POLICY STATEMENT Organizational Principles to Guide and Define the Child Health Care System and/or Improve the Health of all Children

Recommendations for Prevention and Control of Influenza in Children, 2020–2021 Committee on Infectious Diseases

This statement updates the recommendations of the American Academy of abstract Pediatrics for the routine use of influenza vaccine and antiviral in the prevention and treatment of influenza in children during the 2020–2021 season. fl The American Academy of Pediatrics (AAP) recommends routine in uenza Policy statements from the American Academy of Pediatrics benefit immunization of all children without medical contraindications, starting at from expertise and resources of liaisons and internal (AAP) and external reviewers. However, policy statements from the American 6 months of age. Influenza vaccination is an important intervention to protect Academy of Pediatrics may not reflect the views of the liaisons or the vulnerable populations and reduce the burden of respiratory illnesses during organizations or government agencies that they represent. the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) . The guidance in this statement does not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking Any licensed, recommended, age-appropriate vaccine available can be into account individual circumstances, may be appropriate. administered, without preference for one product or formulation over another. All policy statements from the American Academy of Pediatrics Antiviral treatment of influenza with any licensed, recommended, age- automatically expire 5 years after publication unless reaffirmed, revised, or retired at or before that time. appropriate influenza antiviral is recommended for children with fi fl This document is copyrighted and is property of the American suspected or con rmed in uenza who are hospitalized, have severe or Academy of Pediatrics and its Board of Directors. All authors have filed progressive disease, or have underlying conditions that increase their risk of conflict of interest statements with the American Academy of Pediatrics. Any conflicts have been resolved through a process complications of influenza. Antiviral treatment may be considered for any approved by the Board of Directors. The American Academy of previously healthy, symptomatic outpatient not at high risk for influenza Pediatrics has neither solicited nor accepted any commercial involvement in the development of the content of this publication. complications in whom an influenza diagnosis is confirmed or suspected, if DOI: https://doi.org/10.1542/peds.2020-024588 treatment can be initiated within 48 hours of illness onset, and for children whose siblings or household contacts either are younger than 6 months or PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). have a high-risk condition that predisposes them to complications of influenza. Copyright © 2020 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: Dr Munoz has a royalties relationship with Up to Date, Pfizer, and Moderna.

FUNDING: No external funding.

UPDATES FOR THE 2020–2021 SEASON POTENTIAL CONFLICT OF INTEREST: Dr Munoz had a previous research relationship with BioCryst and research relationships with the 1. The composition of the influenza vaccines for 2020–2021 has been European Society of Pediatric Infectious Diseases (ESPID) and International Neonatal and Maternal Immunization Symposium (INMIS). updated. The recommended influenza A(H1N1)pdm09 and A(H3N2) components and the influenzaB/Victoriacomponentofthevaccineare new for this season. The B/Yamagata component is unchanged from the To cite: Infectious Diseases Con. Recommendations for fl previous season. All quadrivalent influenza vaccines include these 4 Prevention and Control of In uenza in Children, 2020–2021. Pediatrics. 2020;146(4):e2020024588 components. The trivalent vaccines do not include influenza B/Yamagata.

Downloaded from www.aappublications.org/news by guest on October 2, 2021 PEDIATRICS Volume 146, number 4, October 2020:e2020024588 FROM THE AMERICAN ACADEMY OF PEDIATRICS 2. All pediatric vaccines are INTRODUCTION rates of influenza-related 3–5 quadrivalent. There are no Children consistently have the highest hospitalization, and high mortality. fl trivalent vaccines available for attack rates of influenza in the In uenza A (H3N2) predominated children. community during seasonal influenza early, followed by a second wave of fl 3. The vaccine formulations available . They play a pivotal role in in uenza B/Yamagata from March for children 6 through 35 months the transmission of influenza virus 2018 onward. Although of age have been updated. Afluria infection to household and other hospitalization rates for children that Quadrivalent will be the only close contacts and can experience season did not exceed those reported vaccine for children 6 through substantial morbidity, including during the 2009 pandemic, they did 35 months of age with a dosing severe or fatal complications from surpass rates reported in previous volume of 0.25 mL. Fluzone influenza infection.1 Children younger high-severity A(H3N2)-predominant Quadrivalent, which is licensed in than 5 years, especially those younger seasons. Excluding the 2009 a 0.25-mL and a 0.5-mL dosing than 2 years, and children with pandemic, the 188 pediatric deaths – volume, will likely be available certain underlying medical conditions reported during the 2017 2018 only in a 0.5-mL dosing volume for are at increased risk of season (approximately half of which this age group this season. The hospitalization and complications occurred in otherwise healthy dosing volume for the 2 other attributable to influenza.1 School- children) were the highest reported fl vaccines available for this age aged children bear a large influenza since in uenza-associated pediatric group, Fluarix and FluLaval, is 0.5 disease burden and are more likely to mortality became a nationally fi 3–5 mL. The AAP has no preference for seek influenza-related medical care noti able condition in 2004. one product over another. compared with healthy adults.1,2 Among pediatric deaths of children 6 months and older who were eligible 4. Children 6 months through 8 years Reducing influenza virus for vaccination and for whom of age who are receiving influenza transmission among children vaccination status was known, vaccine for the first time, who have decreases the burden of childhood approximately 80% had not received received only 1 dose ever before influenza and transmission of influenza vaccine during the July 1, 2020, or whose vaccination influenza virus to household contacts 2017–2018 season.3 Influenza status is unknown should be and community members of all 1,2 vaccine effectiveness (VE) for the offered vaccination as soon as ages. Influenza vaccination is 2017–2018 season in children is influenza vaccines become particularly important during the shown in Table 1.4 available and should receive 2 severe acute respiratory syndrome- doses of vaccine, ideally by the end coronavirus 2 (SARS-CoV-2) The 2018–2019 season was of of October. Children needing only pandemic to reduce the burden of moderate severity, with similar 1 dose of influenza vaccine, respiratory illnesses and hospitalization rates in children as regardless of age, should also hospitalizations and preserve the during the 2017–2018 season (71/ receive vaccination ideally by the capacity of the health care 100 000 among children 0 through end of October. infrastructure. The American 4 years old and 20.4/100 000 among Academy of Pediatrics (AAP) 5. The contraindications for live children 5 through 17 years old), recommends routine influenza attenuated influenza vaccine which were higher than those (LAIV) have been updated to vaccination and antiviral agents for the prevention and treatment of observed in previous seasons from harmonize with recommendations – – 7 influenza in children, respectively. 2013 2014 to 2016 2017. Among of the Advisory Committee on 1132 children hospitalized with Immunization Practices (ACIP). influenza and for whom data were Although there are no reports of SUMMARY OF RECENT INFLUENZA available, 55% had at least 1 additional safety risks for LAIV in SEASONS IN THE UNITED STATES underlying medical condition; the fi children with immunode ciencies, most commonly reported underlying 2017–2018 and 2018–2019 Influenza anatomic or functional asplenia, conditions were asthma or reactive Seasons cochlear implants, or active airway disease (26%), neurologic fl cerebrospinal uid leaks, because The 2017–2018 influenza season had disorders (15.6%), and obesity the vaccine is a live attenuated an important impact in pediatric (11.6%).8 A total of 144 influenza- product, it is not recommended in patients. It was the first classified as associated pediatric deaths were these populations. a high-severity season for all age reported. The 2017–2018 influenza 6. The importance of influenza groups, with high levels of outpatient season was the longest-lasting season vaccination during the SARS-CoV-2 clinic and emergency department reported in the United States in the pandemic is discussed. visits for influenza-like illness, high past decade, with elevated levels of

Downloaded from www.aappublications.org/news by guest on October 2, 2021 2 FROM THE AMERICAN ACADEMY OF PEDIATRICS TABLE 1 Adjusted Vaccine Effectiveness (VE) in Children in the United States, by Season, as Reported implementation of social distancing by the Centers for Disease Control and Prevention (CDC), US Influenza Vaccine Effectiveness measures for mitigation of the Network pandemic. Although influenza Influenza Type/Age 2017–2018 2018–2019 2019–2020a B/Victoria viruses predominated Group H3N2 and B/Yamagata VE% H1N1 and H3N2 VE% B/Victoria and H1N1 VE% early in the season, influenza (95% CI) (95% CI) (95% CI) A(H1N1)pdm09 viruses were the Influenza A and B most predominant circulating strain Overall all ages 38 (31 to 43) 29 (21 to 35) 45 (36 to 53) this season. Influenza A(H3N2) and 6mo–17 y Not reported Not reported 55 (42 to 65) B/Yamagata lineage represented – 6mo 8 y 68 (55 to 77) 48 (37 to 58) NA approximately 4.1% and 0.8% of 9–17 y 32 (16 to 44) 7 (–20 to 28) NA Influenza A(H1N1)pdm09 circulating strains, respectively. The Overall all ages 62 (50 to 71) 44 (37 to 51) 37 (19 to 52) majority of characterized influenza 6mo–17 y Not reported Not reported 51 (22 to 69) A(H1N1)pdm09 (82.5%) and 6mo–8 y 87 (71 to 95) 59 (47 to 69) Not reported influenza B/Victoria (59.7%) viruses 9–17 y 70 (46 to 67) 24 (–18 to 51) Not reported fl were antigenically similar to the In uenza A(H3N2) – Overall all ages 22 (12 to 31) 9 (–4 to 20) NA viruses included in the 2019 2020 6mo–17 y Not reported Not reported NA influenza vaccine. Less than half 6mo–8 y 54 (33 to 69) 24 (1 to 42) NA (46.5%) of influenza A(H3N2) viruses 9–17 y 18 (-6 to 36) 3 (–30 to 28) NA were antigenically similar to the fl In uenza B Victoria A(H3N2) component of the Overall all ages 76 (45 to 89) Not reported 50 (39 to 50) – 6mo–17 y Not reported Not reported 56 (42 to 67) 2019 2020 vaccine. During this 6mo–8 y Not reported Not reported Not reported season, the predominant A(H3N2) 9–17 y Note reported Not reported Not reported circulating clade was 3C.2a, subclade Influenza B yamagata 3C.2a1, with cocirculation of a small Overall all ages 48 (39 to 55) Not reported NA – proportion of 3C.3a, in contrast to the 6mo 17 y Not reported Not reported NA – 6mo–8 y 77 (49 to 90) Not reported NA 2018 2019 season, when 3C.3a 9–17 y 28 (1 to 48) Not reported NA strains predominated. Preliminary Vaccine effectiveness is estimated as 100% 3 (1 2 odds ratio [ratio of odds of being vaccinated among outpatients with estimates of the effectiveness of the CDC’s real-time RT-PCR influenza-positive test results to the odds of being vaccinated among outpatients with influenza- 2019–2020 seasonal influenza negative test results]); odds ratios were estimated using logistic regression. Adjusted for study site, age group, sex, race/ vaccines against medically attended ethnicity, self-rated general health, number of days from illness onset to enrollment, and month of illness using logistic fl regression. in uenza illness from the US Flu VE a Interim results as of February 21, 2020.6 Network are shown in Table 1.6 These are preliminary data and are not vaccine specific. Susceptibility to influenza-like illness activity for Circulating viruses identified available antiviral agents remains a total duration of 21 consecutive belonged to subclade 3C.2a1 or clade greater than 99% for all circulating weeks (compared with an average 3C.3a, with 3C.3a viruses accounting strains, but 0.5% of A(H1N1)pdm09 duration of 16 weeks).7 Variations in for .70% of the A(H3N2) in the isolates tested by the Centers for circulating strains affected vaccine United States. This likely contributed Disease Control and Prevention (CDC) efficacy. Influenza A(H1N1)pdm09 to an overall lower vaccine exhibited highly reduced inhibition to viruses predominated from October effectiveness (VE) against influenza and . Reduced to mid-February, and influenza A(H3N2) this season, despite susceptibility to baloxavir has not A(H3N2) viruses were identified achieving the highest vaccination been reported in the United States more frequently from February to coverage reported in the last decade to date. May. Influenza B (B/Victoria lineage in children (62.6% overall) (Table 1 predominant) represented and Fig 1).7,9 The 2019–2020 season was of approximately 5% of circulating moderate severity, although 3 peaks 2019–2020 Influenza Season strains. Most characterized influenza of influenza-like illness activity and A(H3N2) viruses were antigenically The 2019–2020 influenza season was the highest hospitalization rates in distinct from the A(H3N2) component unusual and complicated by the children, 68.2 per 100 000 population of the 2018–2019 vaccine. The emergence of the SARS-CoV-2 overall, were reported this season. vaccine’s A(H3N2) virus belonged to pandemic in early 2020. Influenza The first peak of activity occurred in subclade 3C.2a1. Cocirculation of activity began early in October 2019, early January, likely associated with multiple genetically diverse subclades continuing through mid-March 2020, influenza B circulation; the second of A(H3N2) was documented. with an abrupt decline after the peak occurred in February, when

Downloaded from www.aappublications.org/news by guest on October 2, 2021 PEDIATRICS Volume 146, number 4, October 2020 3 23-month-olds, and 5.5% were younger than 6 months.  Among 63 children who died and were tested, 46.0% had a bacterial coinfection.  Among 141 children who were 6 months or older at the time of illness onset, and therefore, would have been eligible for influenza vaccination and for whom vaccination status was known, most (74%) were unvaccinated. Only 37 (26%) had received at least 1 dose of influenza vaccine (30 had complete vaccination, and FIGURE 1 7 had received 1 of 2 ACIP- Influenza vaccination coverage in children 6 months to 17 years of age in the United States, 2010 to recommended doses). 2019. Source: Centers for Disease Control and Prevention (https://www.cdc.gov/flu/fluvaxview/ coverage-1819estimates.htm). INFLUENZA MORBIDITY AND MORTALITY IN CHILDREN influenza A(H1N1)pdm09 became  There were 182 laboratory- predominant; and the third peak in confirmed influenza-associated Influenza viruses are a common cause March is thought to be associated pediatric deaths. Most (63.0%) of of acute lower respiratory tract fl with cocirculation of in uenza and those children died after being infection (ALRTI) in children. SARS-CoV-2. The CDC has now admitted to the hospital. The Pediatric hospitalizations and deaths fl established a separate surveillance median age of the pediatric deaths caused by in uenza can be report for novel coronavirus disease was 6.1 years (range, 2 months to substantial. A recent study estimated 2019 (COVID-19)-like illness.10 The that globally, influenza virus accounts 17 years). cumulative influenza hospitalization for 7% of all ALRTIs, 5% of ALRTI ○ rates per 100 000 population were Seventy of the pediatric deaths hospitalizations, and 4% of ALRTI fl 95.1 among children 0 through were associated with in uenza A deaths in children younger than 4 years old, and 24.8 among viruses, and 112 were 5 years.11 In the United States, the children 5 through 17 years old. associated with influenza B rates of influenza-associated Hospitalization rates in children 0 to viruses. hospitalization for children younger 4 years old were higher than those  Among the 168 children with than 5 years consistently exceed the seen for this age group during the known medical history, 42.9% of rates for children 5 through 17 years 2009 influenza pandemic, higher than deaths occurred in children who of age, and during the 2019–2020 the rate in adults 50 to 64 years old had at least 1 underlying medical season, they exceeded the this season (91.8/100 000), and the condition recognized by the hospitalization rates of adults 50 to 8 highest on record for this age group. Advisory Committee on 64 years of age. Children 5 through Among 168 children hospitalized Immunization Practices (ACIP) to 17 years of age also experienced fl with in uenza and for whom data increase the risk of influenza- higher than usual hospitalization rates during the 2019–2020 season. were available, 57.1% had no attributable disease severity. The impact of the anticipated SARS- recorded underlying condition, and Therefore, most (57.1%) had no 42.9% had at least 1 underlying CoV-2 cocirculation with influenza in known underlying medical medical condition; the most the 2020–2021 season is unknown at conditions. fl commonly reported underlying  this time. Elevated rates of in uenza- conditions were asthma or reactive The majority of the deaths like illness hospitalization and airway disease (19.7%), neurologic occurred in children between 2 mortality were observed toward the disorders (17.0%), and obesity through 12 years of age: 37.4% end of the 2019–2020 season, (11.9%). were 5- through 11-year-olds, suggesting the possibility of 20.9% were 2- through 4-year- comorbidity. It is, therefore, As of June 6, 2020, the following data olds, 20.3% were 12- through 17- particularly important that children were reported by the CDC: year-olds, 15.9% were 6- through are protected against influenza

Downloaded from www.aappublications.org/news by guest on October 2, 2021 4 FROM THE AMERICAN ACADEMY OF PEDIATRICS through timely vaccination in the States New Vaccine Surveillance conditions in Australia in 2018, VE of 2020–2021 influenza season. Network (NVSN), among 1653 influenza vaccine in preventing children enrolled from 7 pediatric influenza hospitalization was hospitals, the adjusted VE in children estimated to be 78.8% (95% CI, HIGH-RISK GROUPS IN PEDIATRICS with complete influenza 66.9% to 86.4%).19 In the United Children and adolescents with certain immunization against any influenza- Kingdom, during the 2018–2019 underlying medical conditions have associated hospitalization was 56% season, the overall adjusted VE a high risk of complications from (95% confidence interval [CI], 34% to against influenza-confirmed influenza (Table 2). While universal 71%), against A(H1N1)pdm09 was hospitalization was reported to be influenza vaccination is 68% (95% CI, 36% to 84%), and 53% (95% CI, 33.3% to 66.8%), with recommended for everyone starting against B viruses was 44% (95% CI, protection varying by strain. at 6 months of age, emphasis should –1% to 69%).17 A study in children Protection was 63.5% (95% CI, be placed in ensuring that people in 6 months to 8 years of age conducted 34.4% to 79.7%) against influenza high-risk groups and their household in Israel over 3 influenza seasons A(H1N1)pdm09, but there was no contacts and caregivers receive from 2015 to 2017 demonstrated that protection against influenza annual influenza vaccine. over all seasons, fully vaccinated A(H3N2).20 Finally, a systematic children had a VE against review and meta-analysis of 28 hospitalization of 53.9% (95% CI, studies conducted by Kalligeros EFFECTIVENESS OF INFLUENZA 38.6% to 68.3%), while partial et al21 concluded that influenza VACCINATION ON HOSPITALIZATION AND vaccination was not effective (25.6%; vaccine offered significant protection MORTALITY 95% CI, –3% to 47%).18 In this study, against any type of influenza-related Several studies demonstrate that a VE against hospitalization as high as hospitalization in children 6 months influenza vaccination can effectively 60% to 80% was observed when through 17 years of age, with VE of decrease hospitalization in children circulating and vaccine influenza A 57.5% (95% CI, 54.8% to 65.5%). where universal pediatric and B strains matched. After Strain-specific VE was higher for immunization has been implemented. establishing free vaccination for influenza A(H1N1)pdm09 (75.1%; In a study during the 2015–2016 preschool children and children at 95% CI, 54.8% to 93.3%) and season conducted by the United risk because of comorbid medical influenza B (50.9%; 95% CI, 41.7% to 59.9%), compared with influenza TABLE 2 People at High Risk of Influenza Complications A(H3N2) (40.8%; 95% CI, 25.6% to Children ,5 y, and especially those ,2y,a regardless of the presence of underlying medical conditions 55.9%). As expected, children who Adults $50 y, and especially those $65 y were fully vaccinated were better Children and adults with chronic pulmonary (including asthma and cystic fibrosis); hemodynamically protected (VE 61.8%; 95% CI, 54.4% fi signi cant cardiovascular disease (except hypertension alone); or renal, hepatic, hematologic to 69.1%) compared with those who (including sickle cell disease and other hemoglobinopathies), or metabolic disorders (including diabetes mellitus) were partially vaccinated (VE Children and adults with immunosuppression attributable to any cause, including that caused by 33.91%; 95% CI, 21.1% to 46.7%). medications or by HIV infection Notably, VE was higher in children Children and adults with neurologic and neurodevelopment conditions (including disorders of the younger than 5 years of age (61.7%; brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy, stroke, intellectual 95% CI, 49.3% to 74.1%) than in disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury) Children and adults with conditions that compromise respiratory function or handling of secretions children 6 to 17 years old (54.4%; (including tracheostomy and mechanical ventilation)12 95% CI, 35.1% to 73.6%). In the Women who are pregnant or postpartum during the influenza season United States, the CDC estimates that Children and adolescents ,19 y who are receiving long-term or salicylate-containing during the 2018–2019 season, medications (including those with Kawasaki disease and rheumatologic conditions) because of influenza vaccination prevented 20% increased risk of American Indian/Alaska Native peopleb of projected hospitalizations Children and adults with extreme obesity (ie, BMI [BMI] $40 for adults, and based on age for children) associated with infection with Residents of chronic care facilities and nursing homes A(H1N1)pdm09 virus among children Source: Adapted from Centers for Disease Control and Prevention. Prevention and control of seasonal influenza with 5 through 17 years, and 43% among vaccines: recommendations of the Advisory Committee on Immunization Practices—United States, 2020–21 influenza children 6 months through 4 years.22 season. MMWR Recomm Rep. 2020; in press. a The 2019–2020 CDC recommendations state: Although all children younger than 5 years old are considered at higher fl risk for complications from influenza, the highest risk is for those younger than 2 years old, with the highest hospi- Historically, up to 80% of in uenza- talization and death rates among infants younger than 6 months old. associated pediatric deaths have 13–16 b American Indian/Alaska Native (AI/AN) children have higher rate of influenza complications. Most at-risk AI/AN occurred in unvaccinated children children will also qualify in other high-risk categories to receive appropriate antiviral treatment. In the setting of fl a shortage, AI/AN children should be prioritized to receive influenza vaccine or anti-viral medications according to local 6 months and older. In uenza public health guidelines. vaccination is associated with

Downloaded from www.aappublications.org/news by guest on October 2, 2021 PEDIATRICS Volume 146, number 4, October 2020 5 reduced risk of laboratory-confirmed Committee (VRBPAC) for the formulations (Table 3). Four are egg- influenza-related pediatric death.23 In Northern Hemisphere.26 Both based (seed strains grown in eggs), one case-cohort analysis comparing influenza A(H1N1) and A(H3N2) and and one is -based (seed vaccination uptake among laboratory- the B/Victoria components are strains grown in Madin-Darby canine confirmed influenza-associated different in this season’s vaccine. The kidney cells). All inactivated egg- pediatric deaths with estimated B/Yamagata component is based vaccines (Afluria Quadrivalent, vaccination coverage among pediatric unchanged. The influenza A strains Fluarix Quadrivalent, Flulaval cohorts in the United States from are different for egg-based versus Quadrivalent, and Fluzone 2010 to 2014, Flannery et al23 found cell- or recombinant-based vaccines Quadrivalent) are licensed for that only 26% of children had this year on the basis of their optimal children 6 months and older and received vaccine before illness onset, characteristics for each platform, but available in single-dose, thimerosal- compared with an average all are matched to the strains free, prefilled syringes. The only vaccination coverage of 48%. Overall expected to circulate in the pediatric cell culture-based vaccine VE against influenza-associated death 2020–2021 season. (Flucelvax Quadrivalent) is licensed 1 in children was 65% (95% CI, 54% to 1. Quadrivalent vaccines contain: for children 4 years and older. 74%). More than half of children in a. Influenza A(H1N1) component: A quadrivalent recombinant this study who died of influenza had baculovirus-expressed hemagglutinin $1 underlying medical condition i. Egg-based vaccines: influenza vaccine (RIV4, Flublok associated with increased risk of A/Guangdong-Maonan/ Quadrivalent) is licensed only for severe influenza-related SWL1536/2019 (H1N1) people 18 years and older. A new complications; only 1 in 3 of these at- pdm09-like virus (new this quadrivalent high-dose inactivated risk children had been vaccinated; season) influenza vaccine (HD-IIV4, Fluzone yet, VE against death in children with ii. Cell- or recombinant-based High Dose Quadrivalent) containing underlying conditions was 51% (95% vaccines: A/Hawaii/70/2019 4 times the amount of for CI, 31% to 67%). Similarly, influenza (H1N1) pdm09-like virus (new each virus strain than the standard vaccination reduces by three quarters this season) dose vaccines, is licensed only for the risk of severe, life-threatening b. Influenza A(H3N2) component: people 65 years and older. A trivalent laboratory-confirmed influenza in high-dose formulation is no longer children requiring admission to the i. Egg-based vaccines: A/Hong available. Both trivalent and ICU.24 The influenza virus type might Kong/2671/2019 (H3N2)-like quadrivalent MF-59 adjuvanted also affect the severity of disease. In virus (new this season) inactivated vaccines (aIIV3 Fluad and a study of hospitalizations for ii. Cell- or recombinant-based aIIV4 Fluad Quadrivalent) are now influenza A versus B, the odds of vaccines: A/Hong Kong/45/ licensed for people 65 years and mortality were significantly greater 2019 (H3N2)-like virus (new older. The quadrivalent formulation is with influenza B than with influenza this season) new this year (licensed in February A and not entirely explained by c. B/Victoria component: 2020).1 Adjuvants may be included in underlying health conditions.25 i. All vaccines: B/Washington/02/ a vaccine to elicit a more robust 2019-like virus (B/Victoria/2/ immune response, which could lead SEASONAL INFLUENZA VACCINES 87 lineage) (new this season) to a reduction in the number of doses d. B/Yamagata component: required for children. In one pediatric The seasonal influenza vaccines study, the relative vaccine efficacy of licensed for children and adults for i. All vaccines: B/Phuket/3073/ a MF-59 adjuvanted influenza vaccine the 2020–2021 season are shown in 2013-like virus (B/Yamagata/ was significantly greater than Table 3. More than one product may 16/88 lineage) (unchanged). nonadjuvanted vaccine in the 6- be appropriate for a given patient, 2. Trivalent vaccines do not include through 23-month age group.27 and vaccination should not be the B/Yamagata component. Adjuvanted seasonal influenza delayed to obtain a specific product. vaccines are not licensed for children Inactivated Influenza Vaccine in the United States. All 2020–2021 seasonal influenza vaccines contain the same influenza For the 2020–2021 season, all Children36months(3years)and strains as recommended by the World licensed inactivated influenza older can receive any age- Health Organization (WHO) and the vaccines (IIVs) for children in the appropriate licensed IIV, US Food and Drug Administration United States are quadrivalent administered at a 0.5-mL dose (FDA)’s Vaccines and Related unadjuvanted vaccines, with specific containing 15 mg of hemagglutinin Biological Products Advisory age indications for available (HA) from each strain. Children 6

Downloaded from www.aappublications.org/news by guest on October 2, 2021 6 FROM THE AMERICAN ACADEMY OF PEDIATRICS TABLE 3 Recommended Seasonal Influenza Vaccines for Different Age Groups: United States, 2020–2021 Influenza Season Vaccine Trade Name Age Presentation Hemagglutinin Antigen Content (IIVs and Thimerosal Mercury CPT (Manufacturer) Group RIV4) or Virus Count (LAIV4) per dose for Each Antigen Content (mg Code Hg/0.5-mL dose) Quadrivalent standard dose – egg-based vaccines IIV4 Afluria Quadrivalent 6–35 0.25-mL prefilled syringea (7.5 mg/0.25 mL) 0 (Seqirus) mo $36 mo 0.5-mL prefilled syringe (15 mg/0.5 mL) 0 90686 $6 mo 5.0-mL multidose vialb (15 mg/0.5 mL) 24.5 90688 IIV4 Fluarix Quadrivalent $6 mo 0.5-mL prefilled syringe (15 mg/0.5 mL) 0 90686 (GlaxoSmithKline) IIV4 FluLaval Quadrivalent $6 mo 0.5-mL prefilled syringe (15 mg/0.5 mL) 0 90686 (GlaxoSmithKline) 90688 IIV4 Fluzone Quadrivalent $6 mo 0.5-mL prefilled syringe (15 mg/0.5 mL)c 0 90686 (Sanofi Pasteur) $6 mo 0.5-mL single-dose vial (15 mg/0.5 mL) 0 90687 $6 mo 5.0-mL multidose vialb (15 mg/0.5 mL) 25 90688 Quadrivalent standard dose – cell-based vaccines ccIIV4 Flucelvax Quadrivalent $4 y 0.5-mL prefilled syringe (15 mg/0.5 mL) 0 90674 (Seqirus) $4 y 5.0 mL multidose vial (15 mg/0.5 mL) 25 90756 Standard dose – egg-based with adjuvant vaccines aIIV3 Fluad Trivalent Seqirus $65 y 0.5-mL prefilled syringe (15 mg/0.5 mL) 0 90653 MF-59 adjuvanted aIIV4 Fluad Quadrivalent Seqirus $65 y 0.5-mL prefilled syringe (15 mg/0.5 mL) 0 90653 MF-59 adjuvanted Quadrivalent high dose – egg-based vaccine IIV4 Fluzone High-dose (Sanofi $65 y 0.7-mL prefilled syringe (60 mg/0.7 mL) 0 90662 Pasteur) Recombinant vaccine RIV4 Flublok Quadrivalent $18 y 0.5-mL prefilled syringe (45 mg/0.5 mL) 0 90682 (Sanofi Pasteur) Live attenuated vaccine LAIV4 FluMist Quadrivalent 2–49 y 0.2-mL prefilled intranasal sprayer (Virus dose: 10 6.5–7.5 0 90672 (MedImmune) FFU/0.2 mL) Data sources: Centers for Disease Control and Prevention. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP)—United States, 2020–2021 influenza season. MMWR Recomm Rep. 2020; in press. Implementation guidance on supply, pricing, payment, CPT coding, and liability issues can be found at www.aapredbook.org/implementation. (Table has been reformatted and updated). a For Afluria Quadrivalent, children 6 through 35 months of age should receive 0.25 mL per dose; people $36 months ($3 years) of age should receive 0.5 mL per dose. b For vaccines that include a multidose vial presentation a maximum of 10 doses can be drawn from a multidose vial. c The 7.5-mg/0.25-mL dosing volume is no longer available this season. through 35 months of age may immunogenicity in a single Given that different formulations of – receive any age-appropriate licensed randomized, multicenter study.28 30 IIV for children 6 through 35 months IIV without preference for one over Only the 0.5-mL Fluzone product is of age are available, care should be another. Several vaccines have been expected to be available this season. taken to administer the appropriate licensed for children 6 through In addition, 2 other vaccines, Fluarix volume and dose for each product. In 35 months of age since 2017 Quadrivalent31 and FluLaval each instance, the recommended (Table 3). All are quadrivalent, but Quadrivalent,32 are licensed for volume may be administered from an thedosevolumeand,therefore,the a 0.5-mL dose in children 6 through appropriate prefilled syringe, antigen content vary among different 35 months of age. These 2 vaccines a single-dose vial, or multidose vial, IIV products. In addition to a 0.25- do not have a 0.25-mL dose as supplied by the manufacturer. For mL (7.5 mg of HA per vaccine virus) formulation. Afluria Quadrivalent is vaccines that include a multidose vial Fluzone Quadrivalent vaccine, a 0.5- the only pediatric vaccine that has presentation, a maximum of 10 doses mL formulation of Fluzone a 0.25-mL (7.5 mg of HA per vaccine can be drawn from a multidose vial. Quadrivalent containing 15 mgofHA virus) presentation for children 6 Importantly, dose volume is different per vaccine virus per dose was through 35 months of age. Afluria from the number of doses needed to licensed in January 2019 after these Quadrivalent 0.5 mL (15 mgofHA complete vaccination. Children 2 formulations were shown to have per vaccine virus) is licensed for 6 months through 8 years of age who comparable safety and children 3 years and older only.33 require 2 doses of vaccine for the

Downloaded from www.aappublications.org/news by guest on October 2, 2021 PEDIATRICS Volume 146, number 4, October 2020 7 2020–2021 season should receive 2 Similarly, in a subsequent sentinel nonvaccine–proximate febrile separate doses at the recommended CBER/PRISM surveillance report . dose volume specified for each evaluating influenza vaccines and Thimerosal-containing vaccines are product. febrile seizures, there was no not associated with an increased risk evidence of an elevated risk of febrile Inactivated influenza vaccines are of autism spectrum disorder in seizures in children 6 through well tolerated in children and can be children. Thimerosal from vaccines 23 months of age following IIV used in healthy children as well as has not been linked to any neurologic administration during the 2013–2014 those with underlying chronic condition. The American Academy of and 2014–2015 seasons, noting that medical conditions. The most Pediatrics (AAP) supports the current the risk of seizures after PCV13 or common injection site adverse WHO recommendations for use of concomitant PCV13 and IIV was low reactions following administration of thimerosal as a preservative in compared with a child’s lifetime risk IIV in children are injection site pain, multiuse vials in the global vaccine of febrile seizures from other redness, and swelling. The most supply.39 Despite the lack of evidence causes.36 Using a self-controlled common systemic adverse events are of harm, some states have legislation interval study design, Baker et al37 drowsiness, irritability, loss of restricting the use of vaccines that further evaluated the relative risk of appetite, fatigue, muscle aches, contain even trace amounts of febrile seizures following IIV or headache, arthralgia, and thimerosal. The benefits of protecting PCV13 in children 6 through 23 gastrointestinal tract symptoms. children against the known risks of months, using the PRISM health care influenza are clear. Therefore, to the IIV can be administered claims during those same 2 influenza extent permitted by state law, concomitantly with other inactivated seasons. When the febrile rate children should receive any available or live vaccines. During the 2 was compared in a risk interval formulation of IIV rather than influenza seasons spanning (0–1 days post vaccination) versus delaying vaccination while waiting for 2010–2012, there were increased a control interval (14–20 days after reduced thimerosal-content or reports of febrile seizures in the vaccination), adjusting by age, thimerosal-free vaccines. IIV United States in young children who calendar time, and concomitant formulations that are free of even received trivalent IIV (IIV3) and the administration of the other vaccine, trace amounts of thimerosal are 13-valent pneumococcal conjugate an elevated risk of febrile seizures widely available (Table 3). vaccine (PCV13) concomitantly. was identified after vaccination with Subsequent retrospective analyses of PCV13 (incidence rate ratio [IRR], Live Attenuated (Intranasal) past seasons demonstrated a slight 1.80; 95% CI, 1.29 to 2.52), but not Influenza Vaccine increase in the risk of febrile seizures after IIV (IRR, 1.12; 95% CI, 0.80 to The intranasal live attenuated in children 6 through 23 months of 1.56). Furthermore, in a study of influenza vaccine (LAIV) was initially age when PCV13 vaccines were children 12 to 16 months of age licensed in the United States in 2003 administered concomitantly with vaccinated during the 2017–2018 for people 5 through 49 years of age IIV.34 The concomitant administration season, no difference was observed in as a trivalent formulation (LAIV3), of IIV3, PCV13, and diphtheria and the occurrence of when IIV and the approved age group was toxoids and acellular administration was delayed for extended to 2 years of age in 2007. pertussis vaccine (DTaP) was 2 weeks after PCV13 and DTaP The quadrivalent formulation (LAIV4) associated with the greatest relative vaccination (9.3%) compared with licensed in 2012 was first available risk estimate, corresponding to PCV13, DTaP and IIV given on the during the 2013–2014 influenza a maximum additional 30 febrile same day (8.1%) (adjusted risk ratio season, replacing LAIV3. The most seizure cases per 100 000 children [aRR], 0.87; 95% CI, 0.36 to 2.19).38 commonly reported reactions of LAIV vaccinated, compared with the On the basis of these findings, in children are runny nose or nasal administration of the vaccines on simultaneous administration of IIV congestion, headache, decreased separate days. In contrast, data from with PCV13 and/or other vaccines activity or lethargy, and . the Post-Licensure Rapid continues to be recommended for the Immunization Safety Monitoring 2020–2021 influenza season when The CDC conducted a systematic (PRISM) program of the FDA, these vaccines are indicated. Overall, review of published studies revealed that there was no significant the benefits of timely vaccination evaluating the effectiveness of LAIV3 increase in febrile seizures associated with same-day administration of IIV and LAIV4 in children from the with concomitant administration of and PCV13 or DTaP outweigh the risk 2010–2011 to the 2016–2017 these 3 vaccines in children 6 through of febrile seizures. Vaccine-proximate influenza seasons, including data 59 months of age during the febrile seizures rarely have any long- from United States and European 2010–2011 influenza season.35 term sequelae, similar to studies.40 The data suggested that the

Downloaded from www.aappublications.org/news by guest on October 2, 2021 8 FROM THE AMERICAN ACADEMY OF PEDIATRICS effectiveness of LAIV3 or LAIV4 for (ie, healthy, without any underlying (95% CI, –18% to 51%) for children 9 influenza A(H1N1)pdm09 strain was chronic medical condition). through 17 years and for A(H3N2) lower than that of IIV in children 2 24% (95% CI, 1% to 42%) in children through 17 years of age. LAIV was In February 2019, the AAP 6 months through 8 years of age, and similarly effective against influenza B Committee of Infectious Diseases 3% (95% CI, –30% to 28%) in and A/H3N2 strains in some age (COID) reviewed available data on children 9 through 17 years of age.43 groups compared with IIV. LAIV was influenza epidemiology and vaccine Direct comparisons cannot be made not recommended by the CDC or AAP effectiveness for the 2018–2019 given differences in reporting of VE for use in children during the season and agreed that harmonizing for various age groups. Other 2016–2017 and 2017–2018 seasons, recommendations between the AAP countries that use LAIV (Canada, given concerns about its effectiveness and CDC for the use of LAIV in the Finland) have not reported LAIV4- – against A(H1N1)pdm09. For the 2019 2020 season was appropriate. specific VE in past several seasons. 2017–2018 season, a new A(H1N1) After the February 2020 ACIP Small case numbers and low LAIV use pdm09-like virus strain (A/Slovenia/ meeting, the AAP COID reviewed may also limit accurate VE 2903/2015) was included in LAIV4, available epidemiologic and calculations in these countries. In replacing the prior A/Bolivia/559/ effectiveness data for the previous general, as long as use of LAIV is low fi 2013 strain. A study conducted by the and current seasons to inform relative to IIV, it will be dif cult to – LAIV4 manufacturer evaluated viral recommendations for the 2020 2021 estimate LAIV VE accurately. shedding and immunogenicity season. Despite the early circulation Furthermore, important variability in associated with the LAIV4 of A(H1N1)pdm09 during the VE against all strains is reported for 2018–2019 season and its formulation containing the new both IIV and LAIV. predominance during the 2019–2020 A(H1N1) pdm09-like virus among US Influenza VE varies from season to season, low utilization of LAIV4 in the children 24 to 48 months of age.41 season and is affected by many United States population has limited Shedding and immunogenicity data factors, including age and health the evaluation of product-specific suggested that the new influenza status of the recipient, influenza type vaccine effectiveness, and no A(H1N1)pdm09-like virus included in and subtype, existing immunity from additional US data on LAIV4 VE are its latest formulation had improved previous infection or vaccination, and available. Although the proportion of replicative fitness over previous degree of antigenic match between LAIV used for vaccination is LAIV4 influenza A(H1N1)pdm09-like vaccine and circulating virus strains. unknown, interim overall VE (not vaccine strains, resulting in an It is possible that VE also differs specific to a type of vaccine) for the improved immune response, among individual vaccine products; 2019–2020 influenza season shows however, product-specific comparable with that of the LAIV3 reassuring protection in children comparative effectiveness data are available prior to the 2009 pandemic. against circulating influenza A and B fi lacking for most vaccines. Additional Shedding and replicative tness are strains (Table 1).6 Furthermore, fi experience over multiple influenza not known to correlate with ef cacy, influenza vaccine coverage rates in seasons will help to determine and no published effectiveness children are stable.9 In European optimal utilization of the available estimates for this revised formulation surveillance networks where fl vaccine formulations in children. The of the vaccine against in uenza A(/ uninterrupted utilization of LAIV has AAP will continue to monitor annual H1N1)pdm09 viruses were available continued from the 2016–2017 – influenza surveillance and VE reports prior to the start of the 2018 2019 through the 2019–2020 seasons, the to update influenza vaccine influenza season, because influenza only country with LAIV VE estimates, recommendations if necessary. A(/H3N2) and influenza B viruses the United Kingdom, reported final predominated during the 2017–2018 VE against medically attended Northern Hemisphere season. influenza for the 2018–2019 season CONTRAINDICATIONS AND PRECAUTIONS Therefore, for the 2018–2019 in children 2 through 17 years of age influenza season, the AAP of 49.9% (95% CI, –14.3% to 78.0%) Anaphylactic reactions to any vaccine recommended IIV4 or IIV3 as the for A(H1N1)pdm09 and of 27.1% are considered a contraindication to primary choice for influenza (95% CI, –130.5% to 77%) for vaccination. The AAP recommends vaccination in children, with LAIV4 A(H3N2).42 The final adjusted VE in that children who have had an allergic use reserved for children who would the United States (where mostly IIV reaction after a previous dose of any not otherwise receive an influenza was used) for 2018–2019 against influenza vaccine should be evaluated vaccine and for whom LAIV A(H1N1)pdm09 was 59% (95% CI, by an allergist to determine whether utilization was appropriate for age 47% to 69%) for children 6 months future receipt of the vaccine is (2 years and older) and health status through 8 years of age but only 24% appropriate. Similarly, consultation

Downloaded from www.aappublications.org/news by guest on October 2, 2021 PEDIATRICS Volume 146, number 4, October 2020 9 with an infectious disease specialist after influenza infection. The benefits People in Whom LAIV is may be sought to assess potential of influenza vaccination might Contraindicated contraindications and precautions outweigh the risks for certain people  Children younger than 2 years. and to determine which influenza who have a history of GBS  Children 2 through 4 years of age vaccine is most appropriate to ensure (particularly if not associated with with a diagnosis of asthma or immunization in special prior influenza vaccination) and who history of recurrent wheezing or circumstances. also are at high risk for severe a medically attended wheezing complications from influenza. Minor illnesses, with or without fever, episode in the previous 12 months are not contraindications to the use of Specific precautions for LAIV include because of the potential for fl in uenza vaccines, including among a diagnosis of asthma in children increased wheezing after children with mild upper respiratory 5 years and older and the presence of immunization. In this age range, infection symptoms or allergic certain chronic underlying medical many children have a history of . In children with a moderate conditions, including metabolic wheezing with respiratory tract to severe febrile illness (eg, high disease, diabetes mellitus, other illnesses and are eventually fever, active infection, requiring chronic disorders of the pulmonary or diagnosed with asthma. hospitalization, etc), on the basis of cardiovascular systems, renal  Children with new cochlear the judgment of the clinician, dysfunction, or hemoglobinopathies. implants or active cerebrospinal vaccination should be deferred until Although the safety of LAIV has not fluid leaks. resolution of the illness. Children with fi been de nitely established in these  Children who have a known or confirmed COVID-19 can receive situations, IIV can be considered. In suspected primary or acquired influenza vaccine when the acute a study comparing a large cohort of immunodeficiency or who are illness has resolved. Children with an children 2 through 17 years old with amount of that receiving immunosuppressive or asthma who received LAIV instead of immunomodulatory . would notably impede vaccine IIV under established practice  Children with anatomic or delivery into the nasopharyngeal guidelines from 2007 to 2016, the functional asplenia, including from mucosa should have LAIV vaccination occurrence of asthma exacerbation deferred until resolution. within 21 to 42 days of vaccination sickle cell disease.  Close contacts and caregivers of A precaution for vaccination is was not higher compared with 44 those who are severely a condition in a recipient that might children who received IIV. In immunocompromised and require increase the risk or seriousness of a prospective open-label phase IV a protected environment. a possible vaccine-related adverse study conducted in the United reaction. A precaution also may exist Kingdom, 478 children aged 2 to  Children and adolescents receiving for conditions that might 18 years with physician-diagnosed aspirin or salicylate-containing compromise the ability of the host to asthma or recurrent wheezing medications. fi develop immunity after vaccination. received LAIV, with no signi cant  Children who have received other Vaccination may be recommended change in asthma symptoms or live-virus vaccines within the inthepresenceofaprecautionif exacerbation in the 4 weeks after previous 4 weeks (except for vaccination.45 However, 14.7% of the benefit of protection from rotavirus vaccine); however, LAIV patients eventually reported a severe the vaccine outweighs the can be administered on the same asthma exacerbation after potential risks. day with other live-virus vaccines vaccination, requiring treatment. In if necessary. History of Guillain-Barré syndrome post-licensure surveillance of LAIV  fl (GBS) following influenza vaccine is (including LAIV3 and LAIV4), the Children taking an in uenza considered a precaution for the Vaccine Adverse Event Reporting antiviral medication and until administration of influenza vaccines. System (VAERS), jointly sponsored by 48 hours (oseltamivir, ) GBS is rare, especially in children, the FDA and CDC, has not identified and up to 2 weeks (peramivir and and there is a lack of evidence on any new or unexpected safety baloxavir) after stopping the fl risk of GBS following influenza concerns, including in people with in uenza antiviral therapy. If vaccine in children. Nonetheless, a contraindication or precaution a child recently received LAIV but regardless of age, a history of GBS (https://www.cdc.gov/vaccinesafety/ has an influenza illness for which less than 6 weeks after a previous ensuringsafety/monitoring/vaers/). antiviral agents are appropriate, dose of influenza vaccine is the antiviral agents should be a precaution for administration of People who should not receive LAIV given. If antiviral agents are influenza vaccine. GBS may occur are listed below. necessary for treatment within 5

Downloaded from www.aappublications.org/news by guest on October 2, 2021 10 FROM THE AMERICAN ACADEMY OF PEDIATRICS to 7 days of LAIV immunization, for a systemic allergic reaction than confirmed influenza hospitalization in reimmunization is indicated those without egg allergy. Therefore, the first few months of life.56 because of the potential effects of precautions such as choice of antiviral medications on LAIV a particular vaccine, special It is safe to administer inactivated replication and immunogenicity. observation periods, or restriction of influenza vaccine to pregnant women  Pregnant women. administration to particular medical during any trimester of gestation and settings are not warranted and postpartum. Any licensed, LAIV and Immunocompromised Hosts constitute an unnecessary barrier to recommended, and age-appropriate influenza vaccine may be used, The inactivated influenza vaccine is immunization. It is not necessary to although experience with the use of the vaccine of choice for anyone in inquire about egg allergy before the fl RIV4 in pregnant women is limited. close contact with a subset of administration of any in uenza LAIV is contraindicated during severely immunocompromised vaccine, including on screening forms. pregnancy. Data on the safety of people (ie, those in a protected Routine prevaccination questions influenza vaccination at any time environment). IIV is preferred over regarding after receipt of during pregnancy continues to LAIV for contacts of severely any vaccine are appropriate. Standard support the safety of influenza immunocompromised people because vaccination practice for all vaccines in immunization during of a theoretical risk of infection children should include the ability to pregnancy.48,50–55,59 In a 5-year attributable to LAIV strain in an respond to rare acute retrospective cohort study from 2003 immunocompromised contact of an hypersensitivity reactions. Children to 2008 with more than 10 000 LAIV-immunized person. Available who have had a previous allergic fl women, influenza vaccination in the data indicate a very low risk of reaction to the in uenza vaccine first trimester was not associated transmission of the virus from both should be evaluated by an allergist to determine whether future receipt of with an increase in the rates of major children and adults vaccinated with 60 LAIV. Health care personnel (HCP) the vaccine is appropriate. congenital malformations. Similarly, immunized with LAIV may continue a and meta- to work in most units of a hospital, analysis of studies of congenital INFLUENZA VACCINES DURING anomalies after vaccination during including the NICU and general PREGNANCY AND BREASTFEEDING oncology ward, using standard pregnancy, including data from 15 fl infection control techniques. As In uenza vaccine is recommended by studies (14 cohort studies and 1 case- a precautionary measure, people the ACIP, the American College of control study) did not show any recently vaccinated with LAIV should Obstetrics and Gynecology (ACOG), association between congenital fl restrict contact with severely and the American Academy of Family defects and in uenza vaccination in Physicians (AAFP) for all women, any trimester, including the first immunocompromised patients for 61 7 days after immunization, although during any trimester of gestation, for trimester of gestation. Assessments fl there have been no reports of LAIV the protection of mothers against of any association with in uenza fl 1,48 transmission from a vaccinated in uenza and its complications. vaccination and preterm birth and person to an immunocompromised Substantial evidence has accumulated small-for-gestational-age infants have fi person. In the theoretical scenario in regarding the ef cacy of maternal yielded inconsistent results, with fl which symptomatic LAIV infection in uenza immunization in preventing most studies reporting a protective laboratory-confirmed influenza effect or no association against these develops in an immunocompromised 62,63 host, LAIV strains are susceptible to disease and its complications in both outcomes. A cohort study from fi antiviral medications. mothers and their infants in the rst the Vaccines and Medications in 2 to 6 months of life.48–53 Pregnant Pregnancy Surveillance System women who are immunized against (VAMPSS) of vaccine exposure during INFLUENZA VACCINES AND EGG influenza at any time during their the 2010–2011 through 2013–2014 ALLERGY pregnancy provide protection to their influenza seasons found no significant There is strong evidence that egg- infants during their first 6 months of association of spontaneous abortion allergic individuals can safely receive life, when they are too young to with influenza vaccine exposure in influenza vaccine without any receive influenza vaccine themselves, the first trimester or within the first additional precautions beyond those through transplacental passage of 20 weeks of gestation.64 One recommended for any vaccine.46,47 .50–58 Infants born to observational Vaccine Safety Datalink The presence of egg allergy in an women who receive influenza (VSD) study conducted during the individual is not a contraindication to vaccination during pregnancy can 2010–2011 and 2011–2012 influenza receive IIV or LAIV. Vaccine recipients have a risk reduction of up to 72% seasons indicated an association with egg allergy are at no greater risk (95% CI, 39% to 87%) for laboratory- between receipt of IIV containing

Downloaded from www.aappublications.org/news by guest on October 2, 2021 PEDIATRICS Volume 146, number 4, October 2020 11 H1N1pdm09 and risk of spontaneous does not recommend use of baloxavir not an aerosol-generating procedure; abortion, when an H1N1pdm-09- for treatment of pregnant women or however, vaccine administrators are containing vaccine had also been breastfeeding mothers. There are no advised to wear gloves when injecting received the previous season.65 A available efficacy or safety data in LAIV given the potential to coming in follow-up study conducted by the pregnant women, and there are no contact with respiratory secretions. same investigators with a larger available data on the presence of Gloves used for intranasal or population and stricter outcome baloxavir in human milk, the effects intramuscular vaccine administration measures did not show this on the breastfed infant, or the effects should be changed with every patient. association and further supported the on milk production. Gowns are not required. safety of influenza vaccine during pregnancy.66 Inactivated Influenza Vaccines VACCINE STORAGE AND Women in the postpartum period ADMINISTRATION IIVs for intramuscular (IM) injection who did not receive influenza are shipped and stored at 2°C to 8°C The AAP Storage and Handling Tip vaccination during pregnancy should (36°F–46°F); vaccines that are Sheet provides resources for practices be encouraged to discuss with their inadvertently frozen should not be to develop comprehensive vaccine obstetrician, family physician, nurse used. These vaccines are management protocols to keep the midwife, or other trusted provider administered intramuscularly into the temperature for vaccine storage receiving influenza vaccine before anterolateral thigh of infants and constant during a power failure or discharge from the hospital. young children and into the deltoid other disaster (https://www.aap.org/ Vaccination during breastfeeding is muscle of older children and adults. en-us/Documents/immunization_ safe for mothers and their infants. Given that various IIVs are available, disasterplanning.pdf). The AAP careful attention should be used to Breastfeeding is strongly recommends the development of ensure that each product is used recommended to protect infants a written disaster plan for all practice according its approved age indication, against influenza viruses by activating settings. Additional information is dosing, and volume of administration innate antiviral mechanisms, available (www.aap.org/disasters). (Table 3). A 0.5-mL unit dose of any specifically type 1 . Human During the COVID-19 pandemic, the IIV should not be split into 2 separate milk from mothers vaccinated during AAP recommends that influenza 0.25-mL doses. If a lower dose than the third trimester also contains vaccine administration follow CDC recommended is inadvertently higher levels of influenza-specific guidance for administration of administered to a child 36 months or immunoglobulin A (IgA).67 Greater immunizations (https://www.cdc. older (eg, 0.25 mL), an additional exclusivity of breastfeeding in the gov/vaccines/pandemic-guidance/ 0.25-mL dose should be administered first 6 months of life decreases the index.html). Vaccination in the to provide a full dose of 0.5 mL as episodes of respiratory illness with medical home is ideal to ensure that soon as possible. The total number of fever in infants of vaccinated pediatric patients receive other full doses appropriate for age should mothers. For infants born to mothers vaccinations and routine care in be administered. If a child is with confirmed influenza illness at a timely manner and receive catch-up inadvertently vaccinated with delivery, breastfeeding is encouraged, immunizations if delays have a formulation only approved for and guidance on breastfeeding occurred because of the pandemic. In adults, the dose should be counted practices can be found at https:// general, infection-prevention as valid. www.cdc.gov/breastfeeding/ measures should be in place for all breastfeeding-special-circumstances/ patient encounters, including Live Attenuated Influenza Vaccine maternal-or-infant-illnesses/ screening for symptoms, physical influenza.html and https://www.cdc. distancing, respiratory and hand The cold-adapted, temperature- gov/flu/professionals/ hygiene, and surface sensitive LAIV4 formulation is infectioncontrol/peri-post-settings. decontamination. In addition to shipped and stored at 2°C to 8°C htm. Breastfeeding should be standard precautions and hand (35°F–46°F) and administered encouraged even if the mother or hygiene, during the COVID-19 intranasally in a prefilled, single-use infant has influenza illness. The pandemic, it is recommended that sprayer containing 0.2 mL of vaccine. mother should pump and feed vaccine administrators wear A removable dose-divider clip is expressed milk if she or her infant are a surgical face mask (not N95 or attached to the sprayer to facilitate too sick to breastfeed. If the respiratory) at all times and eye administration of 0.1 mL separately breastfeeding mother requires protection if the level of community into each nostril. If the child sneezes antiviral agents, treatment with oral spread is moderate or elevated. immediately after administration, the oseltamivir is preferred. The CDC Administration of LAIV intranasally is dose should not be repeated.

Downloaded from www.aappublications.org/news by guest on October 2, 2021 12 FROM THE AMERICAN ACADEMY OF PEDIATRICS VACCINE DOSING RECOMMENDATIONS  Children 6 months through total doses of any trivalent or fl The number of seasonal influenza 8 years of age: quadrivalent in uenza vaccine (IIV or LAIV) before July 1, 2020. vaccine doses recommended for ○ Need 2 doses if they have The 2 previous doses do not children during the 2020–2021 received fewer than 2 doses of need to have been received influenza season depends on the any trivalent or quadrivalent during the same influenza child’sageatthetimeofthefirst influenza vaccine (IIV or LAIV) season or consecutive influenza administered dose and vaccine history. before July 1, 2020, or if their seasons. The recommendations are unchanged vaccination status is unknown. from previous years, as shown in Fig 2. The interval between the 2 doses  Influenza vaccines are not licensed should be at least 4 weeks. Two TIMING OF VACCINATION AND for administration to infants doses should be administered to DURATION OF PROTECTION younger than 6 months and children who receive their first Although peak influenza activity in should not be used in this dose before their ninth birthday, the United States tends to occur from age group. even if their ninth birthday January through March, influenza can  occurs during the same season. Children 9 years and older need circulate from early fall (October) to ○ only 1 dose, regardless of previous Require only 1 dose if they have late spring (May), with one or more vaccination history. previously received 2 or more disease peaks. Predicting the onset and duration or the severity of the influenza season with accuracy is impossible. It is also challenging to balance public health strategies needed to achieve high vaccination coverage with achieving optimal individual immunity for protection against influenza at the peak of seasonal activity, knowing that the duration of immunity after vaccination can wane over time. Initiation of influenza vaccination before influenza is circulating in the community and continuing to vaccinate throughout the influenza season are important components of an effective influenza vaccination strategy, particularly this season, when circulation of SARS-CoV-2 is expected to continue.

Complete influenza vaccination by the end of October is recommended by the CDC and AAP. Children who need 2 doses of vaccine should receive their first dose as soon as possible when vaccine becomes available, to allow sufficient time for receipt of the second dose $4 weeks after the first, before the onset of the influenza season. Children who require only 1 dose of influenza vaccine should also FIGURE 2 ideally be vaccinated by end of Number of 2020–2021 seasonal influenza vaccine doses for children based on age and prior October; however, recent data (mostly vaccination history. * The 2 doses need not have been received during the same season or con- secutive seasons. † Administer 2 doses based on age at receipt of the first dose of influenza vaccine in adults) suggests that very early during the season. Children who receive the first dose before their ninth birthday should receive 2 vaccination (July or August) might be doses, even if they turn 9 years old during the same season. associated with suboptimal immunity

Downloaded from www.aappublications.org/news by guest on October 2, 2021 PEDIATRICS Volume 146, number 4, October 2020 13 before the end of the influenza administration of influenza vaccine Web site – promoting vaccinations season. should not be delayed to a later date, and providing resources for because this increases the likelihood pediatricians to communicate with Although the evidence is limited in of missing influenza vaccination patients, families, and the children, recent reports raise the altogether.81 Providers may continue communities they serve (https:// possibility that early vaccination to offer vaccine until June 30th of www.aap.org/en-us/about-the-aap/ might contribute to reduced each year when the seasonal aap-press-room/campaigns/ protection later in the influenza – influenza vaccine expires, because the immunizations/Pages/default.aspx season.68 79 In these studies, vaccine duration of influenza circulation is and https://www.aap.org/en-us/ effectiveness decreased within unpredictable. Furthermore, a person advocacy-and-policy/aap-health- a single influenza season, and this may experience more than one initiatives/immunizations/Influenza- decrease was correlated with influenza infection during a given Implementation-Guidance/Pages/ increasing time after vaccination. season because of the various Patient-Family-and-Community.aspx). However, this decay in VE was not cocirculating strains. Although consistent across different age groups influenza activity in the United States Pediatricians and other pediatric and varied by season and virus is typically low during the summer, health care providers should plan to subtypes. In some studies, waning VE influenza cases and outbreaks can make influenza vaccine easily was more evident among older adults occur, particularly among accessible for all children. Examples and younger children71,73 and with international travelers, who may be include sending alerts to families that influenza A(H3N2) viruses more than exposed to influenza year-round, vaccine is available (eg, e-mails, texts, influenza A(H1N1) or B depending on destination. letters, patient portals, practice- viruses.72,75,77 A multiseason analysis specific websites, or social media from the US Influenza Vaccine platforms); creating walk-in influenza Effectiveness Network found that VE VACCINE IMPLEMENTATION vaccination clinics; extending hours declined by approximately 7% per beyond routine times during peak month for influenza A (H3N2) and The AAP Partnership for Policy vaccination periods; administering influenza B and by 6% to 11% per Implementation has developed influenza vaccine during both well month for influenza A (H1N1)pdm09 a series of definitions using accepted child examinations and sick visits as in individuals 9 years and older.70 VE health information technology well as in hospitalized patients, remained greater than 0 for at least 5 standards to assist in the especially those at high risk of to 6 months after vaccination. A more implementation of vaccine influenza complications, before recent study including children older recommendations in computer hospital discharge (unless medically than 2 years also found evidence of systems and quality measurement contraindicated); implementing declining vaccine effectiveness with efforts. This document is available at standing orders for influenza an odds ratio increasing www2.aap.org/informatics/PPI.html. vaccination; considering how to approximately 16% with each In addition, the AAP has developed immunize parents, adult caregivers, additional 28 days from vaccine implementation guidance on supply, and siblings (see risk management administration.80 In another study payment, coding, and liability issues; guidance associated with adult evaluating VE from the 2011–2012 these documents can be found at immunizations at http://pediatrics. through the 2013–2014 influenza www.aapredbook.org/ aappublications.org/content/129/1/ seasons demonstrated 54% to 67% implementation. e247) at the same time as children; protection from 0 to 180 days after HCP, influenza campaign organizers, and working with other institutions vaccination.74 Finally, a multiseason and public health agencies are (eg, schools, child care programs, study in Europe from 2011–2012 encouraged to collaborate to develop local public health departments, and through 2014–2015 showed a steady improved strategies for planning, religious organizations) or alternative decline in VE down to 0% protection distribution, communication, and care sites, such as pharmacies and by 111 days after vaccination.75 administration of vaccines. For hospital emergency departments, to Further evaluation is needed before example, pediatricians can play a key expand venues for administering any policy change in timing of role in educating and assisting early vaccine. If a child receives influenza influenza administration is made. An childhood education centers and vaccine outside of his or her medical early onset of the influenza season is schools in educating parents on the home, such as at a pharmacy, retail- a concern when considering delaying importance of influenza based clinic, or another practice vaccination. Until there are definitive immunization. Resources for effective setting, appropriate documentation of data that determine whether waning communication and messaging vaccination should be provided to the immunity influences VE in children, strategies are available on the AAP patient to be shared with his or her

Downloaded from www.aappublications.org/news by guest on October 2, 2021 14 FROM THE AMERICAN ACADEMY OF PEDIATRICS medical home and entered into the which is consistent with the national hcp/admin/mass-clinic-activities/i state or regional immunization Healthy People 2020 target for annual ndex.html?deliveryName=USCDC_7_ information system (ie, registry). influenza vaccination among HCP. 3-DM33813). It is important that Vaccine coverage among HCP was annual delivery of influenza vaccine Concerted efforts among the 81.1% during the 2018–2019 season, to primary care medical homes aforementioned groups, plus vaccine up from 78.4% the previous year.82 should be timely to avoid missed manufacturers, distributors, and Influenza vaccination programs for opportunities. If alternate venues, payers, are necessary to prioritize HCP benefit the health of employees, including pharmacies and other distribution appropriately to the their patients, and members of the retail-based clinics, are used for fi primary care of ce setting and community, especially because HCP vaccination, a system of patient patient-centered medical home frequently come into contact with record transfer is crucial to maintain before other venues, especially when patients at high risk of influenza the accuracy of immunization vaccine supplies are delayed or illness in their clinical settings. records. Immunization information limited. Payers should eliminate Mandatory influenza immunization systems should be used whenever “ ” remaining patient responsibility for all HCP is considered to be ethical, available and prioritized to document fl cost barriers to in uenza vaccine just, and necessary to improve patient influenza vaccination. Two- where they still exist. Similar efforts safety. For the prevention and control dimensional barcodes have been used should be made to eliminate the of influenza, HCP must prioritize the to facilitate more efficient and vaccine supply discrepancy between health and safety of their patients, accurate documentation of vaccine privately insured patients and those honor the requirement of causing no administration with limited eligible for vaccination through the harm, and act as role models for both experience to date. Additional Vaccines for Children (VFC) program. their patients and colleagues by information concerning current American Indian/Alaska Native receiving influenza vaccination vaccines shipped with 2-dimensional children, who are eligible for vaccines annually. barcodes can be found at www.cdc. through the VFC program, are at gov/vaccines/programs/iis/2d- fl higher risk for in uenza vaccine-barcodes/. complications and should be COVERAGE prioritized in a vaccine shortage Children’s likelihood of being fl (Table 2). Although national in uenza immunized according to vaccination coverage among children recommendations appears to be Population health can benefitfrom has not declined in the past several associated with the immunization pediatricians’ discussions about seasons, overall vaccination coverage practices of their parents. One study vaccine safety and effectiveness. remains suboptimal (Fig 1). Achieving found that children were 2.77 times Pediatricians and their office staff can high coverage rates of influenza (95% CI, 2.74 to 2.79) more likely to influence vaccine acceptance by vaccine in infants and children is be immunized against seasonal explaining the importance of annual a priority to protect them against influenza if their parents were influenza vaccination for children and influenza disease and its immunized.49 When parents who emphasizing when a second dose of complications. Timely influenza were previously not immunized had vaccine is indicated. The AAP and vaccination is particularly important received immunization for seasonal CDC have created communication during the 2020–2021 influenza influenza, their children were resources to convey these important season, given the concurrent SARS- 5.44 times (95% CI, 5.35 to 5.53) messages and to help the public CoV-2 pandemic. more likely to receive influenza understand influenza vaccine. recommendations. Resources will be The AAP and CDC recommend fi available on Red Book Online (https:// vaccine administration at any visit to Pediatric of ces may choose to serve fl redbook.solutions.aap.org/selfserve/ the medical home before and during as a venue for providing in uenza fl ssPage.aspx?SelfServeContentId= in uenza season when it is not vaccination for parents and other care influenza-resources). contraindicated, at specially arranged providers of children, if the practice is vaccine-only sessions, and through acceptable to both pediatricians and The AAP supports mandatory cooperation with community sites, the adults who are to be vaccinated. influenza vaccination programs for all schools, and Head Start and child care Medical liability and payment issues HCP in all settings, including facilities to provide influenza vaccine. along with medical record outpatient settings. Optimal The CDC has developed guidance for documentation requirements need to prevention of influenza in the health the planning of vaccination clinics be considered before a pediatrician care setting depends on the during the COVID-19 pandemic begins immunizing adults (see risk vaccination of at least 90% of HCP, (https://www.cdc.gov/vaccines/ management guidance associated

Downloaded from www.aappublications.org/news by guest on October 2, 2021 PEDIATRICS Volume 146, number 4, October 2020 15 with adult immunizations at http:// htm). The AAP offers “What’sthe season, at the dose indicated for pediatrics.aappublications.org/ Latest with the Flu” messages to the vaccine. No product is content/129/1/e247). Pediatric highlight those details most relevant preferred over another for this practices should be aware of payment for AAP members and child care age group. Children 36 months (3 implications including nonpayment providers on a monthly basis during years) and older should receive or having the parent inappropriately influenza season (https://www.aap. a 0.5-mL dose of any available, attributed by a payer as a patient of org/en-us/advocacy-and-policy/aap- licensed, age-appropriate the pediatrician’soffice. The AAP health-initiatives/Pages/What’s-the- inactivated vaccine. supports efforts to overcome these Latest-with-the-Flu.aspx). 5. The number of seasonal influenza payment barriers with insurance vaccine doses recommended to fl payers to maximize in uenza be administered to children in immunization rates. To avoid errors INFLUENZA VACCINATION – fl RECOMMENDATIONS the 2020 2021 in uenza season in claims processing and payment remains unchanged and depends and in the exchange of immunization 1. The AAP recommends annual on the child’s age at the time of data, pediatricians are reminded that influenza vaccination for the first administered dose and parents should have their own basic everyone 6 months and older, vaccine history (Fig 2). fl medical record, where their in uenza including children and 6. Children 6 months through vaccination should be documented. adolescents, during the 8 years of age who are receiving Adults should be encouraged to have – fl 2020 2021 in uenza season. fl fi a medical home and communicate in uenza vaccine for the rst 2. For the 2020–2021 influenza their vaccination status to their time or who have received only 1 season, the AAP recommends primary care provider. Offering adult dose, before July 1, 2020, or that any licensed influenza vaccinations in the pediatric practice whose vaccination status is vaccine appropriate for age and setting should not undermine the unknown should receive 2 doses health status can be used for fl adult medical home model. of in uenza vaccine, ideally by influenza vaccination in children. Vaccination of close contacts of the end of October, and vaccines Inactivated influenza vaccine children at high risk of influenza- should be offered as soon as they (IIV) and live attenuated vaccine related complications (Table 2) is become available. Children (LAIV) are options for children intended to reduce children’s risk of needing only 1 dose of influenza for whom these vaccines are exposure to influenza (ie, vaccine, regardless of age, should appropriate. This “cocooning”). The practice of also receive vaccination, ideally recommendation is based on cocooning also may help protect by the end of October. review of current available data infants younger than 6 months who 7. Efforts should be made to ensure on LAIV and IIV vaccine efficacy are too young to be immunized with vaccination for children in high- (VE). The AAP will continue to influenza vaccine. risk groups (Table 2) and their review VE data as they become contacts, unless contraindicated. available and update these SURVEILLANCE recommendations if necessary. 8. Product-specific contraindications must be Information about influenza 3. The AAP does not have fl considered when selecting the surveillance is available through the a preference for any in uenza vaccine product over another for type of vaccine to administer. CDC Voice Information System Children who have had an (influenza update at 1-800-232-4636) children who have no fl allergic reaction after a previous or at www.cdc.gov/flu/index.htm. contraindication to in uenza dose of any influenza vaccine Although current influenza season vaccination and for whom more should be evaluated by an data on circulating strains do not than one licensed product allergist to determine whether necessarily predict which and in what appropriate for age and health future receipt of the vaccine is proportion strains will circulate in the status is available. Pediatricians appropriate. subsequent season, it is instructive to should administer whichever be aware of 2019–2020 influenza formulation is available in their 9. Children with egg allergy can fl surveillance data and use them as communities to achieve the receive in uenza vaccine without a guide to empirical therapy until highest possible coverage this any additional precautions fl current seasonal data are available in uenza season. beyond those recommended for from the CDC. Information is posted 4. Children 6 through 35 months of all vaccines. weekly on the CDC Web site (www. age may receive any licensed, 10. Pregnant women may receive cdc.gov/flu/weekly/fluactivitysurv. age-appropriate IIV available this inactivated influenza vaccine at

Downloaded from www.aappublications.org/news by guest on October 2, 2021 16 FROM THE AMERICAN ACADEMY OF PEDIATRICS any time during pregnancy, to treatment of acute uncomplicated treatment administration in relation protect themselves and their influenza in nonhospitalized children to the onset of illness, and the child’s infants, who benefit from the 2 years and older who have been age and health status as important transplacental transfer of symptomatic for no more than 2 days. variables. A review of 6 antibodies. Women in the The efficacy of peramivir in patients RCTs involving treatment of 2356 postpartum period who did not with serious influenza requiring children with clinically diagnosed receive vaccination during hospitalization has not been influenza, of whom 1255 had pregnancy should be encouraged established.83 IV zanamivir is not laboratory-confirmed influenza, to receive influenza vaccine approved in the United States and has showed that in children with before discharge from the not been available for compassionate laboratory-confirmed influenza, oral hospital. Influenza vaccination use since the 2017–2018 season.68,69 oseltamivir and inhaled zanamivir during breastfeeding is safe for The FDA-licensed reduced median duration of illness by mothers and their infants. in 2018 for the early treatment of 36 hours (26%; P , .001) and fl , 11. The AAP supports mandatory uncomplicated in uenza in 1.3 days (24%, P .001), 89 vaccination of health care outpatients 12 years and older who respectively. Among the studies personnel as a crucial element in have been ill for no more than 2 reviewed, 1 trial of oseltamivir in 84 preventing influenza and days. This antiviral agent for children with asthma who had fl fi fl reducing health care-associated in uenza has a different mechanism laboratory-con rmed in uenza fi influenza infections, because of action (cap-endonuclease showed only a nonsigni cant health care personnel often care inhibitor) than NAIs and requires reduction in illness duration (10.4 for individuals at high risk for only a single oral dose for treatment hours; 8%; P = .542). Oseltamivir fl fi influenza-related complications. of uncomplicated in uenza. A clinical signi cantly reduced acute otitis trial of baloxavir treatment of media in children 1 through 5 years influenza in hospitalized patients of age with laboratory-confirmed INFLUENZA ANTIVIRALS 12 years and older is ongoing influenza (risk difference [RD], –0.14; – – 89 Antiviral agents available for both (https://clinicaltrials.gov/ct2/show/ 95% CI, 0.24 to 0.04). Another influenza treatment and NCT03684044?cond=baloxavir&ra Cochrane review of RCTs in adults chemoprophylaxis in children of all nk=6). and children, which included 20 ages can be found in Table 4 oseltamivir (9623 participants) and 26 zanamivir trials (14 628 (including doses for preterm infants 86 that have not been evaluated by the participants), found no effect of FDA) and on the CDC Web site (www. Randomized controlled trials (RCTs) oseltamivir in reducing the duration cdc.gov/flu/professionals/antivirals/ conducted to date to evaluate the of illness in asthmatic children, but in fi fl index.htm). These include the ef cacy of in uenza antiviral otherwise healthy children, there was inhibitors (NAIs) medications among outpatients with a reduction by a mean difference of fl (oseltamivir, zanamivir, peramivir) uncomplicated in uenza have found 29 hours (95% CI, 12 to 47 hours; P = fi and a selective inhibitor of influenza that timely treatment can reduce the .001). No signi cant effect was duration of influenza symptoms and observed with zanamivir. Regarding cap-dependent endonuclease 85–89 (baloxavir), all of which have activity fever in pediatric populations. complications, this review did not fi fi against influenza A and B viruses.83 Observational studies in pediatric and nd a signi cant effect of NAIs on adult populations suggest that reducing hospitalizations, , Oral oseltamivir remains the antiviral antiviral agents could reduce the risk bronchitis, , or in drug of choice for the management of of certain influenza complications, children.86 More recently, a meta- illness caused by influenza virus including hospitalization and analysis of 5 new RCTs that included – infections. Although more difficult to death.90 93 The number of published 1598 children with laboratory- administer, inhaled zanamivir RCTs in children is limited, and confirmed influenza showed that (Relenza) is an equally acceptable interpretation of the results of these treatment with oseltamivir alternative for patients who do not studies needs to take into significantly reduced the duration of have chronic respiratory disease. consideration the size of the study illness in this population by 17.6 Options are limited for children who (the number of events might not be hours (95% CI, –34.7 to –0.62 cannot absorb orally or enterally sufficient to assess specific outcomes hours).87 When children with asthma administered oseltamivir or tolerate in small studies), the variations in the were excluded, this difference was inhaled zanamivir. Intravenous (IV) case definition of influenza illness larger (–29.9 hours; 95% CI, –53.9 to peramivir (Rapivab), a third NAI, was (clinically diagnosed versus –5.8 hours). The risk of otitis media approved in September 2017 as laboratory confirmed), the time of was 34% lower in this group as well.

Downloaded from www.aappublications.org/news by guest on October 2, 2021 PEDIATRICS Volume 146, number 4, October 2020 17 TABLE 4 Recommended Dosage and Schedule of Influenza Antiviral Medications for Treatment and Chemoprophylaxis in Children for the 2020–2021 Influenza Season: United States Medication Treatment (5 Days) Chemoprophylaxis (10 Days)a Oseltamivirb Adults 75 mg, twice daily 75 mg, once daily Children $12 mo (based on body wt) #15 kg (#33 lb) 30 mg, twice daily 30 mg, once daily .15 kg–23 kg (33 lb–51 lb) 45 mg, twice daily 45 mg, once daily .23 kg–40 kg (.51 lb–88 lb) 60 mg, twice daily 60 mg, once daily .40 kg (.88 lb) 75 mg, twice daily 75 mg, once daily Infants 9–11 moc 3.5 mg/kg per dose, twice daily 3.5 mg/kg per dose, once daily Term infants 0–8moc 3 mg/kg per dose, twice daily 3 mg/kg per dose, once daily for infants 3–8mo Not recommended for infants ,3 mo old because of limited safety and efficacy data in this age group Preterm infantsd ,38 wks’ postmenstrual age 1.0 mg/kg per dose, twice daily 38 through 40 wks’ 1.5 mg/kg per dose, twice daily postmenstrual age .40 wks’ postmenstrual age 3.0 mg/kg per dose, twice daily Zanamivire Adults 10 mg (two 5-mg inhalations), twice daily 10 mg (two 5-mg inhalations), once daily Children 10 mg (two 5-mg inhalations), twice daily 10 mg (two 5-mg inhalations), once daily $7 y for treatment $5 y for chemoprophylaxis Peramivir Adults One 600-mg intravenous infusion, given over Not recommended 15–30 min Children (2–12 y) One 12 mg/kg dose, up to 600 mg maximum, via Not recommended intravenous infusion for 15–30 min Children (13–17 y) One 600 mg dose, via intravenous infusion for Not recommended 15–30 min Baloxavir People $12 y who weigh more 40–80 kg: one 40-mg dose, orally Not recommended than 40 kg $80 kg: one 80-mg dose, orally Sources: 2018 IDSA Guidelines78 and https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm. a CDC recommends for 7 days, and 10 days only if part of institutional outbreak (https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm). b Oseltamivir is administered orally without regard to meals, although administration with meals may improve gastrointestinal tolerability. Oseltamivir is available as Tamiflu in 30-, 45-, and 75-mg capsules and as a powder for oral suspension that is reconstituted to provide a final concentration of 6 mg/mL. For the 6-mg/mL suspension, a 30-mg dose is given with 5 mL of oral suspension, a 45-mg dose is given with 7.5 mL oral suspension, a 60-mg dose is given with 10 mL oral suspension, and a 75-mg dose is given with 12.5 mL oral suspension. If the commercially manufactured oral suspension is not available, a suspension can be compounded by retail pharmacies (final concentration also 6 mg/mL), based on instructions contained in the package label. In patients with renal insufficiency, the dose should be adjusted on the basis of creatinine clearance. For treatment of patients with creatinine clearance 10–30 mL/ min: 75 mg, once daily, for 5 days. For chemoprophylaxis of patients with creatinine clearance 10–30 mL/min: 30 mg, once daily, for 10 days after exposure or 75 mg, once every other day, for 10 days after exposure (5 doses). See https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm and IDSA Guidelines.83 c Approved by the FDA for children as young as 2 weeks of age. Given preliminary pharmacokinetic data and limited safety data, oseltamivir can be used to treat influenza in both term and preterm infants from birth because benefits of therapy are likely to outweigh possible risks of treatment. Of note, the CDC recommends a 3 mg/kg/dose, twice daily, for all infants ,12 months old; the IDSA guidelines83 include both AAP and CDC recommendations. d Oseltamivir dosing for preterm infants. The weight-based dosing recommendation for preterm infants is lower than for term infants. Preterm infants may have lower clearance of oseltamivir because of immature renal function, and doses recommended for full-term infants may lead to very high drug concentrations in this age group. Limited data from the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group provides the basis for dosing preterm infants using their postmenstrual age (gestational age 1 chronologic age). For extremely preterm infants (,28 wk), please consult a pediatric infectious disease physician. e Zanamivir is administered by inhalation using a proprietary “Diskhaler” device distributed together with the medication. Zanamivir is a dry powder, not an aerosol, and should not be administered using nebulizers, ventilators, or other devices typically used for administering medications in aerosolized solutions. Zanamivir is not recommended for people with chronic respiratory diseases, such as asthma or chronic obstructive pulmonary disease, which increase the risk of bronchospasm.

Overall, efficacy outcomes are best harms should be considered when hospitalized patients or pediatric demonstrated in patients with making decisions about the use of patients with comorbidities have not laboratory confirmed influenza. All NAIs for either treatment or been conducted, and prospectively these studies confirmed as chemoprophylaxis of influenza. collected data to determine the role of an occasional adverse effect of antiviral agents in treating severe oseltamivir, occurring in Although prospective comparative influenza are limited, on the basis of approximately 5% of treated patients. studies to determine the efficacy of information obtained from The balance between benefits and influenza antiviral medications in retrospective observational studies

Downloaded from www.aappublications.org/news by guest on October 2, 2021 18 FROM THE AMERICAN ACADEMY OF PEDIATRICS and meta-analyses conducted to date benefit exists for double-dose NAI ANTIVIRAL TREATMENT AND INFLUENZA in both adults and children, most therapy on reduction of mortality or TESTING CONSIDERATIONS experts support the use of antiviral virologic clearance, compared with Clinical judgment (on the basis of medications as soon as possible to standard-dose therapy, on the basis underlying conditions, disease treat pediatric patients with severe of a recent systematic review and severity, time since symptom onset, fl in uenza, including hospitalized meta-analysis of 10 published and local influenza activity) is an 88,90–94 98 patients. An observational studies (4 RCT and 6 observational important factor in treatment epidemiologic study conducted in studies) involving 20 947 adult and decisions for pediatric patients who adult patients hospitalized with pediatric patients. present with influenza-like illness. fi severe laboratory-con rmed Antiviral treatment should be started fl fl in uenza in Spain over 6 in uenza Children younger than 2 years are at as soon as possible after illness onset – seasons (2010 2016) evaluated the an increased risk of hospitalization and should not be delayed while effectiveness of NAIs, concluding that and complications attributable to waiting for a definitive influenza test fl when started early after the onset of in uenza. The FDA has approved result, because early therapy provides # # symptoms ( 48 hours or 5 days), oseltamivir for treatment of children the best outcomes. Influenza NAI treatment was associated with as young as 2 weeks. Given diagnostic tests vary by method, fl a reduction in in uenza-associated preliminary pharmacokinetic data availability, processing time, deaths (adjusted odds ratio [aOR], and limited safety data, the CDC and sensitivity, and cost (Table 5), all of 0.37; 95% CI, 0.22 to 0.63; and aOR, AAP support the use of oseltamivir to which should be considered in fl 0.50; 95% CI, 0.32 to 0.79, treat in uenza in both term and making the best clinical decision. 90 respectively). However, treatment preterm infants from birth, because Positive and negative predictive fi initiation more than 5 days after the bene ts of therapy of neonatal values of influenza test results are fl onset of influenza symptoms was not in uenza are likely to outweigh influenced by the level of influenza associated with reduction in mortality possible risks of treatment. activity in the population being in hospitalized adults. tested, the characteristics of a test Oseltamivir is available in capsule compared with a gold standard, Importantly, and despite limited and oral suspension formulations. pretest probability, whether the evidence from prospectively The available capsule doses are 30, influenza virus is actively replicating conducted trials, treatment with 45, and 75 mg, and the commercially in the person, proper collection and oseltamivir for children with serious, manufactured liquid formulation has transport of specimens, and proper complicated, or progressive disease a concentration of 6 mg/mL in a 60- test procedures. Testing should be fi presumptively or de nitively caused mL bottle. If the commercially performed when timely results will fl by in uenza, irrespective of manufactured oral suspension is not be available to influence clinical fl in uenza vaccination status (the available, the capsule may be opened management or infection control circulating strains may not be well and the contents mixed with simple measures. Given the similarities in matched with vaccine strains) or syrup or Ora-Sweet SF (sugar free) clinical presentation, testing for fi whether illness began greater than by retail pharmacies to a nal influenza and for SARS-CoV-2 48 hours before admission, is concentration of 6 mg/mL. infection should be offered to patients recommended by the AAP, CDC, with a febrile respiratory illness or Infectious Diseases Society of In adverse event data collected influenza-like illness. America (IDSA),83 and Pediatric systematically in prospective trials, Infectious Diseases Society (PIDS). vomiting was the only adverse effect Although decisions on treatment and Earlier treatment provides better reported more often with oseltamivir infection control can be made on the clinical responses. However, compared with placebo when studied basis of positive rapid influenza treatment after 48 hours of in children 1 through 12 years of age diagnostic test (RIDT) results, symptoms in adults and children (ie, 15% of treated children versus negative results should not always be with moderate to severe disease or 9% receiving placebo). In addition, used in a similar fashion because of with progressive disease has been following reports from Japan of the suboptimal sensitivity and shown to provide some benefitand oseltamivir-attributable potential for false-negative results. An – should be offered.95 97 In neuropsychiatric adverse effects, updated list of RIDTs is available at: a retrospective study of 653 PICU a review of controlled https://www.cdc.gov/flu/ admissions from 2009 to 2012, the data and ongoing surveillance has professionals/diagnosis/table-ridt. estimated risk of death was reduced failed to establish a link between this html. Positive results of RIDTs are in NAI treated cases (OR 0.36, 95% drug and neurologic or psychiatric helpful, because they may reduce CI: 0.16 to 0.83).95 No additional events.99,100 additional testing to identify

Downloaded from www.aappublications.org/news by guest on October 2, 2021 PEDIATRICS Volume 146, number 4, October 2020 19 TABLE 5 Comparison of Types of Influenza Diagnostic Tests Testing Category Method Influenza Viruses Detected Distinguishes Influenza Time to Performance A Virus Subtypes Results Rapid molecular assay Nucleic acid Influenza A or B viral RNA No 15–30 min High sensitivity; high specificity amplification Rapid influenza diagnostic test Antigen detection Influenza A or B virus No 10–15 min Low to moderate sensitivity (higher with analyzer devise); high specificity Direct and indirect Antigen detection Influenza A or B virus antigens No 1–4 h Moderate sensitivity; high immunofluorescence specificity assays Molecular assays (including Nucleic acid Influenza A or B viral RNA Yes, if subtype primers 1–8 h High sensitivity; high specificity RT-PCR) amplification are used Multiplex molecular assays Nucleic acid Influenza A or B viral RNA, Yes, if subtype primers 1–2 h High sensitivity; high specificity amplification other viral or bacterial are used targets (RNA or DNA) Rapid cell culture (shell vial Virus isolation Influenza A or B virus Yes 1–3 d High sensitivity; high specificity and cell mixtures) Viral culture (tissue cell Virus isolation Influenza A or B virus Yes 3–10 d High sensitivity; high specificity culture) 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 (.95%) for all tests compared with reverse transcriptase-polymerase chain reaction (RT-PCR). FDA-cleared rapid influenza diagnostic tests are CLIA-waived; most FDA-cleared rapid influenza molecular assays are CLIA-waived, depending on the specimen. Source: Uyeki.83 alternative causes of the child’s treatment with antiviral medications INFLUENZA CHEMOPROPHYLAXIS fl in uenza-like illness, provide the (Table 2). Efforts should be made to Randomized placebo-controlled opportunity for early antiviral minimize treatment of patients who studies showed that oral oseltamivir fl treatment, promote appropriate are not infected with in uenza. and inhaled zanamivir were stewardship, and allow Otherwise healthy children who have efficacious when administered as fl the timely implementation of suspected in uenza with an chemoprophylaxis to household appropriate strategies to prevent uncomplicated presentation should contacts after a family member had transmission. Available FDA- 83 be considered for antiviral laboratory-confirmed influenza. approved rapid molecular assays medication, particularly if they are in There are no data on IV peramivir or based on nucleic acid detection are contact with other children who oral baloxavir for chemoprophylaxis. highly sensitive and specific either are younger than 6 months (as Decisions on whether to administer diagnostic tests that can provide fl they are not able to receive in uenza antiviral chemoprophylaxis should rapid results. An updated list of vaccine) or have high-risk conditions take into account the exposed these tests is available here: https:// (including age ,5 years) that person’s risk of influenza www.cdc.gov/flu/professionals/ predispose them to complications of complications, vaccination status, the diagnosis/table-nucleic-acid- influenza, when influenza viruses are type and duration of contact, detection.html. Molecular assays are known to be circulating in the recommendations from local or preferred in hospitalized patients, community. If there is a local public health authorities, and clinical because they are more sensitive shortage of antiviral medications, judgment. Optimally, postexposure compared with antigen detection. local public health authorities should chemoprophylaxis should only be Early detection, prompt antiviral be consulted to provide additional used when antiviral agents can be treatment, and infection control guidance about testing and started within 48 hours of exposure; interventions can lead to improved treatment. In previous years, local the lower once-daily dosing for individual patient outcomes and shortages of oseltamivir suspension chemoprophylaxis with oral allow for effective cohorting and have occurred because of uneven disease containment. This oseltamivir or inhaled zanamivir drug distribution, although national containment strategy is particularly should not be used for treatment of shortages have not occurred since fl relevant during the SARS-CoV-2 children symptomatic with in uenza. 2009, particularly given the pandemic. Early, full treatment doses (rather availability of the capsule than chemoprophylaxis doses) should People with suspected influenza who formulation that can be made into be used in high-risk symptomatic are at higher risk of influenza a suspension for young children if patients without waiting for complications should be offered needed (Table 4). laboratory confirmation.

Downloaded from www.aappublications.org/news by guest on October 2, 2021 20 FROM THE AMERICAN ACADEMY OF PEDIATRICS Chemoprophylaxis should not be surveillance for resistance among guidance. Oseltamivir (oral), considered a substitute for circulating influenza viruses is zanamivir (inhaled), peramivir (IV), vaccination. Influenza vaccine should ongoing in Japan and the United and baloxavir (oral) are FDA- – always be offered before and States.106 108 In contrast, high levels approved for treatment of throughout the influenza season of resistance to and uncomplicated influenza virus when not contraindicated. Antiviral persist among the infection in pediatric outpatients; medications are important adjuncts influenza A viruses currently published data exist to support the to influenza vaccination for control circulating. medications use of oseltamivir (oral) for and prevention of influenza disease. are not recommended for use against hospitalized and children at high risk. Toxicities may be associated with influenza unless resistance patterns For more serious influenza virus antiviral agents, and indiscriminate change.83 infections, particularly in immune use might limit availability. Viral surveillance and resistance data compromised children, seeking the Pediatricians should inform from the CDC and WHO indicate that advice of an infectious diseases recipients of antiviral the majority of currently circulating specialist is suggested. chemoprophylaxis that risk of influenza viruses likely to cause influenza is lowered but still remains influenza in North America during the ANTIVIRAL TREATMENT while taking the medication, and 2020–2021 influenza season continue fl RECOMMENDATIONS susceptibility to in uenza returns to be susceptible to oseltamivir, fl when medication is discontinued. zanamivir, peramivir, and baloxavir Regardless of in uenza vaccination Oseltamivir use is not (https://www.cdc.gov/flu/weekly/). status, antiviral treatment should be a contraindication to vaccination with If a newly emergent oseltamivir- or offered as early as possible to: IIV, although LAIV effectiveness will peramivir-resistant virus is a concern,  Any hospitalized child with be decreased for the child receiving fi fl 83 recommendations for alternative suspected or con rmed in uenza oseltamivir. No data are available on treatment will be available from the disease, regardless of duration of the impact of inhaled zanamivir, IV CDC and AAP. Resistance symptoms. peramivir or oral baloxavir on characteristics can change for an  effectiveness of LAIV, but it is likely Any child, inpatient or outpatient, individual patient over the duration with severe, complicated, or that all antiviral agents will have of a treatment course, especially in some impact on effectiveness of LAIV. progressive illness attributable to those who are severely influenza, regardless of duration of Among some high-risk people, both immunocompromised. Up-to-date symptoms. vaccination with IIV and antiviral information on current  Influenza virus infection of any chemoprophylaxis may be recommendations and therapeutic severity in children at high risk of considered. Updates will be available options can be found on the AAP Web fl complications of influenza, as at www.aapredbook.org/ u and site (www.aap.org or www. fl listed in Table 2, regardless of www.cdc.gov/ u/professionals/ aapredbook.org/flu), through state- duration of symptoms. antivirals/index.htm. specific AAP chapter websites, or on the CDC Web site (www.cdc.gov/ Antiviral treatment may be ANTIVIRAL RESISTANCE flu/). considered for the following individuals: Antiviral resistance to any drug can INFLUENZA ANTIVIRALS  emerge, necessitating continuous Any previously healthy, RECOMMENDATIONS population-based assessment that is symptomatic outpatient not at fl conducted by the CDC. During the Treatment recommendations for high risk for in uenza 2019–2020 season, .99% of antiviral medications for the complications in whom an fl fi influenza A(/H1N1)pdm09 and 2020–2021 influenza season are in uenza diagnosis is con rmed B/Victoria viruses tested were applicable to infants and children or suspected on the basis of susceptible to oseltamivir, peramivir, with suspected influenza when clinical judgment, if treatment can and zanamivir, and all were influenza viruses are known to be be initiated within 48 hours of susceptible to baloxavir. All tested circulating in the community, or when illness onset. influenza A(H3N2) and B/Yamagata infants or children are tested and  Children with suspected or viruses were susceptible to these confirmed to have influenza. confirmed influenza disease antiviral agents. Decreased Continuous monitoring of the whose siblings or household susceptibility to baloxavir has been epidemiology, change in severity, and contacts either are younger than reported in Japan, where utilization resistance patterns of influenza virus 6 months or have a high-risk has been more common,101–105 and strains by CDC may lead to new condition that predisposes them

Downloaded from www.aappublications.org/news by guest on October 2, 2021 PEDIATRICS Volume 146, number 4, October 2020 21 to complications of influenza as  As postexposure antiviral the potential role of previous listed in Table 2. chemoprophylaxis for family influenza vaccination on overall members and close contacts of an vaccine effectiveness, and vaccine Shared informed decision making infected person if those people are effectiveness by vaccine formulation, between providers and parents/ at high risk of complications from virus strain, timing of vaccination, legally authorized caregivers is influenza. and subject age and health status, in encouraged to initiate therapy and preventing outpatient medical visits,  For children at high risk of monitor children for safety and hospitalizations, and deaths continue complications and their family efficacy while receiving antiviral to be evaluated. For the 2020–2021 members and close contacts, as agents. Efforts should be made to influenza season, it will be well as for HCP, when circulating minimize treatment of patients who particularly important to understand strains of influenza virus in the are not infected with influenza the effect of SARS-CoV-2 and community are not well matched viruses. influenza virus cocirculation on the by seasonal influenza vaccine epidemiology and morbidity of virus strains, on the basis of influenza in the pediatric population. current data from the CDC and Understanding how to better educate state or local health departments. ANTIVIRAL CHEMOPROPHYLAXIS parents about influenza symptoms RECOMMENDATIONS These recommendations apply to and how to recognize when to seek Although vaccination is the preferred routine circumstances, but it should medical attention would be approach to prevention of infection, be noted that guidance may change informative. Additionally, with limited chemoprophylaxis during an on the basis of updated data on the use of antiviral agents in influenza season is recommended in recommendations from the CDC in hospitalized children and in children the following situations: concert with antiviral availability, with underlying medical conditions, local resources, clinical judgment, prospective clinical trials to inform  For children at high risk of recommendations from local or optimal timing and efficacy of complications from influenza for public health authorities, risk of antiviral treatment in these whom influenza vaccine is influenza complications, type and populations are warranted. This is contraindicated.  duration of exposure contact, and particularly relevant as new antiviral For children at high risk during change in epidemiology (resistance, agents or new indications for existing fl the 2 weeks after IIV in uenza antigenic shift) or severity of antiviral agents become available. At vaccination, before optimal influenza. Children who have higher this time, the FDA has accepted immunity is achieved. Prophylaxis rates of influenza complications, supplemental new drug applications after LAIV may decrease vaccine including American Indian/Alaska for baloxavir marboxil. One fi ef cacy. Native children, should be prioritized application concerns the treatment of  For family members or HCP who to receive influenza antiviral agents in acute, uncomplicated influenza in are unvaccinated and are likely to the setting of a shortage according to pediatric patients from 1 year of age have ongoing, close exposure to: local public health guidelines through 12 years of age. Another ○ unvaccinated children at high (Table 2). Chemoprophylaxis is not application addresses the use of risk; or routinely recommended for infants baloxavir marboxil for postexposure younger than 3 months given limited prophylaxis (https://www.biospace. ○ unvaccinated infants and safety and efficacy data in this com/article/releases/fda-accepts- toddlers who are younger than age group. -s-new-drug-application- 24 months. for-xofluza-for-the-treatment-of-  fl For control of in uenza outbreaks influenza-in-children-/). for unvaccinated staff and children FUTURE DIRECTIONS in a closed institutional setting Safety and effectiveness data for There is also a need for more with children at high risk (eg, influenza vaccines used during the systematic health services research extended-care facilities). 2020–2021 influenza season will be on influenza vaccine uptake and  As a supplement to IIV vaccination analyzed as they become available refusal as well as identification of among children at high risk, and reported by CDC as they are each methods to enhance uptake. Further including children who are season. Continued evaluation of the investigation is needed about vaccine immunocompromised and may safety, immunogenicity, and acceptance and hesitancy and not respond with sufficient effectiveness of influenza vaccines, methods to overcome parental protective immune responses especially for at risk populations, is concerns and improve coverage. This following influenza vaccination. important. The duration of protection, may include evaluating the strategy of

Downloaded from www.aappublications.org/news by guest on October 2, 2021 22 FROM THE AMERICAN ACADEMY OF PEDIATRICS offering to immunize parents and establishment of immunity against 3. The AAP does not have adult child care providers in the influenza in early life and the a preference for any influenza pediatric office setting and development of a safe, immunogenic vaccine product over another for understanding the level of family vaccine for infants younger than children who have no contact satisfaction with this 6 months are essential. Studies on the contraindication to influenza approach; how practices handle the effectiveness and safety of influenza vaccination and for whom more logistic, liability, legal, and financial vaccines containing adjuvants that than one licensed product barriers that limit or complicate this enhance immune responses to appropriate for age and health service; and most importantly, how influenza vaccines or that use novel status is available. Pediatricians this practice may affect disease rates routes of administration are needed. should administer whichever in children and adults. Furthermore, Efforts to improve the vaccine formulation is available in their ongoing efforts should include development process to allow for communities to achieve the broader implementation and a shorter interval between highest possible coverage this evaluation of mandatory HCP identification of vaccine strains and influenza season. vaccination programs in both vaccine production continue. New 4. Children 6 through 35 months of inpatient and outpatient settings. antiviral drugs are in various age may receive any licensed, development phases, given the age-appropriate IIV available this Efforts should be made to create need to improve options for the season, at the dose indicated for adequate outreach (eg, mobile treatment and chemoprophylaxis the vaccine. No product is integrated health care) and fl of in uenza. preferred over another for this infrastructure to facilitate the optimal age group. Children 36 months (3 distribution of vaccine so that more Pediatricians can remain informed of years) and older should receive people are immunized. Given the advances and other updates during a 0.5-mL dose of any available, experience with COVID-19, the influenza season by following the licensed, age-appropriate pediatricians should become more CDC Influenza page (www.cdc/gov/ inactivated vaccine. involved in pandemic preparedness flu) and the AAP Red Book Online and disaster planning efforts. A Influenza Resource Page (www. 5. The number of seasonal influenza bidirectional partner dialogue aapredbook.org/flu). vaccine doses recommended between pediatricians and public to be administered to children health decision makers assists efforts in the 2020–2021 influenza SUMMARY OF RECOMMENDATIONS to address children’s issues during season remains unchanged and ’ the initial state, regional, and local 1. The AAP recommends annual depends on the child s age at fi plan development stages. Additional influenza vaccination for the time of the rst administered information can be found at www. everyone 6 months and older, dose and vaccine history aap.org/disasters/resourcekit and including children and (Fig 2). https://pediatrics.aappublications. adolescents, during the 6. Children 6 months through org/content/pediatrics/early/2017/ 2020–2021 influenza season. 8 years of age who are receiving fl fi 05/11/peds.2016-3690.full.pdf. 2. For the 2020–2021 influenza in uenza vaccine for the rst time or who have received only 1 Access to care issues, lack of season, the AAP recommends fl dose, before July 1, 2020, or immunization records, and questions that any licensed in uenza whose vaccination status is regarding who can provide consent vaccine appropriate for age and unknown, should receive 2 doses may be addressed by linking children health status can be used for fl of influenza vaccine, ideally by (eg, those in foster care/juvenile in uenza vaccination in children. fl the end of October, and vaccines justice system or refugee, immigrant, Inactivated in uenza vaccine should be offered as soon as they or homeless children) with a medical (IIV) and live attenuated vaccine become available. Children home, using all health care (LAIV) are options for children needing only 1 dose of influenza encounters as vaccination for whom these vaccines are vaccine, regardless of age, should opportunities, and more consistently appropriate. This also receive vaccination, ideally using immunization registry data. recommendation is based on review of current available data by the end of October. Development efforts continue for on LAIV and IIV vaccine efficacy 7. Efforts should be made to ensure universal influenza vaccines that (VE). The AAP will continue to vaccination for children in high- induce broader protection and review VE data as they become risk groups (Table 2) and eliminate the need for annual available and update these their contacts, unless vaccination. Understanding the recommendations if necessary. contraindicated.

Downloaded from www.aappublications.org/news by guest on October 2, 2021 PEDIATRICS Volume 146, number 4, October 2020 23 8. Product-specific the child is treated within for whom influenza vaccine is contraindications must be 48 hours of symptom onset, contraindicated. considered when selecting the antiviral therapy should still be  For children at high risk type of vaccine to administer. considered beyond 48 hours of during the 2 weeks after Children who have had an symptom onset in children with influenza vaccination, before allergic reaction after a previous severe disease or those at high optimal immunity is achieved. dose of any influenza vaccine risk of complications.  For family members or HCP should be evaluated by an 13. Antiviral treatment should be who are unvaccinated and are allergist to determine whether offered as early as possible to the likely to have ongoing, close future receipt of the vaccine is following individuals, regardless exposure to: appropriate. of influenza vaccination status: ○ unvaccinated children at high 9. Children with egg allergy can  Any hospitalized child with risk; or receive influenza vaccine without suspected or confirmed any additional precautions ○ unvaccinated infants and influenza disease, regardless beyond those recommended for toddlers who are younger than of duration of symptoms. all vaccines. 24 months.  Any child, inpatient or 10. Pregnant women may receive  For control of influenza outpatient, with severe, inactivated influenza vaccine at outbreaks for unvaccinated complicated, or progressive any time during pregnancy, to staff and children in a closed illness attributable to protect themselves and their institutional setting with influenza, regardless of infants, who benefit from the children at high risk (eg, duration of symptoms. transplacental transfer of extended-care facilities).  fl antibodies. Women in the In uenza infection of any  As a supplement to postpartum period who did not severity in children at high vaccination among children at receive vaccination during risk of complications of high risk, including children fl pregnancy should be encouraged in uenza infection (Table 2), who are to receive influenza vaccine regardless of duration of immunocompromised and before discharge from the symptoms. may not respond with hospital. Influenza vaccination 14. Treatment may be considered for sufficient protective immune during breastfeeding is safe for the following individuals: responses following influenza mothers and their infants.  Any previously healthy, vaccination. 11. The AAP supports mandatory symptomatic outpatient not at  As postexposure antiviral vaccination of health care high risk for influenza chemoprophylaxis for family personnel as a crucial element in complications in whom members and close contacts fl preventing in uenza and influenza is confirmed or of an infected person if those reducing health care-associated suspected on the basis of people are at high risk of fl in uenza infections, because clinical judgment, if treatment complications from influenza. health care personnel often care can be initiated within  For children at high risk of for individuals at high risk for 48 hours of illness onset. complications and their family influenza-related complications.  Children with suspected or members and close contacts, 12. Antiviral medications are confirmed influenza disease as well as HCP, when fl important in the control of whose siblings or household circulating strains of in uenza fl in uenza but are not a substitute contacts either are younger virus in the community are fl for in uenza vaccination. than 6 months or have a high- not well matched by seasonal fl Pediatricians should promptly risk condition that predisposes in uenza vaccine virus identify their patients suspected them to complications of strains, on the basis of current fl of having in uenza infection for influenza (Table 2). data from the CDC and state timely initiation of antiviral or local health departments. treatment, when indicated and 15. Antiviral chemoprophylaxis is based on shared decision making recommended after known or fl ADDITIONAL RESOURCES between the pediatrician and suspected exposure in uenza in child’s caregiver, to reduce the following situations: Lessin HR; Edwards KM; American morbidity and mortality. Although  For children at high risk of Academy of Pediatrics, Committee best results are observed when complications from influenza on Practice and Ambulatory

Downloaded from www.aappublications.org/news by guest on October 2, 2021 24 FROM THE AMERICAN ACADEMY OF PEDIATRICS Medicine, Committee on Infectious Grove Village, IL: American STAFF Diseases. Immunizing parents and Academy of Pediatrics; 2018: Jennifer M. Frantz, MPH other close family contacts in the 476–489. Available at: http:// pediatric office setting. Pediatrics. aapredbook.aappublications.org/flu. 2012;129(1):e247. ABBREVIATIONS American Academy of Pediatrics, COMMITTEE ON INFECTIOUS DISEASES, AAP: American Academy of Committee on Infectious Diseases. 2019–2020 Pediatrics fl Policy statement: In uenza Yvonne A. Maldonado, MD, FAAP, WHO: World Health Organization immunization for all health care Chairperson ACIP: Advisory Committee on ’ personnel: keep it mandatory. Sean T. O Leary, MD, MPH, FAAP, Vice Immunization Practices Pediatrics. 2015;136(4):809-818. Chairperson Ritu Banerjee, MD, PhD, FAAP ANE: acute necrotizing American Academy of Pediatrics, Elizabeth D. Barnett, MD, FAAP encephalopathy Committee on Pediatric Emergency James D. Campbell, MD, MS, FAAP ccIIV4: quadrivalent cell culture- Medicine. Preparation for Mary T. Caserta, MD, FAAP based inactivated influenza emergencies in the offices of Jeffrey S. Gerber, MD, PhD, FAAP vaccine Athena P. Kourtis, MD, PhD, MPH, FAAP pediatricians and pediatric primary Ruth Lynfield, MD, FAAP CDC: Centers for Disease Control care providers. Pediatrics. 2007; Flor M. Munoz, MD, MSc, FAAP and Prevention 120(1):200-212. Reaffirmed Dawn Nolt, MD, MPH, FAAP FDA: US Food and Drug June 2011. Ann-Christine Nyquist, MD, MSPH, FAAP Administration ’ Sean T. O Leary, MD, MPH, FAAP GBS: Guillain-Barré syndrome American Academy of Pediatrics, William J. Steinbach, MD, FAAP Committee on Practice and Kenneth M. Zangwill, MD, FAAP HA: hemagglutinin Ambulatory Medicine, AAP Theoklis E. Zaoutis, MD, MSCE, FAAP HCP: health care personnel fl Committee on Infectious Diseases, IAE: in uenza-associated AAP Committee on State encephalopathy EX OFFICIO fl Government Affairs, AAP Council IIV: inactivated in uenza vaccine David W. Kimberlin, MD, FAAP – Red Book IIV3: trivalent inactivated on School Health, AAP Section on Editor influenza vaccine Administration and Practice Mark H. Sawyer, MD, FAAP – Red Book IIV4: quadrivalent inactivated Management. Medical Versus Associate Editor – influenza vaccine Nonmedical Immunization Henry H. Bernstein, DO, MHCM, FAAP Red Book Online Associate Editor IM: intramuscular Exemptions for Child Care and H. Cody Meissner, MD, FAAP – Visual Red LAIV4: quadrivalent live School Attendance. Pediatrics. Book Associate Editor attenuated influenza vaccine 2016;138(3):e20162145. NAIs: neuraminidase inhibitors Edwards KM, Hackell JM; American LIAISONS PCR: polymerase chain reaction Academy of Pediatrics, Committee Amanda C. Cohn, MD, FAAP, Centers for PCV13: 13-valent pneumococcal on Infectious Diseases, Committee Disease Control and Prevention conjugate vaccine on Practice and Ambulatory Karen M. Farizo, MD, US Food and Drug RIV4: quadrivalent recombinant Medicine. Countering vaccine Administration influenza vaccine Marc Fischer, MD, FAAP, Centers for Disease hesitancy. Pediatrics. 2016;138(3): SARS-CoV-2: severe acute e20162146. Control and Prevention Natasha B. Halasa, MD, MPH, FAAP, Pediatric respiratory syndrome- American Academy of Pediatrics, Infectious Diseases Society coronavirus 2 Committee on Pediatric Emergency Nicole Le Saux, MD, FRCP(C), Canadian VE: vaccine effectiveness Medicine; American Academy of Paediatric Society Eduardo Lopez, MD, Sociedad Pediatrics Committee on Medical Latinoamericana de Infectologia Pediatrica Liability; Task Force on Terrorism. Scot B. Moore, MD, FAAP, Committee on The pediatrician and disaster Practice Ambulatory Medicine REFERENCES preparedness. Pediatrics. 2006; Neil S. Silverman, MD, American College of 117(2):560-565. Reaffirmed Obstetricians and Gynecologists 1. Grohskopf LA, Alyanak E, Broder KR, Judith Steinberg, MD, HHS Office of Infectious September 2013. et al. Prevention and control of Disease and HIV/AIDS Policy seasonal influenza with vaccines: Jeffrey R. Starke, MD, FAAP, American American Academy of Pediatrics. recommendations of the Advisory Influenza. In: Kimberlin DW, Brady Thoracic Society James J. Stevermer, MD, MSPH, FAAFP, Committee on Immunization Practices, MT, Jackson MA, Long SS, eds. Red American Academy of Family Physicians United States, 2020–21 influenza Book: 2018 Report of the Committee Kay M. Tomashek, MD, MPH, DTM, National season. MMWR Recomm Rep. 2020; on Infectious Diseases. 31st ed. Elk Institutes of Health 69(RR-8):1–24

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