Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 12, Number 1—January 2006
Policy Review

Nonpharmaceutical Interventions for Pandemic Influenza, International Measures

World Health Organization Writing Group

Main Article

Table A1

Presymptomatic or asymptomatic influenza viral shedding and relationship of shedding with symptoms, as determined in representative studies

First author Nature of study Pertinent results Pertinent conclusions
Frank (35) Surveillance in families, Houston, Texas, 1975–1979 In a study of 50 influenza A illnesses in 41 children <4 years of age, presymptomatic viral shedding was noted in 4 (8%) from whom positive samples were obtained 6, 4, 3, and 3 days, respectively, before symptom onset. Samples were not cultured for most children before symptom onset. Peak shedding occurred during week 1 of illness, when 73% of cultures were positive; 10% were positive on days 8–11, 5% on days 12–15, and 0% days 16–19. Illness duration and shedding were not correlated. In children, at least 8% of illnesses in a seasonal outbreak were associated with presymptomatic shedding, which was noted up to 6 days before illness; 5% continued to shed at the end of week 2. Peak rates of shedding correlated with symptoms.
Hall (36) Children with respiratory illness seeking medical care during influenza outbreaks, Rochester, New York, 1977 and 1986 In an influenza B study of 43 children (mean age 8 y), 74% had typical influenzalike illness, 7% had afebrile upper respiratory infections, and 19% had croup. Peak virus titers occurred on day 1 of illness, and 93% of children shed virus on days 1–3, 75% on day 4, and 30% on day 6. Severe illness and prolonged fever were associated with higher virus titers, and a trend (p<0.07) for younger children to shed higher-titer virus occurred. In an influenza A study, symptoms and the highest viral shedding occurred early in illness; 30% of patients still shed at day 7. Peak shedding early in illness, correlated with symptoms and fever.
Davis (37) Surveillance in families, Washington, DC area, 1951–1956 Influenza A virus was recovered from 0/4 and 2/3 throat swab samples obtained 3–5 and 1–2 days, respectively, before symptoms, compared with 75 (59%) of 127 swab specimens collected within 3 days after onset of illness. Shedding at low levels occurred 1–2 days before symptoms
Foy (38) Surveillance in families, Seattle, Washington, 1984 12/37 persons, all >12 y of age, from whom influenza B virus was isolated were asymptomatic. Virus cultures from asymptomatic persons required longer incubation time than those from symptomatic persons to become positive (12.7 vs. 8.7 days, p<0.007), suggesting low titers of virus in these specimens. The study design did not permit assessment of whether asymptomatic persons transmitted influenza. Asymptomatic shedding at a low titer may be common during a seasonal outbreak.
Murphy (39) In the control arm of a study, 7 adult volunteers were nasally infected with wild-type H3N2 virus Peak virus shedding occurred 2 days after nasal inoculation, and shedding ceased by day 6. Titer of virus shed and daily fever score (reflects height and duration of fever) were strongly correlated (p<0.001). 1/7 study participants had mild symptoms without fever and shed less virus. Fever score and quantity of virus shed were strongly correlated.
Couch (40) In a vaccine study, 29 adults received vaccines, and 11 controls received saline. All were nasally infected with H3N2 The vaccinated group had a reduced rate and severity of illness. Among controls (without specific antibody), titer of virus shed and daily severity of illness scores (p<0.001) were strongly correlated. In the combined group, peak viral shedding occurred 3 days after infection. Virus was shed a mean of 5.7 days. 6/29 vaccine recipients and 5/11 controls shed low levels of virus but did not become ill. Severity of illness and quantity of virus shed were strongly correlated; a substantial rate of asymptomatic shedding occurred at low titer.
Khakpour (41) Daily cultures of 29 adult prisoners after natural exposure to influenza, Iran, 1968 Virus was isolated from 5/29 contacts. One person had influenza isolated from a throat washing and blood, which is rare, 12 h before symptoms. Four persons had virus isolated from throat washings but never had symptoms; acute antibody titer was high in 2. Virus titrations were not performed. Presymptomatic and asymptomatic shedding can occur.
Philip (42) Surveillance in families, Washington, DC area, 1952–1955 In households with proven influenza illness, influenza A was isolated from 8 (38%) of 21 contacts with acute afebrile respiratory illness and 2 (5%) of 40 healthy contacts. Influenza B virus was isolated from 2 (11%) of 19 contacts with acute afebrile respiratory illness and 0 of 47 contacts. Age distribution of culture-positive contacts was not reported. Symptomatic household contacts commonly shed influenza A virus. Asymptomatic shedding of influenza A and B viruses was uncommon.
Monto (43) Surveillance in families, Tecumseh, Michigan, 1976–1981 During seasonal epidemics among persons with serologically proven influenza A (H3N2) infection, at least 15%–25% were ill. Among persons with serologically proven influenza B, at least 19%–34% were ill. Among persons with febrile respiratory illness, influenza virus was isolated from 19.7%. ≈60% of seasonal infections were asymptomatic. (This includes persons with partial immunity due to infection with the same subtype as in previous years; the percentage of asymptomatic infections would be lower in a pandemic.) Viral shedding in asymptomatic persons is likely to be quite low.
Hayden (44) 19 volunteers infected with influenza A H1N1 All study participants were symptomatic, and symptom scores peaked on day 2 and returned to normal by day 8. Virus titers correlated with symptoms. Viral shedding was correlated with symptoms.

Main Article

References
  1. World Health Organization. Avian influenza: assessing the pandemic threat. 2005 [cited 2005 Jan]. Available from http://www.who.int/csr/disease/influenza/WHO_CDS_2005_29/en/index.html
  2. World Health Organization. WHO global influenza preparedness plan: the role of WHO and recommendations for national measures before and during pandemics. Annex 1. 2005 [cited 2005 Apr]. Available from http://www.who.int/csr/resources/publications/influenza/WHO_CDS_CSR_GIP_2005_5/en
  3. World Health Organization. Non-pharmaceutical interventions: their role in reducing transmission and spread. 2005 [cited 2005 Nov]. Available from http://www.who.int/csr/disease/avian_influenza/pharmaintervention2005_11_3/en/index.html
  4. World Health Organization Writing Group. Nonpharmaceutical public health interventions for pandemic influenza, national and community measures. Emerg Infect Dis. 2006;12:88–94.PubMedGoogle Scholar
  5. 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;144:433–41. DOIPubMedGoogle Scholar
  6. Hall  CB, Douglas  RG Jr, Geiman  JM, Meagher  MP. Viral shedding patterns of children with influenza B infection. J Infect Dis. 1979;140:610–3. DOIPubMedGoogle Scholar
  7. Sheat  K. An investigation into an explosive outbreak of influenza—New Plymouth. Communicable Disease New Zealand. 1992;92:18–9.
  8. Bridges  CB, Kuehnert  MJ, Hall  CB. Transmission of influenza: implications for control in health care settings. Clin Infect Dis. 2003;37:1094–101. DOIPubMedGoogle Scholar
  9. Moser  MR, Bender  TR, Margolis  HS, Noble  GR, Kendal  AP, Ritter  DG. An outbreak of influenza aboard a commercial airliner. Am J Epidemiol. 1979;110:1–6.PubMedGoogle Scholar
  10. Alford  RH, Kasel  JA, Gerone  PJ, Knight  V. Human influenza resulting from aerosol inhalation. Proc Soc Exp Biol Med. 1966;122:800–4.PubMedGoogle Scholar
  11. Morens  DM, Rash  VM. Lessons from a nursing home outbreak of influenza A. Infect Control Hosp Epidemiol. 1995;16:275–80. DOIPubMedGoogle Scholar
  12. Bean  B, Moore  BM, Sterner  B, Peterson  LR, Gerding  DN, Balfour  HH Jr. Survival of influenza viruses on environmental surfaces. J Infect Dis. 1982;146:47–51. DOIPubMedGoogle Scholar
  13. World Health Organization. Consensus document on the epidemiology of severe acute respiratory syndrome (SARS). 2003 [cited 2005 Oct 27]. p. 25–27. Available from http://www.who.int/csr/sars/en/WHOconsensus.pdf
  14. Mills  CE, Robins  JM, Lipsitch  M. Transmissibility of 1918 pandemic influenza. Nature. 2004;432:904–6. DOIPubMedGoogle Scholar
  15. Ferguson  NM, Cummings  DA, Cauchemez  S, Fraser  C, Riley  S, Meeyai  A, Strategies for containing an emerging influenza pandemic in Southeast Asia. Nature. 2005;437:209–14. DOIPubMedGoogle Scholar
  16. Neuzil  KM, Hohlbein  C, Zhu  Y. Illness among schoolchildren during influenza season: effect on school absenteeism, parental absenteeism from work, and secondary illness in families. Arch Pediatr Adolesc Med. 2002;156:986–91.PubMedGoogle Scholar
  17. Cumpston  JHL. Influenza and maritime quarantine in Australia. Report no. 18. Melbourne: Commonwealth of Australia, Quarantine Service; 1919.
  18. McQueen  H. "Spanish 'flu"—1919: political, medical and social aspects. Med J Aust. 1975;1:565–70.PubMedGoogle Scholar
  19. New South Wales Department of Public Health. Report on the influenza epidemic in New South Wales in 1919. Section V. Sydney: William Applegate Gullick; 1920. p 139–272.
  20. Camail. In: Huot. L'épidémie d'influenza de 1918–1919 dans les colonies françaises. 3. Colonies de la côte orientale d'Afrique. Madagascar. Annales de Médecine et Pharmacie Coloniales. 1921;19:463–5.
  21. Patterson  KD, Pyle  GF. The diffusion of influenza in sub-Saharan Africa during the 1918–1919 pandemic. Soc Sci Med. 1983;17:1299–307. DOIPubMedGoogle Scholar
  22. Barry  JM. The great epidemic: the epic story of the deadliest plague in history. New York: Viking Penguin; 2004.
  23. Peltier. L'épidémie d'influenza qui a sévi en Nouvelle Calédonie en 1921. Bulletin de l'Office International d'Hygiène Publique. 1922;14:676–85.
  24. Patterson  KD. The influenza epidemic of 1918–1919 in the Gold Coast. J Afr Hist. 1983;24:485–502. DOIPubMedGoogle Scholar
  25. World Health Organization. Expert committee on respiratory virus disease: first report. World Health Organ Tech Rep Ser. 1959;58:1–59.PubMedGoogle Scholar
  26. Bell  DM; World Health Organization Working Group on Prevention of International and Community Transmission of SARS. Public health interventions and SARS spread, 2003. Emerg Infect Dis. 2004;10:1900–6.PubMedGoogle Scholar
  27. St John  RK, King  A, de Jong  D, Bodie-Collins  M, Squires  SG, Tam  TW. Border screening for SARS. Emerg Infect Dis. 2005;11:6–10.PubMedGoogle Scholar
  28. Pitman  RJ, Cooper  BS, Trotter  CL, Gay  NJ, Edmunds  WJ. Entry screening for SARS or influenza, policy evaluation. BMJ. 2005;331:1242–3. DOIPubMedGoogle Scholar
  29. Centers for Disease Control and Prevention. Use of quarantine to prevent transmission of severe acute respiratory syndrome—Taiwan, 2003. MMWR Morb Mortal Wkly Rep. 2003;52:680–3.PubMedGoogle Scholar
  30. Mangili  A, Gendreau  MA. Transmission of infectious diseases during commercial air travel. Lancet. 2005;365:989–96. DOIPubMedGoogle Scholar
  31. Miller  JM, Tam  TW, Maloney  S, Fukuda  K, Cox  N, Hockin  J, Cruise ships: high-risk passengers and the global spread of new influenza viruses. Clin Infect Dis. 2000;31:433–8. DOIPubMedGoogle Scholar
  32. Marsden  AG. Influenza outbreak related to air travel. Med J Aust. 2003;179:172–3.PubMedGoogle Scholar
  33. Centers for Disease Control and Prevention. Preliminary guidelines for the prevention and control of influenza-like illness among passengers and crew members on cruise ships. 1999 [cited 2005 Sep]. Available from http://www.cdc.gov/travel/CDCguideflufnl.pdf
  34. Olsen  SJ, Chang  HL, Cheung  TY, Tang  AF, Fisk  TL, Ooi  SP, Transmission of the severe acute respiratory syndrome on aircraft. N Engl J Med. 2003;349:2416–22. DOIPubMedGoogle Scholar
  35. 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;144:433–41. DOIPubMedGoogle Scholar
  36. Hall  CB, Dolin  R, Gala  CL, Markovitz  DM, Zhang  YQ, Madore  PH, Children with influenza A infection: treatment with rimantadine. Pediatrics. 1987;80:275–82.PubMedGoogle Scholar
  37. Davis  DJ, Philip  RN, Bell  JA, Vogel  JE, Jensen  DV. Epidemiologic studies on influenza in familial and general population groups. 1951–1956. III. Laboratory observations. Am J Hyg. 1961;73:138–47.PubMedGoogle Scholar
  38. Foy  HM, Cooney  MK, Allan  ID, Albrecht  JK. Influenza B in households: virus shedding without symptoms or antibody response. Am J Epidemiol. 1987;126:506–15.PubMedGoogle Scholar
  39. Murphy  BR, Chalhub  EG, Nusinoff  SR, Kasel  J, Chanock  RM. Temperature-sensitive mutants of influenza virus. 3. Further characterization of the ts-1(E) influenza A recombinant (H3N2) virus in man. J Infect Dis. 1973;128:479–87. DOIPubMedGoogle Scholar
  40. Couch  RB, Douglas  RG Jr, Fedson  DS, Kasel  JA. Correlated studies of a recombinant influenza-virus vaccine. 3. Protection against experimental influenza in man. J Infect Dis. 1971;124:473–80. DOIPubMedGoogle Scholar
  41. Khakpour  M, Saidi  A, Naficy  K. Proved viraemia in Asian influenza (Hong Kong variant) during incubation period. BMJ. 1969;4:208–9. DOIPubMedGoogle Scholar
  42. Philip  RN, Bell  JA, Davis  DJ, Beem  MO, Beigelman  PM, Engler  JI, Epidemiologic studies on influenza in familial and general population groups, 1951–1956. II. Characteristics of occurrence. Am J Hyg. 1961;73:123–37.PubMedGoogle Scholar
  43. Monto  AS, Koopman  JS, Longini  IM Jr. Tecumseh study of illness. XIII. Influenza infection and disease, 1976–1981. Am J Epidemiol. 1985;121:811–22.PubMedGoogle Scholar
  44. Hayden  FG, Fritz  R, Lobo  MC, Alvord  W, Strober  W, Straus  SE. Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense. J Clin Invest. 1998;101:643–9. DOIPubMedGoogle Scholar

Main Article

1The writing group was established by request of the WHO Global Influenza Programme. It consisted of the following persons: David Bell, Centers for Disease Control and Prevention, Atlanta, Georgia, USA (coordinator); Angus Nicoll, European Centre for Disease Prevention and Control, Stockholm, Sweden, and Health Protection Agency, London, United Kingdom (working group chair); Keiji Fukuda, WHO, Geneva, Switzerland; Peter Horby, WHO, Hanoi, Vietnam; and Arnold Monto, University of Michigan, Ann Arbor, Michigan, USA. The following persons made substantial contributions: Frederick Hayden, University of Virginia, Charlottesville, Virginia, USA; Clare Wylks and Lance Sanders, Australian Government Department of Health and Ageing, Canberra, Australian Capital Territory, Australia; and Jonathan Van Tam, Health Protection Agency, London, United Kingdom.

Page created: February 16, 2012
Page updated: February 16, 2012
Page reviewed: February 16, 2012
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external