Abstract
The recent avian influenza outbreaks underscore the importance of improving our preparedness for an impending influenza pandemic. Various strategies, including pharmaceutical interventions (such as vaccines and antivirals) and nonpharmaceutical interventions (such as quarantine, isolation, and social distancing) may be implemented to mitigate the impact of a pandemic. It is necessary to understand the potential benefits and limitations of each strategy to determine the most appropriate strategies to be implemented. In this article, each strategy is reviewed to define its potential benefits and limitations during a pandemic. Vaccines are probably the most effective measure to reduce morbidity and mortality. However, vaccines are not likely to be available at an early stage of a pandemic. The supply of vaccines is most likely to be insufficient due to limited worldwide production capacity. Antivirals, particularly neuraminidase inhibitors, are expected to be effective against a pandemic influenza strain and are the only available pharmaceutical intervention until enough vaccines are produced. Shortage of supply and high cost is still a major limiting factor in amassing large stockpiles of neuraminidase inhibitors. The possible emergence of resistant strains should also be considered. Nonpharmaceutical interventions can be effective in preventing the spread of the virus under certain conditions. The effectiveness of nonpharmaceutical interventions depends on how influenza viruses are transmitted. There are still significant gaps in the scientific evidence of the way in which influenza viruses are transmitted. Further studies should be conducted to define the basic transmission patterns of influenza viruses.
Key words: Influenza, Pandemic, Mitigating strategy
References
- 1.Nguyen-Van-Tam J.S., Hampson A.W. The epidemiology and clinical impact of pandemic influenza. Vaccine. 2003;21:1762–1768. doi: 10.1016/s0264-410x(03)00069-0. 10.1016/S0264-410X(03)00069-0. [DOI] [PubMed] [Google Scholar]
- 2.Nichol K.L. The efficacy, effectiveness and cost-effectiveness of inactivated influenza virus vaccines. Vaccine. 2003;21:1769–1775. doi: 10.1016/s0264-410x(03)00070-7. 10.1016/S0264-410X(03)00070-7. [DOI] [PubMed] [Google Scholar]
- 3.Langley J.M., Faughnan M.E. Prevention of influenza in the general population: recommendation statement from the Canadian Task Force on Preventive Health Care. CMAJ. 2004;171:1169–1170. doi: 10.1503/cmaj.1041375. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Monto A.S. Vaccines and antiviral drugs in pandemic preparedness. Emerg Infect Dis. 2006;12:55–60. doi: 10.3201/eid1201.051068. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Germann T.C., Kadau K., Longini I.M., Jr., Macken C.A. Mitigation strategies for pandemic influenza in the United States. Proc Natl Acad Sci U S A. 2006;103:5935–5940. doi: 10.1073/pnas.0601266103. 10.1073/pnas.0601266103. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Ferguson NM, Cummings DA, Fraser C, Cajka JC, Cooley PC, Burke DS. Strategies for mitigating an influenza pandemic. Nature 2006 Available from: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature04795.html [DOI] [PMC free article] [PubMed]
- 7.Lipatov A.S., Govorkova E.A., Webby R.J., Ozaki H., Peiris M., Guan Y., et al. Influenza: emergence and control. J Virol. 2004;78:8951–8959. doi: 10.1128/JVI.78.17.8951-8959.2004. 10.1128/JVI.78.17.8951-8959.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Dowdle W.R. Influenza pandemic periodicity, virus recycling, and the art of risk assessment. Emerg Infect Dis. 2006;12:34–39. doi: 10.3201/eid1201.051013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Smith D.J. Predictability and preparedness in influenza control. Science. 2006;312:392–394. doi: 10.1126/science.1122665. 10.1126/science.1122665. [DOI] [PubMed] [Google Scholar]
- 10.The World Health Organization Global Influenza Program Surveillance Network Evolution of H5N1 avian influenza viruses in Asia. Emerg Infect Dis. 2005;11:1515–1521. doi: 10.3201/eid1110.050644. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Poland G.A. Vaccines against avian influenza – a race against time. N Engl J Med. 2006;354:1411–1413. doi: 10.1056/NEJMe068047. 10.1056/NEJMe068047. [DOI] [PubMed] [Google Scholar]
- 12.Wood J.M. Developing vaccines against pandemic influenza. Philos Trans R Soc Lond B Biol Sci. 2001;356:1953–1960. doi: 10.1098/rstb.2001.0981. 10.1098/rstb.2001.0981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.World Health Organization Influenza vaccines: WHO position paper. Wkly Epidemiol Rec. 2005;80:279–288. [Google Scholar]
- 14.Fedson D.S. Pandemic influenza and the global vaccine supply. Clin Infect Dis. 2003;36:1552–1661. doi: 10.1086/375056. 10.1086/375056. [DOI] [PubMed] [Google Scholar]
- 15.Stephenson I., Nicholson K.G., Wood J.M., Zambon M.C., Katz J.M. Confronting the avian influenza threat: vaccine development for a potential pandemic. Lancet Infect Dis. 2004;4:499–509. doi: 10.1016/S1473-3099(04)01105-3. 10.1016/S1473-3099(04)01105-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Treanor J.J., Campbell J.D., Zangwill K.M., Rowe T., Wolff M. Safety and immunogenicity of an inactivated subvirion influenza A (H5N1) vaccine. N Engl J Med. 2006;354:1343–1351. doi: 10.1056/NEJMoa055778. 10.1056/NEJMoa055778. [DOI] [PubMed] [Google Scholar]
- 17.Nicholson K.G., Colegate A.E., Podda A., Stephenson I., Wood J., Ypma E., et al. Safety and antigenicity of non-adjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a randomised trial of two potential vaccines against H5N1 influenza. Lancet. 2001;357:1937–1943. doi: 10.1016/S0140-6736(00)05066-2. 10.1016/S0140-6736(00)05066-2. [DOI] [PubMed] [Google Scholar]
- 18.Hayden F.G. Perspectives on antiviral use during pandemic influenza. Philos Trans R Soc Lond B Biol Sci. 2001;356:1877–1884. doi: 10.1098/rstb.2001.1007. 10.1098/rstb.2001.1007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Suzuki H., Saito R., Masuda H., Oshitani H., Sato M., Sato I. Emergence of amantadine-resistant influenza A viruses: epidemiological study. J Infect Chemother. 2003;9:195–200. doi: 10.1007/s10156-003-0262-6. 10.1007/s10156-003-0262-6. [DOI] [PubMed] [Google Scholar]
- 20.Bright R.A., Medina M.J., Xu X., Perez-Oronoz G., Wallis T.R., Davis X.M., et al. Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Lancet. 2005;366:1175–1181. doi: 10.1016/S0140-6736(05)67338-2. 10.1016/S0140-6736(05)67338-2. [DOI] [PubMed] [Google Scholar]
- 21.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. 10.1016/S0140-6736(06)67970-1. [DOI] [PubMed] [Google Scholar]
- 22.Le Q.M., Kiso M., Someya K., Sakai Y.T., Nguyen T.H., Nguyen K.H., et al. Avian flu: isolation of drug-resistant H5N1 virus. Nature. 2005;437:1108. doi: 10.1038/4371108a. 10.1038/4371108a. [DOI] [PubMed] [Google Scholar]
- 23.de Jong M.D., Tran T.T., Truong H.K., Vo M.H., Smith G.J., Nguyen V.C., et al. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med. 2005;353:2667–2672. doi: 10.1056/NEJMoa054512. 10.1056/NEJMoa054512. [DOI] [PubMed] [Google Scholar]
- 24.The Writing Committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5 Avian influenza A (H5N1) infection in humans. N Engl J Med. 2005;353:1374–1385. doi: 10.1056/NEJMra052211. 10.1056/NEJMra052211. [DOI] [PubMed] [Google Scholar]
- 25.Yen H.L., Monto A.S., Webster R.G., Govorkova E.A. Virulence may determine the necessary duration and dosage of oseltamivir treatment for highly pathogenic A/Vietnam/1203/04 influenza virus in mice. J Infect Dis. 2005;192:665–672. doi: 10.1086/432008. 10.1086/432008. [DOI] [PubMed] [Google Scholar]
- 26.Bell D.M. Non-pharmaceutical interventions for pandemic influenza, national and community measures. Emerg Infect Dis. 2006;12:88–94. doi: 10.3201/eid1201.051371. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Bell D.M. Non-pharmaceutical interventions for pandemic influenza, international measures. Emerg Infect Dis. 2006;12:81–87. doi: 10.3201/eid1201.051370. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Day T., Park A., Madras N., Gumel A., Wu J. When is quarantine a useful control strategy for emerging infectious diseases? Am J Epidemiol. 2006;163:479–485. doi: 10.1093/aje/kwj056. 10.1093/aje/kwj056. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Anonymous. Use of quarantine to prevent transmission of severe acute respiratory syndrome – Taiwan, 2003. MMWR Morb Mortal Wkly Rep. 2003;52:680–683. [PubMed] [Google Scholar]
- 30.Riley S., Fraser C., Donnelly C.A., Ghani A.C., Abu-Raddad L.J., Hedley A.J., et al. Transmission dynamics of the etiological agent of SARS in Hong Kong: impact of public health interventions. Science. 2003;300:1961–1966. doi: 10.1126/science.1086478. 10.1126/science.1086478. [DOI] [PubMed] [Google Scholar]
- 31.Fraser C., Riley S., Anderson R.M., Ferguson N.M. Factors that make an infectious disease outbreak controllable. Proc Natl Acad Sci U S A. 2004;101:6146–6151. doi: 10.1073/pnas.0307506101. 10.1073/pnas.0307506101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Gostin L. Public health strategies for pandemic influenza ethics and the law. JAMA. 2006;295:1700–1704. doi: 10.1001/jama.295.14.1700. 10.1001/jama.295.14.1700. [DOI] [PubMed] [Google Scholar]
- 33.Hawryluck L., Gold W.L., Robinson S., Pogorski S., Galea S., Styra R. SARS control and psychological effects of quarantine, Toronto Canada. Emerg Infect Dis. 2004;10:1206–1212. doi: 10.3201/eid1007.030703. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Lau J.T., Yang X., Tsui H.Y., Pang E. SARS related preventive and risk behaviours practised by Hong Kong-mainland China cross border travellers during the outbreak of the SARS epidemic in Hong Kong. J Epidemiol Community Health. 2004;58:988–996. doi: 10.1136/jech.2003.017483. 10.1136/jech.2003.017483. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Heymann A., Chodick G., Reichman B., Kokia E., Laufer J. Influence of school closure on the incidence of viral respiratory diseases among children and on health care utilization. Pediatr Infect Dis J. 2004;23:675–677. doi: 10.1097/01.inf.0000128778.54105.06. [DOI] [PubMed] [Google Scholar]
- 36.Luby S.P., Agboatwalla M., Feikin D.R., Painter J., Billhimer W., Altaf A., et al. Effect of handwashing on child health: a randomised controlled trial. Lancet. 2005;366:225–233. doi: 10.1016/S0140-6736(05)66912-7. 10.1016/S0140-6736(05)66912-7. [DOI] [PubMed] [Google Scholar]
- 37.Ryan M.A., Christian R.S., Wohlrabe J. Handwashing and respiratory illness among young adults in military training. Am J Prev Med. 2001;21:79–83. doi: 10.1016/s0749-3797(01)00323-3. 10.1016/S0749-3797(01)00323-3. [DOI] [PubMed] [Google Scholar]
- 38.Bean B., Moore B.M., Sterner B., Peterson L.R., Gerding D.N., Balfour H.H., Jr. Survival of influenza viruses on environmental surfaces. J Infect Dis. 1982;146:47–51. doi: 10.1093/infdis/146.1.47. [DOI] [PubMed] [Google Scholar]
- 39.Luckingham B. To mask or not to mask: a note on the 1918 Spanish influenza epidemic in Tucson. J Ariz Hist. 1984;25:191–204. [PubMed] [Google Scholar]
- 40.Wu J., Xu F., Zhou W., Feikin D.R., Lin C.Y., He X., et al. Risk factors for SARS among persons without known contact with SARS patients, Beijing China. Emerg Infect Dis. 2004;10:210–216. doi: 10.3201/eid1002.030730. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.Lau J.T., Tsui H., Lau M., Yang X. SARS transmission risk factors and prevention in Hong Kong. Emerg Infect Dis. 2004;10:587–592. doi: 10.3201/eid1004.030628. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42.Lo J.Y., Tsang T.H., Leung Y.H., Yeung E.Y., Wu T., Lim W.W. Respiratory infections during SARS outbreak, Hong Kong, 2003. Emerg Infect Dis. 2005;11:1738–1741. doi: 10.3201/eid1111.050729. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43.Bridges C.B., Kuehnert M.J., Hall C.B. Transmission of influenza: implications for control in health care settings. Clin Infect Dis. 2003;37:1094–1101. doi: 10.1086/378292. 10.1086/378292. [DOI] [PubMed] [Google Scholar]
- 44.Salgado C.D., Farr B.M., Hall K.K., Hayden F.G. Influenza in the acute hospital setting. Lancet Infect Dis. 2002;2:145–155. doi: 10.1016/s1473-3099(02)00221-9. 10.1016/S1473-3099(02)00221-9. [DOI] [PubMed] [Google Scholar]
- 45.Goldmann D.A. Transmission of viral respiratory infections in the home. Pediatr Infect Dis J. 2000;19:S97–S102. doi: 10.1097/00006454-200010001-00002. [DOI] [PubMed] [Google Scholar]
- 46.Bell D.M. Public health interventions and SARS spread, 2003. Emerg Infect Dis. 2004;10:1900–1906. doi: 10.3201/eid1011.040729. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 47.Cooper B.S., Pitman R.J., Edmunds W.J., Gay N.J. Delaying the international spread of pandemic influenza. PLoS Med. 2006;3:e212. doi: 10.1371/journal.pmed.0030212. 10.1371/journal.pmed.0030212. [DOI] [PMC free article] [PubMed] [Google Scholar]