What the Paediatrician Needs to Know When Pandemic Influenza Arrives in Clinical Practice

  • Nicole Ritz
  • Nigel Curtis
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 609)

Avian (H5N1) influenza or “bird ‘flu” has received considerable attention in both the medical literature and the mass media in the last few years. Despite the tabloids’ portrayal of an imminent threat, to date there have been relatively few cases in humans in spite of large numbers of infected poultry (Hien et al. 2004). However, this may be falsely reassuring. Most indications suggest that it is just a matter of time until the next influenza pandemic occurs (Osterholm 2005). In the words of the UK Chief Medical Officer: “most experts believe that it is not a question of whether there will be another severe influenza pandemic but when” (Department of Health 2005). Although experts are agreed that a future influenza pandemic is almost inevitable, its timing is unpredictable and it is uncertain whether the virus responsible will be H5N1 or another, novel, influenza strain (Osterholm 2005). A recent editorial described avian influenza as a “predicament of extraordinary proportions” (Anonymous 2006). The next influenza pandemic will have a dramatic impact on all levels of health care including the everyday work of doctors. This chapter focuses on the clinical aspects of pandemic influenza about which paediatricians need to be familiar.


Influenza Virus Avian Influenza Avian Influenza Virus Pandemic Influenza H5N1 Influenza 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. (2007) New Concerns about Oseltamivin. Lancet, 369–1016.Google Scholar
  2. Anonymous (2006) A reappraisal of H5N1 avian influenza. Lancet, 367 1550.Google Scholar
  3. Apisarnthanarak A, Kitphati R, Thongphubeth K, Patoomanunt P, Anthanont P, Auwanit W, Thawatsupha P, Chittaganpitch M, Saeng-aroon S, Waicharoen S, Apisarnthanarak P, Storch GA, Mundy LM, and Fraser VJ. (2004) Atypical avian influenza (H5N1). Emerging Infectious Diseases, 10, 1321–1324.PubMedGoogle Scholar
  4. Beigel JH, Farrar J, Han AM, Hayden FG, Hyer R, De Jong MD, Lochindarat S, Nguyen TKT, Nguyen TH, Tran TH, Nicoll A, Touch S, Yuen K-y, and Writing Committee of The World Health Organization Consultation on Human Influenza, A. H. (2005) Avian influenza A (H5N1) infection in humans. New England Journal of Medicine, 353, 1374–1385.PubMedCrossRefGoogle Scholar
  5. Brett AS, and Zuger A. (2005) The run on tamiflu–should physicians prescribe on demand? New England Journal of Medicine, 353, 2636–2637.PubMedCrossRefGoogle Scholar
  6. Bridges CB, Kuehnert MJ, and Hall CB. (2003) Transmission of influenza: implications for control in health care settings. Clinical Infectious Diseases, 37, 1094–1101.PubMedCrossRefGoogle Scholar
  7. Centers For Disease Control and Prevention (2003) Respiratory Hygiene/Cough Etiquette in Healthcare Settings. (accessed 28 August, 2006 at
  8. Centers for Disease Control and Prevention (2006) Antiviral Medications for Influenza. (accessed 28 August, 2006 at ).
  9. Chen H, Deng G, Li Z, Tian G, Li Y, Jiao P, Zhang L, Liu Z, Webster RG, and Yu K. (2004) The evolution of H5N1 influenza viruses in ducks in southern China. Proceedings of the National Academy of Sciences of the United States of America, 101, 10452–10457.PubMedCrossRefGoogle Scholar
  10. Cheung C-l, Rayner JM, Smith GJD, Wang P, Naipospos TSP, Zhang J, Yuen K-y, Webster RG, Peiris JSM, Guan Y, and Chen H. (2006) Distribution of amantadine-resistant H5N1 avian influenza variants in Asia. Journal of Infectious Diseases, 193, 1626–1629.PubMedCrossRefGoogle Scholar
  11. Chotpitayasunondh T, Ungchusak K, Hanshaoworakul W, Chunsuthiwat S, Sawanpanyalert P, Kijphati R, Lochindarat S, Srisan P, Suwan P, Osotthanakorn Y, Anantasetagoon T, Kanjanawasri S, Tanupattarachai S, Weerakul J, Chaiwirattana R, Maneerattanaporn M, Poolsavathitikool R, Chokephaibulkit K, Apisarnthanarak A, and Dowell SF. (2005) Human disease from influenza A (H5N1), Thailand, 2004. Emerging Infectious Diseases, 11, 201–209.PubMedGoogle Scholar
  12. De Jong MD, Bach VC, Phan TQ, Vo MH, Tran TT, Nguyen BH, Beld M, Le TP, Truong HK, Nguyen VVC, Tran TH, Do QH, and Farrar J. (2005a) Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma. New England Journal of Medicine, 352, 686–691.PubMedCrossRefGoogle Scholar
  13. De Jong MD, Tran TT, Truong HK, Vo MH, Smith GJD, Nguyen VC, Bach VC, Phan TQ, Do QH, Guan Y, Peiris JSM, Tran TH, and Farrar J. (2005b) Oseltamivir resistance during treatment of influenza A (H5N1) infection. New England Journal of Medicine, 353, 2667–2672.PubMedCrossRefGoogle Scholar
  14. Department Of Health HSIP, Monitoring And Surveillance (2005) UK Health Departments’ Influenza pandemic contingency plan. (Accessed August 18 2006 at GuidanceArticle/fs/en?CONTENTID=4121735&chk=Z6kjQY ).
  15. Dolin R. (2005) Influenza–interpandemic as well as pandemic disease. N Engl J Med, 353, 2535–2537.PubMedCrossRefGoogle Scholar
  16. Frank AL, Taber LH, Wells CR, Wells JM, Glezen WP, and Paredes A. (1981) Patterns of shedding of myxoviruses and paramyxoviruses in children. J Infect Dis, 144, 433–441.PubMedGoogle Scholar
  17. Freund B, Gravenstein S, Elliott M, and Miller I. (1999) Zanamivir: a review of clinical safety. Drug Safety, 21, 267–81.PubMedCrossRefGoogle Scholar
  18. Gambaryan A, Tuzikov A, Pazynina G, Bovin N, Balish A, and Klimov A. (2006) Evolution of the receptor binding phenotype of influenza A (H5) viruses. Virology, 344, 432–438.PubMedCrossRefGoogle Scholar
  19. Goicoechea M. (2007) Human H5N1 influenza. N Engl J Med, 356, 1375; author reply 1376–7.PubMedCrossRefGoogle Scholar
  20. Gupta RK, and Nguyen-van-tam JS. (2006) Oseltamivir resistance in influenza A (H5N1) infection. New England Journal of Medicine, 354, 1423–4; author reply 1423–1424.PubMedCrossRefGoogle Scholar
  21. Harper SA, Fukuda K, Uyeki TM, Cox NJ, and Bridges, C. B. (2005) Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep, 54, 1–40.PubMedGoogle Scholar
  22. Hayden FG. (2004) Pandemic influenza: is an antiviral response realistic? Pediatric Infectious Disease Journal, 23, S262–S269.PubMedCrossRefGoogle Scholar
  23. Hayden FG. (2006) Antiviral resistance in influenza viruses–implications for management and pandemic response. New England Journal of Medicine, 354, 785–788.PubMedCrossRefGoogle Scholar
  24. Hayden FG, Treanor JJ, Fritz RS, Lobo M, Betts RF, Miller M, Kinnersley N, Mills RG, Ward P, and Straus SE. (1999) Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment. JAMA, 282, 1240–1246.PubMedCrossRefGoogle Scholar
  25. Hien TT, De Jong M, and Farrar J. (2004) Avian influenza–a challenge to global health care structures. New England Journal of Medicine, 351, 2363–2365.PubMedCrossRefGoogle Scholar
  26. Howton JC. (2006) Probenecid with oseltamivir for human influenza A (H5N1) virus infection? New England Journal of Medicine, 354, 879–880.PubMedCrossRefGoogle Scholar
  27. Ilyushina NA, Bovin NV, Webster RG, and Govorkova EA. (2006) Combination chemotherapy, a potential strategy for reducing the emergence of drug-resistant influenza A variants. Antiviral Res, 70, 121–131.PubMedCrossRefGoogle Scholar
  28. Jefferson T, Demicheli V, Rivetti D, Jones M, Di Pietrantonj C, and Rivetti A. (2006) Antivirals for influenza in healthy adults: systematic review. Lancet, 367, 303–313.PubMedCrossRefGoogle Scholar
  29. Kuiken T, Rimmelzwaan G, Van Riel D, Van Amerongen G, Baars M, Fouchier R, and Osterhaus A. (2004) Avian H5N1 influenza in cats. Science, 306, 241.PubMedCrossRefGoogle Scholar
  30. Leneva IA, Goloubeva O, Fenton RJ, Tisdale M, and Webster RG. (2001) Efficacy of zanamivir against avian influenza A viruses that possess genes encoding H5N1 internal proteins and are pathogenic in mammals. Antimicrobial Agents & Chemotherapy, 45, 1216–1224.CrossRefGoogle Scholar
  31. Maines TR, Lu X H, Erb SM, Edwards L, Guarner J, Greer PW, Nguyen DC, Szretter KJ, Chen L-m, Thawatsupha P, Chittaganpitch M, Waicharoen S, Nguyen DT, Nguyen T, Nguyen HHT, Kim J-h, Hoang LT, Kang C, Phuong LS, Lim W, Zaki S, Donis RO, Cox NJ, Katz JM, and Tumpey TM. (2005) Avian influenza (H5N1) viruses isolated from humans in Asia in 2004 exhibit increased virulence in mammals. Journal of Virology, 79, 11788–11800.PubMedCrossRefGoogle Scholar
  32. Matrosovich M, Tuzikov A, Bovin N, Gambaryan A, Klimov A, Castrucci MR, Donatelli I, and Kawaoka Y. (2000) Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals. Journal of Virology, 74, 8502–8512.PubMedCrossRefGoogle Scholar
  33. Mccullers JA. (2006) The clinical need for new antiviral drugs directed against influenza virus. Journal of Infectious Diseases, 193, 751–753.PubMedCrossRefGoogle Scholar
  34. Mckimm-breschkin JL. (2002) Neuraminidase inhibitors for the treatment and prevention of influenza. Expert Opinion on Pharmacotherapy, 3, 103–112.PubMedCrossRefGoogle Scholar
  35. Mckimm-breschkin JL. (2005) Management of influenza virus infections with neuraminidase inhibitors: detection, incidence, and implications of drug resistance. Treatments in Respiratory Medicine, 4, 107–116.PubMedCrossRefGoogle Scholar
  36. Monto AS, Pichichero ME, Blanckenberg SJ, Ruuskanen O, Cooper C, Fleming DM, and Kerr C. (2002) Zanamivir prophylaxis: an effective strategy for the prevention of influenza types A and B within households. Journal of Infectious Diseases, 186, 1582–1588.PubMedCrossRefGoogle Scholar
  37. Moscona A. (2005a) Neuraminidase inhibitors for influenza. New England Journal of Medicine, 353, 1363–1373.PubMedCrossRefGoogle Scholar
  38. Moscona A. (2005b) Oseltamivir resistance–disabling our influenza defenses. New England Journal of Medicine, 353, 2633–2636.PubMedCrossRefGoogle Scholar
  39. Okamoto S, Kamiya I, Kishida K, Shimakawa T, Fukui T, and Morimoto, T. (2005) Experience with oseltamivir for infants younger than 1 year old in Japan. Pediatric Infectious Disease Journal, 24, 575–576.PubMedCrossRefGoogle Scholar
  40. Osterholm MT. (2005) Preparing For The Next Pandemic. N Engl J Med, 352, 1839–1842.PubMedCrossRefGoogle Scholar
  41. Perkins LEL, and Swayne DE. (2002) Pathogenicity of a Hong Kong-origin H5N1 highly pathogenic avian influenza virus for emus, geese, ducks, and pigeons. Avian Diseases, 46, 53–63.PubMedCrossRefGoogle Scholar
  42. Pinto LH, and Lamb RA. (2006) The M2 proton channels of influenza A and B viruses. Journal of Biological Chemistry, 281, 8997–9000.PubMedCrossRefGoogle Scholar
  43. Schunemann HJ, Hill SR, Kakad M, Bellamy R, Uyeki TM, Hayden FG, Yazdanpanah Y, Beigel J, Chotpitayasunondh T, Del Mar C, Farrar J, Tran TH, Ozbay B, Sugaya N, Fukuda K, Shindo N, Stockman L, Vist GE, Croisier A, Nagjdaliyev A, Roth C, Thomson G, Zucker H, and Oxman AD. (2007) WHO Rapid Advice Guidelines for pharmacological management of sporadic human infection with avian influenza A (H5N1) virus. Lancet Infect Dis, 7, 21–31.PubMedCrossRefGoogle Scholar
  44. Shortridge KF. (2006) Influenza pandemic preparedness: gauging from EU plans. Lancet, 367, 1374–1375.PubMedCrossRefGoogle Scholar
  45. Smith J, Dutkowski R, and Ward P. (2006) Antivirals for influenza in healthy adults. Lancet, 367, 1571; author reply 1573.PubMedCrossRefGoogle Scholar
  46. Tran TH, Nguyen TL, Nguyen TD, Luong TS, Pham PM, Nguyen VVC, Pham TS, Vo CD, Le TQM, Ngo TT, Dao BK, Le PP, Nguyen TT, Hoang TL, Cao VT, Le TG, Nguyen DT, Le HN, Nguyen KT, Le HS, Le VT, Christiane D, Tran TT, Menno DJ, Schultsz C, Cheng P, Lim W, Horby P, Farrar J, and World Health Organization International Avian Influenza Investigative, T. (2004) Avian influenza A (H5N1) in 10 patients in Vietnam. New England Journal of Medicine, 350, 1179–1188.PubMedCrossRefGoogle Scholar
  47. Ungchusak K, Auewarakul P, Dowell SF, Kitphati R, Auwanit W, Puthavathana P, Uiprasertkul M, Boonnak K, Pittayawonganon C, Cox NJ, Zaki SR, Thawatsupha P, Chittaganpitch M, Khontong, R, Simmerman JM, and Chunsutthiwat S. (2005) Probable person-to-person transmission of avian influenza A (H5N1). New England Journal of Medicine, 352, 333–340.PubMedCrossRefGoogle Scholar
  48. Ward P, Small I, Smith J, Suter P, and Dutkowski R. (2005) Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic. Journal of Antimicrobial Chemotherapy, 55 Suppl 1, i5–i21.PubMedCrossRefGoogle Scholar
  49. Webster RG, and Govorkova EA. (2006) H5N1 influenza–continuing evolution and spread. N Engl J Med, 355, 2174–2177.PubMedCrossRefGoogle Scholar
  50. Whitley RJ, Hayden FG, Reisinger KS, Young N, Dutkowski R, Ipe D, Mills RG, and Ward P. (2001) Oral oseltamivir treatment of influenza in children. Pediatric Infectious Disease Journal, 20, 127–133.PubMedCrossRefGoogle Scholar
  51. Wong SSY, and Yuen K-y. (2006) Avian influenza virus infections in humans. Chest, 129, 156–68.PubMedCrossRefGoogle Scholar
  52. World Health Organization (2005a) Assessing the pandemic threat. (Accessed August 17, 2006 at ).
  53. World Health Organization (2005b) Current WHO phase of pandemic allert. (accessed August 17 2006 at ).
  54. World Health Organization (2005c) WHO guidelines for the collection of human specimens for laboratory diagnosis of avian influenza infection. (Accessed August 17, 2006 at ).
  55. World Health Organization (2006a) Avian Influenza, Including Influenza A (H5N1), in Humans: WHO Interim Infection Control Guideline for Health Care Facilities. (accessed August 28, 2006 at–688D-4316–91DF-5553E7B1DBCD/ 0/InfectionControlAIinhumansWHOInterimGuidelinesfor2b_0628.pdf).
  56. World Health Organization (2006b) Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHOC. (accessed August 17, 2006, at ).
  57. World Health Organization (2006c) Epidemiology of WHO-confirmed human cases of avian influenza A(H5N1) infection. Weekly epidemiological record, 26, 249–260.Google Scholar
  58. Yen H-l, Monto AS, Webster RG, and Govorkova EA. (2005) Virulence may determine the necessary duration and dosage of oseltamivir treatment for highly pathogenic A/Vietnam/1203/04 influenza virus in mice. Journal of Infectious Diseases, 192, 665–672.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Nicole Ritz
  • Nigel Curtis
    • 1
  1. 1.Associate Professor, Department of PaediatricsUniversity of Melbourne, Head of Paediatric Infectious Diseases Unit, Department of General Medicine, Leader of Microbiology & Infectious Diseases Research Group, Murdoch Children's Research Institute, Royal Children's Hospital MelbourneParkvilleAustralia

Personalised recommendations