Skip to main content
Log in

Estimates of the Public Health Impact of a Pediatric Vaccination Program Using an Intranasal Tetravalent Live-Attenuated Influenza Vaccine in Belgium

  • Original Research Article
  • Published:
Pediatric Drugs Aims and scope Submit manuscript

Abstract

Objectives

Our objectives were to estimate the public health outcomes of vaccinating Belgian children using an intranasal tetravalent live-attenuated influenza vaccine (QLAIV) combined with current coverage of high-risk/elderly individuals using the trivalent inactivated vaccine.

Methods

We used a deterministic, age-structured, dynamic model to simulate seasonal influenza transmission in the Belgian population under the current coverage or after extending vaccination with QLAIV to healthy children aged 2–17 years. Differential equations describe demographic changes, exposure to infectious individuals, infection recovery, and immunity dynamics. The basic reproduction number (R 0) was calibrated to the observed number of influenza doctor visits/year. Vaccine efficacy was 80 % (live-attenuated) and 59–68 % (inactivated). The 10-year incidence of symptomatic influenza was calculated with different coverage scenarios (add-on to current coverage).

Results

Model calibration yielded R 0 = 1.1. QLAIV coverage of 75 % of those aged 2–17 years averted 374,000 symptomatic cases/year (57 % of the current number), 244,000 of which were among adults (indirect effect). Vaccinating 75 % of those aged 2–11 years and 50 % of those aged 12–17 years averted 333,200 cases/year (213,000 adult cases/year). Vaccinating only healthy children aged 2–5 years generated direct protection but limited indirect protection, even with 90 % coverage (40,800 averted adult cases/year; –8.4 %). Targeting all children averted twice as many high-risk cases as targeting high-risk children only (8485 vs. 4965/year with 75 % coverage). Sensitivity analyses showed the robustness of results.

Conclusions

The model highlights the direct and indirect protection benefits when vaccinating healthy children with QLAIV in Belgium. Policies targeting only high-risk individuals or the youngest provide limited herd protection, as school-age children are important influenza vectors in the community.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Haas J, Braun S, Wutzler P. Burden of influenza in Germany: a retrospective claims database analysis for the influenza season 2012/2013. Eur J Health Econ. 2015 (Epub 5 July 2015). doi:10.1007/s10198-015-0708-7.

  2. Ehlken B, Anastassopoulou A, Hain J, Schröder C, Wahle K. Cost for physician-diagnosed influenza and influenza-like illnesses on primary care level in Germany—results of a database analysis from May 2010 to April 2012. BMC Public Health. 2015;15:578.

    Article  PubMed  PubMed Central  Google Scholar 

  3. McLaughlin JM, McGinnis JJ, Tan L, Mercatante A, Fortuna J. Estimated human and economic burden of four major adult vaccine-preventable diseases in the United States, 2013. J Prim Prev. 2015;36(4):259–73.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Crott R, Pouplier I, Roch I, Chen YC, Closon MC. Pneumonia and influenza, and respiratory and circulatory hospital admissions in Belgium: a retrospective database study. Arch Public Health. 2014;72(1):33.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Silva ML, Perrier L, Späth HM, Grog I, Mosnier A, Havet N, et al. Economic burden of seasonal influenza B in France during winter 2010–2011. BMC Public Health. 2014;14:56.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Plass D, Mangen MJ, Kraemer A, Pinheiro P, Gilsdorf A, Krause G, et al. The disease burden of hepatitis B, influenza, measles and salmonellosis in Germany: first results of the burden of communicable diseases in Europe study. Epidemiol Infect. 2014;142(10):2024–35.

    Article  CAS  PubMed  Google Scholar 

  7. Ambrose CS, Antonova EN. The healthcare and societal burden associated with influenza in vaccinated and unvaccinated European and Israeli children. Eur J Clin Microbiol Infect Dis. 2014;33(4):569–75.

    Article  CAS  PubMed  Google Scholar 

  8. Chow MY, Yin JK, Heron L, Morrow A, Dierig A, Booy R, et al. The impact of influenza-like illness in young children on their parents: a quality of life survey. Qual Life Res. 2014;23(5):1651–60.

    Article  PubMed  Google Scholar 

  9. Hollmann M, Garin O, Galante M, Ferrer M, Dominguez A, Alonso J. Impact of influenza on health-related quality of life among confirmed (H1N1) 2009 patients. PLoS One. 2013;8(3):e60477.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Pradas Velasco R, Villar FA, Puy Martínez-Zárate M. Use of European Quality of Life-5 Dimensions (EQ-5D) questionnary to value the health related quality of life variation because of influenza. Gac Sanit. 2009;23(2):104–8.

  11. Bilcke J, Coenen S, Beutels P. Influenza-like-illness and clinically diagnosed flu: disease burden, costs and quality of life for patients seeking ambulatory care or no professional care at all. PLoS One. 2014;9(7):e102634.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Antonova EN, Rycroft CE, Ambrose CS, Heikkinen T, Principi N. Burden of paediatric influenza in Western Europe: a systematic review. BMC Public Health. 2012;12:968.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Fischer WA, Gong M, Bhagwanjee S, Sevransky J. Global burden of influenza as a cause of cardiopulmonary morbidity and mortality. Glob Heart. 2014;9(3):325–36.

    Article  PubMed  PubMed Central  Google Scholar 

  14. WHO. Influenza (Seasonal). Fact sheet No. 211. March 2014. Available from: http://www.who.int/mediacentre/factsheets/fs211/en/. Accessed 26 May 2016.

  15. Hanquet G, Jonckheer P, Vlayen J, Vrijens F, Thiry N, Beutels P. Seasonal influenza vaccination: priority target groups—part 1. Good clinical practice (GCP). Brussels: Belgian Health Care Knowledge Centre (KCE). KCE Reports 162C D/2011/10273/452011. Available from: http://kce.fgov.be/publication/report/seasonal-influenza-vaccination-priority-target-groups-%E2%80%93-part-i#.V0btT_mLRhE. Accessed 26 May 2016.

  16. Peltola V, Ziegler T, Ruuskanen O. Influenza A and B virus infections in children. Clin Infect Dis. 2003;36(3):299–305.

    Article  PubMed  Google Scholar 

  17. Poehling KA, Edwards KM, Griffin MR, Szilagyi PG, Staat MA, Iwane MK, et al. The burden of influenza in young children, 2004–2009. Pediatrics. 2013;131(2):207–16.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Johnson BF, Wilson LE, Ellis J, Elliot AJ, Barclay WS, Pebody RG, et al. Fatal cases of influenza A in childhood. PLoS One. 2009;4(10):e7671.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Wong KK, Jain S, Blanton L, Dhara R, Brammer L, Fry AM, et al. Influenza-associated pediatric deaths in the United States, 2004–2012. Pediatrics. 2013;132(5):796–804.

    Article  PubMed  Google Scholar 

  20. CDC. Seasonal influenza (flu) 2013. Available from: http://www.cdc.gov/flu/spotlights/children-flu-deaths.htm. Accessed 26 May 2016.

  21. Santesso N, Hsu J, Mustafa R, Brozek J, Chen YL, Hopkins JP, et al. Antivirals for influenza: a summary of a systematic review and meta-analysis of observational studies. Influenza Other Respir Viruses. 2013;7(Suppl 2):76–81.

    Article  PubMed  Google Scholar 

  22. Michiels B, Van Puyenbroeck K, Verhoeven V, Vermeire E, Coenen S. The value of neuraminidase inhibitors for the prevention and treatment of seasonal influenza: a systematic review of systematic reviews. PLoS One. 2013;8(4):e60348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. CDC. Prevention—flu vaccine. CDC says “Take 3” actions to fight the flu. 2014. Available from: http://www.cdc.gov/flu/protect/preventing.htm. Accessed 26 May 2016.

  24. Belgium.be. Informations et services officiels. Available from: http://www.belgium.be/fr/sante/risques_pour_la_sante/epidemies/grippe. Accessed 26 May 2016.

  25. Pebody RG, Green HK, Andrews N, Zhao H, Boddington N, Bawa Z, et al. Uptake and impact of a new live attenuated influenza vaccine programme in England: early results of a pilot in primary school-age children, 2013/14 influenza season. Euro Surveill. 2014;19(22). pii: 20823.

  26. Pebody RG, Green HK, Andrews N, Boddington NL, Zhao H, Yonova I, et al. Uptake and impact of vaccinating school age children against influenza during a season with circulation of drifted influenza A and B strains, England, 2014/15. Euro Surveill. 2015;20(39). doi:10.2807/1560-7917.ES.2015.20.39.30029. pii:30029

  27. WHO. Vaccines against influenza WHO position paper. WER November 20122012:461–76.

  28. Loeb M, Russell ML, Moss L, Fonseca K, Fox J, Earn DJ, et al. Effect of influenza vaccination of children on infection rates in Hutterite communities: a randomized trial. JAMA. 2010;303(10):943–50.

    Article  CAS  PubMed  Google Scholar 

  29. Glezen WP, Gaglani MJ, Kozinetz CA, Piedra PA. Direct and indirect effectiveness of influenza vaccination delivered to children at school preceding an epidemic caused by 3 new influenza virus variants. J Infect Dis. 2010;202(11):1626–33.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Weycker D, Edelsberg J, Halloran ME, Longini IM, Nizam A, Ciuryla V, et al. Population-wide benefits of routine vaccination of children against influenza. Vaccine. 2005;23(10):1284–93.

    Article  PubMed  Google Scholar 

  31. Vynnycky E, Pitman R, Siddiqui R, Gay N, Edmunds WJ. Estimating the impact of childhood influenza vaccination programmes in England and Wales. Vaccine. 2008;26(41):5321–30.

    Article  PubMed  Google Scholar 

  32. Pitman RJ, White LJ, Sculpher M. Estimating the clinical impact of introducing paediatric influenza vaccination in England and Wales. Vaccine. 2012;30(6):1208–24.

    Article  CAS  PubMed  Google Scholar 

  33. Pitman RJ, Nagy LD, Sculpher MJ. Cost-effectiveness of childhood influenza vaccination in England and Wales: results from a dynamic transmission model. Vaccine. 2013;31(6):927–42.

    Article  CAS  PubMed  Google Scholar 

  34. Pitman R, Fisman D, Zaric GS, Postma M, Kretzschmar M, Edmunds J, et al. Dynamic transmission modeling: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force–5. Value Health. 2012;15(6):828–34.

    Article  PubMed  Google Scholar 

  35. Baguelin M, Flasche S, Camacho A, Demiris N, Miller E, Edmunds WJ. Assessing optimal target populations for influenza vaccination programmes: an evidence synthesis and modelling study. PLoS Med. 2013;10(10):e1001527.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Rose MA, Damm O, Greiner W, Knuf M, Wutzler P, Liese JG, et al. The epidemiological impact of childhood influenza vaccination using live-attenuated influenza vaccine (LAIV) in Germany: predictions of a simulation study. BMC Infect Dis. 2014;14:40.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Damm O, Eichner M, Rose MA, Knuf M, Wutzler P, Liese JG, et al. Public health impact and cost-effectiveness of intranasal live attenuated influenza vaccination of children in Germany. Eur J Health Econ. 2015;16(5):471–88.

    Article  PubMed  Google Scholar 

  38. Gerlier L, Weil-Olivier C, Carrat F, Lenne X, Greneche S, Lamotte M, et al. Public health and economic impact of vaccinating children with a quadrivalent live attenuated influenza vaccine in France using a dynamic transmission model. In: ISPOR 17th Annual European Congress: Amsterdam; 2014.

  39. StatBel. Statistics Belgium. SPF/FOD Economie. Available from: http://statbel.fgov.be/en/statistics/figures/. Accessed 26 May 2016.

  40. Weil-Olivier C, Lina B. Vaccination coverage with seasonal and pandemic influenza vaccines in children in France, 2009–2010 season. Vaccine. 2011;29(40):7075–9.

    Article  PubMed  Google Scholar 

  41. ISP/WIV. Belgian Health Interview Survey (HIS)—interactive analysis. Available from: https://hisia.wiv-isp.be/SitePages/Home.aspx. Accessed 26 May 2016.

  42. Mossong J, Hens N, Jit M, Beutels P, Auranen K, Mikolajczyk R, et al. Social contacts and mixing patterns relevant to the spread of infectious diseases. PLoS Med. 2008;5(3):e74.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Carrat F, Vergu E, Ferguson NM, Lemaitre M, Cauchemez S, Leach S, et al. Time lines of infection and disease in human influenza: a review of volunteer challenge studies. Am J Epidemiol. 2008;167(7):775–85.

    Article  PubMed  Google Scholar 

  44. Whitley RJ, Hayden FG, Reisinger KS, Young N, Dutkowski R, Ipe D, et al. Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J. 2001;20(2):127–33.

    Article  CAS  PubMed  Google Scholar 

  45. Heikkinen T, Silvennoinen H, Peltola V, Ziegler T, Vainionpaa R, Vuorinen T, et al. Burden of influenza in children in the community. J Infect Dis. 2004;190(8):1369–73.

    Article  PubMed  Google Scholar 

  46. WHA (World Health Assembly). Prevention and control of influenza pandemics and annual epidemics, 56th World Health Assembly. Geneva: World Health Organisation; 2003.

  47. Tuppin P, Samson S, Weill A, Ricordeau P, Allemand H. Influenza vaccination coverage in France in 2007–2008: contribution of vaccination refund data from the general health insurance scheme. Med Mal Infect. 2009;39(10):780–8.

    Article  CAS  PubMed  Google Scholar 

  48. Jefferson T, Rivetti A, Harnden A, Di Pietrantonj C, Demicheli V. Vaccines for preventing influenza in healthy children. Cochrane Database Syst Rev. 2008;(2):CD004879.

  49. Rhorer J, Ambrose CS, Dickinson S, Hamilton H, Oleka NA, Malinoski FJ, et al. Efficacy of live attenuated influenza vaccine in children: a meta-analysis of nine randomized clinical trials. Vaccine. 2009;27(7):1101–10.

    Article  CAS  PubMed  Google Scholar 

  50. Monto AS, Ohmit SE, Petrie JG, Johnson E, Truscon R, Teich E, et al. Comparative efficacy of inactivated and live attenuated influenza vaccines. N Engl J Med. 2009;361(13):1260–7.

    Article  CAS  PubMed  Google Scholar 

  51. Jefferson T, Di Pietrantonj C, Al-Ansary LA, Ferroni E, Thorning S, Thomas RE. Vaccines for preventing influenza in the elderly. Cochrane Database Syst Rev. 2010(2):CD004876.

  52. Ambrose CS, Wu X, Belshe RB. The efficacy of live attenuated and inactivated influenza vaccines in children as a function of time postvaccination. Pediatr Infect Dis J. 2010;29(9):806–11.

    Article  PubMed  Google Scholar 

  53. Belongia EA, Sundaram ME, McClure DL, Meece JK, Ferdinands J, VanWormer JJ. Waning vaccine protection against influenza A (H3N2) illness in children and older adults during a single season. Vaccine. 2015;33(1):246–51.

    Article  CAS  PubMed  Google Scholar 

  54. Tam JS, Capeding MR, Lum LC, Chotpitayasunondh T, Jiang Z, Huang LM, et al. Efficacy and safety of a live attenuated, cold-adapted influenza vaccine, trivalent against culture-confirmed influenza in young children in Asia. Pediatr Infect Dis J. 2007;26(7):619–28.

    Article  PubMed  Google Scholar 

  55. Beutels P, Vandendijck Y, Willem L, Goeyvaerts N, Blommaert A, Van Kerckhove K, et al. Seasonal influenza vaccination: prioritizing children or other target groups? Part II: cost-effectiveness analysis. Health Technology Assessment (HTA) Brussels: Belgian Health Care Knowledge Centre (KCE). KCE Reports 204. 2013. Available from: https://kce.fgov.be/fr/publication/report/vaccination-contre-la-grippe-saisonni%C3%A8re-priorit%C3%A9-aux-enfants-ou-%C3%A0-d%E2%80%99autres-group#.V0btlPmLRhE. Accessed 26 May 2016.

  56. Prosser LA, Meltzer MI, Fiore A, Epperson S, Bridges CB, Hinrichsen V, Lieu TA. Effects of adverse events on the projected population benefits and cost-effectiveness of using live attenuated influenza vaccine in children aged 6 months to 4 years. Arch Pediatr Adolesc Med. 2011;165(2):112–8. doi:10.1001/archpediatrics.2010.182.

    Article  PubMed  Google Scholar 

  57. Rajaram S, Blak B, Steffey A, Caspard H. Impact of universal versus targeted vaccination policy on childhood influenza vaccination rates in children with asthma in the United Kingdom. Abstract ESPID-0471 presented at the 33rd Annual Meeting of the European Society for Paediatric Infectious Diseases, Leipzig, 12–16 May 2015.

  58. Sreenivasan MV, He HH, Park SY. Administration time between seasonal live-attenuated influenza vaccine and trivalent influenza vaccine during the “Stop Flu at School” Campaign-Hawaii, 2009. Public Health Rep. 2014;129(3):229–36.

    PubMed  PubMed Central  Google Scholar 

  59. Flood EM, Block SL, Hall MC, Rousculp MD, Divino VM, Toback SL, Mahadevia PJ. Children’s perceptions of influenza illness and preferences for influenza vaccine. J Pediatr Health Care. 2011;25(3):171–9. doi:10.1016/j.pedhc.2010.04.007.

  60. Kwong JC, Pereira JA, Quach S, Pellizzari R, Dusome E, Russell ML, et al. Public Health Agency of Canada/Canadian Institutes of Health Research Influenza Research Network (PCIRN) Program Delivery and Evaluation Group. Randomized evaluation of live attenuated vs. inactivated influenza vaccines in schools (RELATIVES) pilot study: a cluster randomized trial. Vaccine. 2015;33(4):535–41. doi:10.1016/j.vaccine.2014.11.044.

  61. Block SL, Toback SL, Yi T, Ambrose CS. Efficacy of a single dose of live attenuated influenza vaccine in previously unvaccinated children: a post hoc analysis of three studies of children aged 2 to 6 years. Clin Ther. 2009;31(10):2140–7.

    Article  PubMed  Google Scholar 

  62. Department of Health. Summary of JCVI consideration of the number of doses of influenza vaccine for influenza vaccine-naïve children, March-April 2013. Published 26 July 2013. Available from: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/225425/JCVI_summary_-_number_doses_flu_vaccine_-_final.pdf. Accessed 26 May 2016.

  63. Carrat F, Valleron AJ. Influenza mortality among the elderly in France, 1980–90: how many deaths may have been avoided through vaccination? J Epidemiol Community Health. 1995;49(4):419–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. HAS. Fluenz—Avis de la Commission de Transparence du 18 juillet 2012. 18 Juillet 2012. Available from: http://www.has-sante.fr/portail/jcms/c_1284808/en/fluenz. Accessed 26 May 2016.

  65. SPILF. Société de Pathologie Infectieuse de Langue Française (SPILF): Prise en charge de la grippe en dehors d’une situation de pandémie en 2005—Texte Long. Médecine et maladies infectieuses 35 (2005). p. S237–244. doi:10.1016/j.medmal.2005.09.001.

  66. Vesikari T, Knuf M, Wutzler P, Karvonen A, Kieninger-Baum D, Schmitt HJ, et al. Oil-in-water emulsion adjuvant with influenza vaccine in young children. N Engl J Med. 2011;365(15):1406–16.

    Article  CAS  PubMed  Google Scholar 

  67. Meier CR, Napalkov PN, Wegmüller Y, Jefferson T, Jick H. Population-based study on incidence, risk factors, clinical complications and drug utilisation associated with influenza in the United Kingdom. Eur J Clin Microbiol Infect Dis. 2000;19(11):834–42.

Download references

Authorship

ME and OD conceptualised the study, carried out the simulations, and interpreted the results. MS designed and developed the simulation tool and provided technical support. LG provided local data input, analysed the simulation results, and drafted the manuscript. ML and SDSM provided expertise and guidance on data input and assumptions. All authors critically appraised, corrected, and validated the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Laetitia Gerlier.

Ethics declarations

Funding

This study was funded by an unrestricted grant from S.A. AstraZeneca N.V., Belgium.

Conflict of interest

LG and ML are employees of IMS Health, which has received consulting fees from AstraZeneca. SDSM is an employee of AstraZeneca. OD has conducted studies for and received honoraria from Herescon GmbH, which has received research support and consulting fees from AstraZeneca and MedImmune. MS is employee and shareholder of ExploSYS GmbH, which has received payments from Epimos GmbH, a contract research and consulting institute, which has received research support and consulting fees from AstraZeneca. ME is partner and shareholder of the contract research and consulting institute Epimos GmbH, which has received consulting fees and research support from AstraZeneca, Novartis, and GlaxoSmithKline.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 154 kb)

Supplementary material 2 (DOCX 14 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gerlier, L., Lamotte, M., Dos Santos Mendes, S. et al. Estimates of the Public Health Impact of a Pediatric Vaccination Program Using an Intranasal Tetravalent Live-Attenuated Influenza Vaccine in Belgium. Pediatr Drugs 18, 303–318 (2016). https://doi.org/10.1007/s40272-016-0180-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40272-016-0180-6

Keywords

Navigation