This technical report accompanies the recommendations of the 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 influenza. This technical report summarizes recent influenza seasons, morbidity and mortality in children, vaccine effectiveness, and vaccination coverage, and provides detailed guidance on vaccine storage, administration, and implementation. The report also provides a brief background on inactivated and live-attenuated influenza vaccines, available vaccines this season, vaccination during pregnancy and breastfeeding, diagnostic testing for influenza, and antiviral medications for treatment and chemoprophylaxis. Strategies to promote vaccine uptake are emphasized.
Introduction
This technical report accompanies the recommendations of the American Academy of Pediatrics (AAP) for the routine use of influenza vaccine and antiviral medications in the prevention and treatment of influenza in children during the 2023–2024 season.1
Summary of Recent Influenza Activity in the United States
Recent influenza seasons in the United States have varied by severity, duration, and impact on children’s health (Table 1). Influenza vaccine effectiveness (VE) has likewise varied by year, influenza type and influenza A virus subtype, and age group of the child immunized (Fig 1).
. | 2018–2019 . | 2019–2020 . | 2020–2021 . | 2021–2022 . |
---|---|---|---|---|
Severity | Moderate | Moderate | Low | Low |
Duration | 21 wk | — | — | — |
Predominant viruses | Influenza A (H1N1) pdm09, early; influenza A (H3N2), late | Influenza B/Victoria, early; influenza A (H1N1) pdm09, late | Influenza A (H3N2), influenza B (Victoria) | Influenza A (H3N2) |
Vaccination coverage in children | 62.5% | 62.3% | 58.2% | 57.8% |
Hospitalization rate | 71 per 100 000 (0–4 y)20.4 per 100 000 (5–17 y) | 92.3 per 100 000 (0–4 y)23.5 per 100 000 (5–17 y) | 0.8 per 100 000 overall rate | 21.5 per 100 000 (0–4 y)9.1 per 100 000 (5–17 y) |
Characteristics of hospitalized children | 55% had ≥1 underlying condition
| 42.9% had ≥1 underlying condition
| Not available because of low case numbers | 65.7% had ≥1 underlying condition
|
Pediatric deaths | 144 | 199
| 1 | 4415
|
Notable findings | Longest season in a decade |
|
|
|
. | 2018–2019 . | 2019–2020 . | 2020–2021 . | 2021–2022 . |
---|---|---|---|---|
Severity | Moderate | Moderate | Low | Low |
Duration | 21 wk | — | — | — |
Predominant viruses | Influenza A (H1N1) pdm09, early; influenza A (H3N2), late | Influenza B/Victoria, early; influenza A (H1N1) pdm09, late | Influenza A (H3N2), influenza B (Victoria) | Influenza A (H3N2) |
Vaccination coverage in children | 62.5% | 62.3% | 58.2% | 57.8% |
Hospitalization rate | 71 per 100 000 (0–4 y)20.4 per 100 000 (5–17 y) | 92.3 per 100 000 (0–4 y)23.5 per 100 000 (5–17 y) | 0.8 per 100 000 overall rate | 21.5 per 100 000 (0–4 y)9.1 per 100 000 (5–17 y) |
Characteristics of hospitalized children | 55% had ≥1 underlying condition
| 42.9% had ≥1 underlying condition
| Not available because of low case numbers | 65.7% had ≥1 underlying condition
|
Pediatric deaths | 144 | 199
| 1 | 4415
|
Notable findings | Longest season in a decade |
|
|
|
RAD, reactive airways disease; —, not reported.
2022–2023 Influenza Season
The 2022–2023 influenza season began earlier than is typically expected in many states and was characterized by a high burden of disease in children, including high rates of hospitalization. A field investigation conducted in middle Tennessee is illustrative: Among patients tested for influenza in outpatient settings, children were more likely to have positive test results than adults (33% [714 of 2164] vs 20% [483 of 2462], respectively; P < .001). In November 2022, the influenza-associated hospitalization rate among children <5 years of age was 12.6 per 100 000, comparable to peak levels typically seen in high severity seasons.2
Nationally, between October 1, 2022, and April 30, 2023, the Centers for Disease Control and Prevention (CDC) estimated the burden of influenza to include 27 to 54 million illnesses and 300 000 to 650 000 hospitalizations (https://www.cdc.gov/flu/about/burden/preliminary-in-season-estimates.htm). The cumulative hospitalization rate of 62.6 per 100 000 was similar to that observed during the 2018–2019 and 2019–2020 seasons. Among people younger than 65 years, hospitalization rates were highest among children 0 to 4 years of age (80.9 per 100 000). In a sample of hospitalized children reported to the Influenza Hospital Surveillance Network, 66.3% had at least 1 underlying medical condition. As in previous years, the most common underlying condition observed in hospitalized children was asthma (https://gis.cdc.gov/grasp/fluview/FluHospChars.html).
During the 2022–2023 season, the CDC estimated influenza-related deaths to be between 19 000 and 58 000; 160 deaths were reported in children through July 1, 2023 (Fig 2). In an interim analysis of 106 pediatric influenza deaths during the 2022–2023 influenza season, 41 occurred in children younger than 5 years. Approximately half of the deaths were in healthy children without medical conditions that would predispose to severe influenza, and 90% occurred in children who were not fully vaccinated (https://www.cdc.gov/flu/spotlights/2022-2023/pediatric-flu-deaths.htm).
Through July 1, 2023, more than 97.6% of the influenza viruses identified were influenza A with a predominance of H3N2 (71.9%). In an interim analysis through February 2023, most influenza A viruses tested were genetically and antigenically similar to viruses contained in seasonal influenza vaccines, and this was reflected in estimates of VE.3 Through January 25, 2023, children who were vaccinated against influenza were 68% less likely to be hospitalized because of influenza illness or influenza-associated complications, according to data from the New Vaccine Surveillance Network. Vaccinated children were 42% less likely to visit an emergency department because of influenza-related illness. The overall VE in children against laboratory-confirmed influenza A in hospital and emergency department settings was 49% (https://www.cdc.gov/flu/spotlights/2022-2023/flu-vaccine-protection.htm). Two concurrent studies from Wisconsin reported that influenza VE was 71% for preventing symptomatic influenza A illness among children and adolescents younger than 18 years.3 Information about influenza surveillance is available through the CDC Voice Information System (1-800-232-4636) and is posted weekly on the CDC Web site (www.cdc.gov/flu/index.htm).
Influenza Morbidity and Mortality in Children
In a typical influenza season, the disease burden among children is substantial. Each year, an estimated 9% of US children develop symptomatic influenza virus infection. Children infected with influenza virus are more likely to exhibit symptoms than adults. In 2 community-based prospective cohort studies conducted in Managua, Nicaragua, influenza was asymptomatic in just 6.6% infected children ≤14 years of age, although the asymptomatic fraction increased with age (1.7%, 3.5%, and 9.1% for ages 0–1, 2–4, and 5–14 years, respectively; P < .001).4
Clinical syndromes associated with influenza virus infection include a nonspecific febrile illness with or without upper respiratory symptoms, bronchiolitis, croup, or a pertussis-like illness. Bacterial complications include otitis media, pneumonia, and sinusitis.
Viral infections, including influenza, have been identified as risk factors for invasive bacterial infections, including invasive group A streptococcal (iGAS) infections.5 In the fall of 2022, some communities experienced increases in iGAS infections coincident with increases in influenza and respiratory syncytial virus cases.6 According to the CDC, from 2016 to 2022, increases in iGAS infections coincided with seasonal peaks in respiratory syncytial virus and influenza hospitalization rates during most years except 2021.
Neurologic complications of influenza include febrile seizures, nonfebrile seizures, and encephalopathy. Approximately 8% to 11% of hospitalized children experience neurologic complications, and these are more frequent in children with underlying neurologic conditions and children who are unimmunized.7,8 Thromboembolic events, including stroke, occur in children with influenza but are rare.9
Hospitalization rates of children with influenza are highest in those younger than 5 years.10,11 Deaths from influenza occur in children with and without other underlying medical conditions.12 Over 9 influenza seasons in the United States after the 2009 H1N1 pandemic, adjusted influenza-associated hospitalization incidence rates ranged from 10 to 375 per 100 000 persons <18 years of age each season; rates were highest among infants <6 months of age and decreased with increasing age.13 In this cross-sectional study that included data from 14 US Influenza Hospitalization Surveillance Network sites, 13 235 children were hospitalized, and of these, 2676 (20%) were admitted to the ICU, 2262 (17%) had pneumonia, and 690 (5%) required mechanical ventilation. Seventy-two children (0.5%) died during hospitalization. In multivariable models, the odds of severe outcomes, including in-hospital death, were highest in children 13 to 17 years of age.
In a cohort of 179 children 8 months to 17 years of age admitted to intensive care or a high acuity unit with influenza during the 2019–2020 season, one-third required mechanical ventilation for respiratory failure, approximately one-fifth were treated with vasopressors, and 2.2% required extracorporeal membrane oxygenation.14 Morbidity was similar to children admitted to an ICU with coronavirus disease 2019 (COVID-19) between March 2020 and December 31, 2020.14 Death occurred in 2.2% of children admitted with influenza, compared with 2.9% of children with COVID-19.
Limited data suggest that children hospitalized with influenza and concurrent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have more severe disease. During the 2021–2022 influenza season, 6% of children hospitalized with influenza had concurrent SARS-CoV-2 infection. Compared with patients without coinfection, higher proportions of children with coinfections received invasive mechanical ventilation (13% vs 4%; P = .03) and bilevel positive air pressure or continuous positive air pressure (16% vs 6%; P = .05).15
Postdischarge respiratory sequelae occur in children hospitalized with critical influenza. In one study (n = 165), 78% of children with preexisting asthma experienced asthma symptoms in the 90 days after discharge and 13% required readmission to the hospital.16 Among patients without preexisting asthma, 11.1% had asthma newly diagnosed (n = 10).
Health disparities are apparent in both influenza morbidity and mortality. In another cross-sectional study that included 10 influenza seasons, higher rates of severe influenza disease were reported in Black, Hispanic, American Indian/Alaska Native, and Asian/Pacific Islander people compared with white people, and differences were pronounced in children ≤4 years of age.17 In this age group, hospitalization rates were higher in Black children (relative risk [RR]: 2.21; 95% confidence interval [CI]: 2.10–2.33), Hispanic children (RR: 1.87; 95% CI: 1.77–1.97), American Indian/Alaska Native children (RR: 3.00; 95% CI: 2.55–3.53), and Asian/Pacific Islander children (RR: 1.26; 95% CI: 1.16–1.38) compared with white children. Rates of ICU admission were also higher (Black children: RR: 2.74; 95% CI: 2.43–3.09; Hispanic children: RR: 1.96; 95% CI: 1.73–2.23; American Indian/Alaska Native children: RR: 3.51; 95% CI: 2.45–5.05). The rate of in-hospital death was threefold to fourfold higher in Black, Hispanic, and Asian/Pacific Islander children compared with white children. Importantly, factors associated with disparities observed with other respiratory viruses (eg, SARS-CoV-2 and respiratory syncytial virus), including lack of access to quality health care, crowded living conditions, and social vulnerability, were not evaluated in this study.18,19
High-Risk Groups in Pediatrics
Children younger than 5 years (especially those younger than 2 years) and children of any age with certain underlying medical conditions have a high risk of complications from influenza (see Table 4 in the policy statement [www.pediatrics.org/cgi/doi/10.1542/peds.2023-063772]). These medical conditions include obesity, a condition that affects more than 14 million children and adolescents in the United States.20 In a recent systematic review and meta-analysis, obesity increased the odds of hospitalization in children with influenza, although the definition of obesity varied among included studies.21 Additionally, in children hospitalized for influenza, obesity was associated with a worse prognosis, including ICU admission and death.
In addition, influenza vaccination is particularly important in certain populations disproportionately affected by COVID-19.17,22 These populations may also be disproportionately affected by influenza virus infection. Although protecting all children against influenza through timely vaccination remains critically important, increased efforts are needed to eliminate barriers to immunization in all people experiencing higher rates of complications from infection with influenza viruses.
Effectiveness of Influenza Vaccination on Antibiotic Use, Laboratory-Confirmed Influenza Illness in Ambulatory Children, Hospitalization, and Mortality
Although influenza vaccination does not prevent all cases of influenza, it does offer substantial health benefits, including protection against severe and life-threatening disease and reduced health resources utilization.
Antibiotic Use in Ambulatory Children
In one population-based retrospective cohort study spanning 2012 to 2017, the antibiotic prescription rate in ambulatory children declined by 3 per 1000 person-months for each 1% increase in influenza vaccination coverage.23
Laboratory-Confirmed Influenza Illness and Medically Attended Influenza Illness in Ambulatory Children
In an analysis of US Influenza VE Network data that included 9 seasons (from 2011 to 2012 through 2019 to 2020), pooled VE against outpatient influenza illness was 46% (95% CI: 43%–50%).24 VE was lowest against influenza A(H3N2)-associated illness (33% [95% CI: 27%–39%]), and estimates were similar for influenza B (54% [95% CI: 49%–59%]) and influenza A(H1N1)pdm09 (57% [95% CI: 51%–62%]). VE was highest for children 6 through 59 months of age compared with older children. During the 2021–2022 influenza season, influenza A H3N2 viruses predominated. Circulating viruses had genetic differences from the influenza A H3N2 strain included in the seasonal vaccine. Nevertheless, VE against medically attended influenza A(H3N2) infection in ambulatory children 6 months to 8 years of age was 51% (95% CI: 19%–70%).25
Hospitalization
A robust body of evidence supports the effectiveness of influenza vaccination in preventing hospitalization in children, even during seasons in which overall VE is lower (Table 2).26–36 According to a systematic review, VE is the highest in children younger than 5 years.32 During the 2021–2022 influenza season, the CDC estimates that influenza vaccination prevented 414 295 medical visits and 4311 hospitalizations in children 6 months to 4 years of age.37,38
Author/Setting . | Seasons Included . | Population Studied . | N . | Adjusted VE Partially Vaccinateda (95% CI) . | Adjusted VE Fully Vaccinated (95% CI) . |
---|---|---|---|---|---|
Feldstein/US New Vaccine Surveillance Network | 2015–2016 | 6 mo–17 y | 1653 | 18% (–44 to 54) | 56% (34–71) |
Israel/Segaloff | 2015–2016, 2016–2017, 2017–2018 | 6 mo–8 y | 3147 | 25.6% (−3.0 to 47.0) | 53.9% (38.6–68.3) |
Australia/Blyth | 2018 | ≤16 y | 458 | NR | 86.1% (76.3–91.9). |
United Kingdom/Pebody | 2018–2019 | 2–17 y | 986 | NR | 53.0% (33.3–66.8)
|
Systematic Review/Kalligeros | 2005–2019 | 6 mo–17 y | NR | 33.91(21.12–46.69) | 61.79 (54.45–69.13) |
Japan/Shinjoh | 2018–2019 | 6 mo–15 y | 205 | NR | 56% (16–77)b |
Atlanta, Georgia/Yildirim | 2012–2013, 2013–2014, 2014–2015, 2016–2016, 2016–2017 | 6 mo–17 y | 980 | 46.8% (23.8–62.8) | 55.3% (31.7–70.7) |
Author/Setting . | Seasons Included . | Population Studied . | N . | Adjusted VE Partially Vaccinateda (95% CI) . | Adjusted VE Fully Vaccinated (95% CI) . |
---|---|---|---|---|---|
Feldstein/US New Vaccine Surveillance Network | 2015–2016 | 6 mo–17 y | 1653 | 18% (–44 to 54) | 56% (34–71) |
Israel/Segaloff | 2015–2016, 2016–2017, 2017–2018 | 6 mo–8 y | 3147 | 25.6% (−3.0 to 47.0) | 53.9% (38.6–68.3) |
Australia/Blyth | 2018 | ≤16 y | 458 | NR | 86.1% (76.3–91.9). |
United Kingdom/Pebody | 2018–2019 | 2–17 y | 986 | NR | 53.0% (33.3–66.8)
|
Systematic Review/Kalligeros | 2005–2019 | 6 mo–17 y | NR | 33.91(21.12–46.69) | 61.79 (54.45–69.13) |
Japan/Shinjoh | 2018–2019 | 6 mo–15 y | 205 | NR | 56% (16–77)b |
Atlanta, Georgia/Yildirim | 2012–2013, 2013–2014, 2014–2015, 2016–2016, 2016–2017 | 6 mo–17 y | 980 | 46.8% (23.8–62.8) | 55.3% (31.7–70.7) |
Laboratory-confirmed influenza hospitalization. NR, not reported.
Included only patients aged 6 months to 8 years.
Included patients with full and partial vaccination.
Mortality
Historically, up to 80% of influenza-associated pediatric deaths have occurred in unvaccinated children 6 months and older. Influenza vaccination is associated with reduced risk of laboratory-confirmed influenza-related pediatric death.34 In one case–cohort analysis of laboratory-confirmed influenza-associated pediatric deaths in the United States from 2010 to 2014, overall VE against influenza-associated death in all children was 65% (95% CI: 54%–74%) and 51% (95% CI: 31%–67%) in children with underlying conditions.34 Similarly, in a case control study conducted over 2 influenza seasons (2010–2012), influenza vaccination was associated with a three-quarters reduction in the risk of life-threatening influenza illness in children.39
Seasonal Influenza Vaccines
The seasonal influenza vaccines licensed for children and adolescents for the 2023–2024 season are described in Table 2 in the policy statement (www.pediatrics.org/cgi/doi/10.1542/peds.2023-063772). All 2023–2024 seasonal influenza vaccines are quadrivalent and contain hemagglutinin (HA) derived from the same influenza strains as recommended by the World Health Organization and the US Food and Drug Administration (FDA)’s Vaccines and Related Biological Products Advisory Committee for the Northern Hemisphere (see Table 1 in the policy statement [www.pediatrics.org/cgi/doi/10.1542/peds.2023-063772]).40,41 The influenza A(H1N1) component is different this season compared with last season, whereas the influenza A (H3N2), influenza B Victoria lineage, and influenza B Yamagata lineage components are unchanged. Different but antigenically related influenza A strains are included in this season’s egg-based and cell-based or recombinant vaccines. However, they are still matched to the strains expected to circulate in the 2023–2024 season.
Inactivated Influenza Vaccine
For the 2023–2024 season, among inactivated vaccines available for children, 4 are egg-based (seed strains grown in eggs), and 1 is cell culture-based (seed strains grown in Madin-Darby canine kidney cells) (see Table 2 in policy statement [www.pediatrics.org/cgi/doi/10.1542/peds.2023-063772]). All inactivated egg-based vaccines (Afluria Quadrivalent, Fluarix Quadrivalent, FluLaval Quadrivalent, and Fluzone Quadrivalent) are licensed for children 6 months and older, and all are available in single-dose, thimerosal-free, prefilled syringes. The only pediatric cell culture-based vaccine (Flucelvax Quadrivalent) is licensed for children 6 months and older.42
A quadrivalent recombinant baculovirus-expressed HA influenza vaccine (quadrivalent recombinant influenza vaccine [RIV4] [Flublok Quadrivalent]) is licensed only for people 18 years and older. A high-dose quadrivalent inactivated influenza vaccine (IIV4 [Fluzone High Dose Quadrivalent]), and a quadrivalent MF59 adjuvanted inactivated vaccine (Fluad Quadrivalent) are licensed for people 65 years and older.42 In June 2022, the Advisory Committee on Immunization Practices (ACIP) recommended preferential use of a higher dose or adjuvanted influenza vaccine for adults 65 years and older; recommended vaccines include Fluzone High-Dose Quadrivalent, Flublok Quadrivalent, and Fluad Quadrivalent.42 Adjuvanted seasonal influenza vaccines are not licensed for children in the United States; however, studies of adjuvanted vaccines in children are ongoing.43–46
Children 6 months and older can receive any licensed, age-appropriate inactivated influenza vaccine (IIV). Quadrivalent egg-based and cell culture-based IIVs contain 15 µg HA from each strain in 0.5 mL. The recommended dose volume (and, therefore, the recommended antigen content) for younger children varies by product. The dose of Fluarix Quadrivalent, FluLaval Quadrivalent, and Flucelvax Quadrivalent is 0.5 mL for all children 6 months of age and older.47–50 Children 6 through 35 months of age can receive a 0.25-mL or 0.5-mL dose of Fluzone Quadrivalent.51 These 2 doses demonstrated comparable safety and immunogenicity in a single, randomized multicenter study.52 The Fluzone Quadrivalent 0.25-mL prefilled syringe is no longer available, but the smaller dose can be administered from a single or multidose vial. Children 3 years and older should receive 0.5 mL. Afluria Quadrivalent has a 0.5-mL product for children 3 years and older only.53 For children 6 through 35 months of age, the recommended 0.25-mL dose must be obtained from a multidose vial.
IIV Storage
The CDC has published Best Practice Guidelines (https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/index.html and https://www.cdc.gov/vaccines/hcp/admin/storage/toolkit/index.html) for vaccine storage and administration. Additionally, the AAP offers guidance on the components of a written disaster plan, including a comprehensive vaccine management protocol to keep the vaccine storage temperature constant during a power failure or other disaster (see the AAP Pediatric Preparedness Resource Kit at https://downloads.aap.org/AAP/PDF/PedPreparednessKit.pdf).
IIVs for intramuscular injection are shipped and stored at 2°C to 8°C (36°F–46°F); vaccines that are inadvertently frozen should not be used.
IIV Administration
Vaccines are administered intramuscularly into the anterolateral thigh of infants and young children and into the deltoid muscle of older children and adults. Given that various IIV formulations are available, careful attention should be paid to ensure that each product is used according to its approved age indication, dosing, and volume of administration (see Table 2 in the policy statement [www.pediatrics.org/cgi/doi/10.1542/peds.2023-063772]). For vaccines that include a multidose vial presentation, the maximum number of doses drawn from a multidose vial is specified in the package insert and should not be exceeded; residual product must be discarded regardless of the remaining volume in the vial. A 0.5-mL prefilled syringe of any IIV should not be split into 2 separate 0.25-mL doses. 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 dose.
Coadministration of Inactivated Influenza Vaccine and Other Vaccines
Recommendations for concomitant administration of influenza vaccine and other vaccines is detailed in the policy statement. Influenza vaccine can be administered to children concomitantly or at any time before or after administration of the currently available COVID-19 vaccines. Extensive experience with vaccines other than COVID-19 has demonstrated that immunogenicity and adverse event profiles are generally similar when vaccines are administered simultaneously as when they are administered alone.54–58 A systematic review that included only clinical studies of individuals 18 years and older identified no safety concerns and no evidence of immune interference.59 Limited data exist on coadministration of COVID-19 vaccines and influenza vaccines in children. Through June 20, 2022, reports to the Vaccine Adverse Event Reporting System after coadministration of messenger RNA (mRNA) COVID-19 and seasonal influenza vaccines in persons 6 months and older did not reveal any unusual or unexpected patterns of adverse events.60 Reports to v-safe, a CDC-sponsored smartphone-based safety surveillance system, identified a significant increase in systemic adverse reactions in persons 12 years and older during the week after vaccination who received simultaneous administration of COVID-19 mRNA booster and seasonal influenza vaccines compared with those who received only a COVID-19 mRNA booster alone.61 Reactions were generally mild, and pediatric-specific data were not reported. Providers are encouraged to consult the most current guidance from the AAP and the CDC ACIP regarding coadministration of COVID-19 vaccines with other vaccines.62 Overall, the benefits of timely vaccination with same-day administration of IIV and other recommended vaccines outweigh the risk of potential reactogenicity in children.
Safety of IIV
IIVs are well tolerated in children and can be used in healthy children, as well as those with underlying chronic medical conditions. The most common injection site adverse reactions after administration of IIV in children are injection site pain (17%–67%), redness (13%–37%), and swelling (10%–25%). The most commonly reported systemic adverse events are drowsiness (13%–38%), irritability (14%–54%), abnormal crying (33%–41%), loss of appetite (11%–32%), fatigue (10%–20%), muscle aches (10%–39%), headache (10%–23%), arthralgia (10%–13%), and gastrointestinal tract symptoms (10%–20%). Recombinant influenza vaccine (RIV) is well tolerated in older adolescents and adults. In people 18 to 49 years of age, the most common injection site reactions were tenderness (48%) and pain (37%). The most common (≥10%) solicited systemic adverse reactions were headache (20%), fatigue (17%), myalgia (13%), and arthralgia (10%). Adverse reactions for each vaccine are described in package inserts that can be accessed at https://www.cdc.gov/vaccinesafety/vaccines/flu-vaccine.html#fda.
The AAP supports the current World Health Organization recommendations for use of thimerosal as a preservative in multiuse vials in the global vaccine supply.63 Thimerosal-containing vaccines are not associated with an increased risk of autism spectrum disorder in children.64,65 Thimerosal from vaccines has not been linked to any neurologic condition. Despite the lack of evidence of harm, some states have legislation restricting the use of vaccines that contain even trace amounts of thimerosal. The benefits of protecting children against the known risks of influenza are clear. Therefore, to the extent permitted by state law, children should receive any available formulation of IIV rather than delaying vaccination while waiting for reduced thimerosal-content or thimerosal-free vaccines. IIV formulations that are free of even trace amounts of thimerosal are widely available, as described in Table 2 in the policy statement [www.pediatrics.org/cgi/doi/10.1542/peds.2023-063772]. Additional information to assist clinicians in responding to parental concerns about thimerosal is available at https://www.cdc.gov/vaccinesafety/concerns/thimerosal/index.html.
Vaccination in the Setting of Immunosuppression
Nonlive vaccines, including IIVs, are safe in persons with altered immune competence, but immunogenicity may be diminished. Decreases in immunogenicity vary by underlying condition. Guidelines for the immunization of immunocompromised children and adults have been published by the Infectious Diseases Society of America.66,67 Guidelines for the immunization of solid organ transplant recipients have been published by the American Society of Transplantation.68
Live Attenuated (Intranasal) Influenza Vaccine
Overview
The intranasal live-attenuated influenza vaccine (LAIV) was initially licensed in the United States in 2003 for people 5 through 49 years of age as a trivalent formulation, and the approved age group was extended to 2 years of age in 2007. The quadrivalent LAIV (LAIV4) formulation licensed in 2012 was first available during the 2013–2014 influenza season, replacing trivalent LAIV. The history of LAIV use in the United States, along with a detailed discussion of vaccine efficacy over serial seasons, is available in the 2021 technical report.69
Storage and Administration
The cold-adapted, temperature-sensitive LAIV4 formulation is shipped and stored at 2°C to 8°C (36°F–46°F). It is administered intranasally in a prefilled, single-use sprayer containing 0.2-mL of vaccine. A removable dose-divider clip is attached to the sprayer to facilitate administration of 0.1 mL separately into each nostril. If the child sneezes immediately after administration, the dose should not be repeated. Administration of LAIV intranasally is not an aerosol-generating procedure; however, vaccine administrators are advised to wear gloves when administering LAIV given the potential for contact with respiratory secretions.
Coadministration of LAIV and Other Vaccines
LAIV4 may be administered simultaneously with other inactivated or live vaccines. If not administered simultaneously, it is recommended that administration of other nonoral live vaccines is separated by a 4-week interval from LAIV4 vaccination.
Safety of LAIV
The most commonly reported reactions of LAIV4 in children are runny nose or nasal congestion (32%), headache (13%), decreased activity (10%), sore throat (9%), decreased appetite (6%), muscle aches (4%), and fever (7%).70
LAIV and Immunocompromised Hosts
IIV (or RIV if age-eligible) is the vaccine of choice for severely immunocompromised patients and anyone in close contact with a subset of severely immunocompromised people (ie, those requiring a protected environment). This preference is based on the theoretical risk of infection attributable to an LAIV strain in an immunocompromised contact of an LAIV-immunized person. Health care personnel (HCP) immunized with LAIV may continue to work in most units of a hospital, including the NICU and general oncology ward, using standard infection control techniques. As a precautionary measure, people recently vaccinated with LAIV should restrict contact with severely immunocompromised patients (eg, those requiring a protective environment) for 7 days after vaccination, although there have been no reports of LAIV transmission from an LAIV-vaccinated person to an immunocompromised person. In the theoretical scenario in which an immunocompromised host develops a symptomatic LAIV infection, the LAIV strains are susceptible to antiviral medications.
Timing of Influenza Vaccination and Duration of Protection
Although peak influenza activity in the United States typically occurs from January through March, influenza viruses can begin to circulate in early fall (October), as occurred in the 2022–2023 season. Circulation can continue to late spring (May or later), with one or more disease peaks, as was the case in the 2021–2022 season. The typical pattern of circulation was substantially altered during the COVID-19 pandemic. Predicting the onset and duration or the severity of the influenza season with accuracy is impossible. Timely influenza vaccination is important to ensure that individuals are optimally protected before influenza viruses are circulating in the community.
Thus, the AAP and CDC recommend children, especially those who need 2 doses, should be immunized as soon as vaccine becomes available and complete influenza vaccination by the end of October. Because the duration of the influenza season is unpredictable, practices should continue to vaccinate individuals as long as influenza viruses are circulating and unexpired vaccine is available.
Immunity after influenza vaccination can wane over time.71 Studies in adults suggest that very early vaccination (July or August) might be associated with suboptimal immunity before the end of the influenza season, and the CDC now discourages influenza vaccination in the summer months for most adults.42 The data are less definitive in children. In some studies, VE decreased within a single influenza season, and this decrease correlated with increasing time after vaccination. However, this decay in VE was not consistent across different age groups and varied by season and virus types and influenza A virus subtypes.72–80 Waning VE was more evident among older adults and younger children73,75 and with influenza A (H3N2) viruses more than influenza A (H1N1) or B viruses.74,76,79 A multiseason analysis from the US Flu VE Network found that VE declined by approximately 7% per month for influenza A (H3N2) and influenza B, and by 6% to 11% per month for influenza A (H1N1) pdm09 in individuals 9 years and older.72 VE remained greater than 0 for at least 5 to 6 months after vaccination. Another study that included children older than 2 years also found evidence of declining VE with an odds ratio (OR) increasing approximately 16% with each additional 28 days from vaccine administration.78 A study evaluating VE in both adults and children from the 2011–2012 through the 2013–2014 influenza seasons demonstrated 54% to 67% protection from 0 to 180 days after vaccination.76 A single-center study of 3595 children during the 2017–2018 season demonstrated an overall VE of 52% with no evidence of waning immunity in children up to 183 days after vaccination (median, 81 [interquartile range, 52–111] days), although the study may have been underpowered for this outcome.81 A multisite study that included pooled data across 5 seasons identified only small, nonsignificant decreases in VE against hospitalization (∼2% per month) in vaccinated children 6 months to 17 years of age.82 In a cohort of influenza vaccine-naive patients 6 to <24 months in Nicaragua who received a single dose of vaccine, VE against laboratory-confirmed influenza illness declined 9% per month in the first 4 months after immunization and then plateaued.83 Waning of immunity after 2 doses of vaccine, as is recommended in the United States, was not studied. Collectively, these studies support the current recommendation to immunize children as soon as possible after vaccine becomes available. An early onset of the influenza season, as occurred for the 2022–2023 season, is a concern when considering delaying vaccination, and delays increase the likelihood of missing influenza vaccination altogether.42
Although influenza activity in the United States is typically low during the summer, influenza cases and outbreaks can occur, particularly among international travelers, who may be exposed to influenza year-round, depending on destination. Influenza can occur throughout the year in the tropics. The CDC has recommended that individuals who did not receive the current seasonal influenza vaccine during the Northern Hemisphere fall/winter season and who are traveling to parts of the world where influenza activity is ongoing should consider influenza vaccination ≥2 weeks before departure, if available.84 This includes persons traveling to the tropics, to destinations in the Southern Hemisphere during the Southern Hemisphere influenza season (April–September), or on cruise ships or with organized tourist groups during an influenza season.42
Influenza Vaccine Considerations for Subpopulations Including Contraindications and Precautions
Contraindications and precautions to available influenza vaccines are detailed in Table 5 in the policy statement (www.pediatrics.org/cgi/doi/10.1542/peds.2023-063772). A precaution for vaccination is a condition that might increase the risk or seriousness of a vaccine-related adverse reaction. A precaution also may exist for conditions that might compromise the ability of the host to develop immunity after vaccination. Vaccination may be recommended in the presence of a precaution if the benefit of protection from the vaccine outweighs the potential risks.
Previous Allergic Reaction: Contraindication
Although a severe allergic reaction (eg, anaphylaxis) to a previous dose of any influenza vaccine is generally a contraindication to future receipt of influenza vaccines, the AAP recommends that children who have had an allergic reaction after a previous dose of any influenza vaccine be evaluated by an allergist to determine whether future receipt of the vaccine is appropriate. Children who are allergic to gelatin (very rare) should receive IIV4 instead of LAIV. RIV4 is an option for patients with gelatin allergy ≥18 years of age.
Moderate or Severe Illness, Including COVID-19: Delay Is Recommended
Mild illnesses, with or without fever, are not contraindications to the use of influenza vaccines, including among children with mild upper respiratory infection symptoms or allergic rhinitis. In children judged by the clinician to have a moderate to severe illness, vaccination should be deferred until resolution of the illness. Children with confirmed COVID-19 are generally advised to defer visits for routine vaccination, including influenza vaccination, until criteria (https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html) have been met for them to discontinue isolation and until they are no longer moderately to severely ill (https://www.cdc.gov/vaccines/pandemic-guidance/index.html). However, if they are already in a health care setting and their illness is mild, they can receive influenza vaccine. Children with an amount of nasal congestion that would notably impede vaccine delivery into the nasopharyngeal mucosa may receive IIV or should have LAIV deferred until symptom resolution.
Guillain-Barré Syndrome: Precaution
History of Guillain-Barré syndrome (GBS) after influenza vaccine is considered a precaution for the administration of influenza vaccines. GBS is rare, especially in children, and there is a lack of evidence on the risk of GBS after influenza vaccination in children. Nonetheless, regardless of age, a history of GBS less than 6 weeks after a previous dose of influenza vaccine is a precaution for administration of influenza vaccine. GBS may occur after influenza virus infection. The benefits of influenza vaccination might outweigh the risks for certain people who have a history of GBS (particularly if not temporally occurring after previous influenza vaccination) and who also are at high risk for severe complications from influenza.
Influenza Vaccines and Egg Allergy: Not a Contraindication or Precaution
There is strong evidence that individuals with egg allergy can safely receive influenza vaccine without any additional precautions beyond those recommended for any vaccine.85,86 The presence of egg allergy in an individual is not a contraindication to receive IIV or LAIV. Vaccine recipients with egg allergy are at no greater risk for a systemic allergic reaction than those without egg allergy. Therefore, precautions such as choice of a particular vaccine, special observation periods, or restriction of administration to particular medical settings are not warranted and constitute an unnecessary barrier to vaccination. It is not necessary to inquire about egg allergy before the administration of any influenza vaccine, including on screening forms. Routine prevaccination questions regarding anaphylaxis after receipt of any vaccine are appropriate. Standard vaccination practice for all vaccines in children should include the ability to respond to rare acute hypersensitivity reactions. Children who have had a previous allergic reaction to the influenza vaccine should be evaluated by an allergist to determine whether future receipt of the vaccine is appropriate.
Pregnancy: IIV Recommended, Not a Contraindication or Precaution
Influenza vaccination is recommended by the ACIP, the American College of Obstetrics and Gynecology, and the American Academy of Family Physicians for all pregnant individuals, during any trimester of gestation, to protect against influenza and its complications.42,87 Substantial evidence has accumulated regarding the efficacy of influenza vaccination in preventing laboratory-confirmed influenza disease and its complications in both pregnant individuals and their infants in the first months of life (up to 6 months) through transplacental passage of antibodies.87–97 Infants born to persons who receive influenza vaccine during pregnancy have been shown to have a risk reduction of up to 72% (95% CI: 39%–87%) for laboratory-confirmed influenza hospitalization in the first few months of life.97
Any licensed, recommended, and age-appropriate IIV may be administered to pregnant individuals during any trimester of gestation and postpartum, although experience with the use of RIV4 in pregnant individuals is limited. LAIV is contraindicated during pregnancy. Data on the safety of influenza vaccination at any time during pregnancy continues to support the safety of influenza immunization during pregnancy.87,89–94,98 Vaccination during pregnancy, including during the first trimester, is not associated with a risk of spontaneous abortion in most studies.99–102 Large retrospective cohort studies that collectively involved more than 80 000 pregnancies, as well as a systematic review and meta-analysis of studies, found no association between influenza vaccine in any trimester and major congenital malformations.103–105 Assessments of any association with influenza vaccination and preterm birth and small-for-gestational-age infants have yielded inconsistent results, with most studies reporting a protective effect or no association with these outcomes.102,106–108 A recent retrospective cohort study that included 84 730 pairs of birthing parents and children found no association between influenza immunization during pregnancy and autism spectrum disorder in children.109 Despite clear evidence of benefit to pregnant individuals and their infants, influenza vaccination in this population remains below target levels. During the 2022–2023 influenza season, 49% of pregnant individuals were vaccinated through April 22, 2023.110 Rates were highest in non-Hispanic Asian individuals (66.6%) and lowest in non-Hispanic Black individuals (30.4%). Racial disparities in uptake of influenza vaccine during pregnancy have been identified previously, with Black women consistently having the lowest rates.111 Black women report a lower rate of being offered or recommended to receive influenza vaccine, despite evidence that a provider recommendation is associated with vaccine acceptance.111 Lower influenza vaccination coverage also has been reported in Medicaid-insured pregnant women compared with privately insured women, and in women residing in rural areas compared with those residing in urban areas.112,113
Breastfeeding: Recommended, Not a Contraindication or Precaution
Influenza vaccination with either IIV or LAIV during breastfeeding is safe for lactating individuals and their infants. Breastfeeding is strongly recommended to protect infants against influenza viruses by activating innate antiviral mechanisms, specifically type-1 interferons. Human milk from pregnant individuals vaccinated during the third trimester also contains higher levels of influenza-specific immunoglobulin A.114 Greater exclusivity of breastfeeding in the first 6 months of life decreases the episodes of respiratory illness with fever in infants of vaccinated lactating parents. For infants whose birthing parent has confirmed influenza illness at delivery, breastfeeding is encouraged, and guidance on breastfeeding practices is available on the CDC Web site (https://www.cdc.gov/breastfeeding/breastfeeding-special-circumstances/maternal-or-infant-illnesses/influenza.html and https://www.cdc.gov/flu/professionals/infectioncontrol/peri-post-settings.htm). Birthing parents may pump and feed expressed breast milk if they or their infants are too sick to breastfeed.
Influenza Vaccination Coverage
Influenza vaccination coverage has decreased in recent seasons and remains below the Healthy People 2030 target of 70% (Fig 3).115 This decrease in influenza vaccination coverage mirrors the declines in delivery of other routine pediatric vaccines during the COVID-19 pandemic.116–119 Influenza immunization coverage has continued to lag during the 2022–2023 season.120 Through April 15, 2023, only 55.1% of children 6 months to 17 years had been vaccinated. Coverage levels remained lower in non-Hispanic Black children (51%) compared with non-Hispanic white children (53.6%), Hispanic children (58%), and children identified as non-Hispanic/other (60%), and among children residing in rural areas (41.1%) compared with suburban (55.3.0%) or urban (59.8%) areas. Influenza immunization rates may be even lower in some populations. In a large national cohort of commercially insured children (2010–2017), vaccination coverage was 51.4% lower than estimates of vaccination coverage reported through the National Immunization Survey-Flu during the same period.121
The reasons for low influenza vaccination coverage are likely multifactorial. For some families, logistical barriers, including lack of transportation and altered school and work schedules, may have reduced access to routine medical care.122 Other families may have avoided care in medical offices out of fear of contracting SARS-CoV-2.123 Pandemic mitigation strategies, including masking and social distancing, as well as decreased influenza activity in the community, could have created a perception of decreased risk from influenza, limiting a sense of urgency for influenza vaccination. Hesitancy around COVID-19 vaccination may have impacted hesitancy toward other vaccines, including seasonal influenza vaccine. Finally, rates of influenza vaccine hesitancy, reasons for vaccine hesitancy, and factors facilitating vaccination may vary by race and ethnicity. In one small mixed-methods study of parents and legal guardians presenting with their children to a pediatric emergency department during the 2021–2022 influenza season, Black caregivers expressed more hesitancy to vaccinate their children for influenza than did white caregivers (42% vs 21%; P = .01).124 Black caregivers highlighted the importance of providers communicating about vaccines in a transparent, nonjudgmental way. Facilitators of vaccination emphasized by Black and Hispanic caregivers included desire to protect others, employer facilitation of vaccination, and personal stories from others.
Achieving high influenza vaccination coverage of infants, children, and adolescents remains a priority to protect them against influenza disease and its complications. Multifaceted strategies are needed to increase influenza vaccination coverage, especially in vulnerable, high-risk populations.
Influenza Vaccine Delivery and Implementation Strategies
Timely annual distribution of influenza vaccine to health care facilities serving children and adolescents may help avoid missed opportunities. Placing initial vaccine orders early and creating systems for tracking and reordering when necessary throughout the season may optimize supply. Such efforts may be particularly important when there are disruptions in vaccine delivery because of supply chain issues, inclement weather, or other unforeseen circumstances, along with prioritizing delivery to primary care settings, especially when supply is limited or delayed. The AAP has developed guidance for addressing influenza vaccine supply, payment, coding, and liability issues (https://www.aap.org/influenza).
The AAP and CDC recommend influenza vaccination at any visit to the medical home during influenza season. Influenza vaccination in the medical home is ideal, especially for the youngest children. Administering influenza vaccine in diverse locations, such as subspecialty practices, urgent care clinics, emergency departments, schools, and pharmacies, may increase uptake among patients who do not have or cannot readily access their medical home and those at high risk for influenza-related complications.125,126 This may be particularly useful for children residing in rural areas where coverage levels are markedly lower than in suburban or urban areas. The number of children immunized by pharmacists has been increasing but still remains relatively low. In one retrospective cohort study that used an administrative health claims database to analyze influenza vaccines administered to children between July 1, 2010, and June 30, 2017, only 3.2% of vaccines were administered by pharmacists, although the proportion did increase over time.121
Hospitalized patients should be vaccinated before discharge, unless medically contraindicated. Historically, a substantial proportion of children hospitalized for influenza have been hospitalized previously during the same season; failure to offer vaccine to hospitalized children is a missed opportunity.127 An automated, hospital-based influenza vaccination screening program integrated into the hospital medical record may increase vaccination of eligible patients.128
A system for reporting influenza vaccine administrations is crucial to ensure adequate communication and maintain accurate patient records across settings. Integration of immunization information systems with electronic health record (EHR) systems can enhance data accuracy and up-to-date vaccination status.129 For areas with a fragmented medical home or high external resource utilization for vaccination, querying the immunization information system before administration of vaccination may prevent unnecessary product utilization. Use of patient portals for parents to self-report vaccination is one strategy for systems looking to calculate coverage and to decrease unnecessary communications to patients who received vaccinations outside the medical home.
Practices that prepare in advance for their influenza vaccine campaign and leverage a range of evidence-based strategies130,131 throughout the season can increase vaccination rates in their patient population (see Table 3 in the policy statement [www.pediatrics.org/cgi/doi/10.1542/peds.2023-063772]). The AAP has created tools to help practices in this work (https://www.aap.org/influenza). Some practices expand their hours of operation (ie, evenings, weekends) or schedule vaccine-only clinics to increase patient access to influenza vaccine early in the season and during peak periods. Sending reminder/recall messages using a modality (ie, telephone, text, letter, e-mail, messaging via the patient portal) that is feasible for their practice and aligns with the preferences of their patient population may improve immunization rates.132,133 A Cochrane Review from 2018 concluded that reminder/recall improves childhood influenza vaccination with moderate certainty of evidence (RR: 1.51; 95% CI: 1.14–1.99).134 Effective messages notify families of influenza vaccine availability and provide other key information such as the child’s vaccination status and where, when, and why the child should receive the vaccine. This information is beneficial early in the campaign, as well as throughout the season. For example, one clinical trial135 found that sending text message reminders to parents of children who remain unvaccinated in the late fall increased influenza vaccine uptake. Another trial136 demonstrated the effectiveness of using text message reminders for children requiring two doses in a season, particularly when the messages embedded information regarding the need for a timely second dose. Making vaccine-related information readily available (ie, via a practice Web site, social media platform, or educational handout)137,138 and tailoring this information for their patients and families (ie, materials in preferred language) has also been effective. Resources are available from the AAP at https://www.aap.org/en/news-room/campaigns-and-toolkits/flu-campaign-toolkit/.
Effective influenza vaccine communication with patients and families is crucial. Exact language is particularly important in vaccine risk discussions in languages other than English. For example, in Spanish, the term “gripe” is commonly used to refer to viral influenza but is a nonprecise term referring to respiratory illnesses. Using this term may cause confusion about the actual illness prevented by influenza vaccine and result in decreased confidence about VE. “Influenza” should be used rather than “la gripe” when discussing influenza and influenza vaccine with Spanish-speaking patients and families.
Messaging should be consistent across all members of the care team, including front office staff, medical assistants, nurses, and all provider types (including primary care and subspecialty care providers). Practices should educate their staff and providers about influenza and influenza vaccine-related topics, including the importance of annual vaccination, VE and safety, the 2-dose requirement for certain children, vaccine contraindications, and common parental concerns. Providers should use evidence-based communication strategies in their conversations with families. These include offering a strong, presumptive influenza vaccine recommendation, bundling their recommendation for influenza vaccine with recommendations for other needed vaccines, and pursuing their initial recommendation when families initially decline the vaccine.139–141 Moreover, communication should be tailored to address the specific vaccine-related concerns of patients and families. Resources regarding effective vaccine communication techniques are available on the AAP Web site at https://aap.org/vaccinecommunication.
Strategies to reduce missed opportunities during patient visits include standardization of practice workflow to screen all patients for influenza vaccine eligibility and administer the vaccine to any patient who is due for the vaccine. This workflow could be used at all visit types, including preventive care, acute care, and mental/behavioral health visits. Influenza vaccination can be administered when patients present for other needed vaccines, as well. Practices may identify influenza vaccine champion(s) within their practice to spearhead these efforts. Informatic tools can also facilitate influenza vaccination. For example, studies have shown that standing vaccine orders and vaccine prompts in the EHR increase influenza vaccine uptake in both inpatient and outpatient settings.142,143 Audits and performance feedback for providers have also been shown to be effective as part of multimodal interventions.131 Additionally, these tools can be used to identify patients who need repeat vaccinations and support future dose scheduling, or who have contraindications/precautions for particular formulations. Systems looking to identify patients at high risk for severe influenza illness can leverage information from the EHR to identify patients at risk and provide targeted communications. Sample value sets for use in creating electronic clinical decision support tools are presented in Table 3. Implementation can be challenging, but some institutions have used these sources. Local adaptation may be needed.
Category . | Description . | Established Value Setsa . | Object Identifier . | Code System . | Steward . |
---|---|---|---|---|---|
Underlying condition or treatment with common examplesa | |||||
Chronic pulmonary disease | Asthma | Asthma diagnosis ICD-10 | 2.16.840.1.113762.1.4.1047.308 | ICD-10-CM | American Academy of Allergy, Asthma, and Immunology |
Asthma diagnosis grouping | 2.16.840.1.113762.1.4.1047.309 | ICD-10-CM ICD-9-CM SNOMED CT | American Academy of Allergy, Asthma, and Immunology | ||
Cystic fibrosis | Cystic fibrosis | 2.16.840.1.113883.3.464.1003.102.12.1002 | ICD-10-CM ICD-9-CM SNOMED CT | National Committee for Quality Assurance | |
Cystic fibrosis lung disease | 2.16.840.1.113762.1.4.1219.15 | ICD-10-CM SNOMED CT | CMS Documentation Requirement Lookup Service | ||
Compromised respiratory function (eg, requiring mechanical ventilation, tracheostomy, or baseline oxygen requirement) | Mechanical ventilation | 2.16.840.1.113762.1.4.1248.107 | ICD-10-PCS SNOMED CT | American Institutes for Research | |
Cardiovascular disease | Hemodynamically significant conditions (excluding hypertension alone) | — | — | — | — |
Kidney disease | Dialysis; chronic kidney disease, including end-stage kidney disease | Dialysis services | 2.16.840.1.113883.3.464.1003.109.11.1026 | CPT | National Committee for Quality Assurance |
Hepatic disease | Chronic liver disease, cirrhosis | Chronic liver disease | 2.16.840.1.113883.3.464.1003.199.12.1035 | ICD-10-CM ICD-9-CM SNOMED CT | National Committee for Quality Assurance |
Cirrhosis | 2.16.840.1.113762.1.4.1248.149 | ICD-10-CM SNOMED CT | American Institutes for Research | ||
Hematologic disease | Sickle cell disease | Sickle cell anemia and HBS disease | 2.16.840.1.113762.1.4.1235.222 | ICD-10-CM SNOMED CT | B.well Connected Health |
Other hemoglobinopathies | — | — | — | — | |
Metabolic disorders | Diabetes mellitus | Diabetes | 2.16.840.1.113883.3.464.1003.103.12.1001 | ICD-10-CM SNOMED CT | National Committee for Quality Assurance |
Neurologic and neurodevelopmental conditions | Cerebral palsy | Congenital or infantile Cerebral Palsy Group | 2.16.840.1.113883.3.666.5.1580 | ICD-10-CM ICD-9-CM SNOMED CT | Lantana |
Epilepsy | Epilepsy | 2.16.840.1.113762.1.4.1034.51 | ICD-10-CM ICD-9-CM SNOMED CT | American Academy of Neurology | |
Seizure disorder | 2.16.840.1.113883.3.464.1003.105.12.1206 | ICD-10-CM ICD-9-CM SNOMED CT | National Committee for Quality Assurance | ||
Stroke | Stroke | 2.16.840.1.113762.1.4.1248.176 | ICD-10-CM | American Institutes for Research | |
Intellectual developmental disorder | — | — | — | — | |
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 ICD-9-CM SNOMED CT | American Academy of Physical Medicine and Rehabilitation | |
Extreme obesity | BMI ≥40 for adultsc | — | — | — | — |
Immunosuppression | Receipt of immunocompromising medications | — | — | — | — |
Congenital or acquired immune deficiency, including HIV | Immunodeficiency syndromes | 2.16.840.1.113762.1.4.1200.189 | ICD-10-CM | Cliniwiz | |
HIV | 2.16.840.1.113883.3.464.1003.120.12.1003 | ICD-10-CM ICD-9-CM SNOMED CT | National Committee for Quality Assurance | ||
Asplenia | Anatomic or functional Asplenia HDCN grouping | 2.16.840.1.113762.1.4.1235.219 | ICD-10-CM ICD-9-CM SNOMED CT | B.well Connected Health | |
Receiving treatment with aspirin or salicylate-containing therapiesb | — | — | — | — | |
Pregnancy and up to 2 weeks postpartum | — | — | — | — |
Category . | Description . | Established Value Setsa . | Object Identifier . | Code System . | Steward . |
---|---|---|---|---|---|
Underlying condition or treatment with common examplesa | |||||
Chronic pulmonary disease | Asthma | Asthma diagnosis ICD-10 | 2.16.840.1.113762.1.4.1047.308 | ICD-10-CM | American Academy of Allergy, Asthma, and Immunology |
Asthma diagnosis grouping | 2.16.840.1.113762.1.4.1047.309 | ICD-10-CM ICD-9-CM SNOMED CT | American Academy of Allergy, Asthma, and Immunology | ||
Cystic fibrosis | Cystic fibrosis | 2.16.840.1.113883.3.464.1003.102.12.1002 | ICD-10-CM ICD-9-CM SNOMED CT | National Committee for Quality Assurance | |
Cystic fibrosis lung disease | 2.16.840.1.113762.1.4.1219.15 | ICD-10-CM SNOMED CT | CMS Documentation Requirement Lookup Service | ||
Compromised respiratory function (eg, requiring mechanical ventilation, tracheostomy, or baseline oxygen requirement) | Mechanical ventilation | 2.16.840.1.113762.1.4.1248.107 | ICD-10-PCS SNOMED CT | American Institutes for Research | |
Cardiovascular disease | Hemodynamically significant conditions (excluding hypertension alone) | — | — | — | — |
Kidney disease | Dialysis; chronic kidney disease, including end-stage kidney disease | Dialysis services | 2.16.840.1.113883.3.464.1003.109.11.1026 | CPT | National Committee for Quality Assurance |
Hepatic disease | Chronic liver disease, cirrhosis | Chronic liver disease | 2.16.840.1.113883.3.464.1003.199.12.1035 | ICD-10-CM ICD-9-CM SNOMED CT | National Committee for Quality Assurance |
Cirrhosis | 2.16.840.1.113762.1.4.1248.149 | ICD-10-CM SNOMED CT | American Institutes for Research | ||
Hematologic disease | Sickle cell disease | Sickle cell anemia and HBS disease | 2.16.840.1.113762.1.4.1235.222 | ICD-10-CM SNOMED CT | B.well Connected Health |
Other hemoglobinopathies | — | — | — | — | |
Metabolic disorders | Diabetes mellitus | Diabetes | 2.16.840.1.113883.3.464.1003.103.12.1001 | ICD-10-CM SNOMED CT | National Committee for Quality Assurance |
Neurologic and neurodevelopmental conditions | Cerebral palsy | Congenital or infantile Cerebral Palsy Group | 2.16.840.1.113883.3.666.5.1580 | ICD-10-CM ICD-9-CM SNOMED CT | Lantana |
Epilepsy | Epilepsy | 2.16.840.1.113762.1.4.1034.51 | ICD-10-CM ICD-9-CM SNOMED CT | American Academy of Neurology | |
Seizure disorder | 2.16.840.1.113883.3.464.1003.105.12.1206 | ICD-10-CM ICD-9-CM SNOMED CT | National Committee for Quality Assurance | ||
Stroke | Stroke | 2.16.840.1.113762.1.4.1248.176 | ICD-10-CM | American Institutes for Research | |
Intellectual developmental disorder | — | — | — | — | |
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 ICD-9-CM SNOMED CT | American Academy of Physical Medicine and Rehabilitation | |
Extreme obesity | BMI ≥40 for adultsc | — | — | — | — |
Immunosuppression | Receipt of immunocompromising medications | — | — | — | — |
Congenital or acquired immune deficiency, including HIV | Immunodeficiency syndromes | 2.16.840.1.113762.1.4.1200.189 | ICD-10-CM | Cliniwiz | |
HIV | 2.16.840.1.113883.3.464.1003.120.12.1003 | ICD-10-CM ICD-9-CM SNOMED CT | National Committee for Quality Assurance | ||
Asplenia | Anatomic or functional Asplenia HDCN grouping | 2.16.840.1.113762.1.4.1235.219 | ICD-10-CM ICD-9-CM SNOMED CT | B.well Connected Health | |
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 relevant 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, Clinical Terms. —, not available.
Value sets were not available for all conditions.
Applies to children and adolescents aged <19 years who may be at increased risk of Reye syndrome.
Not well defined in children but could consider BMI ≥99% for age.
Testing Categorya . | Method . | Influenza Viruses Detected . | Distinguishes Influenza 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 diagnostic test | Antigen detection | Influenza A or B virus antigens | No | 10–15 min | Moderate sensitivity (higher with analyzer reader device); high specificity |
Direct and indirect immunofluorescence assays | Antigen detection | Influenza A or B virus antigens | No | 1–4 h | Moderate sensitivity; high specificity |
Molecular assays (including RT-PCR) | Nucleic acid amplification | Influenza A or B viral RNA | Yes, if subtype primers are used | 1–8 h | High sensitivity; high specificity |
Multiplex molecular assays | Nucleic acid amplification | Influenza A or B viral RNA, other viral or bacterial targets (RNA or DNA) | Yes, if subtype primers are used | 1–2 h | High sensitivity; high specificity |
Rapid cell culture (shell vial and cell mixtures) | Virus isolation | Influenza A or B virus | Yes | 1–3 d | High sensitivity; high specificity |
Viral culture (tissue cell culture) | Virus isolation | Influenza A or B virus | Yes | 3–10 d | High sensitivity; high specificity |
Testing Categorya . | Method . | Influenza Viruses Detected . | Distinguishes Influenza 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 diagnostic test | Antigen detection | Influenza A or B virus antigens | No | 10–15 min | Moderate sensitivity (higher with analyzer reader device); high specificity |
Direct and indirect immunofluorescence assays | Antigen detection | Influenza A or B virus antigens | No | 1–4 h | Moderate sensitivity; high specificity |
Molecular assays (including RT-PCR) | Nucleic acid amplification | Influenza A or B viral RNA | Yes, if subtype primers are used | 1–8 h | High sensitivity; high specificity |
Multiplex molecular assays | Nucleic acid amplification | Influenza A or B viral RNA, other viral or bacterial targets (RNA or DNA) | Yes, if subtype primers are used | 1–2 h | High sensitivity; high specificity |
Rapid cell culture (shell vial and cell mixtures) | Virus isolation | Influenza A or B virus | Yes | 1–3 d | High sensitivity; high specificity |
Viral culture (tissue cell culture) | Virus isolation | Influenza A or B virus | Yes | 3–10 d | High sensitivity; high specificity |
Source: Uyeki149 and https://www.cdc.gov/flu/professionals/diagnosis/overview-testing-methods.htm#tests. RT-PCR, reverse transcription polymerase chain reaction.
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 reaction. 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 Improvement Amendments waived, depending on the specimen.
For practices that choose to offer influenza vaccine to family members and other close contacts of children and adolescent patients, the AAP technical report, “Immunizing Parents and Other Close Family Contacts in the Pediatric Office Setting,” provides medical liability risk management guidance on documenting in a separate record screening, informed consent, and National Vaccine Injury Compensations Program-required immunization administration data.144 Guidance is also provided on ascertaining whether immunizing adults is covered by customary pediatric medical liability insurance policies for any adverse events not covered by the National Vaccine Injury Compensations Program. Additional resources are available at https://aap.org/immunization.
Partnership with community stakeholders, including early childhood learning centers, schools, school-based health centers, public health agencies, pharmacies, and other organizations, can optimize influenza vaccine distribution, communication, and administration. This may be particularly important for reaching patients with limited access to care, including those residing in rural areas. For example, practices could help with outreach initiatives such as influenza vaccine fairs or mobile vaccine vans. Partnering with faith-based organizations may be an effective intervention to increase immunization rates in communities in which mistrust and vaccine hesitancy are high.145 Collectively, practices and partners can educate families and community members on the importance of influenza vaccination and address common concerns. The AAP has created communication resources to convey key messages and to help the public understand influenza vaccination recommendations on the AAP Web site at https://www.aap.org/en/newsroom/campaigns-and-toolkits/flu-campaign-toolkit/.
The AAP supports mandatory influenza vaccination programs for HCP in all settings, including outpatient locations. Optimal prevention of influenza in these settings requires that at least 90% of HCP are vaccinated. Estimated influenza vaccination coverage of HCP was only 79.9% during the 2021–2022 season, compared with 75.9% in the 2020–2021 season.146 Coverage levels were highest among HCP whose employers required vaccination (95.8%–97.3%). Coverage levels were also higher among HCP working in hospitals (92%) compared with those working in long-term care settings (66.4%). Influenza vaccination programs for HCP benefit the health of employees, their patients, and members of the community, especially because HCP frequently come into contact with high-risk patients in their clinical settings. The programs reduce HCP absenteeism and may reduce disruptions in care delivery associated with personnel shortages.147 Mandatory influenza vaccination of HCPs is considered ethical, just, and necessary to improve patient safety. For the prevention and control of influenza, HCP must prioritize the health and safety of their patients, honor the requirement of causing no harm, and act as role models for both their patients and colleagues by receiving influenza vaccination annually.
Influenza Treatment and Chemoprophylaxis
Antiviral Therapy
Antiviral agents available for both influenza treatment and chemoprophylaxis in children of all ages can be found in Table 6 in the policy statement (www.pediatrics.org/cgi/doi/10.1542/peds.2023-063772) (including doses for preterm infants that have not been evaluated by the FDA) and on the CDC Web site.148 These include the neuraminidase inhibitors (NAIs: oseltamivir, zanamivir, peramivir) and a selective inhibitor of influenza cap-dependent endonuclease (baloxavir), all of which have activity against influenza A and B viruses.149
Oral oseltamivir (Tamiflu) remains the antiviral drug of choice for the management of illness caused by influenza virus infections and is the only drug approved for treatment of hospitalized children. Oseltamivir is preferred because of the cumulative experience of this drug in children, relative cost, and ease of administration. Although more difficult to administer, inhaled zanamivir (Relenza) is an acceptable alternative for patients who do not have chronic respiratory disease. In one nationwide, population-based cohort study that included ambulatory children and adults who were treated with antiviral medications within 48 hours of a clinical diagnosis of influenza, inhaled zanamivir was not inferior to oral oseltamivir in preventing influenza-related hospitalization or death, but an exploratory subgroup analysis favored oseltamivir in children 5 to 17 years of age. This may reflect the ability of children to correctly use a zanamivir inhaler. A single dose of intravenous (IV) peramivir (Rapivab) is approved for the treatment of acute uncomplicated influenza in ambulatory children 6 months and older who have been symptomatic for no more than 2 days. The efficacy of peramivir in patients with serious influenza requiring hospitalization has not been established.149 In a retrospective cohort study of children 0 to 5 years of age hospitalized with influenza in China, oral oseltamivir and IV peramivir were associated with similar clinical outcomes when used for the treatment of influenza B.150 In children with influenza A, oseltamivir treatment was associated with improved recovery and short hospital stays (5 vs 6 days; P = .02).
A single dose of baloxavir marboxil (Xofluza) is approved for treatment of acute uncomplicated influenza in otherwise healthy individuals as young as 5 years of age and all individuals 12 years and older.151,152 Outcomes are similar to those for NAIs.153,154 In a randomized controlled trial that enrolled adolescents and adults, baloxavir had better efficacy than oseltamivir in the treatment of influenza B.155 The oral suspension formulation of baloxavir was not available in the United States for the 2022–2023 influenza season, limiting use in children who were old enough to receive the drug but weigh less than 20 kg.156 Availability of this formulation is not expected in the United States for the 2023–2024 influenza season.
During the 2022–2023 influenza season, there was a shortage of generic oseltamivir. The CDC published recommendations for the prioritizing use of antiviral agents for patients at greatest risk of influenza-related complications and those who are hospitalized.157
Rationale for Influenza Treatment in Children
Randomized controlled trials (RCTs) to evaluate the efficacy of influenza antiviral medications among outpatients with uncomplicated influenza have found that timely treatment (optimally ≤2 days from symptom onset) can reduce the duration of influenza symptoms and fever in pediatric populations.158–162 Observational studies in pediatric and adult populations suggest that antiviral agents are safe and could reduce the risk of certain influenza complications, including hospitalization and death.163–167 Potential limitations of the trials conducted to date in children include the study size (the number of events might not be sufficient to assess specific outcomes in small studies), variations in the case definition of influenza illness (clinically diagnosed versus laboratory confirmed), time of treatment administration in relation to the onset of illness, and inclusion of children of varying ages and underlying health conditions. Several studies also suggest that treatment of index patients with influenza reduces transmission to household contacts to some extent, but the magnitude of the effect is inconsistent across published reports.168 The totality of available evidence supports the treatment of children with influenza.
A Cochrane review of 6 RCTs involving treatment of 2356 children with clinically diagnosed influenza, of whom 1255 had laboratory-confirmed influenza, showed that, in children with laboratory-confirmed influenza, oral oseltamivir and inhaled zanamivir reduced median duration of illness by 36 hours (26%; P < .001) and 1.3 days (24%, P < .001), respectively.162 Among the studies reviewed, one trial of oseltamivir in children with asthma who had laboratory-confirmed influenza showed a nonsignificant reduction in illness duration (10.4 hours; 8%; P = .542). Oseltamivir significantly reduced acute otitis media in children 1 through 5 years of age with laboratory-confirmed influenza (risk difference: –0.14; 95% CI: –0.24 to –0.04).162 Another Cochrane review of RCTs in adults and children, which included 20 oseltamivir (9623 participants) and 26 zanamivir trials (14 628 participants),158 found no effect of oseltamivir in reducing the duration of illness in asthmatic children, but in otherwise healthy children, there was a reduction by a mean difference of 29 hours (95% CI: 12 hours–47 hours; P = .001). No significant effect was observed with zanamivir. Regarding complications, this review did not find a significant effect of NAIs on reducing hospitalizations, pneumonia, bronchitis, otitis media, or sinusitis in children.162 More recently, a meta-analysis of 5 new RCTs that included 1598 children with laboratory-confirmed influenza showed that treatment with oseltamivir significantly reduced the duration of illness in this population by 17.6 hours (95% CI: –34.7 hours to –0.62 hours).160 When children with asthma were excluded, this difference was larger (–29.9 hours; 95% CI: –53.9 hours to –5.8 hours). The risk of otitis media was 34% lower in this group, as well. Similarly, a meta-analysis conducted by Tejada et al showed a statistically significant reduction in the risk of acute otitis media occurrence among treated children over placebo recipients (OR: 0.48; 95% CI: 0.30–0.77).167 Overall, efficacy outcomes are best demonstrated in patients with laboratory-confirmed influenza.
There are no prospective, fully enrolled, completed RCTs of antiviral agents versus placebo for treatment of influenza in hospitalized children or pediatric patients with comorbidities, and prospectively collected data to determine the role of antiviral agents in treating severe influenza are limited. One RCT of oseltamivir treatment of influenza in hospitalized children in El Salvador and Panama suggested clinical benefit, but no statistically significant findings were reported, because only 21% of the target sample size was enrolled and therefore the study was substantially underpowered.169 Nevertheless, on the basis of information obtained from retrospective observational studies and meta-analyses conducted to date in both adults and children, most experts support the use of antiviral medications as soon as possible to treat pediatric patients with severe influenza, including hospitalized patients.161–166,169
In a retrospective study of 784 PICU admissions from 2009 to 2012, the estimated risk of death was reduced in 653 NAI-treated individuals (OR: 0.36; 95% CI: 0.16–0.83).170 In a retrospective analysis of data from the US Influenza Hospitalization Surveillance Network, administration of antiviral agents ≤2 days after illness onset was associated with shorter lengths of stay in children admitted to the ICU (adjusted hazard ratio: 1.46; P = .007) and in children with underlying medical conditions not admitted to the ICU (adjusted hazard ratio: 1.37; P = .02). In the relatively small number of patients studied, antiviral treatment ≥3 days after illness onset had no significant effect in either cohort.171 Similarly, early antiviral treatment of children with tracheostomy hospitalized with influenza reduced length of stay by 1 day (6.4 vs 7.5 days; P = .01).172 In a multicenter, retrospective cohort study involving 55 799 children hospitalized with influenza between 2007 and 2020, oseltamivir use on hospital day 0 or 1 was associated with shorter hospital stays and lower odds of readmission within 7 days, transfer to the ICU, and the composite outcome use of extracorporeal membrane oxygenation and in-hospital mortality.173
No additional benefit exists for double-dose NAI therapy on reduction of mortality or viral clearance, compared with standard-dose therapy, on the basis of a recent systematic review and meta-analysis of 10 published studies174 (4 RCT and 6 observational studies) involving 20 947 adult and pediatric patients. In a randomized, parallel-group, double-blind, placebo-controlled, superiority trial, combining baloxavir with NAIs did not result in superior clinical outcomes compared with NAIs alone in patients 12 years and older hospitalized with laboratory-confirmed influenza.175
The AAP, CDC, Infectious Diseases Society of America,149 and Pediatric Infectious Diseases Society recommend treatment with oseltamivir for children with serious, complicated, or progressive disease presumptively or definitively caused by influenza, irrespective of influenza vaccination status (the circulating strains may not be well matched with vaccine strains) or whether illness began >48 hours before presentation. Earlier treatment provides better clinical responses, but treatment after 48 hours of symptoms in adults and children with moderate to severe disease or with progressive disease has been shown to provide some benefit and should be offered.170,176,177 Additionally, the AAP recommends treatment of children at risk for severe complications of influenza, regardless of duration of symptoms. Children younger than 2 years are at an increased risk of hospitalization and complications attributable to influenza. The FDA has approved oseltamivir for treatment of children as young as 2 weeks of age. Given preliminary pharmacokinetic data and limited safety data, the CDC and AAP support the use of oseltamivir to treat influenza in both term and preterm infants from birth, because benefits of therapy of neonatal influenza are likely to outweigh possible risks of treatment. Otherwise healthy children who have suspected influenza with an uncomplicated presentation should be considered for antiviral medication, particularly if they are in contact with other children who either are younger than 6 months (because they are not able to receive influenza vaccine) or have high-risk conditions (including age <5 years) that predispose them to complications of influenza, when influenza viruses are known to be circulating in the community. Antiviral treatment should be started as soon as possible after illness onset and should not be delayed while waiting for a definitive influenza test result, because early therapy provides the best outcomes. Algorithms for interpreting positive and negative influenza tests are available (https://www.cdc.gov/flu/professionals/diagnosis/algorithm-results-circulating.htm). The balance between benefits and harms should be considered when making decisions about the use of NAIs for either treatment or chemoprophylaxis of influenza. The cost of antiviral therapy may be a barrier to treatment of some families.
If the breastfeeding parent requires antiviral agents, treatment with oral oseltamivir is preferred. The CDC does not recommend use of baloxavir for treatment of pregnant or breastfeeding individuals. There are no available efficacy or safety data in pregnant individuals, and there are no available data regarding the presence of baloxavir in human milk, the effects on the breastfed infant, or the effects on milk production.
Oseltamivir Adverse Effects
In adverse event data collected systematically in prospective trials, vomiting was the only adverse effect reported more often with oseltamivir compared with placebo when studied in children 1 through 12 years of age (ie, 15% of treated children versus 9% receiving placebo). Diarrhea was reported in clinical trials of oseltamivir in 7% of treated children <1 year of age. After reports from Japan of possible oseltamivir-attributable neuropsychiatric adverse effects, a review of controlled clinical trial data and ongoing surveillance has failed to establish a link between this drug and neurologic or psychiatric events.178,179 Neurologic and neuropsychiatric complications including abnormal behavior occur in children with influenza in the absence of exposure to oseltamivir.180
Adherence to Antiviral Treatment Guidance
Despite the body of evidence supporting antiviral treatment of children hospitalized with confirmed or suspected influenza and expert guidance recommending antiviral use in children at high risk for complications, antiviral prescribing is suboptimal. In studies examining antiviral use in hospitalized children with influenza, half or fewer eligible children were prescribed antiviral treatment.181,182 In a cross-sectional study of ambulatory children at high risk for complications, 58.1% of children diagnosed with influenza during the 2016–2019 influenza seasons received antiviral treatment.183 Children 2 to 5 years of age, residents of chronic care facilities, and children who received care in an emergency department were less likely to be treated. In a multicenter retrospective cross-sectional study conducted between 2007 and 2020 at 36 US children’s hospitals participating in the Public Health Information System, oseltamivir use in children hospitalized with influenza increased over time. Use was lowest in the 2007–2008 influenza season (20.2%) and highest in the 2017–2018 influenza season (77.9), but there was significant variability by hospital.184 Odds of receiving oseltamivir therapy were less in children younger than 2 years of age and children 2 to 5 years of age compared with older children. Multifactorial interventions are urgently needed to increase adherence to antiviral treatment guidelines for children at high risk for complications of influenza, including those who are hospitalized.
Influenza Chemoprophylaxis
Antiviral medications are important adjuncts to influenza vaccination for control and prevention of influenza disease in children who are at least 3 months of age. Randomized placebo-controlled studies showed that oral oseltamivir and inhaled zanamivir were efficacious when administered as chemoprophylaxis to household contacts after a family member had laboratory-confirmed influenza.149 The efficacy of baloxavir was demonstrated in a randomized, placebo-controlled trial in Japan conducted during the 2018–2019 influenza season. One percent of household members 12 years and older treated with a single dose of baloxavir within 48 hours of exposure to a symptomatic household contact with influenza developed influenza compared with 13% in the placebo-treated group (adjusted RR: 0.10; 95% CI: 0.04–0.28).185 For additional context, 73% started baloxavir within 24 hours of the index case’s symptom onset, an exercise that would be difficult to replicate in practice in the United States. There are no data on IV peramivir for chemoprophylaxis.
Decisions on whether to administer antiviral chemoprophylaxis should include consideration of the exposed person’s risk of influenza complications, vaccination status, type and duration of contact, time since exposure, recommendations from local or public health authorities, and clinical judgment. Optimally, postexposure chemoprophylaxis should only be used when antiviral agents can be started within 48 hours of exposure; the lower once-daily dosing for chemoprophylaxis with oral oseltamivir or inhaled zanamivir should not be used for treatment of children symptomatic with influenza.149 Early, full-treatment dosing (rather than once-daily chemoprophylaxis dosing) should be used in high-risk symptomatic patients without waiting for laboratory confirmation.
Toxicities may be associated with antiviral agents, and indiscriminate use might limit availability. Pediatricians should inform recipients of antiviral chemoprophylaxis that risk of influenza is lowered, but not eliminated, while taking the medication, and susceptibility to influenza returns when medication is discontinued. Chemoprophylaxis is not a substitute for vaccination and among some high-risk people, both vaccination with IIV and antiviral chemoprophylaxis may be considered.149 The effectiveness of LAIV but not IIV or RIV will be decreased for children receiving oseltamivir or other influenza antiviral agents.149 Updates will be available at www.aapredbook.org and www.cdc.gov/flu/professionals/antivirals/index.htm.
Antiviral Resistance
Resistance to any antiviral drug can emerge, necessitating continuous population-based assessment by the CDC. During the 2022–2023 season to date, all viruses evaluated have retained susceptibility to baloxavir, peramivir, and zanamivir. One influenza A (H1N1) pdm09 isolate (<0.1% of all viruses tested) exhibited reduced inhibition to oseltamivir (https://www.cdc.gov/flu/weekly/weeklyarchives2022-2023/week20.htm).
Globally, detection of viruses with reduced susceptibility to neuraminidase inhibitors was low in the 2018–2019 (0.5%) and 2019–2020 (0.6%) influenza seasons. Reduced susceptibility to baloxavir was also rarely observed (0.5% during the 2018–2019 season and 0.1% during the 2019–2020 season).186 The rate was higher in Japan (4.5% in the 2018–2019 season), where baloxavir use is the highest. In clinical trials, isolates with amino acid substitutions conferring reduced susceptibility to baloxavir have been identified in baloxavir-treated patients and are more common in children 5 years and younger.187,188
High levels of resistance to amantadine and rimantadine persist among the influenza A viruses currently circulating; neither drug is effective against influenza B viruses. Adamantane medications are not recommended for use against influenza unless resistance patterns change.149
If a newly emergent antiviral-resistant virus is a concern, recommendations for alternative treatment will be available from the AAP and CDC. Resistance characteristics can change for an individual patient over the duration of a treatment course, especially in those who are severely immunocompromised. Information on current recommendations and therapeutic options can be found on the AAP Web site (www.aap.org or www.aapredbook.org), through state-specific AAP chapter Web sites, or on the CDC Web site (www.cdc.gov/flu/).
Diagnostic Tests for Influenza
Diagnostic testing for influenza may be beneficial when results will be used to inform clinical management or infection prevention measures and to distinguish from other respiratory viruses with similar symptoms (eg, SARS-CoV-2). Performance characteristics of tests vary and are impacted by duration of illness in the person being tested and proper specimen collection and handling. Test results must be interpreted in the context of community influenza activity (Table 4); false-positive tests may occur during periods of low influenza activity.
Molecular assays include rapid molecular tests, reverse-transcription polymerase chain reaction test, and other nucleic acid amplification tests. Multiplex assays that allow for the simultaneous detection of influenza viruses, plus SARS-CoV-2 or influenza viruses, SARS-CoV-2, and RSV, are available. These assays can be particularly useful when these viruses are cocirculating; because signs and symptoms of these viruses may be similar, clinical differentiation is difficult, and different treatment strategies are recommended. A current list of authorized tests is available at https://www.cdc.gov/flu/professionals/diagnosis/table-flu-covid19-detection.html.
Antigen detection tests include rapid influenza diagnostic tests (RIDTs) and immunofluorescence assays. Some available RIDTs detect SARS-CoV-2, as well as influenza A and B. An updated list of RIDTs is available at https://www.cdc.gov/flu/professionals/diagnosis/table-ridt.html.
Rapid molecular assays are highly sensitive and are preferred over RIDTs in ambulatory children in whom testing is performed. During periods of high community influenza activity, clinicians should consider confirming negative RIDTs with a molecular test. When influenza is circulating in the community, hospitalized patients with signs and symptoms of influenza should be tested with a molecular assay with high sensitivity and specificity.
In February 2023, the FDA issued an emergency use authorization for the first over-the-counter, at-home test to diagnose both influenza A and B and SARS-CoV-2 in symptomatic individuals as young as 2 years of age.189 The test is performed on a nasal swab that can be self-collected in persons 14 years and older. The test must be obtained by a caregiver in younger children. Results are available in 30 minutes. In individuals with symptoms, the test correctly identified 99.3% of negative and 90% of positive influenza A samples and 99.9% of negative influenza B samples. Low circulation of influenza B precluded assessment of the test’s ability to detect influenza B in real-world settings. The utility of these tests in managing pediatric patients with symptoms of influenza merits exploration. At a minimum, parents of children at high risk for complications of influenza will benefit from counseling about timely communication with the medical home about the results of home tests and education that a negative test cannot completely exclude influenza.
Future Directions
Safety and Effectiveness of Available Influenza Vaccines
Continued evaluation of the safety, immunogenicity, and effectiveness of influenza vaccines, especially for at-risk and diverse populations, is important. The duration of protection, potential role of previous influenza vaccination on overall VE, and VE by vaccine formulation, virus strain, timing of vaccination, and subject age and health status in preventing outpatient medical visits, hospitalizations, and deaths continue to be evaluated.
Influenza Vaccines in Development
Development efforts continue for universal influenza vaccines that induce broader protection and eliminate the need for annual vaccination. The success of mRNA and other novel technologies used in the development of COVID-19 vaccines may accelerate the prospects of broad influenza vaccines. Understanding the establishment of immunity against influenza in early life and developing a safe, immunogenic vaccine for infants younger than 6 months are essential. Studies on the effectiveness and safety of influenza vaccines containing adjuvants that enhance immune responses to influenza vaccines or that use novel routes of administration are needed in children. Efforts to improve the vaccine development process to allow for a shorter interval between identification of vaccine strains and vaccine production continue.
Promoting Vaccine Confidence and Increasing Vaccination Coverage
Systematic health services research is needed to examine influenza vaccination coverage, factors associated with undervaccination, and interventions to increase uptake in diverse populations. National data from 2019 found that 25.8% of parents were hesitant about influenza vaccine.190 Children of parents who were hesitant about childhood vaccines had 25.6% lower influenza vaccination coverage in the influenza 2018–2019 season compared with children of parents not reporting hesitancy.191 Vaccine hesitancy remains a major public health threat. Future studies should aim to improve our understanding of influenza vaccine hesitancy and identify effective strategies to address parental concerns, foster greater vaccine confidence, and increase influenza vaccine acceptance.141 Engagement of key stakeholder groups in this work is crucial, including patients and families; health care professionals; practices, as well as health systems; public health officials; and community leaders. Enhanced collaboration may facilitate more equitable influenza vaccine supply and delivery and more effective community outreach, particularly to vulnerable populations. Novel approaches for reducing barriers to accessing preventive care services may also help to reduce disparities in influenza vaccination coverage. Ongoing efforts should include broader implementation and evaluation of mandatory HCP vaccination programs in both inpatient and outpatient settings. Lastly, additional controlled data are needed to inform the timing, schedule, and type of influenza vaccine for optimal vaccine immunogenicity among immunocompromised children.
Antiviral Treatment
New antiviral drugs are in various development phases, given the need to improve options for the treatment and chemoprophylaxis of influenza. Additionally, with limited data on the use of antiviral agents in hospitalized children and in children with underlying medical conditions, prospective clinical trials to inform optimal timing and efficacy of antiviral treatment in these populations are warranted, particularly as new antiviral agents or new indications for existing antiviral agents become available. Barriers to treatment of children at high risk for complications, especially hospitalized patients, must be explored.
Additional Resources
Pediatricians can remain informed of advances and other updates during the influenza season by following the CDC Influenza page (www.cdc/gov/flu) and the AAP Red Book Online Influenza News and Resource Page (www.aapredbook.org).
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Committee on Infectious Diseases, 2022–2023
Sean T. O’Leary, MD, MPH, FAAP, Chairperson
James D. Campbell, MD, MS, FAAP, Vice Chairperson
Monica I. Ardura, DO, MSCS, FAAP
Ritu Banerjee, MD, PhD, FAAP
Kristina A. Bryant, MD, FAAP
Mary T. Caserta, MD, FAAP
Robert W. Frenck, Jr, MD, FAAP
Jeffrey S. Gerber, MD, PhD, FAAP
Chandy C. John, MD, MS, FAAP
Athena P. Kourtis, MD, PhD, MPH, FAAP
Angela Myers, MD, MPH, FAAP
Pia Pannaraj, MD, MPH, FAAP
Adam J. Ratner, MD, MPH, FAAP
Samir S. Shah, MD, MSCE, FAAP
Contributors
Kristina A. Bryant, MD, FAAP
Annika M. Hofstetter, MD, PhD, MPH, FAAP
Partnership for Policy Implementation
Juan D. Chaparro, MD, MS, FAAP
Jeremy J. Michel, MD, MHS, FAAP
Ex Officio
David W. Kimberlin, MD, FAAP – Red Book editor
Elizabeth D. Barnett MD, FAAP – Red Book associate editor
Ruth Lynfield, MD, FAAP – Red Book associate editor
Mark H. Sawyer, MD, FAAP – Red Book associate editor
Henry H. Bernstein, DO, MHCM, FAAP – Red Book online associate editor
Liaisons
Cristina V. Cardemil, MD, MPH, FAAP – National Institutes of Health
Karen M. Farizo, MD – US Food and Drug Administration
Lisa M. Kafer, MD, FAAP – Committee on Practice Ambulatory Medicine
David Kim, MD, MA – HHS Office of Infectious Disease and HIV/AIDS Policy
Eduardo López Medina, MD, MSc – Sociedad Latinoamericana de Infectologia Pediatrica
Denee Moore, MD, FAAFP – American Academy of Family Physicians
Lakshmi Panagiotakopoulos, MD, MPH – Centers for Disease Control and Prevention
José R. Romero, MD, FAAP – Centers for Disease Control and Prevention
Laura Sauvé, MD, MPH, FAAP, FRCPS – Canadian Pediatric Society
Jeffrey R. Starke, MD, FAAP – American Thoracic Society
Jennifer Thompson, MD – American College of Obstetricians and Gynecologists
Melinda Wharton, MD, MPH – Centers for Disease Control and Prevention
Charles R. Woods, Jr, MD, MS, FAAP – Pediatric Infectious Diseases Society
Staff
Jennifer M. Frantz, MPH
Gillian Gibbs, MPH
Acknowledgments
The Committee on Infectious Diseases thanks Kristina A. Bryant, MD, FAAP, and Annika M. Hofstetter, MD, PhD, MPH, FAAP, for their leadership in drafting the policy statement and technical report; and Juan D. Chaparro, MD, MS, FAAP, and Jeremy J. Michel, MD, MHS, FAAP, for their significant contributions in providing input on the initial drafts on behalf of the AAP Partnership for Policy Initiative.
Technical reports from the American Academy of Pediatrics benefit from expertise and resources of liaisons and internal (AAP) and external reviewers. However, technical reports from the American Academy of Pediatrics may not reflect the views of the liaisons or the organizations or government agencies that they represent.
The guidance in this report does not indicate an exclusive course 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.
COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2023-063772.
This document is copyrighted and is property of the American Academy of Pediatrics and its Board of Directors. All authors have filed conflict of interest statements with the American Academy of Pediatrics. Any conflicts have been resolved through a process approved by the Board of Directors. The American Academy of Pediatrics has neither solicited nor accepted any commercial involvement in the development of the content of this publication.
- AAP
American Academy of Pediatrics
- ACIP
Advisory Committee on Immunization Practices
- CDC
Centers for Disease Control and Prevention
- CI
confidence interval
- COVID-19
coronavirus disease 2019
- EHR
electronic health record
- FDA
US Food and Drug Administration
- GBS
Guillain-Barré syndrome
- HA
hemagglutinin
- HCP
health care personnel
- iGAS
invasive group A streptococcal
- IIV
inactivated influenza vaccine
- IIV4
quadrivalent inactivated influenza vaccine
- IV
intravenous
- LAIV
live attenuated influenza vaccine
- LAIV4
quadrivalent live attenuated influenza vaccine
- mRNA
messenger RNA
- NAI
neuraminidase inhibitor
- OR
odds ratio
- RCT
randomized controlled trial
- RIDT
rapid influenza diagnostic test
- RIV
recombinant influenza vaccine
- RIV4
quadrivalent recombinant influenza vaccine
- RR
relative risk
- SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
- VE
vaccine effectiveness
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