The effects of strain heterology on the epidemiology of equine influenza in a vaccinated population

We assess the effects of strain heterology (strains that are immunologically similar but not identical) on equine influenza in a vaccinated population. Using data relating to individual animals, for both homologous and heterologous vaccinees, we estimate distributions for the latent and infectious periods, quantify the risk of becoming infected in terms of the quantity of cross–reactive antibodies to a key surface protein of the virus (haemagglutinin) and estimate the probability of excreting virus (i.e. becoming infectious) given that infection has occurred. The data suggest that the infectious period, the risk of becoming infected (for a given vaccine–induced level of cross–reactive antibodies) and the probability of excreting virus are increased for heterologously vaccinated animals when compared with homologously vaccinated animals. The data are used to parameterize a modified susceptible, exposed, infectious and recovered/resistant (SEIR) model, which shows that these relatively small differences combine to have a large effect at the population level, where populations of heterologous vaccinees face a significantly increased risk of an epidemic occurring.

[1]  Scott R. Eliason Maximum likelihood estimation: Logic and practice. , 1994 .

[2]  B T Grenfell,et al.  Effect of variability in infection period on the persistence and spatial spread of infectious diseases. , 1998, Mathematical biosciences.

[3]  H. McCallum,et al.  How should pathogen transmission be modelled? , 2001, Trends in ecology & evolution.

[4]  G. Schild,et al.  Studies with inactivated equine influenza vaccine: 2. Protection against experimental infection with influenza virus A/equine/Newmarket/79 (H3N8) , 1983, Journal of Hygiene.

[5]  J. Mumford,et al.  Equine influenza vaccine efficacy: the significance of antigenic variation. , 2000, Veterinary microbiology.

[6]  W. Dowdle,et al.  U.S. EPIZOOTIC OF EQUINE INFLUENZA, 1963. , 1964, Public health reports.

[7]  O. Pybus,et al.  Unifying the Epidemiological and Evolutionary Dynamics of Pathogens , 2004, Science.

[8]  D. V. Gokhale,et al.  Stochastic Processes and Applications in Biology and Medicine. , 1974 .

[9]  W. O. Kermack,et al.  A contribution to the mathematical theory of epidemics , 1927 .

[10]  I. Wilson,et al.  Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation , 1981, Nature.

[11]  J. Wood,et al.  It's all in the mix: infection transmission in populations. , 2010, Equine veterinary journal.

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

[13]  J. Mumford,et al.  Studies with inactivated equine influenza vaccine: 1. Serological responses of ponies to graded doses of vaccine , 1983, Journal of Hygiene.

[14]  A L Lloyd,et al.  Realistic distributions of infectious periods in epidemic models: changing patterns of persistence and dynamics. , 2001, Theoretical population biology.

[15]  C. Turkington,et al.  The Encyclopedia of Infectious Diseases , 1998 .

[16]  M. Pike,et al.  An improved approximate formula for calculating sample sizes for comparing two binomial distributions. , 1978, Biometrics.

[17]  O. Diekmann,et al.  On the definition and the computation of the basic reproduction ratio R0 in models for infectious diseases in heterogeneous populations , 1990, Journal of mathematical biology.

[18]  Jonathan Dushoff,et al.  Hemagglutinin sequence clusters and the antigenic evolution of influenza A virus , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Denis Mollison,et al.  Spatial Contact Models for Ecological and Epidemic Spread , 1977 .

[20]  D. Haines,et al.  Risk factors for disease associated with influenza virus infections during three epidemics in horses. , 2000, Journal of the American Veterinary Medical Association.

[21]  Bryan T Grenfell,et al.  Dynamics and selection of many-strain pathogens , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[22]  M. S. Bartlett,et al.  Monte Carlo Studies in Ecology and Epidemiology , 1961 .

[23]  J. Mumford The equine influenza surveillance program. , 1999, Advances in Veterinary Medicine.

[24]  N. Dimmock Mechanisms of neutralization of animal viruses. , 1984, The Journal of general virology.

[25]  J. Wood,et al.  Risk factors for equine influenza serum antibody titres in young thoroughbred racehorses given an inactivated vaccine. , 2000, Preventive veterinary medicine.

[26]  G. Schild,et al.  Single-radial-hemolysis: a new method for the assay of antibody to influenza haemagglutinin. Applications for diagnosis and seroepidemiologic surveillance of influenza. , 1975, Bulletin of the World Health Organization.

[27]  J. Steward Evolution And Ecology , 1977 .

[28]  A L Lloyd,et al.  Destabilization of epidemic models with the inclusion of realistic distributions of infectious periods , 2001, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[29]  Ron R. Hightower,et al.  Deriving shape space parameters from immunological data. , 1997, Journal of theoretical biology.

[30]  Herbert W. Hethcote,et al.  Epidemic models: Their structure and relation to data , 1996 .

[31]  George W. Williams,et al.  Spatial Aspects of Influenza Epidemics. , 1988 .

[32]  R. Watson,et al.  On the spread of a disease with gamma distributed latent and infectious periods , 1980 .

[33]  N. Cox,et al.  Antigenic and genetic variation in influenza A (H1N1) virus isolates recovered from a persistently infected immunodeficient child , 1991, Journal of virology.

[34]  J. Wood,et al.  Immunity to equine influenza: relationship of vaccine-induced antibody in young Thoroughbred racehorses to protection against field infection with influenza A/equine-2 viruses (H3N8). , 2000, Equine veterinary journal.

[35]  J. Skehel,et al.  Structural studies on viral escape from antibody neutralization. , 2001, Current topics in microbiology and immunology.

[36]  J. Wood,et al.  Evidence supporting the inclusion of strains from each of the two co-circulating lineages of H3N8 equine influenza virus in vaccines. , 2004, Vaccine.

[37]  A. S. Beare,et al.  The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses , 1972, Epidemiology and Infection.

[38]  B. Grenfell,et al.  Optimising vaccination strategies in equine influenza. , 2003, Vaccine.

[39]  T. Kimman,et al.  Experimental quantification of vaccine-induced reduction in virus transmission. , 1994, Vaccine.

[40]  W. Fitch,et al.  Long term trends in the evolution of H(3) HA1 human influenza type A. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[41]  D. Mollison Epidemic models : their structure and relation to data , 1996 .

[42]  Andrew P. Dobson,et al.  Ecology of Infectious Diseases in Natural Populations: Frontmatter , 1995 .

[43]  M E Halloran,et al.  Measuring vaccine efficacy for both susceptibility to infection and reduction in infectiousness for prophylactic HIV-1 vaccines. , 1996, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[44]  A. S. Beare Basic and applied influenza research , 1982 .

[45]  N. Ferguson,et al.  Ecological and immunological determinants of influenza evolution , 2003, Nature.

[46]  B. Grenfell,et al.  Modelling equine influenza 1: a stochastic model of within-yard epidemics , 2002, Epidemiology and Infection.