Detecting Emerging Transmissibility of Avian Influenza Virus in Human Households

Accumulating infections of highly pathogenic H5N1 avian influenza in humans underlines the need to track the ability of these viruses to spread among humans. A human-transmissible avian influenza virus is expected to cause clusters of infections in humans living in close contact. Therefore, epidemiological analysis of infection clusters in human households is of key importance. Infection clusters may arise from transmission events from (i) the animal reservoir, (ii) humans who were infected by animals (primary human-to-human transmission), or (iii) humans who were infected by humans (secondary human-to-human transmission). Here we propose a method of analysing household infection data to detect changes in the transmissibility of avian influenza viruses in humans at an early stage. The method is applied to an outbreak of H7N7 avian influenza virus in The Netherlands that was the cause of more than 30 human-to-human transmission events. The analyses indicate that secondary human-to-human transmission is plausible for the Dutch household infection data. Based on the estimates of the within-household transmission parameters, we evaluate the effectiveness of antiviral prophylaxis, and conclude that it is unlikely that all household infections can be prevented with current antiviral drugs. We discuss the applicability of our method for the detection of emerging human-to-human transmission of avian influenza viruses in particular, and for the analysis of within-household infection data in general.

[1]  S. Baigent,et al.  Influenza type A in humans, mammals and birds: determinants of virus virulence, host-range and interspecies transmission. , 2003, BioEssays : news and reviews in molecular, cellular and developmental biology.

[2]  O. Diekmann Mathematical Epidemiology of Infectious Diseases , 1996 .

[3]  R. Webster,et al.  A pandemic warning? , 1997, Nature.

[4]  V Demicheli,et al.  Antivirals for influenza in healthy adults: systematic review , 2006, The Lancet.

[5]  F. Ball A unified approach to the distribution of total size and total area under the trajectory of infectives in epidemic models , 1986, Advances in Applied Probability.

[6]  Prasert Auewarakul,et al.  Probable person-to-person transmission of avian influenza A (H5N1). , 2005, The New England journal of medicine.

[7]  M. Koopmans,et al.  Measurement of antibodies to avian influenza virus A(H7N7) in humans by hemagglutination inhibition test. , 2006, Journal of virological methods.

[8]  Armin Elbers,et al.  Risk Maps for the Spread of Highly Pathogenic Avian Influenza in Poultry , 2007, PLoS Comput. Biol..

[9]  Marion Koopmans,et al.  Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[10]  A. Klimov,et al.  Evolution of the receptor binding phenotype of influenza A (H5) viruses. , 2006, Virology.

[11]  D. Lewis,et al.  Avian flu to human influenza. , 2006, Annual review of medicine.

[12]  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.

[13]  N. Cox,et al.  Lack of transmission of H5N1 avian–human reassortant influenza viruses in a ferret model , 2006, Proceedings of the National Academy of Sciences.

[14]  P. O’Neill,et al.  Bayesian inference for stochastic multitype epidemics in structured populations via random graphs , 2005 .

[15]  A. Fauci,et al.  The next influenza pandemic: can it be predicted? , 2007, JAMA.

[16]  M. Begon,et al.  A clarification of transmission terms in host-microparasite models: numbers, densities and areas , 2002, Epidemiology and Infection.

[17]  M. Halloran,et al.  Antiviral effects on influenza viral transmission and pathogenicity: observations from household-based trials. , 2006, American journal of epidemiology.

[18]  C. Fraser,et al.  Public Health Risk from the Avian H5N1 Influenza Epidemic , 2004, Science.

[19]  N. Cox,et al.  Avian Influenza (H5N1) Viruses Isolated from Humans in Asia in 2004 Exhibit Increased Virulence in Mammals , 2005, Journal of Virology.

[20]  F. Rousset,et al.  Inclusive fitness for traits affecting metapopulation demography. , 2004, Theoretical population biology.

[21]  I. Longini,et al.  A generalized stochastic model for the analysis of infectious disease final size data. , 1991, Biometrics.

[22]  Samson S. Y. Wong,et al.  Avian Influenza Virus Infections in Humans , 2006, Chest.

[23]  Human cases of avian influenza A (H5N1) in North-West Frontier Province, Pakistan, October-November 2007. , 2008, Releve epidemiologique hebdomadaire.

[24]  Timothy M. Uyeki,et al.  Family Clustering of Avian Influenza A (H5N1) , 2005, Emerging infectious diseases.

[25]  M. Woolhouse Population biology of emerging and re-emerging pathogens. , 2002, Trends in microbiology.

[26]  Yi Guan,et al.  Avian Influenza Virus (H5N1): a Threat to Human Health , 2007, Clinical Microbiology Reviews.

[27]  David R. Anderson,et al.  Model Selection and Multimodel Inference , 2003 .

[28]  Y. Guan,et al.  H5N1 Outbreaks and Enzootic Influenza , 2006, Emerging infectious diseases.

[29]  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.

[30]  C. Viboud,et al.  A Bayesian MCMC approach to study transmission of influenza: application to household longitudinal data , 2004, Statistics in medicine.

[31]  Angus Nicoll,et al.  Avian influenza A (H5N1) infection in humans. , 2005, The New England journal of medicine.

[32]  P. E. Kopp,et al.  Superspreading and the effect of individual variation on disease emergence , 2005, Nature.

[33]  Highly pathogenic avian influenza virus A(H7N7) infection of humans and human-to-human transmission during avian influenza outbreak in the Netherlands , 2004 .

[34]  H. Klenk,et al.  The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[35]  Frank Ball,et al.  The distribution of general final state random variables for stochastic epidemic models , 1999 .

[36]  Keiji Fukuda,et al.  Evolution of H5N1 Avian Influenza Viruses in Asia , 2005, Emerging infectious diseases.

[37]  J. André,et al.  The effect of disease life history on the evolutionary emergence of novel pathogens , 2005, Proceedings of the Royal Society B: Biological Sciences.

[38]  Damian Clancy,et al.  Exact Bayesian Inference and Model Selection for Stochastic Models of Epidemics Among a Community of Households , 2007 .

[39]  Declan Butler Family tragedy spotlights flu mutations , 2006, Nature.

[40]  M. Koopmans,et al.  Human-to-human transmission of avian influenza A/H7N7, The Netherlands, 2003. , 2005, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[41]  E. Holmes,et al.  Host Species Barriers to Influenza Virus Infections , 2006, Science.

[42]  R. Webster,et al.  Inefficient Transmission of H5N1 Influenza Viruses in a Ferret Contact Model , 2007, Journal of Virology.

[43]  Gabriele Neumann,et al.  Host Range Restriction and Pathogenicity in the Context of Influenza Pandemic , 2006, Emerging infectious diseases.

[44]  A. Osterhaus,et al.  For Personal Use. Only Reproduce with Permission from the Lancet , 2022 .

[45]  A. Nizam,et al.  Containing Pandemic Influenza at the Source , 2005, Science.

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