The purpose of this statement is to update current recommendations for routine use of trivalent seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children.
- novel influenza A (H1N1) virus
- live-attenuated influenza vaccine
- trivalent inactivated influenza vaccine
The American Academy of Pediatrics (AAP) recommends annual trivalent seasonal influenza immunization for the following groups:
All children, both healthy and with conditions that increase the risk of complications from influenza, aged 6 months through 18 years
Household contacts and out-of-home care providers of
children with conditions that place them at high risk
healthy children younger than 5 years
Health care professionals
KEY POINTS RELEVANT FOR THE 2009–2010 INFLUENZA SEASON
All children 6 months through 18 years of age should receive annual trivalent seasonal influenza immunization, with particular attention to those at high risk of influenza complications (eg, children with chronic medical conditions or immunosuppression). School-aged children bear the greatest influenza disease burden and are at significantly higher risk of needing influenza-related medical care compared with healthy adults. In addition, reducing influenza transmission among school-aged children is expected to reduce transmission of influenza to household contacts and community members.
Household members and out-of-home care providers of all children and adolescents at high risk and of all healthy children younger than 5 years of age should also receive influenza vaccine each year. Immunization of the close contacts of children at high risk is intended to reduce the risk of exposure to influenza for these young children, who are at serious risk of influenza infection, hospitalization, and complications. The risk of influenza-associated hospitalization of healthy children younger than 24 months has been shown to be equal to or greater than the risk in previously recognized high-risk groups. Children aged 24 through 59 months experience increased morbidity as a result of influenza illness, with increased rates of outpatient visits and antimicrobial agent use. Influenza vaccine has not been approved for children younger than 6 months.
All children aged 6 months through 18 years, especially those at high risk of complications from influenza, should be identified, and their parents should be informed, when possible, that annual influenza immunization is available and recommended.
On the basis of global surveillance of circulating influenza strains, the B vaccine strain has been changed in the trivalent seasonal vaccine for the 2009–2010 influenza season to match the anticipated predominant strain.
The declaration of a pandemic by the World Health Organization supports the ongoing development of a vaccine to protect against the novel influenza A (H1N1) virus. The novel strain's pattern of spread during the influenza season in the Southern Hemisphere is expected to help guide recommendations for the use of an additional monovalent pandemic influenza vaccine in the 2009–2010 season. It is critically important for providers to be aware of their local and state health department recommendations. Up-to-date information can be found at www.cdc.gov/flu and www.aapredbook.org/flu. Details regarding novel influenza A (H1N1) virus for pediatricians and families will be updated frequently on the AAP Web site (www.aap.org).
Seasonal influenza vaccine should be offered to all children as soon as vaccine is available, even as early as August or September; a protective response to immunization remains throughout the influenza season. Immunization efforts should continue throughout the entire influenza season, even after influenza activity has been documented in a community. Each influenza season often extends well into March and beyond (Fig 1), and there may be more than 1 peak of activity in the same season. Thus, immunization through at least May 1 can still protect recipients during that particular season and also provide ample opportunity to administer a second dose of vaccine to children who require 2 doses in that season.
The number of trivalent seasonal influenza vaccine dose(s) to be administered is age dependent (Fig 2):
Children aged 9 years and older who previously have not received the trivalent seasonal influenza vaccine need only 1 dose in their first season of immunization.
In contrast, any child younger than 9 years who is receiving the trivalent seasonal influenza vaccine for the first time should receive a second dose during the same season and at least 4 weeks after the first.
Children younger than 9 years who received only 1 dose of trivalent seasonal influenza vaccine in the first season they were vaccinated should receive 2 doses of trivalent seasonal influenza vaccine the following season and 1 dose each season thereafter. This recommendation applies only to the influenza season that follows the first year that a child younger than 9 years receives influenza vaccine. Data are not available for other trivalent seasonal influenza vaccine-administration scenarios.
The use of antiviral medications (amantadine, rimantadine, oseltamivir, and zanamivir) recommended for chemoprophylaxis or treatment remains more complex than in previous years because of the anticipated concurrent circulation of multiple strains of influenza with different susceptibility patterns during the 2009–2010 influenza season (Table 1).
Health care professionals, influenza campaign organizers, and public health agencies should cooperate to develop and implement plans for expanding outreach and infrastructure to achieve the target immunization of all children 6 months through 18 years of age. Efforts to consider in making trivalent seasonal influenza vaccine easily accessible for all children include creating walk-in influenza clinics, making vaccine available during all clinical hours, extending hours during vaccination periods, and working with other institutions (eg, schools, child care centers, churches) to expand venues for administering vaccine. Concerted effort among the aforementioned groups, plus vaccine manufacturers, distributors, and payers, also is necessary to appropriately prioritize administration of trivalent seasonal influenza vaccine whenever vaccine supplies are delayed or limited.
TRIVALENT SEASONAL INFLUENZA VACCINES
Tables 2 and 3 summarize information on the 2 types of trivalent seasonal influenza vaccine used to immunize both children and adults: trivalent inactivated influenza vaccine (TIV) and live-attenuated influenza vaccine (LAIV). Both vaccines contain the same 2 strains of influenza A subtypes (ie, H1N1 and H3N2) and the 1 strain of influenza B anticipated to circulate during the upcoming influenza season. The 2009–2010 trivalent seasonal influenza vaccine virus strains are an A/Brisbane/59/2007 (H1N1)-like virus, an A/Brisbane/10/2007 (H3N2)-like virus, and a B/Brisbane 60/2008-like (Victoria lineage) virus. The A strains will remain unchanged, and the B strain will be changed from the Yamagata lineage strain used in the 2008–2009 vaccines.
TIV is an inactivated vaccine that contains viral protein but no live virus and, therefore, cannot produce an active virus infection. TIV is administered intramuscularly to people who are 6 months and older, including those who are healthy and those with chronic medical conditions. The most common symptoms associated with TIV administration are soreness at the injection site and fever. Any fever usually occurs within 24 hours after immunization and affects approximately 10% to 35% of children younger than 2 years; the frequency of fever after TIV injection is much lower in older children and adults. Mild systemic symptoms, such as nausea, lethargy, headache, muscle aches, and chills, also can occur with TIV injection.
Oculorespiratory syndrome, an acute, self-limited, rare reaction with prominent ocular and respiratory symptoms (eg, bilateral red eyes and/or facial edema and/or respiratory symptoms), has been reported within 24 hours after TIV administration. The symptoms are generally mild, may not typically be concerning enough to cause vaccine recipients to seek medical care, and usually resolve quickly without treatment. The cause of oculorespiratory syndrome has not been established, but 1 study suggests the reaction is not immunoglobulin E–mediated.
LAIV is a live-attenuated influenza vaccine that is administered intranasally and is licensed by the US Food and Drug Administration (FDA) for healthy people 2 through 49 years of age. Safety and effectiveness have not been demonstrated for people with chronic medical conditions that confer higher risk of influenza complications; therefore, LAIV should not be administered to persons in these groups. LAIV has the potential to produce mild signs or symptoms related to attenuated influenza virus infection, including fever. LAIV should not be delivered to people with nasal congestion if the amount of congestion is anticipated to impede the delivery of the vaccine to the nasopharyngeal mucosa until the congestion-inducing illness is resolved.
Because viruses for both vaccines are grown in eggs, neither should be administered to anyone with known allergic reactions (ie, hives, angioedema, allergic asthma, and systemic anaphylaxis) to chicken and egg proteins. Less severe or local manifestations of allergy to eggs or feathers are not contraindications to administration of influenza vaccine.
Although the efficacy of TIV and LAIV vary depending on recipient age and dosage, both vaccines are cost-effective strategies for preventing influenza among children and their families when circulating and vaccine strains are closely matched. Current data directly comparing 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 1 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.
Concerns about the minute amounts of thimerosal in vaccines continue to be raised by some people. There is no evidence that the incidence of autism spectrum disorders is higher among children who receive thimerosal-containing vaccines than among children who do not. The benefits of protecting children against the known risks of influenza are clear. Therefore, children should receive the formulation of TIV available rather than have immunization delayed because of the thimerosal content of the available vaccine; this includes children at high risk with underlying central nervous system disorders. Some formulations of TIV contain only a trace amount of thimerosal, but certain thimerosal-free types can be obtained (eg, single-dose Fluzone [Sanofi Pasteur, Swiftwater, PA]). LAIV does not contain thimerosal. Vaccine manufacturers are delivering increasing amounts of thimerosal-free influenza vaccine each year.
VACCINE STORAGE AND ADMINISTRATION
TIV is a split-virus vaccine made up of inactivated, disrupted virus particles administered intramuscularly into the anterolateral thigh of infants and young children and into the deltoid muscle of older children and adults. The cold-adapted LAIV formulation currently licensed in the United States must be shipped and stored at 2°C to 8°C. LAIV doses are 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. How concurrent administration of LAIV with other vaccines affects the safety or efficacy of either LAIV or the simultaneously administered vaccine has not been well studied, but general consensus is that inactivated or live vaccines can be administered simultaneously with LAIV. After administration of a live vaccine, at least 4 weeks should pass before another live vaccine is administered.
Trivalent seasonal influenza immunization is recommended for all children aged 6 months through 18 years. Healthy children aged 2 through 18 years can receive either TIV or LAIV. Immunization efforts should continue to focus on
Use of TIV (not LAIV) for all children and adolescents with underlying medical conditions that are ass ociated with an increased risk for complications from influenza, including
asthma or other chronic pulmonary diseases, including cystic fibrosis;
hemodynamically significant cardiac disease;
immunosuppressive disorders or therapy;
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; or
any condition that can compromise respiratory function or handling of secretions or can increase the risk for aspiration, such as cognitive dysfunction, spinal cord injuries, seizure disorders, or other neuromuscular disorders.
Household contacts and out-of-home care providers of children younger than 5 years and children of all ages who are at risk. Young children are at serious risk of influenza infection, hospitalization, and complications. The risk of influenza-associated hospitalization of healthy children younger than 24 months has been shown to be equal to or greater than the risk in previously recognized high-risk groups. Children aged 24 through 59 months experience increased morbidity as a result of influenza illness, with increased rates of outpatient visits and antimicrobial agent use. Immunization of close contacts of children younger than 6 months is particularly important, because these infants are too young to be immunized. Healthy contacts 2 through 49 years of age can receive either TIV or LAIV.
Any female who will be pregnant during influenza season (TIV only).
Health care professionals.
In addition, immunization with either TIV or LAIV is recommended for the following people to prevent transmission of influenza to those at risk, unless contraindicated:
healthy contacts and caregivers of other children or adults at high risk of complications from influenza infection;
close contacts of immunosuppressed people; and
health care professionals or volunteers.
CONTRAINDICATIONS AND PRECAUTIONS
Minor illnesses, with or without fever, do not contraindicate the use of influenza vaccines, particularly among children with mild upper respiratory infection symptoms or allergic rhinitis.
Children Who Should Not Be Vaccinated With TIV
those younger than 6 months;
those who have a moderate-to-severe febrile illness;
those who have a history of hypersensitivity, including anaphylaxis, to eggs, to any previous influenza vaccine dose, or to any of the vaccine components; and
those who are known to have experienced Guillain-Barré syndrome (GBS) within 6 weeks after a previous influenza vaccination (whether influenza vaccination specifically might increase the risk for recurrence of GBS is unknown).
Children Who Should Not Be Vaccinated With LAIV
those younger than 2 years;
those who have a moderate-to-severe febrile illness;
those who have received other live vaccines within the last 4 weeks (however, other live vaccines can be given on the same day as LAIV);
those with asthma, reactive airways disease, or other chronic disorders of the pulmonary or cardiovascular systems;
those with underlying medical conditions, including metabolic disease such as diabetes mellitus, renal dysfunction, and hemoglobinopathies;
those who have known or suspected immunodeficiency disease or are receiving immunosuppressive therapies;
those who are receiving aspirin or other salicylates;
those who are known to have experienced GBS within 6 weeks after a previous influenza vaccination (whether influenza vaccination specifically might increase the risk for recurrence of GBS is unknown);
adolescents who are pregnant;
those who have a history of hypersensitivity, including anaphylaxis, to eggs, to any previous influenza vaccine dose, or to any of its components; and
those with any condition that can compromise respiratory function or handling of secretions or can increase the risk for aspiration, such as cognitive dysfunction, spinal cord injuries, seizure disorders, or other neuromuscular disorders.
LAIV is not recommended for children with a history of asthma. In the 2- through 4-year-old age group, there are children who have a history of wheezing with respiratory tract illnesses in whom reactive airways disease is diagnosed and in whom asthma may later be diagnosed. Therefore, because of the potential for increased wheezing after immunization, children younger than 5 years with recurrent wheezing or a wheezing episode in the past 12 months should not routinely receive LAIV.
When offering LAIV to children younger than 5 years, a clinician should screen young children who might be at higher risk of asthma by asking parents/guardians of 2-, 3-, and 4-year-olds (24- through 59-month-olds) the question: “In the past 12 months, has a health care professional ever told you that your child had wheezing?” If the parents answer “yes” to this question, LAIV is not recommended for those children. TIV would be recommended for the child for whom LAIV is not given because of history of wheezing.
In addition, TIV is the trivalent seasonal influenza vaccine of choice for anyone in close contact with a person who is severely compromised (ie, in a protected environment). The preference of TIV over LAIV for these people is because of the theoretical risk of infection in an immunocompromised contact of an LAIV-immunized child. Available data indicate that both children and adults vaccinated with LAIV can shed vaccine virus after vaccination. As a precautionary measure, recently vaccinated people should restrict contact with severely immunocompromised patients (eg, hematopoietic stem cell transplant recipients during periods that require a protected environment) for 7 days after LAIV immunization, although there have been no reports of LAIV transmission from a vaccinated person to an immunocompromised person. No data exist on treatment of symptomatic LAIV infections in immunocompromised hosts.
Information about influenza surveillance is available through the Centers for Disease Control and Prevention (CDC) voice information system (influenza update, 888-232-3228) or at www.cdc.gov/flu.
USE OF ANTIVIRAL MEDICATIONS
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 2008–2009 influenza-surveillance data and use them as a guide to empiric 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). From the 2008–2009 season, roughly equal percentages of seasonal A H1N1, novel influenza A (H1N1) virus, and seasonal B influenza were reported, and seasonal A H3N2 was found less frequently.
Because of the complex resistance patterns of circulating influenza strains, empiric therapy of serious influenza-like illness during the influenza season depends on the availability of rapid testing for influenza A or B virus. Routine laboratory testing is not generally available to distinguish between strains of influenza A (eg, H1N1 seasonal, novel H1N1, and H3N2 seasonal) or to determine antiviral susceptibility.
If no testing is available or performed, or if rapid testing results document influenza A and treatment is considered, both oseltamivir and an adamantane (amantadine or rimantadine) should be provided. Note that for children aged 7 years and older, zanamivir may be used as single-drug therapy, similar to past recommendations in the 2008–2009 season.
If rapid testing results document influenza B infection, then either oseltamivir or zanamivir can be used as single-drug empiric therapy.
If local or national influenza-surveillance data indicate a predominance of a particular influenza strain with a known antiviral susceptibility profile, then empiric treatment can be directed toward that strain. For example, during the summer of 2009, more than 98% of influenza viruses tested were a novel influenza A (H1N1) virus. Treatment and chemoprophylaxis recommendations from the CDC have indicated that either oseltamivir or zanamivir could be used. Novel influenza A (H1N1) virus is resistant to adamantane medications.
The accuracy of rapid tests for novel influenza A (H1N1) virus has not been studied extensively. One report suggested a sensitivity of 50%.
Current treatment guidelines (Tables 4 and 5) are applicable to infants and children documented to have infection caused by known seasonal strains or novel influenza A (H1N1) virus. The morbidity and mortality rates of the novel influenza A (H1N1) virus in the United States do not seem to be substantially different from seasonal influenza strains. Continuous monitoring of the epidemiology, change in severity, and resistance patterns of influenza strains may lead to new guidance.
Treatment should be considered for
Influenza infection of any severity in children at high risk, regardless of immunization status.
Any otherwise healthy child with influenza infection who may benefit from the decrease in duration of clinical symptoms documented to occur with therapy. Earlier treatment provides more optimal clinical responses. Dosages for antiviral agents for both treatment and chemoprophylaxis in children, including emergency-use dosing recommendations for oseltamivir in infants, can be found on the CDC Web site at www.cdc.gov/flu/professionals/antivirals/index.htm.
Clinical judgment is an important factor in treatment decisions. Antiviral treatment should be started as soon as possible after illness onset. Persons with suspected influenza who present with an uncomplicated febrile illness typically do not require treatment unless they are at higher risk of influenza complications. In areas with limited antiviral medication availability, local public health authorities might provide additional guidance about diagnostic testing and prioritizing treatment within groups at higher risk of infection.
Recommendations for chemoprophylaxis when there is a seasonal influenza outbreak in a community remain unchanged. This applies to routine circumstances, but it should be noted that guidance may change on the basis of updated antiviral recommendations from the CDC in concert with antiviral availability and local resources.
Children at high risk during the 2 weeks after influenza immunization
Children at high risk for whom influenza vaccine is contraindicated
Family members or health care providers who are unimmunized and are likely to have ongoing, close exposure to
unimmunized children at high risk; or
infants and toddlers who are younger than 24 months
Control of influenza outbreaks for unimmunized staff and children in a closed institutional setting with high-risk pediatric residents (eg, extended-care facilities)
As a supplement to immunization among children at high risk, including those who are immunocompromised and may not respond to vaccine
Postexposure prophylaxis in a family setting
Children at high risk and their family members and close contacts, as well as health care workers, when circulating strains of influenza virus in the community are not matched with trivalent seasonal influenza vaccine strains
Chemoprophylaxis should not be considered a substitute for immunization in most cases. However, the influenza antiviral medications currently licensed are important adjuncts to influenza immunization for control and prevention of influenza disease. Because of high rates of resistance to amantadine and rimantadine among influenza A (H3N2), novel influenza A (H1N1), and B strains and resistance to oseltamivir in seasonal influenza A (H1N1), recommendations for use of these drugs for chemoprophylaxis may vary according to location and season, depending on susceptibility patterns (Table 1). In addition, recommendations for chemoprophylaxis against novel influenza A (H1N1) virus are important to consider. No natural immunity existed for this virus in the pediatric population before the 2008–2009 influenza season, and no previously administered trivalent seasonal influenza vaccine provides protection against novel influenza A (H1N1) virus.
For recommendations about chemoprophylaxis and treatment against influenza, see Tables 4 and 5. Updates will be made on www.cdc.gov/flu/professionals/antivirals/index.htm or www.aapredbook.org/flu.
Although expansion of the recommended age cohort of children for annual immunization can be seen as progress toward universal immunization, the resulting increases in demand for vaccine and overall costs of coverage pose public health challenges that must be faced.
The CDC estimates that the new universal childhood influenza vaccination policy adds 30 million more children to be immunized. Manufacturers anticipate being able to provide adequate supplies of vaccine.
Efforts to build outreach and infrastructure are being created 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 who seek influenza immunization. Because of the increased demand for immunization during each influenza season, the AAP and the CDC have suggested providing the vaccine at any visit to the medical home during influenza season when it is not contraindicated or at specially arranged “shot-only” sessions and cooperating with community clinics, schools, and child care centers to provide influenza vaccine. If alternate venues are indeed used, a system of patient-record transfer is optimal to ensure maintenance of accurate immunization records. Immunization-information systems should be used whenever available.
Cost-effectiveness and logistic feasibility of vaccinating such a large segment of the population continue to be legitimate concerns for many. As plans for immunization are made, particular attention is being paid to vaccine supply, distribution, implementation, and financing. Also, population-based studies from the 2008–2009 influenza season are being analyzed to determine the cost-effectiveness of universal expansion to this childhood age group. Potential benefits among recipients, their contacts, and the community of more widespread childhood immunization 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 work time for parents.
Continued evaluation of the safety, immunogenicity, and effectiveness of LAIV for young children is important. Development of a safe, immunogenic vaccine for infants younger than 6 months also would be valuable. Consideration of how best to administer influenza vaccine to the parents of patients in the office is being explored. Lastly, efforts are being explored to improve the vaccine-development process to allow for a shorter interval between identification of vaccine strains to be included each year and vaccine production. This idea has been put to the test most recently with the novel influenza A (H1N1) virus strain pandemic outbreak, which began in Mexico in April 2009.
COMMITTEE ON INFECTIOUS DISEASES, 2009–2010
Joseph A. Bocchini Jr, MD, Chairperson
Henry H. Bernstein, DO
John S. Bradley, MD
Michael T. Brady, MD
Carrie L. Byington, MD
Margaret C. Fisher, MD
Mary P. Glode, MD
Mary Anne Jackson, MD
Harry L. Keyserling, MD
David W. Kimberlin, MD
Walter A. Orenstein, MD
Gordon E. Schutze, MD
Rodney E. Willoughby, MD
FORMER COMMITTEE MEMBERS
Penelope H. Dennehy, MD
Robert W. Frenck Jr, MD
Lorry G. Rubin, MD
Beth Bell, MD, MPH
Centers for Disease Control and Prevention
Robert Bortolussi, MD
Canadian Paediatric Society
Richard D. Clover, MD
American Academy of Family Physicians
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
R. Douglas Pratt, MD
Food and Drug Administration
Lucia Lee, MD
Food and Drug Administration
Jennifer S. Read, MD
National Institutes of Health
Jeffrey R. Starke, MD
American Thoracic Society
Jack Swanson, MD
Committee on Practice Ambulatory Medicine
Carol J. Baker, MD
Associate Editor, Red Book
Sarah S. Long, MD
Associate Editor, Red Book
Larry K. Pickering, MD
Editor, Red Book
Edgar O. Ledbetter, MD
H. Cody Meissner, MD
J. Dennis O'Dell, MD
Medical Home Expert
Stuart T. Weinberg, MD
Partnership for Policy Implementation
Jennifer Frantz, MPH
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.
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.
- American Academy of Pediatrics. Influenza. In: Pickering LK, Baker CJ, Long SS, Kimberlin DW, eds. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:400– 412. Available at: www.aapredbook.org/flu
- Centers for Disease Control and Prevention. Antiviral agents for the prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep.2009; In press
- Harper SA, Bradley JS, Englund JA, et al; Expert Panel of the Infectious Diseases Society of America. Seasonal influenza in adults and children: diagnosis, treatment, chemoprophylaxis, and institutional outbreak management—clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis.2009;48 (8):1003– 1032
- Copyright © 2009 by the American Academy of Pediatrics