POLICY STATEMENT

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

Recommendations– for Prevention andCOMMITTEE ONControl INFECTIOUS DISEASES of Influenza in Children, 2018 2019 The authors of this statement update the recommendations of the American abstract Academy of Pediatrics for the routine use of influenza vaccine and antiviral medications in the prevention and treatment of influenza in children. Highlights for the upcoming 2018–2019 season include the following: 1. Annual influenza immunization is recommended for everyone 6 months and older, including children and adolescents.

2. The American Academy of Pediatrics recommends an inactivated influenza This document is copyrighted and is property of the American Academy of Pediatrics and its Board of Directors. All authors have vaccine (IIV), trivalent or quadrivalent, as the primary choice for influenza filed conflict of interest statements with the American Academy vaccination in children because the effectiveness of a live attenuated of Pediatrics. Any conflicts have been resolved through a process approved by the Board of Directors. The American Academy of influenza vaccine against influenza A(H1N1) was inferior during past influenza Pediatrics has neither solicited nor accepted any commercial seasons and is unknown for this upcoming season. involvement in the development of the content of this publication. Policy statements from the American Academy of Pediatrics benefit 3. A live attenuated influenza vaccine may be used for children who would not from expertise and resources of liaisons and internal (AAP) and otherwise receive an influenza vaccine (eg, refusal of an IIV) and for whom external reviewers. However, policy statements from the American Academy of Pediatrics may not reflect the views of the liaisons or the it is appropriate because of age (2 years of age and older) and health status organizations or government agencies that they represent.

(ie, healthy and without any underlying chronic medical condition). The guidance in this statement does not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking 4. All 2018–2019 seasonal influenza vaccines contain an influenza A(H1N1) into account individual circumstances, may be appropriate. vaccine strain similar to that included in the 2017 2018 seasonal vaccines. – All policy statements from the American Academy of Pediatrics In contrast, the influenza A(H3N2) and influenza B (Victoria lineage) vaccine automatically expire 5 years after publication unless reaffirmed, revised, or retired at or before that time. strains included in the 2018–2019 trivalent and quadrivalent vaccines differ from those in the 2017–2018 seasonal vaccines. DOI: https://​doi.​org/​10.​1542/​peds.​2018-​2367 a. Trivalent vaccines contain an influenza A(Michigan/45/2015[H1N1]) PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). pdm09–like virus, an influenza A(Singapore/INFIMH-16-0019/2016[H3N2])– Copyright © 2018 by the American Academy of Pediatrics like virus (updated), and an influenza B (Colorado/60/2017)–like virus FINANCIAL DISCLOSURE: The authors have indicated they have no (B/Victoria lineage; updated). financial relationships relevant to this article to disclose. FUNDING: No external funding. b. Quadrivalent vaccines contain an additional B virus (Phuket/3073/2013– POTENTIAL CONFLICT OF INTEREST: The authors have indicated they like virus; B/Yamagata lineage). have no potential conflicts of interest to disclose. 5. All children with egg allergy of any severity can receive an influenza vaccine without any additional precautions beyond those recommended for To cite: AAP COMMITTEE ON INFECTIOUS DISEASES. Recom­ all vaccines. mendations for Prevention and Control of Influenza in Children, 2018–2019. Pediatrics. 2018;142(4):e20182367

Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 142, number 4, October 2018:e20182367 FROM THE AMERICAN ACADEMY OF PEDIATRICS 6. Pregnant women may receive an influenza vaccine (IIV only) at any time during pregnancy to protect themselves as well as their infants, who benefit from the transplacental transfer of antibodies. Postpartum women who did not receive vaccination during pregnancy should be encouraged to receive an influenza vaccine before discharge from the hospital. Influenza vaccination during breastfeeding is safe for mothers and their infants. 7. The vaccination of health care workers is a crucial step in preventing influenza and reducing health care-associated influenza infections because health care personnel often care for individuals at high risk for influenza-related complications. 8. Pediatricians should attempt to promptly identify their patients who are suspected of having an influenza infection for timely initiation of antiviral treatment when indicated and on the basis of shared decision-making between each pediatrician and child caregiver to reduce morbidity and mortality. Although best results are seen when a child is treated within 48 hours of symptom onset, antiviral therapy should still be considered beyond 48 hours of symptom onset in children with severe disease or those at high risk of complications (see Table 2 in the full policy statement).

KEY POINTS RELEVANT TO THE 2018– 2019 INFLUENZA SEASON younger than 5 years, especially United States, almost two-thirds 1. The American Academy of •• infants younger than 6 months; of children younger than 6 years Pediatrics (AAP) recommends – and nearly all children 6 years and annual influenza vaccination children and adolescents (6 older spend significant time in for everyone 6 months and months 18 years of age) receiving child care or school settings outside older, including children and an aspirin- or salicylate-containing the home. Exposure to groups medication, which places them adolescents, during the 2018– of children increases the risk of2 2019 influenza season. at risk for Reye syndrome after contracting infectious diseases. •• influenza virus infection; Children younger than 2 years are Special children who are American Indians at increased risk of hospitalization effort should be made to vaccinate and complications attributable to •• and/or Alaskan natives; 1 •individuals• in the following groups: influenza. School-aged children bear a large influenza disease all children, including infants •• all health care personnel (HCP); burden and have a significantly born preterm, 6 months and older all child care providers and staff; higher chance of seeking influenza- (based on chronologic age) with •• and related medical care compared with chronic medical conditions that 1 healthy adults. Reducing influenza increase the risk of complications all women who are pregnant, virus transmission (eg, by using from influenza, such as pulmonary are considering pregnancy, are appropriate hand hygiene and diseases (eg, asthma), metabolic in the postpartum period, or are respiratory hygiene and/or cough diseases (eg, diabetes mellitus), breastfeeding during the influenza etiquette) among children who hemoglobinopathies (eg, sickle season. attend out-of-home child care or cell disease), hemodynamically Children often have the highest school has been shown to decrease significant cardiac disease, attack rates of influenza in the the burden of childhood influenza immunosuppression, renal and community during seasonal influenza and transmission of influenza virus to hepatic disorders, or neurologic epidemics, play a pivotal role in the household contacts and community and neurodevelopmental transmission of influenza infection 2 2.members The 2017 of –all2018 ages. influenza season disorders; •• to household and other close was a high-severity season, with contacts, and experience relatively all household contacts and out-of- high levels of outpatient clinic elevated morbidity, including home care providers of children and emergency department severe or fatal complications with high-risk conditions or 1 from influenza infection. In the

Downloaded from www.aappublications.org/news by guest on September 25, 2021 2 FROM THE AMERICAN ACADEMY OF PEDIATRICS Highlights for the 2018–2019 Influenza Season •• •• Vaccination remains the best available preventive measure to prevent influenza illness. •• Annual influenza vaccine is recommended for everyone– 6 months and older. •• ACIP reintroduced LAIV4 as an option for the 2018 2019 influenza season. The AAP recommends an IIV (IIV3 or IIV4) as the primary choice for all children because the effectiveness of LAIV4 was inferior •• against influenza A (/H1N1) during past seasons and is unknown against influenza A (/H1N1) for this upcoming season. LAIV4 may be used for children who would not otherwise receive an influenza vaccine (eg, refusal of an IIV) and for whom it is appropriate according to age (ie, 2 years of age and older) and health status (ie, healthy and without any underlying chronic •• medical condition). – •• As always, families should receive counseling on these revised recommendations for the 2018 2019 season. Children should receive the influenza vaccine as soon as possible after it is available in their community, preferably by the end of •• October. ’ The No. recommended doses of an influenza vaccine depends on a child s age at the time of the first administered dose and vaccine •• history. All children with egg allergy of any severity can receive either an IIV or LAIV without any additional precautions beyond those •• recommended for any vaccine. Pregnant women may receive an IIV at any time during pregnancy. Postpartum women who did not receive vaccination during pregnancy should be encouraged to receive the vaccine before discharge from the hospital. Vaccination is safe during •• breastfeeding for mothers and their infants. – All HCP should receive an annual influenza vaccine, which is a crucial step in preventing influenza and reducing health care •• associated influenza infections. Antiviral medications are important in the control of influenza but are not a substitute for influenza vaccination. visits for influenza-like illness (ILI), high influenza-related 2009 pandemic, the 179 pediatric the predominant circulating strain hospitalization rates, high numbers – of pediatric deaths, and elevated deaths reported through August 18, and from one season to the next and geographically widespread 2018, during the 2017 2018 season (Table 1). Historically, 80% to 85% influenza activity across the (approximately half of which occurred of pediatric deaths have occurred country for an extended period. in otherwise healthy children) are in unvaccinated children 6 months 3,​ the highest reported since influenza- and older. Among pediatric deaths 4 ‍ associated pediatric mortality became of children 6 months and older who ‍ Influenza A(H3N2) viruses a nationally notifiable condition were eligible for influenza vaccination predominated overall for the season in 2004. Analyses of the influenza and for whom vaccination status was through February 2018; influenza B known, only 22% had received at – A(H1N1)pdm09, influenza A(H3N2), – viruses predominated from March and influenza B (Yamagata lineage) least 1 dose of an influenza vaccine3 2018 onward. The 2017 2018 during the 2017 2018 season. – viruses showed that circulating season ranks as the third most viruses were antigenically and Influenza vaccination is associated with severe since the 2003 2004 season genetically similar to the cell-grown reduced risk of laboratory-confirmed5 – influenza-related pediatric death. and was the first to be classified3 as reference viruses representing the high severity for all age groups. 2017 2018 Northern Hemisphere In one case cohort analysis in which The peak percentage of outpatient researchers compared vaccination – influenza vaccine viruses. Although visits for ILI was the third highest the overall number of circulating uptake among laboratory-confirmed recorded since the 1997 1998 influenza B (Victoria lineage) influenza-associated pediatric deaths season. Although the hospitalization viruses was low, a substantial with estimated vaccination coverage rates for children this season did not amount of antigenic drift from the among pediatric cohorts in the United States5 from 2010 to 2014, Flannery et exceed the rates reported during vaccine reference virus influenza 3 the 2009 pandemic, hospitalization al found that only 26% of case patients – B(Brisbane/60/2008) was observed. surpassed rates reported in previous received a vaccine before illness onset high-severity influenza A(H3N2) Pediatric hospitalizations and compared with average vaccination predominant seasons. Excluding the deaths caused by influenza vary by coverage of 48%. The overall vaccine Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 142, number 4, October 2018 3 TABLE 1 Pediatric Deaths and Hospitalizations by Season and Predominant Strain Influenza Season Predominant Strain Pediatric Deaths Hospitalizations (0–4 y Old) per 100 000 Hospitalizations (5–17 y Old) per 100 000 2017–2018 H3N2 179 71.4 19.7 (preliminary data) 2016–2017 H3N2 101 43.7 16.7 2015–2016 pH1N1 92 42.4 9.7 2014–2015a H3N2 148 57.2 16.6 2013–2014 pH1N1 111 47.2 9.4 2012–2013 H3N2 171 67 14.6 2011–2012a H3N2 37 16 4 2010–2011 H3N2 124 49.4 9.1 2009–2010 pH1N1 288 77.4 27.2 2008–2009 H1N1 137 28 5 2007–2008 H3N2 88 40.3 5.5 Adapted from Centers for Disease Control and Prevention. FluView 2017–2018 data as of August 18, 2018. Available at: www.​cdc.​gov/​flu/​weekly/​fluviewinteractiv​e.​htm. a Vaccine strains did not change from previous influenza season.

effectiveness against influenza- 2 were associated with both influenza influenza vaccination because overall associated death in children was 65% A and influenza B viruses. influenza vaccination rates have been ’ (95% confidence interval [CI] 54% to suboptimal during past seasons in ≥ Among the 154 children with known 74%). More than one-half of pediatric medical history, 51% of the deaths both children and adults. Children s deaths in this study had 1 underlying occurred in children with at least likelihood of being immunized medical condition with increased risk of one underlying medical condition according to recommendations severe influenza-related complications; that is recognized by the Advisory appears to be associated with the notably, only 1 in 3 of these at-risk Committee on Immunization immunization practices of their children had been vaccinated, yet parents. One study revealed that Practices (ACIP) to increase the vaccine effectiveness against death in children were 2.77 times (95% CI risk of influenza-attributable children with underlying conditions 2.74 to 2.79) more likely to also be disease severity. Among children was 51% (95% CI 31% to 67%). immunized for seasonal influenza hospitalized with influenza and for 8 Similarly, influenza vaccination reduces if their parents were immunized. whom medical record data were by three-fourths the risk of severe, When parents who were previously available, approximately 43% had life-threatening laboratory-confirmed not immunized had received no recorded underlying condition, influenza in children requiring immunization for seasonal influenza, 6 whereas 26.2% had asthma or a admission to the ICU. During the past their children were 5.44 times (95% reactive airway disease, 16.8% had a 11 seasons, the rates of influenza- CI 5.35 to 5.53) more likely to receive neurologic disorder, and 10.5% had associated hospitalization for children 3 an influenza vaccine. obesity (Fig 1). In a recent study 4. The AAP recommends a trivalent younger than 5 years have always of hospitalizations for influenza inactivated influenza vaccine exceeded the rates for children 5 A versus influenza B, the odds of (IIV3) or quadrivalent inactivated through 17 years of age. mortality were significantly greater influenza vaccine (IIV4) as the primary choice for influenza As of August 18, 2018, the following with influenza B than with influenza vaccination in children because data were reported by the Centers A and were not entirely explained7 by – underlying health conditions. the effectiveness of quadrivalent for Disease Control and Prevention 3. Vaccination remains the best live attenuated influenza vaccine (CDC) during the 2017 2018 available preventive measure (LAIV4) against influenza A(H1N1) influenza season: against influenza illness. was inferior during past influenza 179 laboratory-confirmed influenza- The seasons, and effectiveness is associated pediatric deaths universal administration of a unknown for this upcoming occurred; seasonal vaccine to everyone 6 season. months and older is the best strategy Both the AAP Committee on 106 were associated with influenza available for preventing illness from Infectious Diseases and the ACIP of A viruses, 68 were associated with influenza. Any licensed and age- the CDC have reviewed and carefully influenza B viruses; appropriate inactivated influenza considered all influenza vaccine vaccine (IIV) available should be 3 were associated with an efficacy data available to date as well used to vaccinate children. There is undetermined type of influenza as new information regarding the virus; and notable room for improvement in Downloaded from www.aappublications.org/news by guest on September 25, 2021 4 FROM THE AMERICAN ACADEMY OF PEDIATRICS FIGURE 1 Selected underlying medical conditions in patients hospitalized with laboratory-confirmed influenza (Influenza Hospitalization Surveillance Network 2017–2018). Asthma includes a medical diagnosis of asthma or a reactive airway disease. Cardiovascular diseases include conditions such as coronary heart disease, cardiac valve disorders, congestive heart failure, pulmonary hypertension, and aortic stenosis; hypertension disease alone is not included. Chronic lung diseases include conditions such as chronic obstructive pulmonary disease, bronchiolitis obliterans, chronic aspiration pneumonia, and interstitial lung disease. Immune suppression includes conditions such as immunoglobulin deficiency, leukemia, lymphoma, HIV and/ or AIDS, and individuals taking immunosuppressive medications. Metabolic disorders include conditions such as diabetes mellitus, thyroid dysfunction, adrenal insufficiency, and liver disease. Neurologic disorders include conditions such as seizure disorders, cerebral palsy, and cognitive dysfunction. Neuromuscular disorders include conditions such as multiple sclerosis and muscular dystrophy. Obesity was assigned if indicated in a patient's medical chart of if BMI was >30. Pregnancy percentage was calculated by using the number of female case patients between 15 and 44 years of age as the denominator. Renal diseases include conditions such as acute or chronic renal failure, nephrotic syndrome, glomerulonephritis, and impaired creatinine clearance. No known condition indicates that the case patient did not have any known underlying medical condition indicated in the medical chart at the time of hospitalization. (Reprinted from Centers for Disease Control and Prevention. FluView 2017–2018 preliminary data as of August 18, 2018. Available at: gis.​cdc.​gov/​grasp/​fluview/​FluHospChars.​html.)

Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 142, number 4, October 2018 5 •• Children 6 months through 8 years ⚬of⚬ age need the following: 2 doses if they have received fewer than 2 doses of any trivalent or quadrivalent influenza vaccine (IIV or live attenuated influenza vaccine [LAIV]) before July 1, 2018. The interval between the 2 doses ⚬⚬should be at least 4 weeks; or Only 1 dose if they have previously received 2 or more total doses of any trivalent or quadrivalent influenza vaccine FIGURE 2 (IIV or LAIV) before July 1, The number of 2018–2019 seasonal influenza vaccine doses for children 6 months through 8 years of age. a The 2 doses need not have been received during the same season or consecutive seasons. b 2018. The 2 previous doses do Receipt of LAIV4 in the past is still expected to have primed a child’s immune system despite recent not need to have been received evidence for poor effectiveness. There currently are no data that suggest otherwise. during the same influenza season or consecutive influenza seasons. Vaccination should not be delayed to – – updated LAIV4 formulation available A(Michigan/45/2015[H1N1]) obtain a specific product for either for the 2018 2019 season to provide pdm09 like virus, an influenza dose. Any available age-appropriate – their latest recommendations. A(Singapore/INFIMH-16- trivalent or quadrivalent vaccine can – Although the AAP and CDC each 0019/2016[H3N2]) like virus, and be used. A child who receives only – support the use of LAIV4 for the an influenza B(Colorado/60/2017) 1 of the 2 doses as a quadrivalent 2018 2019 influenza season with like virus (B/Victoria lineage). The formulation is likely to be less primed the aim of achieving adequate influenza A(H3N2) virus component against the additional influenza B 7. Pediatric offices may vaccination coverage and optimal is updated because the egg- virus. choose to serve as a venue for protection in children of all ages, propagated influenza A (Singapore) providing influenza vaccination the AAP recommends vaccination vaccine virus is antigenically more for parents and other care with IIV3 or IIV4 for all children similar to circulating viruses. The providers of children if the and LAIV4 for children who would influenza B component is updated practice is acceptable to both not otherwise receive an influenza because of the increasing global pediatricians and the adults who vaccine (eg, refusal of an IIV) and for circulation of an antigenically are to be vaccinated. whom it is appropriate according to drifted influenza B (Victoria lineage) 1 age (ie, 2 years of age and older) and virus. The quadrivalent vaccine – ‍ Medical health status (ie, healthy and without contains an additional influenza liability issues and medical record any underlying chronic medical B(Phuket/3073/2013) like virus (B/ documentation requirements 5. Both trivalent and quadrivalent condition). Yamagata lineage), which is the same need to be considered before a influenza vaccines are available 6. The number of seasonal as last season. pediatrician begins immunizing in the United States for the influenza vaccine doses to be 9 adults. (see risk management 2018–2019 season. administered in the 2018–2019 guidance associated with adult influenza season remains the same To vaccinate immunizations at http://​pediatrics.​ and depends on a child’s age at the aappublications.​org/​content/​129/​ as many people as possible for this time of the first administered dose 1/e247).​ Pediatricians are reminded influenza season, neither vaccine and vaccine history : ’ formulation is preferred over the to document the recommendation other. Although manufacturers •• (Fig 2) for adult vaccination in the child s medical record. In addition, adults anticipate an adequate supply Influenza vaccines are not licensed should still be encouraged to have of the quadrivalent vaccine, for administration to infants a medical home and communicate pediatricians should administer •• younger than 6 months. whichever formulation is available their vaccination status to their in their communities. The trivalent Children 9 years and older need primary care providers. Offering vaccine contains an influenza only 1 dose. adult vaccinations in the pediatric Downloaded from www.aappublications.org/news by guest on September 25, 2021 6 FROM THE AMERICAN ACADEMY OF PEDIATRICS TABLE 2 People at High Risk of Influenza Complications and Thus Recommended for Antiviral reatmentT of Suspected or Confirmed Influenza Children <5 years and especially <2 years Adults ≥50 years People with chronic pulmonary (including asthma), cardiovascular (except hypertension alone), renal, hepatic, hematologic (including sickle cell disease), or metabolic disorders (including diabetes mellitus) or neurologic and neurodevelopment conditions (including disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy [seizure disorders], stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury) People with immunosuppression, including that caused by medications or by HIV infection All women who are pregnant, are considering pregnancy, or are in the postpartum period during the influenza season People <19 years old who are receiving long-term aspirin therapy American Indian and/or Alaskan native people People with extreme obesity (ie, BMI ≥40) Residents of nursing homes and other chronic care facilities Hospitalized patients at high risk of influenza complications Adapted from Grohskopf LA, Sokolow LZ, Broder KR, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices—United States, 2018–19 influenza season. MMWR Recomm Rep. 2018;67(3):1–20.

practice setting would not be and Gynecologists for all women revealed no significant association of intended to undermine the adult at any trimester of gestation for spontaneous abortion with influenza medical home model but could serve the protection of mothers against1,​ vaccine exposure in the first as an additional venue for parents 10influenza and its complications. trimester or 20within the first 20 weeks and other care providers of children ‍ Substantial evidence has been of gestation. Although researchers to receive influenza vaccines. accumulated regarding the efficacy in previous studies have not noted Vaccination of close contacts of of maternal influenza immunization any association between influenza children at high risk of influenza- in preventing laboratory- vaccination and adverse pregnancy ’ related complications (Table 2) confirmed influenza disease and its outcomes, one recent observational – is intended to reduce children s complications in both mothers and Vaccine Safety Datalink (VSD) study “ ” – – risk of exposure to influenza (ie, their infants11 17 in the first 2 to 6 months conducted during the 2010 2011 and cocooning ). The practice of of life. ‍‍ Infants born to women 2011 2012 influenza seasons noted cocooning also may help protect who receive an influenza vaccination an association between the receipt of infants younger than 6 months who during pregnancy can have a risk an IIV containing H1N1pdm09 and – are too young to be immunized with reduction of 72% (95% CI 39% early spontaneous abortion when 8.the Pregnant influenza women vaccine. who are to 87%) for laboratory-confirmed an H1N1pdm-09 containing vaccine immunized against influenza at influenza hospitalization18 in the first had also21 been received the previous any time during their pregnancy few months of life. season. A follow-up study is in progress. The ACIP influenza vaccine can provide protection for infants Any licensed, recommended, and age- recommendations for pregnant during their first 6 months of life, appropriate trivalent or quadrivalent when they are too young to receive women have not been changed for inactivated vaccine may be used to 9. As soon as a seasonal influenza the influenza vaccine themselves, this coming season. vaccinate pregnant women, including vaccine becomes available through transplacental passage quadrivalent recombinant1 inactivated locally, pediatricians or vaccine of antibodies. vaccine (RIV4). However, experience administrators should encourage with the use of RIVs in pregnant Postpartum women immunization of HCP, notify women 18 years and older is limited who did not receive an influenza – parents and caregivers of vaccine because RIVs have been available vaccination during pregnancy should availability and the importance only since the 2013 2014 influenza be encouraged to discuss with their of annual vaccination, and season. Substantial data indicate obstetricians receipt of the vaccine immunize children 6 months that an IIV does not cause fetal harm before discharge from the hospital. and older per recommendations, when administered to a pregnant Vaccination during breastfeeding is especially those at high risk of woman, although data on the safety safe for mothers and their infants. complications from influenza. of influenza vaccination in the Pregnant women are a population 19 early first trimester are limited. This of special concern because they are A cohort study from the Vaccines strategy is particularly important at increased risk for complications and Medications in Pregnancy for children who need 2 doses of from influenza. Influenza vaccination – Surveillance System of vaccine the influenza vaccine to achieve is recommended by the ACIP and the – exposure during the 2010 2011 optimal protection before the American College of Obstetricians through 2013 2014 seasons circulation of influenza viruses in the Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 142, number 4, October 2018 7 10. To effectively protect children, providers may continue to offer community. Children should receive the vaccine until June 30 of each http://​pediatrics.aappublications.​ 9 ​ the first dose as soon as possible year, when the seasonal influenza org/​content/​129/1/​ ​e247) at after a vaccine becomes available the same time in the same office ≥ vaccine expires, because the to allow sufficient time for receipt duration of influenza circulation setting as children; and working of the second dose 4 weeks later, is unpredictable. with other institutions (eg, schools, preferably by the end of October. child care programs, local public The onset and duration of influenza Although peak health departments, and religious circulation is unpredictable. To influenza activity in the United organizations) or alternative effectively protect children, prompt States tends to occur from January care sites, such as emergency initiation of influenza vaccination and through March, influenza activity departments, to expand venues continuing to vaccinate throughout can occur in early fall (October) or for administering the vaccine. If a the influenza season, regardless of late spring (end of May) and may child receives the influenza vaccine whether influenza is circulating (or have more than one disease peak. outside of his or her medical home, has circulated) in the community, are Similarly, although influenza activity such as at a pharmacy, retail-based important components of an effective in the United States is typically clinic, or another practice setting, vaccination strategy. Protective low during the summer, influenza appropriate documentation of immune responses generally persist cases and outbreaks also can vaccination should be provided to in children throughout the influenza occur. Furthermore, this approach the patient to be shared with his or season. Although there is limited also allows for optimal ability to her medical home and entered into evidence that waning immunity from immunize travelers, particularly the state or regional immunization early administration of the vaccine international travelers, who may •• information system (ie, registry). increases the risk of infection in be exposed to influenza yearround Concerted efforts among children, authors of recent reports depending11. HCP, influenza on their destinations.campaign the aforementioned groups, raise the possibility that early organizers, and public health plus vaccine manufacturers, vaccination of adults, particularly agencies are encouraged to distributors, and payers, are the elderly, might contribute to collaborate to develop improved necessary to appropriately reduced protection later in the strategies for the planning, prioritize distribution to the influenza season. Older adults are distribution, communication, and primary care office setting and recognized as having a less robust administration of vaccines. patient-centered medical homes immune response to influenza These before other venues, especially vaccines. A multiseason analysis •• include the following: when vaccine supplies are delayed from the US Influenza Vaccine or limited. Similar efforts should be Effectiveness Network revealed that Plan to make influenza vaccination made to assuage the vaccine supply vaccine effectiveness declined by easily accessible for all children. discrepancy between privately approximately 7% per month for Examples include sending alerts to insured patients and those eligible H3N2 and influenza B and by 6% families that a vaccine is available for vaccination through the to 11% per month for H1N1pdm09 (eg, e-mails, texts, letters, and 22 •• Vaccines for Children Program. in individuals 9 years and older. patient portals); creating walk-in ’ Vaccine effectiveness remained influenza vaccination clinics; Public health will benefit from greater than zero for at least 5 to 6 extending hours beyond routine pediatricians discussions about months after vaccination. Further times during peak vaccination vaccine safety, effectiveness, and evaluation is needed before any periods; administering an influenza indications. Pediatricians can policy change in timing is made. An vaccine during both well-child influence vaccine acceptance early onset of the influenza season examinations and sick visits as well by explaining the importance is another concern about delayed as to patients who are hospitalized, of annual influenza vaccination vaccination. Until there are definitive especially those at high risk of for children, emphasizing when data that can be used to determine influenza complications, before a second dose of the vaccine is whether waning immunity influences discharge from the hospital (unless indicated, and explaining why vaccine effectiveness in children, medically contraindicated); the intranasal formulation is not the administration of the influenza implementing standing orders for recommended for routine use in vaccine should not be delayed to influenza vaccination; considering all children. The AAP and CDC a later date because this increases how to immunize parents, adult have created communication the likelihood of missing influenza caregivers, and siblings (see risk resources to convey these vaccination altogether. management guidance associated important messages and help with adult immunizations at the public understand influenza Downloaded from www.aappublications.org/news by guest on September 25, 2021 8 FROM THE AMERICAN ACADEMY OF PEDIATRICS Red Bookrecommendations. Online Resources influenza infection in those children years, it has proven difficult to will be available in the who cannot absorb orally or enterally predict consistently which influenza (https://​redbook.​ administered oseltamivir or tolerate B lineage will predominate during a solutions.​aap.​org/​selfserve/​ inhaled zanamivir. given influenza season. Therefore, a ssPage.​aspx?​SelfServeContentI​d=​ quadrivalent vaccine with influenza 23 Recent viral surveillance and •• influenza-​resources). B strains of both lineages would resistance data from the CDC and be predicted to offer additional The AAP supports mandatory the World Health Organization protection, but there is no evidence at influenza vaccination programs reveal that the majority of currently this time that a quadrivalent vaccine for all HCP in all settings, including circulating influenza viruses – is more effective. Table 3 includes a outpatient settings. HCP should likely to cause influenza in North summary of information on the types act as role models for both America during the 2018 2019 – of influenza vaccines licensed for their patients and colleagues by season continue to be susceptible children and adults during the 2018 receiving influenza vaccination to oseltamivir, zanamivir, and 1 2019 season. More than 1 product annually and letting others know peramivir. If a newly emergent may be appropriate for a given that they have received the oseltamivir- or peramivir-resistant patient. Vaccination should not be vaccine, highlighting the safety and virus is a concern, recommendations delayed to obtain a specific product. effectiveness of annual influenza for alternative system treatment, IIVs

vaccination. Influenza vaccination such as the25, use26​ of intravenous programs for HCP benefit the zanamivir,​ ‍ will be available – health of employees, their patients, from the CDC and AAP. Resistance For the 2018 2019 season, an IIV and members of the community. characteristics can also change will be available for intramuscular Mandatory influenza immunization for an individual child over the injection in both IIV3 and IIV4 for all HCP is considered to be duration of a treatment course, formulations. IIVs do not contain ethical, just, and necessary to especially in those who are severely a live virus. The available IIV improve patient safety. Employees immunocompromised and may formulations and age groups for of health care institutions are receive extended courses of which use is approved are presented asked to act in the best interests of antiviral medications because of in Table 4. IIV formulations can the health of their patients and to prolonged viral shedding. Up-to- be used in healthy children as honor the requirement of causing date information on current well as those with underlying 12.no Antiviral harm. medications are recommendations and therapeutic Red chronic medical conditions. The important in the control of options can be found on the AAP Book Online most common adverse events influenza but are not a substitute Web site (www.​aap.​org) or in the after IIV3 administration are local for influenza vaccination. , through state-specific injection site pain and tenderness. AAP chapter Web sites, or on the CDC The 27 Fever occurs within 24 hours after Web site. neuraminidase inhibitors (NAIs) immunization in approximately oral oseltamivir (Tamiflu) and SEASONAL INFLUENZA VACCINES 10% to 35% of children younger inhaled zanamivir (Relenza) are the than 2 years but rarely in older – best-studied antiviral medications children and adults. Mild systemic recommended for chemoprophylaxis Before the 2013 2014 influenza symptoms, such as nausea, lethargy, – or the treatment of influenza in season, only trivalent influenza headache, muscle aches, and chills, children24 during the 2018 2019 vaccines that included a single may occur after the administration season. Intravenous peramivir influenza B strain were available. of IIV3. Several formulations of (Rapivab), a third NAI, was approved Since the 1980s, 2 antigenically IIV4 are now available with specific in September 2017 as a treatment distinct lineages (ie, Victoria or age indications, including brands of acute uncomplicated influenza Yamagata) of influenza B viruses licensed for use in children as young in children 2 years and older who have circulated globally. Vaccination as 6 months. In children, the most are not hospitalized and have been against 1 influenza B viral lineage common injection site adverse symptomatic for no more than 2 generally confers little cross- reactions after the administration of days. Intravenous zanamivir is not protection against the other influenza IIV4 are pain, redness, and swelling. approved in the United States and B viral lineage. Thus, trivalent The most common systemic adverse is not25 available for compassionate vaccines offer limited immunity events are drowsiness, irritability, use. Intravenous formulations against circulating influenza B loss of appetite, fatigue, muscle are especially important as the strains of the lineage not present in aches, headache, arthralgia, and only treatment option for serious the vaccine. Furthermore, in recent gastrointestinal tract symptoms. Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 142, number 4, October 2018 9 TABLE 3 Recommended Seasonal Influenza Vaccines for Different Age Groups: United States, 2018–2019 Influenza Season Vaccine Trade Name Manufacturer Presentation Thimerosal Mercury Age Group CPT Code Content (μm of Hg per 0.5 mL Dose) Inactivated IIV3 Fluzone high-dose Sanofi Pasteur 0.5 mL prefilled syringe 0 ≥65 y 90662 IIV3 Afluria Seqirus 0.5 mL prefilled syringe 0 ≥5 y 90656 5.0 mL multidose vial 24.5 ≥5 y 90658 aIIV3 Fluad Seqirus 0.5 mL prefilled syringe 0 ≥65 y 90653 ccIIV4 Flucelvax quadrivalent Seqirus 0.5 mL prefilled syringe 0 ≥4 y 90674 5.0 mL multidose vial 25 ≥4 y 90756 IIV4 Fluzone quadrivalent Sanofi Pasteur 0.25 mL prefilled syringe 0 6–35 mo 90685 0.5-mL prefilled syringe 0 ≥36 mo 90686 5.0 mL multidose vial 25 ≥6 mo 90687, 90688 IIV4 Fluarix quadrivalent GlaxoSmithKline 0.5 mL prefilled syringe 0 ≥6 mo 90686 IIV4 FluLaval quadrivalent ID Biomedical 0.5 mL prefilled syringe 0 ≥6 mo 90686 Corporation of Quebec Distributed by 5.0 mL multidose vial <25 ≥6 mo 90688 GlaxoSmithKline IIV4 Afluria quadrivalent Seqirus 0.5 mL prefilled syringe 0 ≥5 y 90686 5.0 mL multidose vial 24.5 ≥5 y 90688 Recombinant RIV4 Flublok quadrivalent Protein Sciences 0.5 mL prefilled syringe 0 ≥18 y 90682 Corporation (distributed by Sanofi Pasteur) Live attenuated LAIV4 FluMist quadrivalent MedImmune 0.2 mL prefilled 0 2–49 y 90672 intranasal sprayer aIIV3, adjuvanted inactivated influenza vaccine trivalent; ccIIV4, quadrivalent cell culture–based inactivated influenza vaccine; CPT, Current Procedural Terminology. Implementation guidance on supply, pricing, payment, CPT coding, and liability issues can be found in the Red Book Online.28 Adapted from American Academy of Pediatrics, Committee on Infectious Diseases. Recommendations for prevention and control of influenza in children, 2017–2018. Pediatrics. 2017;140(4):e20172550; and Grohskopf LA, Sokolow LZ, Broder KR, et al. Prevention and control of seasonal in uenza with vaccines: recommendations of the Advisory Committee on Immunization Practices—United States, 2018–19 influenza season. MMWR Recomm Rep. 2018;67(3):1–20.

TABLE 4 Summary of Antiviral Treatment of Clinical Influenza During the 2018–2019 Season Offer Treatment ASAP to Children Consider Treatment ASAP for These events are reported with comparable frequency with IIV3s. Hospitalized with suspected influenza Any healthy child with suspected influenza ≥ Therefore, an IIV4 is available Hospitalized for severe, complicated, Healthy children with suspected influenza who live or progressive illness attributable at home with a sibling or household contact who for people 6 months old when to influenza regardless of duration is <6 months old or has a medical condition that otherwise appropriate and may of symptoms predisposes to complications offer broader protection against With suspected influenza (of any severity) and at circulating influenza B strains than high risk of complications an IIV3. ASAP, as soon as possible. This is the first influenza season during which several vaccine products are licensed for children 6 Before November 2016, the only IIV after older influenza vaccines, through 35 months of age, as listed formulations licensed for children primarily whole-virus inactivated µ in Table 3. All of these vaccines 6 through 35 months of age were vaccines. Currently available split- are quadrivalent, but the dose the 0.25 mL (containing 7.5 g of virus inactivated products have 1 volumes and antigen amounts hemagglutinin per vaccine virus) demonstrated less reactogenicity. vary among different IIV products. μ dose formulations of Fluzone Given that the formulations of IIV4 In addition to the 0.25 mL (7.5 and Fluzone Quadrivalent. The g of hemagglutinin per vaccine vaccines for children 6 through μ recommendation for the use of 35 months of age are different, virus) Fluzone vaccine, 2 other a reduced dose and volume for ≥ care should be taken to administer IIV4 vaccines containing 15 g of children in this age group (half of that hemagglutinin per vaccine virus per the appropriate, recommended recommended for people 3 years volume and dose for each product. 0.5 mL dose (Fluarix and FluLaval) of age) was based on the increased are now available for children 6 In each instance, the recommended reactogenicity noted among children volume may be administered from through 35 months of age. (particularly younger children) Downloaded from www.aappublications.org/news by guest on September 25, 2021 10 FROM THE AMERICAN ACADEMY OF PEDIATRICS – – an appropriate prefilled syringe, required for children. In 1 recent 2013 2014 and 2014 2015 seasons. a single-dose vial, or a multidose study of children, the relative vaccine It was concluded that the risk of vial (a maximum of 10 doses can be efficacy of an MF-59 adjuvanted seizures after PCV13 or concomitant ’ withdrawn from a multidose vial) as influenza vaccine was significantly PCV13 and IIV administration is low supplied by the manufacturer. Note greater than a nonadjuvanted compared with a child s lifetime that for Fluzone, if a 0.5 mL single- vaccine in 29the 6- through 23-month risk of febrile32 seizures due to other use vial of Fluzone Quadrivalent is age group. However, adjuvanted causes. Although the possibility of used for a child between 6 and 35 seasonal influenza vaccines are not increased risk for febrile seizures months of age, only half the volume licensed for children at this time. cannot be ruled out, the simultaneous – (0.25 mL) should be administered administration of an IIV with PCV13 to provide the currently approved During the 2 influenza seasons and/or other vaccines for the 2018 dose for this product, and the other spanning 2010 through 2012, 2019 influenza season continues half should be discarded. A 0.5 mL there were increased reports to be recommended when these unit dose of any IIV should not be of febrile seizures in the United vaccines are indicated. Overall, the split into 2 separate 0.25 mL doses States in young children who benefits of timely vaccination with because of safety concerns for lack of received an IIV3 and the 13-valent same-day administration of an IIV sterility, variance with the package pneumococcal conjugate vaccine and PCV13 or the diphtheria-tetanus- insert, and potential compliance (PCV13) concomitantly. Subsequent acellular pertussis vaccine outweigh difficulties with vaccine excise taxes. retrospective analyses of past the risk of febrile seizures, which Children 36 months of age and older seasons revealed a slight increase in rarely have any long-term sequelae. can receive any licensed IIV. All IIVs the risk of febrile seizures in children licensed for children of this age in 6 through 23 months of age when A large body of scientific evidence the United States are split-product, PCV13 vaccines are administered30 reveals that thimerosal-containing egg-based, inactivated vaccines concomitantly with an IIV. The vaccines are not associated with μ administered in a 0.5 mL dose and concomitant administration of an increased risk of autism1 spectrum containing 15 g of hemagglutinin IIV3, PCV13, and the diphtheria- disorders in children. Thimerosal from each strain in the vaccine. tetanus-acellular pertussis vaccine from vaccines has not been linked was associated with the greatest to any medical condition. As such, Two quadrivalent influenza vaccines relative risk estimate, corresponding the AAP extends its strongest manufactured by using newer – to a maximum additional 30 febrile support to the current World Health technologies will be available seizure cases per 100000 children Organization recommendations to during the 2018 2019 season, 1 vaccinated compared with the retain the use of thimerosal as a of which can be used in children. A administration of the vaccines on preservative in multiuse vials in the recombinant baculovirus-expressed separate days. In contrast, data global vaccine supply. Some people hemagglutinin influenza vaccine from the Post-Licensure Rapid may still raise concerns about the (RIV4) for people 18 years and older – Immunization Safety Monitoring trace amount of thimerosal in some is produced in cell culture, and a (PRISM) program of the FDA, the IIV vaccine formulations (Table quadrivalent cell culture based IIV largest vaccine safety surveillance 3), and in some states, including is available for individuals 4 years program in the United States, California, Delaware, Illinois, and older. Both of these vaccines are revealed that there was no significant Missouri, New York, and Washington, also administered intramuscularly. increase in febrile seizures associated there is a legislated restriction on No preference is expressed for with the concomitant administration the use of thimerosal-containing – RIV4 versus IIVs within specified of these 3 vaccines in children 6 to 59 vaccines. The benefits of protecting indications. months31 of age during the 2010 2011 children against the known risks The US Food and Drug season. In a subsequent sentinel of influenza are clear. Therefore, to – Administration (FDA) licensed Center for Biologics Evaluation and the extent authorized by state law, a trivalent MF59 adjuvanted IIV Research Post-Licensure Rapid children should receive any available for people 65 years and older in Immunization Safety Monitoring formulation of an IIV rather than November 2015; it was the first surveillance report looking at delay vaccination while waiting – – adjuvanted influenza vaccine influenza vaccines and febrile for reduced thimerosal content or marketed in the United States. seizures in the 2013 2014 and 2014 thimerosal-free vaccines. Although Adjuvants may be included in a 2015 influenza seasons, there was no some IIV formulations contain a trace vaccine to elicit a more robust evidence of an elevated risk of febrile amount of thimerosal, thimerosal- immune response, which could lead seizures in children 6 to 23 months free IIV products can be obtained to a reduction in the number of doses of age after IIV vaccination during the (Table 3). To respond to consumer Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 142, number 4, October 2018 11 requests, vaccine manufacturers are children were runny nose or nasal evaluated viral shedding and delivering increasing amounts of congestion, headache, decreased immunogenicity associated with the – thimerosal-free influenza vaccines activity or lethargy, and sore throat. LAIV4 formulation containing the Liveeach Attenuated year. (Intranasal) LAIV4 should not be administered new influenza A(/H1N1)pdm09 like Influenza Vaccine to people with notable nasal virus among US children 24 months congestion because that can impede through 3 years of age. Shedding and – vaccine delivery. The safety of LAIV immunogenicity data provided by – in people with a history of asthma, For the 2018 2019 influenza season, the manufacturer reveal that the new diabetes mellitus, or other high-risk the AAP recommends LAIV4 to be influenza A(H1N1)pdm09 like virus medical conditions associated with used for children who would not included in its latest formulation has an elevated risk of complications otherwise receive an influenza improved replicative fitness over from influenza (see the section on – vaccine (eg, refusal of an IIV) and for previous LAIV4 influenza A(H1N1) contraindications and precautions) whom it is appropriate according to pdm09 like vaccine strains, resulting has not been firmly established. In age (ie, 2 years of age and older) and in an improved immune response postlicensure surveillance of LAIV health status (ie, healthy and without comparable to that of the LAIV3 over 7 seasons, the Vaccine Adverse any underlying chronic medical available before the 2009 pandemic. Event Reporting System, jointly condition). This recommendation Shedding and replicative fitness – – sponsored by the FDA and CDC, did represents a change from the are not known to be correlated not identify any new or unexpected 2016 2017 and 2017 2018 influenza with efficacy, and no published safety concerns, although there seasons, when intranasal LAIV4 was effectiveness estimates for this were reports of the use of LAIV in not recommended in any setting formulation of the vaccine against people with a contraindication or in light of the evidence of its poor influenza A(H1N1)pdm09 viruses precaution. Although the use of effectiveness in previous seasons are available because influenza LAIV in young children with chronic – against influenza A(H1N1)pdm09 A(H3N2) and influenza B viruses medical conditions, including viruses. After reviewing studies on predominated during the 2017 2018 asthma, has been implemented the effectiveness of LAIV4 during Northern Hemisphere season. outside of the United States, data are past seasons, the ACIP of the CDC considered insufficient to support recommended that LAIV4 be an an expanded recommendation in the The effectiveness of influenza option for influenza vaccination in – United States. vaccines varies and is affected people for whom it is appropriate1 for by many factors, including age the 2018 2019 season. Although – The CDC conducted a systematic and health status of the recipient, the AAP and the CDC each support review of all published studies influenza type and subtype, previous the use of LAIV4 for the 2018 2019 evaluating the effectiveness of – – vaccinations, and degree of antigenic season with the aim of achieving LAIV3 and LAIV4 in children from match between the vaccine and adequate vaccination coverage and the 2010 2011 to the 2016 2017 circulating viruses. It is possible that optimal protection in children of seasons, including data from 1,United33​ vaccine effectiveness also differs all ages and both acknowledge that States and European studies. ‍ The among different individual vaccine efficacy data are not available for data revealed that the effectiveness products (for example, different the current LAIV4 formulation, the of LAIV3 or LAIV4 for influenza strain IIVs); however, product-specific AAP recommends IIV3 or IIV4 as the A (H1N1) was lower than that of an comparative effectiveness data are primary choice of influenza vaccine IIV in children 2 to 17 years of age. lacking for most vaccines. Although for all children. A LAIV was more effective against national influenza vaccination influenza B strains and similarly LAIV was initially licensed in coverage among children did not effective against influenza A(H3N2) the United States in 2003 as a decline during the past 2 seasons, in some age groups compared with trivalent formulation. LAIV4 has when LAIV was not recommended in an IIV. – been licensed in the United States the United States, overall vaccination – since 2012 and was first available For the 2017 2018 season, coverage remains suboptimal. – during the 2013 2014 influenza a new influenza A(/H1N1) Additional options for the vaccination season, replacing trivalent live pdm09 like virus, influenza of children may provide a means to attenuated influenza vaccine A/Slovenia/2903/2015, was improve coverage, particularly in (LAIV3). Recommended for people included in LAIV4, replacing school-based settings. 2 through 49 years of age, LAIV4 is influenza A/Bolivia/559/2013. Particular focus should be placed administered intranasally. The most In a study conducted by the on the administration of an IIV in commonly reported reactions in LAIV4 manufacturer, researchers Downloaded from www.aappublications.org/news by guest on September 25, 2021 12 FROM THE AMERICAN ACADEMY OF PEDIATRICS VACCINE STORAGE AND ADMINISTRATION all children and adolescents with with the package insert, and potential underlying medical conditions compliance difficulties with vaccine associated with an elevated risk The AAP Storage and Handling LAIV4excise taxes. of complications from influenza. Tip Sheet provides resources for Achieving high coverage rates of practices to develop comprehensive influenza vaccine in infants and vaccine management protocols to The cold-adapted, temperature- children is a priority to protect them keep the temperature for vaccine sensitive LAIV4 formulation against influenza disease and its storage constant during a power ° currently licensed in the United complications. Additional experience failure or other disaster (https://​ ° ° – ° States is shipped and stored at 2 C to over multiple influenza seasons will www.​aap.​org/​en-​us/​Documents/​ 8 C (35 F 46 F) and administered help to determine optimal use of the immunization_​disasterplanning.​ 36 intranasally in a prefilled, single-use available vaccine formulations in pdf). The AAP recommends the sprayer containing 0.2 mL of the children. development of a written disaster vaccine. A removable dose-divider plan for all practice settings. INFLUENZA VACCINES AND EGG clip is attached to the sprayer to Additional information is available on ALLERGY 37 facilitate the administration of 0.1 the AAP Web site. mL separately into each nostril. After Any of the influenza vaccines can the administration of any live virus It is not necessary to inquire about be administered at the same visit vaccine, at least 4 weeks should pass egg allergy before the administration with all other recommended routine before another live-virus vaccine is of any influenza vaccine, including Intramuscularvaccines. Vaccine administered. on screening forms. There is CURRENT AAP RECOMMENDATIONS strong evidence that individuals ° ° with egg allergy can safely receive IIVs for intramuscular injection are ° – ° an influenza vaccine without any shipped and stored at 2 C to 8 C Seasonal influenza vaccination additional precautions beyond those (36 F 46 F); frozen vaccines should 1,34,​ ​ is recommended for all children recommended for any vaccine. ‍ not be used. These vaccines are 35 6 months and older. The AAP ‍ The presence of egg allergy in an administered intramuscularly into recommends an IIV (IIV3 or IIV4) individual is not a contraindication the anterolateral thigh of infants and as the primary influenza vaccine to receive an IIV or LAIV. Influenza young children and into the deltoid choice for all children because the vaccine recipients with egg allergy muscle of older children and adults. effectiveness of LAIV4 was inferior are at no greater risk for a systemic Most vaccines have variable immune against influenza A(H1N1) during allergic reaction than those without responses in young children. This is past seasons, and effectiveness is egg allergy. Precautions, such as the first influenza season for which unknown against influenza A(H1N1) choice of a particular vaccine, special 3 vaccine products are available for for this upcoming season. LAIV4 observation periods, or restriction of children 6 through 35 months of age, may be used for children who would administration to particular medical as listed in Table 3. The dose volume not otherwise receive an influenza settings, are not warranted and of the available vaccines, 2 of which vaccine (eg, refusal of an IIV) and for constitute an unnecessary barrier to contain twice the amount of antigen whom it is appropriate according to immunization. Standard vaccination in this young age group, varies for age (ie, 2 years of age and older) and practice for all vaccines in children these different brands, so care should health status (ie, healthy and without should include the ability to respond be taken by clinicians to administer any underlying chronic medical to rare acute hypersensitivity the correct dose. Clinical data reveal condition). Additional details on the reactions. Patients who refuse to comparable immunogenicity and contraindications and precautions for receive an egg-based vaccine may be reactogenicity for these vaccines the use of all influenza vaccines are vaccinated with an age-appropriate with the one used in this age group in listed below. recombinant or cell-cultured recent seasons and administered as product. Children who have had a 0.25 mL per dose (Table 3). Although Children and adolescents with certain previous allergic reaction to any the amount of antigen differs, the underlying medical conditions have component of the influenza vaccine, number of doses required with either an elevated risk of complications for any reason, should be evaluated vaccine for this age group is the from influenza, including the by an allergist to determine whether same. A 0.5 mL unit dose of any IIV •following:• future receipt of the vaccine is should not be split into 2 separate appropriate. 0.25 mL doses because of safety asthma or other chronic pulmonary concerns for lack of sterility, variance diseases, including cystic fibrosis; Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 142, number 4, October 2018 13 •• hemodynamically significant limited. LAIV is contraindicated exposure in the first trimester •• cardiac disease; during pregnancy. Studies have or within 20the first 20 weeks of immunosuppressive disorders or shown that infants born to gestation. Although researchers •• therapy; women who are immunized have in most studies have not noted •• better influenza-related health an association between influenza HIV infection; outcomes compared with infants vaccination and adverse pregnancy of women who are unimmunized. outcomes, 1 recent observational sickle cell anemia and other – •• However, according to Internet- Vaccine Safety Datalink study hemoglobinopathies; – diseases that necessitate long- based panel surveys conducted conducted during the 2010 2011 by the CDC, only approximately and 2011 2012 seasons revealed term aspirin therapy or salicylate- – containing medication, including 47% of pregnant women during an association between receipt the 2016 2017 influenza season of an IIV containing H1N1pdm09 juvenile idiopathic arthritis – – or Kawasaki disease, that may and 35.6% of pregnant women and risk of spontaneous abortion place a child at increased risk of during the 2017 2018 season when an H1N1pdm-09 containing Reye syndrome if infected with (according to preliminary data) vaccine had also been21 received •• influenza; reported receiving an influenza the previous season. A follow-up study is in progress, •• vaccine, although both pregnant chronic renal dysfunction; women and their newborn and ACIP influenza vaccine chronic metabolic disease, infants are at a higher risk of recommendations for pregnant •• including diabetes mellitus; complications. More data on the women have not been changed for safety of influenza vaccination this coming season; any condition that can compromise •• respiratory function or handling in the early first trimester are becoming available. In a 5-year of secretions or increase the breastfeeding mothers. risk of aspiration, such as retrospective cohort study from Breastfeeding is strongly neurodevelopmental disorders, 2003 to 2008 of more than 10000 recommended to protect against spinal cord injuries, seizure women, influenza vaccination influenza viruses because disorders, or neuromuscular in the first trimester was not it activates innate antiviral •• abnormalities; and associated with an increase in mechanisms, specifically type 1 the rates of major18 congenital interferons. Human milk from pregnancy. malformations. Similarly, a mothers vaccinated during the Particular efforts should be made to systematic review and meta- third trimester also contains ensure vaccination in the following analysis of studies of congenital higher levels of influenza-specific39 groups to prevent the transmission anomalies after vaccination during immunoglobulin A. Greater of influenza to those at risk, unless pregnancy including data from 15 exclusivity of breastfeeding in the •contraindicated:• studies (14 cohort studies and 1 first 6 months of life decreases household contacts and out-of- case control study) did not reveal the episodes of respiratory illness home care providers of children any association between congenital with fever in infants of mothers younger than 5 years and at-risk defects and influenza vaccination who are vaccinated mothers. •• children of all ages; in any trimester, including 38the For infants born to mothers first trimester of gestation. with confirmed influenza illness close contacts of people with •• Assessments of any association at delivery, breastfeeding is immunosuppression; with influenza vaccination and encouraged, and guidance on any woman who is pregnant preterm birth and small-for- breastfeeding practices can be or considering pregnancy, is gestational-age infants have found at https://​www.​cdc.​gov/​ in the postpartum period, or yielded inconsistent results, with breastfeeding/breastfeeding-​ ​ is breastfeeding during the most studies reporting a protective special-​circumstances/​maternal-​ influenza season. It is safe to effect or no association with these or-infant-​ ​illnesses/​influenza.​html administer an IIV to pregnant outcomes. A cohort study from and https://​www.​cdc.​gov/​flu/​

women during any trimester of the Vaccines and Medications in professionals/infectioncontrol/​ 40,​ ​ gestation and postpartum. Any Pregnancy Surveillance System peri-post-​ ​settings.​htm.‍ – – 41 licensed, recommended, and of vaccine exposure during the ‍ Breastfeeding should be age-appropriate trivalent or 2010 2011 through 2013 2014 encouraged even if the mother or quadrivalent IIV or RIV4 may be seasons revealed no significant infant has influenza. The mother used, although experience with the association of spontaneous should pump and feed expressed use of RIV4 in pregnant women is abortion with influenza vaccine breast milk if she or her infant Downloaded from www.aappublications.org/news by guest on September 25, 2021 14 FROM THE AMERICAN ACADEMY OF PEDIATRICS TABLE 5 Recommended Dosage and Schedule of Influenza Antiviral Medications for reatmentT and Chemoprophylaxis in Children for the 2018–2019 Influenza Season: United States Medication Treatment (5 d) Chemoprophylaxis (10 d) Oseltamivira Adults 75 mg twice daily 75 mg once daily Children ≥12 mo 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 ages 9–11 mob 3.5 mg/kg per dose twice daily 3.5 mg/kg per dose once daily Term infants ages 0–8 mob 3 mg/kg per dose twice daily 3 mg/kg per dose once daily for infants 3–8 mo old; not recommended for infants <3 mo old unless situation judged critical because of limited safety and efficacy data in this age group Preterm infants See details in footnotec — Zanamivird Adults 10 mg (two 5 mg inhalations) twice daily 10 mg (two 5 mg inhalations) once daily Children (≥7 y old for treatment; ≥5 y 10 mg (two 5 mg inhalations) twice daily 10 mg (two 5 mg inhalations) once daily old for chemoprophylaxis) Peramivir Adults 600 mg intravenous infusion once given over 15–30 — min Children (2–12 y old) One 12 mg/kg dose, up to 600 mg maximum, via — intravenous infusion for 15–30 min Children (13–17 y old) One 600 mg dose via intravenous infusion for 15–30 — min Adapted from Centers for Disease Control and Prevention. Antiviral agents for the treatment and chemoprophylaxis of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011;60(RR–1):1–24; and Kimberlin DW, Acosta EP, Prichard MN, et al; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Oseltamivir pharmacokinetics, dosing, and resistance among children aged <2 y with influenza. J Infect Dis. 2013;207(5):709–720. — indicates not applicable. a Oseltamivir is administered orally without regard to meals, although administration with meals may improve gastrointestinal tolerability. Oseltamivir is available as Tamiflu in 30 mg, 45 mg, and 75 mg capsules and as a powder for oral suspension that is reconstituted to provide a final concentration of 6 mg/mL. For the 6 mg/mL suspension, a 30 mg dose is given with 5 mL of oral suspension, a 45 mg dose is given with 7.5 mL oral suspension, a 60 mg dose is given with 10 mL oral suspension, and a 75 mg dose is given with 12.5 mL oral suspension. If the commercially manufactured oral suspension is not available, a suspension can be compounded by retail pharmacies (final concentration also 6 mg/mL) 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 the treatment of patients with creatinine clearance 10 to 30 mL per min: 75 mg once daily for 5 days. For the chemoprophylaxis of patients with creatinine clearance 10 to 30 mL per min: 30 mg once daily for 10 days after exposure or 75 mg once every other day for 10 days after exposure (5 doses). b 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 treat influenza in both term and preterm infants from birth because benefits of therapy are likely to outweigh possible risks of treatment. c 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 provide the basis for dosing preterm infants by using their postmenstrual age (gestational age plus chronological age): 1.0 mg/kg per dose orally twice daily for those <38 wk postmenstrual age; 1.5 mg/kg per dose orally twice daily for those 38 through 40 wk postmenstrual age; and 3.0 mg/kg per dose orally twice daily for those >40 wk postmenstrual age. For extremely preterm infants (<28 wk), please consult a pediatric infectious diseases physician. d Zanamivir is administered by inhalation by using a proprietary Diskhaler device distributed together with the medication. Zanamivir is a dry powder, not an aerosol, and should not be administered by 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.

are too sick to breastfeed. If the HCP remain unvaccinated. With an at least 90% of HCP, which is breastfeeding mother requires increasing number of organizations consistent with the national antiviral agents, treatment with mandating influenza vaccination, Healthy People 2020 target for – oral oseltamivir is preferred. coverage among HCP was 78.6% annual influenza vaccination However, none of the antiviral for the 2016 2017 season, which among HCP. However, overall – agents are reasons to discontinue is similar to the 79.0% in the vaccination rates for this group – •• breastfeeding; 2015 2016 season. Early season remain consistently below this American Indian and/or Alaskan 2017 2018 vaccine coverage goal. The AAP recently reaffirmed among HCP was 67.6%, which its support for a mandatory •• native children and adolescents; – is similar to the early season influenza vaccination policy for all HCP or health care volunteers. coverage during the 2016 2017 HCP nationwide, including those Despite the AAP recommendation season. Optimal prevention of in outpatient settings. Mandating for mandatory influenza influenza in the health care setting influenza vaccination for all HCP immunization for all HCP, many depends on the vaccination of is ethical, just, and necessary to Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 142, number 4, October 2018 15 TABLE 6 Comparison of Types of Influenza Diagnostic Tests Testing Category Method Influenza Viruses Distinguished Influenza A Time to Results Performance Detected Virus Subtypes Rapid molecular assay Nucleic acid Influenza A or B viral No 15–30 min High sensitivity; high amplification RNA specificity Rapid influenza diagnostic test Antigen detection Influenza A or B virus No 10–15 min Low-to-moderate sensitivity antigens (higher with analyzer devise); high specificity Direct and indirect Antigen detection Influenza A or B virus No 1–4 h Moderate sensitivity; high immunofluorescence assays antigens specificity Molecular assays (including Nucleic acid Influenza A or B viral Yes, if subtype primers 1–8 h High sensitivity; high RT PCR) amplification RNA are used specificity Multiplex molecular assays Nucleic acid Influenza A or B viral Yes, if subtype primers 1–2 h High sensitivity; high amplification RNA; other viral or are used specificity bacterial targets (RNA or DNA) Rapid cell culture (shell vial and Virus isolation Influenza A or B virus Yes 1–3 d High sensitivity; high cell mixtures) specificity Viral culture (tissue cell culture) Virus isolation Influenza A or B virus Yes 3–10 d High sensitivity; high specificity Negative results may not be used to rule out influenza. Respiratory tract specimens should be collected as close to illness onset as possible for testing. Clinicians should consult the manufacturer’s package insert for the specific test for the approved respiratory specimen(s). Specificities are generally high (>95%) for all tests compared with RT PCR. FDA-cleared rapid influenza diagnostic tests are Clinical Laboratory Improvement Amendments waived; most FDA-cleared rapid influenza molecular assays are Clinical Laboratory Improvement Amendments waived depending on the specimen. RT, reverse transcriptase. Adapted from Uyeki T, Bernstein H, Bradley JS, et al. Clinical practice guidelines by the Infectious Diseases Society of America (IDSA): 2018 update: diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenza. Clin Infect Dis. 2018;67: in press.

improve patient safety, especially associated with respiratory (GBS) is considered to be a precaution because HCP frequently come into illnesses and to promptly initiate for the administration of influenza contact with patients at high risk antiviral treatment along with vaccine. The estimated risk for GBS is of influenza illness in their clinical influenza testing. low, especially in children. Although settings. For the prevention and CONTRAINDICATIONS AND influenza infection is recognized control of influenza, all HCP must PRECAUTIONS to be associated with GBS, there continue to prioritize the health is no elevated risk of GBS from •• and safety of patients; and influenza vaccination in children. As a precaution, people who are not at people with influenza-associated An anaphylactic or serious allergic high risk for severe influenza and who encephalopathy (IAE). One reaction to any component of are known to have experienced GBS complication associated with the vaccine is the only medical within 6 weeks of influenza vaccination influenza observed in young contraindication to influenza generally should not be vaccinated. children is encephalopathy, the vaccination. Children who have However, the benefits of influenza most severe category being acute had a previous allergic reaction to vaccination might outweigh the risks necrotizing encephalopathy (ANE). any component of the influenza for certain people who have a history During the 2009 pandemic, a large vaccine, for any reason, should of GBS (particularly if not associated increase in pediatric IAE was be evaluated by an allergist to with previous influenza vaccination) observed in Japan, and there have determine whether future receipt – and who also are at high risk for severe been sporadic cases of influenza of the vaccine is appropriate. Minor complications from influenza. A(H1N1)pdm09 associated illnesses, with or without fever, are IAE in children reported in the42 not contraindications to the use CHILDREN WHO SHOULD NOT BE United States and worldwide. VACCINATED WITH LAIV ≥ of influenza vaccines, particularly Studies support annual influenza among children with mild upper vaccination for all children 6 respiratory infection symptoms months of age in the United States, or allergic rhinitis. Children with a The following should not be and it might be especially important moderate-to-severe febrile illness, •vaccinated• with LAIV: in survivors of ANE, their household based on the judgment of the contacts, and their caregivers. clinician, should not be vaccinated •• children younger than 2 years; Because of the potential for ANE until resolution of the illness. children who have a moderate-to- recurrence, it also is important to severe febrile illness as judged by closely monitor children with a Specific to influenza vaccination, a the clinician; history of neurologic complications history of Guillain-Barre syndrome Downloaded from www.aappublications.org/news by guest on September 25, 2021 16 FROM THE AMERICAN ACADEMY OF PEDIATRICS •• •• children with an amount of nasal children taking an influenza infection attributable to the LAIV congestion that would notably antiviral medication (oseltamivir, strain in an immunocompromised •• impede vaccine delivery; zanamivir, or peramivir) until 48 contact of a person who is LAIV hours after stopping the influenza immunized. Available data indicate children 2 through 4 years of antiviral therapy. If a child recently a low risk of transmission of age with a history of recurrent received LAIV but has an influenza the virus in both children and wheezing or a medically attended illness for which antiviral agents adults vaccinated with LAIV. HCP wheezing episode in the previous are appropriate, the antiviral immunized with LAIV may continue 12 months because of the potential agents should be given. If antiviral to work in most units of a hospital, for increased wheezing after including the NICU and general immunization. In this age range, agents are necessary for treatment oncology ward, using standard many children have a history within 5 to 7 days of LAIV infection control techniques. As of wheezing with respiratory immunization, reimmunization a precautionary measure, people tract illnesses and are eventually may be indicated because of recently vaccinated with LAIV should diagnosed with asthma. Therefore, the potential effects of antiviral restrict contact with patients who when offering LAIV to children medications on LAIV replication are severely immunocompromised 24 through 59 months of age, and immunogenicity; and •• for 7 days after immunization, pediatricians should screen them “ although there have been no reports by asking the parents or guardians, children with chronic underlying of LAIV transmission from a person In the previous 12 months, has a medical conditions that may ” who is vaccinated to a person health care professional ever told predispose them to complications “ ” who is immunocompromised. In you that your child had wheezing? after wild-type influenza the theoretical scenario in which If a parent answers yes to this infection, including metabolic question, an IIV, rather than LAIV, disease, diabetes mellitus, symptomatic LAIV infection develops •• is recommended; other chronic disorders of the in an immunocompromised host, oseltamivir or zanamivir could be children with a diagnosis of pulmonary or cardiovascular systems, renal dysfunction, or prescribed because LAIV strains •• asthma; hemoglobinopathies. The safety of are susceptible to these antiviral children who have received other LAIV in these populations has not medications. live-virus vaccines within the been established. These conditions SURVEILLANCE previous 4 weeks; however, LAIV are not contraindications but are can be administered on the same listed under the warnings and day as other live-virus vaccines if precautions section of the LAIV •• necessary; package insert. A precaution is a Information about influenza condition in a recipient that might surveillance is available through the children who have a known or increase the risk or seriousness of CDC Voice Information System (for suspected immunodeficiency an adverse reaction or complicate influenza updates, call 1-800-232- disease or who are receiving making another diagnosis because 4636)29 or at www.​cdc.​gov/​flu/​index.​ immunosuppressive or htm.‍ Although current influenza •• of a possible vaccine-related immunomodulatory therapies; reaction. A precaution also may season data on circulating strains can children who are receiving aspirin exist for conditions that might not necessarily be used to predict •• or other salicylates; compromise the ability of the which and in what proportion strains will circulate in the subsequent vaccine to produce immunity. – women who are pregnant or Vaccination may be recommended season, it is instructive to be aware •• considering pregnancy; in the presence of a precaution if of 2018 2019 influenza surveillance children with any condition that the benefit of protection from the data and use them as a guide for can compromise respiratory vaccine outweighs any risk. empirical therapy until current seasonal data are available from the function or the handling of An IIV is the vaccine of choice for CDC. Information is posted weekly on secretions or can increase the anyone in close contact with a subset the CDC Web site (www.​cdc.gov/​ flu/​ ​ risk for aspiration, such as of severely immunocompromised “ ’ 43 weekly/​fluactivitysurv.​htm). The neurodevelopmental disorders, people (ie, those in a protected ” AAP offers What s the Latest with spinal cord injuries, seizure environment). An IIV is preferred the Flu (www.​aap.​org/​disasters/flu)​ disorders, or neuromuscular over LAIV for contacts of people who 44 messages to highlight those details abnormalities; are severely immunocompromised most relevant to AAP members and because of a theoretical risk of Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 142, number 4, October 2018 17 – child care providers on a monthly Compassionate use was not available pharmacies for a final concentration basis during influenza season. for the 2017 2018 season and is of 6 mg/mL (Table 5). – VACCINE IMPLEMENTATION not likely to be available during the Continuous monitoring of the 2018 2019 influenza season. epidemiology, change in severity, Antiviral resistance to any drug can and resistance patterns of influenza The AAP Partnership for Policy emerge, necessitating continuous strains by the CDC may lead to new Implementation has developed population-based assessment that guidance. a series of definitions using is conducted by the CDC. If local or Regardless of influenza vaccination accepted health information national influenza surveillance data status, antiviral treatment should technology standards to assist indicate emergence of an influenza be offered as early as possible to the in the implementation of these strain with a known antiviral •following• individuals (Table 4): recommendations in computer resistance profile, then according systems and quality measurement to the CDC, empirical treatment Children hospitalized with •• efforts. This document is available can be directed toward that strain suspected influenza; – at https://​www.​aap.​org/​en-​us/​ with an effective antiviral agent. Children hospitalized for severe, advocacy-​and-​policy/​aap-​health-​ During the 2017 2018 season, 99% complicated, or progressive initiatives/​immunizations/​Influenza-​ of the influenza A(H1N1)pdm09 illness attributable to influenza, Implementation-45 ​Guidance/​Pages/​ viruses tested were susceptible regardless of duration of default.​aspx.‍ In addition, the AAP to oseltamivir and peramivir, and •• symptoms; and has developed implementation all of the tested influenza strains Children with suspected influenza guidance on supply, payment, coding, Red Book Online were susceptible to zanamivir. (of any severity) and at high risk of and liability issues; these documents 28 All tested influenza A(H3N2) and complications (Table 2). can be found in the . influenza B viruses were susceptible USE OF ANTIVIRAL MEDICATIONS to oseltamivir, zanamivir, and Efforts should be made to minimize peramivir. In contrast, high levels treatment in patients who are not of resistance to amantadine and infected with influenza. rimantadine persist among the Oral oseltamivir remains the antiviral Treatment may be considered for the influenza A viruses currently •• drug of choice for the management following individuals (Table 4): circulating. Adamantane drugs of influenza infections. Although any otherwise healthy child are not recommended for use more difficult to administer, inhaled suspected of having influenza against influenza at this time zanamivir is an equally acceptable disease. The greatest effect on unless resistance patterns change alternative for patients who do not 1 outcome is expected to occur if significantly. have chronic respiratory disease. treatment can be initiated within Current treatment guidelines for Options are limited for children who – 48 hours of illness onset, but it cannot absorb orally or enterally antiviral medications (Table 4) still should be considered if later administered oseltamivir or tolerate are unchanged for the 2018 2019 in the course of a progressive, inhaled zanamivir. Intravenous season and are applicable to both •• symptomatic illness; and peramivir (Rapivab), a third NAI, infants and children with suspected children suspected of having was approved in September 2017 as influenza when strains are known to influenza disease and whose treatment of acute uncomplicated be circulating in the community or siblings or household contacts influenza in children 2 years and when infants or children are tested either are younger than 6 months older who are not hospitalized and and confirmed to have influenza. or have underlying medical have been symptomatic for no more Oseltamivir is available in capsule conditions that predispose them to than 2 days. Intravenous zanamivir and oral suspension formulations. complications of influenza. is not approved in the United The available capsule doses are Studies conducted to date to evaluate States. A prospective, open-label 30 mg, 45 mg, and 75 mg, and the pediatric clinical trial was conducted the efficacy of NAIs have revealed commercially manufactured liquid that timely treatment can reduce to investigate pharmacokinetics formulation has a concentration of and the clinical and/or virologic the duration of influenza symptoms 6 mg/mL in a 60 mL bottle. If the and fever as well as the risk of response to treatment with commercially manufactured oral intravenous zanamivir for children certain complications, including– suspension is not available, the hospitalization and death, in pediatric 6 months or older with a serious capsule may be opened and the 24,46​ 51 influenza infection and who could and adult populations. ‍ ‍ ‍ The 25 contents mixed with simple syrup or number of published randomized, not tolerate oral or inhaled NAIs. Ora-Sweet SF (sugar free) by retail Downloaded from www.aappublications.org/news by guest on September 25, 2021 18 FROM THE AMERICAN ACADEMY OF PEDIATRICS controlled clinical (RCT) studies in influenza, treatment with oseltamivir of symptoms in adults and children children is limited, and interpretation significantly reduced the duration with a moderate-to-severe disease or − − of the results of these studies needs of illness in this population by 17.6 progressive disease has been shown to take into consideration the size hours (95% CI 34.7 to 0.62 hours), to provide some benefit and should of the study (the number of events and when children with asthma be offered. No benefit exists for − − were excluded, this difference was double-dose NAI therapy compared might not be sufficient to assess − specific outcomes in small studies), larger ( 29.9 hours; 95% CI 53.9 with standard-dose therapy based on the variations in the case definition to 5.8 hours). The risk of otitis published data from a randomized of influenza illness (clinical versus media was47 34% lower in this group prospective trial enrolling 75% 1,of54​ laboratory confirmed), the time of as well. Overall, efficacy outcomes subjects younger than 15 years. ‍ ’ treatment administration in relation are best demonstrated in patients Dosages of antiviral agents for both to the onset of illness, and the child s with laboratory-confirmed influenza. treatment and chemoprophylaxis age and health status as important Researchers in all these studies in children can be found in Table 5 variables. A Cochrane review of 6 confirmed vomiting as a frequent (for children of all ages, including RCTs of treatment involving 2356 side effect of oseltamivir, occurring doses for preterm infants that have children with clinical influenza, 1255 in approximately 5% of treated not been evaluated by the FDA) of whom had laboratory-confirmed patients. The balance between and on the CDC Web site (www.​cdc.​ influenza, revealed that in children benefits and harms should be gov/​flu/​professionals/55 antivirals/​ ​ with laboratory-confirmed influenza, considered when making decisions index.​htm). Children younger than about the use of NAIs for either oseltamivir and Pzanamivir reduced 2 years are at an increased risk of the median duration of illness by the treatment or prophylaxis of hospitalization and complications P influenza. 36 hours (26%; < .001) and 1.3 52 attributable to influenza. The FDA days (24%; < .001), respectively. Although prospective comparative has approved oseltamivir for the Among the studies reviewed, 1 studies to determine the efficacy treatment of children as young trial of oseltamivir in children of NAIs in patients who are as 2 weeks. Given preliminary with asthma who had laboratory- hospitalized or pediatric patients pharmacokinetic data and limited confirmed influenza revealedP only with comorbidities have not been safety data, the AAP supports the a nonsignificant reduction in illness conducted and prospectively use of oseltamivir to treat influenza duration (10.4 hours [8%]; = .542). collected data to determine the in both term and preterm infants Oseltamivir significantly reduced role of NAIs in treating severe from birth because the benefits of acute otitis media in children aged 1 therapy for neonatal influenza are − influenza are limited, on the basis to 5 years with laboratory-confirmed of information obtained from likely to outweigh the possible risks − − of treatment. influenza (risk difference52 0.14; retrospective observational studies 95% CI 0.24 to 0.04). Another and meta-analyses conducted to date In adverse event data collected Cochrane review of RCTs of adult in both adults and children, most systematically in prospective trials, and children, which included 20 experts support the use of NAIs to vomiting was the only adverse effect oseltamivir (9623 participants) treat pediatric patients with severe seen more often with oseltamivir and 26 zanamivir53 trials (14628 influenza, including patients who are compared with a placebo when participants),​ revealed no effect of hospitalized. studied in children 1 through 12 oseltamivir in reducing the duration Importantly, treatment with years of age (ie, 15% of treated of illness in children with asthma; but oseltamivir for children with serious, children versus 9% receiving a in otherwise healthy children, there complicated, or progressive diseases placebo). In addition, following Pwas a reduction by a mean difference presumptively or definitively reports from Japan of oseltamivir- of 29 hours (95% CI 12 to 47 hours; caused by influenza, irrespective attributable neuropsychiatric = .001). No significant effect was of influenza vaccination status or adverse effects, reviewers of observed with zanamivir. Regarding whether illness began greater than controlled clinical trial data and complications, the authors of this 48 hours before admission, continues ongoing surveillance have failed to review did not find a significant effect to be recommended by the AAP, establish a link between this drug of NAIs on reducing hospitalizations, CDC, Infectious Diseases Society of and neurologic or psychiatric events. pneumonia, bronchitis, otitis 53 America, and Pediatric Infectious Information is56 available through the media, or sinusitis in children. Diseases Society. Earlier treatment FDA Web site. More recently, in a meta-analysis provides better clinical responses. Clinical judgment (on the basis of 5 new RCTs that included 1598 However, treatment after 48 hours children with laboratory-confirmed of underlying conditions, disease Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 142, number 4, October 2018 19 severity, time since symptom onset, although the sensitivity is lower. whether to administer antiviral ’ and local influenza activity) is Early detection, prompt antiviral chemoprophylaxis should take into an important factor in treatment treatment, and infection control account the exposed person s risk of decisions for pediatric patients who interventions can lead to improved influenza complications, vaccination present with ILI. Antiviral treatment individual patient outcomes and status, the type and duration of should be started as soon as possible allow for effective cohorting and contact, recommendations from after illness onset and should not be disease containment. local or public health authorities, delayed while waiting for a definitive and clinical judgment. Optimally, influenza test result because early People with suspected influenza postexposure chemoprophylaxis therapy provides the best outcomes. who present with an uncomplicated should only be used when antiviral Influenza diagnostic tests vary by febrile illness should be offered agents can be started within 48 method, availability, processing treatment with antiviral medications hours of exposure; the lower dose time, sensitivity, and cost (Table 6), if they are at higher risk of influenza for prophylaxis should not be all of which should be considered in complications (Table 2). Efforts used for the treatment of children making the best clinical judgment. should be made to minimize symptomatic with influenza. Early, Positive and negative predictive treatment in patients who are not full treatment doses (rather than values of influenza test results are infected with influenza. Otherwise prophylaxis doses) provided to influenced by the level of influenza healthy children who have suspected patients who are at high-risk and activity in the population being influenza with an uncomplicated symptomatic without waiting tested, the characteristics of a test presentation should be considered for laboratory confirmation is an compared with a gold standard, for antiviral medication, particularly alternate strategy. pretest probability, whether the if they are in contact with other Although vaccination is the preferred influenza virus is actively replicating children who either are younger approach to the prevention of in the person, proper collection and than 6 months or have underlying infection, chemoprophylaxis during transport of specimens, and proper medical conditions that predispose an influenza outbreak, as defined test procedures. Testing should be them to complications of influenza. If by the CDC (http://​www.​cdc.​gov/​ performed when timely results will there is a local shortage of antiviral ophss/csels/​ ​dsepd/57 ss1978/​ lesson1/​ ​ be available to influence clinical medications, local public health section11.html),​ ​ is recommended management or infection control authorities should be consulted to in•• the following situations: measures. Although decisions on provide additional guidance about treatment and infection control can testing and treatment. In past for children at high risk of be made on the basis of positive years, local shortages of oseltamivir complications from influenza for rapid antigen test results, negative suspension have occurred because whom an influenza vaccine is •• results should not always be used of uneven local drug distribution, contraindicated; in a similar fashion because of although national shortages have for children at high risk during the suboptimal sensitivity and not occurred since 2009, particularly the 2 weeks after influenza potential for false-negative results. given the availability of the capsule vaccination, before optimal Positive results of rapid influenza formulation that can be made into •• immunity is achieved; tests are helpful because they a suspension for young children if ’ for family members or HCP who may reduce additional testing to needed (Table 5). are unimmunized and are likely identify the cause of a child s ILI and to have ongoing, close exposure promote appropriate antimicrobial Randomized placebo-controlled to unimmunized children at high stewardship. Available FDA- studies revealed that oral oseltamivir risk or unimmunized infants and approved rapid molecular assays and inhaled zanamivir were toddlers who are younger than 24 are highly sensitive and specific efficacious when administered as •• months; diagnostic tests performed in less chemoprophylaxis to household than 20 minutes by using RNA for control of influenza outbreaks contacts after a family member had1,​ detection. These molecular assays for unimmunized staff and children 24laboratory-confirmed influenza. and polymerase chain reaction (PCR) ‍ During the 2009 pandemic, the in a closed institutional setting test confirmation are preferred emergence of oseltamivir resistance with children at high risk (eg, in patients who are hospitalized was noted rarely among people •• extended-care facilities); because they are more sensitive receiving postexposure prophylaxis, as a supplement to vaccination compared with antigen detection. highlighting the need to be aware of among children at high risk, Immunofluorescence assays may the possibility of emerging resistance including children who are be an alternative to PCR testing, in this population. Decisions on Downloaded from www.aappublications.org/news by guest on September 25, 2021 20 FROM THE AMERICAN ACADEMY OF PEDIATRICS immunocompromised and may and indiscriminate use might as the number of formulations of not respond with sufficient limit availability. Pediatricians IIV4 increase. Additionally, with protective immune responses after should inform recipients of limited data on the use of NAIs in •• vaccination; antiviral chemoprophylaxis that children who are hospitalized or in as postexposure prophylaxis risk of influenza is lowered but children with comorbid conditions, for family members and close still remains while taking the prospective randomized clinical trials contacts of an infected person if medication, and susceptibility to in this population are warranted. influenza returns when medication is those people are at high risk for Immunizing all HCP, which is a discontinued. Oseltamivir use is not a – •• complications from influenza; and crucial step in efforts to reduce contraindication to vaccination with health care associated influenza for children at high risk of an IIV, although LAIV effectiveness infections, serves as an example complications and their family will be decreased for the children to patients, highlighting the members and close contacts, as receiving oseltamivir. No data are safety and effectiveness of annual well as HCP, when circulating available on the impact of inhaled vaccination. Ongoing efforts should strains of influenza virus in the zanamivir on the effectiveness of include broader implementation community are not matched LAIV. For recommendations about and evaluation of mandatory with seasonal influenza vaccine treatment and chemoprophylaxis vaccination programs in both strains on the basis of current against influenza, see Table 5. inpatient and outpatient settings. data from the CDC and local health Among some people at high risk, Further investigation into the extent departments. both vaccination and antiviral of offering to immunize parents and chemoprophylaxis may be These recommendations apply to Red Book Online adult child care providers in the considered. Updates will be available routine circumstances, but it should 58 pediatric office setting; the level of in the ‍ and the CDC be noted that guidance may be 55 family contact satisfaction with this Web site. changed on the basis of updated practice; how practices handle the recommendations from the CDC in FUTURE DIRECTIONS logistic, liability, legal, and financial concert with antiviral availability, – barriers that limit or complicate local resources, clinical judgment, this service; and most importantly, recommendations from local or For the 2018 2019 season, the how this practice will affect disease public health authorities, risk of safety and effectiveness of influenza rates in children and adults is influenza complications, type and vaccines will be analyzed as they needed. There is also a need for more duration of exposure contact, and become available and reported59 by systematic health services research change in epidemiology (resistance the CDC as it is each season. The on influenza vaccine uptake and and antigenic shift) or severity of manufacturer of LAIV4 reported that refusal as well as for an identification influenza. Chemoprophylaxis is not it will employ additional vaccine of methods to enhance uptake. routinely recommended for infants virus evaluation techniques in Efforts should be made to create younger than 3 months given limited its selection of candidate vaccine adequate outreach and infrastructure safety and efficacy data in this age viruses for inclusion in LAIV4 with to facilitate the optimal distribution group. the expectation that this will result – of vaccines so that more people CHEMOPROPHYLAXIS SHOULD NOT BE in improved effectiveness of the are immunized. Pediatricians also CONSIDERED AS A SUBSTITUTE FOR formulation for the 2018 2019 might consider becoming more VACCINATION season. Continued evaluation of involved in pandemic preparedness the safety, immunogenicity, and and disaster planning efforts. A effectiveness of the influenza vaccine, bidirectional partner dialogue especially for young children and An influenza vaccine should always between pediatricians and public pregnant women, is important. ’ be offered before and during health decision-makers assists efforts The potential role of previous the influenza season when not to address children s issues during influenza vaccination on overall contraindicated even after the the initial state, regional, and local vaccine effectiveness by vaccine influenza virus has been circulating in plan development stages. Pandemic formulation, virus strain, and the community. Antiviral medications influenza preparedness of directors subject age in preventing outpatient currently licensed are important of child care centers also needs to medical visits, hospitalizations, and adjuncts to influenza vaccination improve. Additional information deaths continues to be evaluated. for the control and prevention of can be found in the Pediatric Furthermore, complete analysis of 60 influenza disease. Toxicities are Preparedness Resource Kit. associated with antiviral agents, quadrivalent vaccines is needed Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 142, number 4, October 2018 21 Pandemic influenza preparedness is information systems should be used development phases given the need of particular interest because of the whenever available and prioritized to improve options for the treatment increase in the number of human to document influenza vaccination. and chemoprophylaxis of influenza. infections with Asian lineage avian Two-dimensional barcodes have One recent example, baloxavir influenza A(H7N9) reported in China been used to facilitate more efficient marboxil, a new antiviral for (updates are available at https://​ and accurate documentation of influenza that works by a different www.​cdc.​gov/​flu/​avianflu/​h7n9-​ vaccine administration with limited mechanism than NAIs and requires virus.htm).​ A few human infections experience to date. Additional only a single dose for the treatment of Asian lineage avian influenza information concerning current of infection, has recently been A(H7N9) have been reported outside vaccines shipped with 2-dimensional approved in Japan for adults and of mainland China, but most of these barcodes 61can be found on the CDC children. The FDA recently granted infections have occurred among Web site. a priority review of this new drug, people who had traveled to China Access to care issues, a lack of for which impact on the treatment63 of before becoming ill. These Asian immunization records, and questions influenza will be followed closely. lineage avian influenza A(H7N9) regarding who can provide consent Finally, pediatricians should remain viruses have not been detected may be addressed by linking informed during the influenza seasonRed64 in people or birds in the United ’ children (eg, those in foster care byBook following Online the CDC influenza page States. Although the current risk and/or the juvenile justice system (www.​cdc/​gov/​flu) and the AAP to the public s health from this or who are refugees, immigrants, influenza resource58 page virus is low, Asian lineage avian or homeless) with a medical home, (www.​aapredbook.​org/​flu) . influenza A(H7N9) virus is among using all health care encounters as ACKNOWLEDGMENTS the nonhuman influenza viruses that vaccination opportunities, and more are most concerning to public health officials because of their pandemic consistently using immunization This AAP Policy Statement was potential and ability to cause registry data. One new strategy ’ prepared in parallel with CDC severe disease in infected humans. of interest is an IIV delivered by recommendations and reports. The current risk to the public s a dissolvable microneedle patch, Much of this statement is based health from the virus remains low; which has the potential to improve on literature reviews, analyses of however, the CDC is monitoring the vaccine acceptability and coverage n unpublished data, and deliberations situation carefully and taking routine and reduce costs. Data from the first of CDC staff in collaboration with the preparedness measures, including phase 1 human clinical trial ( = 100) ACIP Influenza Working Group with testing candidate vaccines. found that the microneedle patch immunization was well tolerated COMMITTEEliaison from ON the INFECTIOUS AAP. DISEASES, With the increased demand for 2018 2019 and generated62 robust antibody – vaccination during each influenza responses. Yvonne A. Maldonado, MD, FAAP, Chairperson season, the AAP and the CDC Theoklis E. Zaoutis, MD, MSCE, FAAP, Vice recommend vaccine administration Chairperson Development efforts continue for at any visit to the medical home Ritu Banerjee, MD, PhD, FAAP a universal influenza vaccine that during influenza season when it is Elizabeth D. Barnett, MD, FAAP induces broader protection and James D. Campbell, MD, MS, FAAP not contraindicated, at specially eliminates the need for annual Jeffrey S. Gerber, MD, PhD, FAAP arranged vaccine-only sessions, and vaccination. In addition, the Athena P. Kourtis, MD, PhD, MPH through cooperation with community Ruth Lynfield, MD, FAAP development of a safe, immunogenic sites, schools, and Head Start and Flor M. Munoz, MD, MSc, FAAP vaccine for infants younger than 6 child care facilities to provide the Dawn Nolt, MD, MPH, FAAP months is essential. Studies on the Ann-Christine Nyquist, MD, MSPH, FAAP influenza vaccine. It is important effectiveness and safety of influenza Sean T. O’Leary, MD, MPH, FAAP that the annual delivery of influenza vaccines containing adjuvants Mark H. Sawyer, MD, FAAP vaccines to primary care medical William J. Steinbach, MD, FAAP that enhance immune responses homes should be timely to avoid Tina Q. Tan, MD, FAAP missed opportunities. If alternative to influenza vaccines are ongoing. venues, including pharmacies Efforts to improve the vaccine FORMER COMMITTEE MEMBERS and other retail-based clinics, are development process to allow for Carrie L. Byington, MD, FAAP used for vaccination, a system of a shorter interval between the patient record transfer is beneficial identification of vaccine strains and in maintaining the accuracy of vaccine production continue. Lastly, immunization records. Immunization many antiviral drugs are in various Downloaded from www.aappublications.org/news by guest on September 25, 2021 22 FROM THE AMERICAN ACADEMY OF PEDIATRICS EX OFFICIO 3. Gar ten R, Blanton L, Elal AIA, et al. ABBREVIATIONS Update: influenza activity in the United Henry H. Bernstein, DO, MHCM, FAAP – Red Book Online Associate Editor States during the 2017–18 season and Michael T. Brady, MD, FAAP, Red Book Associate composition of the 2018–19 influenza Editor AAP: American Academy of vaccine. MMWR Morb Mortal Wkly Rep. Mary Anne Jackson, MD, FAAP, Red Book Associate Pediatrics 2018;67(22):634–642 Editor ACIP: Advisory Committee on 4. Biggerstaff M, Kniss K, Jernigan DB, et David W. Kimberlin, MD, FAAP – Red Book Editor Immunization Practices al. Systematic assessment of multiple Sarah S. Long, MD, FAAP – Red Book Associate Editor ANE: acute necrotizing routine and near real-time indicators H. Cody Meissner, MD, FAAP – Visual Red Book encephalopathy to classify the severity of influenza Associate Editor CDC: Centers for Disease Control seasons and pandemics in the United and Prevention States, 2003-2004 through 2015-2016. CONTRIBUTORS CI: confidence interval Am J Epidemiol. 2018;187(5):1040–1050 Stuart T. Weinberg, MD, FAAP – Partnership for FDA: Food and Drug 5. Flannery B, Reynolds SB, Blanton L, Policy Implementation Administration et al. Influenza vaccine effectiveness Angie Lee, BA Research Assistant, Cohen – against pediatric deaths: 2010-2014. Children s Medical Center GBS: Guillain-Barre syndrome ’ Pediatrics. 2017;139(5):e20164244 Shannon Cleary, BA – Research Assistant, Cohen HCP: health care personnel Children’s Medical Center IAE: influenza-associated 6. Ferdinands JM, Olsho LE, Agan AA, Victoria Chi, BA – Research Assistant, Cohen encephalopathy et al; Pediatric Acute Lung Injury Children’s Medical Center IIV: inactivated influenza vaccine and Sepsis Investigators (PALISI) Tiffany Wang, BA – Second-year Medical Student, Network. Effectiveness of influenza Donald and Barbara Zucker School of Medicine at IIV3: trivalent inactivated vaccine against life-threatening Hofstra/Northwell, Hofstra University influenza vaccine RT-PCR-confirmed influenza illness in Yingna Wang, BA – Research Assistant, Cohen IIV4: quadrivalent inactivated US children, 2010-2012. J Infect Dis. Children’s Medical Center influenza vaccine 2014;210(5):674 683 Irene Song, BA – Research Assistant, Cohen ILI: influenza-like illness – Children’s Medical Center 7. T ran D, Vaudry W, Moore D, et John M. Kelso, MD, FAAP Division of Allergy, LAIV: live attenuated influenza – al; Members of the Canadian Asthma, and Immunology, Scripps Clinic vaccine Immunization Monitoring Program John S. Bradley, MD, FAAP – Rady Children’s LAIV3: trivalent live attenuated Active. Hospitalization for Hospital influenza vaccine influenza A versus B. Pediatrics. Caroline Braun, BA – Research Assistant, Cohen LAIV4: quadrivalent live attenu- Children’s Medical Center 2016;138(3):e20154643 Y. Amanda Wang, BA Research Assistant, Cohen ated influenza vaccine – 8. Robison SG, Osborn AW. The Children’s Medical Center NAI: neuraminidase inhibitor PCR: polymerase chain reaction concordance of parent and child immunization. Pediatrics. LIAISONS PCV13: 13-valent pneumococcal 2017;139(5):e2016883 Amanda C. Cohn, MD, FAAP – Centers for Disease conjugate vaccine Control and Prevention RCT: randomized controlled trial 9. Lessin HR, Edwards KM; Committee Jamie Deseda-Tous, MD – Sociedad RIV4: quadrivalent recombinant on Practice and Ambulatory Medicine; Latinoamericana de Infectologia Pediatrica influenza vaccine Committee on Infectious Diseases. Karen M. Farizo, MD – US Food and Drug Immunizing parents and other close Administration family contacts in the pediatric Marc Fischer, MD, FAAP Centers for Disease – office setting.Pediatrics. 2012;129(1). 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Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 142, number 4, October 2018 25 Medicine. Preparation for emergencies Edwards KM, Hackell JM; Committee on 31st ed. Elk Grove Village, IL: American in the offices of pediatricians and Infectious Diseases, The Committee Academy of Pediatrics; 2018:476–489 pediatric primary care providers. on Practice and Ambulatory Medicine. Uyeki T., Bernstein H., Bradley J.S. et al; Pediatrics. 2007;120(1):200-212. Countering vaccine hesitancy. Pediatrics. Expert Panel of the Infectious Diseases Reaffirmed June 2011 2016;138(3):e20162146 Society of America. Seasonal influenza in Committee on Practice and Ambulatory Committee on Pediatric Emergency adults and children-diagnosis, treatment, Medicine; Committee on Infectious Medicine; Committee on Medical Liability; chemoprophylaxis, and institutional Diseases; Committee on State Task Force on Terrorism. The pediatrician outbreak management: clinical practice Government Affairs; Council on and disaster preparedness. Pediatrics. guidelines of the Infectious Diseases School Health; Section on 2006;117(2):560-565. Reaffirmed Society of America. Clin Infect Dis. 2018;67 Administration and Practice September 2013 In Press. Management. Medical versus nonmedical American Academy of Pediatrics. Influenza. Centers for Disease Control and Prevention. immunization exemptions for child In: Kimberlin DW, Brady MT, Jackson MA, Antiviral Drugs. Available at: www.cdc. care and school attendance. Pediatrics. Long SS, eds. Red Book: 2018 Report of gov/flu/professionals/antivirals/antiviral- 2016;138(3):e20162145 the Committee on Infectious Diseases. drug-resistance.htm.

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