In winter 2016-7, Europe was severely hit by an unprecedented epidemic of highly pathogenic avian influenza viruses (HPAIVs), causing a significant impact on animal health, wildlife conservation, and livestock economic sustainability. By applying phylodynamic tools to virus sequences collected during the epidemic, we investigated when the first infections occurred, how many infections were unreported, which factors influenced virus spread, and how many spillover events occurred. HPAIV was likely introduced into poultry farms during the autumn, in line with the timing of wild birds' migration. In Germany, Hungary, and Poland, the epidemic was dominated by farm-to-farm transmission, showing that understanding of how farms are connected would greatly help control efforts. In the Czech Republic, the epidemic was dominated by wild bird-to-farm transmission, implying that more sustainable prevention strategies should be developed to reduce HPAIV exposure from wild birds. Inferred transmission parameters will be useful to parameterize predictive models of HPAIV spread. None of the predictors related to live poultry trade, poultry census, and geographic proximity were identified as supportive predictors of HPAIV spread between farms across borders. These results are crucial to better understand HPAIV transmission dynamics at the domestic-wildlife interface with the view to reduce the impact of future epidemics.

DaNAm Vet Molbiol Herman Ottó utca 5 Kőszeg 9730 Hungary

Department of Biosystems Science and Engineering ETH Zurich Mattenstrasse Basel 4058 Switzerland

Department of Poultry Diseases National Veterinary Research Institute Al Partyzantow 57 Pulawy 24 100 Poland

Friedrich Loeffler Institut Suedufer 10 Greifswald Insel Riems 17489 Germany

IHAP Université de Toulouse INRAE ENVT 23 chemin des capelles Toulouse 31076 France

State Veterinary Institute Prague Sidlistni 136 24 Prague 165 03 Czech Republic

Swiss Institute of Bioinformatics Quartier Sorge Lausanne 1015 Switzerland

Zobrazit více v PubMed

Alarcon P. et al. (2018) ‘Comparison of 2016–17 and Previous Epizootics of Highly Pathogenic Avian Influenza H5 Guangdong Lineage in Europe’, Emerging Infectious Diseases, 24: 2270. PubMed PMC

Anderson R. M., and May R. M. (1979) ‘Population Biology of Infectious Diseases: Part I’, Nature, 280: 361–7. PubMed

Andronico A. et al. (2019) ‘Highly Pathogenic Avian Influenza H5N8 in South-west France 2016–2017: A Modeling Study of Control Strategies’, Epidemics, 28: 100340. PubMed

Artois M. et al. (2009) ‘Outbreaks of Highly Pathogenic Avian Influenza in Europe: The Risks Associated with Wild Birds’, Revue Scientifique Et Technique de l’OIE, 28: 69. PubMed

Atkinson P. W. et al. (2006) ‘Urgent preliminary assessment of ornithological data relevant to the spread of avian influenze in Europe’. Wetlands International.

Ayres D. L. et al. (2012) ‘BEAGLE: An Application Programming Interface and High-performance Computing Library for Statistical Phylogenetics’, Systematic Biology, 61: 170–3. PubMed PMC

Beerens N. et al. (2017) ‘Multiple Reassorted Viruses as Cause of Highly Pathogenic Avian Influenza A(H5N8) Virus Epidemic, the Netherlands, 2016’, Emerging Infectious Diseases, 23: 1974–81. PubMed PMC

Blanchong J. A. et al. (2016) ‘Application of Genetics and Genomics to Wildlife Epidemiology’, The Journal of Wildlife Management, 80: 593–608.

Bloomfield S. et al. (2019) ‘Investigation of the Validity of Two Bayesian Ancestral State Reconstruction Models for Estimating Salmonella Transmission during Outbreaks’, PLoS One, 14: e0214169. PubMed PMC

Bouckaert R. et al. (2014) ‘BEAST 2: A Software Platform for Bayesian Evolutionary Analysis’, PLoS Computational Biology, 10: e1003537. PubMed PMC

BTO . (2017), British Trust for Ornithology (BTO) <https://www.bto.org> accessed May 2021.

De Maio N. et al. (2015) ‘New Routes to Phylogeography: A Bayesian Structured Coalescent Approximation’, PLoS Genetics, 11: e1005421. PubMed PMC

Drummond A. J. et al. (2006) ‘Relaxed Phylogenetics and Dating with Confidence’, PLoS Biology, 4: e88. PubMed PMC

du Plessis L., and Stadler T. (2015) ‘Getting to the Root of Epidemic Spread with Phylodynamic Analysis of Genomic Data’, Trends in Microbiology, 23: 383–6. PubMed

Dudas G. et al. (2018) ‘MERS-CoV Spillover at the Camel-human Interface’, Elife, 7: e31257. PubMed PMC

EFSA, European Centre For Disease Prevention And Control, European Union Reference Laboratory For Avian Influenza et al. (2017) ‘Avian Influenza Overview October 2016–August 2017’, EFSA Journal, 15: e05018. PubMed PMC

FAO . (2021), Global Animal Disease Information System (Empres-i) <https://empres-i.review.fao.org/#/> accessed Jan 2021.

FAOSTAT . (2016), Production and Trade of Live Animals <http://www.fao.org/faostat/en/#compare> accessed May 2021.

Faria N. R. et al. (2018) ‘Genomic and Epidemiological Monitoring of Yellow Fever Virus Transmission Potential’, Science, 361: 894–9. PubMed PMC

Freyman W. A., and Höhna S. (2019) ‘Stochastic Character Mapping of State-dependent Diversification Reveals the Tempo of Evolutionary Decline in Self-compatible Onagraceae Lineages’, Systematic Biology, 68: 505–19. PubMed

Fusaro A. et al. (2017) ‘Genetic Diversity of Highly Pathogenic Avian Influenza A(H5N8/H5N5) Viruses in Italy, 2016–17’, Emerging Infectious Diseases, 23: 1543–7. PubMed PMC

Globig A. et al. (2018) ‘Highly Pathogenic Avian Influenza H5N8 Clade 2.3.4.4b In Germany in 2016/2017’, Frontiers in Veterinary Science, 4: 240.doi: 10.3389/fvets.2017.00240 PubMed DOI PMC

Grear D. A. et al. (2018) ‘Inferring Epidemiologic Dynamics from Viral Evolution: 2014-2015 Eurasian/North American Highly Pathogenic Avian Influenza Viruses Exceed Transmission Threshold, R0 = 1, in Wild Birds and Poultry in North America’, Evolutionary Applications, 11: 547–57. PubMed PMC

Guinat C. et al. (2020a) ‘Biosecurity Risk Factors for Highly Pathogenic Avian Influenza (H5N8) Virus Infection in Duck Farms, France’, Transboundary and Emerging Diseases, 67: 2961–70. PubMed

——— et al. (2020b) ‘Role of Live-Duck Movement Networks in Transmission of Avian Influenza, France, 2016–2017’, Emerging Infectious Diseases, 26: 472–80. PubMed PMC

——— et al. (2018) ‘Exploring the Wind-Borne Spread of Highly Pathogenic Avian Influenza H5N8 during the 2016–2017 Epizootic in France’, Avian Diseases, 63: 246–8. PubMed

——— et al. (2021) ‘What Can Phylodynamics Bring to Animal Health Research?’, Trends in Ecology & Evolution, 36: 837–47. PubMed

Hill N. J. et al. (2016) ‘Transmission of Influenza Reflects Seasonality of Wild Birds across the Annual Cycle’, Ecology Letters, 19: 915–25. PubMed

Iglesias I. et al. (2011) ‘Reproductive Ratio for the Local Spread of Highly Pathogenic Avian Influenza in Wild Bird Populations of Europe, 2005–2008’, Epidemiology and Infection, 139: 99–104. PubMed

Kass R. E., and Raftery A. E. (1995) ‘Bayes Factors’, Journal of the American Statistical Association, 90: 773–95.

Katoh K., and Standley D. M. (2013) ‘MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability’, Molecular Biology and Evolution, 30: 772–80. PubMed PMC

Keawcharoen J. et al. (2008) ‘Wild Ducks as Long-distance Vectors of Highly Pathogenic Avian Influenza Virus (H5N1)’, Emerging Infectious Diseases, 14: 600. PubMed PMC

Kühnert D. et al. (2016) ‘Phylodynamics with Migration: A Computational Framework to Quantify Population Structure from Genomic Data’, Molecular Biology and Evolution, 33: 2102–16. PubMed PMC

Larsson A. (2014) ‘AliView: A Fast and Lightweight Alignment Viewer and Editor for Large Datasets’, Bioinformatics, 30: 3276–8. PubMed PMC

Lemey P. et al. (2014) ‘Unifying Viral Genetics and Human Transportation Data to Predict the Global Transmission Dynamics of Human Influenza H3N2’, PLoS Pathogens, 10: e1003932. PubMed PMC

——— et al. (2009) ‘Bayesian Phylogeography Finds Its Roots’, PLOS Computational Biology, 5: e1000520. PubMed PMC

Leyson C. et al. (2019) ‘Pathogenicity and Genomic Changes of a 2016 European H5N8 Highly Pathogenic Avian Influenza Virus (Clade 2.3. 4.4) In Experimentally Infected Mallards and Chickens’, Virology, 537: 172–85. PubMed PMC

Lycett S. et al. (2016) ‘Global Consortium for H5N8 and Related Influenza Viruses. Role for Migratory Wild Birds in the Global Spread of Avian Influenza H5N8’, Science, 354: 213–7. PubMed PMC

Magee D. et al. (2015) ‘Combining Phylogeography and Spatial Epidemiology to Uncover Predictors of H5N1 Influenza A Virus Diffusion’, Archives of Virology, 160: 215–24. PubMed PMC

Mulatti P. et al. (2018) ‘Integration of Genetic and Epidemiological Data to Infer H5N8 HPAI Virus Transmission Dynamics during the 2016-2017 Epidemic in Italy’, Scientific Reports, 8: 18037. PubMed PMC

Müller N. F., Dudas G., and Stadler T. (2019) ‘Inferring Time-dependent Migration and Coalescence Patterns from Genetic Sequence and Predictor Data in Structured Populations’, Virus Evolution, 5: vez030. PubMed PMC

Müller N. F., Rasmussen D. A., and Stadler T. (2017) ‘The Structured Coalescent and Its Approximations’, Molecular Biology and Evolution, 34: 2970–81. PubMed PMC

Nadeau S. A. et al. (2021) ‘The Origin and Early Spread of SARS-CoV-2 in Europe’, Proceedings of the National Academy of Sciences, 118: 9. PubMed PMC

Nagy A. et al. (2018) ‘Microevolution and Independent Incursions as Main Forces Shaping H5 Hemagglutinin Diversity during a H5N8/H5N5 Highly Pathogenic Avian Influenza Outbreak in Czech Republic in 2017’, Archives of Virology, 163: 2219–24. PubMed

Napp S. et al. (2018) ‘Emergence and Spread of Highly Pathogenic Avian Influenza A(H5N8) in Europe in 2016-2017’, Transboundary and Emerging Diseases, 65: 1217–26. PubMed

Pohlmann A. et al. (2018) ‘Swarm Incursions of Reassortants of Highly Pathogenic Avian Influenza Virus Strains H5N8 and H5N5, Clade 2.3. 4.4 B, Germany, Winter 2016/17’, Scientific Reports, 8: 1–6. PubMed PMC

Rambaut A. et al. (2018) ‘Posterior Summarization in Bayesian Phylogenetics Using Tracer 1.7’, Systematic Biology, 67: 901. PubMed PMC

Scire J. et al. (2020), ‘Phylodynamic Analysis of Genetic Sequencing Data from Structured Populations’, Viruses 2022, 14: 1648. PubMed PMC

Scoizec A. et al. (2018) ‘Airborne Detection of H5N8 Highly Pathogenic Avian Influenza Virus Genome in Poultry Farms, France’, Frontiers in Veterinary Science, 5: 15.doi: 10.3389/fvets.2018.00015 PubMed DOI PMC

Śmietanka K. et al. (2020) ‘Highly Pathogenic Avian Influenza H5N8 in Poland in 2019–2020’, Journal of Veterinary Research, 64: 469. PubMed PMC

Świętoń E., and Śmietanka K. (2018) ‘Phylogenetic and Molecular Analysis of Highly Pathogenic Avian Influenza H5N8 and H5N5 Viruses Detected in Poland in 2016–2017’, Transboundary and Emerging Diseases, 65: 1664–70. PubMed

Team R. C. (2013) R: A Language and Environment for Statistical Computing.

Trovão N. S. et al. (2015) ‘Bayesian Inference Reveals Host-Specific Contributions to the Epidemic Expansion of Influenza A H5N1’, Molecular Biology and Evolution, 32: 3264–75. PubMed PMC

Vaughan T. (2022), BDMM-Prime Package <https://github.com/tgvaughan/BDMM-Prime> accessed Mar 2022.

Vaughan T. G. et al. (2014) ‘Efficient Bayesian Inference under the Structured Coalescent’, Bioinformatics (Oxford, England), 30: 2272–9. PubMed PMC

——— et al. (2019) ‘Estimating Epidemic Incidence and Prevalence from Genomic Data’, Molecular Biology and Evolution, 36: 1804–16. PubMed PMC

Volz E. M., Koelle K., and Bedford T. (2013) ‘Viral Phylodynamics’, PLoS Computational Biology, 9: e1002947. PubMed PMC

Wikipedia . (2021), World Population <https://en.wikipedia.org/wiki/World_population> accessed Jul 2021.

Willgert K. et al. (2020) ‘Transmission of Highly Pathogenic Avian Influenza in the Nomadic Free-grazing Duck Production System in Viet Nam’, Scientific Reports, 10: 1–11. PubMed PMC

Yang J. et al. (2019) ‘Inferring Host Roles in Bayesian Phylodynamics of Global Avian Influenza A Virus H9N2’, Virology, 538: 86–96. PubMed

Yu G. et al. (2017) ‘Ggtree: An R Package for Visualization and Annotation of Phylogenetic Trees with Their Covariates and Other Associated Data’, Methods in Ecology and Evolution, 8: 28–36.