pediatrics
October 2012, VOLUME130 /ISSUE 4

Recommendations for Prevention and Control of Influenza in Children, 2012–2013

  1. COMMITTEE ON INFECTIOUS DISEASES

    Abstract

    The purpose of this statement is to update recommendations for routine use of trivalent seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children. The key points for the upcoming 2012–2013 season are: (1) this year’s trivalent influenza vaccine contains A/California/7/2009 (H1N1)–like antigen (derived from influenza A [H1N1] pdm09 [pH1N1] virus); A/Victoria/361/2011 (H3N2)–like antigen; and B/Wisconsin/1/2010–like antigen (the influenza A [H3N2] and B antigens differ from those contained in the 2010–2011 and 2011–2012 seasonal vaccines); (2) annual universal influenza immunization is indicated; and (3) an updated dosing algorithm for administration of influenza vaccine to children 6 months through 8 years of age has been created. Pediatricians, nurses, and all health care personnel should promote influenza vaccine use and infection control measures. In addition, pediatricians should promptly identify influenza infections to enable rapid treatment, when indicated, to reduce morbidity and mortality.

    KEY WORDS
    • children
    • influenza
    • immunization
    • live-attenuated influenza vaccine
    • pediatrics
    • trivalent inactivated influenza vaccine
    • vaccine
  1. Abbreviations:
    AAP
    American Academy of Pediatrics
    CDC
    Centers for Disease Control and Prevention
    FDA
    Food and Drug Administration
    HCP
    health care personnel
    ID
    intradermal
    IM
    intramuscular
    LAIV
    live-attenuated influenza vaccine
    TIV
    trivalent inactivated influenza vaccine
  2. Introduction

    The American Academy of Pediatrics (AAP) recommends annual trivalent seasonal influenza immunization for all individuals, including all children and adolescents, aged ≥6 months during the 2012–2013 influenza season. In addition, special efforts should be made to vaccinate individuals in the following groups:

    • All children, including infants born preterm, who are ≥6 months of age who have conditions that increase the risk of complications from influenza (eg, children with chronic medical conditions such as asthma, diabetes mellitus, immunosuppression, or neurologic disorders);

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

      • ○ children with high-risk conditions; and

      • ○ children aged <5 years, especially infants aged <6 months

    • All health care personnel (HCP); and

    • All women who are pregnant, are considering pregnancy, have just delivered, or are breastfeeding during the influenza season.

    Key Points Relevant for the 2012–2013 Influenza Season

    1. All individuals aged ≥6 months should receive the trivalent seasonal influenza vaccine each year. This includes people at high risk of influenza complications (eg, children with chronic medical conditions such as asthma, diabetes mellitus, immunosuppression, or neurologic disorders). In the United States, more than two-thirds of children <6 years of age and almost all children aged >6 years spend significant time in child care and school settings outside the home. Exposure to groups of children increases the risk of infectious diseases. Children aged <2 years are at an increased risk of hospitalization and complications attributable to influenza. School-aged children bear a large influenza disease burden and have a significantly higher chance of seeking influenza-related medical care compared with healthy adults. Therefore, reducing influenza transmission among children who attend child care or school should decrease the burden of childhood influenza and transmission of influenza to household contacts and community members of all ages.

    2. An annual trivalent seasonal influenza vaccine is recommended for all individuals, including all children and adolescents, ≥6 months of age during the 2012–2013 influenza season. It is also important that household contacts and out-of-home care providers of children aged <5 years, especially infants aged <6 months, and children of any age at high risk of complications of influenza (eg, children with chronic medical conditions such as asthma, diabetes mellitus, immunosuppression, or neurologic disorders) receive an annual influenza vaccine. Pediatric offices should consider serving as an alternate venue to provide influenza immunization to parents and other adults who care for children, if this approach is acceptable to both the pediatrician and the adult to be immunized. Pediatricians should still encourage adults to have a medical home and communicate their immunization status to their primary care provider. Immunization of close contacts of children at high risk of influenza-related complications is intended to reduce their risk of contagion (ie, “cocooning”). The concept of cocooning is particularly important to help protect infants <6 months of age because they are too young to be immunized with influenza vaccine. The risk of influenza-associated hospitalization in healthy children aged <24 months has been shown to be greater than the risk of hospitalization in previously recognized high-risk groups, such as the elderly, during the influenza season. Children aged 24 through 59 months have shown increased rates of outpatient visits and antimicrobial use associated with influenza-like illnesses.

    3. The 2011–2012 influenza season was mild compared with recent years, with a lower percentage of outpatient visits for influenza-like illness, lower rates of hospitalizations, and fewer deaths attributed to pneumonia and influenza. A total of 26 laboratory-confirmed influenza-associated pediatric deaths were reported to the Centers for Disease Control and Prevention (CDC) during the 2011–2012 influenza season. Six of the 26 deaths were associated with influenza B virus, 5 deaths were associated with influenza A (H3) virus, 7 deaths were associated with influenza A (H1N1) pdm09 (pH1N1) virus, 7 deaths were associated with an influenza A virus for which the subtype was not determined, and 1 death was associated with an influenza virus with the type not determined. Influenza A (H3N2) predominated overall, but virus subtype activity varied regionally. Among children hospitalized with influenza, ∼48% did not have any known underlying conditions, whereas an additional 19% had underlying asthma or reactive airway disease (Fig 1). Although children who have certain conditions are at higher risk of complications, substantial proportions of seasonal influenza morbidity and mortality occur among healthy children.

    4. The recommended trivalent vaccine for the 2012–2013 influenza season contains the following 3 virus strains:

      • A/California/7/2009 (H1N1)–like antigen (derived from influenza A [H1N1] pdm09 [pH1N1] virus);

      • A/Victoria/361/2011 (H3N2)–like antigen; and

      • B/Wisconsin/1/2010–like antigen.

      • The influenza A (H3N2) and B antigens differ from those contained in the 2010–2011 and 2011–2012 seasonal vaccines.

    5. The number of trivalent seasonal influenza vaccine doses to be administered in the 2012–2013 influenza season depends on the child’s age at the time of the first administered dose and his or her vaccine history (Fig 2):

      • Infants aged <6 months are too young to be immunized with influenza vaccine.

      • Children aged ≥9 years need only 1 dose.

      • Children 6 months through 8 years of age receiving the trivalent seasonal influenza vaccine (administered either by injection for children aged ≥6 months or intranasally for children aged ≥2 years) for the first time should receive a second dose this season at least 4 weeks after the first dose.

      • Children 6 months through 8 years of age who received trivalent seasonal influenza vaccine before the 2012–2013 influenza season:

        • ○ Need only 1 dose of vaccine, if they previously received a total of ≥2 doses of seasonal vaccine since July 1, 2010

        • ○ Need 2 doses of vaccine, if they did not previously receive a total of ≥2 doses of seasonal vaccine since July 1, 2010

        • ○ Need only 1 dose of influenza vaccine if there is clear documentation of having received at least 2 seasonal influenza vaccines from any previous season and at least 1 dose of a pH1N1-containing vaccine, which could have been in 1 of the seasonal vaccines (2010–2011 or 2011–2012) or as the monovalent pH1N1 vaccine from 2009–2010.

    6. As soon as the trivalent seasonal influenza vaccine is available locally, HCP should be immunized, parents and caregivers should be notified about vaccine availability, and immunization of all children aged ≥6 months, especially children at high risk of complications from influenza, should begin. HCP endorsement plays a major role in vaccine uptake. A strong correlation exists between HCP endorsement of influenza vaccine and patient acceptance. Prompt initiation of influenza immunization and continuance of immunization throughout the influenza season, whether or not influenza is circulating (or has circulated) in the community, are critical components of an effective immunization strategy. Giving the vaccine promptly and early during the influenza season does not pose a risk that immunity might wane before the end of the season.

    7. Providers should continue to offer vaccine until the vaccine expiration date because influenza is so unpredictable. Protective immune responses persist throughout the influenza season, which can have >1 disease peak and often extends into March or later. Although most influenza activity in the United States tends to occur in January through March, influenza activity can occur in early fall (ie, October and November) or late spring (eg, 1 state reported widespread activity during the third week in May 2012). This approach provides ample opportunity to administer a second dose of vaccine because children aged <9 years may require 2 doses to confer optimal protection. In addition, with international travel so common, there is potential exposure to influenza virtually year-round.

    8. HCP, influenza campaign organizers, and public health agencies should collaborate to develop improved strategies for planning, communication, and administration of vaccines.

      • Plan to make trivalent seasonal influenza vaccine easily accessible for all children. Examples include creating walk-in influenza clinics, extending hours beyond routine times during peak vaccination periods, considering how to immunize parents and adult caregivers at the same time in the same office setting as children,1 and working with other institutions (eg, schools, child care centers, religious organizations) or alternative care sites, such as emergency departments, to expand venues for administering vaccine, with appropriate documentation of immunization to be provided to the medical homes of children and adults immunized.

      • Concerted efforts among the aforementioned groups, plus vaccine manufacturers, distributors, and payers, also are necessary to appropriately prioritize distribution to the primary care office setting before other venues, especially when vaccine supplies are delayed or limited.

      • Vaccine safety, effectiveness, and indications must be properly communicated to the public. HCP should act as role models by receiving influenza immunization annually as well as recommending annual immunizations to both colleagues and patients.

      • Beginning in 2012, as an immunization core measure, the Centers for Medicare & Medicaid Services, the US federal agency that administers Medicare, Medicaid, and the State Children’s Health Insurance Program, requires hospitals and certain other inpatient facilities to screen for and immunize against influenza all hospitalized patients aged ≥6 months between October and March, unless contraindicated or the patient or family refuses.

    9. Antiviral medications also are important in the control of influenza. The neuraminidase inhibitors oral oseltamivir (Tamiflu [Roche Laboratories, Nutley, NJ]) and inhaled zanamivir (Relenza [GlaxoSmithKline, Research Triangle Park, NC]) are the only antiviral medications routinely recommended for chemoprophylaxis or treatment during the 2012–2013 season. Intravenous preparations are not routinely available at the present time. With infectious diseases consultation, intravenous use through experimental protocols could be considered for some critically ill children, especially those who are immunocompromised. All strains of influenza currently anticipated to circulate are susceptible to neuraminidase inhibitors but have high rates of resistance to amantadine and rimantadine (Table 1). Resistance characteristics may change rapidly; pediatricians should verify susceptibility data at the start of the influenza season and monitor them during the season. Up-to-date information can be found on the AAP Web site (www.aap.org or http://aapredbook.aappublications.org/flu), through state-specific AAP chapter Web sites, or on the CDC Web site (www.cdc.gov/flu/index.htm).

    FIGURE 1

    Selected underlying medical conditions in patients hospitalized with influenza, FluSurv-NET 2011–2012. Asthma includes a diagnosis of asthma or reactive airway disease; chronic lung disease includes asthma as well as other conditions such as bronchiolitis obliterans, chronic aspiration pneumonia, and interstitial lung disease; cardiovascular disease includes conditions such as coronary heart disease, cardiac valve disorders, congestive heart failure, pulmonary hypertension, and aortic stenosis; immune suppression includes conditions such as immunoglobulin deficiency, leukemia, lymphoma, HIV/AIDS, and individuals taking immunosuppressive medications; metabolic disorder includes conditions such as diabetes mellitus, thyroid dysfunction, adrenal insufficiency, and liver disease; neurologic disorder includes conditions such as seizure disorders, cerebral palsy, and cognitive dysfunction; neuromuscular disorder includes conditions such as multiple sclerosis and muscular dystrophy; obesity was assigned if indicated in patients’ medical charts or if BMI was >30; and renal disease includes conditions such as acute or chronic renal failure, nephrotic syndrome, glomerulonephritis, and impaired creatinine clearance. Asthma is included in both the “asthma” and “chronic lung disease” categories; otherwise, the categories are mutually exclusive. Data given here only include cases for which data collection has been completed through the medical chart review stage. Source: Centers for Disease Control and Prevention. FluView 2011–2012 influenza season week 20 ending May 19, 2012. Available at: http://www.cdc.gov/flu/weekly.

    FIGURE 2

    Number of 2012–2013 seasonal influenza vaccine doses for children 6 months through 8 years of age. aThe interval between 2 doses is 4 weeks.

    TABLE 1

    Antiviral Drug Sensitivities of Influenza Strains Expected to Circulate During the 2012–2013 Influenza Seasona,b

    Trivalent Seasonal Influenza Vaccines

    Tables 2 and 3 summarize information on the 2 types of 2012–2013 trivalent seasonal influenza vaccines licensed for immunization of children and adults: injectable trivalent inactivated influenza vaccine (TIV) and intranasally administered live-attenuated influenza vaccine (LAIV). Both vaccines contain the identical strains of influenza A subtypes (ie, H1N1 and H3N2) and influenza B anticipated to circulate during the 2012–2013 influenza season.

    TABLE 2

    Recommended Trivalent Seasonal Influenza Vaccines for Different Age Groups: United States, 2012–2013 Influenza Season

    TABLE 3

    LAIV Compared With TIV

    TIV is an inactivated vaccine that contains no live virus. TIV formulations are now available for intramuscular (IM) and intradermal (ID) use. The IM formulation of TIV is licensed and recommended for children aged ≥6 months and adults, including people with and without chronic medical conditions. The most common adverse events after administration are local injection site pain and tenderness. Fever may occur within 24 hours after immunization in ∼10% to 35% of children <2 years of age but rarely in older children and adults. Mild systemic symptoms, such as nausea, lethargy, headache, muscle aches, and chills, may occur after administration of TIV.

    Increased reports of febrile seizures in the United States during the 2010–2011 influenza season were noted by the Vaccine Adverse Event Reporting System and were associated with TIV manufactured by Sanofi Pasteur (Fluzone [the only influenza vaccine licensed for children aged <2 years]. Swiftwater, PA), mainly in children in the 12- through 23-month age group (the peak age for febrile seizures). The most common vaccine administered concomitantly with TIV when a febrile seizure was reported was the 13-valent pneumococcal conjugate vaccine. This disproportionate reporting of febrile seizures persisted through the 2011–2012 influenza season as well. It was not unexpected because the influenza vaccine composition for the 2011–2012 influenza season was unchanged from the 2010–2011 influenza season. All children fully recovered. On the basis of current data, prophylactic use of antipyretic agents in TIV-immunized children is not indicated, and current AAP and CDC Advisory Committee on Immunization Practices recommendations for administration of TIV in this age group are unchanged. Febrile seizures can occur anytime a child has a fever, but the typical child who has a febrile seizure quickly and fully recovers.

    Previous febrile seizures or seizure disorders are not a contraindication to use of TIV or LAIV in otherwise eligible children. Because use of antipyretic agents in febrile children does not reduce the incidence of febrile seizures, routine use of antipyretic agents to avoid febrile seizures in children receiving influenza vaccine is not recommended. Approximately 2% to 5% of children 6 months through 5 years of age will have at least 1 febrile seizure not associated with vaccines in their lifetime. A report of a febrile seizure to the Vaccine Adverse Event Reporting System does not mean that there is a causal relationship between the event and the vaccine. There is no change in the recommendations for the use of TIV or 13-valent pneumococcal conjugate vaccine for the 2012–2013 influenza season. Simultaneous administration should be used when both vaccines are indicated.

    An ID formulation of TIV is licensed for the 2012–2013 influenza season for use in individuals aged 18 through 64 years. ID vaccine administration involves a microinjection with a needle 90% shorter than needles used for IM administration. The most common adverse events are redness, induration, swelling, pain, and itching at the site of administration at a slightly higher rate than occurs with the IM formulation of TIV. Headache, myalgia, and malaise may occur and tend to occur at the same rate as that with the IM formulation of TIV. There is no preference for IM or ID immunization in individuals aged ≥18 years; pediatricians may therefore choose to use either the IM or ID product in their late adolescent and young adult patients.

    LAIV is administered intranasally and is licensed by the US Food and Drug Administration (FDA) for healthy individuals 2 through 49 years of age. It is not recommended for those who have a history of asthma or other high-risk medical conditions associated with an increased risk of complications from influenza (see Contraindications and Precautions). LAIV has the potential to produce mild symptoms, including rhinitis, headache, wheezing, vomiting, muscle aches, and fever. LAIV should not be administered to people with notable nasal congestion that would impede vaccine delivery.

    Both TIV and LAIV are produced in eggs and contain measurable amounts of egg protein, expressed as the concentration of ovalbumin per dose (Table 2). However, recent data have shown that TIV administered in a single, age-appropriate dose is well tolerated by nearly all recipients who have egg allergy. More conservative approaches, such as skin testing or a 2-step graded challenge, no longer are recommended. No data exist on the safety of administering LAIV to egg-allergic recipients.

    As a precaution, pediatricians should determine whether the presumed egg allergy is based on a mild (ie, hives alone) or severe (ie, anaphylaxis involving cardiovascular changes, respiratory and/or gastrointestinal tract symptoms, or reactions that required the use of epinephrine) reaction. Pediatricians should consult with an allergist for children who have a history of severe reaction. Most vaccine administration to individuals with egg allergy can happen without the need for referral. Data indicate that only ∼1% of children have immunoglobulin E–mediated sensitivity to egg, and of those, a very small minority have a severe allergy.

    Standard immunization practice should include the ability to respond to acute hypersensitivity reactions. Therefore, influenza vaccine should be given to individuals with egg allergy with the following preconditions (Fig 3):

    • Appropriate resuscitative equipment must be readily available.2

    • The vaccine recipient should be observed in the office for 30 minutes after immunization, the standard observation time for receiving immunotherapy.

    FIGURE 3

    Precautions for administering TIV to presumed egg-allergic individuals. BP, blood pressure.

    Both TIV and LAIV are cost-effective strategies for preventing influenza among children and their families when circulating and vaccine strains are matched closely, but efficacy varies according to the age of the recipient. Current data from direct comparisons of the efficacy or effectiveness of these 2 vaccines are limited because studies were conducted in a variety of settings and in populations using several different clinical end points. In one study that compared LAIV with TIV in infants and young children without severe asthma or a recent history of wheezing, LAIV showed significantly better efficacy than TIV; results of other studies suggest that TIV may be more effective in young adults. The CDC has recently begun a new, comprehensive, and systematic approach to grading the quality of evidence and strength of recommendations for influenza vaccines using an evidence-based framework called “Grading of Recommendations Assessment, Development and Evaluation.” Initial assessments will focus on the use of influenza vaccines in healthy children and the basis for age-based preferential recommendations of TIV or LAIV.

    A large body of evidence demonstrates that thimerosal-containing vaccines are not associated with increased risk of autism spectrum disorders in children. As such, the AAP extends its strongest support to the recent World Health Organization recommendations to retain the use of thimerosal in the global vaccine supply. Some individuals may still raise concerns about the minute amounts of thimerosal in TIV vaccines, and in some states, there is a legislated restriction on the use of thimerosal-containing vaccines. The benefits of protecting children against the known risks of influenza are clear. Therefore, children should receive any available formulation of TIV rather than delaying immunization while waiting for vaccines with reduced-thimerosal content or for thimerosal-free vaccine. Although some formulations of TIV contain only a trace amount of thimerosal, certain types can be obtained thimerosal free. LAIV does not contain thimerosal. Vaccine manufacturers are delivering increasing amounts of thimerosal-free influenza vaccine each year.

    Vaccine Storage and Administration

    Any of the influenza vaccines can be administered at the same visit with all other recommended routine vaccines.

    IM Vaccine

    The IM formulation of TIV is shipped and stored at 2°C to 8°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 dependent; infants and toddlers 6 months through 35 months of age should receive a dose of 0.25 mL, and all individuals 3 years (36 months) and older should receive 0.5 mL per dose.

    ID Vaccine

    The ID formulation of TIV also is shipped and stored at 2°C to 8°C (35°F–46°F). It is administered intradermally only to individuals 18 through 64 years of age, preferably over the deltoid muscle, and only using the device included in the vaccine package. Vaccine is supplied in a single-dose, prefilled microinjection system (0.1 mL) for adults. The package insert should be reviewed for full administration details of this product.

    Live-Attenuated (Intranasal) Vaccine

    The cold-adapted LAIV formulation currently licensed in the United States must be shipped and stored at 2°C to 8°C (35°F–46°F) and administered intranasally in a prefilled, single-use sprayer containing 0.2 mL of vaccine. A removable dose-divider clip is attached to the sprayer to administer 0.1 mL separately into each nostril. After administration of any live virus vaccine, at least 4 weeks should pass before another live virus vaccine is administered.

    Current Recommendations

    Trivalent seasonal influenza immunization is recommended for all children aged ≥6 months. Healthy children aged ≥2 years can receive either TIV or LAIV. Particular focus should be on the administration of TIV for all children and adolescents who have underlying medical conditions associated with an increased risk of complications from influenza, including:

    • Asthma or other chronic pulmonary diseases, including cystic fibrosis.

    • Hemodynamically significant cardiac disease.

    • Immunosuppressive disorders or therapy.

    • HIV infection.

    • Sickle cell anemia and other hemoglobinopathies.

    • Diseases that require long-term aspirin therapy, including juvenile idiopathic arthritis or Kawasaki disease.

    • Chronic renal dysfunction.

    • Chronic metabolic disease, including diabetes mellitus.

    • Any condition that can compromise respiratory function or handling of secretions or can increase the risk of aspiration, such as neurodevelopmental disorders, spinal cord injuries, seizure disorders, or neuromuscular abnormalities.

    Although universal immunization for all individuals aged ≥6 months is recommended for the 2012–2013 influenza season, particular immunization efforts with either TIV or LAIV should be made for the following groups to prevent transmission of influenza to those at risk, unless contraindicated:

    • Household contacts and out-of-home care providers of children aged <5 years and at-risk children of all ages (healthy contacts 2–49 years of age can receive either TIV or LAIV).

    • Any female who is pregnant, is considering pregnancy, has just delivered, or is breastfeeding during the influenza season (TIV only). Studies have shown that infants born to immunized women have better influenza-related health outcomes. However, the estimated median seasonal vaccination coverage among women with a live birth was only 47.1% during the 2009–2010 influenza season, even though both pregnant women and their infants are at higher risk of complications. In addition, data from some studies suggest that influenza vaccination in pregnancy may decrease the risk of preterm birth.

    • HCP or health care volunteers. Despite the recent AAP recommendation for mandatory influenza immunization for all health care personnel,3 many HCP remain unvaccinated. As of November 2011, the CDC estimated that only 63.4% of HCP received the seasonal influenza vaccine. The AAP recommends mandatory vaccination of HCP because they frequently come into contact in their clinical settings with patients at high risk of influenza illness.

    • Close contacts of immunosuppressed people.

    Contraindications and Precautions

    Minor illnesses, with or without fever, are not contraindications to the use of influenza vaccines, particularly among children who have mild upper respiratory tract infection symptoms or allergic rhinitis.

    Children Who Should Not Be Vaccinated With TIV

    • Infants aged <6 months.

    • Children who have a moderate to severe febrile illness, on the basis of clinical judgment of the pediatrician.

    Children Who Should Not Be Vaccinated With LAIV

    • Children aged <2 years.

    • Children who have a moderate to severe febrile illness.

    • Children with an amount of nasal congestion that would notably impede vaccine delivery.

    • Children who have received other live virus vaccines within the last 4 weeks; however, other live virus vaccines can be given on the same day as LAIV.

    • Children with chronic underlying medical conditions, including metabolic disease, diabetes mellitus, asthma, other chronic disorders of the pulmonary or cardiovascular system, renal dysfunction, or hemoglobinopathies.

    • Children who have known or suspected immunodeficiency disease or who are receiving immunosuppressive or immunomodulatory therapies.

    • Children who are receiving aspirin or other salicylates.

    • Any female who is pregnant or considering pregnancy.

    • Children with any condition that can compromise respiratory function or handling of secretions or can increase the risk for aspiration, such as neurodevelopmental disorders, spinal cord injuries, seizure disorders, or neuromuscular abnormalities.

    • Children aged 2 through 4 years with a history of recurrent wheezing or a medically attended wheezing episode in the previous 12 months because of the potential for increased wheezing after immunization. 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 children 24 through 59 months of age, the pediatrician should screen them by asking the parent/guardian the question, “In the previous 12 months, has a health care professional ever told you that your child had wheezing?” If a parent answers “yes” to this question, LAIV is not recommended for the child. TIV would be recommended for the child to whom LAIV is not given.

    • Children taking an influenza antiviral medication should not receive LAIV until 48 hours after stopping the influenza antiviral therapy. If a child recently received LAIV but has an influenza illness for which antiviral agents are appropriate, the antiviral agents should be given. Reimmunization may be indicated because of the potential effects of antiviral medications on LAIV replication and immunogenicity.

    Precautions

    TIV is the vaccine of choice for anyone in close contact with a subset of severely immunocompromised people (ie, individuals in a protected environment). TIV is preferred over LAIV for contacts of severely immunocompromised people (ie, in a protected environment) because of the theoretical risk of infection 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 standard infection control techniques. As a precautionary measure, people recently vaccinated with LAIV should restrict contact with severely immunocompromised patients (eg, hematopoietic stem cell transplant recipients during periods that require a protected environment) for 7 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, oseltamivir or zanamivir could be prescribed, because LAIV strains are susceptible to these antiviral medications.

    SURVEILLANCE

    Information about influenza surveillance is available through the CDC Voice Information System (influenza update, 888-232-3228) or at www.cdc.gov/flu/index.htm. Although current influenza season data on circulating strains do not necessarily predict which and in what proportion strains will circulate in the subsequent season, it is instructive to be aware of 2011–2012 influenza surveillance data and use them as a guide to empirical therapy until current seasonal data are available from the CDC. Information is posted weekly on the CDC Web site (www.cdc.gov/flu/weekly/fluactivity.htm).

    Vaccine Implementation

    These updated recommendations for prevention and control of influenza in children will have considerable operational and fiscal effect on pediatric practice. Therefore, the AAP has developed implementation guidance on supply, payment, coding, and liability issues; these documents can be found at http://aapredbook.aappublications.org/site/implementation/.

    Use of Antiviral Medications

    Antiviral resistance can emerge quickly from 1 season to the next. If local or national influenza surveillance data indicate a predominance of a particular influenza strain with a known antiviral susceptibility profile, then empirical treatment can be directed toward that strain. For example, all of the influenza B and influenza A (H3N2) viruses tested were sensitive to oseltamivir and zanamivir during the 2011–2012 influenza season. Among the pH1N1 viruses tested for resistance, only 1.4% were found to be resistant to oseltamivir and none was found to be resistant to zanamivir. High levels of resistance to amantadine and rimantadine persist, and these drugs should not be used in the upcoming season unless resistance patterns change significantly (Table 1).

    • Current treatment guidelines for antiviral medications (Table 4) are applicable to both infants and children with suspected influenza when known virus strains are circulating in the community or when infants or children are confirmed to have seasonal influenza.

    • Oseltamivir is available in capsule and oral suspension formulations. The commercially manufactured liquid formulation has a concentration of 6 mg/mL. If the commercially manufactured oral suspension is not available, the capsule may be opened and the contents mixed with a sweetened liquid by retail pharmacies to a final concentration of 15 mg/mL.

    • Continuous monitoring of the epidemiology, change in severity, and resistance patterns of influenza strains may lead to new guidance.

    TABLE 4

    Recommended Dosage and Schedule of Influenza Antiviral Medications for Treatment and Chemoprophylaxis for the 2012–2013 Influenza Season: United States

    Treatment should be offered for:

    • Any child hospitalized with presumed influenza or with severe, complicated, or progressive illness attributable to influenza, regardless of influenza immunization status.

    • Influenza infection of any severity in children at high risk of complications of influenza infection (Table 5).

    TABLE 5

    Individuals at Higher Risk of Influenza Complications Recommended for Antiviral Treatment of Suspected/Confirmed Influenza

    Treatment should be considered for:

    • Any otherwise healthy child with influenza infection for whom a decrease in duration of clinical symptoms is felt to be warranted by his or her pediatrician if treatment can be initiated within 48 hours of illness onset.

    Reviews of available studies by the CDC, the World Health Organization, and independent investigators have consistently found that timely oseltamivir treatment can reduce the risks of complications, including those resulting in hospitalization and death. Earlier treatment provides more optimal clinical responses; treatment after 48 hours of symptoms in the child with moderate to severe disease or with progressive disease is likely to provide some benefit.

    Dosages for antiviral agents for both treatment and chemoprophylaxis in children can be found in Table 4 and on the CDC Web site (http://www.cdc.gov/flu/professionals/antivirals/index.htm). Children aged <1 year are at increased risk of influenza-related complications. Although there are no antiviral medications licensed by the FDA for this age group and the 2009 H1N1 pandemic Emergency Use Authorization has expired, the 2009 recommendations for use of oseltamivir in this young age group can still be followed and are provided in Table 4.

    Clinical judgment (on the basis of underlying conditions, disease severity, time since symptom onset, and local influenza activity) is an important factor in treatment decisions for pediatric patients who present with influenza-like illness. Antiviral treatment should be started as soon as possible after illness onset and should not be delayed while waiting for a definitive influenza test result. Currently available rapid antigen tests have low sensitivity, particularly for the influenza A (H1N1) pdm09 (pH1N1) virus strain, and should not be used to rule out influenza. Negative results from rapid antigen tests should not be used to make decisions regarding treatment or infection control. Rapid antigen tests are not helpful in the management of children with suspected influenza, unless a positive test result will be of use to curtail additional testing.

    Individuals with suspected influenza who present with an uncomplicated febrile illness typically do not require treatment with antiviral medications unless they are at higher risk of influenza complications (eg, children with chronic medical conditions such as asthma, diabetes mellitus, immunosuppression, or neurologic disorders), especially in situations with limited antiviral medication availability. Should there be a shortage of antiviral medications, local public health authorities might provide additional guidance about testing and treatment.

    Randomized placebo-controlled studies showed that oseltamivir and zanamivir were efficacious when administered as chemoprophylaxis to household contacts after a family member had laboratory-confirmed influenza. During the 2009 pandemic, the emergence of oseltamivir resistance was observed among people receiving postexposure prophylaxis. Decisions on whether to administer antiviral agents for chemoprophylaxis should take into account the exposed person’s risk of influenza complications, the type and duration of contact, recommendations from local or public health authorities, and clinical judgment. Generally, postexposure chemoprophylaxis should be used only when antiviral agents can be started within 48 hours of exposure. Early treatment of high-risk patients without waiting for laboratory confirmation is an alternate strategy.

    Chemoprophylaxis during an influenza outbreak is recommended:

    • For children at high risk of complications from influenza for whom influenza vaccine is contraindicated.

    • For children at high risk during the 2 weeks after influenza immunization.

    • For family members or HCP who are unimmunized and are likely to have ongoing, close exposure to unimmunized children at high risk or infants and toddlers who are aged <24 months.

    • For control of influenza outbreaks for unimmunized staff and children in a closed institutional setting with children at high risk (eg, extended-care facilities).

    • As a supplement to immunization among children at high risk, including children who are immunocompromised and may not respond to vaccine.

    • As postexposure prophylaxis for family members and close contacts of an infected person if those people are at high risk of complications from influenza.

    • For children at high risk and their family members and close contacts, as well as HCP, when circulating strains of influenza virus in the community are not matched with trivalent seasonal influenza vaccine strains, on the basis of current data from the CDC and local health departments.

    These recommendations apply to routine 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 influenza complications, type and duration of exposure contact, and change in epidemiology or severity of influenza.

    Chemoprophylaxis should not be considered a substitute for immunization. Influenza vaccine should always be offered when not contraindicated, even when influenza virus is circulating in the community. Antiviral medications currently licensed are important adjuncts to influenza immunization for control and prevention of influenza disease, but there are toxicities associated with antiviral agents, and indiscriminate use might limit availability (Table 1). Pediatricians should inform recipients of antiviral chemoprophylaxis that risk of influenza is lowered but still remains while taking the medication, and susceptibility to influenza returns when medication is discontinued. For recommendations about treatment and chemoprophylaxis against influenza, see Table 4. Updates will be available at www.aapredbook.org/flu and http://www.cdc.gov/flu/professionals/antivirals/index.htm.

    Future Needs

    Currently, influenza vaccines are trivalent and contain antigens from only a single influenza B virus. However, since 1985, there have been 2 antigenically distinct lineages of influenza B viruses circulated globally, the Victoria and the Yamagata lineages. Because there is little cross-protection conferred against B virus strains of 1 lineage by vaccination against a B virus strain in the other lineage, trivalent vaccines offer limited immunity against circulating influenza B strains of the lineage not present in the vaccine. Furthermore, in recent years, it has proven difficult to predict which B lineage will predominate during a given influenza season. Therefore, it has been proposed that a quadrivalent influenza vaccine, containing influenza B strains of both lineages, would offer superior protection.

    The FDA approved a new quadrivalent LAIV, FluMist Quadrivalent (MedImmune [Gaithersburg, MD]), in February 2012. However, this vaccine is not expected to be available during the 2012–2013 influenza season. It will likely first be used during the 2013–2014 influenza season, when it is anticipated to replace the current trivalent LAIV formulation. In addition, inactivated quadrivalent vaccines are currently in development.

    Manufacturers predict being able to provide adequate supplies of vaccine. Efforts should be made to create adequate outreach and infrastructure to ensure an optimal distribution of vaccine so that more people are immunized. Health care for children should be provided in the child’s medical home. However, medical homes may have limited capacity to accommodate all patients (and their families) seeking influenza immunization. Because of the increased demand for immunization during each influenza season, the AAP and the CDC recommend vaccine administration at any visit to the medical home during influenza 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 influenza vaccine. If alternate venues are used, a system of patient record transfer is beneficial to ensuring maintenance of accurate immunization records. Immunization information systems should be used whenever available.

    Cost-effectiveness and logistic feasibility of vaccinating everyone continue to be concerns. With universal immunization, particular attention is being paid to vaccine supply, distribution, implementation, and financing. Potential benefits of more widespread childhood immunization among recipients, their contacts, and the community include fewer influenza cases, fewer outpatient visits and hospitalizations for influenza infection, and a decrease in the use of antimicrobial agents, absenteeism from school, and lost parent work time. To optimally administer antiviral therapy in hospitalized patients with influenza who cannot tolerate oral or inhaled antiviral agents, intravenous neuraminidase inhibitors for children also are needed.

    Continued evaluation of the safety, immunogenicity, and effectiveness of influenza vaccine, especially for children aged <2 years, is important. Development of a safe, immunogenic vaccine for infants aged <6 months is essential. Until such a vaccine is available for infants <6 months of age, breastfeeding is recommended to protect against influenza viruses by activating innate antiviral mechanisms, specifically type 1 interferons, in the host. Mandatory annual influenza immunization has been implemented successfully at pediatric institutions, and future efforts should include broader implementation of mandatory immunization programs. Optimal prevention of influenza in the health care setting depends on coverage of at least 90% of HCP. Further studies are needed to investigate the extent of offering to immunize parents and adult child care providers in the pediatric office setting; the level of family contact satisfaction with this practice; how practices handle the logistic, liability, legal, and financial barriers that limit or complicate this service; and, most importantly, how this practice will affect disease rates in children and adults. Finally, efforts are underway to improve the vaccine development process to allow for a shorter interval between identification of vaccine strains and vaccine production.

    Committee On Infectious Diseases, 2011–2012

    Michael T. Brady, MD, Chairperson

    Carrie L. Byington, MD

    H. Dele Davies, MD

    Kathryn M. Edwards, MD

    Mary P. Glode, MD

    Mary Anne Jackson, MD

    Harry L. Keyserling, MD

    Yvonne A. Maldonado, MD

    Dennis L. Murray, MD

    Walter A. Orenstein, MD

    Gordon E. Schutze, MD

    Rodney E. Willoughby, MD

    Theoklis E. Zaoutis, MD

    Former Committee Member

    John Bradley, MD

    Liaisons

    Marc A. Fischer, MD—Centers for Disease Control and Prevention

    Bruce Gellin, MD—National Vaccine Program Office

    Richard L. Gorman, MD—National Institutes of Health

    Lucia Lee, MD—US Food and Drug Administration

    R. Douglas Pratt, MD—US Food and Drug Administration

    Jennifer S. Read, MD—National Vaccine Program Office

    Joan Robinson, MD—Canadian Pediatric Society

    Marco Aurelio Palazzi Safadi, MD—Sociedad Latinoamericana de Infectologia Pediatrica (SLIPE)

    Jane Seward, MBBS, MPH—Centers for Disease Control and Prevention

    Jeffrey R. Starke, MD—American Thoracic Society

    Geoffrey Simon, MD—Committee on Practice Ambulatory Medicine

    Tina Q. Tan, MD—Pediatric Infectious Diseases Society

    Ex Officio

    Carol J. Baker, MD—Red Book Associate Editor

    Henry H. Bernstein, DO—Red Book Online Associate Editor

    David W. Kimberlin, MD—Red Book Associate Editor

    Sarah S. Long, MD—Red Book Associate Editor

    H. Cody Meissner, MD—Visual Red Book Associate Editor

    Larry K. Pickering, MD—Red Book Editor

    Consultants

    Lorry G. Rubin, MD

    Contributors

    Stuart T. Weinberg, MD—Partnership for Policy Implementation

    Jenna Katz, BA—Research Assistant, Cohen Children’s Medical Center of NY

    John M. Kelso, MD

    Staff

    Jennifer Frantz, MPH

    ACKNOWLEDGMENTS

    This AAP policy statement was prepared in parallel with CDC recommendations and reports. Much of this statement is based on literature reviews, analyses of unpublished data, and deliberations of CDC staff in collaborations with the Advisory Committee on Immunization Practices Influenza Working Group, with liaison from the AAP.

    Footnotes

    • This document is copyrighted and is property of the American Academy of Pediatrics and its Board of Directors. All authors have filed conflict of interest statements with the American Academy of Pediatrics. Any conflicts 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.

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

    References

    Additional Resources