Feasibility of diagnosing influenza within 24 hours of symptom onset in children 1–3 years of age

  • S. Heinonen
  • H. Silvennoinen
  • P. Lehtinen
  • R. Vainionpää
  • T. Heikkinen


Diagnosing influenza at an early stage of illness is important for the initiation of effective antiviral treatment. However, especially in young children, influenza often commences with an abrupt onset of fever, with full-blown respiratory symptoms developing only later. We determined the feasibility of diagnosing influenza in young children already during the first signs of the illness. During confirmed influenza activity, we obtained nasal swabs from children aged 1–3 years who presented as outpatients within 24 hours of the onset of fever (≥38.0°C). The specimens were tested for influenza viruses with viral culture, antigen detection, PCR, and a rapid point-of-care test (Actim Influenza A&B, Medix Biochemica, Finland). In addition, follow-up specimens were obtained from a proportion of children 3–7 days later. Influenza virus was detected already within 24 hours of symptom onset in 56 of 61 (92%; 95% CI 82–97%) children in whom influenza was eventually confirmed in the laboratory. A total of 158 rapid tests performed within 24 hours of symptom onset yielded a sensitivity of 90% (95% CI 74–98%) for influenza A viruses but only 25% (95% CI 3–61%) for influenza B viruses (P < 0.001), resulting in an overall sensitivity of 77% (95% CI 61–89%) and specificity of 99% (95% CI 95–100%) for all influenza viruses. In most young children, influenza can already be accurately diagnosed within 24 hours of symptom onset. The rapid point-of-care test used was sensitive and specific for diagnosing influenza A, but its sensitivity for influenza B was limited.


  1. 1.
    Heikkinen T, Silvennoinen H, Peltola V, Ziegler T, Vainionpää R, Vuorinen T, Kainulainen L, Puhakka T, Jartti T, Toikka P, Lehtinen P, Routi T, Juven T (2004) Burden of influenza in children in the community. J Infect Dis 190(8):1369–1373CrossRefPubMedGoogle Scholar
  2. 2.
    Poehling KA, Edwards KM, Weinberg GA, Szilagyi P, Staat MA, Iwane MK, Bridges CB, Grijalva CG, Zhu YW, Bernstein DI, Herrera G, Erdman D, Hall CB, Seither R, Griffin MR; New vaccine surveillance network (2006) The underrecognized burden of influenza in young children. N Engl J Med 355(1):31–40CrossRefPubMedGoogle Scholar
  3. 3.
    Monto AS, Sullivan KM (1993) Acute respiratory illness in the community. Frequency of illness and the agents involved. Epidemiol Infect 110(1):145–160CrossRefPubMedGoogle Scholar
  4. 4.
    Neuzil KM, Mellen BG, Wright PF, Mitchel EF, Griffin MR (2000) The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med 342(4):225–231CrossRefPubMedGoogle Scholar
  5. 5.
    CDC (2009) Centers for Disease Control and Prevention: updated interim recommendations for the use of antiviral medications in the treatment and prevention of influenza for the 2009–2010 season. http://www.cdc.gov/H1N1flu/recommendations.htm. Accessed 15 March 2010
  6. 6.
    Whitley RJ, Hayden FG, Reisinger KS, Young N, Dutkowski R, Ipe D, Mills RG, Ward P (2001) Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J 20(2):127–133CrossRefPubMedGoogle Scholar
  7. 7.
    Hedrick JA, Barzilai A, Behre U, Henderson FW, Hammond J, Reilly L, Keene O (2000) Zanamivir for treatment of symptomatic influenza A and B infection in children five to twelve years of age: a randomized controlled trial. Pediatr Infect Dis J 19(5):410–417CrossRefPubMedGoogle Scholar
  8. 8.
    Aoki FY, Macleod MD, Paggiaro P, Carewicz O, El Sawy A, Wat C, Griffiths M, Waalberg E, Ward P; IMPACT Study Group (2003) Early administration of oral oseltamivir increases the benefits of influenza treatment. J Antimicrob Chemother 51(1):123–129CrossRefPubMedGoogle Scholar
  9. 9.
    Silvennoinen H, Peltola V, Lehtinen P, Vainionpää R, Heikkinen T (2009) Clinical presentation of influenza in unselected children treated as outpatients. Pediatr Infect Dis J 28(5):372–375CrossRefPubMedGoogle Scholar
  10. 10.
    Heikkinen T, Ziegler T, Peltola V, Lehtinen P, Toikka P, Lintu M, Jartti T, Juven T, Kataja J, Pulkkinen J, Kainulainen L, Puhakka T, Routi T (2003) Incidence of influenza in Finnish children. Pediatr Infect Dis J 22(10):S204–S206PubMedGoogle Scholar
  11. 11.
    Zambon MC, Stockton JD, Clewley JP, Fleming DM (2001) Contribution of influenza and respiratory syncytial virus to community cases of influenza-like illness: an observational study. Lancet 358(9291):1410–1416CrossRefPubMedGoogle Scholar
  12. 12.
    Peltola V, Reunanen T, Ziegler T, Silvennoinen H, Heikkinen T (2005) Accuracy of clinical diagnosis of influenza in outpatient children. Clin Infect Dis 41(8):1198–1200CrossRefPubMedGoogle Scholar
  13. 13.
    Cazacu AC, Greer J, Taherivand M, Demmler GJ (2003) Comparison of lateral-flow immunoassay and enzyme immunoassay with viral culture for rapid detection of influenza virus in nasal wash specimens from children. J Clin Microbiol 41(5):2132–2134CrossRefPubMedGoogle Scholar
  14. 14.
    Grijalva CG, Poehling KA, Edwards KM, Weinberg GA, Staat MA, Iwane MK, Schaffner W, Griffin MR (2007) Accuracy and interpretation of rapid influenza tests in children. Pediatrics 119(1):e6–e11. doi:10.1542/peds.2006-1694 CrossRefPubMedGoogle Scholar
  15. 15.
    Agoritsas K, Mack K, Bonsu BK, Goodman D, Salamon D, Marcon MJ (2006) Evaluation of the Quidel QuickVue test for detection of influenza A and B viruses in the pediatric emergency medicine setting by use of three specimen collection methods. J Clin Microbiol 44(7):2638–2641CrossRefPubMedGoogle Scholar
  16. 16.
    Ghebremedhin B, Engelmann I, König W, König B (2009) Comparison of the performance of the rapid antigen detection actim influenza A&B test and RT-PCR in different respiratory specimens. J Med Microbiol 58(3):365–370CrossRefPubMedGoogle Scholar
  17. 17.
    Steininger C, Redlberger M, Graninger W, Kundi M, Popow-Kraupp T (2009) Near-patient assays for diagnosis of influenza virus infection in adult patients. Clin Microbiol Infect 15(3):267–273CrossRefPubMedGoogle Scholar
  18. 18.
    Uyeki TM, Prasad R, Vukotich C, Stebbins S, Rinaldo CR, Ferng YH, Morse SS, Larson EL, Aiello AE, Davis B, Monto AS (2009) Low sensitivity of rapid diagnostic test for influenza. Clin Infect Dis 48(9):e89–e92CrossRefPubMedGoogle Scholar
  19. 19.
    Cazacu AC, Chung SE, Greer J, Demmler GJ (2004) Comparison of the directigen flu A+B membrane enzyme immunoassay with viral culture for rapid detection of influenza A and B viruses in respiratory specimens. J Clin Microbiol 42(8):3707–3710CrossRefPubMedGoogle Scholar
  20. 20.
    Chiu SS, Tse CYC, Lau YL, Peiris M (2001) Influenza A infection is an important cause of febrile seizures. Pediatrics 108(4):e63. doi:10.1542/peds.108.4.e63 CrossRefPubMedGoogle Scholar
  21. 21.
    Heinonen S, Silvennoinen H, Lehtinen P, Vainionpää R, Vahlberg T, Ziegler T, Ikonen N, Puhakka T, Heikkinen T (2010) Early oseltamivir treatment of influenza in children 1–3 years of age: a randomized controlled trial. Clin Infect Dis 51(8):887–894CrossRefPubMedGoogle Scholar
  22. 22.
    Waris M, Ziegler T, Kivivirta M, Ruuskanen O (1990) Rapid detection of respiratory syncytial virus and influenza-A virus in cell-cultures by immunoperoxidase staining with monoclonal-antibodies. J Clin Microbiol 28(6):1159–1162PubMedGoogle Scholar
  23. 23.
    Nikkari S, Halonen P, Kharitonenkov I, Kivivirta M, Khristova M, Waris M, Kendal A (1989) One-incubation time-resolved fluoroimmunoassay based on monoclonal antibodies in detection of influenza A and B viruses directly in clinical specimens. J Virol Methods 23(1):29–40CrossRefPubMedGoogle Scholar
  24. 24.
    Serwint JR, Miller RM (1993) Why diagnose influenza infections in hospitalized pediatric-patients. Pediatr Infect Dis J 12(3):200–204CrossRefPubMedGoogle Scholar
  25. 25.
    Noyola DE, Demmler GJ (2000) Effect of rapid diagnosis on management of influenza A infections. Pediatr Infect Dis J 19(4):303–307CrossRefPubMedGoogle Scholar
  26. 26.
    Woo PCY, Chiu SS, Seto WH, Peiris M (1997) Cost-effectiveness of rapid diagnosis of viral respiratory tract infections in pediatric patients. J Clin Microbiol 35(6):1579–1581PubMedGoogle Scholar
  27. 27.
    Stripeli F, Sakkou Z, Papadopoulos N, Georgiou V, Gratsia P, Christodoulou I, Tsolia M (2010) Performance of rapid influenza testing in hospitalized children. Eur J Clin Microbiol Infect Dis 29(6):683–688CrossRefPubMedGoogle Scholar
  28. 28.
    Rouleau I, Charest H, Douville-Fradet M, Skowronski DM, De Serres G (2009) Field performance of a rapid diagnostic test for influenza in an ambulatory setting. J Clin Microbiol 47(9):2699–2703CrossRefPubMedGoogle Scholar
  29. 29.
    Stein J, Louie J, Flanders S, Maselli J, Hacker JK, Drew WL, Gonzales R (2005) Performance characteristics of clinical diagnosis, a clinical decision rule, and a rapid influenza test in the detection of influenza infection in a community sample of adults. Ann Emerg Med 46(5):412–419CrossRefPubMedGoogle Scholar
  30. 30.
    Hall CB, Douglas RG, Geiman JM, Meagher MP (1979) Viral shedding patterns of children with influenza B infection. J Infect Dis 140(4):610–613PubMedGoogle Scholar
  31. 31.
    Frank AL, Taber LH, Wells CR, Wells JM, Glezen WP, Paredes A (1981) Patterns of shedding of myxoviruses and paramyxoviruses in children. J Infect Dis 144(5):433–441PubMedGoogle Scholar
  32. 32.
    Cheng CKY, Cowling BJ, Chan KH, Fang VJ, Seto WH, Yung R, Uyeki TM, Houck PM, Peiris JSM, Leung GM (2009) Factors affecting QuickVue Influenza A + B rapid test performance in the community setting. Diagn Microbiol Infect Dis 65(1):35–41CrossRefPubMedGoogle Scholar
  33. 33.
    Steininger C, Kundi M, Aberle SW, Aberle JH, Popow-Kraupp T (2002) Effectiveness of reverse transcription-PCR, virus isolation, and enzyme-linked immunosorbent assay for diagnosis of influenza A virus infection in different age groups. J Clin Microbiol 40(6):2051–2056CrossRefPubMedGoogle Scholar
  34. 34.
    Ruest A, Michaud S, Deslandes S, Frost EH (2003) Comparison of the directigen Flu A + B test, the QuickVue influenza test, and clinical case definition to viral culture and reverse transcription-PCR for rapid diagnosis of influenza virus infection. J Clin Microbiol 41(8):3487–3493CrossRefPubMedGoogle Scholar
  35. 35.
    Carrat F, Vergu E, Ferguson NM, Lemaitre M, Cauchemez S, Leach S, Valleron AJ (2008) Time lines of infection and disease in human influenza: A review of volunteer challenge studies. Am J Epidemiol 167(7):775–785CrossRefPubMedGoogle Scholar
  36. 36.
    Sato M, Hosoya M, Kato K, Suzuki H (2005) Viral shedding in children with influenza virus infections treated with neuraminidase inhibitors. Pediatr Infect Dis J 24(10):931–932CrossRefPubMedGoogle Scholar
  37. 37.
    Watanabe M, Nakagawa N, Ito M, Ihara T (2009) Sensitivity of rapid immunoassay for influenza A and B in the early phase of the disease. Pediatr Int 51(2):211–215CrossRefPubMedGoogle Scholar
  38. 38.
    Gordon A, Videa E, Saborio S, Lopez R, Kuan G, Reingold A, Balmaseda A, Harris E (2009) Performance of an influenza rapid test in children in a primary healthcare setting in Nicaragua. PLoS ONE 4:e7907. doi:10.1371/journal.pone.0007907 CrossRefPubMedGoogle Scholar
  39. 39.
    Heikkinen T, Salmi AA, Ruuskanen O (2001) Comparative study of nasopharyngeal aspirate and nasal swab specimens for detection of influenza. BMJ 322(7279):138CrossRefPubMedGoogle Scholar
  40. 40.
    Heikkinen T, Marttila J, Salmi AA, Ruuskanen O (2002) Nasal swab versus nasopharyngeal aspirate for isolation of respiratory viruses. J Clin Microbiol 40(11):4337–4339CrossRefPubMedGoogle Scholar
  41. 41.
    Abu-Diab A, Azzeh M, Ghneim R, Zoughbi M, Turkuman S, Rishmawi N, Issa AER, Siriani I, Dauodi R, Kattan R, Hindiyeh MY (2008) Comparison between pernasal flocked swabs and nasopharyngeal aspirates for detection of common respiratory viruses in samples from children. J Clin Microbiol 46(7):2414–2417CrossRefPubMedGoogle Scholar
  42. 42.
    Chan KH, Peiris JSM, Lim W, Nicholls JM, Chiu SS (2008) Comparison of nasopharyngeal flocked swabs and aspirates for rapid diagnosis of respiratory viruses in children. J Clin Virol 42(1):65–69CrossRefPubMedGoogle Scholar
  43. 43.
    Hurt AC, Alexander R, Hibbert J, Deed N, Barr IG (2007) Performance of six influenza rapid tests in detecting human influenza in clinical specimens. J Clin Virol 39(2):132–135CrossRefPubMedGoogle Scholar
  44. 44.
    Cruz AT, Cazacu AC, Greer JM, Demmler GJ (2008) Rapid assays for the diagnosis of influenza A and B viruses in patients evaluated at a large tertiary care children’s hospital during two consecutive winter seasons. J Clin Virol 41(2):143–147CrossRefPubMedGoogle Scholar
  45. 45.
    Lau LLH, Cowling BJ, Fang VJ, Chan KH, Lau EHY, Lipsitch M, Cheng CKY, Houck PM, Uyeki TM, Peiris JSM, Leung GM (2010) Viral shedding and clinical illness in naturally acquired influenza virus infections. J Infect Dis 201(10):1509–1516CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • S. Heinonen
    • 1
  • H. Silvennoinen
    • 1
  • P. Lehtinen
    • 1
  • R. Vainionpää
    • 2
  • T. Heikkinen
    • 1
  1. 1.Department of PediatricsTurku University HospitalTurkuFinland
  2. 2.Department of VirologyUniversity of TurkuTurkuFinland

Personalised recommendations