Pediatric Drugs

, Volume 4, Issue 1, pp 65–71

Universal Vaccination of Healthy Children Against Influenza

A Role for the Cold-Adapted Intranasal Influenza Vaccine
  • Robert M. Jacobson
  • Gregory A. Poland
Review Article

Abstract

The incidence of influenza in children well exceeds that of the elderly and has been identified as the basis for 20% of doctor visits for children during the winter. The disease results in over 100 hospitalizations per 100 000 person-months in children <2 years of age. Furthermore, children serve as the major vector in the community; thus, influenza in children results in significant costs to society.

Although efficacious, the current intramuscular, inactivated influenza vaccine is infrequently used in children, and is currently targeted only at children at high risk and those who are household members of such individuals. Experts believe that vaccinating only high risk individuals has little impact on the cycle of annual epidemics, but that universal vaccination of children may very well have a substantial impact. Experimental data support this. A recently published cost-benefit analysis indicated that routine, school-aged vaccination through individual visits to a clinician would save $US4 per child vaccinated. A group program such as a school-based one would save $US35. One obstacle to universal vaccination includes the real and perceived resistance to the addition of yet another annual injection to the already crowded schedule of routine childhood immunizations.

Nearing licensure is an intranasal, live attenuated, cold-adapted intranasal influenza vaccine. Cold-adaptation prevents replication in the lower respiratory tract. Trials have demonstrated immunogenicity, safety, and tolerability in adults as well as children. Placebo-controlled trials have shown efficacy rates of 83 to 94%. This novel vaccine addresses obstacles to universal childhood immunization and would permit a program of routine use that would dramatically reduce transmission and stem epidemics of influenza.

References

  1. 1.
    Longini Jr IM, Koopman JS, Haber M, et al. Statistical inference for infectious diseases: risk-specific household and community transmission parameters. Am J Epidemiol 1988; 128(4): 845–59PubMedGoogle Scholar
  2. 2.
    Monto AS, Davenport FM, Napier JA, et al. Modification of an outbreak of influenza in Tecumseh, Michigan by vaccination of school children. J Infect Dis 1970; 122(1): 16–25PubMedCrossRefGoogle Scholar
  3. 3.
    Reichert TA, Sugaya N, Fedson DS, et al. The Japanese experience with vaccinating school children against influenza. N Engl J Med 2001; 344(12): 889–96PubMedCrossRefGoogle Scholar
  4. 4.
    Langmuir AD, Henderson DA, Serfling RE. The epidemiological basis for the control of influenza. Am J Public Health 1964; 54: 563–71CrossRefGoogle Scholar
  5. 5.
    Elveback LR, Fox JP, Ackerman E, et al. An influenza simulation model for immunization studies. Am J Epidemiol 1976; 103: 152–65PubMedGoogle Scholar
  6. 6.
    Longini IM, Ackerman E, Elveback LR. An optimization model for influenza A epidemics. Math Biosci 1978; 38: 141–57CrossRefGoogle Scholar
  7. 7.
    Monto AS, Koopman JS, Longini Jr IM. Tecumseh study of illness, XIII, influenza infection and disease, 1976–1981. Am J Epidemiol 1985; 121(6): 811–22PubMedGoogle Scholar
  8. 8.
    Fox JP, Hall CE, Cooney MK, et al. Influenzavirus infections in Seattle families, 1975–1979, I: study design, methods and the occurrence of infections by time and age. Am J Epidemiol 1982; 116(2): 212–27PubMedGoogle Scholar
  9. 9.
    Carrat F, Flahault A, Boussard E, et al. Surveillance of influenza-like illness in France: the example of the 1995/1996 epidemic. J Epidemiol Comm Health 1998; 52 (1 Suppl.): 32–38SGoogle Scholar
  10. 10.
    Long CE, Hall CB, Cunningham CK, et al. Influenza surveillance in community-dwelling elderly compared with children. Arch Fam Med 1997; 6(5): 459–65PubMedCrossRefGoogle Scholar
  11. 11.
    Izurieta HS, Thomspon 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(4): 232–9PubMedCrossRefGoogle Scholar
  12. 12.
    Longini Jr IM, Koopman JS, Monto AS, et al. Estimating household and community transmission parameters for influenza. Am J Epidemiol 1982; 115(5): 736–51PubMedGoogle Scholar
  13. 13.
    White T, Lavoie S, Nettleman MD. Potential cost savings attributable to influenza vaccination of school-aged children. Pediatrics 1999; 103(6): E73PubMedCrossRefGoogle Scholar
  14. 14.
    Longini Jr IM, Halloran ME, Nizam A, et al. Estimation of the efficacy of live, attenuated influenza vaccine from a two-year, multi-center vaccine trial: implications for influenza epidemic control. Vaccine 2000; 18(18): 1902–9PubMedCrossRefGoogle Scholar
  15. 15.
    American Academy of Pediatrics. Influenza. In: Pickering L, editor. 2000 Red Book: report of the Committee on Infectious Diseases. 25th ed. Elk Grove Village (IL): American Academy of Pediatrics, 2000: 351–360Google Scholar
  16. 16.
    Farley TA, St Germain JM, Chamberlain LA, et al. The impact of influenza vaccination on respiratory illness at a boarding school. J Am Coll Health 1992; 41(3): 127–31PubMedCrossRefGoogle Scholar
  17. 17.
    Heikkinen T, Ruuskanen O, Waris M, et al. Influenza vaccination in the prevention of acute otitis media in children. Am J Dis Child 1991; 145(4): 445–8PubMedGoogle Scholar
  18. 18.
    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(10): 1113–7PubMedCrossRefGoogle Scholar
  19. 19.
    Forsyth BW, Horwitz BI, Acampora D, et al. New epidemiologic evidence confirming that bias does not explain the aspirin/Reye’s syndrome association. JAMA 1989; 261(17): 2517–24PubMedCrossRefGoogle Scholar
  20. 20.
    Centers for Disease Control and Prevention. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2000; 49(RR-3): 1–38Google Scholar
  21. 21.
    American Academy of Pediatrics. Influenza. In: Peter G, editor. 1997 Red Book: report of the Committee on Infectious Diseases. 24th ed. Elk Grove Village (IL): American Academy of Pediatrics, 1997: 307–315Google Scholar
  22. 22.
    Mossad SB. Underused options for preventing and treating influenza. Cleve Clin J Med 1999; 66(1): 19–23PubMedGoogle Scholar
  23. 23.
    Kramarz P, DeStefano F, Gargiullo PM, et al. Influenza vaccination in children with asthma in health maintenance organizations. Vaccine Safety Datalink Team. Vaccine 2000; 18(21): 2288–94Google Scholar
  24. 24.
    Chung EK, Casey R, Pinto-Martin JA, et al. Routine and influenza vaccination rates in children with asthma. Ann Allergy Asthma Immunol 1998; 80(4): 318–22PubMedCrossRefGoogle Scholar
  25. 25.
    Cates CJ, Jefferson TO, Bara A, et al. Vaccines for preventing influenza in people with asthma. Cochrane Database of Systematic Reviews. Available in The Cochr-ane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 4. Oxford: Update Software, 2001: CD000364Google Scholar
  26. 26.
    Ipp M, Macarthur C, Winders P, et al. Influenza vaccination of high-risk children: a survey of three physician groups. Can J Pub Health 1998; 89(6): 415–8Google Scholar
  27. 27.
    Glezen WP, Six HR, Frank AL, et al. Impact of epidemics upon communities and families. In: Kendal AP, Patriarca PA, editors. Options for the control of influenza: proceedings of a Viratek-UCLA symposium held in Keystone, Colorado, Apr 20–25 1985. New York: Alan R Liss, Inc, 1985: 63–73Google Scholar
  28. 28.
    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(3): 537–42PubMedGoogle Scholar
  29. 29.
    Hirota Y, Kaji M. Scepticism about influenza vaccine efficacy in Japan [letter]. Lancet 1994; 344(8919): 408–9PubMedCrossRefGoogle Scholar
  30. 30.
    Hirota Y, Fedson DS, Kaji M. Japan lagging in influenza jabs [letter]. Nature 1996; 380(6569): 18PubMedCrossRefGoogle Scholar
  31. 31.
    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(13): 1677–82PubMedCrossRefGoogle Scholar
  32. 32.
    Poland GA, Hall CB. Influenza immunization of school children: can we interrupt community epidemics? Pediatrics 1999; 103 (6 Pt 1): 1280–2PubMedCrossRefGoogle Scholar
  33. 33.
    Poland GA, Couch R. Intranasal influenza vaccine: adding to the armamentarium for influenza control. JAMA 1999; 282(2): 182–4PubMedCrossRefGoogle Scholar
  34. 34.
    Department of Communicable Disease Surveillance and Response, Influenza Pandemic Preparedness Plan. The Role of WHO and guidelines for national and regional planning. Geneva: World Health Organization, 1999: 66Google Scholar
  35. 35.
    Chalumeau HP. Vaccine manufacture at the time of a pandemic influenza. Eur J Epidemiol 1994; 10(4): 487–90PubMedCrossRefGoogle Scholar
  36. 36.
    Mackenzie JS. The potential advantages and requirements of live attenuated influenza virus vaccines. Aust NZ J Med 1977; 7(4): 431–7CrossRefGoogle Scholar
  37. 37.
    Chanock RM, Murphy BR. Use of temperature-sensitive and cold-adapted mutant viruses in immunoprophylaxis of acute respiratory tract disease. Rev Infect Dis 1980; 2(3): 421–32PubMedCrossRefGoogle Scholar
  38. 38.
    Belshe RB, Van Voris LP, Bartram J, et al. Live attenuated influenza A virus vaccines in children: results of a field trial. J Infect Dis 1984; 150(6): 834–40PubMedCrossRefGoogle Scholar
  39. 39.
    Couch RB, Quaries JM, Cate TR, et al. Clinical trials with live cold-reassortant influenza virus vaccines. In: Kendal AP, Patriarca PA, editors. Options for the control of influenza: proceedings of a Viratek-UCLA symposium held in Keystone, Colorado, Apr 20–25 1985. New York: Alan R Liss, Inc, 1985: 223–41Google Scholar
  40. 40.
    Gorse GJ, Belshe RB, Munn NJ. Safety of and serum antibody response to cold-recombinant influenza A and inactivated trivalent influenza virus vaccines in older adults with chronic diseases. J Clin Microbiol 1986; 24(3): 336–42PubMedGoogle Scholar
  41. 41.
    Murphy B. Use of live attenuated cold-adapted influenza A reassortant virus vaccines in infants, children, young adults, and elderly adults. Infect Dis Clin Pract 1993; 2: 174–81CrossRefGoogle Scholar
  42. 42.
    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(1): 68–76PubMedCrossRefGoogle Scholar
  43. 43.
    Gruber WC, Belshe RB, King JC, et al. Evaluation of live attenuated influenza vaccines in children 6–18 months of age: safety, immunogenicity, and efficacy. National Institute of Allergy and Infectious Diseases, Vaccine and Treatment Evaluation Program and the Wyeth-Ayerst ca Influenza Vaccine Investigators Group. J Infect Dis 1996; 173(6): 1313–9PubMedCrossRefGoogle Scholar
  44. 44.
    Gorse GJ, Belshe RB, Munn NJ. Local and systemic antibody responses in high-risk adults given live-attenuated and inactivated influenza A virus vaccines. J Clin Microbiol 1988; 26(5): 911–8PubMedGoogle Scholar
  45. 45.
    Anderson EL, Belshe RB, Burk B, et al. Evaluation of cold-recombinant influenza A/Korea (CR-59) virus vaccine in infants. J Clin Microbiol 1989; 27(5): 909–14PubMedGoogle Scholar
  46. 46.
    Gorse GJ, Belshe RB. Enhanced lymphoproliferation to influenza A virus following vaccination of older, chronically ill adults with live-attenuated viruses. Scand J Infect Dis 1991; 23(1): 7–17PubMedCrossRefGoogle Scholar
  47. 47.
    Edwards KM, King JC, Steinhoff MC, et al. Safety and immunogenicity of live attenuated cold-adapted influenza B/Ann Arbor/1/86 reassortant virus vaccine in infants and children. J Infect Dis 1991; 163(4): 740–5PubMedCrossRefGoogle Scholar
  48. 48.
    Anderson EL, Newman FK, Maassab HF, et al. Evaluation of a cold-adapted influenza B/Texas/84 reassortant virus (CRB-87) vaccine in young children. J Clin Microbiol 1992; 30(9): 2230–4PubMedGoogle Scholar
  49. 49.
    Belshe RB, Swierkosz EM, Anderson EL, et al. Immunization of infants and young children with live attenuated trivalent cold-recombinant influenza A H1N1, H3N2, and B vaccine. J Infect Dis 1992; 165(4): 727–32PubMedCrossRefGoogle Scholar
  50. 50.
    Swierkosz EM, Newman FK, Anderson EL, et al. Multidose, live attenuated, cold-recombinant, trivalent influenza vaccine in infants and young children. J Infect Dis 1994; 169(5): 1121–4PubMedCrossRefGoogle Scholar
  51. 51.
    King Jr JC, Lagos R, Bernstein DI, et al. Safety and immunogenicity of low and high doses of trivalent live cold-adapted influenza vaccine administered intranasally as drops or spray to healthy children. J Infect Dis 1998; 177(5): 1394–7PubMedCrossRefGoogle Scholar
  52. 52.
    Belshe RB, Mendelman PM, Treanor J, et al. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children. N Engl J Med 1998; 338(20): 1405–12PubMedCrossRefGoogle Scholar
  53. 53.
    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(3): 1133–7PubMedCrossRefGoogle Scholar
  54. 54.
    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(2): 168–75PubMedCrossRefGoogle Scholar
  55. 55.
    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(2): 137–44PubMedCrossRefGoogle Scholar
  56. 56.
    Boyce TG, Gruber WC, Coleman-Dockery SD, et al. Mucosal immune response to trivalent live attenuated intranasal influenza vaccine in children. Vaccine 1999; 18(1–2): 82–8PubMedCrossRefGoogle Scholar
  57. 57.
    Boyce TG, Poland GA. Promises and challenges of live-attenuated intranasal influenza vaccines across the age spectrum: a review. Biomed Pharmacother 2000; 54(4): 210–8PubMedCrossRefGoogle Scholar
  58. 58.
    King Jr JC, Treanor J, Fast PE, et al. Comparison of the safety, vaccine virus shedding, and immunogenicity of influenza virus vaccine, trivalent, types A and B, live cold-adapted, administered to human immunodeficiency virus (HIV)-infected and non-HIV-infected adults. J Infect Dis 2000; 181(2): 725–8PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  • Robert M. Jacobson
    • 1
  • Gregory A. Poland
    • 2
  1. 1.Department of Pediatric and Adolescent MedicineVaccine Research Group, Mayo Clinic E9RochesterUSA
  2. 2.Department of Pediatric and Adolescent MedicineVaccine Research Group, Mayo ClinicRochesterUSA

Personalised recommendations