Skip to main content
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2008;609:164–184. doi: 10.1007/978-0-387-73960-1_13

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

Nicole Ritz, Nigel Curtis 3
Editors: Adam Finn1, Andrew J Pollard2
PMCID: PMC7123866  PMID: 18193665

Abstract

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.

Keywords: Influenza Virus, Avian Influenza, Avian Influenza Virus, Pandemic Influenza, H5N1 Influenza

References

  1. (2007) New Concerns about Oseltamivin. Lancet, 369–1016.
  2. Anonymous (2006) A reappraisal of H5N1 avian influenza. Lancet, 367 1550. [DOI] [PubMed]
  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, Fraser VJ. Atypical avian influenza (H5N1) Emerging Infectious Diseases. 2004;10:1321–1324. doi: 10.3201/eid1007.040415. [DOI] [PMC free article] [PubMed] [Google 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, Writing Committee of The World Health Organization Consultation on Human Influenza Avian influenza A (H5N1) infection in humans. New England Journal of Medicine. 2005;353:1374–1385. doi: 10.1056/NEJMra052211. [DOI] [PubMed] [Google Scholar]
  5. Brett AS, Zuger A. The run on tamiflu–should physicians prescribe on demand? New England Journal of Medicine. 2005;353:2636–2637. doi: 10.1056/NEJMp058290. [DOI] [PubMed] [Google Scholar]
  6. Bridges CB, Kuehnert MJ, Hall CB. Transmission of influenza: implications for control in health care settings. Clinical Infectious Diseases. 2003;37:1094–1101. doi: 10.1086/378292. [DOI] [PubMed] [Google Scholar]
  7. Centers For Disease Control and Prevention (2003) Respiratory Hygiene/Cough Etiquette in Healthcare Settings. (accessed 28 August, 2006 athttp://www.cdc.gov/flu/professionals/infectioncontrol/resphygiene.htm).
  8. Centers for Disease Control and Prevention (2006) Antiviral Medications for Influenza. (accessed 28 August, 2006 athttp://www.cdc.gov/flu/professionals/treatment/0506antiviralguide.htm).
  9. Chen H, Deng G, Li Z, Tian G, Li Y, Jiao P, Zhang L, Liu Z, Webster RG, Yu K. The evolution of H5N1 influenza viruses in ducks in southern China. Proceedings of the National Academy of Sciences of the United States of America. 2004;101:10452–10457. doi: 10.1073/pnas.0403212101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cheung C-l, Rayner JM, Smith GJD, Wang P, Naipospos TSP, Zhang J, K-y Y, Webster RG, Peiris JSM, Guan Y, Chen H. Distribution of amantadine-resistant H5N1 avian influenza variants in Asia. Journal of Infectious Diseases. 2006;193:1626–1629. doi: 10.1086/504723. [DOI] [PubMed] [Google 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, Dowell SF. Human disease from influenza A (H5N1), Thailand, 2004. Emerging Infectious Diseases. 2005;11:201–209. doi: 10.3201/eid1102.041061. [DOI] [PMC free article] [PubMed] [Google 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, Farrar J. Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma. New England Journal of Medicine. 2005;352:686–691. doi: 10.1056/NEJMoa044307. [DOI] [PubMed] [Google 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, Farrar J. Oseltamivir resistance during treatment of influenza A (H5N1) infection. New England Journal of Medicine. 2005;353:2667–2672. doi: 10.1056/NEJMoa054512. [DOI] [PubMed] [Google Scholar]
  14. Department Of Health HSIP, Monitoring And Surveillance (2005) UK Health Departments’ Influenza pandemic contingency plan. (Accessed August 18 2006 athttp:www.dh.gov.uk/PublicationsAndStatistics/Publications/PublicationsPolicyAndGuidence/PublicationsPolicyAnd GuidanceArticle/fs/en?CONTENTID=4121735&chk=Z6kjQY).
  15. Dolin R. Influenza–interpandemic as well as pandemic disease. N Engl J Med. 2005;353:2535–2537. doi: 10.1056/NEJMp058276. [DOI] [PubMed] [Google Scholar]
  16. Frank AL, Taber LH, Wells CR, Wells JM, Glezen WP, Paredes A. Patterns of shedding of myxoviruses and paramyxoviruses in children. J Infect Dis. 1981;144:433–441. doi: 10.1093/infdis/144.5.433. [DOI] [PubMed] [Google Scholar]
  17. Freund B, Gravenstein S, Elliott M, Miller I. Zanamivir: a review of clinical safety. Drug Safety. 1999;21:267–81. doi: 10.2165/00002018-199921040-00003. [DOI] [PubMed] [Google Scholar]
  18. Gambaryan A, Tuzikov A, Pazynina G, Bovin N, Balish A, Klimov A. Evolution of the receptor binding phenotype of influenza A (H5) viruses. Virology. 2006;344:432–438. doi: 10.1016/j.virol.2005.08.035. [DOI] [PubMed] [Google Scholar]
  19. Goicoechea M. Human H5N1 influenza. N Engl J Med. 2007;356:1375. doi: 10.1056/NEJMc063637. [DOI] [PubMed] [Google Scholar]
  20. Gupta RK, Nguyen-van-tam JS. Oseltamivir resistance in influenza A (H5N1) infection. New England Journal of Medicine. 2006;354:1423–4. doi: 10.1056/NEJMc060077. [DOI] [PubMed] [Google Scholar]
  21. Harper SA, Fukuda K, Uyeki TM, Cox NJ, Bridges CB. Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR Recomm Rep. 2005;54:1–40. [PubMed] [Google Scholar]
  22. Hayden FG. Pandemic influenza: is an antiviral response realistic? Pediatric Infectious Disease Journal. 2004;23:S262–S269. doi: 10.1097/01.inf.0000144680.39895.ce. [DOI] [PubMed] [Google Scholar]
  23. Hayden FG. Antiviral resistance in influenza viruses–implications for management and pandemic response. New England Journal of Medicine. 2006;354:785–788. doi: 10.1056/NEJMp068030. [DOI] [PubMed] [Google Scholar]
  24. Hayden FG, Treanor JJ, Fritz RS, Lobo M, Betts RF, Miller M, Kinnersley N, Mills RG, Ward P, Straus SE. Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment. JAMA. 1999;282:1240–1246. doi: 10.1001/jama.282.13.1240. [DOI] [PubMed] [Google Scholar]
  25. Hien TT, De Jong M, Farrar J. Avian influenza–a challenge to global health care structures. New England Journal of Medicine. 2004;351:2363–2365. doi: 10.1056/NEJMp048267. [DOI] [PubMed] [Google Scholar]
  26. Howton JC. Probenecid with oseltamivir for human influenza A (H5N1) virus infection? New England Journal of Medicine. 2006;354:879–880. doi: 10.1056/NEJMc052951. [DOI] [PubMed] [Google Scholar]
  27. Ilyushina NA, Bovin NV, Webster RG, Govorkova EA. Combination chemotherapy, a potential strategy for reducing the emergence of drug-resistant influenza A variants. Antiviral Res. 2006;70:121–131. doi: 10.1016/j.antiviral.2006.01.012. [DOI] [PubMed] [Google Scholar]
  28. Jefferson T, Demicheli V, Rivetti D, Jones M, Di Pietrantonj C, Rivetti A. Antivirals for influenza in healthy adults: systematic review. Lancet. 2006;367:303–313. doi: 10.1016/S0140-6736(06)67970-1. [DOI] [PubMed] [Google Scholar]
  29. Kuiken T, Rimmelzwaan G, Van Riel D, Van Amerongen G, Baars M, Fouchier R, Osterhaus A. Avian H5N1 influenza in cats. Science. 2004;306:241. doi: 10.1126/science.1102287. [DOI] [PubMed] [Google Scholar]
  30. Leneva IA, Goloubeva O, Fenton RJ, Tisdale M, Webster RG. Efficacy of zanamivir against avian influenza A viruses that possess genes encoding H5N1 internal proteins and are pathogenic in mammals. Antimicrobial Agents & Chemotherapy. 2001;45:1216–1224. doi: 10.1128/AAC.45.4.1216-1224.2001. [DOI] [PMC free article] [PubMed] [Google 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, Tumpey TM. Avian influenza (H5N1) viruses isolated from humans in Asia in 2004 exhibit increased virulence in mammals. Journal of Virology. 2005;79:11788–11800. doi: 10.1128/JVI.79.18.11788-11800.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Matrosovich M, Tuzikov A, Bovin N, Gambaryan A, Klimov A, Castrucci MR, Donatelli I, Kawaoka Y. Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals. Journal of Virology. 2000;74:8502–8512. doi: 10.1128/JVI.74.18.8502-8512.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Mccullers JA. The clinical need for new antiviral drugs directed against influenza virus. Journal of Infectious Diseases. 2006;193:751–753. doi: 10.1086/500477. [DOI] [PubMed] [Google Scholar]
  34. Mckimm-breschkin JL. Neuraminidase inhibitors for the treatment and prevention of influenza. Expert Opinion on Pharmacotherapy. 2002;3:103–112. doi: 10.1517/14656566.3.2.103. [DOI] [PubMed] [Google Scholar]
  35. Mckimm-breschkin JL. Management of influenza virus infections with neuraminidase inhibitors: detection, incidence, and implications of drug resistance. Treatments in Respiratory Medicine. 2005;4:107–116. doi: 10.2165/00151829-200504020-00004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Monto AS, Pichichero ME, Blanckenberg SJ, Ruuskanen O, Cooper C, Fleming DM, Kerr C. Zanamivir prophylaxis: an effective strategy for the prevention of influenza types A and B within households. Journal of Infectious Diseases. 2002;186:1582–1588. doi: 10.1086/345722. [DOI] [PubMed] [Google Scholar]
  37. Moscona A. Neuraminidase inhibitors for influenza. New England Journal of Medicine. 2005;353:1363–1373. doi: 10.1056/NEJMra050740. [DOI] [PubMed] [Google Scholar]
  38. Moscona A. Oseltamivir resistance–disabling our influenza defenses. New England Journal of Medicine. 2005;353:2633–2636. doi: 10.1056/NEJMp058291. [DOI] [PubMed] [Google Scholar]
  39. Okamoto S, Kamiya I, Kishida K, Shimakawa T, Fukui T, Morimoto T. Experience with oseltamivir for infants younger than 1 year old in Japan. Pediatric Infectious Disease Journal. 2005;24:575–576. doi: 10.1097/01.inf.0000164799.33635.fe. [DOI] [PubMed] [Google Scholar]
  40. Osterholm MT. Preparing For The Next Pandemic. N Engl J Med. 2005;352:1839–1842. doi: 10.1056/NEJMp058068. [DOI] [PubMed] [Google Scholar]
  41. Perkins LEL, Swayne DE. Pathogenicity of a Hong Kong-origin H5N1 highly pathogenic avian influenza virus for emus, geese, ducks, and pigeons. Avian Diseases. 2002;46:53–63. doi: 10.1637/0005-2086(2002)046[0053:POAHKO]2.0.CO;2. [DOI] [PubMed] [Google Scholar]
  42. Pinto LH, Lamb RA. The M2 proton channels of influenza A and B viruses. Journal of Biological Chemistry. 2006;281:8997–9000. doi: 10.1074/jbc.R500020200. [DOI] [PubMed] [Google 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, Oxman AD. WHO Rapid Advice Guidelines for pharmacological management of sporadic human infection with avian influenza A (H5N1) virus. Lancet Infect Dis. 2007;7:21–31. doi: 10.1016/S1473-3099(06)70684-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Shortridge KF. Influenza pandemic preparedness: gauging from EU plans. Lancet. 2006;367:1374–1375. doi: 10.1016/S0140-6736(06)68512-7. [DOI] [PubMed] [Google Scholar]
  45. Smith J, Dutkowski R, Ward P. Antivirals for influenza in healthy adults. Lancet. 2006;367:1571. doi: 10.1016/S0140-6736(06)68683-2. [DOI] [PubMed] [Google 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, World Health Organization International Avian Influenza Investigative Avian influenza A (H5N1) in 10 patients in Vietnam. New England Journal of Medicine. 2004;350:1179–1188. doi: 10.1056/NEJMoa040419. [DOI] [PubMed] [Google 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, Chunsutthiwat S. Probable person-to-person transmission of avian influenza A (H5N1) New England Journal of Medicine. 2005;352:333–340. doi: 10.1056/NEJMoa044021. [DOI] [PubMed] [Google Scholar]
  48. Ward P, Small I, Smith J, Suter P, Dutkowski R. Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic. Journal of Antimicrobial Chemotherapy. 2005;55(1):i5–i21. doi: 10.1093/jac/dki018. [DOI] [PubMed] [Google Scholar]
  49. Webster RG, Govorkova EA. H5N1 influenza–continuing evolution and spread. N Engl J Med. 2006;355:2174–2177. doi: 10.1056/NEJMp068205. [DOI] [PubMed] [Google Scholar]
  50. Whitley RJ, Hayden FG, Reisinger KS, Young N, Dutkowski R, Ipe D, Mills RG, Ward P. Oral oseltamivir treatment of influenza in children. Pediatric Infectious Disease Journal. 2001;20:127–133. doi: 10.1097/00006454-200102000-00002. [DOI] [PubMed] [Google Scholar]
  51. Wong SSY, Yuen K-y. Avian influenza virus infections in humans. Chest. 2006;129:156–68. doi: 10.1378/chest.129.1.156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. World Health Organization (2005a) Assessing the pandemic threat. (Accessed August 17, 2006 athttp://www.who.int/csr/disease/influenza/WHO_CDS_2005_29/en/index.html).
  53. World Health Organization (2005b) Current WHO phase of pandemic allert. (accessed August 17 2006 athttp://www.who.int/csr/disease/avian_influenza/phase/en/index.html).
  54. World Health Organization (2005c) WHO guidelines for the collection of human specimens for laboratory diagnosis of avian influenza infection. (Accessed August 17, 2006 athttp://www.who.int/csr/disease/avian_influenza/guidelines/humanspecimens/en/index.html).
  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 athttp://www.wpro.who.int/NR/rdonlyres/EA6D9DF3–688D-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, athttp://www.who.int/csr/disease/avian_influenza/country/cases_table_2006_08_14/en/index.html).
  57. World Health Organization Epidemiology of WHO-confirmed human cases of avian influenza A(H5N1) infection. Weekly epidemiological record. 2006;26:249–260. [PubMed] [Google Scholar]
  58. Yen H-l, Monto AS, Webster RG, Govorkova EA. 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. 2005;192:665–672. doi: 10.1086/432008. [DOI] [PubMed] [Google Scholar]

Articles from Hot Topics in Infection and Immunity in Children IV are provided here courtesy of Nature Publishing Group

RESOURCES