Surveillance and outbreak report Open Access
Like 0


For future decisions on respiratory syncytial virus (RSV)-vaccination strategies and implementation into national immunisation-programmes, we used national registry data (hospitalisation, microbiology and vital statistics) to determine the age-specific incidence and direct medical costs of annual RSV-associated admissions in children < 5 years-old for the period of 2010–2015. We identified ca 2,500 RSV-associated hospitalisations annually amounting to total direct medical-costs of ca EUR 4.1 million per year. The incidence of RSV-associated hospitalisations peaked in infants 1–2 months of age followed by infants 2–3 months of age, and infants < 1 month of age, respectively. Infant boys were at higher risk of severe RSV infection as compared to infant girls: male-to-female ratio peaked with 1.4 at four months of age and gradually levelled out with increasing age to 1.0 at 4 years of age. Five RSV-associated deaths were identified. Our findings demonstrate that in a western country as Denmark, RSV constitutes a considerable burden on childhood health. Furthermore, the best approach to reduce the high incidence of RSV-associated hospitalisations in young infants < 3 months of age may be maternal vaccination due to general challenges in achieving sufficient and protective immune responses in young infants.


Article metrics loading...

Loading full text...

Full text loading...



  1. Nair H, Nokes DJ, Gessner BD, Dherani M, Madhi SA, Singleton RJ, et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet. 2010;375(9725):1545-55.  https://doi.org/10.1016/S0140-6736(10)60206-1  PMID: 20399493 
  2. Bardach A, Rey-Ares L, Cafferata ML, Cormick G, Romano M, Ruvinsky S, et al. Systematic review and meta-analysis of respiratory syncytial virus infection epidemiology in Latin America. Rev Med Virol. 2014;24(2):76-89.  https://doi.org/10.1002/rmv.1775  PMID: 24757727 
  3. Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, Staat MA, et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med. 2009;360(6):588-98.  https://doi.org/10.1056/NEJMoa0804877  PMID: 19196675 
  4. Chi H, Chang IS, Tsai FY, Huang LM, Shao PL, Chiu NC, et al. Epidemiological study of hospitalization associated with respiratory syncytial virus infection in Taiwanese children between 2004 and 2007. J Formos Med Assoc. 2011;110(6):388-96.  https://doi.org/10.1016/S0929-6646(11)60057-0  PMID: 21741007 
  5. Zhou H, Thompson WW, Viboud CG, Ringholz CM, Cheng PY, Steiner C, et al. Hospitalizations associated with influenza and respiratory syncytial virus in the United States, 1993-2008. Clin Infect Dis. 2012;54(10):1427-36.  https://doi.org/10.1093/cid/cis211  PMID: 22495079 
  6. Weigl JAI. RSV--a substantial slice of the airway disease burden and the way to a vaccine. Paediatr Int Child Health. 2012;32(sup2) Suppl 2;S9-15.  https://doi.org/10.1179/2046904712Z.00000000073  PMID: 23394753 
  7. Nolan T, Borja-Tabora C, Lopez P, Weckx L, Ulloa-Gutierrez R, Lazcano-Ponce E, et al. Prevalence and Incidence of Respiratory Syncytial Virus and Other Respiratory Viral Infections in Children Aged 6 Months to 10 Years With Influenza-like Illness Enrolled in a Randomized Trial. Clin Infect Dis. 2015;60(11):e80-9.  https://doi.org/10.1093/cid/civ065  PMID: 25673560 
  8. Jain S, Williams DJ, Arnold SR, Ampofo K, Bramley AM, Reed C, et al. CDC EPIC Study Team. Community-acquired pneumonia requiring hospitalization among U.S. children. N Engl J Med. 2015;372(9):835-45.  https://doi.org/10.1056/NEJMoa1405870  PMID: 25714161 
  9. Homaira N, Oei JL, Mallitt KA, Abdel-Latif ME, Hilder L, Bajuk B, et al. High burden of RSV hospitalization in very young children: a data linkage study. Epidemiol Infect. 2016;144(8):1612-21.  https://doi.org/10.1017/S0950268815003015  PMID: 26626237 
  10. Graham BS, Anderson LJ. Challenges and Opportunities for Respiratory Syncytial Virus Vaccines. In: Anderson LJ, Graham BS, editors. Challenges and Opportunities for Respiratory Syncytial Virus Vaccines. Berlin, Heidelberg: Springer Berlin Heidelberg; 2013. p. 391-404.
  11. Agoti CN, Mwihuri AG, Sande CJ, Onyango CO, Medley GF, Cane PA, et al. Genetic relatedness of infecting and reinfecting respiratory syncytial virus strains identified in a birth cohort from rural Kenya. J Infect Dis. 2012;206(10):1532-41.  https://doi.org/10.1093/infdis/jis570  PMID: 22966119 
  12. Ohuma EO, Okiro EA, Ochola R, Sande CJ, Cane PA, Medley GF, et al. The natural history of respiratory syncytial virus in a birth cohort: the influence of age and previous infection on reinfection and disease. Am J Epidemiol. 2012;176(9):794-802.  https://doi.org/10.1093/aje/kws257  PMID: 23059788 
  13. Hall CB, Walsh EE, Long CE, Schnabel KC. Immunity to and frequency of reinfection with respiratory syncytial virus. J Infect Dis. 1991;163(4):693-8.  https://doi.org/10.1093/infdis/163.4.693  PMID: 2010624 
  14. Hall CB. Respiratory syncytial virus in young children. Lancet. 2010;375(9725):1500-2.  https://doi.org/10.1016/S0140-6736(10)60401-1  PMID: 20399494 
  15. American Academy of Pediatrics Committee on Infectious Diseases American Academy of Pediatrics Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics. 2014;134(2):415-20.  https://doi.org/10.1542/peds.2014-1665  PMID: 25070315 
  16. Kim HW, Canchola JG, Brandt CD, Pyles G, Chanock RM, Jensen K, et al. Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am J Epidemiol. 1969;89(4):422-34.  https://doi.org/10.1093/oxfordjournals.aje.a120955  PMID: 4305198 
  17. Green CA, Scarselli E, Sande CJ, Thompson AJ, de Lara CM, Taylor KS, et al. Chimpanzee adenovirus and MVA-vectored respiratory syncytial virus vaccine is safe and expands humoral and cellular immunity in adults. Sci Transl Med. 2015;7(300):300ra126.  https://doi.org/10.1126/scitranslmed.aac5745  PMID: 26268313 
  18. Phan SI, Chen Z, Xu P, Li Z, Gao X, Foster SL, et al. A respiratory syncytial virus (RSV) vaccine based on parainfluenza virus 5 (PIV5). Vaccine. 2014;32(25):3050-7.  https://doi.org/10.1016/j.vaccine.2014.03.049  PMID: 24717150 
  19. Acosta PL, Caballero MT, Polack FP. Brief history and characterization of enhanced respiratory syncytial virus disease. Clin Vaccine Immunol. 2016;23(3):189-95.  https://doi.org/10.1128/CVI.00609-15  PMID: 26677198 
  20. Modjarrad K, Giersing B, Kaslow DC, Smith PG, Moorthy VSWHO RSV Vaccine Consultation Expert Group. WHO consultation on Respiratory Syncytial Virus Vaccine Development Report from a World Health Organization Meeting held on 23-24 March 2015. Vaccine. 2016;34(2):190-7.  https://doi.org/10.1016/j.vaccine.2015.05.093  PMID: 26100926 
  21. Falsey AR, McElhaney JE, Beran J, van Essen GA, Duval X, Esen M, et al. Respiratory syncytial virus and other respiratory viral infections in older adults with moderate to severe influenza-like illness. J Infect Dis. 2014;209(12):1873-81.  https://doi.org/10.1093/infdis/jit839  PMID: 24482398 
  22. Hall CB, Weinberg GA, Blumkin AK, Edwards KM, Staat MA, Schultz AF, et al. Respiratory syncytial virus-associated hospitalizations among children less than 24 months of age. Pediatrics. 2013;132(2):e341-8.  https://doi.org/10.1542/peds.2013-0303  PMID: 23878043 
  23. Nair H, Simões EAF, Rudan I, Gessner BD, Azziz-Baumgartner E, Zhang JSF, et al. Severe Acute Lower Respiratory Infections Working Group. Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis. Lancet. 2013;381(9875):1380-90.  https://doi.org/10.1016/S0140-6736(12)61901-1  PMID: 23369797 
  24. Voldstedlund M, Haarh M, Mølbak K, the MiBa Board of Representatives CMiBa Board of Representatives. The danish microbiology database (MIBA) 2010 to 2013. Euro Surveill. 2014;19(1):20667.  https://doi.org/10.2807/1560-7917.ES2014.19.1.20667  PMID: 24434175 
  25. World Health Organization (WHO). International Statistical Classification of Diseases and Health-related Problems, 10th Revision. Geneva: WHO; 2015. [Accessed 13 Jan 2017]. Available from: http://apps.who.int/classifications/icd10/browse/2016/en
  26. Juel K, Helweg-Larsen K. The Danish registers of causes of death. Dan Med Bull. 1999;46(4):354-7. PMID: 10514943 
  27. Gubbels S, Nielsen KS, Sandegaard J, Mølbak K, Nielsen J. The development and use of a new methodology to reconstruct courses of admission and ambulatory care based on the Danish National Patient Registry. Int J Med Inform. 2016;95:49-59.  https://doi.org/10.1016/j.ijmedinf.2016.08.003  PMID: 27697232 
  28. Sundhedsdatastyrelsen. DRG-takster 2016. 2016. [Accessed 13 Jan 2017]. Available from: http://sundhedsdatastyrelsen.dk/da/afregning-og-finansiering/takster-drg/takster-2016
  29. Hacimustafaoglu M, Celebi S, Aynaci E, Sinirtas M, Koksal N, Kucukerdogan A, et al. The progression of maternal RSV antibodies in the offspring. Arch Dis Child. 2004;89(1):52-3.  https://doi.org/10.1136/adc.2002.017780  PMID: 14709507 
  30. Munoz FM, Piedra PA, Glezen WP. Safety and immunogenicity of respiratory syncytial virus purified fusion protein-2 vaccine in pregnant women. Vaccine. 2003;21(24):3465-7.  https://doi.org/10.1016/S0264-410X(03)00352-9  PMID: 12850361 
  31. Laxminarayan R, Jamison DT, Krupnick AJ, Norheim OF. Valuing vaccines using value of statistical life measures. Vaccine. 2014;32(39):5065-70.  https://doi.org/10.1016/j.vaccine.2014.07.003  PMID: 25045822 
  32. Reyes M, Eriksson M, Bennet R, Hedlund KO, Ehrnst A. Regular pattern of respiratory syncytial virus and rotavirus infections and relation to weather in Stockholm, 1984--1993. Clin Microbiol Infect. 1997;3(6):640-6.  https://doi.org/10.1111/j.1469-0691.1997.tb00471.x  PMID: 11864206 
  33. Eriksson M, Bennet R, Rotzén-Ostlund M, von Sydow M, Wirgart BZ. Population-based rates of severe respiratory syncytial virus infection in children with and without risk factors, and outcome in a tertiary care setting. Acta Paediatr. 2002;91(5):593-8.  https://doi.org/10.1111/j.1651-2227.2002.tb03282.x  PMID: 12113331 
  34. White LJ, Waris M, Cane PA, Nokes DJ, Medley GF. The transmission dynamics of groups A and B human respiratory syncytial virus (hRSV) in England & Wales and Finland: seasonality and cross-protection. Epidemiol Infect. 2005;133(2):279-89.  https://doi.org/10.1017/S0950268804003450  PMID: 15816153 
  35. Haynes AK, Prill MM, Iwane MK, Gerber SICenters for Disease Control and Prevention (CDC). Respiratory syncytial virus--United States, July 2012-June 2014. MMWR Morb Mortal Wkly Rep. 2014;63(48):1133-6. PMID: 25474034 
  36. Doucette A, Jiang X, Fryzek J, Coalson J, McLaurin K, Ambrose CS. Trends in Respiratory Syncytial Virus and Bronchiolitis Hospitalization Rates in High-Risk Infants in a United States Nationally Representative Database, 1997-2012. PLoS One. 2016;11(4):e0152208.  https://doi.org/10.1371/journal.pone.0152208  PMID: 27050095 
  37. Waris M. Pattern of respiratory syncytial virus epidemics in Finland: two-year cycles with alternating prevalence of groups A and B. J Infect Dis. 1991;163(3):464-9.  https://doi.org/10.1093/infdis/163.3.464  PMID: 1995719 
  38. Weigl JAI, Puppe W, Schmitt HJ. Seasonality of respiratory syncytial virus-positive hospitalizations in children in Kiel, Germany, over a 7-year period. Infection. 2002;30(4):186-92.  https://doi.org/10.1007/s15010-002-2159-1  PMID: 12236558 
  39. Duppenthaler A, Gorgievski-Hrisoho M, Frey U, Aebi C. Two-year periodicity of respiratory syncytial virus epidemics in Switzerland. Infection. 2003;31(2):75-80.  https://doi.org/10.1007/s15010-002-3124-8  PMID: 12682811 
  40. Avendaño LF, Palomino MA, Larrañaga C. Surveillance for respiratory syncytial virus in infants hospitalized for acute lower respiratory infection in Chile (1989 to 2000). J Clin Microbiol. 2003;41(10):4879-82.  https://doi.org/10.1128/JCM.41.10.4879-4882.2003  PMID: 14532249 
  41. Deshpande SA, Northern V. The clinical and health economic burden of respiratory syncytial virus disease among children under 2 years of age in a defined geographical area. Arch Dis Child. 2003;88(12):1065-9.  https://doi.org/10.1136/adc.88.12.1065  PMID: 14670770 
  42. Svensson C, Berg K, Sigurs N, Trollfors B. Incidence, risk factors and hospital burden in children under five years of age hospitalised with respiratory syncytial virus infections. Acta Paediatr. 2015;104(9):922-6.  https://doi.org/10.1111/apa.13061  PMID: 26036725 
  43. La Via WV, Grant SW, Stutman HR, Marks MI. Clinical profile of pediatric patients hospitalized with respiratory syncytial virus infection. Clin Pediatr (Phila). 1993;32(8):450-4.  https://doi.org/10.1177/000992289303200801  PMID: 8104752 
  44. Numa A. Outcome of respiratory syncytial virus infection and a cost-benefit analysis of prophylaxis. J Paediatr Child Health. 2000;36(5):422-7.  https://doi.org/10.1046/j.1440-1754.2000.00303.x  PMID: 11036794 
  45. Hussey GD, Apolles P, Arendse Z, Yeates J, Robertson A, Swingler G, et al. Respiratory syncytial virus infection in children hospitalised with acute lower respiratory tract infection. S Afr Med J. 2000;90(5):509-12. PMID: 10901825 
  46. Fjaerli HO, Farstad T, Bratlid D. Hospitalisations for respiratory syncytial virus bronchiolitis in Akershus, Norway, 1993-2000: a population-based retrospective study. BMC Pediatr. 2004;4(1):25.  https://doi.org/10.1186/1471-2431-4-25  PMID: 15606912 
  47. Tsolia MN, Kafetzis D, Danelatou K, Astral H, Kallergi K, Spyridis P, et al. Epidemiology of respiratory syncytial virus bronchiolitis in hospitalized infants in Greece. Eur J Epidemiol. 2003;18(1):55-61.  https://doi.org/10.1023/A:1022556215190  PMID: 12705624 
  48. Hon KL, Leung TF, Cheng WY, Ko NM, Tang WK, Wong WW, et al. Respiratory syncytial virus morbidity, premorbid factors, seasonality, and implications for prophylaxis. J Crit Care. 2012;27(5):464-8.  https://doi.org/10.1016/j.jcrc.2011.12.001  PMID: 22227087 
  49. Gil-Prieto R, Gonzalez-Escalada A, Marín-García P, Gallardo-Pino C, Gil-de-Miguel A. Respiratory Syncytial Virus Bronchiolitis in Children up to 5 Years of Age in Spain: Epidemiology and Comorbidities: An Observational Study. Medicine (Baltimore). 2015;94(21):e831.  https://doi.org/10.1097/MD.0000000000000831  PMID: 26020386 
  50. Bont L, Checchia PA, Fauroux B, Figueras-Aloy J, Manzoni P, Paes B, et al. Defining the Epidemiology and Burden of Severe Respiratory Syncytial Virus Infection Among Infants and Children in Western Countries. Infect Dis Ther. 2016;5(3):271-98.  https://doi.org/10.1007/s40121-016-0123-0  PMID: 27480325 

Data & Media loading...

Submit comment
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error