirical           high levels of resistance to amanta-          treatment can be initiated within
therapy until current seasonal data            dine and rimantadine exist, so these          48 hours of illness onset but still
are available from the CDC. Informa-           drugs should not be used in the up-           should be considered if later in the
tion is posted weekly on the CDC               coming season unless resistance               course of illness.
Web site (www.cdc.gov/flu/weekly/               patterns change significantly.              Reviews of available studies by the
fluactivity.htm).                                Current treatment guidelines for         CDC, the World Health Organization,
                                                  antiviral medications (Table 3) are     and independent investigators have
VACCINE IMPLEMENTATION                            applicable to both infants and chil-    consistently found that timely oselta-
These updated recommendations for                 dren with suspected influenza when       mivir treatment can reduce the risks
prevention and control of influenza in             known virus strains are circulating     of complications, including those re-
children will have operational and                in the community or when infants        sulting in hospitalization and death.
fiscal effects on pediatric practice.              or children are confirmed to have        Although a 2012 Cochrane review of
Therefore, the AAP has developed                  seasonal influenza.                      studies primarily in outpatient settings
implementation guidance on supply,              Oseltamivir is available in capsule      suggested that oseltamivir may not be
payment, coding, and liability issues;            and oral suspension formulations.       effective in preventing complications
these documents can be found at                   The commercially manufactured liq-      or hospitalizations from influenza, its
www.aapredbook.org/implementation.                uid formulation has a concentration     authors correctly pointed out that the
In addition, the AAP’s Partnership for            of 6 mg/mL. If the commercially         data reviewed were not always com-
Policy Implementation has developed               manufactured oral suspension is         plete, were analyzed in a variety of
a series of definitions using accepted             not available, the capsule may be       treated populations, and used a num-
health information technology stand-              opened and the contents mixed           ber of clinical trial designs. In addition,
ards to assist in the implementation              with simple syrup or Oral-Sweet         a recently revised 2014 Cochrane

12   FROM THE AMERICAN ACADEMY OF PEDIATRICS
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FROM THE AMERICAN ACADEMY OF PEDIATRICS

review of NAIs for influenza further                             to assess the effect on severe out-                              been shown to provide some benefit
evaluated published and previously                              comes such as hospitalizations or                                and should be strongly considered. In
unpublished data from randomized                                deaths.                                                          previous years, the use of double-dose
clinical trials largely in healthy out-                         Importantly, treatment with oseltamivir                          oseltamivir, particularly for those hos-
patients with mild illness. Unlike other                        for children with presumed serious,                              pitalized with severe illness caused by
analyses of the efficacy of antiviral                            complicated, or progressive disease,                             pH1N1, was believed to provide better
drugs, this Cochrane analysis included                          irrespective of influenza immunization                            outcomes. However, recently published
both influenza virus–infected and                                status or even whether illness began                             data from a randomized, prospective
noninfected people with influenza-like                           greater than 48 hours before admis-                              trial with 75% of subjects younger than
illness. Given the specific antiviral                            sion, continues to be recommended by                             15 years documented no benefit of
activity of NAIs against influenza viru-                         the AAP, CDC, and Infectious Diseases                            double-dose therapy over standard-
ses, this analytic approach under-                              Society of America (IDSA) (http://www.                           dose therapy.
estimates the treatment efficacy of                              idsociety.org/Influenza_Statement.aspx).                          Dosages for antiviral agents for both
NAIs and their valuable role in helping                         Earlier treatment provides better clini-                         treatment and chemoprophylaxis in
to lessen complications in those at                             cal responses. However, treatment after                          children can be found in Table 3 and
high risk for them, including hospi-                            48 hours of symptoms in adults and                               on the CDC Web site (http://www.cdc.
talized patients. Furthermore, this re-                         children with moderate to severe dis-                            gov/flu/professionals/antivirals/index.
view of outpatients was not designed                            ease or with progressive disease has                             htm). Children younger than 2 years

TABLE 3 Recommended Dosage and Schedule of Influenza Antiviral Medications for Treatment and Chemoprophylaxis for the 2014–2015 Influenza
            Season: United States
                  Medication                                            Treatment (5 d)                                                 Chemoprophylaxis (10 d)
Oseltamivira
  Adults                                                 75 mg twice daily                                         75 mg once daily
  Children ≥12 mo
     Body wt
     ≤15 kg (≤33 lb)                                     30 mg twice daily                                         30 mg once daily
     >15–23 kg (33–51 lb)                                45 mg twice daily                                         45 mg once daily
     >23–40 kg (>51–88 lb)                               60 mg twice daily                                         60 mg once daily
     >40 kg (>88 lb)                                     75 mg twice daily                                         75 mg once daily
  Infants 9–11 mob                                       3.5 mg/kg per dose twice daily                            3.5 mg/kg per dose once daily
  Term infants 0–8 mob                                   3 mg/kg per dose twice daily                              3 mg/kg per dose once daily for infants 3–8 mo; not
                                                                                                                      recommended for infants
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