Decision Making with Regard to Antiviral Intervention during an Influenza Pandemic

Background. Antiviral coverage is defined by the proportion of the population that takes antiviral prophylaxis or treatment. High coverage of an antiviral drug has epidemiological and evolutionary repercussions. Antivirals select for drug resistance within the population, and individuals may experience adverse effects. To determine optimal antiviral coverage in the context of an influenza outbreak, we compared 2 perspectives: 1) the individual level (the Nash perspective), and 2) the population level (utilitarian perspective). Methods. We developed an epidemiological game-theoretic model of an influenza pandemic. The data sources were published literature and a national survey. The target population was the US population. The time horizon was 6 months. The perspective was individuals and the population overall. The interventions were antiviral prophylaxis and treatment. The outcome measures were the optimal coverage of antivirals in an influenza pandemic. Results. At current antiviral pricing, the optimal Nash strategy is 0% coverage for prophylaxis and 30% coverage for treatment, whereas the optimal utilitarian strategy is 19% coverage for prophylaxis and 100% coverage for treatment. Subsidizing prophylaxis by $440 and treatment by $85 would bring the Nash and utilitarian strategies into alignment. For both prophylaxis and treatment, the optimal antiviral coverage decreases as pricing of antivirals increases. Our study does not incorporate the possibility of an effective vaccine and lacks probabilistic sensitivity analysis. Our survey also does not completely represent the US population. Because our model assumes a homogeneous population and homogeneous antiviral pricing, it does not incorporate heterogeneity of preference. Conclusions. The optimal antiviral coverage from the population perspective and individual perspectives differs widely for both prophylaxis and treatment strategies. Optimal population and individual strategies for prophylaxis and treatment might be aligned through subsidization.

[1]  T. Uyeki,et al.  Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. , 2008, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[2]  L. A. Rvachev,et al.  A mathematical model for the global spread of influenza , 1985 .

[3]  D. Richman,et al.  Antiviral drug resistance. , 2006, Antiviral research.

[4]  H. J. Rose The use of amantadine and influenza vaccine in a type A influenza epidemic in a boarding school. , 1980, The Journal of the Royal College of General Practitioners.

[5]  J. Robins,et al.  Transmissibility of 1918 pandemic influenza , 2004, Nature.

[6]  R. Webster,et al.  Are We Ready for Pandemic Influenza? , 2003, Science.

[7]  Eduardo Massad,et al.  Yellow fever vaccination: how much is enough? , 2005, Vaccine.

[8]  A S Perelson,et al.  Emergence of drug resistance during an influenza epidemic: insights from a mathematical model. , 1998, The Journal of infectious diseases.

[9]  S. Emery,et al.  Antivirals in the management of an influenza pandemic , 2006, The Medical journal of Australia.

[10]  N. Roberts,et al.  Treatment of influenza with neuraminidase inhibitors: virological implications. , 2001, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[11]  M. Elizabeth Halloran,et al.  Detecting Human-to-Human Transmission of Avian Influenza A (H5N1) , 2007, Emerging Infectious Diseases.

[12]  Jeroen K Medema,et al.  Modeling pandemic preparedness scenarios: health economic implications of enhanced pandemic vaccine supply. , 2004, Virus research.

[13]  E. Garman,et al.  The Origin and Control of Pandemic Influenza , 2001, Science.

[14]  N. Cox,et al.  Low incidence of rimantadine resistance in field isolates of influenza A viruses. , 1999, The Journal of infectious diseases.

[15]  A. Monto Antivirals and influenza: frequency of resistance. , 2008, The Pediatric infectious disease journal.

[16]  Michael B Rothberg,et al.  Vaccination versus treatment of influenza in working adults: a cost-effectiveness analysis. , 2005, The American journal of medicine.

[17]  D. Haydon,et al.  The generation and persistence of genetic variation in foot-and-mouth disease virus. , 2001, Preventive veterinary medicine.

[18]  C. Macken,et al.  Modeling targeted layered containment of an influenza pandemic in the United States , 2008, Proceedings of the National Academy of Sciences.

[19]  W. H. Frost Statistics of Influenza Morbidity: With Special Reference to Certain Factors in Case Incidence and Case Fatality , 1920 .

[20]  F. Hayden,et al.  Selection of influenza virus mutants in experimentally infected volunteers treated with oseltamivir. , 2001, The Journal of infectious diseases.

[21]  R. J. Moser,et al.  Parasite screening and treatment among Indochinese refugees. Cost-benefit/utility and the General Health Policy Model. , 1985, JAMA.

[22]  Nadav Davidovitch,et al.  Cost-Benefit of Stockpiling Drugs for Influenza Pandemic , 2005, Emerging infectious diseases.

[23]  A. Nizam,et al.  Containing pandemic influenza with antiviral agents. , 2004, American journal of epidemiology.

[24]  J. Watmough,et al.  Reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease transmission. , 2002, Mathematical biosciences.

[25]  W. P. Glezen,et al.  Influenza virus infections in infants. , 1997, The Pediatric infectious disease journal.

[26]  M. Meltzer,et al.  The economic impact of pandemic influenza in the United States: priorities for intervention. , 1999, Emerging infectious diseases.

[27]  L. Macwilliam,et al.  Measuring the Health of the Population , 1995, Medical care.

[28]  C. Bauch Imitation dynamics predict vaccinating behaviour , 2005, Proceedings of the Royal Society B: Biological Sciences.

[29]  D. Earn,et al.  Group interest versus self-interest in smallpox vaccination policy , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[30]  B. Ruf,et al.  Reducing the Burden of Influenza-Associated Complications with Antiviral Therapy , 2009, Infection.

[31]  Tanja Popovic,et al.  Oseltamivir-resistant 2009 pandemic influenza A (H1N1) virus infection in two summer campers receiving prophylaxis--North Carolina, 2009. , 2009, MMWR. Morbidity and mortality weekly report.

[32]  M. Johannesson,et al.  The value of the change in health in Sweden 1980/81 to 1996/97. , 2003, Health economics.

[33]  A. Moscona Neuraminidase inhibitors for influenza. , 2005, The New England journal of medicine.

[34]  N. Cox,et al.  Prevention and Control of Influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). , 2006, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[35]  A. Monto,et al.  Influenza viruses resistant to the antiviral drug oseltamivir: transmission studies in ferrets. , 2004, The Journal of infectious diseases.

[36]  Larry R. Smith,et al.  Cross-Reactive Neuraminidase Antibodies Afford Partial Protection against H5N1 in Mice and Are Present in Unexposed Humans , 2007, PLoS medicine.

[37]  R. Jacobson,et al.  Influenza virus resistance to antiviral agents: a plea for rational use. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[38]  Timothy C. Reluga,et al.  Long-standing influenza vaccination policy is in accord with individual self-interest but not with the utilitarian optimum , 2007, Proceedings of the National Academy of Sciences.

[39]  B. Levin,et al.  Antiviral Resistance and the Control of Pandemic Influenza , 2007, PLoS medicine.

[40]  Sebastian Bonhoeffer,et al.  This PDF file includes: SOM Text , 2022 .

[41]  R. Douglas,et al.  Correlated studies of a recombinant influenza-virus vaccine. 3. Protection against experimental influenza in man. , 1971, The Journal of infectious diseases.

[42]  Ping Yan,et al.  Emergence of drug resistance: implications for antiviral control of pandemic influenza , 2007, Proceedings of the Royal Society B: Biological Sciences.

[43]  L. Huson,et al.  Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza. , 1999, The New England journal of medicine.

[44]  M Elizabeth Halloran,et al.  Design and evaluation of prophylactic interventions using infectious disease incidence data from close contact groups , 2006, Journal of the Royal Statistical Society. Series C, Applied statistics.

[45]  J. Nash Equilibrium Points in N-Person Games. , 1950, Proceedings of the National Academy of Sciences of the United States of America.

[46]  Alex J. Sutton,et al.  Cost-effectiveness and value of information analyses of neuraminidase inhibitors for the treatment of influenza. , 2008, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[47]  Timothy C. Reluga,et al.  Evolving public perceptions and stability in vaccine uptake. , 2006, Mathematical biosciences.

[48]  C. Cheung,et al.  Oseltamivir-Resistant Influenza A Pandemic (H1N1) 2009 Virus, Hong Kong, China , 2009, Emerging infectious diseases.

[49]  F. Hayden,et al.  John F. Enders lecture 2006: antivirals for influenza. , 2007, The Journal of infectious diseases.

[50]  D. Cutler,et al.  Measuring the Health of the U.S. Population , 1997 .

[51]  T. Jefferson,et al.  Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children , 2010, The Cochrane database of systematic reviews.

[52]  A. Moscona,et al.  Global transmission of oseltamivir-resistant influenza. , 2009, The New England journal of medicine.

[53]  D. Cutler,et al.  The Value of Health: 1970-1990 , 1998 .

[54]  M. Lipsitch,et al.  The Severity of Pandemic H1N1 Influenza in the United States, from April to July 2009: A Bayesian Analysis , 2009, PLoS medicine.

[55]  M. Kremer Integrating Behavioral Choice into Epidemiological Models of AIDS , 1996 .

[56]  K Abrams,et al.  Systematic review and economic decision modelling for the prevention and treatment of influenza A and B. , 2003, Health technology assessment.

[57]  J. Brundage Cases and deaths during influenza pandemics in the United States. , 2006, American journal of preventive medicine.

[58]  D. Earn,et al.  Vaccination and the theory of games. , 2004, Proceedings of the National Academy of Sciences of the United States of America.