OR Spectrum

, Volume 33, Issue 3, pp 751–786 | Cite as

A predictive decision-aid methodology for dynamic mitigation of influenza pandemics

  • Andrés Uribe-Sánchez
  • Alex SavachkinEmail author
  • Alfredo Santana
  • Diana Prieto-Santa
  • Tapas K. Das
Regular Article


In a recent report, the Institute of Medicine has stressed the need for dynamic mitigation strategies for pandemic influenza. In response to the need, we have developed a simulation-based optimization methodology for generating dynamic predictive mitigation strategies for pandemic outbreaks affecting several regions. Our methodology can accommodate varying virus and population dynamics. It progressively allocates a limited budget to procure vaccines and antivirals, capacities for their administration, and resources required to enforce social distancing. The methodology uses measures of morbidity, mortality, and social distancing, which are translated into the costs of lost productivity and medical services. The simulation model was calibrated using historic pandemic data. We illustrate the use of our methodology on a mock outbreak involving over four million people residing in four major population centers in Florida, USA. A sensitivity analysis is presented to estimate the impact of changes in the budget availability and variability of some of the critical parameters of mitigation strategies. The methodology is intended to assist public health policy makers.


Pandemic influenza Mitigation Dynamic Vaccination Antiviral Social distancing 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Arino J, Brauer F, den Driessche P, Watmough J, Wu J (2006) Simple models for containment of a pandemic. J R Soc Interface 3: 453–457CrossRefGoogle Scholar
  2. Atkinson M, Wein L (2008) Quantifying the routes of transmission for pandemic influenza. Bull Math Biol 70(3): 820–867CrossRefGoogle Scholar
  3. Aunins J, Lee A, Volkin D (2000) Vaccine production, 2nd edn. CRC Press LLC, Boca RatonGoogle Scholar
  4. Ball F, Lyne O (2002) Optimal vaccination policies for stochastic epidemics among a population of households. Math Biosci 177–178: 333–354CrossRefGoogle Scholar
  5. Blendon R, DesRoches C, Cetron M, Benson J, Meinhardt T, Pollard W (2006) Attitudes toward the use of quarantine in a public health emergency in four countries. Health Aff 25(2): 15–25CrossRefGoogle Scholar
  6. Blendon R, Koonin L, Benson J, Cetron M, Pollard W, Mitchell E, Weldon K, Herrmann M (2008) Public response to community mitigation measures for pandemic influenza. Emerg Infect Dis 14(5): 778CrossRefGoogle Scholar
  7. Bootsma M, Ferguson N (2007) The effect of public health measures on the 1918 influenza pandemic in the US cities. PNAS 104(18): 7588–7593CrossRefGoogle Scholar
  8. Brundage J, Shanks G (2008) Deaths from bacterial pneumonia during 1918–19 influenza pandemic. Emerg Infect Dis 14(8): 1193CrossRefGoogle Scholar
  9. Bureau of Transportation Statistics (2002) 2001 National household travel survey (NTHS). Last accessed on 12/09/2008
  10. Carrat F, Lavenu A, Cauchemez S, Deleguer S (2005) Repeated influenza vaccination of healthy children and adults: borrow now, pay later?. Epidemiol Infect 134: 63–70CrossRefGoogle Scholar
  11. Cauchemez S, Carrat F, Viboud C, Valleron A, Boelle P (2004) A Bayesian (MCMC) approach to study transmission of influenza: application to household longitudinal data. Stat Med 23: 3469–3487CrossRefGoogle Scholar
  12. Centers for Disease Control and Prevention (CDC) (2006) CDC influenza operational plan. Last accessed on 03/27/2009
  13. Centers for Disease Control and Prevention (CDC) (2007a) Preparing for pandemic influenza. Last accessed on 04/27/2009
  14. Centers for Disease Control and Prevention (CDC) (2007b) Interim pre-pandemic planning guidance: community strategy for pandemic influenza mitigation in the United States. Last accessed on 04/01/2009
  15. Centers for Disease Control and Prevention (CDC) (2008) Avian influenza: current H5N1 situation. Last accessed on 02/09/2008
  16. Centers for Disease Control and Prevention (2009) CDC vaccine price list. Last accessed on 12/28/2009
  17. Colorado Department of Human Services Division of Mental Health (2009) Pandemic influenza: quarantine, isolation and social distancing. Last accessed on 10/28/2009
  18. Colizza V, Barrat A, Barthelemy M, Vespignani A (2006) The role of the airline transportation network in the prediction and predictability of global epidemics. PNAS 103: 2015–2020CrossRefGoogle Scholar
  19. Colizza V, Barrat A, Barthelemy AVM, Vespignani A (2007) Modeling the worldwide spread of pandemic influenza: baseline case and containment interventions. PLOS Med 4: 95–110CrossRefGoogle Scholar
  20. Committee on Modeling Community Containment for Pandemic Influenza (2006) Modeling community containment for pandemic influenza: a letter report. Last accessed on 12/09/2008
  21. Cooley P, Ganapathi L, Ghneim G, Holmberg S, Wheaton W, Hollingsworth C (2008) Using influenza-like illness data to reconstruct an influenza outbreak. Math Comput Model 48: 929–939CrossRefGoogle Scholar
  22. Cummings K, Jette A, Brock B, Haefner D (1979) Psychosocial determinants of immunization behavior in a swine influenza campaign. Med Care 17(6): 639–649CrossRefGoogle Scholar
  23. Dargatz C, Georgescu V, Held L (2006) Stochastic modelling of the spatial spread of influenza in Germany. Austrian J Stat 35(1): 5–20Google Scholar
  24. Das T, Savachkin A (2008) A large scale simulation model for assessment of societal risk and development of dynamic mitigation strategies. IIE Trans 40(9): 893–905CrossRefGoogle Scholar
  25. Diekmann O, Heesterbeek J (2000) Mathematical epidemiology of infectious diseases: model building, analysis and interpretation. Wiley, ChichesterGoogle Scholar
  26. Eclipse F (2009) The spatio-temporal epidemiological modeler. Last accessed on 11/06/2009
  27. Epstein J, Goedecke D, Yu F, Morris R, Wagener D, Bobashev G (2007) Controlling pandemic flu: the value of international air travel restrictions. PLoS One 2(5): 1–11CrossRefGoogle Scholar
  28. Epstein J, Parker J, Cummings D, Hammond R (2008) Coupled contagion dynamics of fear and disease: mathematical and computational explorations. PLoS One 3(12): e3955CrossRefGoogle Scholar
  29. Eubank S, Guclu H, Kumar V, Marathe M, Srinivasan A, Toroczkai Z, Wang N (2004) Modelling disease outbreaks in realistic urban social networks. Nature 429: 180–184CrossRefGoogle Scholar
  30. Fedson D, Hant S (2003) Pandemic influenza and the global vaccine supply. Clin Infect Dis 36: 1552–1561CrossRefGoogle Scholar
  31. Ferguson N, Mallett S, Jackson H, Roberts N, Ward P (2003) A population-dynamic model for evaluating the potential spread of drug-resistant influenza virus infections during community-based use of antivirals. J Antimicrob Chemother 51: 977–990CrossRefGoogle Scholar
  32. Ferguson NM, Cummings D, Cauchemez S, Fraser C, Riley S, Aronrag M, Lamsirithaworn S, Burke D (2005) Strategies for containing an emerging influenza pandemic in Southeast Asia. Nature 437: 209–214CrossRefGoogle Scholar
  33. Ferguson N, Cummings DA, Fraser C, Cajka J, Cooley PCC, Burke DS (2006) Strategies for mitigating an influenza pandemic. Nature 442(27): 448–452CrossRefGoogle Scholar
  34. Fraser C, Riley S, Anderson R, Ferguson N, May R (2004) Factors that make an infectious disease outbreak controllable. PNAS 101(16): 6146–6151CrossRefGoogle Scholar
  35. Germann T, Kadau K, Longini IM, Macken C (2006) Mitigation strategies for pandemic influenza in the United States. PNAS 103: 5935–5940CrossRefGoogle Scholar
  36. Glass R, Beyeler W, Min H (2006) Targeted social distancing design for pandemic influenza. Emerg Infect Dis 12(11): 1671–1681Google Scholar
  37. Halder N, Kelso J, Milne G (2010) Analysis of the effectiveness of interventions used during the 2009 A/H1N1 influenza pandemic. BioMed Central 10(168): 1–14Google Scholar
  38. Halfhill T (2009) Inflation calculator. Last accessed on 12/04/2009
  39. Halloran M (2006) Invited commentary: challenges of using contact data to understand acute respiratory disease transmission. Am J Epidemiol 164(10): 945CrossRefGoogle Scholar
  40. Halloran ME, Longini IM, Nizam A, Yang Y (2002) Containing bioterrorist smallpox. Science 298: 1428–1432CrossRefGoogle Scholar
  41. Halloran ME, Ferguson NM, Eubank S, Longini I (2008) Modeling targeted layered containment of an influenza pandemic in the United States. PNAS 105(12): 4639–4644CrossRefGoogle Scholar
  42. Handel A, Longini I, Antia R (2009) Towards a quantitative understanding of the within-host dynamics of influenza A infections. Epidemics 1(3): 185–195CrossRefGoogle Scholar
  43. HHS (2007) Pandemic planning update iv.
  44. Institute of Medicine (IOM) (2008) Antivirals for pandemic influenza: guidance on developing a distribution and dispensing program. The National Academies Press, Washington, DCGoogle Scholar
  45. Jacksonville Aviation Authority: daily traffic volume data (2010) Last accessed on 04/07/2010
  46. Keane M, Walter M, Patel B, Moorthy S, Stevens R, Bradley K, Buford J, Anderson E, Anderson L, Tibbals K (2005) Confidence in vaccination: a parent model. Vaccine 23(19): 2486–2493CrossRefGoogle Scholar
  47. Kelso J, Milne G, Kelly H (2009) Simulation suggests that rapid activation of social distancing can arrest epidemic development due to a novel strain of influenza. BMC Public Health 9(1): 1–10CrossRefGoogle Scholar
  48. Larson R (2007) Simple models of influenza progression within a heterogeneous population. Oper Res 55(399–412): 165–195Google Scholar
  49. Lawless J, Lawless J (1982) Statistical models and methods for lifetime data. Wiley, New YorkGoogle Scholar
  50. Lipsitch M, Cohen T, Murray M, Levin B (2007) Antiviral resistance and the control of pandemic influenza. PLoS Med 4(1): 111–115CrossRefGoogle Scholar
  51. Longini IM (1986) The generalized discrete-time epidemic model with immunity: a synthesis. Math Biosci 82: 19–41CrossRefGoogle Scholar
  52. Longini IM, Koopman JS (1982) Household and community transmission parameters from final distributions of infections in households. Biometrics 38: 115–126CrossRefGoogle Scholar
  53. Longini IM, Halloran ME, Nizam A, Yang Y (2004) Containing pandemic influenza with antiviral agents. Am J Epidemiol 159(7): 623–633CrossRefGoogle Scholar
  54. Longini IM, Nizam A, Shufu X, Ungchusak K, Hanshaoworakul W, Cummings D, Halloran ME (2005) Containing pandemic influenza at the source. Science 309: 1083–1087CrossRefGoogle Scholar
  55. Maunder R, Hunter J, Vincent L, Bennett J, Peladeau N, Leszcz M, Sadavoy J, Verhaeghe L, Steinberg R, Mazzulli T (2003) The immediate psychological and occupational impact of the 2003 SARS outbreak in a teaching hospital. Can Med Assoc J 168(10): 1245–1251Google Scholar
  56. Meltzer M, Cox N, Fukuda K (1999) The economic impact of pandemic influenza in the United States: priorities for intervention. Emerg Infect Dis 5(5): 659–671CrossRefGoogle Scholar
  57. Miami International Airport: daily traffic volume data (2010) Last accessed on 04/07/2010
  58. Mills C, Robins J, Lipsitch M (2004) Transmissibility of 1918 pandemic influenza. Nature 432: 904–906CrossRefGoogle Scholar
  59. Milne G, Kelso J, Kelly H, Huband S, McVernon J (2008) A small community model for the transmission of infectious diseases: comparison of school closure as an intervention in individual-based models of an influenza pandemic. PLoS One 3(12): 1–7CrossRefGoogle Scholar
  60. Niederhauser V, Baruffi G, Heck R (2001) Parental decision-making for the varicella vaccine. J Pediatr Health Care 15(5): 236–243Google Scholar
  61. Nigmatulina KR, Larson RC (2009) Living with influenza: impacts of government imposed and voluntarily selected interventions. Eur J Oper Res 195(6/1): 613–627CrossRefGoogle Scholar
  62. Ortutay B (2010) How thermal-imaging cameras spot flu fevers. Last accessed on 03/19/2010
  63. Pasteur S (2009) Influenza A(H1N1) 2009 monovalent vaccine. Last accessed on 11/18/2009
  64. Patel R, Longini I, Halloran M (2005) Finding optimal vaccination strategies for pandemic influenza using genetic algorithms. J Theor Biol 234: 201–212CrossRefGoogle Scholar
  65. PayScale (2009) Job: registered nurse (rn). Last accessed on 12/28/2009
  66. Pearson M, Bridges C, Harper S (2006) Influenza vaccination of health-care personnel. Recommendations of the Healthcare Infection Control Practices Advisory Committee (HICPAC) and the Advisory Committee on Immunization Practices (ACIP) [Internet]. Last accessed on 10/28/2009Google Scholar
  67. (2009) Pricing & ordering comparisons. Last accessed on 12/28/2009
  68. Pitzer V, Olsen S, Bergstrom C, Dowell S, Lipsitch M (2007a) Little evidence for genetic susceptibility to influenza A (H5N1) from family clustering data. Emerg Infect Dis 13(7): 1074–1076Google Scholar
  69. Pitzer V, Leung G, Lipsitch M (2007b) Estimating variability in the transmission of severe acute respiratory syndrome to household contacts in Hong Kong, China. Am J Epidemiol 166(3): 355–359CrossRefGoogle Scholar
  70. Pourbohloul B, Ahued A, Davoudi B, Meza R, Meyers L, Skowronski D, Villaseñor I, Galván F, Cravioto P, Earn D et al (2009) Initial human transmission dynamics of the pandemic (H1N1) 2009 virus in North America. Influenza Other Respir Viruses 3(5): 215–222CrossRefGoogle Scholar
  71. Rhodes S, Hergenrather K (2002) Exploring hepatitis B vaccination acceptance among young men who have sex with men: facilitators and barriers. Prevent Med 35(2): 128–134CrossRefGoogle Scholar
  72. Robertson E, Hershenfield K, Grace S, Stewart D (2004) The psychosocial effects of being quarantined following exposure to SARS: a qualitative study of Toronto health care workers. Can J Psychiatry 49: 403–407Google Scholar
  73. Rosenthal S, Kottenhahn R, Biro F, Succop P (1995) Hepatitis B vaccine acceptance among adolescents and their parents. J Adolesc Health 17(4): 248–255CrossRefGoogle Scholar
  74. Sadique M, Edmunds W, Smith R, Meerding W, de Zwart O, Brug J, Beutels P (2007) Precautionary behavior in response to perceived threat of pandemic influenza. Emerg Infect Dis 13(9): 1307Google Scholar
  75. Safranek T, Lawrence D, Kuriand L, Culver D, Wiederholt W, Hayner N, Osterholm M, O’Brien P, Hughes J (1991) Reassessment of the association between Guillain-Barré syndrome and receipt of swine influenza vaccine in 1976–1977: results of a two-state study. Am J Epidemiol 133(9): 940Google Scholar
  76. Savachkin A, Uribe-Sánchez A, Das T, Prieto D, Santana A, Martinez D (2010a) Supplemental data and model parameter values for cross-regional simulation-based optimization testbed. Last accessed on 04/15/2010
  77. Savachkin A, Uribe A, Das T, Prieto D (2010b) Developing dynamic predictive strategies for mitigation of cross-regional pandemic outbreaks. IIE Trans (in review)Google Scholar
  78. Scharfstein D, Halloran M, Chu H, Daniels M (2006) On estimation of vaccine efficacy using validation samples with selection bias. Biostatistics 7(4): 615CrossRefGoogle Scholar
  79. Schoenstadt A (2009) Spanish flu. Last accessed on 12/15/2009
  80. Smailbegovic M, Laing G, Bedford H (2003) Why do parents decide against immunization? The effect of health beliefs and health professionals. Child Care Health Dev 29(4): 303CrossRefGoogle Scholar
  81. Svensson A (2007) A note on generation times in epidemic models. Math Biosci 208(1): 300–311CrossRefGoogle Scholar
  82. Treanor J, Campbell J, Zangwill K, Rowe T, Wolff M (2006) Safety and immunogenicity of an inactivated subvirion influenza A(H5N1) vaccine. N Engl J Med 3554(13): 1343CrossRefGoogle Scholar
  83. Tallahassee Regional Airport: daily traffic volume data (2010) Last accessed on 04/07/2010
  84. Tampa International Airport: daily traffic volume data (2010) Last accessed on 04/07/2010
  85. Tang Y, Longini I, Halloran M (2006) Design and evaluation of prophylactic interventions using disease incidence data from close contact groups. Appl Stat 55(3): 317–330Google Scholar
  86. The New Yorker (2009) The fear factor. Last accessed on 10/28/2009
  87. The New York Times (2009) Doctors swamped by swine flu vaccine fears. Last accessed on 10/28/2009
  88. Uribe A, Prieto D, Savachkin A, Das T, Zhu Y (2008) A cross-regional pandemic outbreak simulation model: an aid to national resource allocation policy making. In: Proceedings of the 3rd INFORMS workshop on data mining and health informatics (DM-DI 2008)Google Scholar
  89. US Census Bureau (2000) 2001 American community survey. Last accessed on 03/27/2009
  90. US Department of Health & Human Services (2007) HHS pandemic influenza plan. Last accessed on 03/27/2009
  91. WHO Global Influenza Programme (2009) Pandemic influenza preparedness and response. Tech. Rep. World Health OrganizationGoogle Scholar
  92. World Health Organization (WHO) (2004) WHO guidelines on the use of vaccine and antivirals during influenza pandemics. Retrieved 03/27/2009
  93. World Health Organization (2009) Pandemic (h1n1) 2009 vaccine deployment update, 17 December 2009.
  94. World Health Organization (WHO) (2010a) Cumulative number of confirmed human cases of Avian Influenza A(H5N1) reported to WHO.
  95. World Health Organization (2010b) Pandemic (H1N1) 2009—update 107. Last accessed on 07/08/2010
  96. Writing Committee of the World Health Organization (WHO): (2005) Consultation on human influenza A/H5. Avian influenza A(H5N1) infection in humans. N Engl J Med 353(13): 1374–1385CrossRefGoogle Scholar
  97. Wu JT, Riley S, Fraser C, Leung G (2006a) Spatial considerations for the allocation of pre-pandemic influenza vaccination in the United States. Proc R Soc Biol Sci 274(1627): 2811–2817CrossRefGoogle Scholar
  98. Wu JT, Riley S, Fraser C, Leung G (2006b) Reducing the impact of the next influenza pandemic using household-based public health interventions. PLoS Med 3(9): 1532–1540CrossRefGoogle Scholar
  99. Yang Y, Sugimoto J, Halloran M, Basta N, Chao D, Matrajt L, Potter G, Kenah E, Longini I Jr (2009a) The transmissibility and control of pandemic influenza A (H1N1) virus. Science 326(5953): 729–733CrossRefGoogle Scholar
  100. Yang Y, Halloran M, Longini I Jr (2009b) A Bayesian model for evaluating influenza antiviral efficacy in household studies with asymptomatic infections. Biostatistics 10(2): 390CrossRefGoogle Scholar
  101. Yang Y, Halloran M, Sugimoto J, Longini I Jr (2007) Detecting human-to-human transmission of avian influenza A (H5N1). Emerg Infect Dis 13(9): 1348–1353Google Scholar
  102. Yasuda H, Suzuki K (2009) Measures against transmission of pandemic H1N1 influenza in Japan in 2009: simulation model. Eur Commun Dis Bull [Euro surveillance: bulletin européen sur les maladies transmissibles] 14(44): 1–7Google Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Andrés Uribe-Sánchez
    • 1
  • Alex Savachkin
    • 1
    Email author
  • Alfredo Santana
    • 1
  • Diana Prieto-Santa
    • 1
  • Tapas K. Das
    • 1
  1. 1.Department of Industrial and Management Systems EngineeringUniversity of South FloridaTampaUSA

Personalised recommendations