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Seasonal influenza in children: Prevention with vaccines

Seasonal influenza in children: Prevention with vaccines
Authors:
Flor M Munoz, MD, MSc
Morven S Edwards, MD
Section Editor:
Sheldon L Kaplan, MD
Deputy Editor:
Diane Blake, MD
Literature review current through: Sep 2023.
This topic last updated: Sep 19, 2023.

INTRODUCTION — Influenza is an acute respiratory illness caused by influenza A or B viruses, and rarely influenza C viruses, which occurs in outbreaks worldwide every year, mainly during the winter seasons (in temperate climates) (figure 1).

Influenza usually is an acute, self-limited, and uncomplicated disease in healthy children, but it can be associated with severe morbidity and mortality. Certain groups of children are at increased risk of severe or complicated influenza infection (table 1).

Immunization is the most effective means of preventing influenza infection. This topic will discuss seasonal influenza vaccination in children. The clinical features, diagnosis, and management of influenza; influenza chemoprophylaxis in children; and seasonal vaccination in adults are discussed separately.

●(See "Seasonal influenza in children: Clinical features and diagnosis".)

●(See "Seasonal influenza in children: Management".)

●(See "Seasonal influenza in children: Prevention with antiviral drugs".)

●(See "Seasonal influenza vaccination in adults".)

INFLUENZA ACTIVITY — Information about influenza activity at the national, regional, and state level is available from the United States Centers for Disease Control and Prevention (FluView) and the World Health Organization (FluNet). Surveillance information is updated regularly during influenza season.

The coronavirus disease 2019 (COVID-19) pandemic was associated with atypical influenza activity during 2020-2021 in the northern hemisphere and 2021 in the southern hemisphere, when influenza activity was far lower than usual, with only sporadic detections of influenza A or B viruses [1,2]. The 2022-2023 season was characterized by unusually early influenza activity, with a peak in late November to early December, and predominance of influenza A viruses (H3N2 and H1N1), with reports of influenza B continuing into the spring [3].

INFLUENZA VACCINES

Types of vaccine — Several types of influenza vaccine are licensed for use in infants, children, and adolescents (table 2), including inactivated influenza vaccines (IIV), live attenuated influenza vaccine (LAIV), and recombinant influenza vaccine (RIV) (table 3) [4]. (See 'Choice of vaccine' below.)

●IIV4 – Quadrivalent IIV (IIV4) that are available for children age 6 months through 17 years of age in the United States include (table 2) [4]:

•Standard dose inactivated egg-based preparations of subvirion components derived from seed strains grown in eggs.

•Inactivated cell culture-based quadrivalent vaccines (ccIIV4), which are egg free [5-8].

●LAIV4 – LAIV4 (Flumist) is a quadrivalent live-attenuated vaccine that is administered intranasally. It is licensed for use in healthy nonpregnant individuals 2 through 49 years of age (table 2) [4].

LAIV4 is a cold-adapted vaccine prepared through genetic reassortment [9,10]. Reversion of the vaccine virus to a virulent strain in vaccine recipients has not been observed [11,12]. LAIV4 may contain residual amounts of egg protein.

●RIV4 – Quadrivalent RIV (RIV4) is produced using recombinant deoxyribonucleic acid (DNA) technology. It is egg free and available for use in individuals ≥18 years of age (table 2) [4].

Antigenic composition — The strains included in seasonal influenza vaccine are updated each year to correlate with the strains anticipated to circulate during the coming influenza season. Available influenza vaccines may contain two strains of influenza A and one strain of influenza B (trivalent vaccines) or two strains of influenza A and two strains of influenza B (quadrivalent vaccines). For the 2023-2024 influenza season in the northern hemisphere, all of the vaccines licensed in the United States are quadrivalent (table 2).

●Northern hemisphere – The World Health Organization and US Food and Drug Administration recommend that egg-based influenza vaccines for the 2023-2024 influenza season in the northern hemisphere (October to May) contain the following strains [4,13]:

•A/Victoria/4897/2022(H1N1)pdm09-like virus

•A/Darwin/9/2021 (H3N2)-like virus

•B/Austria/1359417/2021 (Victoria lineage)-like virus

•B/Phuket/3073/2013 (B/Yamagata lineage)-like virus

The World Health Organization and US Food and Drug Administration recommend that cell culture-based and recombinant influenza vaccines for the 2023-2024 influenza season in the northern hemisphere (October to May) contain the following strains [4,13]:

•A/Wisconsin/67/2022(H1N1)pdm09-like virus

•A/Darwin/6/2021 (H3N2)-like virus

•B/Austria/1359417/2021 (Victoria lineage)-like virus

•B/Phuket/3073/2013 (B/Yamagata lineage)-like virus

●Southern hemisphere – The WHO recommends that egg-based influenza vaccines for the 2023 influenza season in the southern hemisphere (April through September) contain the following strains [14]:

•A/Sydney/5/2021 (H1N1)pdm09-like virus

•A/Darwin/9/2021 (H3N2)-like virus

•B/Austria/1359417/2021 (B/Victoria lineage)-like virus

•B/Phuket/3073/2013 (B/Yamagata lineage)-like virus (quadrivalent vaccines only)

The WHO recommends that cell culture-based and recombinant influenza vaccines for the 2023 influenza season in the southern hemisphere (April through September) contain the following strains [14]:

•A/Sydney/5/2021 (H1N1)pdm09-like virus

•A/Darwin/6/2021 (H3N2)-like virus

•B/Austria/1359417/2021 (B/Victoria lineage)-like virus

•B/Phuket/3073/2013 (B/Yamagata lineage)-like virus (quadrivalent vaccines only)

Supply — The supply of influenza vaccine for the 2023-2024 influenza season in the United States is expected to be sufficient [15]. The Centers for Disease Control and Prevention will update information about vaccine supply as necessary. Priority groups for immunization when the vaccine supply is limited are discussed separately. (See 'Limited supply of vaccine' below.)

TARGET GROUPS

United States — In the United States, the Center for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices and the American Academy of Pediatrics (AAP) recommend universal annual influenza vaccination for persons ≥6 months [4,16]. The CDC recommends influenza vaccination even when the vaccine strains are not well matched to circulating strains.

High-priority groups for seasonal influenza immunization include:

●Individuals at risk for severe or complicated influenza (table 1)

●Health care personnel, for whom the AAP supports mandatory influenza immunization [16]

●Migrant and refugee children (who are at increased risk for influenza) [17]

Universal immunization of everyone older than six months has the potential to reduce influenza disease, influenza-related complications, medical resource use [18,19], and influenza-related school or work absence. Increasing the numbers of immunized individuals also may reduce influenza among unimmunized contacts within the household and community ("community immunity" or "herd immunity") [20,21]. This may be particularly helpful in preventing influenza infection among infants younger than six months and high-risk individuals who did not receive the vaccine. (See 'Prevention of illness and death' below and 'Community ("herd") immunity' below.)

Other countries — Recommendations for influenza vaccine vary from country to country. Schedules for individual countries are available through the World Health Organization.

ADMINISTRATION

Contraindications and precautions — Contraindications and precautions for influenza immunization are summarized in the table (table 4) [4].

Allergy to eggs — Although the prescribing information for egg-based vaccines (table 2) includes severe allergic reaction to egg protein as a contraindication, the Advisory Committee on Immunization Practices (ACIP) recommends any licensed vaccine that is appropriate for age and health status for individuals with egg allergy of any severity [4].

The ACIP no longer recommends that children with severe allergy to eggs (ie, reaction involving angioedema or swelling, respiratory distress, lightheadedness, or recurrent vomiting) receive egg-based inactivated influenza vaccines (IIV) in a setting in which vaccine administration is supervised by a health care provider experienced in the recognition and management of severe allergic reactions [4,22]. However, the ACIP also reaffirms that all vaccines should be administered in settings in which personnel and equipment needed for rapid recognition and treatment of acute hypersensitivity reactions are available.

The administration of influenza vaccine to children who are allergic to eggs is discussed separately. (See "Influenza vaccination in persons with egg allergy".)

Contraindications — Contraindications to influenza vaccine vary with the type of vaccine (table 4) [4,23,24].

●Egg-based quadrivalent IIV (IIV4) – History of severe allergic reaction to any component of the vaccine (other than eggs) or to a previous dose of any influenza vaccine (egg-based, inactivated cell-cultured influenza vaccines [ccIIV], recombinant influenza vaccine [RIV], or live attenuated influenza vaccine [LAIV])

Children with sensitivity to thimerosal should be given a single-dose prefilled syringe of IIV; single-dose formulations do not contain thimerosal (table 2) [4].

●Quadrivalent ccIIV (ccIIV4) – History of severe allergic reaction to a previous dose of any ccIIV or any component of ccIIV4

●Quadrivalent LAIV (LAIV4)

•History of severe allergic reaction to any component of the vaccine (other than eggs) or to a previous dose of any influenza vaccine (egg-based, ccIIV, RIV, or LAIV)

•Concomitant receipt of aspirin- or salicylate-containing therapy in children and adolescents (6 months through 17 years)

•Children age two through four years with:

-A diagnosis of asthma

-Parent- or caregiver-reported wheezing or asthma verified by a health care provider in the past 12 months

-Documented wheezing in the past 12 months

•Any cause of compromised immunity (including human immunodeficiency virus [HIV] infection or medication-related immunosuppression, congenital or acquired immunodeficiency, anatomic or functional asplenia [including that due to sickle cell disease])

•Close contact of a person who is severely immunosuppressed and requires a protected environment

•Pregnancy

•Active communication between the cerebrospinal fluid (CSF) and the oropharynx, nasopharynx, nose, or ear or any other CSF leak

•Cochlear implant

•Receipt of:

-Oseltamivir or zanamivir within the past 48 hours

-Peramivir within the past 5 days

-Baloxavir within the past 17 days

These intervals are based upon the half-life of the antiviral agent [4].

●Quadrivalent RIV (RIV4) – History of severe allergic reaction to a previous dose of any RIV or any component of RIV

Precautions — Precautions are conditions that may increase the risk for a serious reaction to immunization, cause diagnostic confusion or compromise the ability of the vaccine to produce immunity [25]. Influenza immunization generally should be deferred in children with precautions, but in certain cases, the potential benefit outweighs the risk (eg, moderate acute illness in a child with a high-risk condition who will not be able to return for seasonal influenza vaccine for several weeks).

●Precautions for all influenza vaccines

•Moderate or severe acute illness with or without fever.

Influenza immunization usually should be withheld from children with moderate to severe acute febrile illness until their symptoms have resolved. However, minor illnesses with or without fever do not contraindicate influenza immunization, particularly among children with upper respiratory tract infection or allergic rhinitis.

•History of Guillain-Barré syndrome (GBS) within six weeks of receipt of influenza vaccine.

The theoretic risk of GBS should be balanced against the potential morbidity and mortality of influenza infection when making decisions about influenza immunization [4].

●Additional precautions for ccIIV4 – History of severe allergic reaction to a previous dose of any other influenza vaccine (egg-based IIV, RIV, or LAIV); ccIIV4 should be given in a medical setting and supervised by a health care provider who can recognize and manage severe allergic reactions.

●Additional precautions for LAIV

•Asthma in children ≥5 years of age.

•Other medical conditions (regardless of age) that predispose to complications after wild-type influenza (eg, chronic pulmonary, cardiovascular [except isolated hypertension], renal, hepatic, neurologic, hematologic, or metabolic disorders [including diabetes mellitus]) (table 1). We prefer IIV for children with these conditions (table 5). (See 'Choice of vaccine' below.)

●Additional precautions for RIV4 – History of severe allergic reaction to a previous dose of any other influenza vaccine (egg-based IIV, ccIIV, or LAIV); RIV4 should be given in a medical setting and supervised by a health care provider who can recognize and manage severe allergic reactions.

Choice of vaccine — The choice of vaccine is limited by age, clinical features, and contraindications. IIV4 is available for all persons ≥6 months of age, including those with underlying medical conditions. LAIV4 is available for nonpregnant persons age 2 through 49 years. RIV4 is available for persons ≥18 years of age. Contraindications and precautions are discussed separately. (See 'Contraindications and precautions' above.)

●IIV preferred given contraindications or precautions to LAIV4 – IIV4 is preferred for the following groups of children (table 5) [4,23]:

•Children between 6 and 24 months of age

Although LAIV4 is not licensed for use in children <2 years of age, if a dose of LAIV4 is inadvertently administered to a child age 6 through 24 months, the dose does not need to be repeated [26].

•Children with contraindications to LAIV (table 4) (see 'Contraindications and precautions' above)

•Children ≥5 years with asthma

•Children with other medical conditions that predispose to complications after wild-type influenza (table 1)

●Children without contraindications or precautions to IIV or LAIV4 – When choosing influenza vaccine for children ≥2 years of age without contraindications to IIV or LAIV4, we prioritize vaccine coverage. We do not have a preference between IIV and LAIV and encourage shared decision-making with the patient and caregivers to determine which among the available vaccines (IIV4, LAIV4) is most acceptable.

For children and adolescents, neither the ACIP nor the American Academy of Pediatrics makes a preferential recommendation for one influenza vaccine type or brand over another [4,16]. Influenza vaccination should not be delayed while awaiting a particular product.

Schedule — Seasonal influenza is administered annually. Annual immunization is necessary even if the previous season's vaccine contained one or more of the current season's antigens because immunity declines in the year after vaccination [4,27-31].

If possible, influenza vaccine should be offered before the onset of influenza activity in the community (by the end of October in the northern hemisphere and by April in the southern hemisphere) [4]. In the northern hemisphere, influenza circulation typically peaks any time from October through March (figure 1). However, the COVID-19 pandemic has been associated with atypical influenza activity. (See 'Influenza activity' above.)

Seasonal influenza vaccine should be provided as long as influenza viruses are circulating and unexpired influenza vaccine is available (ie, before June 30 in the United States) [4,32,33]. (See "Influenza: Epidemiology and pathogenesis".)

Influenza vaccine should be offered at every opportunity, including during hospitalization [33]. (See 'Improving vaccine coverage' below.)

●Children ≥9 years of age – Children ≥9 years of age at the start of the influenza season require only a single dose of influenza vaccine [4,34].

●Children six months through eight years of age – Children six months through eight years of age at the start of the influenza season require two doses of influenza vaccine during the first season in which they are vaccinated to optimize immune response [4,34-37].

The recommendations for previously vaccinated children six months through eight years of age vary from year to year.

For the 2023-2024 season [4]:

•Children six months through eight years should receive one dose if they received ≥2 doses of trivalent or quadrivalent influenza vaccine separated by ≥4 weeks before July 1, 2023; the two doses need not have been administered in the same season or in consecutive seasons.

•Children six months through eight years should receive two doses ≥4 weeks apart if they did not receive ≥2 doses of trivalent or quadrivalent influenza vaccine separated by ≥4 weeks before July 1, 2023, or if it is not known whether they received ≥2 doses of trivalent or quadrivalent influenza vaccine before July 1, 2023.

For children who require two doses of vaccine, the first dose should be administered as soon as the vaccine is available, to ensure that both doses are received before the onset of influenza activity [4]. The second dose should be administered even if the child's ninth birthday occurs before the second dose in the same season. The two doses need not be the same type (eg, IIV4, LAIV4) or brand [16].

Route and dose

●IIV4 – For children <18 years, IIV is administered intramuscularly (IM). The preferred site is the anterolateral thigh for infants and young children and the deltoid for older children and adults [4]. (See "Standard immunizations for children and adolescents: Overview", section on 'Injectable vaccines'.)

The dose varies with age and vaccine formulation (table 2) [4,7]:

•For children 6 through 35 months:

-Afluria – 0.25 mL IM

-Fluzone – Either 0.25 mL or 0.5 mL IM

-Fluarix – 0.5 mL IM

-Flucelvax – 0.5 mL IM

-FluLaval – 0.5 mL IM

Whichever vaccine is chosen should be administered at the appropriate volume. The number of doses of vaccine is not affected by the volume (ie, children who need two doses of vaccine should receive two doses regardless of whether the 0.25 mL or the 0.5 mL formulation is used).

•For children ≥36 months – 0.5 mL IM

•Dosing mix-ups in children <36 months of age – When using the Afluria vaccine (0.25 mL dose), if a child <36 months inadvertently receives a dose of 0.5 mL instead of 0.25 mL, the dose may be counted as valid; the child should receive subsequent doses of the vaccine as indicated (eg, if the child requires two doses of influenza vaccine and the 0.5 mL dose was administered for the first dose, the child should receive the second dose [0.25 mL of Afluria] at least four weeks later). In a randomized trial comparing the two doses, immunogenicity and rates of local and systemic reactions were similar [38].

When using Fluarix, FluLaval, or Flucelvax, if a child <36 months inadvertently receives a dose of 0.25 mL instead of 0.5 mL and the child has not yet left the office, the remaining 0.25 mL can be administered. If the child has left the office, they should return to the office for an age-appropriate dose (0.5 mL) [39].

•Dosing mix-ups in children ≥36 months of age – If a child ≥36 months inadvertently receives a dose of 0.25 mL instead of 0.5 mL, and the child has not yet left the office, the remaining 0.25 mL can be administered (or if the remaining volume is uncertain, it is acceptable to administer a full dose of 0.5 mL) [4]. If the child has left the office, they should return to the office for an age-appropriate dose (0.5 mL).

●LAIV4 – The total intranasal dose for LAIV4 is 0.2 mL (0.1 mL to each nostril) [4].

If only one-half of the dose of LAIV4 is administered (ie, 0.1 mL to a single nostril), it should not be counted [39]. A full dose of influenza vaccine must be administered at another visit. The timing of the full dose varies with the type of vaccine: ≥4 weeks after the partial dose for LAIV4; any time after the partial dose for IIV.

Administration with other vaccines

●IIV – IIV may be administered at the same time, but at a different site, as other recommended vaccines, including COVID-19 vaccines [4,40,41].

Although there is a slight increased risk of febrile seizures in children 6 through 23 months of age if IIV is administered on the same day as either pneumococcal conjugate vaccine (PCV) and/or diphtheria-tetanus-acellular pertussis vaccine (DTaP), the absolute risk is small (<30 per 100,000) [42-45] . Given the greater risk of prolonging susceptibility to vaccine-preventable infections if any of these vaccines is delayed, the ACIP does not recommend administering the vaccines on separate days [4]. In a randomized trial, the proportion of children who developed fever within two days of vaccination was similar (8 to 9 percent) whether IIV was administered on the same day as PCV and DTaP or two weeks later [46].

●LAIV – LAIV4 can be administered at the same time as other live and inactivated vaccines, including COVID-19 vaccines [4,47]. However, if it is not administered on the same day as other live vaccines (eg, measles-mumps-rubella, varicella zoster), it should be administered at least four weeks later [48].

●COVID-19 vaccine – Children who are eligible for COVID-19 vaccination may receive COVID-19 vaccine and influenza vaccine at the same visit (at different injection sites) [4,49]. Although information regarding coadministration of these vaccines is limited [50], the benefits of timely immunization against COVID-19 and influenza outweigh the potential reactogenicity.

Anticipatory guidance — Caregivers of infants and children who receive influenza vaccine, particularly children who are susceptible to severe disease from influenza (table 1), should be reminded that they may contract acute influenza infection despite immunization. Such patients may be candidates for antiviral therapy if they acquire influenza infection, the efficacy of which is enhanced by early treatment (within 24 to 48 hours of onset of symptoms). (See 'Documented influenza infection' below and "Seasonal influenza in children: Management", section on 'Antiviral therapy'.)

Improving vaccine coverage — Although estimated seasonal influenza vaccination coverage rates in children in the United States generally have increased since 2009, coverage rates for influenza vaccine are lower than for most other recommended childhood vaccines. Caregivers appear to be more hesitant toward influenza vaccine than other routine childhood immunizations [51]. Text message reminders may increase receipt of the second dose of vaccine for children who need a second dose [52]. (See 'Schedule' above.)

In addition, opportunities to vaccinate individuals for influenza, particularly individuals at increased risk for severe or complicated influenza, often are missed. Seasonal influenza vaccine should be offered at every opportunity, including during hospitalization [4,32,33].

Strategies to address vaccine hesitancy and increase vaccination coverage are discussed separately. (See "Standard childhood vaccines: Parental hesitancy or refusal", section on 'Approach to management' and "Standard immunizations for children and adolescents: Overview", section on 'Vaccination coverage'.)

SPECIAL CIRCUMSTANCES

Limited supply of vaccine — Special effort should be made to immunize the following groups when vaccine supply is limited [4,53]:

●Children and adolescents who are at high risk for severe or complicated influenza infection (table 1)

●Women who are or will be pregnant during the influenza season (see "Immunizations during pregnancy", section on 'Inactivated influenza vaccine')

●Household contacts and out-of-home caregivers of children and adolescents who are at high risk for severe or complicated influenza, including children <59 months of age, and especially contacts of infants <6 months of age

●Children who may transmit influenza to a high-risk household member

Pregnancy — Influenza vaccination during pregnancy is discussed separately. (See "Seasonal influenza and pregnancy".)

Immunocompromised children — Inactivated influenza vaccine (IIV) is recommended for patients with known or suspected immunodeficiency or immunosuppressive therapy. Live attenuated influenza vaccine (LAIV) is contraindicated in such patients. (See 'Contraindications and precautions' above.)

●Cancer – IIV typically elicits a poor response among children receiving immunosuppressive chemotherapy [54-56]. Influenza immunization for children with cancer is discussed separately. (See "Immunizations in solid organ transplant candidates and recipients", section on 'Influenza' and "Immunizations in adults with cancer", section on 'Influenza vaccine' and "Immunizations in hematopoietic cell transplant candidates and recipients".)

Immunization of close contacts is an important influenza prevention strategy for all immunocompromised patients.

●Glucocorticoids

•Brief or alternate day course – The antibody response to influenza vaccine is not affected by brief (<14 days) courses of glucocorticoids or glucocorticoids that are administered every other day [40,57].

•Prolonged course (≥14 days), high dose – Antibody response to influenza vaccine may be impaired by prolonged administration (≥14 days) of high-dose glucocorticoids (equivalent to prednisone 20 mg/day or >2 mg/kg per day for patients weighing <10 kg) [40,57].

For patients receiving high-dose glucocorticoids for ≥14 days, influenza vaccination may be deferred, as long as deferral does not decrease the likelihood of completing immunization before the beginning of influenza season.

For children who are expected to require high-dose glucocorticoids throughout the influenza season, immunization with IIV, chemoprophylaxis, and immunization of close contacts is a reasonable approach. (See "Seasonal influenza in children: Prevention with antiviral drugs".)

●HIV – Influenza immunization of children with HIV infection is discussed separately. (See "Immunizations in persons with HIV", section on 'Influenza vaccine'.)

Travelers — Influenza occurs throughout the year in the tropics and during April through September in the southern hemisphere. Outbreaks of influenza have occurred on cruise ships and within organized tour groups or mass gatherings [58-60]. (See "Influenza: Epidemiology and pathogenesis".)

Children who received an influenza vaccine during the previous influenza season do not require revaccination [61]; information about the benefits of revaccination is lacking.

Those who did not receive an influenza vaccine during the previous influenza season, particularly those with high-risk conditions (table 1), should receive influenza vaccine at least two weeks before travel [4]:

●To the tropics

●With organized tour groups

●On cruise ships

●To the opposite hemisphere during its influenza season (April to September in the southern hemisphere, October to May in the northern hemisphere)

In the United States, the previous influenza season's influenza vaccine usually expires on the following June 30 [62].

The World Health Organization recommends that travelers with high-risk conditions who travel to the opposite hemisphere receive an influenza vaccine that contains the strains recommended for the opposite hemisphere two weeks before travel [63]. If the vaccine recommended for the opposite hemisphere is not available before travel, the traveler (or traveler's caregivers) should try to arrange vaccination as soon as possible after arriving in the opposite hemisphere, recognizing that it will take two weeks to develop protection [64]. The antigenic composition of the northern and southern hemisphere influenza vaccines is discussed separately. (See 'Antigenic composition' above.)

Travelers who receive the previous season's influenza vaccine for summer travel should receive the current season's influenza vaccine in the fall [62].

Documented influenza infection

●Children not vaccinated against influenza – Children who did not receive influenza vaccine for the current influenza season and have recovered from a laboratory-confirmed influenza illness or unconfirmed influenza-like illness should be vaccinated with IIV or recombinant influenza vaccine (RIV; if ≥18 years of age). Multiple influenza virus strains circulate in any given season, and infection with one type of virus does not provide immunity to the other types [65].

●Children vaccinated against influenza – For children and adolescents vaccinated against influenza, the need for revaccination depends upon the type of vaccination and the timing of antiviral therapy (if antiviral therapy was received):

•Vaccinated with IIV – Revaccination is not necessary.

•Vaccinated with LAIV and did not receive antiviral therapy for influenza – Revaccination is not necessary.

•Vaccinated with LAIV and received antiviral therapy for influenza – Revaccination with IIV or RIV (for those ≥18 years of age) should be provided if [4]:

-Oseltamivir or zanamivir was given 48 hours before through two weeks after LAIV

-Peramivir was given 5 days before through two weeks after LAIV

-Baloxavir was given 17 days before through two weeks after LAIV

EFFICACY AND EFFECTIVENESS — The protective effect of influenza vaccine is determined largely by the relationship between the strains in the vaccine and the viruses that circulate during influenza season (closeness of "fit" or "match"). Although effectiveness is decreased when the fit is poor, influenza vaccination prevents a substantial burden of influenza morbidity and mortality [66,67].

Prevention of illness and death

●Laboratory-confirmed influenza – Influenza vaccination prevents laboratory-confirmed influenza infection. In a meta-analysis of randomized trials that compared influenza vaccine with placebo or no intervention, trivalent inactivated influenza vaccine (IIV3) was approximately 65 percent and trivalent live attenuated influenza vaccine (LAIV3) was approximately 80 percent efficacious in preventing laboratory-confirmed influenza in children [68].

Vaccine effectiveness measures how well the vaccine protects against infection when the vaccine is used in routine circumstances in the community. When vaccine strains are closely matched to circulating vaccine strains, vaccine effectiveness in observational studies is similar to vaccine efficacy in randomized trials [69-71].

Influenza vaccine effectiveness in preventing laboratory-confirmed influenza in the United States is available from the Centers for Disease Control and Prevention (CDC) for influenza seasons from 2004-2005 to 2022-2023 (with the exception of the 2020-2021 influenza season because of low influenza virus circulation) and has ranged from 10 to 60 percent [72,73].

During 2022-2023, influenza vaccine effectiveness against influenza A (H3N2 and H1N1) was 54 percent (95% CI 23-73 percent) among persons <65 years of age and 71 percent (95% CI 31-90 percent) among children and adolescents <18 years of age [74].

In addition to preventing laboratory-confirmed influenza, influenza vaccine also appears to reduce the severity of breakthrough influenza in vaccine recipients [75-79].

●Hospitalization for laboratory-confirmed influenza – Influenza vaccination is effective in preventing influenza-related hospitalization and admission to a pediatric intensive care unit [18,80]. In a meta-analysis of observational studies, the effectiveness of influenza vaccination in preventing laboratory-confirmed influenza-related hospitalization in children age <18 years was 53 percent (95% CI 47-59 percent) [80]. Effectiveness varied by influenza type: 36 percent for influenza A/H3N2, 69 percent for influenza A(H1N1)pdm09, and 47 percent for influenza type B. Effectiveness also varied by age (6 months through 5 years: 62 percent; 6 through 17 years: 52 percent) and the closeness of match between vaccine and circulating strains (good match for all or some strains: approximately 60 percent; mismatch: approximately 33 percent). In a subsequent multicenter prospective study, the effectiveness of influenza vaccination in preventing hospitalization in children 6 months to 17 years was sustained throughout the influenza season [81].

●Laboratory-confirmed influenza-associated death – Influenza vaccination prevents influenza-associated death [82,83]. During 2010 to 2014, the estimated effectiveness of influenza vaccine in preventing laboratory-confirmed influenza-associated death was 65 percent (95% CI 47-78) among children without high-risk conditions and 51 percent (95% CI 31-67) among children with high-risk conditions [82].

●Clinical influenza – The effectiveness of influenza vaccines for the outcome of "clinical influenza" generally is lower than that of laboratory-confirmed influenza, given that influenza vaccines have no effect on other viral pathogens that circulate at the same time during the winter, which decreases the specificity of the diagnosis.

In a meta-analysis of seven randomized trials (19,388 patients), the effectiveness of IIV in preventing clinical influenza-like illness in children older than two years was 28 percent (95% CI 21-35) [68]. Randomized trials addressing the effectiveness of IIV in preventing clinical influenza-like illness in children younger than two years were lacking. In cohort studies, the effectiveness of IIV in preventing influenza-like illness among children younger than two years ranges from 25 to 69 to percent [84,85].

●Otitis media – The efficacy of IIV in the prevention of acute otitis media is discussed separately. (See "Acute otitis media in children: Prevention of recurrence", section on 'Influenza vaccine'.)

IIV versus LAIV — In studies published before the 2013-2014 influenza season, LAIV3 was efficacious and appeared to have some advantages over IIV, including greater immunity against mismatched strains, immediate protection during an outbreak, and better T cell responses [9,86-93]. However, observational studies between the 2013-2014 and 2017-2018 influenza seasons in the United States indicated that IIV was more effective than quadrivalent LAIV (LAIV4) in preventing laboratory-confirmed influenza in children, particularly influenza A(H1N1)pdm09 [94-102]. Based on these studies, LAIV was not recommended in the United States during the 2016-2017 and 2017-2018 influenza seasons; during the 2018-2019 influenza season, the American Academy of Pediatrics (AAP) made a preferential recommendation for IIV over LAIV.

LAIV was reformulated for the 2018-2019 influenza season, and this formulation appeared to be effective against influenza A(H1N1) in children. In surveillance in the United Kingdom, where LAIV is the only available vaccine for children age 2 through 17 years, adjusted LAIV effectiveness against influenza A(H1N1)pdm09 was 50 percent (95% CI -14 to 78 percent) during the 2018-2019 influenza season [103]. Data regarding the effectiveness of reformulated LAIV4 in the United States are not available; LAIV4 use in the United States since the 2018-2019 influenza season has been low, and the proportion of influenza vaccines administered since the 2018-2019 influenza season that were LAIV4 is unknown [104]. The CDC and AAP will continue to assess reported vaccine effectiveness to update influenza vaccination recommendations if pertinent.

The relative efficacy of LAIV and IIV in adults is discussed separately. (See "Seasonal influenza vaccination in adults".)

Serial vaccination — Several reports suggest that receiving an influenza vaccine in the previous season may decrease the effectiveness for the current season [105-110]. However, in most of these studies and subsequent studies, effectiveness was greater among those who received consecutive seasonal influenza vaccines than those who received influenza vaccine only during the previous season or were unvaccinated [111-113].

In a meta-analysis of five randomized trials including 11,987 participants, vaccine effectiveness was similar whether participants were immunized in two consecutive seasons (71 percent, 95% CI 62-78 percent) or only in the current season (58 percent, 95% CI 48-66 percent) [114]. Meta-analysis of 28 observational studies including 28,627 participants also found similar effectiveness among those immunized in two consecutive seasons and only in the current season [114].

The mechanism for decreased effectiveness with a single vaccination in the previous season is unclear but may be related to large differences between vaccine antigens in the previous year's vaccine and the current circulating strain (ie, "antigenic distance") [115].

Immunogenicity — The immunogenicity of IIV among children varies with age, dose, number of previous doses, influenza strains, and vaccine manufacturer [116-119]. Most infants ≥6 months of age, including former extremely low-birth weight premature infants, develop protective levels of antibody after two doses of IIV [120]. However, antibody response among previously unvaccinated infants between 6 and 23 months of age appears to increase with increasing age [121]. Antibody response among infants younger than six months can be affected by maternal antibody [122,123]. IIV is not licensed for use in infants younger than six months.

Exposure to influenza infection in previous years may affect the response to vaccination, especially among children <36 months of age [124]. Children with pre-existing hemagglutinin-inhibition antibody to influenza A and influenza B antigen from previous influenza virus infection (ie, not from persistent maternal antibody) are more likely to develop a protective immune response after immunization.

Community ("herd") immunity — Widespread immunization of school and day care attendees appears to be associated with "community immunity" (also called "herd immunity") with diminished influenza infection in unvaccinated children and adults of all ages [20,21,125-128]. In a systematic review, indirect protective effectiveness from community immunity appeared to be strongest in closely connected communities, households, and older adults [127].

ADVERSE EFFECTS

IIV — The most frequent adverse effect of inactivated influenza vaccine (IIV) is a local reaction with soreness at the injection site [9,129-131]. Fever may occur. It is usually low grade and occurs predominately in children younger than two years; 10 to 35 percent of such children become febrile, usually within 24 hours after vaccination [40]. Serious adverse reactions are rare [132].

The safety of IIV in children has been confirmed in population-based studies in which no significant adverse effects or associations were detected during specified time periods (ranging from 0 to 42 days) after IIV administration [133-135].

Among the 512 adverse events reported to the United States Vaccine Adverse Event Reporting System (VAERS) between 2013 and 2015 following quadrivalent IIV administration in children 6 months through 17 years, injection site erythema, injection site swelling, and fever were the most frequent [136].

Increased rates of febrile seizures have been reported among children 6 through 23 months of age who received IIV and the 13-valent pneumococcal conjugate vaccine and/or a diphtheria-tetanus-acellular pertussis-containing vaccine at the same visit. (See 'Administration with other vaccines' above.)

IIV immunization in children with asthma has not been associated with asthma exacerbation [137-139].

Immunization in some years has been associated with a slight increase in Guillain-Barré syndrome in adults, but only rare cases have been reported in children. (See "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis", section on 'Vaccinations'.)

LAIV — The safety of live attenuated influenza vaccine (LAIV) has been evaluated in a number of trials including more than 18,000 children younger than five years [10]. Few adverse events occurred in controlled trials in healthy children 12 months to 18 years of age [10,87,140]. In a meta-analysis of three studies [93,140,141], nasal congestion/runny nose and fever >100°F (37.8°C) occurred in at least 5 percent more of the recipients of vaccine than of placebo after the first dose (58 versus 50 percent and 16 versus 11 percent for congestion and fever, respectively) [10]. Nasal congestion and low-grade fever typically peak within three to four days after the first dose of LAIV [142].

During the 2013-2014 influenza season, approximately 12.7 million individuals age 2 through 49 years received quadrivalent LAIV, and VAERS received 779 reports [143]. Among children age 2 through 17 years, fever (13 percent) and cough (8 percent) were the most frequently reported adverse events. No concerning patterns were identified.

●Asthma and wheezing – Studies evaluating the association between LAIV and asthma, wheezing, or respiratory illnesses in children younger than five years have had conflicting results [9,91,139,144-149]. Among children age five years and older, receipt of LAIV has not been associated with an increased frequency of wheezing or asthma-related events [90,139,149,150].

LAIV is not licensed for use in children younger than two years and is contraindicated in children age two through four years with a diagnosis of asthma, caregiver report or health care provider finding of wheezing or asthma in the previous 12 months, or medical record documented wheezing in the previous 12 months [4]. Asthma is a precaution for LAIV in people ≥5 years of age. (See 'Contraindications and precautions' above.)

●Viral shedding – Viral shedding after immunization with LAIV varies with age, previous receipt of LAIV, and virus type [151,152]. In an observational study, rates of shedding in children decreased with increasing age, receipt of LAIV in the previous season (for influenza B but not influenza A viruses), and with influenza A compared with influenza B viruses [152]. In another observational study in children and adults, viral shedding peaked 2 to 3 days after vaccination and resolved by 10 days in children age 5 through 8 years and 6 days in older subjects [151].

Vaccine virus that is shed after immunization may be detected by respiratory virus polymerase chain reaction assay [153]. (See "Seasonal influenza in children: Clinical features and diagnosis", section on 'Approach to testing'.)

●Transmission – Transmission of the live attenuated influenza strains to unprotected contacts appears to be uncommon. In a randomized trial comparing LAIV and placebo in 197 day care attendees (age 9 to 36 months), although 80 percent of LAIV recipients shed at least one virus strain, there was only one confirmed case of transmission to a placebo recipient [56]. The calculated probability of transmission to a child after contact with a single vaccinated child was 0.58 percent (95% CI 0-1.7 percent).

RESOURCES

●Vaccine information statement for inactivated influenza vaccine (IIV) from the Centers for Disease Control and Prevention (CDC)

●Vaccine information statement for live attenuated influenza vaccine (LAIV) from the CDC

●The Advisory Committee on Immunization Practices (ACIP) recommendation for the prevention and control of influenza with vaccines

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Immunizations in children and adolescents" and "Society guideline links: Seasonal influenza vaccination".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword[s] of interest.)

●Basics topic (see "Patient education: Flu (The Basics)")

●Beyond the Basics topics (see "Patient education: Influenza prevention (Beyond the Basics)" and "Patient education: Influenza symptoms and treatment (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Types of vaccine – Immunization is the major means of influenza prevention. Several types of influenza vaccine are licensed for use in infants, children, and adolescents, including quadrivalent inactivated influenza vaccines (IIV4, for those ≥6 months of age), quadrivalent live attenuated influenza vaccine (LAIV4, for those ≥2 years of age), and quadrivalent recombinant influenza vaccine (RIV4, for those ≥18 years of age) (table 2 and table 3). (See 'Types of vaccine' above.)

●Target groups – For children ≥6 months of age, we recommend annual influenza immunization (Grade 1A). Influenza immunization reduces the risk of influenza disease and influenza-related hospitalization and complications. (See 'Target groups' above and 'Efficacy and effectiveness' above.)

Immunization is particularly important for individuals who are at increased risk of severe and complicated influenza (table 1), household contacts of individuals who are at increased risk of severe and complicated influenza, and household contacts of individuals who cannot be vaccinated (eg, children <6 months of age, children and adolescents with contraindications to vaccination). These groups should be prioritized if vaccine supply is limited. (See 'Target groups' above and 'Limited supply of vaccine' above.)

●Contraindications and precautions – Contraindications and precautions to seasonal influenza immunization are provided in the table (table 4). (See 'Contraindications and precautions' above.)

●Choice of vaccine – Within age limits and contraindications/precautions, we do not have a preference for a particular type or formulation of vaccine (table 5). We encourage shared decision-making with the patient and caregivers to determine which among the available vaccines is most acceptable. (See 'Choice of vaccine' above.)

●Schedule – Annual immunization is necessary because immunity declines after immunization. For children age six months through eight years, the number of doses varies with past history of influenza immunization. For the 2023-2024 season in the northern hemisphere, children age six months through eight years should receive:

•One dose if they received ≥2 doses of influenza vaccine separated by ≥4 weeks before July 1, 2023 (the two doses need not have been administered in the same season)

•Two doses separated by ≥4 weeks if they did not receive ≥2 doses of influenza vaccine separated by ≥4 weeks before July 1, 2023, or if it is not known whether they received ≥2 doses of influenza vaccine before July 1, 2023

Immunization should be completed (ie, one or two doses) in the fall (ideally by the end of October in the northern hemisphere and by April in the southern hemisphere). (See 'Schedule' above.)

●Dose and route – The dose and route of administration vary with age and vaccine formulation as summarized in the table (table 2). (See 'Route and dose' above.)

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  96. Gaglani M, Pruszynski J, Murthy K, et al. Influenza Vaccine Effectiveness Against 2009 Pandemic Influenza A(H1N1) Virus Differed by Vaccine Type During 2013-2014 in the United States. J Infect Dis 2016; 213:1546.
  97. Cost AA, Hiser MJ, Hu Z, et al. Brief report: mid-season influenza vaccine effectiveness estimates for the 2013-2014 influenza season. MSMR 2014; 21:15.
  98. Caspard H, Gaglani M, Clipper L, et al. Effectiveness of live attenuated influenza vaccine and inactivated influenza vaccine in children 2-17 years of age in 2013-2014 in the United States. Vaccine 2016; 34:77.
  99. Valdin HL, Bégué RE. Influenza vaccines effectiveness 2013-14 through 2015-16, a test-negative study in children. Vaccine 2017; 35:4088.
  100. Caspard H, Mallory RM, Yu J, Ambrose CS. Live-Attenuated Influenza Vaccine Effectiveness in Children From 2009 to 2015-2016: A Systematic Review and Meta-Analysis. Open Forum Infect Dis 2017; 4:ofx111.
  101. Chung JR, Flannery B, Ambrose CS, et al. Live Attenuated and Inactivated Influenza Vaccine Effectiveness. Pediatrics 2019; 143.
  102. Jackson ML, Chung JR, Jackson LA, et al. Influenza Vaccine Effectiveness in the United States during the 2015-2016 Season. N Engl J Med 2017; 377:534.
  103. Pebody RG, Whitaker H, Ellis J, et al. End of season influenza vaccine effectiveness in primary care in adults and children in the United Kingdom in 2018/19. Vaccine 2020; 38:489.
  104. COMMITTEE ON INFECTIOUS DISEASES. Recommendations for Prevention and Control of Influenza in Children, 2021-2022. Pediatrics 2021; 148.
  105. Ohmit SE, Petrie JG, Malosh RE, et al. Influenza vaccine effectiveness in the community and the household. Clin Infect Dis 2013; 56:1363.
  106. Ohmit SE, Thompson MG, Petrie JG, et al. Influenza vaccine effectiveness in the 2011-2012 season: protection against each circulating virus and the effect of prior vaccination on estimates. Clin Infect Dis 2014; 58:319.
  107. McLean HQ, Thompson MG, Sundaram ME, et al. Impact of repeated vaccination on vaccine effectiveness against influenza A(H3N2) and B during 8 seasons. Clin Infect Dis 2014; 59:1375.
  108. Ohmit SE, Petrie JG, Malosh RE, et al. Influenza vaccine effectiveness in households with children during the 2012-2013 season: assessments of prior vaccination and serologic susceptibility. J Infect Dis 2015; 211:1519.
  109. Skowronski DM, Chambers C, Sabaiduc S, et al. A Perfect Storm: Impact of Genomic Variation and Serial Vaccination on Low Influenza Vaccine Effectiveness During the 2014-2015 Season. Clin Infect Dis 2016; 63:21.
  110. Saito N, Komori K, Suzuki M, et al. Dose-Dependent Negative Effects of Prior Multiple Vaccinations Against Influenza A and Influenza B Among Schoolchildren: A Study of Kamigoto Island in Japan During the 2011-2012, 2012-2013, and 2013-2014 Influenza Seasons. Clin Infect Dis 2018; 67:897.
  111. Petrie JG, Monto AS. Untangling the Effects of Prior Vaccination on Subsequent Influenza Vaccine Effectiveness. J Infect Dis 2017.
  112. Nichols MK, Andrew MK, Ye L, et al. The Impact of Prior Season Vaccination on Subsequent Influenza Vaccine Effectiveness to Prevent Influenza-related Hospitalizations Over 4 Influenza Seasons in Canada. Clin Infect Dis 2019; 69:970.
  113. Kim SS, Flannery B, Foppa IM, et al. Effects of Prior Season Vaccination on Current Season Vaccine Effectiveness in the United States Flu Vaccine Effectiveness Network, 2012-2013 Through 2017-2018. Clin Infect Dis 2021; 73:497.
  114. Bartoszko JJ, McNamara IF, Aras OAZ, et al. Does consecutive influenza vaccination reduce protection against influenza: A systematic review and meta-analysis. Vaccine 2018; 36:3434.
  115. Skowronski DM, Chambers C, De Serres G, et al. Serial vaccination and the antigenic distance hypothesis: effects on influenza vaccine effectiveness during A(H3N2) epidemics in Canada, 2010-11 to 2014-15. J Infect Dis 2017.
  116. Baxter R, Jeanfreau R, Block SL, et al. A Phase III evaluation of immunogenicity and safety of two trivalent inactivated seasonal influenza vaccines in US children. Pediatr Infect Dis J 2010; 29:924.
  117. Englund JA, Walter E, Black S, et al. Safety and immunogenicity of trivalent inactivated influenza vaccine in infants: a randomized double-blind placebo-controlled study. Pediatr Infect Dis J 2010; 29:105.
  118. Nolan T, McVernon J, Skeljo M, et al. Immunogenicity of a monovalent 2009 influenza A(H1N1) vaccine in infants and children: a randomized trial. JAMA 2010; 303:37.
  119. Skowronski DM, Hottes TS, Chong M, et al. Randomized controlled trial of dose response to influenza vaccine in children aged 6 to 23 months. Pediatrics 2011; 128:e276.
  120. D'Angio CT, Heyne RJ, Duara S, et al. Immunogenicity of trivalent influenza vaccine in extremely low-birth-weight, premature versus term infants. Pediatr Infect Dis J 2011; 30:570.
  121. Walter EB, Rajagopal S, Zhu Y, et al. Trivalent inactivated influenza vaccine (TIV) immunogenicity in children 6 through 23 months of age: do children of all ages respond equally? Vaccine 2010; 28:4376.
  122. Halasa NB, Gerber MA, Chen Q, et al. Safety and immunogenicity of trivalent inactivated influenza vaccine in infants. J Infect Dis 2008; 197:1448.
  123. Walter EB, Englund JA, Blatter M, et al. Trivalent inactivated influenza virus vaccine given to two-month-old children: an off-season pilot study. Pediatr Infect Dis J 2009; 28:1099.
  124. Hurwitz ES, Haber M, Chang A, et al. Studies of the 1996-1997 inactivated influenza vaccine among children attending day care: immunologic response, protection against infection, and clinical effectiveness. J Infect Dis 2000; 182:1218.
  125. Loeb M, Russell ML, Moss L, et al. Effect of influenza vaccination of children on infection rates in Hutterite communities: a randomized trial. JAMA 2010; 303:943.
  126. Pannaraj PS, Wang HL, Rivas H, et al. School-located influenza vaccination decreases laboratory-confirmed influenza and improves school attendance. Clin Infect Dis 2014; 59:325.
  127. Yin JK, Heywood AE, Georgousakis M, et al. Systematic Review and Meta-analysis of Indirect Protection Afforded by Vaccinating Children Against Seasonal Influenza: Implications for Policy. Clin Infect Dis 2017; 65:719.
  128. Hurwitz ES, Haber M, Chang A, et al. Effectiveness of influenza vaccination of day care children in reducing influenza-related morbidity among household contacts. JAMA 2000; 284:1677.
  129. Skowronski DM, Jacobsen K, Daigneault J, et al. Solicited adverse events after influenza immunization among infants, toddlers, and their household contacts. Pediatrics 2006; 117:1963.
  130. Rosenberg M, Sparks R, McMahon A, et al. Serious adverse events rarely reported after trivalent inactivated influenza vaccine (TIV) in children 6-23 months of age. Vaccine 2009; 27:4278.
  131. Ohmit SE, Gross J, Victor JC, Monto AS. Reduced reaction frequencies with repeated inactivated or live-attenuated influenza vaccination. Vaccine 2009; 27:1050.
  132. Jefferson T, Rivetti A, Harnden A, et al. Vaccines for preventing influenza in healthy children. Cochrane Database Syst Rev 2008; :CD004879.
  133. Hambidge SJ, Glanz JM, France EK, et al. Safety of trivalent inactivated influenza vaccine in children 6 to 23 months old. JAMA 2006; 296:1990.
  134. Greene SK, Kulldorff M, Lewis EM, et al. Near real-time surveillance for influenza vaccine safety: proof-of-concept in the Vaccine Safety Datalink Project. Am J Epidemiol 2010; 171:177.
  135. Glanz JM, Newcomer SR, Hambidge SJ, et al. Safety of trivalent inactivated influenza vaccine in children aged 24 to 59 months in the vaccine safety datalink. Arch Pediatr Adolesc Med 2011; 165:749.
  136. Haber P, Moro PL, Lewis P, et al. Post-licensure surveillance of quadrivalent inactivated influenza (IIV4) vaccine in the United States, Vaccine Adverse Event Reporting System (VAERS), July 1, 2013-May 31, 2015. Vaccine 2016; 34:2507.
  137. Cates CJ, Rowe BH. Vaccines for preventing influenza in people with asthma. Cochrane Database Syst Rev 2013; :CD000364.
  138. Vasileiou E, Sheikh A, Butler C, et al. Effectiveness of Influenza Vaccines in Asthma: A Systematic Review and Meta-Analysis. Clin Infect Dis 2017; 65:1388.
  139. Ray GT, Lewis N, Goddard K, et al. Asthma exacerbations among asthmatic children receiving live attenuated versus inactivated influenza vaccines. Vaccine 2017; 35:2668.
  140. Belshe RB, Mendelman PM, Treanor J, et al. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children. N Engl J Med 1998; 338:1405.
  141. Tam JS, Capeding MR, Lum LC, et al. Efficacy and safety of a live attenuated, cold-adapted influenza vaccine, trivalent against culture-confirmed influenza in young children in Asia. Pediatr Infect Dis J 2007; 26:619.
  142. Piedra PA, personal communication.
  143. Haber P, Moro PL, Cano M, et al. Post-licensure surveillance of quadrivalent live attenuated influenza vaccine United States, Vaccine Adverse Event Reporting System (VAERS), July 2013-June 2014. Vaccine 2015; 33:1987.
  144. Piedra PA, Gaglani MJ, Riggs M, et al. Live attenuated influenza vaccine, trivalent, is safe in healthy children 18 months to 4 years, 5 to 9 years, and 10 to 18 years of age in a community-based, nonrandomized, open-label trial. Pediatrics 2005; 116:e397.
  145. Bergen R, Black S, Shinefield H, et al. Safety of cold-adapted live attenuated influenza vaccine in a large cohort of children and adolescents. Pediatr Infect Dis J 2004; 23:138.
  146. Gaglani MJ, Piedra PA, Riggs M, et al. Safety of the intranasal, trivalent, live attenuated influenza vaccine (LAIV) in children with intermittent wheezing in an open-label field trial. Pediatr Infect Dis J 2008; 27:444.
  147. Turner PJ, Southern J, Andrews NJ, et al. Safety of live attenuated influenza vaccine in young people with egg allergy: multicentre prospective cohort study. BMJ 2015; 351:h6291.
  148. Baxter RP, Lewis N, Fireman B, et al. Live Attenuated Influenza Vaccination Before 3 Years of Age and Subsequent Development of Asthma: A 14-year Follow-up Study. Pediatr Infect Dis J 2018; 37:383.
  149. Nordin JD, Vazquez-Benitez G, Olsen A, et al. Safety of guidelines recommending live attenuated influenza vaccine for routine use in children and adolescents with asthma. Vaccine 2019; 37:4055.
  150. Sokolow AG, Stallings AP, Kercsmar C, et al. Safety of Live Attenuated Influenza Vaccine in Children With Asthma. Pediatrics 2022; 149.
  151. Block SL, Yogev R, Hayden FG, et al. Shedding and immunogenicity of live attenuated influenza vaccine virus in subjects 5-49 years of age. Vaccine 2008; 26:4940.
  152. Jackson D, Pitcher M, Hudson C, et al. Viral Shedding in Recipients of Live Attenuated Influenza Vaccine in the 2016-2017 and 2017-2018 Influenza Seasons in the United Kingdom. Clin Infect Dis 2020; 70:2505.
  153. Lumley S, Atkinson C, Haque T. Respiratory PCR detects influenza after intranasal live-attenuated influenza vaccination. Arch Dis Child 2014; 99:301.
Topic 5960 Version 121.0

References

1 : World Health Organization. Recommended composition of influenza virus vaccines for use in the 2021-2022 northern hemisphere influenza season. February 2021. https://www.who.int/publications/m/item/recommended-composition-of-influenza-virus-vaccines-for-use-in-the-2021-2022-northern-hemisphere-influenza-season (Accessed on August 28, 2021).

2 : World Health Organization. Recommended composition of influenza virus vaccines for use in the 2022 southern hemisphere influenza season. Septermber 24, 2021. https://www.who.int/publications/m/item/recommended-composition-of-influenza-virus-vaccines-for-use-in-the-2021-southern-hemisphere-influenza-season (Accessed on September 28, 2021).

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4 : Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021-22 Influenza Season.

5 : Relative Effectiveness of the Cell-Cultured Quadrivalent Influenza Vaccine Compared to Standard, Egg-derived Quadrivalent Influenza Vaccines in Preventing Influenza-like Illness in 2017-2018.

6 : Efficacy of a Cell-Culture-Derived Quadrivalent Influenza Vaccine in Children.

7 : Efficacy of a Cell-Culture-Derived Quadrivalent Influenza Vaccine in Children.

8 : Safety and Immunogenicity of Cell-Based Quadrivalent Influenza Vaccine: A Randomized Trial.

9 : Live attenuated versus inactivated influenza vaccine in infants and young children.

10 : Current status of live attenuated influenza vaccine in the United States for seasonal and pandemic influenza.

11 : Genotypic stability of cold-adapted influenza virus vaccine in an efficacy clinical trial.

12 : Genetic and phenotypic stability of cold-adapted influenza viruses in a trivalent vaccine administered to children in a day care setting.

13 : Genetic and phenotypic stability of cold-adapted influenza viruses in a trivalent vaccine administered to children in a day care setting.

14 : Genetic and phenotypic stability of cold-adapted influenza viruses in a trivalent vaccine administered to children in a day care setting.

15 : Genetic and phenotypic stability of cold-adapted influenza viruses in a trivalent vaccine administered to children in a day care setting.

16 : Recommendations for Prevention and Control of Influenza in Children, 2022-2023.

17 : Multistate Outbreak of Respiratory Infections Among Unaccompanied Children, June 2014-July 2014.

18 : Effectiveness of influenza vaccine against life-threatening RT-PCR-confirmed influenza illness in US children, 2010-2012.

19 : Association Between Hospitalization With Community-Acquired Laboratory-Confirmed Influenza Pneumonia and Prior Receipt of Influenza Vaccination.

20 : Universal vaccination of children against influenza: are there indirect benefits to the community? A systematic review of the evidence.

21 : Direct and indirect effectiveness of influenza vaccination delivered to children at school preceding an epidemic caused by 3 new influenza virus variants.

22 : Administration of influenza vaccines to egg allergic recipients: A practice parameter update 2017.

23 : 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host.

24 : 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host.

25 : 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host.

26 : 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host.

27 : Antibody responses after inactivated influenza vaccine in young children.

28 : Duration of protection provided by live attenuated influenza vaccine in children.

29 : Effectiveness of monovalent 2009 pandemic influenza A virus subtype H1N1 and 2010-2011 trivalent inactivated influenza vaccines in Wisconsin during the 2010-2011 influenza season.

30 : Intraseason Waning of Influenza Vaccine Protection: Evidence From the US Influenza Vaccine Effectiveness Network, 2011-2012 Through 2014-2015.

31 : Duration of Influenza Vaccine Effectiveness: A Systematic Review, Meta-analysis, and Meta-regression of Test-Negative Design Case-Control Studies.

32 : Notes from the Field: Administration of Expired Injectable Influenza Vaccines Reported to the Vaccine Adverse Event Reporting System - United States, July 2018-March 2019.

33 : Safety of Influenza Vaccination Administered During Hospitalization.

34 : Vaccines against influenza WHO position paper–November 2012.

35 : Patterns of Influenza Vaccination and Vaccine Effectiveness Among Young US Children Who Receive Outpatient Care for Acute Respiratory Tract Illness.

36 : Antibody Response and Protection After Receipt of Inactivated Influenza Vaccine: A Systematic Review.

37 : Single-Dose Vaccination Among Infants and Toddlers Provides Modest Protection Against Influenza Illness, Which Wanes After 5 Months.

38 : Safety and Immunogenicity of Full-Dose Trivalent Inactivated Influenza Vaccine (TIV) Compared With Half-Dose TIV Administered to Children 6 Through 35 Months of Age.

39 : Safety and Immunogenicity of Full-Dose Trivalent Inactivated Influenza Vaccine (TIV) Compared With Half-Dose TIV Administered to Children 6 Through 35 Months of Age.

40 : Safety and Immunogenicity of Full-Dose Trivalent Inactivated Influenza Vaccine (TIV) Compared With Half-Dose TIV Administered to Children 6 Through 35 Months of Age.

41 : Safety and Immunogenicity of Full-Dose Trivalent Inactivated Influenza Vaccine (TIV) Compared With Half-Dose TIV Administered to Children 6 Through 35 Months of Age.

42 : Signal identification and evaluation for risk of febrile seizures in children following trivalent inactivated influenza vaccine in the Vaccine Safety Datalink Project, 2010-2011.

43 : Risk of fever after pediatric trivalent inactivated influenza vaccine and 13-valent pneumococcal conjugate vaccine.

44 : Febrile Seizure Risk After Vaccination in Children 6 to 23 Months.

45 : Febrile Seizure Risk After Vaccination in Children 6 to 23 Months.

46 : Fever After Influenza, Diphtheria-Tetanus-Acellular Pertussis, and Pneumococcal Vaccinations.

47 : Safety and immunogenicity of concurrent administration of live attenuated influenza vaccine with measles-mumps-rubella and varicella vaccines to infants 12 to 15 months of age.

48 : Safety and immunogenicity of concurrent administration of live attenuated influenza vaccine with measles-mumps-rubella and varicella vaccines to infants 12 to 15 months of age.

49 : Safety and immunogenicity of concurrent administration of live attenuated influenza vaccine with measles-mumps-rubella and varicella vaccines to infants 12 to 15 months of age.

50 : Safety and immunogenicity of concomitant administration of COVID-19 vaccines (ChAdOx1 or BNT162b2) with seasonal influenza vaccines in adults in the UK (ComFluCOV): a multicentre, randomised, controlled, phase 4 trial.

51 : Parental Hesitancy About Routine Childhood and Influenza Vaccinations: A National Survey.

52 : Text Message Reminders for the Second Dose of Influenza Vaccine for Children: An RCT.

53 : Influenza-associated deaths among children in the United States, 2003-2004.

54 : Influenza vaccines: from surveillance through production to protection.

55 : Influenza vaccination in children being treated with chemotherapy for cancer.

56 : A randomized, double-blind study of the safety, transmissibility and phenotypic and genotypic stability of cold-adapted influenza virus vaccine.

57 : A randomized, double-blind study of the safety, transmissibility and phenotypic and genotypic stability of cold-adapted influenza virus vaccine.

58 : Travellers and influenza: risks and prevention.

59 : Increase in Hospital Admissions for Severe Influenza A/B among Travelers on Cruise Ships to Alaska, 2015.

60 : Influenza Outbreaks Among Passengers and Crew on Two Cruise Ships: A Recent Account of Preparedness and Response to an Ever-Present Challenge.

61 : Influenza Outbreaks Among Passengers and Crew on Two Cruise Ships: A Recent Account of Preparedness and Response to an Ever-Present Challenge.

62 : Influenza Outbreaks Among Passengers and Crew on Two Cruise Ships: A Recent Account of Preparedness and Response to an Ever-Present Challenge.

63 : Influenza Outbreaks Among Passengers and Crew on Two Cruise Ships: A Recent Account of Preparedness and Response to an Ever-Present Challenge.

64 : Influenza vaccines: challenges and solutions.

65 : Consecutive Infections With Influenza A and B Virus in Children During the 2014-2015 Seasonal Influenza Epidemic.

66 : Effects of Influenza Vaccination in the United States During the 2017-2018 Influenza Season.

67 : Vaccine Effectiveness Against Life-Threatening Influenza Illness in US Children.

68 : Vaccines for preventing influenza in healthy children.

69 : Effectiveness of inactivated influenza vaccine in children aged 9 months to 3 years: an observational cohort study.

70 : Vaccine Effectiveness Against Laboratory-confirmed Influenza in Healthy Young Children: A Case-Control Study.

71 : Effectiveness of trivalent flu vaccine in healthy young children.

72 : Effectiveness of trivalent flu vaccine in healthy young children.

73 : Interim Estimates of 2019-20 Seasonal Influenza Vaccine Effectiveness - United States, February 2020.

74 : Interim Estimates of 2022-23 Seasonal Influenza Vaccine Effectiveness - Wisconsin, October 2022-February 2023.

75 : Vaccine for prevention of mild and moderate-to-severe influenza in children.

76 : Clinical Presentation of Influenza in Children 6 to 35 Months of Age: Findings From a Randomized Clinical Trial of Inactivated Quadrivalent Influenza Vaccine.

77 : Influenza vaccine effectiveness in preventing outpatient, inpatient, and severe cases of laboratory-confirmed influenza.

78 : Vaccine-associated reduction in symptom severity among patients with influenza A/H3N2 disease.

79 : Influenza Vaccination Modifies Disease Severity Among Community-dwelling Adults Hospitalized With Influenza.

80 : Effectiveness of Influenza Vaccination in Preventing Hospitalization Due to Influenza in Children: A Systematic Review and Meta-analysis.

81 : Sustained Within-season Vaccine Effectiveness Against Influenza-associated Hospitalization in Children: Evidence From the New Vaccine Surveillance Network, 2015-2016 Through 2019-2020.

82 : Influenza Vaccine Effectiveness Against Pediatric Deaths: 2010-2014.

83 : Influenza Vaccine Effectiveness Against Influenza-Related Mortality in Australian Hospitalized Patients: A Propensity Score Analysis.

84 : Effectiveness of the 2003-2004 influenza vaccine among children 6 months to 8 years of age, with 1 vs 2 doses.

85 : Influenza vaccine effectiveness in healthy 6- to 21-month-old children during the 2003-2004 season.

86 : Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis.

87 : Safety and efficacy of live attenuated influenza vaccine in children 2-7 years of age.

88 : Estimating efficacy of trivalent, cold-adapted, influenza virus vaccine (CAIV-T) against influenza A (H1N1) and B using surveillance cultures.

89 : Trivalent live attenuated intranasal influenza vaccine administered during the 2003-2004 influenza type A (H3N2) outbreak provided immediate, direct, and indirect protection in children.

90 : Comparison of the efficacy and safety of live attenuated cold-adapted influenza vaccine, trivalent, with trivalent inactivated influenza virus vaccine in children and adolescents with asthma.

91 : Superior relative efficacy of live attenuated influenza vaccine compared with inactivated influenza vaccine in young children with recurrent respiratory tract infections.

92 : Live and inactivated influenza vaccines induce similar humoral responses, but only live vaccines induce diverse T-cell responses in young children.

93 : Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine.

94 : Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine.

95 : Seasonal Effectiveness of Live Attenuated and Inactivated Influenza Vaccine.

96 : Influenza Vaccine Effectiveness Against 2009 Pandemic Influenza A(H1N1) Virus Differed by Vaccine Type During 2013-2014 in the United States.

97 : Brief report: mid-season influenza vaccine effectiveness estimates for the 2013-2014 influenza season.

98 : Effectiveness of live attenuated influenza vaccine and inactivated influenza vaccine in children 2-17 years of age in 2013-2014 in the United States.

99 : Influenza vaccines effectiveness 2013-14 through 2015-16, a test-negative study in children.

100 : Live-Attenuated Influenza Vaccine Effectiveness in Children From 2009 to 2015-2016: A Systematic Review and Meta-Analysis.

101 : Live Attenuated and Inactivated Influenza Vaccine Effectiveness.

102 : Influenza Vaccine Effectiveness in the United States during the 2015-2016 Season.

103 : End of season influenza vaccine effectiveness in primary care in adults and children in the United Kingdom in 2018/19.

104 : Recommendations for Prevention and Control of Influenza in Children, 2021-2022.

105 : Influenza vaccine effectiveness in the community and the household.

106 : Influenza vaccine effectiveness in the 2011-2012 season: protection against each circulating virus and the effect of prior vaccination on estimates.

107 : Impact of repeated vaccination on vaccine effectiveness against influenza A(H3N2) and B during 8 seasons.

108 : Influenza vaccine effectiveness in households with children during the 2012-2013 season: assessments of prior vaccination and serologic susceptibility.

109 : A Perfect Storm: Impact of Genomic Variation and Serial Vaccination on Low Influenza Vaccine Effectiveness During the 2014-2015 Season.

110 : Dose-Dependent Negative Effects of Prior Multiple Vaccinations Against Influenza A and Influenza B Among Schoolchildren: A Study of Kamigoto Island in Japan During the 2011-2012, 2012-2013, and 2013-2014 Influenza Seasons.

111 : Untangling the Effects of Prior Vaccination on Subsequent Influenza Vaccine Effectiveness.

112 : The Impact of Prior Season Vaccination on Subsequent Influenza Vaccine Effectiveness to Prevent Influenza-related Hospitalizations Over 4 Influenza Seasons in Canada.

113 : Effects of Prior Season Vaccination on Current Season Vaccine Effectiveness in the United States Flu Vaccine Effectiveness Network, 2012-2013 Through 2017-2018.

114 : Does consecutive influenza vaccination reduce protection against influenza: A systematic review and meta-analysis.

115 : Serial vaccination and the antigenic distance hypothesis: effects on influenza vaccine effectiveness during A(H3N2) epidemics in Canada, 2010-11 to 2014-15.

116 : A Phase III evaluation of immunogenicity and safety of two trivalent inactivated seasonal influenza vaccines in US children.

117 : Safety and immunogenicity of trivalent inactivated influenza vaccine in infants: a randomized double-blind placebo-controlled study.

118 : Immunogenicity of a monovalent 2009 influenza A(H1N1) vaccine in infants and children: a randomized trial.

119 : Randomized controlled trial of dose response to influenza vaccine in children aged 6 to 23 months.

120 : Immunogenicity of trivalent influenza vaccine in extremely low-birth-weight, premature versus term infants.

121 : Trivalent inactivated influenza vaccine (TIV) immunogenicity in children 6 through 23 months of age: do children of all ages respond equally?

122 : Safety and immunogenicity of trivalent inactivated influenza vaccine in infants.

123 : Trivalent inactivated influenza virus vaccine given to two-month-old children: an off-season pilot study.

124 : Studies of the 1996-1997 inactivated influenza vaccine among children attending day care: immunologic response, protection against infection, and clinical effectiveness.

125 : Effect of influenza vaccination of children on infection rates in Hutterite communities: a randomized trial.

126 : School-located influenza vaccination decreases laboratory-confirmed influenza and improves school attendance.

127 : Systematic Review and Meta-analysis of Indirect Protection Afforded by Vaccinating Children Against Seasonal Influenza: Implications for Policy.

128 : Effectiveness of influenza vaccination of day care children in reducing influenza-related morbidity among household contacts.

129 : Solicited adverse events after influenza immunization among infants, toddlers, and their household contacts.

130 : Serious adverse events rarely reported after trivalent inactivated influenza vaccine (TIV) in children 6-23 months of age.

131 : Reduced reaction frequencies with repeated inactivated or live-attenuated influenza vaccination.

132 : Vaccines for preventing influenza in healthy children.

133 : Safety of trivalent inactivated influenza vaccine in children 6 to 23 months old.

134 : Near real-time surveillance for influenza vaccine safety: proof-of-concept in the Vaccine Safety Datalink Project.

135 : Safety of trivalent inactivated influenza vaccine in children aged 24 to 59 months in the vaccine safety datalink.

136 : Post-licensure surveillance of quadrivalent inactivated influenza (IIV4) vaccine in the United States, Vaccine Adverse Event Reporting System (VAERS), July 1, 2013-May 31, 2015.

137 : Vaccines for preventing influenza in people with asthma.

138 : Effectiveness of Influenza Vaccines in Asthma: A Systematic Review and Meta-Analysis.

139 : Asthma exacerbations among asthmatic children receiving live attenuated versus inactivated influenza vaccines.

140 : The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children.

141 : Efficacy and safety of a live attenuated, cold-adapted influenza vaccine, trivalent against culture-confirmed influenza in young children in Asia.

142 : Efficacy and safety of a live attenuated, cold-adapted influenza vaccine, trivalent against culture-confirmed influenza in young children in Asia.

143 : Post-licensure surveillance of quadrivalent live attenuated influenza vaccine United States, Vaccine Adverse Event Reporting System (VAERS), July 2013-June 2014.

144 : Live attenuated influenza vaccine, trivalent, is safe in healthy children 18 months to 4 years, 5 to 9 years, and 10 to 18 years of age in a community-based, nonrandomized, open-label trial.

145 : Safety of cold-adapted live attenuated influenza vaccine in a large cohort of children and adolescents.

146 : Safety of the intranasal, trivalent, live attenuated influenza vaccine (LAIV) in children with intermittent wheezing in an open-label field trial.

147 : Safety of live attenuated influenza vaccine in young people with egg allergy: multicentre prospective cohort study.

148 : Live Attenuated Influenza Vaccination Before 3 Years of Age and Subsequent Development of Asthma: A 14-year Follow-up Study.

149 : Safety of guidelines recommending live attenuated influenza vaccine for routine use in children and adolescents with asthma.

150 : Safety of Live Attenuated Influenza Vaccine in Children With Asthma.

151 : Shedding and immunogenicity of live attenuated influenza vaccine virus in subjects 5-49 years of age.

152 : Viral Shedding in Recipients of Live Attenuated Influenza Vaccine in the 2016-2017 and 2017-2018 Influenza Seasons in the United Kingdom.

153 : Respiratory PCR detects influenza after intranasal live-attenuated influenza vaccination.

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