Abstract
Influenza infection is associated with significant morbidity and mortality in adults, but the highest attack rates for influenza regularly occur in children, particularly those in preschool and elementary school. The consequences of influenza in this younger population — increased rate of hospitalization in those younger than 2 years of age and serious associated morbidity — have been underestimated. Children are also the critical link for spreading influenza in the community. Recent data suggest that mass influenza vaccination of healthy children would not only protect recipients, but also may reduce the burden of influenza throughout the community.
During the past 3 decades, efforts to control influenza have focused on the use of an injectable trivalent inactivated vaccine (TIV) in high-risk persons. The vaccine is ‘safe’ and effective, but its acceptance and uptake by patients and healthcare providers have been modest at best. A new intranasal, live-attenuated, trivalent cold-adapted influenza virus vaccine (CAIV-T) [FluMist™] is ‘safe’, well tolerated, immunogenic, and efficacious in preventing influenza illness in healthy children.
Compared with TIV, CAIV-T is easier to administer and should be more readily acceptable, particularly for mass immunization campaigns. CAIV-T also induces a broader immune response and has demonstrated protection against at least three different variant influenza strains. This vaccine is particularly well suited for routine immunization of children and thus offers the potential for greatly improved control of influenza. However, the acquisition cost per single dose of FluMist™ for the 2003–4 season (≈$US46) significantly hampered its uptake both by practitioners and by managed care organizations, even despite a later ≈$US25 rebate offer.
For the 2004–5 season, CAIV-T is likely to be only modestly more expensive (average wholesale price: $US16.50 for non-returnable doses, $US23 for returnable doses) than TIV. The practitioner must consider the benefits of FluMist™ compared with its likely higher vaccine cost and the issues of reimbursement among multiple insurers.
Similar content being viewed by others
Notes
The use of trade names is for product identification purposes only and does not imply endorsement.
References
Centers for Disease Control and Prevention. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2001; 50(RR-4): 1–44
Sullivan KM. Health impact of influenza in the United States. Pharmacoeconomics 1996; 9Suppl. 3: 26–33
Barnett ED. Influenza immunization for children. N Engl J Med 1998; 338: 1459–61
Szucs TD. Influenza: the role of burden-of-illness research. Pharmacoeconomics 1999; 16Suppl. 1: 27–32
Centers for Disease Control and Prevention. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2002; 51(RR-3): 1–34
Glezen WP. Emerging infections: pandemic influenza. Epidemiol Rev 1996; 18: 64–76
Monto AS, Sullivan KM. Acute respiratory illness in the community: frequency of illness and the agents involved. Epidemiol Infect 1993; 110: 145–60
Neuzil KM, Mellen BG, Wright PF, et al. The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med 2000; 342: 225–31
Glezen WP. Consideration of the risk of influenza in children and indications for prophylaxis. Rev Infect Dis 1980; 2: 408–20
Centers for Disease Control and Prevention. Severe morbidity and mortality associated with influenza in children and young adults: Michigan, 2003. MMWR Morb Mortal Wkly Rep 2003; 52(35): 837–40
Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 2003; 289: 179–86
Izurieta HS, Thompson WW, Kramarz P, et al. Influenza and the rates of hospitalization for respiratory disease among infants and young children. N Engl J Med 2000; 342: 232–9
Quach C, Piché-Walker L, Platt R, et al. Risk factors associated with severe influenza infections in childhood: implications for vaccine strategy. Pediatrics 2003; 112: e197–201
Glezen WP. Influenza vaccination for healthy children. Curr Opin Infect Dis 2002; 15: 283–7
Glezen WP. Influenza viruses. In: Feigin RD, Cherry JD, editors. Textbook of pediatric infectious diseases. 4th ed. Philadelphia (PA): WB Saunders Company, 1998: 2024–40
Loughlin J, Poulios N, Napalkov P, et al. A study of influenza and influenza-related complications among children in a large US health insurance plan database. Pharmacoeconomics 2003; 21: 273–83
Cox NJ, Subbarao K. Influenza. Lancet 1999; 354: 1277–82
Poland GA, Hall CB. Influenza immunization of schoolchildren: can we interrupt the epidemic? Pediatrics 1999; 103: 1280–2
Dawson DA, Cain VS. Childcare arrangements: health of our nation’s children: United States, 1988. Adv Data 1990; 187: 1–12
Fleming DW, Cochi SL, Hightower AW, et al. Childhood upper respiratory tract infections: to what degree is incidence affected by day-care attendance? Pediatrics 1987; 79: 55–60
Hurwitz ES, Haber M, Chang A, et al. Effectiveness of influenza vaccination of day care children in reducing influenza-related morbidity among household contacts. JAMA 2000; 284: 1677–82
Heilman C, La Montagne JR. Influenza: status and prospects for its prevention, therapy, and control. Pediatr Clin North Am 1990; 37: 669–88
Plotkin SA, Orenstein WA. Inactivated influenza vaccines. In: Vaccine. 3rd ed. Philadelphia (PA): WB Saunders Company, 1999: 59
Jacobson RM, Poland GA. Universal vaccination of healthy children against influenza: a role for the cold-adapted intranasal influenza vaccine. Paediatr Drugs 2002; 4: 65–71
Neuzil KM, Dupont WD, Wright PF, et al. Efficacy of inactivated and cold-adapted vaccines against influenza A infection, 1985 to 1990: the pediatric experience. Pediatr Infect Dis J 2001; 20: 733–40
Gonzalez M, Pirez MC, Ward E, et al. Safety and immunogenicity of a pediatric presentation of an influenza vaccine. Arch Dis Child 2000; 83: 488–91
Heikkinen T, Ruuskanen O, Waris M, et al. Influenza vaccination in the prevention of acute otitis media. Am J Dis Child 1991; 145: 445–8
Clements DA, Langdon L, Bland C, et al. Influenza A vaccine decreases the incidence of otitis media in 6- to 30-month-old children in day care. Arch Pediatr Adolesc Med 1995; 149: 1113–7
Hoberman A, Greenberg DP, Paradise JL, et al. Effectiveness of inactivated influenza vaccine in preventing acute otitis media in young children, a randomized controlled trial. JAMA 2003; 290: 1608–16
Znagwill KM, Belshe RB. Safety and efficacy or trivalent inactivated influenza vaccine in young children: a summary for the new era of routine vaccination. Pediatr Infect Dis J 2004; 23: 189–200
Gruber WC, Taber LH, Glezen WP, et al. Live attenuated and inactivated influenza vaccine in school-age children. Am J Dis Child 1990; 144: 595–600
Clover RD, Crawford S, Glezen WP, et al. Comparison of heterotypic protection against influenza A/Taiwan/86 (H1N1) by attenuated and inactivated vaccines to A/Chile/83-like viruses. J Infect Dis 1991; 163: 300–4
Piedra PA, Glezen WP. Influenza in children: epidemiology, immunity, and vaccines. Semin Pediatr Infect Dis 1991; 2: 140–6
Hurwitz ES, Haber M, Chang A, et al. Studies of the 1996–7 inactivated influenza vaccine among children attending day care: immunologic response, protection against infection, and clinical effectiveness. J Infect Dis 2000; 182: 1218–21
Edwards KM, Dupont WD, Westrich MK, et al. A randomized controlled trial of cold-adapted and inactivated vaccines for the prevention of influenza A disease. J Infect Dis 1994; 169: 68–76
Fairchok MP, Trementozzi DP, Carter PS, et al. Effect of prednisone on response to influenza virus vaccine in asthmatic children. Arch Pediatr Adolesc Med 1998; 152: 1191–5
Kramarz P, DeStefano F, Gargiullo PM, et al. Does influenza vaccination exacerbate asthma? Analysis of a large cohort of children with asthma. Arch Fam Med 2000; 9: 617–3
Boyce TG, Poland GA. Promises and challenges of live-attenuated intranasal influenza vaccines across the age spectrum: a review. Biomed Pharmacother 2000; 54: 210–8
Maassab HF, Bryant ML. The development of live attenuated cold-adapted influenza virus vaccine for humans. Rev Med Virol 1999; 9: 237–4
Cohen GM, Nettleman MD. Economic impact of influenza vaccination in preschool children. Pediatrics 2000; 106: 973–6
Centers for Disease Control and Prevention. Using live, attenuated influenza vaccine for prevention and control of influenza: supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2003; 52(RR-13): 1–8
Belshe RB, Gruber WC, Mendelman PM, et al. Efficacy of vaccination with live, attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine. J Pediatr 2000; 136: 168–75
Johnson PR, Feldman S, Thompson JM, et al. Immunity to influenza A virus infection in young children: a comparison of natural infection, live cold-adapted vaccine, and inactivated vaccine. J Infect Dis 1986; 154: 121–7
Block SL. New data on influenza vaccines in children [letter]. Pediatr Infect Dis J 2004; 23: 85
Clements ML, Murphy BR. Development and persistence of local and systemic antibody responses in adults given live attenuated or inactivated influenza A virus vaccine. J Clin Microbiol 1986; 23: 66–72
Belshe RB, Gruber WC, Mendelman PM, et al. Correlates of immune protection induced by live, attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine. J Infect Dis 2000; 181: 1133–7
Gorse GJ, Campbell MJ, Otto EE, et al. Increased anti-influenza A virus cytotoxic T-cell activity following vaccination of the chronically ill elderly with live attenuated or inactivated influenza virus vaccine. J Infect Dis 1995; 172: 1–10
Tomoda T, Morita H, Kurashige T, et al. Prevention of influenza by the intranasal administration of cold-recombinant, live-attenuated influenza vaccine: importance of interferon gamma production and local IgA response. Vaccine 1995; 13: 185–90
McMichael AJ, Gotch FM, Noble GR, et al. Cytotoxic T-cell immunity to influenza. N Engl J Med 1983; 309: 13–7
Wright PF, Johnson PR, Karzon DT. Clinical experience with live, attenuated vaccines in children in options for the control of influenza. In: Kendal AP, Patriarca PA, editors. Options for the control of influenza. Proceedings of a Viratek-UCLA Symposium; 1985 Apr 20–25; Keystone. New York (NY): Alan R. Liss, 1986: 243–53
Johnson PR, Feldman S, Thompson JM, et al. Comparison of long-term systemic and secretory antibody responses in children given live, attenuated, or inactivated influenza A vaccine. J Med Virol 1985; 17: 325–35
Belshe RB, Mendelman PM, Treanor J, et al. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine in children. N Engl J Med 1998; 338: 1405–12
Nichol KL, Mendelman PM, Mallon KP, et al. Effectiveness of live, attenuated, intranasal influenza virus vaccine in healthy, working adults: a randomized controlled trial. JAMA 1999; 282: 137–44
Bridges CB, Thompson WW, Meltzer MI, et al. Effectiveness and cost-benefit of influenza vaccination of healthy working adults: a randomized controlled trial. JAMA 2000; 284: 1655–63
Halloran ME, Longini IM, Gaglani MJ, et al. Estimating efficacy of trivalent, cold-adapted, influenza virus vaccine (CAIV-T) against influenza A (H1N1) and B using surveillance cultures. Am J Epidemiol 2003; 158: 305–11
Mendelman PM, Cordova J, Cho I. Safety, efficacy, and effectiveness of the influenza virus vaccine, trivalent, types A and B, live, cold-adapted (CAIV-T) in healthy children and healthy adults. Vaccine 2001; 19: 2221–6
Redding G, Walker RE, Hessel C, et al. Safety and tolerability of cold-adapted influenza virus vaccine in children and adolescents with asthma. Pediatr Infect Dis J 2002; 21: 44–8
Gruber WC, Campbell PW, Thompson JM, et al. Comparison of live attenuated and inactivated influenza vaccines in cystic fibrosis patients and their families: results of a 3-year study. J Infect Dis 1994; 169: 241–7
Bergen R, Black S, Shinefield H, et al. Safety of cold-adapted live attenuated influenza vaccine in a large cohort of children and adolescents. Pediatr Infect Dis J 2004; 23: 138–44
Wyeth Vaccines. FluMist™ [package insert]. Philadelphia (PA): Wyeth Vaccines, 2003
Data on file, MedImmune Vaccines Inc., 2003
Murphy BR, Coelingh K. Principles underlying the development and use of live attenuated cold-adapted influenza A and B virus vaccines. Viral Immunol 2002; 15: 295–323
Subbarao K. As good as the real thing. J Pediatr 2000; 136: 139–41
Keitel WA, Piedra PA. Live cold-adapted, reassortant influenza vaccines (USA). In: Nicholson KG, Webster RG, Hay AJ, editors. Textbook of influenza. Oxford: Blackwell Science, 1998: 373–90
Vesikari T, Aristegui JF, Ashkenazi S, et al. A randomized, double-blind, placebo-controlled trial of the safety, transmissibility and phenotypic stability of a live, attenuated, cold-adapted influenza virus vaccine (CAIV-T) in children attending day care. Presented at the 41st Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Dec 16–19; Chicago
Ashkenazi S, Vertruyen A, Aristegui J, et al. Comparison of safety and efficacy of a trivalent live attenuated intranasal influenza vaccine (CAIV-T) with trivalent inactivated intramuscular influenza vaccine (TIV) in children aged 6 to <72 months with a history of respiratory tract infections [late breaker abstract no. 7]. Pediatric Academic Societies’ Annual Meeting; 2004 May 1–4; San Francisco
Wahn U, Crovari P, Fleming D, et al. Comparison of safety and efficacy of a trivalent live attenuated intranasal influenza vaccine (CAIV-T) with trivalent inactivated intramuscular influenza vaccine (TIV) in children and adolescents aged 6 to <18 years with asthma [late breaker abstract no. 20]. Pediatric Academic Societies’ Annual Meeting; 2004 May 1–4; San Francisco
Karron RA, Steinhoff MC, Subbarao EK, et al. Safety and immunogenicity of a cold-adapted influenza A (H1N1) reassortant virus vaccine administered to infants less than six months of age. Pediatr Infect Dis J 1995; 14: 10–6
American Academy of Pediatrics Committee on Infectious Diseases. Recommendations for influenza immunization of children. Pediatrics 2004 May; 113(5): 1441–7
Szilagyi PG, Iwane MK, Schaffer S, et al. Potential burden of universal influenza vaccination of young children on visits to primary care practices. Pediatrics 2003; 112: 821–8
Monto AS, Davenport FM, Napier JA, et al. Effect of vaccination of a school-age population upon the course of an A2/Hong Kong influenza epidemic. Bull World Health Organ 1969; 41: 537–42
Reichert TA, Sugaya N, Fedson DS, et al. The Japanese experience with vaccinating schoolchildren against influenza. N Engl J Med 2001; 344: 889–96
Nichol KL. The efficacy and cost effectiveness of vaccination against influenza among elderly persons living in the community. N Engl J Med 1994; 331: 778–84
Nichol KL. Cost-benefit analysis of a strategy to vaccinate healthy working adults against influenza. Arch Intern Med 2001; 161: 749–59
White T, Lavoie S, Nettleman M. Potential cost savings attributable to influenza vaccination of school-aged children. Pediatrics 1999; 103: e73
Luce BR, Zangwill KM, Palmer SC, et al. Cost-effectiveness analysis of an intranasal influenza vaccine for the prevention of influenza in healthy children. Pediatrics 2001; 108: e24
Acknowledgements
The author has received research grants from Medimmune Vaccines, Inc., Aventis Pasteur, and Wyeth. The author would like to thank Meher Dustoor, PhD, Lori Lush, PharmD, and Carla Pellecchia, PharmD, for their assistance in the preparation of this review.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Block, S.L. Role of Influenza Vaccine For Healthy Children in the US. Pediatr-Drugs 6, 199–209 (2004). https://doi.org/10.2165/00148581-200406040-00001
Published:
Issue Date:
DOI: https://doi.org/10.2165/00148581-200406040-00001