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, 2019–2020 COMMITTEE ON INFECTIOUS DISEASES

This statement updates the recommendations of the American Academy of abstract Pediatrics for the routine use of influenza vaccines and antiviral medications in the prevention and treatment of influenza in children during the 2019–2020 season. The American Academy of Pediatrics continues to recommend routine influenza immunization of all children without medical contraindications, starting at 6 months of age. Any licensed, recommended, age-appropriate vaccine available can be administered, without preference of one product or formulation over another. Antiviral treatment of influenza with any licensed, recommended, age-appropriate influenza antiviral medication continues to be recommended for children with suspected or confirmed influenza, particularly Policy statements from the American Academy of Pediatrics benefit those who are hospitalized, have severe or progressive disease, or have from expertise and resources of liaisons and internal (AAP) and fl external reviewers. However, policy statements from the American underlying conditions that increase their risk of complications of in uenza. Academy of Pediatrics may not reflect the views of the liaisons or the organizations or government agencies that they represent.

The guidance in this statement does not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate. – fl The following updates for the 2019 2020 in uenza season are discussed All policy statements from the American Academy of Pediatrics in this document: automatically expire 5 years after publication unless reaffirmed, revised, or retired at or before that time. 1. Both inactivated influenza vaccine (IIV) and live attenuated influenza This document is copyrighted and is property of the American vaccine (LAIV) are options for influenza vaccination in children, with no Academy of Pediatrics and its Board of Directors. All authors have filed preference. conflict of interest statements with the American Academy of Pediatrics. Any conflicts have been resolved through a process 2. The composition of the influenza vaccines for 2019–2020 has been approved by the Board of Directors. The American Academy of Pediatrics has neither solicited nor accepted any commercial updated. The A(H1N1)pdm09 and A(H3N2) components of the vaccine involvement in the development of the content of this publication. are new for this season. The B strains are unchanged from the previous DOI: https://doi.org/10.1542/peds.2019-2478 season. PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). 3. All pediatric influenza vaccines will be quadrivalent vaccines. The age indication for some pediatric vaccines has been expanded; therefore, Copyright © 2019 by the American Academy of Pediatrics there are now 4 egg-based quadrivalent inactivated influenza vaccines (IIV4s) licensed by the US Food and Drug Administration (FDA) for To cite: COMMITTEE ON INFECTIOUS DISEASES. administration to children 6 months and older, 1 inactivated cell-based Recommendations for Prevention and Control of fl – quadrivalent inactivated influenza vaccine (cIIV4) for children 4 years In uenza in Children, 2019 2020. Pediatrics. 2019;144(4): e20192478 and older, and 1 quadrivalent live attenuated influenza vaccine (LAIV4)

Downloaded from www.aappublications.org/news by guest on October 4, 2021 PEDIATRICS Volume 144, number 4, October 2019:e20192478 FROM THE AMERICAN ACADEMY OF PEDIATRICS for children 2 years and older. No influenza and transmission of 8 years of age; 70% in those 9 trivalent vaccines are expected to influenza virus to household contacts through 17 years of age), 25% against be available for children this and community members of all A(H3N2) (54% in those 6 months season. ages.1,2 Routine influenza vaccination through 8 years of age; 18% in those 4. New formulations of licensed and antiviral agents for the treatment 9 through 17 years of age), and 48% fl fl influenza vaccines with a volume and prevention of in uenza are against in uenza B (B/Yamagata 1,2 of 0.5 mL per dose have been recommended for children. predominant) (77% in those approved for children 6 through 6 months through 8 years of age; 28% in those 9 through 17 years 36 months of age. Children 6 SUMMARY OF RECENT INFLUENZA through 35 months of age may ACTIVITY IN THE UNITED STATES of age). now receive either the 0.25- or 2018–2019 Influenza Season 0.5-mL dose, with no preference, 2017–2018 Influenza Season and children $36 months of age The 2017–2018 influenza season was The 2018–2019 influenza season was (3 years and older) continue to the first classified as a high-severity the longest-lasting season reported in receive a 0.5-mL dose. season for all age groups, with high the United States in the past decade, 5. Children 6 months through 8 years levels of outpatient clinic and with elevated levels of influenzalike of age who are receiving influenza emergency department visits for illness activity for a total duration of vaccine for the first time or who influenzalike illness, high influenza- 21 consecutive weeks (compared to 6 have received only 1 dose before related hospitalization rates, and high the average duration of 16 weeks). 3–5 July 1, 2019, should receive 2 numbers of deaths. Influenza Influenza A(H1N1)pdm09 viruses doses of influenza vaccine ideally A(H3N2) viruses predominated predominated from October to mid- fl by the end of October, and vaccines through February 2018; influenza B February, and in uenza A(H3N2) fi should be offered as soon as they viruses predominated from March viruses were identi ed more become available. Children 2018 onward. Although frequently from February to May. fl needing only 1 dose of influenza hospitalization rates for children that In uenza B (B/Victoria lineage vaccine, regardless of age, should season did not exceed those reported predominant) represented also receive vaccination ideally by during the 2009 pandemic, they did approximately 5% of circulating the end of October. surpass rates reported in previous strains. The majority of characterized high-severity A(H3N2)-predominant influenza A(H1N1)pdm09 and 6. A new antiviral medication has seasons. Excluding the 2009 influenza B viruses were antigenically been licensed for treatment of pandemic, the 186 pediatric deaths similar to the viruses included in the influenza in children. reported during the 2017–2018 2018–2019 influenza vaccine, but fl Children often have the highest attack season (approximately half of which most characterized in uenza rates of influenza in the community occurred in otherwise healthy A(H3N2) viruses were antigenically during seasonal influenza epidemics. children) were the highest reported distinct from the A(H3N2) component fl of the 2018–2019 vaccine. Co- They play a pivotal role in the since in uenza-associated pediatric circulation of multiple genetically transmission of influenza virus mortality became a nationally fi 3–5 diverse clades and/or subclades of infection to household and other noti able condition in 2004. A(H3N2) was documented. close contacts and can experience Among pediatric deaths of children Circulating viruses identified morbidity, including severe or fatal 6 months and older who were eligible belonged to clade 3C.2a, subclade complications from influenza for vaccination and for whom 3C.2a1, or clade 3C.3a, with 3C.3a infection.1 Children younger than vaccination status was known, approximately 80% had not received viruses accounting for .70% of the 5 years, especially those younger than the influenza vaccine during the A(H3N2) in the United States. The 2 years, and children with certain 2017–2018 season.3 2018–2019 vaccine’s A(H3N2) virus underlying medical conditions are at belonged to subclade 3C.2a1. This increased risk of hospitalization and Overall vaccine effectiveness (VE) likely contributed to an overall lower complications attributable to against both influenza A and B VE against influenza A(H3N2) for that influenza.1 School-aged children bear viruses during the 2017–2018 season influenza season and supported the a large influenza disease burden and was estimated to be 38%, with higher recommendation to change the are more likely to seek influenza- VE (64%) in children 6 months to A(H3N2) virus strain for the related medical care compared with 8 years of age compared with those 9 upcoming season’s vaccine. healthy adults.1,2 Reducing influenza to 17 years of age (28%).4 Overall VE virus transmission among children against influenza A(H1N1) was 65% The 2018–2019 season was of decreases the burden of childhood (87% in those 6 months through moderate severity, with similar

Downloaded from www.aappublications.org/news by guest on October 4, 2021 2 FROM THE AMERICAN ACADEMY OF PEDIATRICS hospitalization rates in children as known underlying medical 231% to 43%) for A(H3N2). These seen during the 2017–2018 season, conditions. are preliminary data and not vaccine fi which were higher than in those • Among 89 children who were speci c. observed in previous seasons from 6 months or older at the time of 2013–2014 to 2016–2017. The illness onset and, therefore, would INFLUENZA MORBIDITY AND MORTALITY cumulative hospitalization rates per have been eligible for vaccination IN CHILDREN 100 000 population were 72.0 among and for whom vaccination status children 0 through 4 years old and was known, most (70%) were Pediatric hospitalizations and deaths fl 20.4 among children 5 through unvaccinated. Only 30 (34%) had caused by in uenza vary from one 6 17 years old. Among 1132 children received at least 1 dose of influenza season to the next. Historically, up to fl hospitalized with in uenza and for vaccine (25 had complete 80% of pediatric deaths have whom data were available, 45% had vaccination, and 5 had received 1 of occurred in unvaccinated children fl no recorded underlying condition, 2 ACIP-recommended doses). 6 months and older. In uenza and 55% had at least 1 underlying vaccination is associated with medical condition; the most Preliminary estimates of the VE of the reduced risk of laboratory-confirmed – fl commonly reported underlying 2018 2019 seasonal in uenza influenza-related pediatric death.8 In fi conditions were asthma or reactive vaccines (not based on speci c 1 case-cohort analysis comparing products) against medically attended airway disease (27.1%), neurologic vaccination uptake among laboratory- influenza illness from the US disorders (17.7%), and obesity confirmed influenza-associated 7 Influenza VE Network reveal an (11.4%). pediatric deaths with estimated overall adjusted VE of 47% (95% vaccination coverage among pediatric As of June 21, 2019, the following fi con dence interval [CI], 34% to 57%) cohorts in the United States from data were reported by the Centers for for people of all ages against any type 2010 to 2014, Flannery et al8 found Disease Control and Prevention fl 7 of in uenza (A or B). The overall VE that only 26% of children had (CDC): fl against any type of in uenza for received the vaccine before illness children 6 months through 17 years • There were 116 laboratory- onset compared to an average was 61% (95% CI, 44% to 73%). confirmed influenza-associated vaccination coverage of 48%. Overall Virus-specific preliminary VE data pediatric deaths. Most (66%) of VE against influenza-associated death available for influenza A(H1N1) those children died after being in children was 65% (95% CI, 54% to admitted to the hospital. The viruses reveal overall VE of 45% 74%). More than half of children in median age of the pediatric deaths (95% CI, 30% to 58%) in people of all this study who died of influenza had was 6.1 years (range: 2 months–17 ages and 63% (95% CI, 40% to 75%) $1 underlying medical condition years). for children 6 months to 17 years. associated with increased risk of Preliminary VE for influenza A(H3N2) ○ severe influenza-related A total of 107 were associated in people of all ages is 44% (95% CI, fl complications; only 1 in 3 of these at- with in uenza A viruses: 43 with 13% to 64%). No data are yet fl risk children had been vaccinated; in uenza A(H1N1)pdm09, 25 available for children within this yet, VE against death in children with with A(H3N2), and 39 with an network for A(H3N2) or B strains. influenza A virus for which no underlying conditions was 51% (95% fl fl subtyping was available. Preliminary estimates of in uenza VE CI, 31% to 67%). Similarly, in uenza against hospitalization in children, vaccination reduces by three quarters ○ Eight were associated with from the CDC’s New Vaccine the risk of severe, life-threatening influenza B viruses. Surveillance Network, which is laboratory-confirmed influenza in ○ One was associated with an focused on surveillance in children, children requiring admission to the undetermined type of reveal an overall adjusted (for age, ICU.9 The rates of influenza- fl in uenza virus. site, and month) VE in children of associated hospitalization for children • Among the 104 children with 31% (95% CI, 5% to 51%) against younger than 5 years exceed the rates known medical history, 51% of any influenza A or B virus, with 26% for children 5 through 17 years of deaths occurred in children who (95% CI, 26% to 49%) in children age. The influenza virus type might had at least 1 underlying medical 6 months through 8 years of age and also affect the severity of disease. In condition recognized by the 53% (95% CI, 5% to 77%) among a recent study of hospitalizations for Advisory Committee on those 9 through 17 years of age.1 The influenza A versus B, the odds of Immunization Practices (ACIP) to overall adjusted VE against pediatric mortality were significantly greater increase the risk of influenza- hospitalization by virus subtype was with influenza B than with influenza attributable disease severity. 48% (95% CI, 14% to 68%) for A and not entirely explained by Therefore, nearly half had no A(H1N1)pdm09 and 13% (95% CI, underlying health conditions.10

Downloaded from www.aappublications.org/news by guest on October 4, 2021 PEDIATRICS Volume 144, number 4, October 2019 3 HIGH-RISK GROUPS IN PEDIATRICS Committee for the Northern eggs), 1 is cell culture-based (seed 6,14 Children and adolescents with certain Hemisphere : strains grown in Madin-Darby canine underlying medical conditions have 1. Trivalent vaccines contain the kidney cells), and all are available in fi a high risk of complications from following: single-dose, thimerosal-free pre lled fl syringes as well multidose vial in uenza, as described in Table 1. a. A/Brisbane/02/2018 (H1N1) fl presentations. With the FDA approval Although universal in uenza pdm09-like virus (new this vaccination is recommended for of the expansion of the age indication season); fl 15 everyone starting at 6 months of age, for A uria Quadrivalent to children b. A/Kansas/14/2017 (H3N2)- emphasis should be placed on 6 months and older (previously like virus (new this season); ensuring that people in high-risk approved for children 5 years and and groups and their household contacts older) in October 2018, all egg-based fl and caregivers receive an annual c. B/Colorado/60/2017-like virus IIV4s (A uria, Fluarix, Flulaval, and influenza vaccine.11 (B/Victoria/2/87 lineage) Fluzone) are now licensed for (unchanged). children 6 months and older, and the cell culture–based vaccine (Flucelvax) 2. Quadrivalent vaccines contain SEASONAL INFLUENZA VACCINES is licensed for children 4 years a second B virus: and older. Table 2 summarizes information on a. B/Phuket/3073/2013-like fl the types of in uenza vaccines virus (B/Yamagata/16/88 The licensure of the expanded age fl licensed for children and adults lineage) (unchanged). indication for A uria quadrivalent during the 2019–2020 season. More was supported by a single than 1 product may be appropriate randomized, double-blind safety and for a given patient, and vaccination IIV immunogenicity study in children 6 should not be delayed to obtain through 59 months of age who For the 2019–2020 season, all IIVs a specific product. received Afluria quadrivalent or for children in the United States will a comparator licensed quadrivalent All 2019–2020 seasonal influenza be quadrivalent vaccines, with vaccine.15 The vaccine was found to vaccines contain the same influenza specific age indications for available have a similar safety profile and strains as recommended by the World formulations (Table 2). All licensed noninferior immunogenicity as the Health Organization (WHO) as well as inactivated vaccines for children in comparator vaccine. Importantly, the FDA Vaccines and Related the United States are unadjuvanted; 4 there were no febrile seizures in the Biological Products Advisory are egg-based (seed strains grown in 7 days after vaccination. The trivalent formulation is no longer expected to TABLE 1 Persons at High Risk of Influenza Complications be available. The dose volume for Afluria quadrivalent is 0.25 mL for Children ,5 years and especially those ,2 years,a regardless of the presence of underlying medical children 6 through 35 months of age conditions and 0.5 mL for those 36 months and Adults $50 years and especially those $65 years older. This vaccine should only be fi Children and adults with chronic pulmonary (including asthma and cystic brosis), hemodynamically administered by needle and syringe significant cardiovascular disease (except hypertension alone), or renal, hepatic, hematologic (including sickle cell disease and other hemoglobinopathies), or metabolic disorders (including in children, whereas administration diabetes mellitus) via jet injector is an option for Children and adults with immunosuppression attributable to any cause, including that caused by individuals 18 through 64 years medications or by HIV infection of age. Children and adults with neurologic and neurodevelopment conditions (including disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy, stroke, intellectual A quadrivalent recombinant disability, moderate-to-severe developmental delay, muscular dystrophy, or spinal cord injury) baculovirus-expressed hemagglutinin Children and adults with conditions that compromise respiratory function or handling of secretions influenza vaccine (RIV4; Flublok) is (including tracheostomy and mechanical ventilation)12 Women who are pregnant or postpartum during the influenza season licensed only for people 18 years and Children and adolescents ,19 years who are receiving long-term aspirin therapy or salicylate- older. The high-dose trivalent containing medications (including those with Kawasaki disease and rheumatologic conditions) inactivated influenza vaccine (IIV3; because of increased risk of Reye syndrome Fluzone High-Dose), containing American Indian and Alaskan native people 4 times the amount of antigen for Children and adults with extreme obesity (ie, BMI $40 for adults and based on age for children) Residents of chronic care facilities and nursing homes each virus strain than the standard- dose vaccines, is licensed only for a The 2019–2020 CDC recommendations state that “Although all children younger than 5 years old are considered at higher risk for complications from influenza, the highest risk is for those younger than 2 years old, with the highest people 65 years and older. A trivalent hospitalization and death rates among infants younger than 6 months old.” MF59 adjuvanted IIV (Fluad) licensed

Downloaded from www.aappublications.org/news by guest on October 4, 2021 4 FROM THE AMERICAN ACADEMY OF PEDIATRICS TABLE 2 Recommended Seasonal Influenza Vaccines for Different Age Groups: United States, 2019–2020 Influenza Season Vaccine Trade Name Manufacturer Presentation HA Antigen Content (IIVs and Thimerosal Age Group CPT RIV4) or Virus Count (LAIV4) per Dose for Mercury Content, Code Each Vaccine Virus mgof Hg/0.5-mL Dose Inactivated Trivalent IIV3 Fluzone High- Sanofi Pasteur 0.5-mL prefilled syringe (60 mg/0.5 mL) 0 $65 y 90662 Dose aIIV3 Fluad MF59 Seqirus 0.5-mL prefilled syringe (15 mg/0.5 mL) 0 $65 y 90653 adjuvanted Quadrivalent Egg based IIV4 Fluzone Sanofi Pasteur 0.25-mL prefilled syringe (7.5 mg/0.25 mL) 0 6–35 mo 90685 Quadrivalent 0.5-mL prefilled syringe (15 mg/0.5 mL) 0 $6 mo 90686 0.5-mL single-dose vial (15 mg/0.5 mL) 0 $6 mo 90686 5.0-mL multidose viala (7.5 mg/0.25 mL) 25 $6 mo 90687, (15 mg/0.5 mL) 90688 IIV4 Fluarix GlaxoSmithKline 0.5-mL prefilled syringe (15 mg/0.5 mL) 0 $6 mo 90686 Quadrivalent IIV4 FluLaval ID Biomedical Corporation of 0.5-mL prefilled syringe (15 mg/0.5 mL) 0 $6 mo 90686 Quadrivalent Quebec (distributed by 5.0-mL multidose vial (15 mg/0.5 mL) ,25 $6 mo 90688 GlaxoSmithKline) IIV4 Afluria Seqirus 0.25-mL prefilled syringe (7.5 mg/0.25 mL) 0 6–35 mo 90685 Quadrivalent 0.5-mL prefilled syringe (15 mg/0.5 mL) 0 $36 mo 90686 5.0-mL multidose viala (7.5 mg/0.25 mL) 24.5 $6mo 90687, (15 mg/0.5 mL) (needle/ 90688 syringe) 18–64 y (jet injector) Cell based ccIIV4 Flucelvax Seqirus 0.5-mL prefilled syringe (15 mg/0.5 mL) 0 $4 y 90674 Quadrivalent 5.0 mL multidose vial (15 mg/0.5 mL) 25 $4 y 90756 Recombinant RIV4 Flublok Protein Sciences Corporation 0.5-mL prefilled syringe (45 mg/0.5 mL) 0 $18 y 90682 Quadrivalent (distributed by Sanofi Pasteur) Live attenuated LAIV4 FluMist AstraZeneca 0.2-mL prefilled intranasal sprayer (virus 02–49 y 90672 Quadrivalent dose: 106.5–7.5 FFU/0.2 mL) Implementation guidance on supply, pricing, payment, CPT coding, and liability issues can be found at www.aapredbook.org/implementation. Data sources are from references1 and13 . aIIV3, adjuvanted trivalent inactivated influenza vaccine; ccIIV4, quadrivalent cell culture–based inactivated influenza vaccine; CPT, Current Procedural Terminology; FFU, focus-forming unit; —, not applicable. a For vaccines that include a multidose vial presentation and a 0.25-mL dose, a maximum of 10 doses can be drawn from a multidose vial. for people 65 years and older is the Children 36 months (3 years) and Fluzone (IIV3) and Fluzone first adjuvanted influenza vaccine older can receive any age-appropriate Quadrivalent (IIV4). The marketed in the United States. licensed IIV, administered at a 0.5-mL recommendation for use of a reduced Adjuvants may be included in dose and containing 15 mgof dose and volume for children in this a vaccine to elicit a more robust hemagglutinin (HA) from each strain age group (half that recommended for immune response, which could lead in the vaccine. Children 6 through people 3 years and older) was based to a reduction in the number of doses 35 months of age may receive any on increased reactogenicity noted required for children. In a study in licensed IIV at either 0.25 or 0.5 mL among younger children after receipt children, the relative vaccine efficacy per dose, without preference over one of whole-virus inactivated vaccines, of an MF59 adjuvanted influenza or the other. which have since been replaced with vaccine was significantly greater than split virus and subunit IIV. Several nonadjuvanted vaccine in the 6- The only IIV products licensed for vaccines have been licensed for through 23-month age group.16 children 6 through 35 months of age children 6 through 35 months of age Adjuvanted seasonal influenza before 2016 were the 0.25-mL since 2017, which are less vaccines are not licensed for children (containing 7.5 µg of HA for each reactogenic (Table 2).17,18 All are at this time. vaccine virus) dose formulations of quadrivalent, but the dose volume

Downloaded from www.aappublications.org/news by guest on October 4, 2021 PEDIATRICS Volume 144, number 4, October 2019 5 and, therefore, the antigen content headache, arthralgia, and possibility of increased risk for febrile vary among different IIV products. In gastrointestinal tract symptoms. seizures cannot be ruled out, addition to the 0.25-mL (7.5 mgofHA simultaneous administration of IIV per vaccine virus) Fluzone IIV can be administered concomitantly with PCV13 and/or other vaccines for Quadrivalent vaccine, Fluzone with other inactivated or live vaccines. the 2019–2020 influenza season Quadrivalent containing 15 mgofHA During the 2 influenza seasons continues to be recommended when per vaccine virus per 0.5-mL dose was spanning 2010–2012, there were these vaccines are indicated. Overall, licensed in January 201919,20 after increased reports of febrile seizures in the benefits of timely vaccination with these 2 formulations were compared the United States in young children same-day administration of IIV and in a single randomized, multicenter who received IIV3 and the 13-valent PCV13 or diphtheria-tetanus-acellular safety and immunogenicity study. Both pneumococcal conjugate vaccine pertussis vaccine outweigh the risk of products are expected to be available (PCV13) concomitantly. Subsequent febrile seizures. Vaccine-proximate this season because no direct retrospective analyses of past seasons febrile seizures rarely have any long- comparison data are available to revealed a slight increase in the risk of term sequelae, similar to non–vaccine- demonstrate superiority of one over febrile seizures in children 6 through proximate febrile seizures. the other. In addition, 2 other vaccines, 23 months of age when PCV13s were Fluarix Quadrivalent21 and FluLaval administered concomitantly with Thimerosal-containing vaccines are Quadrivalent,22 have been licensed for IIV.23 The concomitant administration not associated with an increased risk of IIV3, PCV13, and diphtheria- of autism spectrum disorder in a 0.5-mL dose in children 6 through 1 35 months of age. These 2 vaccines do tetanus-acellular pertussis vaccine children. Thimerosal from vaccines not have a 0.25-mL dose formulation. was associated with the greatest has not been linked to any neurologic relative risk estimate, corresponding condition. The American Academy of Given that different formulations of to a maximum additional 30 febrile Pediatrics (AAP) supports the current IIV for children 6 through 35 months seizure cases per 100 000 children WHO recommendations for use of of age are available, care should be vaccinated compared to the thimerosal as a preservative in taken to administer the appropriate administration of the vaccines on multiuse vials in the global vaccine volume and dose for each product. In separate days. In contrast, data from supply. Concerns about the residual, each instance, the recommended the Post-Licensure Rapid trace amount of thimerosal in some volume may be administered from an Immunization Safety Monitoring IIV formulations may arise. Despite appropriate prefilled syringe, program of the FDA, the largest the lack of evidence of harm, some a single-dose vial, or multidose vial, vaccine safety active surveillance states, including California, Delaware, as supplied by the manufacturer. For program in the United States, revealed Illinois, Missouri, New York, and vaccines that include a multidose vial that there was no significant increase Washington, have legislation presentation and a 0.25-mL dose, in febrile seizures associated with restricting the use of vaccines that a maximum of 10 doses can be drawn concomitant administration of these 3 contain even trace amounts of from a multidose vial. Importantly, fi vaccines in children 6 through thimerosal. The bene ts of protecting dose volume is different from the 59 months of age during the children against the known risks of number of doses needed to complete fl 2010–2011 season.24 In a subsequent in uenza are clear. Therefore, to the vaccination. Children 6 months sentinel Center for Biologics extent permitted by state law, through 8 years of age who require 2 Evaluation and Research–Post- children should receive any available doses of vaccine for the 2019–2020 Licensure Rapid Immunization Safety formulation of IIV rather than season should receive 2 separate Monitoring surveillance report delaying vaccination while waiting for doses at the recommended dose evaluating influenza vaccines and reduced thimerosal-content or volume specified for each product. febrile seizures in the 2013–2014 and thimerosal-free vaccines. IIV IIVs can be used in healthy children 2014–2015 influenza seasons, there formulations that are free of even as well as those with underlying was no evidence of an elevated risk of trace amounts of thimerosal are chronic medical conditions. IIV is well febrile seizures in children 6 through widely available (Table 2). tolerated in children. The most 23 months of age after IIV Live Attenuated (Intranasal) common injection-site adverse administration during the 2013–2014 Influenza Vaccine reactions after administration of IIV and 2014–2015 seasons. It was in children are injection-site pain, concluded that the risk of seizures The intranasal LAIV was initially redness, and swelling. The most after PCV13 or concomitant PCV13 licensed in the United States in 2003 common systemic adverse events are and IIV is low compared to a child’s for people 5 through 49 years of age drowsiness, irritability, loss of lifetime risk of febrile seizures from as a trivalent live attenuated appetite, fatigue, muscle aches, other causes.25 Although the influenza vaccine (LAIV3)

Downloaded from www.aappublications.org/news by guest on October 4, 2021 6 FROM THE AMERICAN ACADEMY OF PEDIATRICS formulation. The approved age group associated with the LAIV4 no additional US data on LAIV4 VE was extended to 2 years of age in formulation containing the new was anticipated at the end of the 2007. The quadrivalent formulation A(H1N1)pdm09-like virus among US 2018–2019 season. The information (LAIV4) has been licensed in the children 24 months through 3 years reviewed by the Committee on United States since 2012 and was of age.27 Shedding and Infectious Diseases included the first available during the 2013–2014 immunogenicity data provided by the following: influenza season, replacing the LAIV3. manufacturer suggested that the new • The epidemiology of the The most commonly reported fl in uenza A(H1N1)pdm09-like virus 2018–2019 influenza season in the reactions in children are runny nose included in its latest formulation had United States and worldwide, or nasal congestion, headache, improved replicative fitness over showing an early predominance of decreased activity or lethargy, and previous LAIV4 influenza A(H1N1) A(H1N1)pdm09 virus circulation, sore throat. The safety of LAIV in pdm09-like vaccine strains, resulting followed by A(H3N2) (https://www. people with a history of asthma, in an improved immune response cdc.gov/flu/weekly/index.htm). diabetes mellitus, or other high-risk comparable to that of LAIV3 available • – fl medical conditions associated with an before the 2009 pandemic. Shedding Interim VE for 2018 2019 in uenza fl elevated risk of complications from and replicative fitness are not known season showing overall in uenza VE influenza (see Contraindications and to correlate with efficacy, and no against medically attended illness fl Precautions) has not been firmly published effectiveness estimates for for in uenza A(H1N1)pdm09 in established. In postlicensure this revised formulation of the children of approximately 60% (not fi surveillance of LAIV (including LAIV3 vaccine against influenza A(H1N1) product speci c, but most vaccine and LAIV4), the Vaccine Adverse pdm09 viruses were available before used was IIV), approximately 40% Event Reporting System, jointly the start of the 2018–2019 influenza for influenza A(H3N2) overall (given sponsored by the FDA and CDC, did season because influenza A(H3N2) small numbers of H3N2 cases, no not identify any new or unexpected and influenza B viruses predominated pediatric data), and no data for 28 safety concerns, including in people during the 2017–2018 northern influenza B. with a contraindication or precaution. hemisphere season. Therefore, for the • Influenza vaccine coverage rates in Although the use of LAIV in young 2018–2019 season, the AAP children, demonstrating an increase children with chronic medical recommended IIV4 or IIV3 as the to ∼45% compared with ∼38% at conditions, including asthma, has primary choice for influenza the same time point in 2017–2018 been implemented outside of the vaccination in children, with LAIV4 season (interim estimate in United States, data are considered use reserved for children who would November 2018; https://www.cdc. insufficient to support an expanded not otherwise receive an influenza gov/flu/fluvaxview/nifs-estimates- recommendation in the United States. vaccine and for whom LAIV use was nov2018.htm). appropriate for age (2 years and The CDC conducted a systematic • VE data from the European older) and health status (ie, healthy, review of published studies surveillance networks for which without any underlying chronic evaluating the effectiveness of LAIV3 uninterrupted use of LAIV medical condition). and LAIV4 in children from the continued during the 2016–2017 2010–2011 to the 2016–2017 and 2017–2018 seasons (when it After the ACIP meeting in February seasons, including data from US and was not used in the United States) 2019, the AAP convened a meeting of European studies.1,26 The data and through the 2018–2019 its Committee on Infectious Diseases suggested that the effectiveness of season. In this network, the only to discuss the influenza vaccination LAIV3 or LAIV4 for influenza strain recommendations for the 2019–2020 country with interim estimates, the A(H1N1) was lower than that of IIV in season. The group reviewed available United Kingdom, reported VE children 2 through 17 years of age. fl data on influenza epidemiology and against medically attended in uenza LAIV was similarly effective against VE for the 2018–2019 season and in children and adolescents 2 influenza B and A(H3N2) strains in agreed that harmonizing through 17 years of age for some age groups compared to IIV. – – recommendations between the AAP 2017 2018 and 2018 2019 (same . For the 2017–2018 season, a new and CDC for the use of LAIV in the vaccine formulation) of 85% for A(H1N1)pdm09-like virus (A/ 2019–2020 season is appropriate as A(H1N1)pdm09. Estimates were Slovenia/2903/2015) was included more information becomes available. based on a small number of cases in LAIV4, replacing A/Bolivia/559/ Despite the early predominance of and were preliminary but consistent 29 2013. A study conducted by the A(H1N1) circulation, low use of with the previous season. LAIV4 manufacturer evaluated viral LAIV4 in the US population limited • Other countries that use LAIV shedding and immunogenicity evaluation of product-specific VE, and (Canada, Finland) may have LAIV4-

Downloaded from www.aappublications.org/news by guest on October 4, 2021 PEDIATRICS Volume 144, number 4, October 2019 7 specific VE at the end of the season, children with mild upper respiratory history of recurrent wheezing or but this is not certain. Small case infection symptoms or allergic rhinitis. a medically attended wheezing numbers and low LAIV use may In children with a moderate-to-severe episode in the previous 12 months also limit accurate VE calculations febrile illness (eg, high fever, active because of the potential for in these countries. In general, as infection, requiring hospitalization, increased wheezing after long as use of LAIV is low relative etc), on the basis of the judgment of immunization. In this age range, to IIV, it will be difficult to estimate the clinician, vaccination should be many children have a history of LAIV VE accurately. Furthermore, deferred until resolution of the illness. wheezing with respiratory tract variability in VE for other strains (A Similarly, children with an amount of illnesses and are eventually [H3N2] and B strains) remains for nasal congestion that would notably diagnosed with asthma; both IIV and LAIV. impede vaccine delivery into the • children who have known or • The committee noted that LAIV is nasopharyngeal mucosa should have suspected immunodeficiency licensed in the United States and LAIV vaccination deferred until disease or who are receiving recommended by the CDC. resolution. immunosuppressive or History of Guillain-Barré syndrome immunomodulatory therapies; Influenza VE varies from season to (GBS) after influenza vaccine is • season and is affected by many close contacts and caregivers of considered a precaution for the factors, including age and health those who are severely administration of influenza vaccines. status of the recipient, influenza type immunocompromised and require Data on the risk of GBS after and subtype, existing immunity from a protected environment; vaccination with seasonal influenza previous infection or vaccination, and • children and adolescents receiving vaccine are variable and have been degree of antigenic match between aspirin or salicylate-containing inconsistent across seasons. If there is vaccine and circulating virus strains. medications; an increased risk, it is likely small and It is possible that VE also differs • children who have received other primarily in adult patients. GBS is among individual vaccine products; live-virus vaccines within the rare, especially in children, and there however, product-specific previous 4 weeks (except for is a lack of evidence on risk of GBS comparative effectiveness data are rotavirus vaccine); however, LAIV after influenza vaccine in children. lacking for most vaccines. Additional can be administered on the same Nonetheless, regardless of age, experience spanning multiple day with other live-virus vaccines if a history of GBS ,6 weeks after influenza seasons will help to necessary; a previous dose of influenza vaccine determine optimal use of the is a precaution for administration of • children taking an influenza available vaccine formulations in influenza vaccine. The benefits of antiviral medication and until children. The AAP will continue to influenza vaccination might outweigh 48 hours (oseltamivir, zanamivir, monitor annual influenza surveillance the risks for certain people who have peramivir) and up to 2 weeks and VE reports to update influenza a history of GBS (particularly if not (baloxavir) after stopping the vaccine recommendations if associated with previous influenza influenza antiviral therapy. If necessary. vaccination) and who also are at high a child recently received LAIV but risk for severe complications from has an influenza illness for which CONTRAINDICATIONS AND influenza. Additional precautions for antiviral agents are appropriate, PRECAUTIONS LAIV include a diagnosis of asthma in the antiviral agents should be children older than 5 years and the given. If antiviral agents are Children who have had an allergic presence of an underlying medical necessary for treatment within reaction after a previous dose of any condition that increases the risk to 5 to 7 days of LAIV immunization, influenza vaccine should be evaluated severe illness with wild-type reimmunization is indicated by an allergist to determine whether influenza virus (Table 1). Persons because of the potential effects of future receipt of the vaccine is who should not receive LAIV are antiviral medications on LAIV appropriate. An anaphylaxis reaction listed below. replication and immunogenicity; fl after receipt of any in uenza vaccine and (IIV or LAIV) may be Persons in Whom LAIV Is • pregnant women. a contraindication to influenza Contraindicated vaccination. LAIV has specific The safety of LAIV in some high-risk contraindications (see below). Minor populations has not been definitively • illnesses, with or without fever, are not children younger than 2 years; established. These conditions are not contraindications to the use of • children 2 through 4 years of age contraindications but are listed under influenza vaccines, including among with a diagnosis of asthma or the “Warnings and Precautions”

Downloaded from www.aappublications.org/news by guest on October 4, 2021 8 FROM THE AMERICAN ACADEMY OF PEDIATRICS section of the LAIV package insert, INFLUENZA VACCINES AND EGG influenza at any time during their including metabolic disease, diabetes ALLERGY pregnancy provide protection to their fi mellitus, other chronic disorders of There is strong evidence that egg- infants during their rst 6 months of the pulmonary or cardiovascular allergic individuals can safely receive life (when they are too young to fl systems, renal dysfunction, or influenza vaccine without any receive in uenza vaccine themselves) hemoglobinopathies. A precaution is additional precautions beyond those through transplacental passage of 38,39 a condition in a recipient that might recommended for any vaccine.1,30,31 antibodies. Infants born to fl increase the risk or seriousness of an The presence of egg allergy in an women who receive in uenza adverse reaction or complicate individual is not a contraindication to vaccination during pregnancy can making another diagnosis because of receive IIV or LAIV. Vaccine recipients have a risk reduction of 72% (95% a possible vaccine-related reaction. A with egg allergy are at no greater risk CI, 39% to 87%) for laboratory- fi fl precaution also may exist for for a systemic allergic reaction than con rmed in uenza hospitalization in fi 40 conditions that might compromise those without egg allergy. Therefore, the rst few months of life. the ability of the vaccine to produce precautions such as choice of immunity. Vaccination may be a particular vaccine, special It is safe to administer IIV to pregnant recommended in the presence of observation periods, or restriction of women during any trimester of fi a precaution if the bene tof administration to particular medical gestation and postpartum. Any protection from the vaccine settings are not warranted and licensed, recommended, and age- fl outweighs the risk. constitute an unnecessary barrier to appropriate in uenza vaccine may be immunization. It is not necessary to used, although experience with the use of RIV4 in pregnant women is LAIV and Immunocompromised Hosts inquire about egg allergy before the administration of any influenza limited. LAIV is contraindicated IIV is the vaccine of choice for anyone vaccine, including on screening forms. during pregnancy. Data on the safety fl in close contact with a subset of Routine prevaccination questions of in uenza vaccination at any time severely immunocompromised regarding anaphylaxis after receipt of during pregnancy continues to people (ie, those in a protected any vaccine are appropriate. Standard accumulate and support the safety of fl environment). IIV is preferred over vaccination practice for all vaccines in in uenza immunization during LAIV for contacts of severely children should include the ability to pregnancy. In a 5-year retrospective immunocompromised people because respond to rare acute cohort study from 2003 to 2008 with fl of a theoretical risk of infection hypersensitivity reactions. Children more than 10 000 women, in uenza fi attributable to LAIV strain in an who have had a previous allergic vaccination in the rst trimester was immunocompromised contact of an reaction to the influenza vaccine not associated with an increase in the LAIV-immunized person. Available should be evaluated by an allergist to rates of major congenital 41 data indicate a low risk of determine whether future receipt of malformations. Similarly, transmission of the virus from both the vaccine is appropriate. a systematic review and meta- children and adults vaccinated with analysis of studies of congenital LAIV. Health care personnel (HCP) anomalies after vaccination during INFLUENZA VACCINES DURING immunized with LAIV may continue pregnancy, including data from 15 PREGNANCY AND BREASTFEEDING to work in most units of a hospital, studies (14 cohort studies and 1 case- including the NICU and general Influenza vaccine is recommended by control study), did not show any oncology ward, using standard the ACIP, the American College of association between congenital infection control techniques. As Obstetrics and Gynecology, and the defects and influenza vaccination in a precautionary measure, people American Academy of Family any trimester, including the first recently vaccinated with LAIV should Physicians for all women during any trimester of gestation.42 Assessments restrict contact with severely trimester of gestation for the of any association with influenza immunocompromised patients for protection of mothers against vaccination and preterm birth and 7 days after immunization, although influenza and its complications.1,32 infants who are small for gestational there have been no reports of LAIV Substantial evidence has accumulated age have yielded inconsistent results, transmission from a vaccinated regarding the efficacy of maternal with most studies reporting person to an immunocompromised influenza immunization in preventing a protective effect or no association person. In the theoretical scenario in laboratory-confirmed influenza against these outcomes. Authors of which symptomatic LAIV infection disease and its complications in both a cohort study from the Vaccines and develops in an immunocompromised mothers and their infants in the first Medications in Pregnancy host, LAIV strains are susceptible to 2 to 6 months of life.14,32–37 Pregnant Surveillance System of vaccine antiviral medications. women who are immunized against exposure during the 2010–2011

Downloaded from www.aappublications.org/news by guest on October 4, 2021 PEDIATRICS Volume 144, number 4, October 2019 9 through 2013–2014 seasons found no htm. Breastfeeding should be recommended is inadvertently significant association of spontaneous encouraged even if the mother or administered to a child 36 months or abortion with influenza vaccine infant has influenza. The mother older (eg, 0.25 mL), an additional exposure in the first trimester or should pump and feed expressed milk 0.25-mL dose should be administered within the first 20 weeks of if she or her infant are too sick to to provide a full dose of 0.5 mL as gestation.43 One recent observational breastfeed. If the breastfeeding soon as possible. The total number of Vaccine Safety Datalink study mother requires antiviral agents, full doses appropriate for age should conducted during the 2010–2011 and treatment with oral oseltamivir is be administered. If a child is 2011–2012 seasons noted an preferred. The CDC does not inadvertently vaccinated with association between receipt of IIV recommend use of baloxavir for a formulation approved for adults, the containing H1N1pdm09 and risk of treatment of pregnant women or dose should be counted as valid. spontaneous abortion when an breastfeeding mothers. There are no LAIV H1N1pdm-09-containing vaccine had available efficacy or safety data in also been received the previous pregnant women, and there are no The cold-adapted, temperature- season.44 A follow-up study available data on the presence of sensitive LAIV4 formulation currently conducted by the same investigators baloxavir in human milk, the effects licensed in the United States is with a larger population did not on the breastfed infant, or the effects shipped and stored at 2°C to 8°C (35° reveal this association and further on milk production. F–46°F) and administered supported the safety of influenza intranasally in a prefilled, single-use vaccine during pregnancy. VACCINE STORAGE AND sprayer containing 0.2 mL of vaccine. A removable dose-divider clip is Postpartum women who did not ADMINISTRATION attached to the sprayer to facilitate receive influenza vaccination during The AAP Vaccine Storage and administration of 0.1 mL separately pregnancy should be encouraged to Handling Tip Sheet provides into each nostril. If the child sneezes discuss with their obstetrician, family resources for practices to develop immediately after administration, the physician, nurse midwife, or other comprehensive vaccine management dose should not be repeated. trusted provider receipt of the protocols to keep the temperature for vaccine before discharge from the vaccine storage constant during VACCINE DOSING RECOMMENDATIONS hospital. Vaccination during a power failure or other disaster breastfeeding is safe for mothers and (https://www.aap.org/en-us/ The number of seasonal influenza their infants. Documents/immunization_ vaccine doses recommended for Breastfeeding is strongly disasterplanning.pdf). The AAP children during the 2019–2020 recommended to protect infants recommends the development of influenza season depends on the against influenza viruses by activating a written disaster plan for all practice child’s age at the time of the first innate antiviral mechanisms, settings. Additional information is administered dose and vaccine specifically type 1 interferons. Human available at www.aap.org/disasters. history. The recommendations are milk from mothers vaccinated during unchanged from previous years, as IIVs the third trimester also contains shown in Fig 1. higher levels of influenza-specific IIVs for intramuscular injection are 1. Influenza vaccines are not licensed 45 immunoglobulin A. Greater shipped and stored at 2°C to 8°C (36° for administration to infants exclusivity of breastfeeding in the F–46°F); vaccines that are younger than 6 months and should first 6 months of life decreases the inadvertently frozen should not be not be used in this age group. episodes of respiratory illness with used. These vaccines are 2. Children 9 years and older need fever in infants of vaccinated administered intramuscularly into the only 1 dose, regardless of previous mothers. For infants born to mothers anterolateral thigh of infants and vaccination history. with confirmed influenza illness at young children and into the deltoid delivery, breastfeeding is encouraged, muscle of older children and adults. 3. Children 6 months through 8 years and guidance on breastfeeding Given that various IIVs are available, of age: practices can be found at https:// careful attention should be used to a. Need 2 doses if they have www.cdc.gov/breastfeeding/ ensure that each product is used for received fewer than 2 doses of breastfeeding-special-circumstances/ its approved age indication, dosing, any trivalent or quadrivalent maternal-or-infant-illnesses/ and volume of administration influenza vaccine (IIV or LAIV) influenza.html and https://www.cdc. (Table 2). A 0.5-mL unit dose of any before July 1, 2019. The gov/flu/professionals/ IIV should not be split into 2 separate interval between the 2 doses infectioncontrol/peri-post-settings. 0.25-mL doses. If a lower dose than should be at least 4 weeks. Two

Downloaded from www.aappublications.org/news by guest on October 4, 2021 10 FROM THE AMERICAN ACADEMY OF PEDIATRICS doses should be administered high vaccination coverage with immunity before the end of the to children who receive their achieving optimal individual influenza season. first dose before their ninth immunity for protection against birthday, even when they turn influenza at the peak of seasonal Although the evidence is limited that 9 years old during the same activity, knowing that the duration of waning immunity from early season. immunity after vaccination can wane administration of the vaccine b. Require only 1 dose if they have over time. Initiation of influenza increases the risk of infection in previously received 2 or more vaccination before influenza is children, authors of recent reports total doses of any trivalent or circulating in the community and raise the possibility that early quadrivalent influenza vaccine continuing to vaccinate throughout vaccination might contribute to (IIV or LAIV) before July 1, the influenza season are important reduced protection later in the fl 46–55 2019. The 2 previous doses do components of an effective influenza in uenza season. These not need to have been received vaccination strategy. observational studies and a post hoc during the same influenza analysis from a randomized fl season or consecutive influenza Complete in uenza vaccination by the controlled trial (RCT) were reviewed fl seasons. end of October is recommended by by the ACIP in uenza working group the CDC and AAP. Children who need and are summarized in the CDC 2 doses of vaccine should receive recommendations for 2019–2020 TIMING OF VACCINATION AND their first dose as soon as possible influenza prevention.1 In these DURATION OF PROTECTION when the vaccine becomes available studies, VE decreased within a single Although peak influenza activity in to allow sufficient time for receipt of influenza season, and this decrease the United States tends to occur from the second dose $4 weeks after the was correlated with increasing time January through March, influenza can first before the onset of the influenza after vaccination. However, this decay circulate from early fall (October) to season. Children who require only 1 in VE was not consistent across late spring (May), with 1 or more dose of influenza vaccine should also different age groups and varied by disease peaks. Predicting the onset ideally be vaccinated by end of season and virus subtypes. In some and duration or the severity of the October; however, recent data (mostly studies, waning VE was more evident influenza season is impossible. It is in adults) suggest that early among older adults and younger also challenging to balance public vaccination (July or August) might be children,47,49 and with influenza health strategies needed to achieve associated with suboptimal A(H3N2) viruses more than influenza A(H1N1) or B viruses.48,51,53 A multiseason analysis from the US Influenza VE Network found that VE declined by approximately 7% per month for influenza A(H3N2) and influenza B and by 6% to 11% per month for influenza A(H1N1)pdm09 in individuals 9 years and older.46 VE remained greater than 0 for at least 5 to 6 months after vaccination. A more recent study including children older than 2 years of age also found evidence of declining VE with an odds ratio increasing approximately 16% with each additional 28 days from vaccine administration.52 Another study evaluating VE from the 2011–2012 through the 2013–2014 seasons demonstrated 54% to 67% FIGURE 1 protection from 0 to 180 days after Number of 2019–2020 seasonal influenza vaccine doses for children based on age and previous vaccination.50 Finally, a multiseason vaccination history and recommendations for prevention and control of influenza in children, study in Europe from 2011–2012 – a 2019 2020. The 2 doses need not have been received during the same season or consecutive through 2014–2015 revealed a steady seasons. b Administer 2 doses based on age at receipt of the first dose of influenza vaccine during the season. Children who receive the first dose before their ninth birthday should receive 2 doses, decline in VE down to 0% protection even if they turn 9 years old during the same season. by 111 days after vaccination.48,53

Downloaded from www.aappublications.org/news by guest on October 4, 2021 PEDIATRICS Volume 144, number 4, October 2019 11 Further evaluation is needed before (eg, e-mails, texts, letters, patient and those eligible for vaccination any policy change in timing of portals, practice-specific websites through the Vaccines for Children influenza administration is made. An or social media platforms); creating program. fl fl early onset of the in uenza season is walk-in in uenza vaccination • Population health can benefit from a concern when considering delaying clinics; extending hours beyond pediatricians’ discussions about fi vaccination. Until there are de nitive routine times during peak vaccine safety and effectiveness. data that determine if waning vaccination periods; administering Pediatricians and their office staff fl immunity in uences VE in children, the influenza vaccine during both can influence vaccine acceptance by fl administration of in uenza vaccine well-child examinations and sick explaining the importance of should not be delayed to a later date visits as well as in hospitalized annual influenza vaccination for because this increases the likelihood patients, especially those at high children and emphasizing when fl of missing in uenza vaccination risk of influenza complications, a second dose of vaccine is 56,57 altogether. Providers may before hospital discharge (unless indicated. The AAP and CDC have continue to offer the vaccine until medically contraindicated); created communication resources June 30 of each year when the implementing standing orders for to convey these important fl seasonal in uenza vaccine expires influenza vaccination; considering messages and to help the public fl because the duration of in uenza how to immunize parents, adult understand influenza circulation is unpredictable. Although caregivers, and siblings (see risk recommendations. Resources will influenza activity in the United States management guidance associated be available on Red Book Online is typically low during the summer, with adult immunizations at (https://redbook.solutions.aap.o influenza cases and outbreaks can http://pediatrics.aappublications. rg/selfserve/ssPage.aspx?SelfServe occur, particularly among org/content/129/1/e247) at the ContentId=influenza-resources). international travelers, who may be same time as children; and working • exposed to influenza year-round, The AAP supports mandatory with other institutions (eg, schools, fl depending on the destination. in uenza vaccination programs for child care programs, local public all HCP in all settings, including health departments, and religious outpatient settings.58 Optimal VACCINE IMPLEMENTATION organizations) or alternative care prevention of influenza in the sites, such as pharmacies and The AAP Partnership for Policy health care setting depends on the hospital emergency departments, vaccination of at least 90% of HCP, Implementation has developed to expand venues for administering fi which is consistent with the a series of de nitions using accepted vaccine. If a child receives influenza health information technology national Healthy People 2020 vaccine outside of his or her target for annual influenza standards to assist in the medical home, such as at implementation of vaccine vaccination among HCP. Early- a pharmacy, retail-based clinic, or – recommendations in computer season 2018 2019 vaccine another practice setting, systems and quality measurement coverage among HCP was 67.6%. appropriate documentation of fl efforts. This document is available at In uenza vaccination programs for vaccination should be provided to fi www2.aap.org/informatics/PPI.html. HCP bene t the health of the patient to be shared with his or In addition, the AAP has developed employees, their patients, and her medical home and entered into implementation guidance on supply, members of the community, the state or regional immunization payment, coding, and liability issues; especially because HCP frequently information system (ie, registry). these documents can be found at come into contact with patients at • www.aapredbook.org/ Concerted efforts among the high risk of influenza illness in their implementation. aforementioned groups, plus clinical settings. Mandatory vaccine manufacturers, influenza immunization for all HCP fl HCP, in uenza campaign organizers, distributors, and payers, are is considered to be ethical, just, and and public health agencies are necessary to prioritize distribution necessary to improve patient safety. encouraged to collaborate to develop appropriately to the primary care For the prevention and control of improved strategies for planning, office setting and patient-centered influenza, HCP must prioritize the distribution, communication, and medical home before other venues, health and safety of their patients, administration of vaccines. especially when vaccine supplies honor the requirement of causing • Plan to make influenza vaccine are delayed or limited. Similar no harm, and act as role models for easily accessible for all children. efforts should be made to mitigate both their patients and colleagues Examples include sending alerts to the vaccine supply discrepancy by receiving influenza vaccination families that the vaccine is available between privately insured patients annually.

Downloaded from www.aappublications.org/news by guest on October 4, 2021 12 FROM THE AMERICAN ACADEMY OF PEDIATRICS INFLUENZA VACCINE COVERAGE payers to maximize influenza INFLUENZA VACCINATION RECOMMENDATIONS Although national influenza immunization rates. To avoid errors vaccination coverage among children in claims processing and payment and in the exchange of immunization has not declined in the past 3 seasons, 1. The AAP recommends annual data, pediatricians are reminded that overall vaccination coverage remains fl parents should have their own basic in uenza vaccination for suboptimal. Additional options for everyone 6 months and older, vaccination of children may provide medical record in which their fl including children and a means to improve coverage, in uenza vaccination should be documented. Adults should be adolescents, during the particularly in pharmacies and child 2019–2020 influenza season. care and school-based settings. encouraged to have a medical home 2. For the 2019–2020 season, the Achieving high coverage rates of and communicate their vaccination AAP recommends that any influenza vaccine in infants and status to their primary care provider. licensed influenza vaccine children is a priority to protect them Offering adult vaccinations in the appropriate for age and health against influenza disease and its pediatric practice setting should not status can be used for influenza complications. undermine the adult medical home model. Vaccination of close contacts vaccination in children. IIV and Children’s likelihood of being of children at high risk of influenza- LAIV are options for children for immunized according to related complications (Table 1) is whom these vaccines are recommendations appears to be intended to reduce children’s risk of appropriate. This associated with the immunization exposure to influenza (ie, recommendation is based on practices of their parents.59–63 “cocooning”). The practice of review of current available data Authors of 1 study found that cocooning also may help protect on LAIV and IIV VE. The AAP will children were 2.77 times (95% CI, infants younger than 6 months who continue to review VE data as 2.74 to 2.79) more likely to be are too young to be immunized with they become available and immunized against seasonal influenza influenza vaccine. update these recommendations if if their parents were immunized.33 necessary. When parents who were previously SURVEILLANCE 3. The AAP does not have not immunized had received a preference for any influenza fl immunization for seasonal influenza, Information about in uenza vaccine product over another for their children were 5.44 times (95% surveillance is available through the children who have no CI, 5.35 to 5.53) more likely to receive CDC Voice Information System contraindication to influenza fl influenza vaccine. (in uenza update at 1-800-232- vaccination and for whom more fl 4636) or at www.cdc.gov/ u/index. than 1 licensed product fi fl Pediatric of ces may choose to serve htm. Although current in uenza appropriate for age and health fl as a venue for providing in uenza season data on circulating strains do status is available. Pediatricians vaccination for parents and other care not necessarily predict which and in should administer whichever providers of children if the practice is what proportion strains will circulate formulation is available in their acceptable to both pediatricians and in the subsequent season, it is communities to achieve the – the adults who are to be vaccinated. instructive to be aware of 2018 2019 highest possible coverage this Medical liability issues and medical influenza surveillance data and use influenza season. record documentation requirements them as a guide to empirical therapy need to be considered before until current seasonal data are 4. Children 6 through 35 months of a pediatrician begins immunizing available from the CDC. Information is age may receive either a 0.25- or adults (see risk management posted weekly on the CDC Web site 0.5-mL dose of the licensed, age- guidance associated with adult (www.cdc.gov/flu/weekly/ appropriate IIVs available this immunizations at http://pediatrics. fluactivitysurv.htm). The AAP offers season. No product or aappublications.org/content/129/1/ “What’s the Latest with the Flu” formulation is preferred over e247). Pediatric practices should be (https://www.aap.org/en-us/ another for this age group. aware of payment implications, advocacy-and-policy/aap-health- Children 36 months (3 years) and including nonpayment or having the initiatives/Pages/What’s-the-Latest- older should receive a 0.5-mL parent inappropriately attributed by with-the-Flu.aspx) messages to dose of any available, licensed, a payer as a patient of the highlight those details most relevant age-appropriate inactivated pediatrician’soffice. The AAP for AAP members and child care vaccine. supports efforts to overcome these providers on a monthly basis during 5. The number of seasonal influenza payment barriers with insurance influenza season. vaccine doses recommended to

Downloaded from www.aappublications.org/news by guest on October 4, 2021 PEDIATRICS Volume 144, number 4, October 2019 13 be administered to children in is safe for mothers and their virological response to treatment the 2019–2020 influenza infants. with IV zanamivir for children aged season remains unchanged and 11. The AAP supports mandatory 6 months or older with severe fl depends on the child’s age at the vaccination of HCP as a crucial in uenza and who could not tolerate 66 time of the first administered element in preventing influenza oral or inhaled NAIs. IV zanamivir is dose and vaccine history (Fig 1). and reducing health not approved in the United States. IV 6. Children 6 months through care–associated influenza zanamivir for compassionate use has 8 years of age who are receiving infections because HCP often care not been available in the United – 67 the influenza vaccine for the first for individuals at high risk for States since the 2017 2018 season. time or who have received only 1 influenza-related complications. The FDA licensed baloxavir marboxil dose before July 1, 2019, should in 2018 for the early treatment of fl receive 2 doses of influenza uncomplicated in uenza in INFLUENZA ANTIVIRALS outpatients 12 years and older who vaccine ideally by the end of have been ill for no more than 2 days. October, and vaccines should be Antiviral agents available for both This antiviral agent for influenza offered as soon as they become influenza treatment and works by a different mechanism than available. Children needing only chemoprophylaxis in children of all NAIs and requires only a single oral 1 dose of influenza vaccine, ages can be found in Table 3 dose for treatment of uncomplicated regardless of age, should also (including doses for preterm infants influenza.68 A clinical trial of receive the vaccination ideally by that have not been evaluated by the baloxavir treatment of influenza in the end of October. FDA) and on the CDC Web site (www. cdc.gov/flu/professionals/antivirals/ hospitalized patients is ongoing 7. Efforts should be made to index.htm). These include the (https://clinicaltrials.gov/ct2/show/ ensure vaccination for children in neuraminidase inhibitors (NAIs) NCT03684044?cond=baloxavir&ra high-risk groups (Table 1) and (oseltamivir, zanamivir, peramivir) nk=6). their contacts unless and a selective inhibitor of influenza contraindicated. cap-dependent endonuclease INFLUENZA TREATMENT fi 8. Product-speci c (baloxavir),64 all of which have contraindications must be activity against influenza A and B In RCTs conducted to date to evaluate fi fl considered when selecting the viruses. the ef cacy of in uenza antiviral type of vaccine to administer. medications among outpatients with Children who have had an Oral oseltamivir remains the antiviral uncomplicated influenza, researchers allergic reaction after a previous drug of choice for the management of have found that timely treatment can dose of any influenza vaccine illness caused by influenza virus reduce the duration of influenza should be evaluated by an infections. Although more difficult to symptoms and fever, as well as the allergist to determine whether administer, inhaled zanamivir risk of certain complications, future receipt of the vaccine is (Relenza) is an equally acceptable including hospitalization and death in appropriate. alternative for patients who do not pediatric and adult have chronic respiratory disease. populations.30,31,41,42,45,69,70 The 9. Children with egg allergy can Options are limited for children who number of published RCTs in children receive influenza vaccine without cannot absorb orally or enterally is limited, and interpretation of the any additional precautions administered oseltamivir or tolerate results of these studies needs to take beyond those recommended for inhaled zanamivir. Intravenous (IV) into consideration the size of the all vaccines. peramivir (Rapivab), a third NAI, was study (the number of events might 10. Pregnant women may receive IIV approved in September 2017 as not be sufficient to assess specific at any time during pregnancy to treatment of acute uncomplicated outcomes in small studies), the protect themselves and their influenza in nonhospitalized children variations in the case definition of infants who benefit from the 2 years and older who have been influenza illness (clinically diagnosed transplacental transfer of symptomatic for no more than 2 days. versus laboratory confirmed), the antibodies. Postpartum women The efficacy of peramivir in patients time of treatment administration in who did not receive vaccination with serious influenza requiring relation to the onset of illness, and the during pregnancy should be hospitalization has not been child’s age and health status as encouraged to receive influenza established.65 A prospective, open- important variables. A Cochrane vaccine before discharge from label pediatric clinical trial was review of 6 RCTs2,3,71 involving the hospital. Influenza conducted to investigate treatment of 2356 children with vaccination during breastfeeding pharmacokinetics and the clinical and clinical influenza,1,2,72 of whom 1255

Downloaded from www.aappublications.org/news by guest on October 4, 2021 14 FROM THE AMERICAN ACADEMY OF PEDIATRICS TABLE 3 Recommended Dosage and Schedule of Influenza Antiviral Medications for Treatment and Chemoprophylaxis in Children for the 2019–2020 Influenza Season: United States Medication Treatment (5 d) Chemoprophylaxis (10 d)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 .15–23 kg (33–51 lb) 45 mg, twice daily 45 mg, once daily .23–40 kg (.51–88 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 wk’ postmenstrual age 1.0 mg/kg per dose, twice daily — 38 through 40 wk’ 1.5 mg/kg per dose, twice daily — postmenstrual age .40 wk’ 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 IV infusion, given over 15–30 min Not recommended Children (2–12 y) One 12 mg/kg dose, up to 600 mg maximum, via Not recommended IV infusion for 15–30 min Children (13–17 y) One 600 mg dose, via IV infusion for 15–30 min Not recommended 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 Guidelines65 and https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm. —, not applicable. 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 of oral suspension, a 60-mg dose is given with 10 mL of oral suspension, and a 75-mg dose is given with 12.5 mL of 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) on the basis of 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 d. For chemoprophylaxis of patients with creatinine clearance 10–30 mL/min: 30 mg, once daily, for 10 d after exposure or 75 mg, once every other day, for 10 d after exposure (5 doses). See https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm and IDSA guidelines.65 c Approved by the FDA for children as young as 2 wk of age. Given preliminary pharmacokinetic data and limited safety data, oseltamivir can be used to treatinfluenza 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 per dose, twice daily, for all infants ,12 mo old; the IDSA guidelines65 include both AAP and CDC recommendations. d Oseltamivir dosing for preterm infants. The wt-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 term infants may lead to 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. had laboratory-confirmed influenza, children with asthma who had 95% CI, 20.24 to 20.04).73 Authors revealed that in children with laboratory-confirmed influenza of another Cochrane review of RCTs laboratory-confirmed influenza, oral revealed only a nonsignificant in adults and children, which oseltamivir and inhaled zanamivir reduction in illness duration (10.4 included 20 oseltamivir (9623 reduced the median duration of hours; 8%; P = .542). Oseltamivir participants) and 26 zanamivir trials illness by 36 hours (26%; P , .001) significantly reduced acute otitis (14 628 participants),74 found no and 1.3 days (24%, P , .001), media in children 1 through 5 years effect of oseltamivir in reducing the respectively.68 Among the studies of age with laboratory-confirmed duration of illness in asthmatic reviewed, 1 trial of oseltamivir in influenza (risk difference, 20.14; children, but in otherwise healthy

Downloaded from www.aappublications.org/news by guest on October 4, 2021 PEDIATRICS Volume 144, number 4, October 2019 15 children, there was a reduction by severe laboratory-confirmed treat influenza in both term and a mean difference of 29 hours (95% influenza in Spain spanning 6 preterm infants from birth because CI, 12 to 47 hours; P = .001). No influenza seasons (2010–2016), the benefits of therapy of neonatal significant effect was observed with authors evaluated the effectiveness of influenza are likely to outweigh the zanamivir. Regarding complications, NAIs, concluding that when started possible risks of treatment. the authors of this review did not find early after the onset of symptoms a significant effect of NAIs on (#48 hours or #5 days), NAI Oseltamivir is available in capsule reducing hospitalizations, pneumonia, treatment was associated with and oral suspension formulations. bronchitis, otitis media, or sinusitis in a reduction in influenza-associated The available capsule doses are 30, children.75 More recently, a meta- deaths (adjusted odds ratio, 0.37; 45, and 75 mg, and the commercially analysis of 5 new RCTs that included 95% CI, 0.22 to 0.63l, and adjusted manufactured liquid formulation has 1598 children with laboratory- odds ratio, 0.50; 95% CI, 0.32 to 0.79, a concentration of 6 mg/mL in a 60- confirmed influenza revealed that respectively).80,81 However, treatment mL bottle. If the commercially treatment with oseltamivir initiation more than 5 days after the manufactured oral suspension is not significantly reduced the duration of onset of influenza symptoms was not available, the capsule may be opened illness in this population by 17.6 associated with reduction in mortality and the contents mixed with simple hours (95% CI, 234.7 to 20.62 in hospitalized adults. syrup or Ora-Sweet SF (sugar free) by fi hours), and when children with retail pharmacies to a nal Importantly, and despite limited asthma were excluded, this difference concentration of 6 mg/mL. evidence for efficacy, treatment with was larger (229.9 hours; 95% CI, oseltamivir for children with serious, In adverse event data collected 253.9 to 25.8 hours). The risk of complicated, or progressive disease systematically in prospective trials, otitis media was 34% lower in this presumptively or definitively caused vomiting was the only adverse effect group as well.31 Overall, efficacy by influenza, irrespective of influenza reported more often with oseltamivir outcomes are best demonstrated in vaccination status (the circulating compared to placebo when studied in patients with laboratory-confirmed strains may not be well matched with children 1 through 12 years of age (ie, influenza. All these studies confirmed vaccine strains) or whether illness 15% of treated children vs 9% vomiting as an occasional side effect began greater than 48 hours before receiving placebo). In addition, after of oseltamivir, occurring in admission, continues to be reports from Japan of oseltamivir- approximately 5% of treated patients. recommended by the AAP, CDC, attributable neuropsychiatric adverse The balance between benefits and Infectious Diseases Society of effects, authors of a review of harms should be considered when America (IDSA),65 and Pediatric controlled clinical trial data and making decisions about the use of Infectious Diseases Society (PIDS). ongoing surveillance have failed to NAIs for either treatment or Earlier treatment provides better establish a link between this drug and chemoprophylaxis of influenza. 66,82 clinical responses. However, neurologic or psychiatric events. treatment after 48 hours of Although prospective comparative Clinical judgment (based on symptoms in adults and children with studies used to determine the efficacy underlying conditions, disease moderate-to-severe disease or with of influenza antiviral medications in severity, time since symptom onset, progressive disease has been shown hospitalized patients or pediatric and local influenza activity) is an to provide some benefit and should patients with comorbidities have not important factor in treatment be offered. No benefit exists for been conducted, and prospectively decisions for pediatric patients who double-dose NAI therapy, compared collected data used to determine the present with influenzalike illness. to standard-dose therapy, on the basis role of antiviral agents in treating Antiviral treatment should be started of published data from a randomized severe influenza are limited, on the as soon as possible after illness onset prospective trial enrolling 75% of basis of information obtained from and should not be delayed while subjects younger than 15 years.1 retrospective observational studies waiting for a definitive influenza test and meta-analyses conducted to date Children younger than 2 years are at result because early therapy provides in both adults and children, most an increased risk of hospitalization the best outcomes. Influenza experts support the use of antiviral and complications attributable to diagnostic tests vary by method, medications as soon as possible to influenza. The FDA has approved availability, processing time, treat pediatric patients with severe oseltamivir for treatment of children sensitivity, and cost (Table 4), all of influenza, including hospitalized as young as 2 weeks. Given which should be considered in – patients.76 79 In an observational preliminary pharmacokinetic data making the best clinical decision. epidemiological study conducted in and limited safety data, the CDC and Positive and negative predictive adult patients hospitalized with AAP support the use of oseltamivir to values of influenza test results are

Downloaded from www.aappublications.org/news by guest on October 4, 2021 16 FROM THE AMERICAN ACADEMY OF PEDIATRICS influenced by the level of influenza test confirmation are preferred in consulted to provide additional activity in the population being hospitalized patients because they are guidance about testing and treatment. tested, the characteristics of a test more sensitive compared to antigen In previous years, local shortages of compared to a gold standard, pretest detection. Early detection, prompt oseltamivir suspension have occurred probability, whether the influenza antiviral treatment, and infection because of uneven drug distribution, virus is actively replicating in the control interventions can lead to although national shortages have not person, proper collection and improved individual patient occurred since 2009, particularly transport of specimens, and proper outcomes and allow for effective given the availability of the capsule test procedures. Testing should be cohorting and disease containment. formulation that can be made into performed when timely results will a suspension for young children if be available to influence clinical People with suspected influenza who needed (Table 3). management or infection control are at higher risk of influenza measures. Although decisions on complications should be offered INFLUENZA CHEMOPROPHYLAXIS treatment and infection control can treatment with antiviral medications be made on the basis of positive rapid (Table 1). Efforts should be made to Randomized placebo-controlled antigen test results, negative results minimize treatment of patients who studies revealed that oral oseltamivir should not always be used in a similar are not infected with influenza. and inhaled zanamivir were fashion because of the suboptimal Otherwise healthy children who have efficacious when administered as sensitivity and potential for false- suspected influenza with an chemoprophylaxis to household negative results. Positive results of uncomplicated presentation should contacts after a family member had rapid influenza tests are helpful, be considered for antiviral laboratory-confirmed influenza.1,41 because they may reduce additional medication, particularly if they are in There are no data on IV peramivir or testing to identify the cause of the contact with other children who oral baloxavir for chemoprophylaxis. child’sinfluenzalike illness and either are younger than 6 months During the 2009 pandemic, the promote appropriate antimicrobial (because they are not able to receive emergence of oseltamivir resistance stewardship. Available FDA-approved influenza vaccine) or have high-risk was noted rarely among people rapid molecular assays are highly conditions (including young age) that receiving postexposure sensitive and specific in diagnostic predispose them to complications of chemoprophylaxis, highlighting the tests performed in ,20 minutes influenza, when influenza viruses are need to be aware of the possibility of using RNA detection. These and other known to be circulating in the emerging resistance in this FDA-approved influenza molecular community. If there is a local shortage population. Decisions on whether to assays or reverse transcription of antiviral medications, local public administer antiviral polymerase chain reaction (RT-PCR) health authorities should be chemoprophylaxis should take into

TABLE 4 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 antigens 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 assays specificity 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, other Yes, if subtype primers 1–2 h High sensitivity; high specificity amplification viral or bacterial targets are used (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 test 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 to RT-PCR. FDA-cleared rapid influenza diagnostic tests are waived by the Clinical Laboratory Improvement Amendments of 1988; most FDA-cleared rapid influenza molecular assays are waived by the Clinical Laboratory Improvement Amendments of 1988, depending on the specimen. Adapted from Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical practice guidelines by the Infectious Diseases Society of America: 2018 update on diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenza. Clin Infect Dis. 2019;68(6):e13.

Downloaded from www.aappublications.org/news by guest on October 4, 2021 PEDIATRICS Volume 144, number 4, October 2019 17 account the exposed person’s risk of www.cdc.gov/flu/professionals/ medications because of prolonged influenza complications, vaccination antivirals/index.htm. viral shedding. Up-to-date status, the type and duration of information on current contact, recommendations from local recommendations and therapeutic or public health authorities, and ANTIVIRAL RESISTANCE options can be found on the AAP Web clinical judgment. Optimally, Antiviral resistance to any drug can site (www.aap.org or www. fl postexposure chemoprophylaxis emerge, necessitating continuous aapredbook.org/ u), through state- fi should only be used when antiviral population-based assessment that is speci c AAP chapter websites, or on fl agents can be started within 48 hours conducted by the CDC. During the the CDC Web site (www.cdc.gov/ u/). of exposure; the lower once-daily 2018–2019 season, .99% of dosing for chemoprophylaxis influenza A(/H1N1)pdm09 viruses with oral oseltamivir or inhaled INFLUENZA ANTIVIRALS tested were susceptible to oseltamivir RECOMMENDATIONS zanamivir should not be used for the and peramivir, and all of the tested treatment of children symptomatic influenza virus strains were Treatment recommendations for fl with in uenza. Early, full susceptible to zanamivir. All tested antiviral medications for the treatment doses (rather than influenza A(H3N2) viruses were 2019–2020 season are applicable to chemoprophylaxis doses) should be susceptible to oseltamivir, zanamivir, infants and children with suspected used in high-risk symptomatic and peramivir. Influenza B virus influenza when influenza viruses are patients without waiting for strains were all susceptible to known to be circulating in the fi laboratory con rmation. oseltamivir and zanamivir, and .99% community or when infants or were susceptible to peramivir. children are tested and confirmed to Chemoprophylaxis should not be Decreased susceptibility to baloxavir have influenza. Continuous considered a substitute for has been reported in Japan where use monitoring of the epidemiology, fl – vaccination. In uenza vaccine should has been more common,83 85 and change in severity, and resistance always be offered before and surveillance for resistance among patterns of influenza virus strains by fl throughout the in uenza season circulating influenza viruses is the CDC may lead to new guidance. when not contraindicated. Antiviral ongoing in the United States.83,86 In Oseltamivir (oral), zanamivir medications are important adjuncts contrast, high levels of resistance to (inhaled), peramivir (IV), and fl to in uenza vaccination for the amantadine and rimantadine persist baloxavir (oral) are FDA approved for fl control and prevention of in uenza among the influenza A viruses treatment of uncomplicated influenza disease. Toxicities may be associated currently circulating. Adamantane virus infection in pediatric with antiviral agents, and medications are not recommended outpatients; published data exist to indiscriminate use might limit for use against influenza unless support the use of oseltamivir (oral) availability. Pediatricians should resistance patterns change.1 for hospitalized children and children inform recipients of antiviral at high risk. For more serious chemoprophylaxis that the risk of Recent viral surveillance and influenza virus infections, particularly fl in uenza is lowered but still remains resistance data from the CDC and in immune compromised children, while taking the medication, and WHO indicate that the majority of seeking the advice of an infectious fl susceptibility to in uenza returns currently circulating influenza viruses diseases specialist is suggested. when the medication is discontinued. likely to cause influenza in North Oseltamivir use is not America during the 2019–2020 a contraindication to vaccination with season continue to be susceptible to ANTIVIRAL TREATMENT IIV, although LAIV effectiveness will oseltamivir, zanamivir, peramivir, and RECOMMENDATIONS be decreased for the child receiving baloxavir.1 If a newly emergent Regardless of influenza vaccination oseltamivir.66 No data are available on oseltamivir- or peramivir-resistant status, antiviral treatment should be the impact of inhaled zanamivir or virus is a concern, recommendations offered as early as possible to the oral baloxavir on the effectiveness of for alternative treatment, such as use following individuals: LAIV, but it is likely that all antiviral of IV zanamivir,87,88 will be available • medication will have some impact on from the CDC and AAP. Resistance any hospitalized child with fi fl effectiveness of LAIV. Among some characteristics can change for an suspected or con rmed in uenza high-risk people, both vaccination individual child over the duration of disease, regardless of the duration with IIV and antiviral a treatment course, especially in of symptoms; chemoprophylaxis may be those who are severely • any child, inpatient or outpatient, considered. Updates will be available immunocompromised and may with severe, complicated, or at www.aapredbook.org/flu and receive extended courses of antiviral progressive illness attributable to

Downloaded from www.aappublications.org/news by guest on October 4, 2021 18 FROM THE AMERICAN ACADEMY OF PEDIATRICS influenza, regardless of the ongoing, close exposure to the FUTURE DIRECTIONS duration of symptoms; and following: Safety and effectiveness data for • children with influenza virus ○ unvaccinated children at high influenza vaccines used during the infection of any severity who are at risk; or 2019–2020 season will be analyzed high risk of complications of ○ unvaccinated infants and as they become available and fl in uenza, as listed in Table 1, toddlers who are younger than reported by the CDC as they are each 89 regardless of the duration of 24 months; season. Continued evaluation of the symptoms. safety, immunogenicity, and • for control of influenza outbreaks effectiveness of influenza vaccine, Antiviral treatment may be for unvaccinated staff and children especially for at-risk populations, is considered for the following in a closed institutional setting with important. The duration of protection individuals: children at high risk (eg, extended- and the potential role of previous • any previously healthy, care facilities); influenza vaccination on overall VE symptomatic outpatient not at high • as a supplement to IIV vaccination and VE by vaccine formulation, virus risk for influenza complications among children at high risk, strain, timing of vaccination, and who is diagnosed with confirmed including children who are subject age and health status in or suspected influenza, on the basis immunocompromised and may not preventing outpatient medical visits, of clinical judgment, if treatment fi respond with suf cient protective hospitalizations, and deaths continue can be initiated within 48 hours of fl immune responses after in uenza to be evaluated. Research to better illness onset; and vaccination; understand how to educate parents • children with suspected or • as postexposure antiviral about influenza symptoms and how confirmed influenza disease whose chemoprophylaxis for family to recognize when to seek medical siblings or household contacts members and close contacts of an attention would be informative. either are younger than 6 months infected person if those people are Additionally, with limited data on the or have a high-risk condition that at high risk of complications from use of antiviral agents in hospitalized predisposes them to complications influenza; and children and in children with of influenza as listed in Table 1. • for children at high risk of underlying medical conditions, Efforts should be made to minimize complications and their family prospective clinical trials to inform fi treatment of patients who are not members and close contacts, as optimal timing and ef cacy of infected with influenza viruses. well as HCP, when circulating antiviral treatment and in these strains of influenza virus in the populations are warranted. community are not well matched ANTIVIRAL CHEMOPROPHYLAXIS There is also a need for more by seasonal influenza vaccine virus RECOMMENDATIONS systematic health services research strains on the basis of current data Although vaccination is the preferred on influenza vaccine uptake and from the CDC and state or local approach to prevention of infection, refusal as well as identification of health departments. chemoprophylaxis during an methods to enhance uptake. Further influenza season, as defined by the These recommendations apply to investigation is needed about vaccine CDC (https://www.cdc.gov/flu/ routine circumstances, but it should acceptance and hesitancy and professionals/antivirals/summary- be noted that guidance may change methods to overcome parental clinicians.htm), is recommended in on the basis of updated concerns and improve coverage. This the following situations: recommendations from the CDC in may include evaluating the strategy of concert with antiviral availability, offering to immunize parents and • for children at high risk of local resources, clinical judgment, adult child care providers in the complications from influenza for recommendations from local or pediatric office setting and whom influenza vaccine is public health authorities, risk of understanding the level of family contraindicated; influenza complications, type and contact satisfaction with this • for children at high risk during the duration of exposure contact, and approach; how practices handle the fl 2 weeks after IIV in uenza change in epidemiology (resistance, logistic, liability, legal, and financial vaccination, before optimal antigenic shift) or severity of barriers that limit or complicate this immunity is achieved (prophylaxis influenza. Chemoprophylaxis is not service; and most importantly, how after LAIV may decrease vaccine routinely recommended for infants this practice may affect disease rates fi ef cacy); younger than 3 months given limited in children and adults. Furthermore, • for family members or HCP who are safety and efficacy data in this ongoing efforts should include unvaccinated and are likely to have age group. broader implementation and

Downloaded from www.aappublications.org/news by guest on October 4, 2021 PEDIATRICS Volume 144, number 4, October 2019 19 evaluation of mandatory HCP With the increased demand for immunogenic vaccine for infants vaccination programs in both vaccination during each influenza younger than 6 months are essential. inpatient and outpatient settings. season, the AAP and CDC recommend Studies on the effectiveness and vaccine administration at any visit to safety of influenza vaccines Efforts should be made to create the medical home during influenza containing adjuvants that enhance adequate outreach and infrastructure season when it is not contraindicated, immune responses to influenza to facilitate the optimal distribution at specially arranged vaccine-only vaccines or that use novel routes of of vaccine so that more people are sessions, and through cooperation administration (such as microneedle immunized. Pediatricians should with community sites, schools, and patch) are ongoing.90 Efforts to consider becoming more involved in Head Start and child care facilities to improve the vaccine development pandemic preparedness and disaster provide influenza vaccine. It is process to allow for a shorter interval planning efforts (especially in important that the annual delivery of between identification of vaccine collaboration with schools and child influenza vaccine to primary care strains and vaccine production care programs). A bidirectional medical homes should be timely to continue. Many antiviral drugs are in partner dialogue between avoid missed opportunities. If various development phases, given pediatricians and public health alternate venues, including the need to improve options for the decision makers assists efforts to pharmacies and other retail-based treatment and chemoprophylaxis of address children’s issues during the clinics, are used for vaccination, influenza. Finally, pediatricians initial state, regional, and local plan a system of patient record transfer is should remain informed during the development stages. Pandemic beneficial in maintaining the accuracy influenza season by following the CDC influenza preparedness of directors of of immunization records. influenza page (www.cdc/gov/flu) child care centers also needs to Immunization information systems and the AAP Red Book Online improve. Additional information can should be used whenever available Influenza Resource Page (www. be found at www.aap.org/disasters/ and prioritized to document influenza aapredbook.org/flu). resourcekit and https://pediatrics. vaccination. Two-dimensional aappublications.org/content/ barcodes have been used to facilitate pediatrics/early/2017/05/11/peds. more efficient and accurate SUMMARY OF RECOMMENDATIONS 2016-3690.full.pdf. documentation of vaccine administration with limited 1. The AAP recommends annual Pandemic influenza preparedness is experience to date. Additional influenza vaccination for of particular interest because of the information concerning current everyone 6 months and older, increase in the number of human vaccines shipped with two- including children and infections with Asian H7N9 virus dimensional barcodes can be found at adolescents, during the reported in China (updates available www.cdc.gov/vaccines/programs/ 2019–2020 influenza season. at https://www.cdc.gov/flu/avianflu/ iis/2d-vaccine-barcodes/. h7n9-virus.htm). All cases of H7N0 2. For the 2019–2020 season, the Access to care issues, lack of virus infection identified outside of AAP recommends that any immunization records, and questions mainland China (eg, Taiwan, Malaysia, licensed influenza vaccine regarding who can provide consent Canada) had exposure and were appropriate for age and health may be addressed by linking children infected in China and were identified status can be used for influenza (eg, those in foster care or a juvenile outside China after becoming ill. vaccination in children. IIV and justice system or refugee, immigrant, Although the current risk to the LAIV are options for children for or homeless children) with a medical public’s health from this virus is low, whom these vaccines are home, using all health care Asian H7N9 virus is among the appropriate. This encounters as vaccination nonhuman influenza viruses that are recommendation is based on opportunities and more consistently most concerning to public health review of current available data using immunization registry data. officials because of their pandemic on LAIV and IIV VE. The AAP will potential and ability to cause severe Development efforts continue for continue to review VE data as disease in infected humans. The a universal influenza vaccine that they become available and current risk to public health from the induces broader protection and update these recommendations if virus remains low; however, the CDC eliminates the need for annual necessary. is monitoring the situation carefully vaccination. In addition, 3. The AAP does not have and taking routine preparedness understanding the establishment of a preference for any influenza measures, including testing candidate immunity against influenza in early vaccine product over another for vaccines. life and developing a safe, children who have no

Downloaded from www.aappublications.org/news by guest on October 4, 2021 20 FROM THE AMERICAN ACADEMY OF PEDIATRICS contraindication to influenza allergist to determine whether 13. Antiviral treatment should be vaccination and for whom more future receipt of the vaccine is offered as early as possible to the than one licensed product appropriate. following individuals, regardless fl appropriate for age and health 9. Children with egg allergy can of in uenza vaccination status: status is available. Pediatricians receive influenza vaccine without ○ any hospitalized child with should administer whichever any additional precautions suspected or confirmed formulation is available in their beyond those recommended for influenza disease, regardless of communities to achieve the all vaccines. the duration of symptoms; highest possible coverage this 10. Pregnant women may receive an ○ any child, inpatient or influenza season. IIV at any time during outpatient, with severe, 4. Children 6 through 35 months of pregnancy to protect complicated, or progressive age may receive either a 0.25- or themselves and their infants illness attributable to 0.5-mL dose of the licensed, age- who benefitfromthe influenza, regardless of the appropriate IIVs available this transplacental transfer of duration of symptoms; and season. No product or formulation antibodies. Postpartum women ○ children with influenza is preferred over another for this who did not receive vaccination infection of any severity who age group. Children 36 months (3 during pregnancy should be are at high risk of years) and older should receive encouraged to receive an complications of influenza influenza vaccine before a0.5-mLdoseofanyavailable, infection (Table 1), regardless discharge from the hospital. licensed, age-appropriate of the duration of symptoms. inactivated vaccine. Influenza vaccination during 14. Treatment may be considered for fl breastfeeding is safe for 5. The number of seasonal in uenza the following individuals: vaccine doses recommended to mothers and their infants. ○ be administered to children in 11. The AAP supports mandatory any previously healthy, the 2019–2020 influenza season vaccination of HCP as a crucial symptomatic outpatient not at fl remains unchanged and depends element in preventing influenza high risk for in uenza on the child’s age at the time of and reducing health complications who is diagnosed fi the first administered dose and care–associated influenza with con rmed or suspected fl vaccine history (Fig 1). infections because HCP often in uenza, on the basis of care for individuals at high risk clinical judgment, if treatment 6. Children 6 months through 8 years for influenza-related can be initiated within 48 hours of age who are receiving an complications. of illness onset; and influenza vaccine for the first time ○ children with suspected or or who have received only 1 dose 12. Antiviral medications are confirmed influenza disease before July 1, 2019, should receive important in the control of fl whose siblings or household 2dosesofinfluenza vaccine ideally in uenza but are not a substitute fl contacts either are younger by the end of October, and vaccines for in uenza vaccination. than 6 months or have a high- should be offered as soon as they Pediatricians should promptly risk condition that predisposes become available. Children identify their patients suspected fl them to complications of needing only 1 dose of influenza of having in uenza infection for influenza (Table 1). vaccine, regardless of age, should timely initiation of antiviral also receive vaccination ideally by treatment, when indicated and 15. Antiviral chemoprophylaxis is the end of October. based on shared decision-making recommended in the following between the pediatrician and situations: 7. Efforts should be made to ensure child’s caregiver, to reduce ○ for children at high risk of vaccination for children in high- morbidity and mortality. complications from influenza risk groups (Table 1) and their Although the best results are for whom influenza vaccine is contacts, unless contraindicated. observed when the child is contraindicated. 8. Product-specific contraindications treated within 48 hours of ○ must be considered when symptom onset, antiviral therapy for children at high risk during fl selecting the type of vaccine to should still be considered beyond the 2 weeks after in uenza administer. Children who have 48 hours of symptom onset in vaccination, before optimal had an allergic reaction after children with severe disease or immunity is achieved. apreviousdoseofanyinfluenza those at high risk of ○ for family members or HCP vaccine should be evaluated by an complications. who are unvaccinated and are

Downloaded from www.aappublications.org/news by guest on October 4, 2021 PEDIATRICS Volume 144, number 4, October 2019 21 likely to have ongoing, close Dawn Nolt, MD, MPH, FAAP reviews, analyses of unpublished exposure to the following: Ann-Christine Nyquist, MD, MSPH, FAAP data, and deliberations with the ACIP ’ Sean T. O Leary, MD, MPH, FAAP Influenza Work Group, with liaison unvaccinated children at high William J. Steinbach, MD, FAAP risk; or Ken Zangwill, MD, FAAP from the AAP. unvaccinated infants and EX OFFICIO toddlers who are younger ABBREVIATIONS than 24 months. Henry H. Bernstein, DO, MHCM, FAAP, Red AAP: American Academy of ○ for the control of influenza Book Online Associate Editor David W. Kimberlin, MD, FAAP, Red Book Pediatrics outbreaks for unvaccinated Editor ACIP: Advisory Committee on staff and children in a closed H. Cody Meissner, MD, FAAP, Visual Red Immunization Practices institutional setting with Book Associate Editor CDC: Centers for Disease Control children at high risk (eg, Mark H. Sawyer, MD, FAAP, Red Book and Prevention extended-care facilities); Associate Editor CI: confidence interval ○ as a supplement to vaccination CONTRIBUTORS FDA: US Food and Drug among children at high risk, Administration – including children who are Stuart T. Weinberg, MD, FAAP Partnership GBS: Guillain-Barré syndrome immunocompromised and may for Policy Implementation – HA: hemagglutinin not respond with sufficient John M. Kelso, MD, FAAP Scripps Clinic John S. Bradley, MD, FAAP – University of HCP: health care personnel protective immune responses California, San Diego/Rady Children’s IDSA: Infectious Diseases Society fl after in uenza vaccination; Hospital of America – ○ as postexposure antiviral Tim Uyeki, MD Centers for Disease Control IIV: inactivated influenza vaccine and Prevention chemoprophylaxis for family IIV3: trivalent inactivated members and close contacts of influenza vaccine an infected person if those LIAISONS IIV4: quadrivalent inactivated people are at high risk of Amanda C. Cohn, MD, FAAP – Centers for influenza vaccine complications from influenza; Disease Control and Prevention IV: intravenous and Tammy R. Beckman, DVM, PhD, National LAIV: live attenuated influenza Vaccine Advisory Committee ○ for children at high risk of Jamie Deseda-Tous, MD – Sociedad vaccine complications and their family Latinoamericana de Infectologia Pediatrica LAIV3: trivalent live attenuated members and close contacts, as Karen M. Farizo, MD – US Food and Drug influenza vaccine Administration LAIV4: quadrivalent live well as HCP, when circulating – fl Marc Fischer, MD, FAAP Centers for Disease attenuated influenza strains of in uenza virus in the Control and Prevention community are not well Natasha B. Halasa, MD, MPH, FAAP – vaccine matched by seasonal influenza Pediatric Infectious Diseases Society NAI: neuraminidase inhibitor vaccine virus strains on the Nicole Le Saux, MD, FRCP(C) – Canadian PCV13: 13-valent pneumococcal Pediatric Society conjugate vaccine basis of current data from the – Scot Moore, MD, FAAP Committee on RCT: randomized controlled trial CDC and state or local health Practice Ambulatory Medicine departments. Neile S. Silverman, MD – American College of RIV4: quadrivalent recombinant Obstetricians and Gynecologists influenza vaccine Jeffrey R. Starke, MD, FAAP – American RT-PCR: reverse transcription COMMITTEE ON INFECTIOUS DISEASES, Thoracic Society polymerase chain 2019–2020 – James J. Stevermer, MD, MSPH, FAAFP reaction Yvonne A. Maldonado, MD, FAAP, American Academy of Family Physicians Kay M. Tomashek, MD, MPH, DTM, – National VE: vaccine effectiveness Chairperson WHO: World Health Organization Theoklis E. Zaoutis, MD, MSCE, FAAP, Vice Institutes of Health Chairperson Ritu Banerjee, MD, PhD, FAAP STAFF Elizabeth D. Barnett, MD, FAAP, Red Book Associate Editor Jennifer M. Frantz, MPH REFERENCES James D. Campbell, MD, MS, FAAP 1. Centers for Disease Control and Mary T. Caserta, MD, FAAP ACKNOWLEDGMENTS Prevention. Prevention and control of Jeffrey S. Gerber, MD, PhD, FAAP This AAP policy statement was fl Athena P. Kourtis, MD, PhD, MPH in uenza with vaccines: Ruth Lynfield, MD, FAAP, Red Book Associate prepared in parallel with CDC recommendations of the Advisory Editor recommendations and reports. This Committee on Immunization Practices, Flor M. Munoz, MD, MSc, FAAP statement is based on literature United States, 2019–20 influenza

Downloaded from www.aappublications.org/news by guest on October 4, 2021 22 FROM THE AMERICAN ACADEMY OF PEDIATRICS season. MMWR Recomm Rep. 2019; 11. Lessin HR, Edwards KM; Committee on https://www.fda.gov/vaccines-blood- 68(3):1–21 Practice and Ambulatory Medicine; biologics/vaccines/fluzone- Committee on Infectious Diseases. quadrivalent. Accessed June 24, 2019 2. Shope TR, Walker BH, Aird LD, et al. Immunizing parents and other close Pandemic influenza preparedness 20. Robertson CA, Mercer M, Selmani A, family contacts in the pediatric office among child care center directors in et al. Safety and immunogenicity of setting. Pediatrics. 2012;129(1). 2008 and 2016. Pediatrics. 2017;139(6): a full-dose, split-virion, inactivated, Available at: www.pediatrics.org/cgi/ e20163690 quadrivalent influenza vaccine in content/full/129/1/e247 healthy children 6-35 months of age: 3. Garten R, Blanton L, Elal AIA, et al. 12. Miyakawa R, Barreto NB, Kato RM, Neely a randomized controlled clinical trial. fl Update: in uenza activity in the United MN, Russell CJ. Early use of anti- Pediatr Infect Dis J. 2019;38(3):323–328 States during the 2017-18 season and influenza medications in hospitalized composition of the 2018-19 influenza children with tracheostomy. Pediatrics. 21. Claeys C, Zaman K, Dbaibo G, et al; vaccine. MMWR Morb Mortal Wkly Rep. 2019;143(3):e20182608 Flu4VEC Study Group. Prevention of 2018;67(22):634–642 vaccine-matched and mismatched 13. Grohskopf LA, Sokolow LZ, Broder KR, influenza in children aged 6-35 months: 4. Centers for Disease Control and et al. Prevention and control of a multinational randomised trial across fl Prevention. Seasonal in uenza vaccine seasonal influenza with vaccines: five influenza seasons. Lancet Child effectiveness, 2017-2018. Available at: recommendations of the Advisory Adolesc Health. 2018;2(5):338–349 https://www.cdc.gov/flu/vaccines- Committee on Immunization Practices work/2017-2018.html. Accessed May 31, —United States, 2019–20 influenza 22. Jain VK, Domachowske JB, Wang L, et al. 2019 season. MMWR Recomm Rep. 2019 Time to change dosing of inactivated quadrivalent influenza vaccine in young 5. Biggerstaff M, Kniss K, Jernigan DB, 14. World Health Organization. children: evidence from a phase III, fl et al. Systematic assessment of Recommended composition of in uenza randomized, controlled trial. J Pediatric multiple routine and near real-time virus vaccines for use in the 2019-2020 Infect Dis Soc. 2017;6(1):9–19 indicators to classify the severity of northern hemisphere influenza season. influenza seasons and pandemics in the Available at: https://www.who.int/ 23. Duffy J, Weintraub E, Hambidge SJ, et al; United States, 2003-2004 through 2015- influenza/vaccines/virus/ Vaccine Safety Datalink. Febrile seizure 2016. Am J Epidemiol. 2018;187(5): recommendations/2019_20_north/en/. risk after vaccination in children 6 to 1040–1050 Accessed March 21, 2019 23 months. Pediatrics. 2016;138(1): e20160320 6. Xu X, Blanton L, Elal AIA, et al. Update: 15. US Food and Drug Administration. influenza activity in the United States Afluria quadrivalent. 2018. Available at: 24. Thompson CA. Vaccine safety signal during the 2018-19 season and https://www.fda.gov/vaccines-blood- from spontaneous system not composition of the 2019-20 influenza biologics/vaccines/afluria-quadrivalent. supported by active surveillance. Am vaccine. MMWR Morb Mortal Wkly Rep. Accessed June 24, 2019 J Health Syst Pharm. 2014;71(17): – 2019;68(24):544–551 16. Vesikari T, Kirstein J, Devota Go G, et al. 1432 1433 Efficacy, immunogenicity, and safety 7. Centers for Disease Control and 25. Sentinel. Sentinel CBER/PRISM evaluation of an MF59-adjuvanted fl Prevention. Weekly U.S. influenza surveillance report: in uenza vaccines quadrivalent influenza virus vaccine surveillance report (FluView). Available and febrile seizures in the 2013-2014 compared with non-adjuvanted fl at: https://www.cdc.gov/flu/weekly/. and 2014-2015 in uenza seasons. 2017. influenza vaccine in children: Accessed May 31, 2019 Available at: https://www. a multicentre, randomised controlled, sentinelinitiative.org/sites/default/files/ 8. Flannery B, Reynolds SB, Blanton L, observer-blinded, phase 3 trial. Lancet vaccines-blood-biologics/assessments/ et al. Influenza vaccine effectiveness Respir Med. 2018;6(5):345–356 Influenza-Vaccines-Febrile-Seizures- against pediatric deaths: 2010-2014. 17. Groothuis JR, Levin MJ, Rabalais GP, Final-Report.pdf. Accessed June 24, Pediatrics. 2017;139(5):e20164244 Meiklejohn G, Lauer BA. Immunization of 2019 9. Ferdinands JM, Olsho LE, Agan AA, et al; high-risk infants younger than 26. Grohskopf LA, Sokolow LZ, Fry AM, Pediatric Acute Lung Injury and Sepsis 18 months of age with split-product Walter EB, Jernigan DB. Update: ACIP Investigators (PALISI) Network. influenza vaccine. Pediatrics. 1991; recommendations for the use of Effectiveness of influenza vaccine 87(6):823–828 quadrivalent live attenuated influenza against life-threatening RT-PCR- 18. Halasa NB, Gerber MA, Berry AA, et al. vaccine (LAIV4) - United States, 2018-19 confirmed influenza illness in US Safety and immunogenicity of full-dose influenza season. MMWR Morb Mortal children, 2010-2012. J Infect Dis. 2014; trivalent inactivated influenza vaccine Wkly Rep. 2018;67(22):643–645 210(5):674–683 (TIV) compared with half-dose TIV 27. Rondy M, Kissling E, Emborg HD, et al; 10. Tran D, Vaudry W, Moore D, et al; administered to children 6 through I-MOVE/I-MOVE1 group. Interim 2017/18 members of the Canadian Immunization 35 months of age. J Pediatric Infect Dis influenza seasonal vaccine – Monitoring Program Active. Soc. 2015;4(3):214 224 effectiveness: combined results from Hospitalization for influenza A versus B. 19. US Food and Drug Administration. five European studies. Euro Surveill. Pediatrics. 2016;138(3):e20154643 Fluzone quadrivalent. 2018. Available at: 2018;23(9):18–00086

Downloaded from www.aappublications.org/news by guest on October 4, 2021 PEDIATRICS Volume 144, number 4, October 2019 23 28. Blanton L, Dugan VG, Abd Elal AI, et al. 38. Shakib JH, Korgenski K, Presson AP, Sentinel Network; Network for Influenza Update: influenza activity - United et al. Influenza in infants born to Surveillance in Hospitals of Navarre. States, September 30, 2018-February 2, women vaccinated during pregnancy. Decline in influenza vaccine 2019. MMWR Morb Mortal Wkly Rep. Pediatrics. 2016;137(6):e20152360 effectiveness with time after 2019;68(6):125–134 vaccination, Navarre, Spain, season 39. Nunes MC, Madhi SA. Influenza 2011/12. Euro Surveill. 2013;18(5):20388 29. Kissling E, Rose A, Emborg HD, et al; vaccination during pregnancy for European IVE Group. Interim 2018/19 prevention of influenza confirmed 48. Kissling E, Valenciano M, Larrauri A, influenza vaccine effectiveness: six illness in the infants: a systematic et al. Low and decreasing vaccine European studies, October 2018 to review and meta-analysis. Hum Vaccin effectiveness against influenza A(H3) in January 2019. Euro Surveill. 2019;24(8): Immunother. 2018;14(3):758–766 2011/12 among vaccination target groups in Europe: results from the 1900121 40. Thompson MG, Kwong JC, Regan AK, I-MOVE multicentre case-control study. et al; PREVENT Workgroup. Influenza 30. Kelso JM, Greenhawt MJ, Li JT; Joint Euro Surveill. 2013;18(5):20390 Task Force on Practice Parameters vaccine effectiveness in preventing (JTFPP). Update on influenza influenza-associated hospitalizations 49. Belongia EA, Sundaram ME, McClure DL, vaccination of egg allergic patients. Ann during pregnancy: a multi-country et al. Waning vaccine protection against fl Allergy Asthma Immunol. 2013;111(4): retrospective test negative design in uenza A (H3N2) illness in children 301–302 study, 2010-2016. Clin Infect Dis. 2019; and older adults during a single 68(9):1444–1453 season. Vaccine. 2015;33(1):246–251 31. Greenhawt M, Turner PJ, Kelso JM. fi 50. Radin JM, Hawksworth AW, Myers CA, Administration of influenza vaccines to 41. Shef eld JS, Greer LG, Rogers VL, et al. fl et al. Influenza vaccine effectiveness: egg allergic recipients: a practice Effect of in uenza vaccination in the fi maintained protection throughout the parameter update 2017. Ann Allergy rst trimester of pregnancy. Obstet – duration of influenza seasons 2010-2011 Asthma Immunol. 2018;120(1):49–52 Gynecol. 2012;120(3):532 537 through 2013-2014. Vaccine. 2016; 42. Polyzos KA, Konstantelias AA, Pitsa CE, 32. American College of Obstetricians and 34(33):3907–3912 Falagas ME. Maternal influenza Gynecologists. ACOG committee opinion vaccination and risk for congenital 51. Puig-Barberà J, Mira-Iglesias A, no. 732: influenza vaccination during malformations: a systematic review and Tortajada-Girbés M, et al; Valencia pregnancy. Obstet Gynecol. 2018;131(4): meta-analysis. Obstet Gynecol. 2015; Hospital Network for the Study of e109–e114 fl 126(5):1075–1084 In uenza and other Respiratory Viruses 33. Robison SG, Osborn AW. The (VAHNSI, Spain). Waning protection of 43. Nunes MC, Madhi SA. Prevention of concordance of parent and child influenza vaccination during four influenza-related illness in young immunization. Pediatrics. 2017;139(5): influenza seasons, 2011/2012 to 2014/ infants by maternal vaccination during e2016883 2015. Vaccine. 2017;35(43):5799–5807 pregnancy. F1000 Res. 2018;7:122 52. Ray GT, Lewis N, Klein NP, et al. 34. Zaman K, Roy E, Arifeen SE, et al. 44. Omer SB, Clark DR, Aqil AR, et al; for Intraseason waning of influenza vaccine Effectiveness of maternal influenza BMGF Supported Maternal Influenza effectiveness. Clin Infect Dis. 2019; immunization in mothers and infants Immunization Trials Investigators 68(10):1623–1630 [published correction appears in N Engl Group. Maternal influenza 53. Kissling E, Nunes B, Robertson C, et al; J Med. 2009;360(6):648]. N Engl J Med. immunization and prevention of severe – I-MOVE Case–control study team. I-MOVE 2008;359(15):1555 1564 clinical pneumonia in young infants: multicentre case-control study 2010/11 analysis of randomized controlled trials 35. Tapia MD, Sow SO, Tamboura B, et al. to 2014/15: is there within-season conducted in Nepal, Mali and South Maternal immunisation with trivalent waning of influenza type/subtype fl Africa. Pediatr Infect Dis J. 2018;37(5): inactivated in uenza vaccine for vaccine effectiveness with increasing fl 436–440 prevention of in uenza in infants in time since vaccination? Euro Surveill. Mali: a prospective, active-controlled, 45. Schlaudecker EP, Steinhoff MC, Omer 2016;21(16):30201 observer-blind, randomised phase 4 SB, et al. IgA and neutralizing 54. Pebody R, Andrews N, McMenamin J, trial. Lancet Infect Dis. 2016;16(9): antibodies to influenza a virus in et al. Vaccine effectiveness of 2011/12 1026–1035 human milk: a randomized trial of trivalent seasonal influenza vaccine in antenatal influenza immunization. PLoS 36. Madhi SA, Cutland CL, Kuwanda L, et al; preventing laboratory-confirmed One. 2013;8(8):e70867 Maternal Flu Trial (Matflu) Team. influenza in primary care in the United Influenza vaccination of pregnant 46. Ferdinands JM, Fry AM, Reynolds S, Kingdom: evidence of waning intra- women and protection of their infants. et al. Intraseason waning of influenza seasonal protection. Euro Surveill. 2013; N Engl J Med. 2014;371(10):918–931 vaccine protection: evidence from the 18(5):20389 US Influenza Vaccine Effectiveness 37. Steinhoff MC, Katz J, Englund JA, et al. 55. Petrie JG, Ohmit SE, Truscon R, et al. Network, 2011-12 through 2014-15. Clin Year-round influenza immunisation Modest waning of influenza vaccine Infect Dis. 2017;64(5):544–550 during pregnancy in Nepal: a phase 4, efficacy and antibody titers during the randomised, placebo-controlled trial. 47. Castilla J, Martínez-Baz I, Martínez- 2007-2008 influenza season. J Infect Dis. Lancet Infect Dis. 2017;17(9):981–989 Artola V, et al; Primary Health Care 2016;214(8):1142–1149

Downloaded from www.aappublications.org/news by guest on October 4, 2021 24 FROM THE AMERICAN ACADEMY OF PEDIATRICS 56. Ferdinands JM, Patel MM, Foppa IM, Fry 2018 update on diagnosis, treatment, healthy adults and children. Cochrane AM. Influenza vaccine effectiveness. Clin chemoprophylaxis, and institutional Database Syst Rev. 2014;(4):CD008965 Infect Dis. 2019;69(1):190–191 outbreak management of seasonal 76. Venkatesan S, Myles PR, Leonardi-Bee J, influenza. Clin Infect Dis. 2019;68(6): 57. Doll MK, Winters N, Boikos C, et al. et al. Impact of outpatient e1–e47 Safety and effectiveness of neuraminidase inhibitor treatment in neuraminidase inhibitors for influenza 66. Bradley JS, Blumer JL, Romero JR, et al. patients infected with influenza A(H1N1) treatment, prophylaxis, and outbreak Intravenous zanamivir in hospitalized pdm09 at high risk of hospitalization: control: a systematic review of patients with influenza. Pediatrics. an individual participant data systematic reviews and/or meta- 2017;140(5):e20162727 metaanalysis. Clin Infect Dis. 2017; – analyses. J Antimicrob Chemother. 67. Chan-Tack KM, Kim C, Moruf A, Birnkrant 64(10):1328 1334 2017;72(11):2990–3007 DB. Clinical experience with intravenous 77. Muthuri SG, Venkatesan S, Myles PR, 58. Committee on Infectious Diseases. zanamivir under an Emergency IND et al; PRIDE Consortium Investigators. Influenza immunization for all health program in the United States (2011- Effectiveness of neuraminidase care personnel: keep it mandatory. 2014). Antivir Ther. 2015;20(5):561–564 inhibitors in reducing mortality in – Pediatrics. 2015;136(4):809 818 68. Wang K, Shun-Shin M, Gill P, Perera R, patients admitted to hospital with fl 59. Frush K; American Academy of Harnden A. Neuraminidase inhibitors in uenza A H1N1pdm09 virus infection: Pediatrics, Committee on Pediatric for preventing and treating influenza in a meta-analysis of individual Emergency Medicine. Preparation for children (published trials only). participant data. Lancet Respir Med. – emergencies in the offices of Cochrane Database Syst Rev. 2012;(4): 2014;2(5):395 404 pediatricians and pediatric primary CD002744 78. Dawood FS, Jara J, Gonzalez R, et al. A care providers. Pediatrics. 2007;120(1): 69. Howard A, Uyeki TM, Fergie J. Influenza- randomized, double-blind, placebo- 200–212 associated acute necrotizing controlled trial evaluating the safety of 60. Committee on Practice and Ambulatory encephalopathy in siblings. J Pediatric early oseltamivir treatment among Medicine; Committee on Infectious Infect Dis Soc. 2018;7(3):e172–e177 children 0-9 years of age hospitalized with influenza in El Salvador and Diseases; Committee on State 70. Dobson J, Whitley RJ, Pocock S, Monto Panama. Antiviral Res. 2016;133:85–94 Government Affairs; Council on School AS. Oseltamivir treatment for influenza Health; Section on Administration and in adults: a meta-analysis of 79. Uyeki TM. Oseltamivir treatment of Practice Management. Medical versus randomised controlled trials [published influenza in children. Clin Infect Dis. nonmedical immunization exemptions correction appears in Lancet. 2015; 2018;66(10):1501–1503 for child care and school attendance. 385(9979):1728]. Lancet. 2015;385(9979): 80. Domínguez A, Romero-Tamarit A, Pediatrics. 2016;138(3):e20162145 1729–1737 Soldevila N, et al; Surveillance of 61. Edwards KM, Hackell JM; Committee on 71. Koszalka P, Tilmanis D, Roe M, Hospitalized Cases of Severe Influenza Infectious Diseases, The Committee on Vijaykrishna D, Hurt AC. Baloxavir in Catalonia Working Group. Practice and Ambulatory Medicine. marboxil susceptibility of influenza Effectiveness of antiviral treatment in Countering vaccine hesitancy. viruses from the Asia-Pacific, 2012-2018. preventing death in severe hospitalised Pediatrics. 2016;138(3):e20162146 Antiviral Res. 2019;164:91–96 influenza cases over six seasons. – 62. Markenson D, Reynolds S; American 72. Gubareva LV, Mishin VP, Patel MC, et al. Epidemiol Infect. 2018;146(7):799 808 Academy of Pediatrics Committee on Assessing baloxavir susceptibility of 81. South East Asia Infectious Disease Pediatric Emergency Medicine; Task influenza viruses circulating in the Clinical Research Network. Effect of Force on Terrorism. The pediatrician United States during the 2016/17 and double dose oseltamivir on clinical and and disaster preparedness. Pediatrics. 2017/18 seasons. Euro Surveill. 2019; virological outcomes in children and 2006;117(2). Available at: www. 24(3):1800666 adults admitted to hospital with severe pediatrics.org/cgi/content/full/117/2/ 73. Malosh RE, Martin ET, Heikkinen T, et al. influenza: double blind randomised e340 Efficacy and safety of oseltamivir in controlled trial. BMJ. 2013;346:f3039 63. American Academy of Pediatrics. children: systematic review and 82. Takeuchi S, Tetsuhashi M, Sato D. fl In uenza. In: Kimberlin DW, Brady MT, individual patient data meta-analysis of Oseltamivir phosphate-lifting the Jackson MA, Long SS, eds. Red Book: randomized controlled trials. Clin Infect restriction on its use to treat teenagers – 2018 Report of the Committee on Dis. 2018;66(10):1492 1500 with influenza in Japan. Infectious Diseases, 31st ed. Elk Grove 74. Hsu J, Santesso N, Mustafa R, et al. Pharmacoepidemiol Drug Saf. 2019; Village, IL: American Academy of Antivirals for treatment of influenza: 28(4):434–436 Pediatrics; 2018:pp 476–489 a systematic review and meta-analysis 83. Takashita E, Kawakami C, Ogawa R, et al. 64. Heo YA. Baloxavir: first global approval. of observational studies. Ann Intern Influenza A(H3N2) virus exhibiting Drugs. 2018;78(6):693–697 – Med. 2012;156(7):512 524 reduced susceptibility to baloxavir due 65. Uyeki TM, Bernstein HH, Bradley JS, 75. Jefferson T, Jones MA, Doshi P, et al. to a polymerase acidic subunit I38T et al. Clinical practice guidelines by the Neuraminidase inhibitors for substitution detected from Infectious Diseases Society of America: preventing and treating influenza in a hospitalised child without prior

Downloaded from www.aappublications.org/news by guest on October 4, 2021 PEDIATRICS Volume 144, number 4, October 2019 25 baloxavir treatment, Japan, January the novel cap-dependent endonuclease vaccine containing H1N1pdm09 in 2010- 2019. Euro Surveill. 2019;24(12):1900170 inhibitor baloxavir in Japan, 11 and 2011-12. Vaccine. 2017;35(40): – 84. Hayden FG, Sugaya N, Hirotsu N, et al; December 2018. Euro Surveill. 2019; 5314 5322 24(3):1800698 Baloxavir Marboxil Investigators Group. 89. Flannery B, Chung JR, Belongia EA, et al. Baloxavir marboxil for uncomplicated 87. Chambers CD, Johnson DL, Xu R, et al; Interim estimates of 2017-18 seasonal influenza in adults and adolescents. OTIS Collaborative Research Group. influenza vaccine effectiveness - N Engl J Med. 2018;379(10):913–923 Safety of the 2010-11, 2011-12, 2012-13, United States, February 2018. MMWR 85. Omoto S, Speranzini V, Hashimoto T, and 2013-14 seasonal influenza Morb Mortal Wkly Rep. 2018;67(6): et al. Characterization of influenza virus vaccines in pregnancy: birth defects, 180–185 spontaneous abortion, preterm variants induced by treatment with the 90. Rouphael NG, Paine M, Mosley R, et al; delivery, and small for gestational age endonuclease inhibitor baloxavir TIV-MNP 2015 Study Group. The safety, infants, a study from the cohort arm of marboxil. Sci Rep. 2018;8(1):9633 immunogenicity, and acceptability of VAMPSS. Vaccine. 2016;34(37): 86. Takashita E, Kawakami C, Morita H, et al; inactivated influenza vaccine delivered 4443–4449 On Behalf of the Influenza Virus by microneedle patch (TIV-MNP 2015): Surveillance Group of Japan. 88. Donahue JG, Kieke BA, King JP, et al. a randomised, partly blinded, placebo- Detection of influenza A(H3N2) viruses Association of spontaneous abortion controlled, phase 1 trial. Lancet. 2017; exhibiting reduced susceptibility to with receipt of inactivated influenza 390(10095):649–658

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