Recommendations For Prevention and Control of Influenza in Children 2023-2024

TECHNICAL REPORT
Recommendations for Prevention and

Control of Influenza in Children,
2023–2024
COMMITTEE ON INFECTIOUS DISEASES
This technical report accompanies the recommendations of the abstract

American Academy of Pediatrics for the routine use of influenza vaccine
and antiviral medications in the prevention and treatment of influenza
in children during the 2023–2024 season. The rationale for the
American Academy of Pediatrics recommendation for annual influenza
vaccination of all children without medical contraindications starting at
6 months of age is provided. Influenza vaccination is an important
strategy for protecting children and the broader community against This document is copyrighted and is property of the American
Academy of Pediatrics and its Board of Directors. All authors have
influenza. This technical report summarizes recent influenza seasons, filed conflict of interest statements with the American Academy of
morbidity and mortality in children, vaccine effectiveness, and Pediatrics. Any conflicts have been resolved through a process
approved by the Board of Directors. The American Academy of
vaccination coverage, and provides detailed guidance on vaccine Pediatrics has neither solicited nor accepted any commercial
involvement in the development of the content of this publication.
storage, administration, and implementation. The report also provides a
Technical reports from the American Academy of Pediatrics benefit
brief background on inactivated and live-attenuated influenza vaccines, from expertise and resources of liaisons and internal (AAP) and
available vaccines this season, vaccination during pregnancy and external reviewers. However, technical reports from the American
Academy of Pediatrics may not reflect the views of the liaisons or
breastfeeding, diagnostic testing for influenza, and antiviral medications the organizations or government agencies that they represent.
for treatment and chemoprophylaxis. Strategies to promote vaccine The guidance in this report does not indicate an exclusive course
uptake are emphasized. of treatment or serve as a standard of medical care. Variations,
taking into account individual circumstances, may be appropriate.
All technical reports from the American Academy of Pediatrics
automatically expire 5 years after publication unless reaffirmed,
revised, or retired at or before that time.
INTRODUCTION
DOI: https://doi.org/10.1542/peds.2023-063773
This technical report accompanies the recommendations of the American
Address correspondence to Kristina A. Bryant, MD. E-mail: kristina.
Academy of Pediatrics (AAP) for the routine use of influenza vaccine and bryant@louisville.edu
antiviral medications in the prevention and treatment of influenza in PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
children during the 2023–2024 season.1 Copyright © 2023 by the American Academy of Pediatrics
COMPANION PAPER: A companion to this article can be found
SUMMARY OF RECENT INFLUENZA ACTIVITY IN THE UNITED STATES online at www.pediatrics.org/cgi/doi/10.1542/peds.2023-063772.
Recent influenza seasons in the United States have varied by sever-
ity, duration, and impact on children’s health (Table 1). Influenza
vaccine effectiveness (VE) has likewise varied by year, influenza type To cite: AAP Committee on Infectious Diseases.
Recommendations for Prevention and Control of Influenza in
and influenza A virus subtype, and age group of the child immunized
Children, 2023–2024. Pediatrics. 2023;152(4):e2023063773
(Fig 1).
PEDIATRICS Volume 152, number 4, October 2023:e2023063773 FROM THE AMERICAN ACADEMY OF PEDIATRICS
Downloaded from http://publications.aap.org/pediatrics/article-pdf/doi/10.1542/peds.2023-063773/1526224/peds.2023-063773.pdf
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TABLE 1 Summary of Recent Influenza Seasons
2018–2019 2019–2020 2020–2021 2021–2022
Severity Moderate Moderate Low Low
Duration 21 wk — — —
Predominant viruses Influenza A (H1N1) pdm09, Influenza B/Victoria, early; Influenza A (H3N2), influenza Influenza A (H3N2)
early; influenza A (H3N2), influenza A (H1N1) B (Victoria)
late pdm09, late
Vaccination coverage in 62.5% 62.3% 58.2% 57.8%
children
Hospitalization rate 71 per 100 000 (0–4 y) 92.3 per 100 000 (0–4 y) 0.8 per 100 000 overall rate 21.5 per 100 000 (0–4 y)
20.4 per 100 000 (5–17 y) 23.5 per 100 000 (5–17 y) 9.1 per 100 000 (5–17 y)
Characteristics of 55% had $1 underlying 42.9% had $1 underlying Not available because of low 65.7% had $1 underlying
hospitalized children condition condition case numbers condition
Asthma/RAD 26% Asthma/RAD 22.1% Asthma 28.1%
Neurologic disorder Neurologic disorder Neurologic disorder 16.9%
15.6% 17.5% Obesity 13.3%
Obesity 11.6% Obesity 12%
Pediatric deaths 144 199 1 4415
57.4% without underly- 39% without underlying
ing condition condition
50% of pediatric deaths 16% of vaccine-eligible
that were tested had a children fully vaccinated
bacterial coinfection 7 patients with SARS-CoV-2
74% of those who died coinfection
were vaccine-eligible,
but unvaccinated
Notable findings Longest season in a decade Complicated by COVID-19 Low severity season Influenza activity began to
pandemic likely because of COVID- increase in November, de-
0.5% of A (H1N1) pdm09 19 mitigation measures clined in January 2022, in-
isolates exhibited re- reducing spread of all creased again in March
duced inhibition by osel- respiratory illnesses 2022 and remained elevated
tamivir and peramivir 1 reported case of novel until mid-June 2022.
Severity considered high influenza A (H1N2) in Higher number of hospital-
in children United States izations in the second
wave
3 human infections with
novel influenza A virus
identified, including 1 case
of avian influenza A (H5)
virus (first in a human in
the United States)
RAD, reactive airways disease; —, not reported.
2022–2023 Influenza Season illnesses and 300 000 to 650 000 hospitalizations (https://
The 2022–2023 influenza season began earlier than is www.cdc.gov/flu/about/burden/preliminary-in-season-
typically expected in many states and was characterized estimates.htm). The cumulative hospitalization rate of
by a high burden of disease in children, including high rates 62.6 per 100 000 was similar to that observed during the
of hospitalization. A field investigation conducted in middle 2018–2019 and 2019–2020 seasons. Among people youn-
Tennessee is illustrative: Among patients tested for influenza ger than 65 years, hospitalization rates were highest
in outpatient settings, children were more likely to have pos- among children 0 to 4 years of age (80.9 per 100 000). In
itive test results than adults (33% [714 of 2164] vs 20% a sample of hospitalized children reported to the Influenza
[483 of 2462], respectively; P < .001). In November 2022, Hospital Surveillance Network, 66.3% had at least 1 un-
the influenza-associated hospitalization rate among children derlying medical condition. As in previous years, the most
<5 years of age was 12.6 per 100 000, comparable to peak common underlying condition observed in hospitalized
levels typically seen in high severity seasons.2 children was asthma (https://gis.cdc.gov/grasp/fluview/
Nationally, between October 1, 2022, and April 30, 2023, FluHospChars.html).
the Centers for Disease Control and Prevention (CDC) During the 2022–2023 season, the CDC estimated in-
estimated the burden of influenza to include 27 to 54 million fluenza-related deaths to be between 19 000 and 58 000;
2 FROM THE AMERICAN ACADEMY OF PEDIATRICS

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Influenza Type/ 2018–2019 2019–2020 2021-2022
Age Group A(H1N1)pdm09 and B/Victoria and A(H3N2)
H3N2 A(H1N1)pdm09
VE% (95% CI) VE% (95% CI) VE% (95% CI)
Influenza A and B
Overall all ages 29 (21–35) 39 (32–44) †

6 mo–8 y 48 (37–58) 34 (19–46) Not reported
9–17 y 7 (-20 to 28) 40 (22–53) Not reported
Influenza A(H1N1)pdm09
Overall all ages 44 (37–51) 30 (21–39) Not reported

6 mo–8 y 59 (47–69) 23 (-3 to 42) Not reported
9–17 y 24 (-18 to 51) 29 (-7 to 52) Not reported
Influenza A(H3N2)
Overall all ages 9 (-4 to 20) Not reported 36 (20–49)

6 mo–8 y 24 (1–42) Not reported 51 (19–70)
9–17 y 3 (-30 to 28) Not reported 34 (-7 to 59)
Influenza B Victoria
Overall all ages Not reported 45 (37–52) Not reported

6 mo–8 y Not reported 39 (20–54) Not reported
9–17 y Not reported 43 (23–58) Not reported
Influenza B Yamagata
Overall all ages Not reported Not reported Not reported

6 mo–8 y Not reported Not reported Not reported
9–17 y Not reported Not reported Not reported
FIGURE 1
Adjusted VEa in children in the United States, by season, as reported by the CDC, US Influenza VE Network.b † Combined influenza A and B not available, but
overall influenza A VE was 36% (95% CI: 21%, 48%). a VE is estimated as 100% x (1 OR [ratio of odds of being vaccinated among outpatients with CDC’s
real-time reverse transcription polymerase chain reaction influenza-positive test results to the odds of being vaccinated among outpatients with influenza-
negative test results]); ORs were estimated using logistic regression. Adjusted for study site, age group, sex, race/ethnicity, self-rated general health, num-
ber of days from illness onset to enrollment, and month of illness using logistic regression. b VE could not be assessed for 2020–2021 season because of low virus
circulation. However, the A (H1N1) pdm09, A (H3N2), and B/Victoria strains that were genetically characterized were similar to the strains included in the vaccine.
160 deaths were reported in children through July 1, Through July 1, 2023, more than 97.6% of the influ-
2023 (Fig 2). In an interim analysis of 106 pediatric in- enza viruses identified were influenza A with a predomi-
fluenza deaths during the 2022–2023 influenza season, nance of H3N2 (71.9%). In an interim analysis through
41 occurred in children younger than 5 years. Approxi- February 2023, most influenza A viruses tested were ge-
mately half of the deaths were in healthy children with- netically and antigenically similar to viruses contained in
out medical conditions that would predispose to severe seasonal influenza vaccines, and this was reflected in es-
influenza, and 90% occurred in children who were not timates of VE.3 Through January 25, 2023, children who
fully vaccinated (https://www.cdc.gov/flu/spotlights/2022- were vaccinated against influenza were 68% less likely
2023/pediatric-flu-deaths.htm). to be hospitalized because of influenza illness or influenza-
PEDIATRICS Volume 152, number 4, October 2023 3

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FIGURE 2
Influenza-associated pediatric deaths by season. From: https://www.cdc.gov/flu/weekly/. Accessed April 21, 2023.
associated complications, according to data from the New a pertussis-like illness. Bacterial complications include
Vaccine Surveillance Network. Vaccinated children were otitis media, pneumonia, and sinusitis.
42% less likely to visit an emergency department because Viral infections, including influenza, have been identi-
of influenza-related illness. The overall VE in children fied as risk factors for invasive bacterial infections, in-
against laboratory-confirmed influenza A in hospital and cluding invasive group A streptococcal (iGAS) infections.5
emergency department settings was 49% (https://www. In the fall of 2022, some communities experienced in-
cdc.gov/flu/spotlights/2022-2023/flu-vaccine-protection. creases in iGAS infections coincident with increases in in-
htm). Two concurrent studies from Wisconsin reported that fluenza and respiratory syncytial virus cases.6 According
influenza VE was 71% for preventing symptomatic influ- to the CDC, from 2016 to 2022, increases in iGAS infec-
enza A illness among children and adolescents younger tions coincided with seasonal peaks in respiratory syncy-
than 18 years.3 Information about influenza surveillance is
tial virus and influenza hospitalization rates during most
available through the CDC Voice Information System
years except 2021.
(1-800-232-4636) and is posted weekly on the CDC Web
Neurologic complications of influenza include febrile seiz-
site (www.cdc.gov/flu/index.htm).
ures, nonfebrile seizures, and encephalopathy. Approxi-
mately 8% to 11% of hospitalized children experience
INFLUENZA MORBIDITY AND MORTALITY IN CHILDREN neurologic complications, and these are more frequent in
In a typical influenza season, the disease burden among children with underlying neurologic conditions and children
children is substantial. Each year, an estimated 9% of US who are unimmunized.7,8 Thromboembolic events, includ-
children develop symptomatic influenza virus infection. ing stroke, occur in children with influenza but are rare.9
Children infected with influenza virus are more likely to Hospitalization rates of children with influenza are highest in
exhibit symptoms than adults. In 2 community-based those younger than 5 years.10,11 Deaths from influenza occur in
prospective cohort studies conducted in Managua, Nica- children with and without other underlying medical condi-
ragua, influenza was asymptomatic in just 6.6% infected tions.12 Over 9 influenza seasons in the United States after the
children #14 years of age, although the asymptomatic 2009 H1N1 pandemic, adjusted influenza-associated hospitali-
fraction increased with age (1.7%, 3.5%, and 9.1% for zation incidence rates ranged from 10 to 375 per 100 000 per-
ages 0–1, 2–4, and 5–14 years, respectively; P < .001).4 sons <18 years of age each season; rates were highest among
Clinical syndromes associated with influenza virus in- infants <6 months of age and decreased with increasing age.13
fection include a nonspecific febrile illness with or with- In this cross-sectional study that included data from 14 US
out upper respiratory symptoms, bronchiolitis, croup, or Influenza Hospitalization Surveillance Network sites, 13 235

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children were hospitalized, and of these, 2676 (20%) were ad- (eg, SARS-CoV-2 and respiratory syncytial virus), including
mitted to the ICU, 2262 (17%) had pneumonia, and 690 (5%) lack of access to quality health care, crowded living condi-
required mechanical ventilation. Seventy-two children (0.5%) tions, and social vulnerability, were not evaluated in this
died during hospitalization. In multivariable models, the odds study.18,19
of severe outcomes, including in-hospital death, were highest in
children 13 to 17 years of age. HIGH-RISK GROUPS IN PEDIATRICS
In a cohort of 179 children 8 months to 17 years of Children younger than 5 years (especially those younger
age admitted to intensive care or a high acuity unit with than 2 years) and children of any age with certain under-
influenza during the 2019–2020 season, one-third re- lying medical conditions have a high risk of complica-
quired mechanical ventilation for respiratory failure, ap- tions from influenza (see Table 4 in the policy statement
proximately one-fifth were treated with vasopressors, [www.pediatrics.org/cgi/doi/10.1542/peds.2023-063772]).
and 2.2% required extracorporeal membrane oxygena- These medical conditions include obesity, a condition that
tion.14 Morbidity was similar to children admitted to an affects more than 14 million children and adolescents in
ICU with coronavirus disease 2019 (COVID-19) between the United States.20 In a recent systematic review and
March 2020 and December 31, 2020.14 Death occurred in meta-analysis, obesity increased the odds of hospitalization
2.2% of children admitted with influenza, compared with in children with influenza, although the definition of obesity
2.9% of children with COVID-19. varied among included studies.21 Additionally, in children
Limited data suggest that children hospitalized with in- hospitalized for influenza, obesity was associated with a
fluenza and concurrent severe acute respiratory syn- worse prognosis, including ICU admission and death.
drome coronavirus 2 (SARS-CoV-2) infection have more In addition, influenza vaccination is particularly im-
severe disease. During the 2021–2022 influenza season, 6% portant in certain populations disproportionately af-
of children hospitalized with influenza had concurrent SARS- fected by COVID-19.17,22 These populations may also be
CoV-2 infection. Compared with patients without coinfection, disproportionately affected by influenza virus infection.
higher proportions of children with coinfections received inva- Although protecting all children against influenza through
sive mechanical ventilation (13% vs 4%; P 5 .03) and bilevel timely vaccination remains critically important, increased
positive air pressure or continuous positive air pressure (16% efforts are needed to eliminate barriers to immunization in
vs 6%; P 5 .05).15 all people experiencing higher rates of complications from
Postdischarge respiratory sequelae occur in children infection with influenza viruses.
hospitalized with critical influenza. In one study (n 5
165), 78% of children with preexisting asthma experi- EFFECTIVENESS OF INFLUENZA VACCINATION ON ANTIBIOTIC
enced asthma symptoms in the 90 days after discharge USE, LABORATORY-CONFIRMED INFLUENZA ILLNESS IN
and 13% required readmission to the hospital.16 Among AMBULATORY CHILDREN, HOSPITALIZATION, AND MORTALITY
patients without preexisting asthma, 11.1% had asthma Although influenza vaccination does not prevent all cases
newly diagnosed (n 5 10). of influenza, it does offer substantial health benefits, in-
Health disparities are apparent in both influenza mor- cluding protection against severe and life-threatening
bidity and mortality. In another cross-sectional study disease and reduced health resources utilization.
that included 10 influenza seasons, higher rates of severe
influenza disease were reported in Black, Hispanic, American Antibiotic Use in Ambulatory Children
Indian/Alaska Native, and Asian/Pacific Islander people com- In one population-based retrospective cohort study span-
pared with white people, and differences were pronounced ning 2012 to 2017, the antibiotic prescription rate in am-
in children #4 years of age.17 In this age group, hospitaliza- bulatory children declined by 3 per 1000 person-months
tion rates were higher in Black children (relative risk [RR]: for each 1% increase in influenza vaccination coverage.23
2.21; 95% confidence interval [CI]: 2.10–2.33), Hispanic chil-
dren (RR: 1.87; 95% CI: 1.77–1.97), American Indian/Alaska Laboratory-Confirmed Influenza Illness and Medically
Native children (RR: 3.00; 95% CI: 2.55–3.53), and Asian/Pa- Attended Influenza Illness in Ambulatory Children
cific Islander children (RR: 1.26; 95% CI: 1.16–1.38) com- In an analysis of US Influenza VE Network data that included
pared with white children. Rates of ICU admission were also 9 seasons (from 2011 to 2012 through 2019 to 2020),
higher (Black children: RR: 2.74; 95% CI: 2.43–3.09; Hispanic pooled VE against outpatient influenza illness was 46%
children: RR: 1.96; 95% CI: 1.73–2.23; American Indian/ (95% CI: 43%–50%).24 VE was lowest against influenza
Alaska Native children: RR: 3.51; 95% CI: 2.45–5.05). The A(H3N2)-associated illness (33% [95% CI: 27%–39%]), and
rate of in-hospital death was threefold to fourfold higher in estimates were similar for influenza B (54% [95% CI:
Black, Hispanic, and Asian/Pacific Islander children com- 49%–59%]) and influenza A(H1N1)pdm09 (57% [95% CI:
pared with white children. Importantly, factors associated 51%–62%]). VE was highest for children 6 through 59
with disparities observed with other respiratory viruses months of age compared with older children. During the

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TABLE 2 Adjusted Influenza Vaccine Effectiveness (VE) Against Influenza Hospitalization
Adjusted VE Partially Adjusted VE Fully
Author/Setting Seasons Included Population Studied N Vaccinateda (95% CI) Vaccinated (95% CI)
Feldstein/US New 2015–2016 6 mo–17 y 1653 18% (–44 to 54) 56% (34–71)
Vaccine
Surveillance
Network
Israel/Segaloff 2015–2016, 2016–2017, 6 mo–8 y 3147 25.6% ( 3.0 to 47.0) 53.9% (38.6–68.3)
2017–2018
Australia/Blyth 2018 #16 y 458 NR 86.1% (76.3–91.9).
United Kingdom/ 2018–2019 2–17 y 986 NR 53.0% (33.3–66.8)
Pebody A (H1N1): 63.5%
(34.4–79.7)
A(H3N2): 31.1%
(53.9–69.2)
Systematic Review/ 2005–2019 6 mo–17 y NR 33.91(21.12–46.69) 61.79 (54.45–69.13)
Kalligeros
Japan/Shinjoh 2018–2019 6 mo–15 y 205 NR 56% (16–77)b
Atlanta, Georgia/ 2012–2013, 2013–2014, 6 mo–17 y 980 46.8% (23.8–62.8) 55.3% (31.7–70.7)
Yildirim 2014–2015, 2016–2016,
2016–2017
Laboratory-confirmed influenza hospitalization. NR, not reported.
a
Included only patients aged 6 months to 8 years.
b
Included patients with full and partial vaccination.
2021–2022 influenza season, influenza A H3N2 viruses associated with a three-quarters reduction in the risk of life-
predominated. Circulating viruses had genetic differences threatening influenza illness in children.39
from the influenza A H3N2 strain included in the seasonal
vaccine. Nevertheless, VE against medically attended influ- SEASONAL INFLUENZA VACCINES
enza A(H3N2) infection in ambulatory children 6 months The seasonal influenza vaccines licensed for children and
to 8 years of age was 51% (95% CI: 19%–70%).25 adolescents for the 2023–2024 season are described in
Hospitalization Table 2 in the policy statement (www.pediatrics.org/cgi/
doi/10.1542/peds.2023-063772). All 2023–2024 sea-
A robust body of evidence supports the effectiveness of sonal influenza vaccines are quadrivalent and contain
influenza vaccination in preventing hospitalization in hemagglutinin (HA) derived from the same influenza
children, even during seasons in which overall VE is strains as recommended by the World Health Organiza-
lower (Table 2).26–36 According to a systematic review, tion and the US Food and Drug Administration (FDA)’s
VE is the highest in children younger than 5 years.32 Dur- Vaccines and Related Biological Products Advisory Com-
ing the 2021–2022 influenza season, the CDC estimates mittee for the Northern Hemisphere (see Table 1 in the
that influenza vaccination prevented 414 295 medical policy statement [www.pediatrics.org/cgi/doi/10.1542/
visits and 4311 hospitalizations in children 6 months to peds.2023-063772]).40,41 The influenza A(H1N1) compo-
4 years of age.37,38 nent is different this season compared with last season,
whereas the influenza A (H3N2), influenza B Victoria lin-
Mortality
eage, and influenza B Yamagata lineage components are
Historically, up to 80% of influenza-associated pediatric unchanged. Different but antigenically related influenza A
deaths have occurred in unvaccinated children 6 months strains are included in this season’s egg-based and cell-based
and older. Influenza vaccination is associated with re- or recombinant vaccines. However, they are still matched to
duced risk of laboratory-confirmed influenza-related pediatric the strains expected to circulate in the 2023–2024 season.
death.34 In one case–cohort analysis of laboratory-confirmed
influenza-associated pediatric deaths in the United States Inactivated Influenza Vaccine
from 2010 to 2014, overall VE against influenza-associated For the 2023–2024 season, among inactivated vaccines avail-
death in all children was 65% (95% CI: 54%–74%) and able for children, 4 are egg-based (seed strains grown in eggs),
51% (95% CI: 31%–67%) in children with underlying con- and 1 is cell culture-based (seed strains grown in Madin-
ditions.34 Similarly, in a case control study conducted over 2 Darby canine kidney cells) (see Table 2 in policy statement
influenza seasons (2010–2012), influenza vaccination was [www.pediatrics.org/cgi/doi/10.1542/peds.2023-063772]).

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All inactivated egg-based vaccines (Afluria Quadrivalent, the AAP Pediatric Preparedness Resource Kit at https://
Fluarix Quadrivalent, FluLaval Quadrivalent, and Fluzone downloads.aap.org/AAP/PDF/PedPreparednessKit.pdf).
Quadrivalent) are licensed for children 6 months and older, IIVs for intramuscular injection are shipped and stored
and all are available in single-dose, thimerosal-free, pre- at 2 C to 8 C (36 F–46 F); vaccines that are inadver-
filled syringes. The only pediatric cell culture-based vaccine tently frozen should not be used.
(Flucelvax Quadrivalent) is licensed for children 6 months
and older.42 IIV Administration
A quadrivalent recombinant baculovirus-expressed HA Vaccines are administered intramuscularly into the ante-
influenza vaccine (quadrivalent recombinant influenza rolateral thigh of infants and young children and into the
vaccine [RIV4] [Flublok Quadrivalent]) is licensed only deltoid muscle of older children and adults. Given that
for people 18 years and older. A high-dose quadrivalent various IIV formulations are available, careful attention
inactivated influenza vaccine (IIV4 [Fluzone High Dose should be paid to ensure that each product is used ac-
Quadrivalent]), and a quadrivalent MF59 adjuvanted in- cording to its approved age indication, dosing, and volume
activated vaccine (Fluad Quadrivalent) are licensed for of administration (see Table 2 in the policy statement
people 65 years and older.42 In June 2022, the Advisory [www.pediatrics.org/cgi/doi/10.1542/peds.2023-063772]).
Committee on Immunization Practices (ACIP) recom- For vaccines that include a multidose vial presentation, the
mended preferential use of a higher dose or adjuvanted maximum number of doses drawn from a multidose vial is
influenza vaccine for adults 65 years and older; recom- specified in the package insert and should not be exceeded;
mended vaccines include Fluzone High-Dose Quadriva- residual product must be discarded regardless of the re-
lent, Flublok Quadrivalent, and Fluad Quadrivalent.42 maining volume in the vial. A 0.5-mL prefilled syringe of
Adjuvanted seasonal influenza vaccines are not licensed any IIV should not be split into 2 separate 0.25-mL doses.
for children in the United States; however, studies of ad- If a prefilled syringe of Fluzone Quadrivalent is used for a child
younger than 36 months, the dose volume will be 0.5 mL per
juvanted vaccines in children are ongoing.43–46
dose.
Children 6 months and older can receive any licensed,
age-appropriate inactivated influenza vaccine (IIV). Quad- Coadministration of Inactivated Influenza Vaccine and Other
rivalent egg-based and cell culture-based IIVs contain
Vaccines
15 mg HA from each strain in 0.5 mL. The recommended
dose volume (and, therefore, the recommended antigen Recommendations for concomitant administration of in-
content) for younger children varies by product. The fluenza vaccine and other vaccines is detailed in the pol-
dose of Fluarix Quadrivalent, FluLaval Quadrivalent, and icy statement. Influenza vaccine can be administered to
Flucelvax Quadrivalent is 0.5 mL for all children 6 months children concomitantly or at any time before or after ad-
of age and older.47–50 Children 6 through 35 months of ministration of the currently available COVID-19 vac-
cines. Extensive experience with vaccines other than
age can receive a 0.25-mL or 0.5-mL dose of Fluzone
COVID-19 has demonstrated that immunogenicity and
Quadrivalent.51 These 2 doses demonstrated comparable
adverse event profiles are generally similar when vac-
safety and immunogenicity in a single, randomized multi-
cines are administered simultaneously as when they are
center study.52 The Fluzone Quadrivalent 0.25-mL pre-
administered alone.54–58 A systematic review that in-
filled syringe is no longer available, but the smaller dose
cluded only clinical studies of individuals 18 years and
can be administered from a single or multidose vial. Chil-
older identified no safety concerns and no evidence of
dren 3 years and older should receive 0.5 mL. Afluria
immune interference.59 Limited data exist on coadminis-
Quadrivalent has a 0.5-mL product for children 3 years
tration of COVID-19 vaccines and influenza vaccines in
and older only.53 For children 6 through 35 months of children. Through June 20, 2022, reports to the Vaccine
age, the recommended 0.25-mL dose must be obtained Adverse Event Reporting System after coadministration
from a multidose vial. of messenger RNA (mRNA) COVID-19 and seasonal influenza
vaccines in persons 6 months and older did not reveal any
IIV Storage
unusual or unexpected patterns of adverse events.60 Reports
The CDC has published Best Practice Guidelines (https:// to v-safe, a CDC-sponsored smartphone-based safety surveil-
www.cdc.gov/vaccines/hcp/acip-recs/general-recs/index. lance system, identified a significant increase in systemic ad-
html and https://www.cdc.gov/vaccines/hcp/admin/storage/ verse reactions in persons 12 years and older during the
toolkit/index.html) for vaccine storage and administration. week after vaccination who received simultaneous adminis-
Additionally, the AAP offers guidance on the components of tration of COVID-19 mRNA booster and seasonal influenza
a written disaster plan, including a comprehensive vaccine vaccines compared with those who received only a COVID-
management protocol to keep the vaccine storage tempera- 19 mRNA booster alone.61 Reactions were generally mild,
ture constant during a power failure or other disaster (see and pediatric-specific data were not reported. Providers are

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encouraged to consult the most current guidance from the children and adults have been published by the Infectious Dis-
AAP and the CDC ACIP regarding coadministration of eases Society of America.66,67 Guidelines for the immunization of
COVID-19 vaccines with other vaccines.62 Overall, the bene- solid organ transplant recipients have been published by the
fits of timely vaccination with same-day administration of American Society of Transplantation.68
IIV and other recommended vaccines outweigh the risk of
potential reactogenicity in children. Live Attenuated (Intranasal) Influenza Vaccine
Overview
Safety of IIV
The intranasal live-attenuated influenza vaccine (LAIV)
IIVs are well tolerated in children and can be used in healthy was initially licensed in the United States in 2003 for
children, as well as those with underlying chronic medical con- people 5 through 49 years of age as a trivalent formula-
ditions. The most common injection site adverse reactions af- tion, and the approved age group was extended to
ter administration of IIV in children are injection site pain 2 years of age in 2007. The quadrivalent LAIV (LAIV4) for-
(17%–67%), redness (13%–37%), and swelling (10%–25%). mulation licensed in 2012 was first available during the
The most commonly reported systemic adverse events are 2013–2014 influenza season, replacing trivalent LAIV. The
drowsiness (13%–38%), irritability (14%–54%), abnormal history of LAIV use in the United States, along with a de-
crying (33%–41%), loss of appetite (11%–32%), fatigue tailed discussion of vaccine efficacy over serial seasons, is
(10%–20%), muscle aches (10%–39%), headache available in the 2021 technical report.69
(10%–23%), arthralgia (10%–13%), and gastrointestinal
tract symptoms (10%–20%). Recombinant influenza vaccine Storage and Administration
(RIV) is well tolerated in older adolescents and adults. In
The cold-adapted, temperature-sensitive LAIV4 formulation
people 18 to 49 years of age, the most common injection
is shipped and stored at 2 C to 8 C (36 F–46 F). It is admin-
site reactions were tenderness (48%) and pain (37%). The
istered intranasally in a prefilled, single-use sprayer contain-
most common ($10%) solicited systemic adverse reactions
ing 0.2-mL of vaccine. A removable dose-divider clip is
were headache (20%), fatigue (17%), myalgia (13%), and
attached to the sprayer to facilitate administration of 0.1 mL
arthralgia (10%). Adverse reactions for each vaccine are de-
separately into each nostril. If the child sneezes immediately
scribed in package inserts that can be accessed at https://
after administration, the dose should not be repeated. Ad-
www.cdc.gov/vaccinesafety/vaccines/flu-vaccine.html#fda.
ministration of LAIV intranasally is not an aerosol-generating
The AAP supports the current World Health Organiza-
procedure; however, vaccine administrators are advised to
tion recommendations for use of thimerosal as a preser-
wear gloves when administering LAIV given the potential for
vative in multiuse vials in the global vaccine supply.63
contact with respiratory secretions.
Thimerosal-containing vaccines are not associated with
an increased risk of autism spectrum disorder in child- Coadministration of LAIV and Other Vaccines
ren.64,65 Thimerosal from vaccines has not been linked to
any neurologic condition. Despite the lack of evidence of LAIV4 may be administered simultaneously with other
harm, some states have legislation restricting the use of inactivated or live vaccines. If not administered simulta-
vaccines that contain even trace amounts of thimerosal. neously, it is recommended that administration of other
The benefits of protecting children against the known nonoral live vaccines is separated by a 4-week interval
risks of influenza are clear. Therefore, to the extent per- from LAIV4 vaccination.
mitted by state law, children should receive any available
Safety of LAIV
formulation of IIV rather than delaying vaccination while
waiting for reduced thimerosal-content or thimerosal- The most commonly reported reactions of LAIV4 in children
free vaccines. IIV formulations that are free of even trace are runny nose or nasal congestion (32%), headache (13%),
amounts of thimerosal are widely available, as described decreased activity (10%), sore throat (9%), decreased appe-
in Table 2 in the policy statement [www.pediatrics.org/ tite (6%), muscle aches (4%), and fever (7%).70
cgi/doi/10.1542/peds.2023-063772]. Additional informa-
tion to assist clinicians in responding to parental con-
LAIV and Immunocompromised Hosts
cerns about thimerosal is available at https://www.cdc. IIV (or RIV if age-eligible) is the vaccine of choice for severely
gov/vaccinesafety/concerns/thimerosal/index.html. immunocompromised patients and anyone in close contact
with a subset of severely immunocompromised people (ie,
Vaccination in the Setting of Immunosuppression those requiring a protected environment). This preference is
Nonlive vaccines, including IIVs, are safe in persons with based on the theoretical risk of infection attributable to an
altered immune competence, but immunogenicity may be LAIV strain in an immunocompromised contact of an LAIV-
diminished. Decreases in immunogenicity vary by underlying con- immunized person. Health care personnel (HCP) immunized
dition. Guidelines for the immunization of immunocompromised with LAIV may continue to work in most units of a hospital,

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including the NICU and general oncology ward, using standard odds ratio (OR) increasing approximately 16% with each
infection control techniques. As a precautionary measure, peo- additional 28 days from vaccine administration. 78 A
ple recently vaccinated with LAIV should restrict contact with study evaluating VE in both adults and children from the
severely immunocompromised patients (eg, those requiring a 2011–2012 through the 2013–2014 influenza seasons
protective environment) for 7 days after vaccination, although demonstrated 54% to 67% protection from 0 to 180 days
there have been no reports of LAIV transmission from an after vaccination.76 A single-center study of 3595 children
LAIV-vaccinated person to an immunocompromised person. during the 2017–2018 season demonstrated an overall VE
In the theoretical scenario in which an immunocompromised of 52% with no evidence of waning immunity in children
host develops a symptomatic LAIV infection, the LAIV strains up to 183 days after vaccination (median, 81 [interquartile
are susceptible to antiviral medications. range, 52–111] days), although the study may have been
underpowered for this outcome.81 A multisite study that in-
TIMING OF INFLUENZA VACCINATION AND DURATION OF cluded pooled data across 5 seasons identified only small,
PROTECTION nonsignificant decreases in VE against hospitalization (2%
Although peak influenza activity in the United States typi- per month) in vaccinated children 6 months to 17 years of
cally occurs from January through March, influenza viruses age.82 In a cohort of influenza vaccine-naive patients 6 to
can begin to circulate in early fall (October), as occurred <24 months in Nicaragua who received a single dose of
in the 2022–2023 season. Circulation can continue to late vaccine, VE against laboratory-confirmed influenza illness
spring (May or later), with one or more disease peaks, as declined 9% per month in the first 4 months after immuniza-
was the case in the 2021–2022 season. The typical pattern tion and then plateaued.83 Waning of immunity after 2 doses
of circulation was substantially altered during the COVID-19 of vaccine, as is recommended in the United States, was not
pandemic. Predicting the onset and duration or the severity studied. Collectively, these studies support the current recom-
of the influenza season with accuracy is impossible. Timely mendation to immunize children as soon as possible after vac-
influenza vaccination is important to ensure that individuals cine becomes available. An early onset of the influenza
are optimally protected before influenza viruses are circulat- season, as occurred for the 2022–2023 season, is a concern
ing in the community. when considering delaying vaccination, and delays increase
Thus, the AAP and CDC recommend children, especially the likelihood of missing influenza vaccination altogether.42
those who need 2 doses, should be immunized as soon Although influenza activity in the United States is typically
as vaccine becomes available and complete influenza vac- low during the summer, influenza cases and outbreaks can
cination by the end of October. Because the duration of occur, particularly among international travelers, who may
the influenza season is unpredictable, practices should be exposed to influenza year-round, depending on destina-
continue to vaccinate individuals as long as influenza vi- tion. Influenza can occur throughout the year in the tropics.
ruses are circulating and unexpired vaccine is available. The CDC has recommended that individuals who did not re-
Immunity after influenza vaccination can wane over ceive the current seasonal influenza vaccine during the
time.71 Studies in adults suggest that very early vaccina- Northern Hemisphere fall/winter season and who are travel-
tion (July or August) might be associated with subopti- ing to parts of the world where influenza activity is ongoing
mal immunity before the end of the influenza season, should consider influenza vaccination $2 weeks before de-
and the CDC now discourages influenza vaccination in parture, if available.84 This includes persons traveling to the
the summer months for most adults.42 The data are less tropics, to destinations in the Southern Hemisphere during
definitive in children. In some studies, VE decreased the Southern Hemisphere influenza season (April–Septem-
within a single influenza season, and this decrease corre- ber), or on cruise ships or with organized tourist groups
lated with increasing time after vaccination. However, during an influenza season.42
this decay in VE was not consistent across different age
groups and varied by season and virus types and influ- INFLUENZA VACCINE CONSIDERATIONS FOR SUBPOPULATIONS
enza A virus subtypes.72–80 Waning VE was more evident INCLUDING CONTRAINDICATIONS AND PRECAUTIONS
among older adults and younger children73,75 and with Contraindications and precautions to available influenza
influenza A (H3N2) viruses more than influenza A vaccines are detailed in Table 5 in the policy statement
(H1N1) or B viruses.74,76,79 A multiseason analysis from (www.pediatrics.org/cgi/doi/10.1542/peds.2023-063772). A
the US Flu VE Network found that VE declined by ap- precaution for vaccination is a condition that might increase
proximately 7% per month for influenza A (H3N2) and the risk or seriousness of a vaccine-related adverse reaction.
influenza B, and by 6% to 11% per month for influenza A precaution also may exist for conditions that might com-
A (H1N1) pdm09 in individuals 9 years and older.72 VE promise the ability of the host to develop immunity after
remained greater than 0 for at least 5 to 6 months after vaccination. Vaccination may be recommended in the pres-
vaccination. Another study that included children older ence of a precaution if the benefit of protection from the vac-
than 2 years also found evidence of declining VE with an cine outweighs the potential risks.

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Previous Allergic Reaction: Contraindication is not a contraindication to receive IIV or LAIV. Vaccine re-
Although a severe allergic reaction (eg, anaphylaxis) to a cipients with egg allergy are at no greater risk for a sys-
previous dose of any influenza vaccine is generally a con- temic allergic reaction than those without egg allergy.
traindication to future receipt of influenza vaccines, the Therefore, precautions such as choice of a particular vac-
AAP recommends that children who have had an allergic cine, special observation periods, or restriction of adminis-
reaction after a previous dose of any influenza vaccine be tration to particular medical settings are not warranted and
evaluated by an allergist to determine whether future re- constitute an unnecessary barrier to vaccination. It is not
ceipt of the vaccine is appropriate. Children who are al- necessary to inquire about egg allergy before the adminis-
lergic to gelatin (very rare) should receive IIV4 instead tration of any influenza vaccine, including on screening
of LAIV. RIV4 is an option for patients with gelatin al- forms. Routine prevaccination questions regarding anaphy-
lergy $18 years of age. laxis after receipt of any vaccine are appropriate. Standard
vaccination practice for all vaccines in children should in-
Moderate or Severe Illness, Including COVID-19: Delay Is clude the ability to respond to rare acute hypersensitivity
Recommended reactions. Children who have had a previous allergic reac-
Mild illnesses, with or without fever, are not contraindi- tion to the influenza vaccine should be evaluated by an al-
cations to the use of influenza vaccines, including among lergist to determine whether future receipt of the vaccine is
children with mild upper respiratory infection symptoms appropriate.
or allergic rhinitis. In children judged by the clinician to
Pregnancy: IIV Recommended, Not a Contraindication or
have a moderate to severe illness, vaccination should be
Precaution
deferred until resolution of the illness. Children with con-
firmed COVID-19 are generally advised to defer visits for Influenza vaccination is recommended by the ACIP, the
routine vaccination, including influenza vaccination, until American College of Obstetrics and Gynecology, and the
criteria (https://www.cdc.gov/coronavirus/2019-ncov/hcp/ American Academy of Family Physicians for all pregnant
duration-isolation.html) have been met for them to discon- individuals, during any trimester of gestation, to protect
tinue isolation and until they are no longer moderately to se- against influenza and its complications.42,87 Substantial
verely ill (https://www.cdc.gov/vaccines/pandemic-guidance/ evidence has accumulated regarding the efficacy of influ-
index.html). However, if they are already in a health care set- enza vaccination in preventing laboratory-confirmed in-
ting and their illness is mild, they can receive influenza vac- fluenza disease and its complications in both pregnant
cine. Children with an amount of nasal congestion that would individuals and their infants in the first months of life
notably impede vaccine delivery into the nasopharyngeal mu- (up to 6 months) through transplacental passage of anti-
cosa may receive IIV or should have LAIV deferred until bodies.87–97 Infants born to persons who receive influ-
symptom resolution. enza vaccine during pregnancy have been shown to have
a risk reduction of up to 72% (95% CI: 39%–87%) for
Guillain-Barre Syndrome: Precaution laboratory-confirmed influenza hospitalization in the first
History of Guillain-Barre syndrome (GBS) after influenza few months of life.97
vaccine is considered a precaution for the administration Any licensed, recommended, and age-appropriate IIV
of influenza vaccines. GBS is rare, especially in children, may be administered to pregnant individuals during any
and there is a lack of evidence on the risk of GBS after in- trimester of gestation and postpartum, although experi-
fluenza vaccination in children. Nonetheless, regardless ence with the use of RIV4 in pregnant individuals is lim-
of age, a history of GBS less than 6 weeks after a previous ited. LAIV is contraindicated during pregnancy. Data on
dose of influenza vaccine is a precaution for administration the safety of influenza vaccination at any time during
of influenza vaccine. GBS may occur after influenza virus in- pregnancy continues to support the safety of influenza
fection. The benefits of influenza vaccination might outweigh immunization during pregnancy.87,89–94,98 Vaccination during
the risks for certain people who have a history of GBS (par- pregnancy, including during the first trimester, is not as-
ticularly if not temporally occurring after previous influenza sociated with a risk of spontaneous abortion in most
vaccination) and who also are at high risk for severe compli- studies.99–102 Large retrospective cohort studies that col-
cations from influenza. lectively involved more than 80 000 pregnancies, as well
as a systematic review and meta-analysis of studies,
Influenza Vaccines and Egg Allergy: Not a found no association between influenza vaccine in any
Contraindication or Precaution trimester and major congenital malformations.103–105 As-
There is strong evidence that individuals with egg allergy sessments of any association with influenza vaccination
can safely receive influenza vaccine without any addi- and preterm birth and small-for-gestational-age infants
tional precautions beyond those recommended for any have yielded inconsistent results, with most studies re-
vaccine.85,86 The presence of egg allergy in an individual porting a protective effect or no association with these

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outcomes.102,106–108 A recent retrospective cohort study Hispanic white children (53.6%), Hispanic children (58%),
that included 84 730 pairs of birthing parents and children and children identified as non-Hispanic/other (60%), and
found no association between influenza immunization during among children residing in rural areas (41.1%) compared
pregnancy and autism spectrum disorder in children.109 De- with suburban (55.3.0%) or urban (59.8%) areas. Influenza
spite clear evidence of benefit to pregnant individuals and immunization rates may be even lower in some populations.
their infants, influenza vaccination in this population remains In a large national cohort of commercially insured children
below target levels. During the 2022–2023 influenza season, (2010–2017), vaccination coverage was 51.4% lower than
49% of pregnant individuals were vaccinated through April estimates of vaccination coverage reported through the Na-
22, 2023.110 Rates were highest in non-Hispanic Asian indi- tional Immunization Survey-Flu during the same period.121
viduals (66.6%) and lowest in non-Hispanic Black individu- The reasons for low influenza vaccination coverage are
als (30.4%). Racial disparities in uptake of influenza vaccine likely multifactorial. For some families, logistical barriers,
during pregnancy have been identified previously, with including lack of transportation and altered school and
Black women consistently having the lowest rates.111 Black work schedules, may have reduced access to routine
women report a lower rate of being offered or recom- medical care.122 Other families may have avoided care in
mended to receive influenza vaccine, despite evidence that medical offices out of fear of contracting SARS-CoV-2.123
a provider recommendation is associated with vaccine Pandemic mitigation strategies, including masking and
acceptance.111 Lower influenza vaccination coverage also has social distancing, as well as decreased influenza activity
been reported in Medicaid-insured pregnant women compared in the community, could have created a perception of de-
with privately insured women, and in women residing in ru- creased risk from influenza, limiting a sense of urgency
ral areas compared with those residing in urban areas.112,113 for influenza vaccination. Hesitancy around COVID-19
vaccination may have impacted hesitancy toward other
Breastfeeding: Recommended, Not a Contraindication or vaccines, including seasonal influenza vaccine. Finally,
Precaution
rates of influenza vaccine hesitancy, reasons for vaccine
Influenza vaccination with either IIV or LAIV during hesitancy, and factors facilitating vaccination may vary
breastfeeding is safe for lactating individuals and their by race and ethnicity. In one small mixed-methods study
infants. Breastfeeding is strongly recommended to pro- of parents and legal guardians presenting with their chil-
tect infants against influenza viruses by activating innate dren to a pediatric emergency department during the
antiviral mechanisms, specifically type-1 interferons. Hu- 2021–2022 influenza season, Black caregivers expressed
man milk from pregnant individuals vaccinated during more hesitancy to vaccinate their children for influenza
the third trimester also contains higher levels of influ- than did white caregivers (42% vs 21%; P 5 .01).124
enza-specific immunoglobulin A.114 Greater exclusivity of Black caregivers highlighted the importance of providers
breastfeeding in the first 6 months of life decreases the communicating about vaccines in a transparent, nonjudg-
episodes of respiratory illness with fever in infants of mental way. Facilitators of vaccination emphasized by
vaccinated lactating parents. For infants whose birthing Black and Hispanic caregivers included desire to protect
parent has confirmed influenza illness at delivery, breast- others, employer facilitation of vaccination, and personal
feeding is encouraged, and guidance on breastfeeding stories from others.
practices is available on the CDC Web site (https://www. Achieving high influenza vaccination coverage of in-
cdc.gov/breastfeeding/breastfeeding-special-circumstances/ fants, children, and adolescents remains a priority to pro-
maternal-or-infant-illnesses/influenza.html and https://www. tect them against influenza disease and its complications.
cdc.gov/flu/professionals/infectioncontrol/peri-post-settings. Multifaceted strategies are needed to increase influenza
htm). Birthing parents may pump and feed expressed breast vaccination coverage, especially in vulnerable, high-risk
milk if they or their infants are too sick to breastfeed. populations.
INFLUENZA VACCINATION COVERAGE INFLUENZA VACCINE DELIVERY AND IMPLEMENTATION

Influenza vaccination coverage has decreased in recent STRATEGIES
seasons and remains below the Healthy People 2030 tar- Timely annual distribution of influenza vaccine to health
get of 70% (Fig 3).115 This decrease in influenza vaccina- care facilities serving children and adolescents may help
tion coverage mirrors the declines in delivery of other avoid missed opportunities. Placing initial vaccine orders
routine pediatric vaccines during the COVID-19 pande- early and creating systems for tracking and reordering
mic.116–119 Influenza immunization coverage has contin- when necessary throughout the season may optimize
ued to lag during the 2022–2023 season.120 Through April supply. Such efforts may be particularly important when
15, 2023, only 55.1% of children 6 months to 17 years there are disruptions in vaccine delivery because of sup-
had been vaccinated. Coverage levels remained lower in ply chain issues, inclement weather, or other unforeseen
non-Hispanic Black children (51%) compared with non- circumstances, along with prioritizing delivery to primary

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FIGURE 3
Influenza vaccination coverage in children 6 months to 17 years of age in the United States, 2020 to 2021 to 2022 to 2023. From CDC. Influenza vaccination
coverage, children 6 months through 17 years, United States. Data source: NIS-Flu. Available at: https://www.cdc.gov/flu/fluvaxview/dashboard/
vaccination-coverage-race.html. Accessed July 12, 2023.
care settings, especially when supply is limited or delayed. season; failure to offer vaccine to hospitalized children is
The AAP has developed guidance for addressing influenza a missed opportunity.127 An automated, hospital-based
vaccine supply, payment, coding, and liability issues (https:// influenza vaccination screening program integrated into
www.aap.org/influenza). the hospital medical record may increase vaccination of
The AAP and CDC recommend influenza vaccination at eligible patients.128
any visit to the medical home during influenza season. A system for reporting influenza vaccine administrations is
Influenza vaccination in the medical home is ideal, espe- crucial to ensure adequate communication and maintain ac-
cially for the youngest children. Administering influenza curate patient records across settings. Integration of immuni-
vaccine in diverse locations, such as subspecialty practi- zation information systems with electronic health record
ces, urgent care clinics, emergency departments, schools, (EHR) systems can enhance data accuracy and up-to-date
and pharmacies, may increase uptake among patients vaccination status.129 For areas with a fragmented medical
who do not have or cannot readily access their medical home or high external resource utilization for vaccination,
home and those at high risk for influenza-related compli- querying the immunization information system before admin-
cations.125,126 This may be particularly useful for chil- istration of vaccination may prevent unnecessary product uti-
dren residing in rural areas where coverage levels are lization. Use of patient portals for parents to self-report
markedly lower than in suburban or urban areas. The vaccination is one strategy for systems looking to calculate
number of children immunized by pharmacists has been in- coverage and to decrease unnecessary communications to pa-
creasing but still remains relatively low. In one retrospective tients who received vaccinations outside the medical home.
cohort study that used an administrative health claims data- Practices that prepare in advance for their influenza
base to analyze influenza vaccines administered to children vaccine campaign and leverage a range of evidence-based
between July 1, 2010, and June 30, 2017, only 3.2% of vac- strategies130,131 throughout the season can increase vac-
cines were administered by pharmacists, although the pro- cination rates in their patient population (see Table 3 in
portion did increase over time.121 the policy statement [www.pediatrics.org/cgi/doi/10.1542/
Hospitalized patients should be vaccinated before dis- peds.2023-063772]). The AAP has created tools to help practi-
charge, unless medically contraindicated. Historically, a ces in this work (https://www.aap.org/influenza). Some prac-
substantial proportion of children hospitalized for influ- tices expand their hours of operation (ie, evenings, weekends)
enza have been hospitalized previously during the same or schedule vaccine-only clinics to increase patient access to

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influenza vaccine early in the season and during peak periods. the vaccine.139–141 Moreover, communication should be
Sending reminder/recall messages using a modality (ie, tele- tailored to address the specific vaccine-related concerns
phone, text, letter, e-mail, messaging via the patient portal) of patients and families. Resources regarding effective
that is feasible for their practice and aligns with the preferen- vaccine communication techniques are available on the
ces of their patient population may improve immunization AAP Web site at https://aap.org/vaccinecommunication.
rates.132,133 A Cochrane Review from 2018 concluded that re- Strategies to reduce missed opportunities during
minder/recall improves childhood influenza vaccination with patient visits include standardization of practice
moderate certainty of evidence (RR: 1.51; 95% CI: 1.14–1.99). workflow to screen all patients for influenza vaccine
Ć134 Effective messages notify families of influenza vaccine eligibility and administer the vaccine to any patient
availability and provide other key information such as the who is due for the vaccine. This workflow could be
child’s vaccination status and where, when, and why the used at all visit types, including preventive care, acute
child should receive the vaccine. This information is benefi- care, and mental/behavioral health visits. Influenza
cial early in the campaign, as well as throughout the sea- vaccination can be administered when patients pre-
son. For example, one clinical trial135 found that sending sent for other needed vaccines, as well. Practices may
text message reminders to parents of children who remain identify influenza vaccine champion(s) within their
unvaccinated in the late fall increased influenza vaccine up- practice to spearhead these efforts. Informatic tools
take. Another trial136 demonstrated the effectiveness of us- can also facilitate influenza vaccination. For example,
ing text message reminders for children requiring two studies have shown that standing vaccine orders and
doses in a season, particularly when the messages embed- vaccine prompts in the EHR increase influenza vaccine
ded information regarding the need for a timely second uptake in both inpatient and outpatient settings.142,143
dose. Making vaccine-related information readily available Audits and performance feedback for providers have
(ie, via a practice Web site, social media platform, or educa- also been shown to be effective as part of multimodal
tional handout)137,138 and tailoring this information for interventions.131 Additionally, these tools can be used
their patients and families (ie, materials in preferred lan- to identify patients who need repeat vaccinations and
guage) has also been effective. Resources are available from support future dose scheduling, or who have contrain-
the AAP at https://www.aap.org/en/news-room/campaigns- dications/precautions for particular formulations. Sys-
and-toolkits/flu-campaign-toolkit/. tems looking to identify patients at high risk for severe
Effective influenza vaccine communication with pa- influenza illness can leverage information from the
tients and families is crucial. Exact language is particu- EHR to identify patients at risk and provide targeted
larly important in vaccine risk discussions in languages communications. Sample value sets for use in creating
other than English. For example, in Spanish, the term electronic clinical decision support tools are presented
“gripe” is commonly used to refer to viral influenza but in Table 3. Implementation can be challenging, but
is a nonprecise term referring to respiratory illnesses. some institutions have used these sources. Local adap-
Using this term may cause confusion about the actual ill- tation may be needed.
ness prevented by influenza vaccine and result in de- For practices that choose to offer influenza vaccine to fam-
creased confidence about VE. “Influenza” should be used ily members and other close contacts of children and adoles-
rather than “la gripe” when discussing influenza and in- cent patients, the AAP technical report, “Immunizing Parents
fluenza vaccine with Spanish-speaking patients and and Other Close Family Contacts in the Pediatric Office
families. Setting,” provides medical liability risk management guid-
Messaging should be consistent across all members of ance on documenting in a separate record screening, in-
the care team, including front office staff, medical assis- formed consent, and National Vaccine Injury Compensations
tants, nurses, and all provider types (including primary Program-required immunization administration data.144 Guid-
care and subspecialty care providers). Practices should ance is also provided on ascertaining whether immunizing
educate their staff and providers about influenza and in- adults is covered by customary pediatric medical liability in-
fluenza vaccine-related topics, including the importance surance policies for any adverse events not covered by the
of annual vaccination, VE and safety, the 2-dose require- National Vaccine Injury Compensations Program. Additional
ment for certain children, vaccine contraindications, and resources are available at https://aap.org/immunization.
common parental concerns. Providers should use evidence- Partnership with community stakeholders, including
based communication strategies in their conversations with early childhood learning centers, schools, school-based
families. These include offering a strong, presumptive health centers, public health agencies, pharmacies, and
influenza vaccine recommendation, bundling their rec- other organizations, can optimize influenza vaccine dis-
ommendation for influenza vaccine with recommenda- tribution, communication, and administration. This may
tions for other needed vaccines, and pursuing their be particularly important for reaching patients with lim-
initial recommendation when families initially decline ited access to care, including those residing in rural

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14
TABLE 3 Value Sets for Underlying Conditions of High-Risk Groups for Influenza Complications
Category Description Established Value Setsa Object Identifier Code System Steward
a
Underlying condition or treatment with common examples
Chronic pulmonary Asthma Asthma diagnosis ICD-10 2.16.840.1.113762.1.4.1047.308 ICD-10-CM American Academy of Allergy,
disease Asthma, and Immunology
Asthma diagnosis 2.16.840.1.113762.1.4.1047.309 ICD-10-CM American Academy of Allergy,
grouping ICD-9-CM Asthma, and Immunology
SNOMED CT
Cystic fibrosis Cystic fibrosis 2.16.840.1.113883.3.464.1003.102.12.1002 ICD-10-CM National Committee for Quality
ICD-9-CM Assurance
SNOMED CT
Cystic fibrosis lung 2.16.840.1.113762.1.4.1219.15 ICD-10-CM CMS Documentation
disease SNOMED CT Requirement Lookup
Service
Compromised respiratory function (eg, Mechanical ventilation 2.16.840.1.113762.1.4.1248.107 ICD-10-PCS American Institutes for
requiring mechanical ventilation, SNOMED CT Research
tracheostomy, or baseline oxygen
requirement)
Cardiovascular disease Hemodynamically significant conditions — — — —
(excluding hypertension alone)
Kidney disease Dialysis; chronic kidney disease, Dialysis services 2.16.840.1.113883.3.464.1003.109.11.1026 CPT National Committee for Quality
including end-stage kidney disease Assurance
Hepatic disease Chronic liver disease, cirrhosis Chronic liver disease 2.16.840.1.113883.3.464.1003.199.12.1035 ICD-10-CM National Committee for Quality
ICD-9-CM Assurance
SNOMED CT
Cirrhosis 2.16.840.1.113762.1.4.1248.149 ICD-10-CM American Institutes for
SNOMED CT Research

Hematologic disease Sickle cell disease Sickle cell anemia and 2.16.840.1.113762.1.4.1235.222 ICD-10-CM B.well Connected Health
HBS disease SNOMED CT
Other hemoglobinopathies — — — —
Metabolic disorders Diabetes mellitus Diabetes 2.16.840.1.113883.3.464.1003.103.12.1001 ICD-10-CM National Committee for Quality
SNOMED CT Assurance
Neurologic and Cerebral palsy Congenital or infantile 2.16.840.1.113883.3. ICD-10-CM Lantana
neurodevelopmental Cerebral Palsy Group 666.5.1580 ICD-9-CM
conditions SNOMED CT
Epilepsy Epilepsy 2.16.840.1.113762.1.4.1034.51 ICD-10-CM American Academy of
ICD-9-CM Neurology
SNOMED CT
Seizure disorder 2.16.840.1.113883.3.464.1003.105.12.1206 ICD-10-CM National Committee for Quality
ICD-9-CM Assurance
SNOMED CT
Stroke Stroke 2.16.840.1.113762.1.4.1248.176 ICD-10-CM American Institutes for
Research
Intellectual developmental disorder — — — —
FROM THE AMERICAN ACADEMY OF PEDIATRICS

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TABLE 3 Continued
Category Description Established Value Setsa Object Identifier Code System Steward
Moderate to severe developmental delay — — — —
Muscular dystrophy — — — —
Spinal cord injury Spinal cord injury 2.16.840.1.113883.3.7587.3.1009 ICD-10-CM American Academy of Physical
ICD-9-CM Medicine and Rehabilitation
SNOMED CT
Extreme obesity BMI $40 for adultsc — — — —
Immunosuppression Receipt of immunocompromising — — — —
medications
Congenital or acquired immune Immunodeficiency syndromes 2.16.840.1.113762.1.4.1200.189 ICD-10-CM Cliniwiz
deficiency, including HIV HIV 2.16.840.1.113883.3.464.1003.120.12.1003 ICD-10-CM National Committee for Quality
ICD-9-CM Assurance
SNOMED CT
PEDIATRICS Volume 152, number 4, October 2023

Asplenia Anatomic or functional 2.16.840.1.113762.1.4.1235.219 ICD-10-CM B.well Connected Health
Asplenia HDCN grouping ICD-9-CM
SNOMED CT
Receiving treatment with aspirin or salicylate-containing therapiesb — — — —
Pregnancy and up to 2 weeks postpartum — — — —
The sets provided are previously published value sets available at the Value Set Authority Center (a service of the National Library of Medicine) and can be accessed at https://vsac.nlm.nih.org. These sets are provided by the rele-
vant steward listed and are not endorsed by the AAP but may serve as a starting point for organizations creating electronic clinical decision support systems. Source: Adapted from Grohskopf LA, Blanton LH, Ferdinands
JM, Chung JR, Broder KR, Talbot HK. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices—United States, 2023–24 influenza season. MMWR Recomm Rep.
2023;72(RR-2):1–25. CPT, Current Procedural Terminology; HBS, hemoglobin SS disease; ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification; ICD-10, International Classification of Diseases, 10th Revision;
ICD-10-CM, International Classification of Diseases, 10th Revision, Clinical Modification; ICD-10-PCS, International Classification of Diseases, 10th Revision, Procedure Coding System; SNOMED CT, Systemized Nomenclature of Medicine, Clini-
cal Terms. —, not available.
a
Value sets were not available for all conditions.
b
Applies to children and adolescents aged <19 years who may be at increased risk of Reye syndrome.
c
Not well defined in children but could consider BMI $99% for age.

15
TABLE 4 Comparison of Types of Influenza Diagnostic Tests
Influenza Viruses Distinguishes Influenza
Testing Categorya Method Detected A Virus Subtypes Time to Results Performance
Rapid molecular assay Nucleic acid amplification Influenza A or B viral RNA No 15–30 min High sensitivity; high
specificity
Rapid influenza Antigen detection Influenza A or B virus No 10–15 min Moderate sensitivity
diagnostic test antigens (higher with analyzer
reader device); high
specificity
Direct and indirect Antigen detection Influenza A or B virus No 1–4 h Moderate sensitivity;
immunofluorescence antigens high specificity
assays
Molecular assays Nucleic acid amplification Influenza A or B viral RNA Yes, if subtype primers 1–8 h High sensitivity; high
(including RT-PCR) are used specificity
Multiplex molecular Nucleic acid amplification Influenza A or B viral RNA, Yes, if subtype primers 1–2 h High sensitivity; high
assays other viral or bacterial are used specificity
targets (RNA or DNA)
Rapid cell culture (shell Virus isolation Influenza A or B virus Yes 1–3 d High sensitivity; high
vial and cell mixtures) specificity
Viral culture (tissue cell Virus isolation Influenza A or B virus Yes 3–10 d High sensitivity; high
culture) specificity
Source: Uyeki149 and https://www.cdc.gov/flu/professionals/diagnosis/overview-testing-methods.htm#tests. RT-PCR, reverse transcription polymerase chain reaction.
a
Negative results may not rule out influenza. Respiratory tract specimens should be collected as close to illness onset as possible for testing. Clinicians should consult the manufacturer’s
package insert for the specific test for the approved respiratory specimen(s). Specificities are generally high (>90%) for all tests compared with reverse transcriptase-polymerase chain re-
action. Sensitivities of rapid influenza diagnostic tests vary by test and are lower compared with reverse transcriptase-polymerase chain reaction and viral culture. The typical sensitivity of
a rapid test performed in a physician’s office is 50% to 70%, and clinicians may wish to confirm negative test results with molecular assays, especially during peak community influenza
activity. FDA-cleared rapid influenza diagnostic tests are Clinical Laboratory Improvement Amendments-waived; most FDA-cleared rapid influenza molecular assays are Clinical Laboratory Im-
provement Amendments waived, depending on the specimen.
areas. For example, practices could help with outreach into contact with high-risk patients in their clinical set-
initiatives such as influenza vaccine fairs or mobile vac- tings. The programs reduce HCP absenteeism and may
cine vans. Partnering with faith-based organizations may reduce disruptions in care delivery associated with per-
be an effective intervention to increase immunization sonnel shortages.147 Mandatory influenza vaccination of
rates in communities in which mistrust and vaccine hesi- HCPs is considered ethical, just, and necessary to im-
tancy are high.145 Collectively, practices and partners can prove patient safety. For the prevention and control
educate families and community members on the impor- of influenza, HCP must prioritize the health and safety
tance of influenza vaccination and address common con- of their patients, honor the requirement of causing no
cerns. The AAP has created communication resources to harm, and act as role models for both their patients
convey key messages and to help the public understand and colleagues by receiving influenza vaccination
influenza vaccination recommendations on the AAP Web annually.
site at https://www.aap.org/en/newsroom/campaigns-and-
toolkits/flu-campaign-toolkit/.
The AAP supports mandatory influenza vaccination INFLUENZA TREATMENT AND CHEMOPROPHYLAXIS
programs for HCP in all settings, including outpatient lo-
cations. Optimal prevention of influenza in these settings Antiviral Therapy
requires that at least 90% of HCP are vaccinated. Esti- Antiviral agents available for both influenza treatment
mated influenza vaccination coverage of HCP was only and chemoprophylaxis in children of all ages can be
79.9% during the 2021–2022 season, compared with found in Table 6 in the policy statement (www.
75.9% in the 2020–2021 season.146 Coverage levels pediatrics.org/cgi/doi/10.1542/peds.2023-063772) (in-
were highest among HCP whose employers required cluding doses for preterm infants that have not been
vaccination (95.8%–97.3%). Coverage levels were also evaluated by the FDA) and on the CDC Web site. 148
higher among HCP working in hospitals (92%) com- These include the neuraminidase inhibitors (NAIs: osel-
pared with those working in long-term care settings tamivir, zanamivir, peramivir) and a selective inhibitor
(66.4%). Influenza vaccination programs for HCP benefit of influenza cap-dependent endonuclease (baloxavir),
the health of employees, their patients, and members of all of which have activity against influenza A and B vi-
the community, especially because HCP frequently come ruses.149

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Oral oseltamivir (Tamiflu) remains the antiviral Rationale for Influenza Treatment in Children
drug of choice for the management of illness caused Randomized controlled trials (RCTs) to evaluate the effi-
by influenza virus infections and is the only drug cacy of influenza antiviral medications among outpatients
approved for treatment of hospitalized children. with uncomplicated influenza have found that timely
Oseltamivir is preferred because of the cumulative ex- treatment (optimally #2 days from symptom onset) can
perience of this drug in children, relative cost, and reduce the duration of influenza symptoms and fever in
ease of administration. Although more difficult to ad- pediatric populations.158–162 Observational studies in pe-
minister, inhaled zanamivir (Relenza) is an acceptable diatric and adult populations suggest that antiviral agents
alternative for patients who do not have chronic respi- are safe and could reduce the risk of certain influenza
ratory disease. In one nationwide, population-based complications, including hospitalization and death.163–167
cohort study that included ambulatory children and Potential limitations of the trials conducted to date in
adults who were treated with antiviral medications children include the study size (the number of events
might not be sufficient to assess specific outcomes in
within 48 hours of a clinical diagnosis of influenza, in-
small studies), variations in the case definition of influ-
haled zanamivir was not inferior to oral oseltamivir in
enza illness (clinically diagnosed versus laboratory con-
preventing influenza-related hospitalization or death,
firmed), time of treatment administration in relation to
but an exploratory subgroup analysis favored oseltami- the onset of illness, and inclusion of children of varying
vir in children 5 to 17 years of age. This may reflect ages and underlying health conditions. Several studies
the ability of children to correctly use a zanamivir in- also suggest that treatment of index patients with influ-
haler. A single dose of intravenous (IV) peramivir enza reduces transmission to household contacts to some
(Rapivab) is approved for the treatment of acute un- extent, but the magnitude of the effect is inconsistent
complicated influenza in ambulatory children 6 across published reports.168 The totality of available evi-
months and older who have been symptomatic for no dence supports the treatment of children with influenza.
more than 2 days. The efficacy of peramivir in patients A Cochrane review of 6 RCTs involving treatment of
with serious influenza requiring hospitalization has 2356 children with clinically diagnosed influenza, of
not been established.149 In a retrospective cohort whom 1255 had laboratory-confirmed influenza, showed
that, in children with laboratory-confirmed influenza,
study of children 0 to 5 years of age hospitalized with
oral oseltamivir and inhaled zanamivir reduced median
influenza in China, oral oseltamivir and IV peramivir
duration of illness by 36 hours (26%; P < .001) and 1.3 days
were associated with similar clinical outcomes when (24%, P < .001), respectively.162 Among the studies re-
used for the treatment of influenza B.150 In children viewed, one trial of oseltamivir in children with asthma who
with influenza A, oseltamivir treatment was associated had laboratory-confirmed influenza showed a nonsignificant
with improved recovery and short hospital stays (5 vs reduction in illness duration (10.4 hours; 8%; P 5 .542).
6 days; P 5 .02). Oseltamivir significantly reduced acute otitis media in chil-
A single dose of baloxavir marboxil (Xofluza) is ap- dren 1 through 5 years of age with laboratory-confirmed in-
proved for treatment of acute uncomplicated influenza fluenza (risk difference: –0.14; 95% CI: –0.24 to –0.04).162
in otherwise healthy individuals as young as 5 years of Another Cochrane review of RCTs in adults and children,
age and all individuals 12 years and older.151,152 Out- which included 20 oseltamivir (9623 participants) and 26 za-
comes are similar to those for NAIs.153,154 In a ran- namivir trials (14 628 participants),158 found no effect of
domized controlled trial that enrolled adolescents and oseltamivir in reducing the duration of illness in asthmatic
children, but in otherwise healthy children, there was
adults, baloxavir had better efficacy than oseltamivir
a reduction by a mean difference of 29 hours (95% CI:
in the treatment of influenza B.155 The oral suspension
12 hours–47 hours; P 5 .001). No significant effect was
formulation of baloxavir was not available in the
observed with zanamivir. Regarding complications, this re-
United States for the 2022–2023 influenza season, lim- view did not find a significant effect of NAIs on reducing hos-
iting use in children who were old enough to receive pitalizations, pneumonia, bronchitis, otitis media, or sinusitis
the drug but weigh less than 20 kg.156 Availability of in children.162 More recently, a meta-analysis of 5 new RCTs
this formulation is not expected in the United States that included 1598 children with laboratory-confirmed influ-
for the 2023–2024 influenza season. enza showed that treatment with oseltamivir significantly re-
During the 2022–2023 influenza season, there was a duced the duration of illness in this population by 17.6 hours
shortage of generic oseltamivir. The CDC published rec- (95% CI: –34.7 hours to –0.62 hours).160 When children with
ommendations for the prioritizing use of antiviral asthma were excluded, this difference was larger (–29.9
agents for patients at greatest risk of influenza-related hours; 95% CI: –53.9 hours to –5.8 hours). The risk of otitis
complications and those who are hospitalized.157 media was 34% lower in this group, as well. Similarly, a

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meta-analysis conducted by Tejada et al showed a statistically patients 12 years and older hospitalized with laboratory-
significant reduction in the risk of acute otitis media occur- confirmed influenza.175
rence among treated children over placebo recipients (OR: The AAP, CDC, Infectious Diseases Society of America,149
0.48; 95% CI: 0.30–0.77).167 Overall, efficacy outcomes are and Pediatric Infectious Diseases Society recommend treat-
best demonstrated in patients with laboratory-confirmed ment with oseltamivir for children with serious, complicated,
influenza. or progressive disease presumptively or definitively caused
There are no prospective, fully enrolled, completed by influenza, irrespective of influenza vaccination status (the
RCTs of antiviral agents versus placebo for treatment of circulating strains may not be well matched with vaccine
influenza in hospitalized children or pediatric patients strains) or whether illness began >48 hours before presen-
with comorbidities, and prospectively collected data to tation. Earlier treatment provides better clinical responses,
determine the role of antiviral agents in treating severe but treatment after 48 hours of symptoms in adults and chil-
influenza are limited. One RCT of oseltamivir treatment dren with moderate to severe disease or with progressive
of influenza in hospitalized children in El Salvador and disease has been shown to provide some benefit and should
Panama suggested clinical benefit, but no statistically sig- be offered.170,176,177 Additionally, the AAP recommends
nificant findings were reported, because only 21% of the treatment of children at risk for severe complications of in-
target sample size was enrolled and therefore the study fluenza, regardless of duration of symptoms. Children youn-
was substantially underpowered.169 Nevertheless, on the ger than 2 years are at an increased risk of hospitalization
basis of information obtained from retrospective obser- and complications attributable to influenza. The FDA has ap-
vational studies and meta-analyses conducted to date in proved oseltamivir for treatment of children as young as
both adults and children, most experts support the use of 2 weeks of age. Given preliminary pharmacokinetic data and
antiviral medications as soon as possible to treat pediatric limited safety data, the CDC and AAP support the use of osel-
tamivir to treat influenza in both term and preterm infants
patients with severe influenza, including hospitalized
from birth, because benefits of therapy of neonatal influenza
patients.161–166,169
are likely to outweigh possible risks of treatment. Otherwise
In a retrospective study of 784 PICU admissions from
healthy children who have suspected influenza with an un-
2009 to 2012, the estimated risk of death was reduced in
complicated presentation should be considered for antiviral
653 NAI-treated individuals (OR: 0.36; 95% CI: 0.16–0.83).170
medication, particularly if they are in contact with other chil-
In a retrospective analysis of data from the US Influenza Hos-
dren who either are younger than 6 months (because they
pitalization Surveillance Network, administration of antiviral
are not able to receive influenza vaccine) or have high-risk
agents #2 days after illness onset was associated with
conditions (including age <5 years) that predispose them
shorter lengths of stay in children admitted to the ICU
to complications of influenza, when influenza viruses are
(adjusted hazard ratio: 1.46; P 5 .007) and in children
known to be circulating in the community. Antiviral treat-
with underlying medical conditions not admitted to the
ment should be started as soon as possible after illness onset
ICU (adjusted hazard ratio: 1.37; P 5 .02). In the relatively
and should not be delayed while waiting for a definitive in-
small number of patients studied, antiviral treatment $3
fluenza test result, because early therapy provides the best
days after illness onset had no significant effect in either co- outcomes. Algorithms for interpreting positive and negative
hort.171 Similarly, early antiviral treatment of children with influenza tests are available (https://www.cdc.gov/flu/
tracheostomy hospitalized with influenza reduced length of professionals/diagnosis/algorithm-results-circulating.htm).
stay by 1 day (6.4 vs 7.5 days; P 5 .01).172 In a multicenter, The balance between benefits and harms should be consid-
retrospective cohort study involving 55 799 children hospital- ered when making decisions about the use of NAIs for either
ized with influenza between 2007 and 2020, oseltamivir use treatment or chemoprophylaxis of influenza. The cost of anti-
on hospital day 0 or 1 was associated with shorter hospital viral therapy may be a barrier to treatment of some families.
stays and lower odds of readmission within 7 days, transfer If the breastfeeding parent requires antiviral agents,
to the ICU, and the composite outcome use of extracorporeal treatment with oral oseltamivir is preferred. The CDC
membrane oxygenation and in-hospital mortality.173 does not recommend use of baloxavir for treatment of
No additional benefit exists for double-dose NAI therapy pregnant or breastfeeding individuals. There are no avail-
on reduction of mortality or viral clearance, compared able efficacy or safety data in pregnant individuals, and
with standard-dose therapy, on the basis of a recent sys- there are no available data regarding the presence of ba-
tematic review and meta-analysis of 10 published stud- loxavir in human milk, the effects on the breastfed infant,
ies174 (4 RCT and 6 observational studies) involving or the effects on milk production.
20 947 adult and pediatric patients. In a randomized, par-
allel-group, double-blind, placebo-controlled, superiority Oseltamivir Adverse Effects
trial, combining baloxavir with NAIs did not result in su- In adverse event data collected systematically in prospec-
perior clinical outcomes compared with NAIs alone in tive trials, vomiting was the only adverse effect reported

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more often with oseltamivir compared with placebo baloxavir within 48 hours of exposure to a symptomatic
when studied in children 1 through 12 years of age (ie, household contact with influenza developed influenza
15% of treated children versus 9% receiving placebo). compared with 13% in the placebo-treated group (ad-
Diarrhea was reported in clinical trials of oseltamivir in justed RR: 0.10; 95% CI: 0.04–0.28).185 For additional con-
7% of treated children <1 year of age. After reports text, 73% started baloxavir within 24 hours of the index
from Japan of possible oseltamivir-attributable neuropsy- case’s symptom onset, an exercise that would be difficult
chiatric adverse effects, a review of controlled clinical to replicate in practice in the United States. There are no
trial data and ongoing surveillance has failed to establish data on IV peramivir for chemoprophylaxis.
a link between this drug and neurologic or psychiatric Decisions on whether to administer antiviral chemo-
events.178,179 Neurologic and neuropsychiatric complica- prophylaxis should include consideration of the exposed
tions including abnormal behavior occur in children with person’s risk of influenza complications, vaccination sta-
influenza in the absence of exposure to oseltamivir.180 tus, type and duration of contact, time since exposure,
recommendations from local or public health authorities,
Adherence to Antiviral Treatment Guidance
and clinical judgment. Optimally, postexposure chemo-
Despite the body of evidence supporting antiviral treat- prophylaxis should only be used when antiviral agents
ment of children hospitalized with confirmed or sus- can be started within 48 hours of exposure; the lower
pected influenza and expert guidance recommending once-daily dosing for chemoprophylaxis with oral oseltamivir
antiviral use in children at high risk for complications, or inhaled zanamivir should not be used for treatment of
antiviral prescribing is suboptimal. In studies examin- children symptomatic with influenza.149 Early, full-treatment
ing antiviral use in hospitalized children with influenza,
dosing (rather than once-daily chemoprophylaxis dosing)
half or fewer eligible children were prescribed antiviral
should be used in high-risk symptomatic patients without
treatment.181,182 In a cross-sectional study of ambulatory chil-
waiting for laboratory confirmation.
dren at high risk for complications, 58.1% of children di-
Toxicities may be associated with antiviral agents, and indis-
agnosed with influenza during the 2016–2019 influenza
criminate use might limit availability. Pediatricians should in-
seasons received antiviral treatment.183 Children 2 to 5 years
form recipients of antiviral chemoprophylaxis that risk of
of age, residents of chronic care facilities, and children who
influenza is lowered, but not eliminated, while taking the medi-
received care in an emergency department were less likely to
cation, and susceptibility to influenza returns when medication
be treated. In a multicenter retrospective cross-sectional
is discontinued. Chemoprophylaxis is not a substitute for vacci-
study conducted between 2007 and 2020 at 36 US children’s
nation and among some high-risk people, both vaccination
hospitals participating in the Public Health Information Sys-
with IIV and antiviral chemoprophylaxis may be considered.149
tem, oseltamivir use in children hospitalized with influenza
increased over time. Use was lowest in the 2007–2008 in- The effectiveness of LAIV but not IIV or RIV will be decreased
fluenza season (20.2%) and highest in the 2017–2018 influ- for children receiving oseltamivir or other influenza antiviral
enza season (77.9), but there was significant variability by agents.149 Updates will be available at www.aapredbook.org
hospital.184 Odds of receiving oseltamivir therapy were less and www.cdc.gov/flu/professionals/antivirals/index.htm.
in children younger than 2 years of age and children 2 to
5 years of age compared with older children. Multifactorial ANTIVIRAL RESISTANCE
interventions are urgently needed to increase adherence to Resistance to any antiviral drug can emerge, necessitat-
antiviral treatment guidelines for children at high risk ing continuous population-based assessment by the CDC.
for complications of influenza, including those who are During the 2022–2023 season to date, all viruses evalu-
hospitalized. ated have retained susceptibility to baloxavir, peramivir,
and zanamivir. One influenza A (H1N1) pdm09 isolate
INFLUENZA CHEMOPROPHYLAXIS (<0.1% of all viruses tested) exhibited reduced inhibition to
Antiviral medications are important adjuncts to influenza oseltamivir (https://www.cdc.gov/flu/weekly/weeklyarchives
vaccination for control and prevention of influenza disease 2022-2023/week20.htm).
in children who are at least 3 months of age. Randomized Globally, detection of viruses with reduced susceptibility
placebo-controlled studies showed that oral oseltamivir to neuraminidase inhibitors was low in the 2018–2019
and inhaled zanamivir were efficacious when adminis- (0.5%) and 2019–2020 (0.6%) influenza seasons. Reduced
tered as chemoprophylaxis to household contacts after susceptibility to baloxavir was also rarely observed
a family member had laboratory-confirmed influenza.149 (0.5% during the 2018–2019 season and 0.1% during the
The efficacy of baloxavir was demonstrated in a randomized, 2019–2020 season).186 The rate was higher in Japan (4.5%
placebo-controlled trial in Japan conducted during the in the 2018–2019 season), where baloxavir use is the high-
2018–2019 influenza season. One percent of household est. In clinical trials, isolates with amino acid substitutions
members 12 years and older treated with a single dose of conferring reduced susceptibility to baloxavir have been

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identified in baloxavir-treated patients and are more com- In February 2023, the FDA issued an emergency use
mon in children 5 years and younger.187,188 authorization for the first over-the-counter, at-home
High levels of resistance to amantadine and rimantadine test to diagnose both influenza A and B and SARS-CoV-
persist among the influenza A viruses currently circulating; 2 in symptomatic individuals as young as 2 years of
neither drug is effective against influenza B viruses. Ada- age.189 The test is performed on a nasal swab that can
mantane medications are not recommended for use against be self-collected in persons 14 years and older. The
influenza unless resistance patterns change.149 test must be obtained by a caregiver in younger chil-
If a newly emergent antiviral-resistant virus is a con- dren. Results are available in 30 minutes. In individuals
cern, recommendations for alternative treatment will be with symptoms, the test correctly identified 99.3% of
available from the AAP and CDC. Resistance characteris- negative and 90% of positive influenza A samples and
tics can change for an individual patient over the dura- 99.9% of negative influenza B samples. Low circulation
tion of a treatment course, especially in those who are of influenza B precluded assessment of the test’s ability
severely immunocompromised. Information on current to detect influenza B in real-world settings. The utility
recommendations and therapeutic options can be found of these tests in managing pediatric patients with
on the AAP Web site (www.aap.org or www.aapredbook. symptoms of influenza merits exploration. At a mini-
org), through state-specific AAP chapter Web sites, or on mum, parents of children at high risk for complications
the CDC Web site (www.cdc.gov/flu/). of influenza will benefit from counseling about timely
communication with the medical home about the re-
DIAGNOSTIC TESTS FOR INFLUENZA sults of home tests and education that a negative test
Diagnostic testing for influenza may be beneficial when results cannot completely exclude influenza.
will be used to inform clinical management or infection pre-
vention measures and to distinguish from other respiratory
viruses with similar symptoms (eg, SARS-CoV-2). Performance
FUTURE DIRECTIONS
characteristics of tests vary and are impacted by duration of
illness in the person being tested and proper specimen collec- Safety and Effectiveness of Available Influenza Vaccines
tion and handling. Test results must be interpreted in the con- Continued evaluation of the safety, immunogenicity,
text of community influenza activity (Table 4); false-positive and effectiveness of influenza vaccines, especially for
tests may occur during periods of low influenza activity. at-risk and diverse populations, is important. The du-
Molecular assays include rapid molecular tests, reverse-
ration of protection, potential role of previous influ-
transcription polymerase chain reaction test, and other
enza vaccination on overall VE, and VE by vaccine
nucleic acid amplification tests. Multiplex assays that allow
formulation, virus strain, timing of vaccination, and
for the simultaneous detection of influenza viruses, plus
subject age and health status in preventing outpatient
SARS-CoV-2 or influenza viruses, SARS-CoV-2, and RSV,
medical visits, hospitalizations, and deaths continue to
are available. These assays can be particularly useful when
be evaluated.
these viruses are cocirculating; because signs and symp-
toms of these viruses may be similar, clinical differentiation
is difficult, and different treatment strategies are recom-
Influenza Vaccines in Development
mended. A current list of authorized tests is available at
https://www.cdc.gov/flu/professionals/diagnosis/table-flu- Development efforts continue for universal influenza vac-
covid19-detection.html. cines that induce broader protection and eliminate the need
Antigen detection tests include rapid influenza diagnostic for annual vaccination. The success of mRNA and other
tests (RIDTs) and immunofluorescence assays. Some avail- novel technologies used in the development of COVID-19
able RIDTs detect SARS-CoV-2, as well as influenza A and B. vaccines may accelerate the prospects of broad influenza
An updated list of RIDTs is available at https://www.cdc. vaccines. Understanding the establishment of immunity
gov/flu/professionals/diagnosis/table-ridt.html. against influenza in early life and developing a safe, immu-
Rapid molecular assays are highly sensitive and are nogenic vaccine for infants younger than 6 months are es-
preferred over RIDTs in ambulatory children in whom sential. Studies on the effectiveness and safety of influenza
testing is performed. During periods of high community vaccines containing adjuvants that enhance immune re-
influenza activity, clinicians should consider confirming sponses to influenza vaccines or that use novel routes of
negative RIDTs with a molecular test. When influenza is administration are needed in children. Efforts to improve
circulating in the community, hospitalized patients with the vaccine development process to allow for a shorter in-
signs and symptoms of influenza should be tested with a terval between identification of vaccine strains and vac-
molecular assay with high sensitivity and specificity. cine production continue.

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Promoting Vaccine Confidence and Increasing and other close family contacts in the pediatric office setting
Vaccination Coverage [Reaffirmed March 2017]. Pediatrics. 2012;129(1):e247
Systematic health services research is needed to examine American Academy of Pediatrics, Committee on Infec-
influenza vaccination coverage, factors associated with tious Diseases. Influenza immunization for all health care
undervaccination, and interventions to increase uptake in personnel: keep it mandatory [Reaffirmed August 2021].
diverse populations. National data from 2019 found that Pediatrics. 2015;136(4):809–818
25.8% of parents were hesitant about influenza vacci- American Academy of Pediatrics, Committee on Pediat-
ne.190 Children of parents who were hesitant about child- ric Emergency Medicine. Preparation for emergencies in
hood vaccines had 25.6% lower influenza vaccination the offices of pediatricians and pediatric primary care
coverage in the influenza 2018–2019 season compared providers [Reaffirmed June 2019]. Pediatrics. 2007;120(1):200–212
with children of parents not reporting hesitancy.191 Vac- American Academy of Pediatrics, Committee on Practice
cine hesitancy remains a major public health threat. Fu- and Ambulatory Medicine, AAP Committee on Infectious
ture studies should aim to improve our understanding of Diseases, AAP Committee on State Government Affairs, AAP
influenza vaccine hesitancy and identify effective strate- Council on School Health, AAP Section on Administration
gies to address parental concerns, foster greater vaccine and Practice Management. Medical versus nonmedical im-
confidence, and increase influenza vaccine acceptance.141 munization exemptions for child care and school attendance
Engagement of key stakeholder groups in this work is cru- [Reaffirmed July 2022]. Pediatrics. 2016;138(3):e20162145
cial, including patients and families; health care professio- Edwards KM, Hackell JM. American Academy of Pediat-
nals; practices, as well as health systems; public health rics, Committee on Infectious Diseases, Committee on
officials; and community leaders. Enhanced collaboration Practice and Ambulatory Medicine. Countering vaccine
may facilitate more equitable influenza vaccine supply and hesitancy [Reaffirmed January 2022]. Pediatrics. 2016;
delivery and more effective community outreach, particularly 138(3):e20162146
to vulnerable populations. Novel approaches for reducing American Academy of Pediatrics, Committee on Pediat-
barriers to accessing preventive care services may also help ric Emergency Medicine; American Academy of Pediatrics
to reduce disparities in influenza vaccination coverage. Ongo- Committee on Medical Liability; Task Force on Terrorism.
ing efforts should include broader implementation and eval- The pediatrician and disaster preparedness [Reaffirmed
uation of mandatory HCP vaccination programs in both December 2013]. Pediatrics. 2006;117(2):560–565
inpatient and outpatient settings. Lastly, additional controlled American Academy of Pediatrics. Influenza. In: Kimber-
data are needed to inform the timing, schedule, and type of lin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red
influenza vaccine for optimal vaccine immunogenicity among Book: 2021 Report of the Committee on Infectious Dis-
immunocompromised children. eases. 32nd ed. American Academy of Pediatrics; 2021:
447–457
Antiviral Treatment Hackell JM, Palevsky SL, Resnick M. American Academy
New antiviral drugs are in various development phases, of Pediatrics, Committee on Practice and Ambulatory
given the need to improve options for the treatment and Medicine, Council on Clinical Information Technology,
chemoprophylaxis of influenza. Additionally, with limited Section on Early Career Physicians. Immunization Infor-
data on the use of antiviral agents in hospitalized children mation Systems. Pediatrics. 2022;150(4):e2022059281
and in children with underlying medical conditions, prospec-
tive clinical trials to inform optimal timing and efficacy of
COMMITTEE ON INFECTIOUS DISEASES, 2022–2023
antiviral treatment in these populations are warranted, par-
ticularly as new antiviral agents or new indications for exist- Sean T. O’Leary, MD, MPH, FAAP, Chairperson
James D. Campbell, MD, MS, FAAP, Vice Chairperson
ing antiviral agents become available. Barriers to treatment
Monica I. Ardura, DO, MSCS, FAAP
of children at high risk for complications, especially hospital-
Ritu Banerjee, MD, PhD, FAAP
ized patients, must be explored.
Kristina A. Bryant, MD, FAAP
Mary T. Caserta, MD, FAAP
ADDITIONAL RESOURCES Robert W. Frenck, Jr, MD, FAAP
Pediatricians can remain informed of advances and other up- Jeffrey S. Gerber, MD, PhD, FAAP
dates during the influenza season by following the CDC Influ- Chandy C. John, MD, MS, FAAP
enza page (www.cdc/gov/flu) and the AAP Red Book Online Athena P. Kourtis, MD, PhD, MPH, FAAP
Influenza News and Resource Page (www.aapredbook.org). Angela Myers, MD, MPH, FAAP
Lessin HR, Edwards KM. American Academy of Pediat- Pia Pannaraj, MD, MPH, FAAP
rics, Committee on Practice and Ambulatory Medicine, Adam J. Ratner, MD, MPH, FAAP
Committee on Infectious Diseases. Immunizing parents Samir S. Shah, MD, MSCE, FAAP

by guest
CONTRIBUTORS their significant contributions in providing input on the
Kristina A. Bryant, MD, FAAP initial drafts on behalf of the AAP Partnership for Policy
Annika M. Hofstetter, MD, PhD, MPH, FAAP Initiative.
PARTNERSHIP FOR POLICY IMPLEMENTATION

ABBREVIATIONS
Juan D. Chaparro, MD, MS, FAAP
Jeremy J. Michel, MD, MHS, FAAP AAP: American Academy of Pediatrics
ACIP: Advisory Committee on Immunization Practices
EX OFFICIO CDC: Centers for Disease Control and Prevention
CI: confidence interval
David W. Kimberlin, MD, FAAP – Red Book editor
COVID-19: coronavirus disease 2019
Elizabeth D. Barnett MD, FAAP – Red Book associate editor
EHR: electronic health record
Ruth Lynfield, MD, FAAP – Red Book associate editor
FDA: US Food and Drug Administration
Mark H. Sawyer, MD, FAAP – Red Book associate editor
GBS: Guillain-Barre syndrome
Henry H. Bernstein, DO, MHCM, FAAP – Red Book online
HA: hemagglutinin
associate editor HCP: health care personnel
iGAS: invasive group A streptococcal
LIAISONS IIV: inactivated influenza vaccine
Cristina V. Cardemil, MD, MPH, FAAP – National Institutes of IIV4: quadrivalent inactivated influenza vaccine
Health IV: intravenous
Karen M. Farizo, MD – US Food and Drug Administration LAIV: live attenuated influenza vaccine
Lisa M. Kafer, MD, FAAP – Committee on Practice Ambulatory LAIV4: quadrivalent live attenuated influenza vaccine
Medicine mRNA: messenger RNA
David Kim, MD, MA – HHS Office of Infectious Disease NAI: neuraminidase inhibitor
and HIV/AIDS Policy OR: odds ratio
Eduardo L opez Medina, MD, MSc – Sociedad Latinoamericana RCT: randomized controlled trial
de Infectologia Pediatrica RIDT: rapid influenza diagnostic test
Denee Moore, MD, FAAFP – American Academy of Family RIV: recombinant influenza vaccine
Physicians RIV4: quadrivalent recombinant influenza vaccine
Lakshmi Panagiotakopoulos, MD, MPH – Centers for RR: relative risk
Disease Control and Prevention SARS-CoV-2: severe acute respiratory syndrome
Jose R. Romero, MD, FAAP – Centers for Disease Control coronavirus 2
and Prevention VE: vaccine effectiveness
Laura Sauve, MD, MPH, FAAP, FRCPS – Canadian Pediatric
Society
Jeffrey R. Starke, MD, FAAP – American Thoracic Society REFERENCES
Jennifer Thompson, MD – American College of Obstetricians 1. American Academy of Pediatrics, Committee on Infectious
and Gynecologists Diseases. Recommendations for prevention and control of
Melinda Wharton, MD, MPH – Centers for Disease Control influenza in children, 2023–2024. Pediatrics. 2023;152(4):
and Prevention e2023063772
Charles R. Woods, Jr, MD, MS, FAAP – Pediatric Infectious 2. Thomas CM, White EB, Kojima N, et al. Early and increased influ-
Diseases Society enza activity among children–Tennessee, 2022–23 season. MMWR
Morb Mortal Wkly Rep. 2023;72(3):49–54
STAFF 3. McLean HQ, Petrie JG, Hanson KE, et al. Interim estimates of
2022–23 seasonal influenza vaccine effectiveness–Wisconsin,
Jennifer M. Frantz, MPH October 2022–February 2023. MMWR Morb Mortal Wkly Rep.
Gillian Gibbs, MPH 2023;72(8):201–205
4. Hoy G, Kuan G, Lopez R, et al. The spectrum of influenza in chil-
ACKNOWLEDGMENTS dren. Clin Infect Dis. 2023;76(3):e1012–e1020
The Committee on Infectious Diseases thanks Kristina A. 5. Herrera AL, Huber VC, Chaussee MS. The association between in-
Bryant, MD, FAAP, and Annika M. Hofstetter, MD, PhD, vasive group A streptococcal diseases and viral respiratory
MPH, FAAP, for their leadership in drafting the policy tract infections. Front Microbiol. 2016;7:342
statement and technical report; and Juan D. Chaparro, 6. Barnes M, Youngkin E, Zipprich J, et al. Notes from the field: increase
MD, MS, FAAP, and Jeremy J. Michel, MD, MHS, FAAP, for in pediatric invasive group A Streptococcus infections–Colorado and

by guest
Minnesota, October–December 2022. MMWR Morb Mortal Wkly Rep. 22. Centers for Disease Control and Prevention. Flu disparities
2023;72(10):265–267 among racial and ethnic minority groups. Available at: https://
7. Antoon JW, Hall M, Herndon A, et al. Prevalence, risk factors, www.cdc.gov/flu/highrisk/disparities-racial-ethnic-minority-
and outcomes of influenza-associated neurologic complications groups.html. Accessed July 12, 2021
in children. J Pediatr. 2021;239:32–38.e5 23. Younas M, Royer J, Winders HR, et al. Temporal association be-
8. Frankl S, Coffin SE, Harrison JB, Swami SK, McGuire JL. Influ- tween influenza vaccination coverage and ambulatory antibiotic
enza-associated neurologic complications in hospitalized chil- use in children. Pediatr Infect Dis J. 2022;41(7):600–602
dren. J Pediatr. 2021;239:24–31.e1 24. Hood N, Flannery B, Gaglani M, et al. Influenza vaccine effec-
9. Rubino R, Imburgia C, Bonura S, Trizzino M, Iaria C, Cascio A. tiveness among children: 2011–2020. Pediatrics. 2023;151(4):
Thromboembolic events in patients with influenza: a scoping re- e2022059922
view. Viruses. 2022;14(12):2817 25. Price AM, Flannery B, Talbot HK, et al. Influenza vaccine effective-
10. Centers for Disease Control and Prevention. Weekly US influenza ness against influenza A(H3N2)-related illness in the United
surveillance report (FluView). Available at: https://www.cdc.gov/ States during the 2021–2022 influenza season. Clin Infect Dis.
flu/weekly/. Accessed May 31, 2020 2023;76(8):1358–1363
11. Tokars JI, Olsen SJ, Reed C. Seasonal incidence of symptomatic in- 26. Olson SM, Newhams MM, Halasa NB, et al. Pediatric Intensive
fluenza in the United States. Clin Infect Dis. 2018;66(10):1511–1518 Care Influenza Investigators. Vaccine effectiveness against life-
threatening influenza illness in US children. Clin Infect Dis.
12. Shang M, Blanton L, Brammer L, Olsen SJ, Fry AM. Influenza-as- 2022;75(2):230–238
sociated pediatric deaths in the United States, 2010-2016. Pedi-
atrics. 2018;141(4):e20172918 27. Feldstein LR, Ogokeh C, Rha B, et al. Vaccine effectiveness
against influenza hospitalization among children in the United
13. Kamidani S, Garg S, Rolfes MA, et al. Epidemiology, clinical char- States, 2015–2016. J Pediatric Infect Dis Soc. 2021;10(2):75–82
acteristics, and outcomes of influenza-associated hospitaliza-
tions in US children over 9 seasons following the 2009 H1N1 28. Segaloff HE, Leventer-Roberts M, Riesel D, et al. Influenza vac-
pandemic. Clin Infect Dis. 2022;75(11):1930–1939 cine effectiveness against hospitalization in fully and partially
vaccinated children in Israel: 2015–2016, 2016–2017, and 2017–2018.
14. Halasa NB, Spieker AJ, Young CC, et al. Pediatric Intensive Care In- Clin Infect Dis. 2019;69(12):2153–2161
fluenza and Overcoming COVID-19 Investigators. Life-threatening
complications of influenza versus coronavirus disease 2019 29. Blyth CC, Cheng AC, Crawford NW, et al. Paediatric Active En-
(COVID-19) in US children. Clin Infect Dis. 2023;76(3):e280–e290 hanced Disease Surveillance (PAEDS); Influenza Complications
Alert Network; (FluCAN) Collaboration. The impact of new univer-
15. Adams K, Tastad KJ, Huang S, et al. Prevalence of SARS-CoV-2 sal child influenza programs in Australia: vaccine coverage, ef-
and influenza coinfection and clinical characteristics among fectiveness and disease epidemiology in hospitalized children in
children and adolescents aged <18 years who were hospital-
2018. Vaccine. 2020;38(13):2779–2787
ized or died with influenza–United States, 2021–22 influenza sea-
son. MMWR Morb Mortal Wkly Rep. 2022;71(50):1589–1596 30. Kalligeros M, Shehadeh F, Mylona EK, et al. Influenza vaccine ef-
fectiveness against influenza-associated hospitalization in chil-
16. Maddux AB, Grunwell JR, Newhams MM, et al. PALISI Pediatric
dren: a systematic review and meta-analysis. Vaccine. 2020;38(14):
Intensive Care Influenza Network Investigators. Association of
2893–2903
asthma with treatments and outcomes in children with critical
influenza. J Allergy Clin Immunol Pract. 2023;11(3):836–843.e3 31. Pebody RG, Zhao H, Whitaker HJ, et al. Effectiveness of influenza
17. O’Halloran AC, Holstein R, Cummings C, et al. Rates of influenza- vaccine in children in preventing influenza associated hospitali-
associated hospitalization, intensive care unit admission, and zation, 2018–2019, England. Vaccine. 2020;38(2):158–164
in-hospital death by race and ethnicity in the United States 32. Shinjoh M, Sugaya N, Yamaguchi Y, et al. Influenza vaccine effec-
From 2009 to 2019. JAMA Netw Open. 2021;4(8):e2121880 tiveness against influenza A in children based on the results of
18. Mackey K, Ayers CK, Kondo KK, et al. Racial and ethnic dispar- various rapid influenza tests in the 2018–2019 season. PLoS
ities in COVID-19-related infections, hospitalizations, and deaths: One. 2021;16(3):e0249005
a systematic review. Ann Intern Med. 2021;174(3):362–373 33. Yildirim I, Kao CM, Tippett A, et al. A retrospective test-negative
19. Fitzpatrick T, McNally JD, Stukel TA, et al. Family and child case-control study to evaluate influenza vaccine effectiveness in
risk factors for early-life RSV illness. Pediatrics. 2021;147(4): preventing hospitalizations in children. Clin Infect Dis. 2021;
e2020029090 73(10):1759–1767
20. Centers for Disease Control and Prevention. Prevalence of 34. Flannery B, Reynolds SB, Blanton L, et al. Influenza vaccine effec-
childhood obesity in the United States. Available at: https:// tiveness against pediatric deaths: 2010–2014. Pediatrics. 2017;
www.cdc.gov/obesity/data/childhood.html. Accessed October 5, 139(5):e20164244
2022 35. Tran D, Vaundry W, Moore D, et al. Hospitalization for influenza A
21. Vitoratou D-I, Milas G-P, Korovessi P, Kostaridou S, Koletsi P. Obe- versus B. Pediatrics. 2016;138(3):e20154643
sity as a risk factor for severe influenza infection in children 36. Campbell AP, Ogokeh C, Weinberg GA, et al. New Vaccine Surveil-
and adolescents: a systematic review and meta-analysis. Eur J lance Network (NVSN). Effect of vaccination on preventing influ-
Pediatr. 2023;182(1):363–374 enza-associated hospitalizations among children during a severe

by guest
season associated with B/Victoria viruses, 2019–2020. Clin Infect 51. Fluzone Quadrivalent package insert. Available at: https://www.
Dis. 2021;73(4):e947–e954 fda.gov/media/119856/download. Accessed August 21, 2023
37. Chung JR, Rolfes MA, Flannery B, et al. Effects of influenza vacci- 52. Robertson CA, Mercer M, Selmani A, Klein NP, Jeanfreau R,
nation in the United States during the 2018-2019 influenza sea- Greenberg DP. Safety and immunogenicity of a full-dose, split-
son. Clin Infect Dis. 2020;71(8):e368–e376 virion, inactivated, quadrivalent influenza vaccine in healthy children
38. Centers for Disease Control and Prevention. 2021–2022 esti- 6-35 months of age: a randomized controlled clinical trial. Pediatr
mated flu illnesses, medical visits, hospitalizations, and deaths Infect Dis J. 2019;38(3):323–328
prevented by flu vaccination. Available at: https://www.cdc.gov/ 53. US Food and Drug Administration. Afluria quadrivalent. Available
flu/about/burden-averted/2021-2022.htm. Accessed April 24, 2023 at: https://www.fda.gov/vaccines-blood-biologics/vaccines/afluria-
39. Ferdinands JM, Olsho LE, Agan AA, et al. Effectiveness of influenza quadrivalent. Accessed June 24, 2019
vaccine against life-threatening RT-PCR confirmed influenza illness 54. Duffy J, Weintraub E, Hambidge SJ, et al. Febrile seizure risk after vac-
in US children, 2010-2012. J Infect Dis. 2014;210(5):674–683 cination in children 6 to 23 months. Pediatrics. 2016;138(1):e20160320
40. World Health Organization. Recommended composition of influenza 55. Thompson CA. Vaccine safety signal from spontaneous system
virus vaccines for use in the 2023–2024 northern hemisphere in- not supported by active surveillance. Am J Health Syst Pharm.
fluenza season. Available at: https://www.who.int/publications/m/ 2014;71(17):1432–1433
item/recommended-composition-of-influenza-virus-vaccines-for-use- 56. Sentinel. Sentinel CBER/PRISM surveillance report. Influenza vac-
in-the-2023-2024-northern-hemisphere-influenza-season. Accessed cines and febrile seizures in the 2013–2014 and 2014–2015 in-
March 26, 2023 fluenza seasons. Available at: https://www.sentinelinitiative.org/
41. US Food and Drug Administration. Summary Minutes. 180th vaccines sites/default/files/vaccines-blood-biologics/assessments/Influenza-
and related biological products advisory committee. Available at: Vaccines-Febrile-Seizures-Final-Report.pdf. Accessed June 24, 2019
https://www.fda.gov/media/166774/download. Accessed June 6, 2023 57. Baker MA, Jankosky C, Yih WK, et al. The risk of febrile seizures
42. Grohskopf LA, Blanton LH, Ferdinands JM, Chung JR, Broder KR, following influenza and 13-valent pneumococcal conjugate vac-
Talbot HK. Prevention and control of seasonal influenza with vaccines. Vaccine. 2020;38(9):2166–2171
cines: recommendations of the Advisory Committee on Immuniza- 58. Walter EB, Klein NP, Wodi AP, et al. Fever after influenza, diphthe-
tion Practices—United States, 2023–24 influenza season. MMWR ria-tetanus-acellular pertussis, and pneumococcal vaccinations.
Recomm Rep. 2023;72(RR-2):1–25 Pediatrics. 2020;145(3):e20191909
43. Kim JH, Drame M, Puthanakit T, et al. Immunogenicity and safety 59. Janssen C, Mosnier A, Gavazzi G, et al. Coadministration of sea-
of AS03-adjuvanted H5N1 influenza vaccine in children 6–35 sonal influenza and COVID-19 vaccines: a systematic review of
months of age. Pediatr Infect Dis J. 2021;40(9):e333–e339 clinical studies. Hum Vaccin Immunother. 2022;18(6):2131166
44. Vesikari T, Kirstein J, Devota Go G, et al. Efficacy, immunogenicity, 60. Moro PL, Zhang B, Ennulat C, et al. Safety of co-administration
and safety evaluation of an MF59-adjuvanted quadrivalent influ- of mRNA COVID-19 and seasonal inactivated influenza vaccines
enza virus vaccine compared with non-adjuvanted influenza vac- in the vaccine adverse event reporting system (VAERS) during
cine in children: a multicenter, randomized, controlled, observer- July 1, 2021-June 30, 2022. Vaccine. 2023;41(11):1859–1863
blinded, phase 3 trial. Lancet Respir Med. 2018;6(5):345–356
61. Hause AM, Zhang B, Yue X, et al. Reactogenicity of simultaneous
45. Palladino G, Ferrari A, Music N, Settembre EC, Wen Y. Improved im- COVID-19 mRNA booster and influenza vaccination in the United
munologic responses to heterologous influenza strains in children States. JAMA Netw Open. 2022;5(7):e2222241
with low preexisting antibody response vaccinated with MF59-
62. Centers for Disease Control and Prevention. Interim clinical con-
adjuvanted influenza vaccine. Vaccine. 2021;39(38):5351–5357
siderations for use of COVID-19 vaccines currently authorized in
46. Chanthavanich P, Versage E, Van Twuijver E, Hohenboken M. Anti- the United States. Available at: https://www.cdc.gov/vaccines/
body responses against heterologous A/H5N1 strains for an MF59- covid-19/clinical-considerations/covid-19-vaccines-us.html. Accessed
adjuvanted cell culture-derived A/H5N1 (aH5N1c) influenza vaccine August 21, 2023
in healthy pediatric subjects. Vaccine. 2021;39(47):6930–6935
63. World Health Organization. The Global Advisory Committee on Vaccine
47. US Food and Drug Administration. Clinical Review: Flucelvax Safety. Thimerosal Vaccines. Available at: https://www.who.int/groups/
Quadrivalent. Silver Spring, MD: US Department of Health and global-advisory-committee-on-vaccine-safety/topics/thiomersal-and-
Human Services, Food and Drug Administration; 2021 vaccines/thiomersal-vaccines#cms. Accessed August 21, 2023
48. US Food and Drug Administration. Fluarix Quadrivalent package 64. Verstraeten T, Davis RL, DeStefano F, et al. Safety of thimerosal-
insert. Available at: https://www.fda.gov/media/79278/download. containing vaccines: a two-phased study of computerized health main-
Accessed August 21, 2023 tenance organization databases. Pediatrics. 2003;112(5):1039–1048
49. US Food and Drug Administration. Flulaval Quadrivalent package 65. Stehr-Green P, Tull P, Stellfeld M, Mortenson PB, Simpson D. Au-
insert. Available at: https://www.fda.gov/media/115785/download. tism and thimerosal-containing vaccines: lack of consistent evi-
Accessed August 21, 2023 dence for an association. Am J Prev Med. 2003;25(2):101–106
50. US Food and Drug Administration. Flucelvax Quadrivalent pack- 66. Rubin LG, Levin MJ, Ljungman P, et al. Infectious Diseases Society
age insert. Available at: https://www.fda.gov/media/115862/download. of America. 2013 IDSA clinical practice guideline for vaccination of
Accessed August 21, 2023 the immunocompromised host. Clin Infect Dis. 2014;58(3):309–318

by guest
67. Centers for Disease Control and Prevention. Altered immuno- 81. Powell LN, Begue RE. Influenza vaccine effectiveness among chil-
competence: general best practice guidelines for immunization. dren for the 2017–2018 season. J Pediatric Infect Dis Soc.
Available at: https://www.cdc.gov/vaccines/hcp/acip-recs/general- 2020;9(4):468–473
recs/immunocompetence.html. Accessed June 6, 2023 82. Sahni LC, Naioti EA, Olson SM, et al. Sustained within-season vaccine
68. Danziger-Isakov L, Kumar D. AST ID Community of Practice. Vacci- effectiveness against influenza-associated hospitalization in children:
nation of solid organ transplant candidates and recipients: evidence from the New Vaccine Surveillance Network, 2015–2016
guidelines from the American Society of Transplantation Infec- through 2019–2020. Clin Infect Dis. 2023;76(3):e1031–e1039
tious Diseases Community of Practice. Clin Transplant. 2019;33(9): 83. Wagner AL, Sanchez N, Kubale J, et al. Single-dose vaccination
e13563 among infants and toddlers provides modest protection against
69. American Academy of Pediatrics, Committee on Infectious Dis- influenza illness, which wanes after 5 months. J Infect Dis.
eases. Recommendations for prevention and control of influenza 2023;227(1):87–91
in children, 2021–2022. Pediatrics. 2021;148(4):e2021053745 84. Centers for Disease Control and Prevention. CDC Yellow Book:
70. US Food and Drug Administration. FluMist package insert. Avail- health information for international travel. Available at: https://
able at: https://www.fda.gov/media/160349/download. Accessed wwwnc.cdc.gov/travel/page/yellowbook-home-2020. Accessed April 14,
June 6, 2023 2022
71. Petrie JG, Ohmit SE, Truscon R, et al. Modest waning of influenza 85. Kelso JM, Greenhawt MJ, Li JT. Task Force on Joint Parameters.
vaccine efficacy and antibody titers during the 2007-2008 influ- Update on influenza vaccination of egg allergic patients. Ann Al-
enza season. J Infect Dis. 2016;214(8):1142–1149 lergy Asthma Immunol. 2013;111(4):301–302
72. Ferdinands JM, Fry AM, Reynolds S, et al. Intraseason waning of 86. Greenhawt M, Turner PJ, Kelso JM. Administration of influenza
influenza vaccine protection: evidence from the US influenza vaccines to egg allergic recipients: a practice parameter update
vaccine effectiveness network, 2011–2012 through 2014–2015. 2017. Ann Allergy Asthma Immunol. 2018;120(1):49–52
Clin Infect Dis. 2017;64(5):544–550 87. American College of Obstetricians and Gynecologists. ACOG com-
73. Castilla J, Martinez-Baz I, Martinez-Artola V, et al. Decline in mittee opinion No. 732: influenza vaccination during pregnancy.
influenza vaccine effectiveness with time after vaccination, Obstet Gynecol. 2018;131(4):e109–e114
Navarre, Spain, season 2011–2012. Euro Surveill. 2013;18(5): 88. Robinson SG, Osborn AW. The concordance of parent and child
20388 immunization. Pediatrics. 2017;139(5):e20162883
74. Kissling E, Valenciano M, Larrauri A. Low and decreasing vaccine 89. Zaman K, Roy E, Arifeen SE, et al. Effectiveness of maternal influ-
effectiveness against influenza A(H3) in 2011/12 among vaccina- enza immunization in mothers and infants. N Engl J Med. 2008;
tion target groups in Europe: results from the I-MOVE multicen- 359(15):1555–1564
ter case-control study. Euro Surveill. 2013;18(5):20390 90. Tapia MD, Sow SO, Tamboura B, et al. Maternal immunization
75. Belongia EA, Sundaram ME, McClure DL, Meece JK, Ferdinands J, with trivalent inactivated influenza vaccine for prevention of in-
VanWormer JJ. Waning vaccine protection against influenza A fluenza in infants in Mali: a prospective, active controlled, ob-
(H3N2) illness in children and older adults during a single sea- server blind, randomized phase 4 trial. Lancet Infect Dis. 2016;
son. Vaccine. 2015;33(1):246–251 26(9):1026–1035
76. Radin JM, Hawksworth AW, Myers CA, Ricketts MN, Hansen EA, 91. Madhi SA, Cutland CL, Kuwanda L, et al. Maternal Flu Trial (Mat-
Brice GT. Influenza vaccine effectiveness: Maintained protection flu) Team. Influenza vaccination of pregnant women and protec-
throughout the duration of influenza seasons 2010-2011 through tion of their infants. N Engl J Med. 2014;371(10):918–931
2013-2014. Vaccine. 2016;34(33):3907–3912 92. Steinhoff MC, Katz J, Englund JA, et al. Year-round influenza im-
77. Puig-Barbera J, Mira-Iglesias A, Tortajada-Girbes M, et al. munization during pregnancy in Nepal: a phase 4, randomized,
Waning protection of influenza vaccination during four influ- placebo-controlled trial. Lancet Infect Dis. 2017;17(9):981–989
enza seasons, 2011–2012 to 2014–2015. Vaccine. 2017;35(43): 93. Shakib JH, Korgenski K, Presson AP, et al. Influenza in infants born
5799–5807 to women vaccinated during pregnancy. Pediatrics. 2016;137(6):
78. Ray GT, Lewis N, Klein NP, et al. Intraseason waning of influenza e20152360
vaccine effectiveness. Clin Infect Dis. 2019;68(10):1623–1630 94. Nunes MC, Madhi SA. Influenza vaccination during pregnancy
79. Kissling E, Nunes B, Robertson C, et al. I-MOVE multicenter for prevention of influenza confirmed illness in the infants: a
case-control study 2010–2011 to 2014–2015: is there within- systematic review and meta-analysis. Hum Vaccin Immunother.
season waning of influenza type/subtype vaccine effective- 2018;14(3):758–766
ness with increasing time since vaccination? Euro Surveill. 95. Thompson M, Kwong J, Regan A, et al. Influenza vaccine effec-
2016;21(16) tiveness in preventing influenza-associated hospitalizations dur-
80. Pebody R, Andrews N, McMenamin J, et al. Vaccine effectiveness ing pregnancy: a multi-country retrospective test negative
of 2011–2012 trivalent seasonal influenza vaccine in preventing design study, 2010–2016. Clin Infect Dis. 2019;68(9):1444–1453
laboratory-confirmed influenza in primary care in the United 96. Nunes MC, Madhi SA. Prevention of influenza related illness in
Kingdom: evidence of waning intraseasonal protection. Euro young infants by maternal vaccination during pregnancy. F1000
Surveill. 2013;18(5):20389 Res. 2018;7(1):122

by guest
97. Omer SB, Clark DR, Aqil AR, et al. Maternal influenza immunization 111. Callahan AG, Coleman-Cowger VH, Schulkin J, Power ML. Racial
and prevention of severe clinical pneumonia in young infants: disparities in influenza immunization during pregnancy in the
analysis of randomized controlled trials conducted in Nepal, Mali United States: a narrative review of the evidence for disparities
and South Africa. Pediatr Infect Dis J. 2018;37(5):436–440 and potential interventions. Vaccine. 2021;39(35):4938–4948
98. Munoz FM, Jackson LA, Swamy GK, et al. Safety and immunoge- 112. Moll K, Wong HL, Fingar K, et al. Vaccine exposure during preg-
nicity of seasonal trivalent inactivated influenza vaccines in nancy among privately and publicly insured women in the
pregnant women. Vaccine. 2018;36(52):8054–8061 United States, 2016-2018. Vaccine. 2021;39(41):6095–6103
99. Chambers CD, Johnson DL, Xu R, et al. Safety of the 2010–11, 113. Kaur R, Callaghan T, Regan AK. Disparities in maternal influenza
2011–12, 2012–13, and 2013–14 seasonal influenza vaccines in immunization among women in rural and urban areas of the
pregnancy: birth defects, spontaneous abortion, preterm deliv- United States. Prev Med. 2021;147:106531
ery, and small for gestational age infants, a Study From the Co- 114. Schlaudecker EP, Steinhoff MC, Omer SB, et al. IgA and neutraliz-
hort Arm of VAMPSS. Vaccine. 2016;34(37):4443–4449 ing antibodies to influenza A virus in human milk: a randomized
100. Donahue JG, Kieke BA, King JP, et al. Association of spontaneous trial of antenatal influenza immunization. PLoS One. 2013;8(8):
abortion with receipt of inactivated influenza vaccine containing e70867
H1N1pdm09 in 2010–11 and 2011–12. Vaccine. 2017;35(40): 115. US Department of Health and Human Services, Office of Disease
5314–5322 Prevention and Health Promotion. Healthy People 2020 topics
101. Donahue J. Inactivated influenza vaccine and spontaneous abor- and objectives–immunization and infectious diseases. 2019.
tion in the Vaccine Safety Datalink in 2012–13, 2013–14, and Available at: https://www.healthypeople.gov/2020/topics-objectives/
2014–15. Vaccine. 2019;37(44):6673–6681 topic/immunization-and-infectious-diseases. Accessed June 9, 2021
102. Robinson C, Oberye J, van Boxmeer J, et al. A prospective co- 116. Ackerson BK, Sy LS, Glenn SC, et al. Pediatric vaccination during
hort study on pregnancy outcomes of persons immunized with the COVID-19 pandemic. Pediatrics. 2021;148(1):e2020047092
a seasonal quadrivalent inactivated influenza vaccine during 117. Bramer CA, Kimmins LM, Swanson R, et al. Decline in child vac-
pregnancy. Vaccines (Basel). 2022;10(10):1577 cination coverage during the COVID-19 pandemic–Michigan Care
103. Sheffield JS, Greer LG, Rogers VL, et al. Effect of influenza vacci- Improvement Registry, May 2016–May 2020. MMWR Morb Mortal
nation in the first trimester of pregnancy. Obstet Gynecol. Wkly Rep. 2020;69(20):630–631
2012;120(3):532–537 118. O’Leary ST, Trefren L, Roth H, Moss A, Severson R, Kempe A.
104. Polyzos KA, Konstantelias AA, Pitsa CE, Falagas ME. Maternal in- Number of childhood and adolescent vaccinations administered
fluenza vaccination and risk for congenital malformations: a before and after the COVID-19 outbreak in Colorado. JAMA Pe-
systematic review and meta-analysis. Obstet Gynecol. 2015;126(5): diatr. 2021;175(3):305–307
1075–1084 119. Santoli JM, Lindley MC, DeSilva MB, et al. Effects of the COVID-19
105. Peppa M, Thomas SL, Minassian C, et al. Seasonal influenza vac- pandemic on routine pediatric vaccine ordering and adminis-
cination during pregnancy and the risk of major congenital tration–United States, 2020. MMWR Morb Mortal Wkly Rep.
malformations in live-born infants: a 2010–2016 historical co- 2020;69(19):591–593
hort study. Clin Infect Dis. 2021;73(11):e4296–e4304 120. Centers for Disease Control and Prevention. Influenza vaccina-
106. Chambers CD, Johnson D, Xu R, et al. Risks and safety of pan- tion coverage, children 6 months through 17 years, United
demic H1N1 influenza vaccine in pregnancy: birth defects, spon- States. Available at: https://www.cdc.gov/flu/fluvaxview/dash
taneous abortion, preterm delivery, and small for gestational board/vaccination-coverage-race.html. Accessed July 12, 2023
age infants. Vaccine. 2013;31(44):5026–5032 121. Gates DM, Cohen SA, Orr K, Caffrey AR. Pediatric influenza vacci-
107. Nordin JD, Olshen Kharbanda E, Vazquez Benitez G, et al. Mater- nation rates lower than previous estimates in the United States.
nal influenza vaccine and risks for preterm or small for gesta- Vaccine. 2022;40(44):6337–6343
tional age birth. J Pediatr. 2014;164(5):1051–1057.e1052 122. Fogel B, Schaefer EW, Hicks SD. Early influenza vaccination rates
108. Duque J, Howe AS, Azziz-Baumgartner E, Petousis-Harris H. Mul- decline in children during the COVID-19 pandemic. Vaccine.
tidecade national cohort identifies adverse pregnancy and birth 2021;39(31):4291–4295
outcomes associated with acute respiratory hospitalizations 123. Atherly A, Van Den Broek-Altenburg E, Hart V, Gleason K, Car-
during the influenza season. Influenza Other Respir Viruses. ney J. Consumer reported care deferrals due to the COVID-
2023;17(1):e13063 19 pandemic, and the role and potential of telemedicine:
109. Becerra-Culqui TA, Getahun D, Chiu V, Sy LS, Tseng HF. Prena- cross-sectional analysis. JMIR Public Health Surveill. 2020;6(3):
tal influenza vaccination or influenza infection and autism e21607
spectrum disorder in offspring. Clin Infect Dis. 2022;75(7): 124. Baumer-Mouradian SH, Hart RJ, Visotcky A, et al. Under-
1140–1148 standing influenza and SARS-CoV-2 vaccine hesitancy in racial
110. Centers for Disease Control and Prevention. Influenza vaccina- and ethnic minority caregivers. Vaccines (Basel). 2022;10(11):
tion coverage, pregnant persons, United States. Available at: 1968
https://www.cdc.gov/flu/fluvaxview/dashboard/vaccination-coverage- 125. Hofstetter AM, Schaffer S. Childhood and adolescent vaccination
pregnant.html. Accessed May 8, 2023 in alternative settings. Acad Pediatr. 2021;21(4S):S50–S56

by guest
126. Hart RJ, Paul RI, Levine A, Sikes K, Bryant K, Stevenson MD. Par- 143. Stockwell MS, Catallozzi M, Camargo S, et al. Registry-linked
ent intent and willingness to immunize children against influ- electronic influenza vaccine provider reminders: a cluster-
enza in the pediatric emergency department. Pediatr Emerg crossover trial. Pediatrics. 2015;135(1):e75–e82
Care. 2019;35(7):493–497 144. Lessin HR, Edwards KM. American Academy of Pediatrics, Com-
127. Zerr DM, Englund JA, Robertson AS, et al. Hospital-based influ- mittee on Practice and Ambulatory Medicine, Committee on In-
enza vaccination of children: an opportunity to prevent subse- fectious Diseases. Immunizing parents and other close family
quent hospitalization. Pediatrics. 2008;121(2):345–348 contacts in the pediatric office setting. Pediatrics. 2012;129(1):
128. Pollack AH, Kronman MP, Zhou C, Zerr DM. Automated screening e247–e253
of hospitalized children for influenza vaccination. J Pediatric In- 145. Corley AMS, Gomes SM, Crosby LE, et al. Partnering with faith-
fect Dis Soc. 2014;3(1):7–14 based organizations to offer flu vaccination and other preven-
tive services. Pediatrics. 2022;150(3):e2022056193
129. Stockwell MS, Natarajan K, Ramakrishnan R, et al. Immuniza-
tion data exchange with electronic health records. Pediatrics. 146. Razzaghi H, Srivastav A, de Perio MA, Laney AS, Black CL. Influ-
2016;137(6):e20154335 enza and COVID-19 vaccination coverage among health care per-
sonnel–United States, 2021–22. MMWR Morb Mortal Wkly Rep.
130. Stokley S, Kempe A, Stockwell MS, Szilagyi PG. Improving pediat-
2022;71(42):1319–1326
ric vaccination coverage in the United States. Acad Pediatr.
2021;21(4):S1–S2 147. Frederick J, Brown AC, Cummings DA, et al. Protecting health
care personnel in outpatient settings: the influences of manda-
131. Cataldi JR, Kerns ME, O’Leary ST. Evidence-based strategies to
tory versus nonmandatory influenza vaccination policies on
increase vaccination uptake: a review. Curr Opin Pediatr. 2020;
workplace absenteeism during multiple respiratory virus sea-
32(1):151–159
sons. Infect Control Hosp Epidemiol. 2018;39(4):452–461
132. Clark SJ, Butchart A, Kennedy A, Dombkowski KJ. Parents’ expe-
148. Centers for Disease Control and Prevention. Influenza antiviral
riences with and preferences for immunization reminder/recall
medications. Available at: www.cdc.gov/flu/professionals/antivirals/
technologies. Pediatrics. 2011;128(5):e1100–e1105
index.htm. Accessed April 14, 2022
133. Daley MF, Barrow J, Pearson K, et al. Identification and recall of
149. Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical practice
children with chronic medical conditions for influenza vaccina-
guidelines by the Infectious Diseases Society of America (IDSA):
tion. Pediatrics. 2004;113(1):e26–e33
2018 update diagnosis, treatment, chemoprophylaxis and insti-
134. Jacobson Vann JC, Jacobson RM, Coyne-Beasley T, Asafu-Adjei JK, Szi- tutional outbreak management of seasonal influenza. Clin Infect
lagyi PG. Patient reminder and recall interventions to improve immu- Dis. 2019;68(6):e1–e47
nization rates. Cochrane Database Syst Rev. 2018;1(1):CD003941
150. Xu M, Cai T, Yue T, et al. Comparative effectiveness of oseltami-
135. Hofstetter AM, Vargas CY, Camargo S, et al. Impacting delayed vir versus peramivir for hospitalized children (aged 0-5 years)
pediatric influenza vaccination: a randomized controlled trial of with influenza infection. Int J Infect Dis. 2023;128:157–165
text message reminders. Am J Prev Med. 2015;48(4):392–401 151. Heo YA. Baloxavir: first global approval. Drugs. 2018;78(6):693–697
136. Stockwell MS, Hofstetter AM, DuRivage N, et al. Text message re- 152. US Food and Drug Administration. Approval package for XO-
minders for second dose of influenza vaccine: a randomized FLUZA. Available at: https://www.accessdata.fda.gov/drugsatfda_
controlled trial. Pediatrics. 2015;135(1):e83–e91 docs/nda/2019/210854Orig1s001.pdf. Accessed May 29, 2022
137. Scott VP, Opel DJ, Reifler J, et al. Office-based educational hand- 153. Baker J, Block SL, Matharu B, et al. Baloxavir marboxil single-
out for influenza vaccination: a randomized controlled trial. Pe- dose treatment in influenza-infected children: a randomized,
diatrics. 2019;144(2):e20182580 double-blind, active controlled phase 3 safety and efficacy trial
138. Daley MF, Narwaney KJ, Shoup JA, Wagner NM, Glanz JM. Ad- (miniSTONE-2). Pediatr Infect Dis J. 2020;39(8):700–705
dressing parents’ vaccine concerns: a randomized trial of a so- 154. Taieb V, Ikeoka H, Wojciechowski P, et al. Efficacy and safety of
cial media intervention. Am J Prev Med. 2018;55(1):44–54 baloxavir marboxil versus neuraminidase inhibitors in the treat-
139. Hofstetter AM, Robinson JD, Lepere K, Cunningham M, Etsekson N, ment of influenza virus infection in high-risk and uncomplicated
Opel DJ. Clinician-parent discussions about influenza vaccination patients–a Bayesian network meta-analysis. Curr Med Res Opin.
of children and their association with vaccine acceptance. Vac- 2021;37(2):225–244
cine. 2017;35(20):2709–2715 155. Ison MG, Portsmouth S, Yoshida Y, et al. Early treatment with ba-
140. Limaye RJ, Opel DJ, Dempsey A, et al. Communicating with vaccine- loxavir marboxil in high-risk adolescent and adult outpatients
hesitant parents: a narrative review. Acad Pediatr. 2021;21(4S): with uncomplicated influenza (CAPSTONE-2): a randomized, pla-
S24–S29 cebo-controlled, phase 3 trial. Lancet Infect Dis. 2020;20(10):
141. Stephens AB, Hofstetter AM, Stockwell MS. Influenza vaccine 1204–1214
hesitancy: scope, influencing factors, and strategic interven- 156. US Food and Drug Administration. Baloxavir package insert.
tions. Pediatr Clin North Am. 2023;70(2):227–241 Available at: https://www.gene.com/download/pdf/xofluza_prescribing.
142. Rao S, Ziniel SI, Khan I, Dempsey A. Be influential: evaluation of pdf. Accessed August 22, 2022
a multifaceted intervention to increase influenza vaccination 157. Centers for Disease Control and Prevention, Health Alert Net-
rates among pediatric inpatients. Vaccine. 2020;38(6):1370–1377 work. Interim guidance for clinicians to prioritize antiviral

by guest
treatment of influenza in the setting of reduced availability of 172. Miyakawa R, Barreto NB, Kato RM, Neely MN, Russell CJ. Early
oseltamivir. Available at: https://emergency.cdc.gov/han/2022/ use of anti-influenza medications in hospitalized children with
han00482.asp. Accessed April 11, 2023 tracheostomy. Pediatrics. 2019;143(3):e20182608
158. Dobson J, Whitley RJ, Pocock S, Monto AS. Oseltamivir treat- 173. Walsh PS, Schnadower D, Zhang Y, Ramgopal S, Shah SS, Wilson
ment for influenza in adults: a meta-analysis of randomised PM. Association of early oseltamivir with improved outcomes in
controlled trials. Lancet. 2015;385(9979):1729–1737 hospitalized children with influenza, 2007-2020. JAMA Pediatr.
159. Jefferson T, Jones MA, Doshi P, et al. Neuraminidase inhibitors 2022;176(11):e223261
for preventing and treating influenza in healthy adults and chil- 174. Li L, Liu J, Qin K. Comparison of double-dose versus standard-
dren. Cochrane Database Syst Rev. 2014;2014(4):CD008965 dose oseltamivir in the treatment of influenza: a systematic re-
160. Malosh RE, Martin ET, Heikkinen T, Brooks WA, Whitley RJ, Monto view and meta-analysis. J Clin Pharmacol. 2020;45(5):918–926
AS. Efficacy and safety of oseltamivir in children: systematic re- 175. Kumar D, Ison MG, Mira JP, et al. Combining baloxavir marboxil
view and individual patient data meta-analysis of randomized with standard-of-care neuraminidase inhibitor in patients hospi-
controlled trials. Clin Infect Dis. 2018;66(10):1492–1500 talized with severe influenza (FLAGSTONE): a randomized, paral-
161. Uyeki TM. Oseltamivir treatment of influenza in children. Pediat- lel-group, double-blind, placebo-controlled, superiority trial. Lancet
rics. 2018;66(10):1501–1503 Infect Dis. 2022;22(5):718–730
162. Wang K, Shun-Shin M, Gill P, Perera R, Harnden A. Neuraminidase 176. Katzen J, Kohn R, Houk JL, Ison MG. Early oseltamivir after hos-
inhibitors for preventing and treating influenza in Children (pub- pital admission is associated with shortened hospitalization: a
lished trials only). Cochrane Database Syst Rev. 2012;2012(4): 5-year analysis of oseltamivir timing and clinical outcomes. Clin
CD002744 Infect Dis. 2019;69(1):52–58
163. Domınguez A, Romero-Tamarit A, Soldevila N, et al. Effectiveness 177. Ramirez J, Peyrani P, Wiemken T, Chaves SS, Fry AM. A random-
of antiviral treatment in preventing death in severe hospitalized ized study evaluating the effectiveness of oseltamivir initiated
at the time of hospital admission in adults hospitalized with in-
influenza cases over six seasons. Epidemiol Infect. 2018;146(7):
fluenza-associated lower respiratory tract infections. Clin Infect
799–808
Dis. 2018;67(5):736–742
164. Hsu J, Santesso N, Mustafa R, et al. Antivirals for treatment of
178. Howard A, Uyeki TM, Fergie J. Influenza-associated acute necro-
influenza: a systematic review and meta-analysis of observa-
tizing encephalopathy in siblings. J Pediatric Infect Dis Soc.
tional studies. Ann Intern Med. 2012;156(7):512–524
2018;7(3):e172–e177
165. Muthuri SG, Venkatesan S, Myles PR, et al. Effectiveness of neur-
aminidase inhibitors in reducing mortality in patients admitted 179. Takeuchi S, Tetsuhashi M, Sato D. Oseltamivir phosphate–lifting
to hospital with influenza A H1N1 pdm09 virus infection: a the restriction on its use to treat teenagers with influenza in
meta-analysis of individual participant data. Lancet Respir Med. Japan. Pharmacoepidemiol Drug Saf. 2019;28(4):434–436
2014;2(5):395–404 180. Toovey S, Prinssen EP, Rayner CR, et al. Postmarketing assess-
166. Venkatesan S, Myles PR, Leonardi-Bee J, et al. Impact of outpa- ment of neuropsychiatric adverse events in influenza patients
tient neuraminidase inhibitor treatment in patients infected treated with oseltamivir: an updated review. Adv Ther. 2012;29(10):
826–848
with influenza A(/H1N1) pdm09 at high risk of hospitalization:
an individual participant data metaanalysis. Clin Infect Dis. 2017; 181. Hamdan L, Probst V, Haddadin Z, et al. Influenza clinical testing
64(10):1328–1334 and oseltamivir treatment in hospitalized children with acute
respiratory illness, 2015–2016. Influenza Other Respir Viruses.
167. Tejada S, Tejo AM, Pena-Lopez Y, Forero CG, Corbella X, Rello J.
2022;16(2):289–297
Neuraminidase inhibitors and single dose baloxavir are effective
and safe in uncomplicated influenza: a meta-analysis of random- 182. Mehta K, Morris SK, Bettinger JA, et al. Canadian Immunization
ized controlled trials. Expert Rev Clin Pharmacol. 2021;14(7): Monitoring Program Active (IMPACT) Investigators. Antiviral use
901–918 in Canadian children hospitalized for influenza. Pediatrics.
2021;148(4):e2020049672
168. Hayden FG, Asher J, Cowling BJ, et al. Reducing influenza virus
transmission: the potential value of antiviral treatment. Clin In- 183. Antoon JW, Hall M, Feinstein JA, et al. Guideline-concordant anti-
fect Dis. 2022;74(3):532–540 viral treatment in children at high risk for influenza complica-
tions. Clin Infect Dis. 2023;76(3):e1040–e1046
169. Dawood FS, Jara J, Gonzalez R, et al. A randomized, double-
blind, placebo-controlled trial evaluating the safety of early osel- 184. Walsh PS, Schnadower D, Zhang Y, Ramgopal S, Shah SS, Wilson
tamivir treatment among children 0-9 years of age hospitalized PM. Assessment of temporal patterns and patient factors asso-
with influenza in El Salvador and Panama. Antiviral Res. ciated with oseltamivir administration in children hospitalized
2016;133:85–94 with influenza, 2007–2020. JAMA Netw Open. 2022;5(9):e2233027
170. Louie JK, Yang S, Samuel MC, Uyeki TM, Schechter R. Neuramini- 185. Ikematsu H, Hayden FG, Kawaguchi K, et al. Baloxavir marboxil
dase inhibitors for critically ill children with influenza. Pediat- for prophylaxis against influenza in household contacts. N Engl
rics. 2013;132(6):e1539–e1545 J Med. 2020;383(4):309–320
171. Campbell AP, Tokars JI, Reynolds S, et al. Influenza antiviral treat- 186. Govorkova EA, Takashita E, Daniels RS, et al. Global update on
ment and length of stay. Pediatrics. 2021;148(4):e2021050417 the susceptibilities of human influenza viruses to neuraminidase

by guest
inhibitors and the cap-dependent endonuclease inhibitor baloxa- 189. Lucira Health Inc. Fact sheet for health care professionals. Lu-
vir, 2018–2020. Antiviral Res. 2022;200:105281 cira COVID-19 and flu home test. Available at: https://www.fda.
187. Hirotsu N, Sakaguchi H, Sato C, et al. Baloxavir marboxil in Jap- gov/media/163456/download. Accessed April 24, 2023
anese pediatric patients with influenza: safety and clinical and 190. Kempe A, Saville AW, Albertin C, et al. Parental hesitancy about
virologic outcomes. Clin Infect Dis. 2020;71(4):971–981 routine childhood and influenza vaccinations: a national survey.
188. Uehara T, Hayden FG, Kawaguchi K, et al. Treatment-emergent in- Pediatrics. 2020;146(1):e20193852
fluenza variant viruses with reduced baloxavir susceptibility: im- 191. Santibanez TA, Nguyen KH, Greby SM, et al. Parental vaccine hesi-
pact on clinical and virologic outcomes in uncomplicated tancy and childhood influenza vaccination. Pediatrics. 2020;146(6):
influenza. J Infect Dis. 2020;221(3):346–355 e2020007609

by guest

Recommendations For Prevention and Control of Influenza in Children 2023-2024

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Recommendations For Prevention and Control of Influenza in Children 2023-2024

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TECHNICAL REPORT

Recommendations for Prevention and

This technical report accompanies the recommendations of the abstract

2 FROM THE AMERICAN ACADEMY OF PEDIATRICS

Overall all ages 29 (21–35) 39 (32–44) †

Overall all ages 44 (37–51) 30 (21–39) Not reported

Overall all ages 9 (-4 to 20) Not reported 36 (20–49)

Overall all ages Not reported 45 (37–52) Not reported

Overall all ages Not reported Not reported Not reported

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INFLUENZA VACCINATION COVERAGE INFLUENZA VACCINE DELIVERY AND IMPLEMENTATION

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Downloaded from http://publications.aap.org/pediatrics/article-pdf/doi/10.1542/peds.2023-063773/1526224/peds.2023-063773.pdf

FROM THE AMERICAN ACADEMY OF PEDIATRICS

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Downloaded from http://publications.aap.org/pediatrics/article-pdf/doi/10.1542/peds.2023-063773/1526224/peds.2023-063773.pdf

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PARTNERSHIP FOR POLICY IMPLEMENTATION

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