Paradox of Vaccination: Is Vaccination Really Effective against Avian Flu Epidemics?

Background Although vaccination can be a useful tool for control of avian influenza epidemics, it might engender emergence of a vaccine-resistant strain. Field and experimental studies show that some avian influenza strains acquire resistance ability against vaccination. We investigated, in the context of the emergence of a vaccine-resistant strain, whether a vaccination program can prevent the spread of infectious disease. We also investigated how losses from immunization by vaccination imposed by the resistant strain affect the spread of the disease. Methods and Findings We designed and analyzed a deterministic compartment model illustrating transmission of vaccine-sensitive and vaccine-resistant strains during a vaccination program. We investigated how the loss of protection effectiveness impacts the program. Results show that a vaccination to prevent the spread of disease can instead spread the disease when the resistant strain is less virulent than the sensitive strain. If the loss is high, the program does not prevent the spread of the resistant strain despite a large prevalence rate of the program. The epidemic's final size can be larger than that before the vaccination program. We propose how to use poor vaccines, which have a large loss, to maximize program effects and describe various program risks, which can be estimated using available epidemiological data. Conclusions We presented clear and simple concepts to elucidate vaccination program guidelines to avoid negative program effects. Using our theory, monitoring the virulence of the resistant strain and investigating the loss caused by the resistant strain better development of vaccination strategies is possible.

[1]  F. Roger,et al.  Avian influenza vaccines: a practical review in relation to their application in the field with a focus on the Asian experience , 2008, Epidemiology and Infection.

[2]  M. van Boven,et al.  Avian influenza A virus (H7N7) epidemic in The Netherlands in 2003: course of the epidemic and effectiveness of control measures. , 2004, The Journal of infectious diseases.

[3]  D. Suarez,et al.  Effect of Vaccine Use in the Evolution of Mexican Lineage H5N2 Avian Influenza Virus , 2004, Journal of Virology.

[4]  Gavin J. D. Smith,et al.  Emergence and predominance of an H5N1 influenza variant in China , 2006, Proceedings of the National Academy of Sciences.

[5]  R. Webster,et al.  Cross-Reactive, Cell-Mediated Immunity and Protection of Chickens from Lethal H5N1 Influenza Virus Infection in Hong Kong Poultry Markets , 2001, Journal of Virology.

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

[7]  R. May,et al.  Infectious Diseases of Humans: Dynamics and Control , 1991, Annals of Internal Medicine.

[8]  Marius Gilbert,et al.  Highly Pathogenic Avian Influenza H 5 N 1 , Thailand , 2004 , 2005 .

[9]  M. Keeling,et al.  Silent spread of H5N1 in vaccinated poultry , 2006, Nature.

[10]  Xianning Liu,et al.  A geographical spread of vaccine-resistance in avian influenza epidemics. , 2009, Journal of theoretical biology.

[11]  I. Capua,et al.  Control of Avian Influenza in Poultry , 2006, Emerging infectious diseases.

[12]  Marius Gilbert,et al.  Highly Pathogenic Avian Influenza H5N1, Thailand, 2004 , 2005, Emerging Infectious Diseases.

[13]  G. Koch,et al.  Performance of clinical signs in poultry for the detection of outbreaks during the avian influenza A (H7N7) epidemic in The Netherlands in 2003 , 2005, Avian pathology : journal of the W.V.P.A.

[14]  Xianning Liu,et al.  Avian-human influenza epidemic model. , 2007, Mathematical biosciences.

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

[16]  D. Swayne,et al.  Influence of virus strain and antigen mass on efficacy of H5 avian influenza inactivated vaccines. , 1999, Avian pathology : journal of the W.V.P.A.

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

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

[19]  M. Cecchinato,et al.  Use of Vaccination in Avian Influenza Control and Eradication , 2008, Zoonoses and public health.

[20]  Seyed M. Moghadas,et al.  Population-Wide Emergence of Antiviral Resistance during Pandemic Influenza , 2008, PloS one.

[21]  W. J. Bean,et al.  Chemotherapy and vaccination: a possible strategy for the control of highly virulent influenza virus , 1985, Journal of virology.

[22]  Xianning Liu,et al.  Prevention of avian influenza epidemic: what policy should we choose? , 2008, Journal of theoretical biology.

[23]  D. Suarez,et al.  Highly Pathogenic Avian Influenza , 2015, Radiology of Infectious Diseases: Volume 1.

[24]  M. Steensels,et al.  Influenza vaccines and vaccination strategies in birds. , 2008, Comparative immunology, microbiology and infectious diseases.

[25]  Gabriele Neumann,et al.  Human infection with highly pathogenic H5N1 influenza virus , 2008, The Lancet.

[26]  F. Hayden,et al.  Perspectives on antiviral use during pandemic influenza. , 2001, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[27]  M. Nielen,et al.  Transmission of the highly pathogenic avian influenza virus H5N1 within flocks during the 2004 epidemic in Thailand. , 2007, The Journal of infectious diseases.

[28]  D. Cummings,et al.  Strategies for containing an emerging influenza pandemic in Southeast Asia , 2005, Nature.

[29]  N. Seidah,et al.  The H5N1 Influenza Variant Fujian-Like Hemagglutinin Selected Following Vaccination Exhibits a Compromised Furin Cleavage , 2008, Journal of Molecular Neuroscience.

[30]  I. Capua Vaccination for notifiable avian influenza in poultry. , 2007, Revue scientifique et technique.

[31]  A. Pijpers,et al.  The Highly Pathogenic Avian Influenza A (H7N7) Virus Epidemic in the Netherlands in 2003—Lessons Learned from the First Five Outbreaks , 2004, Avian diseases.

[32]  D. Cummings,et al.  Strategies for mitigating an influenza pandemic , 2006, Nature.

[33]  I. Capua,et al.  Human Health Implications of Avian Influenza Viruses and Paramyxoviruses , 2004, European Journal of Clinical Microbiology and Infectious Diseases.

[34]  Andreas Handel,et al.  Correction: The Role of Compensatory Mutations in the Emergence of Drug Resistance , 2007, PLoS Comput. Biol..

[35]  F. Leung Comments on the Fujian-like strain of avian influenza H5N1. , 2007, Poultry science.

[36]  Alessandro Vespignani,et al.  Modeling the Worldwide Spread of Pandemic Influenza: Baseline Case and Containment Interventions , 2007, PLoS medicine.

[37]  I. Capua,et al.  Vaccination for avian influenza in Asia. , 2004, Vaccine.

[38]  Christopher T. McCaw,et al.  Impact of Emerging Antiviral Drug Resistance on Influenza Containment and Spread: Influence of Subclinical Infection and Strategic Use of a Stockpile Containing One or Two Drugs , 2008, PloS one.

[39]  H J Bremermann,et al.  A competitive exclusion principle for pathogen virulence , 1989, Journal of mathematical biology.