Fresh ideas for human and animal health Animal Influenza Surveillance and Risk Asssessment Petra Muellner 8 January 2015 www.epi-interactive.com
Overview EU-funded projects Project Species covered by the project Area covered by the project Human Pig Poultry Other species Surveillance and risk assessment ConFluTech No Yes Yes Yes Medium EPIZONE Yes Yes Yes Yes Low ESNIP2 No Yes No No High ESNIP3 No Yes No No High FLU-LAB-NET No No Yes Yes High FLURESIST No No Yes No Low FLURISK Yes Yes Yes Yes High FLUTEST No No Yes Yes Medium NEW-FLUBIRD No No No Yes High RISKSUR Yes Yes Yes Yes High www.epi-interactive.com
EU-funded projects FLU-LAB-NET (Mar 2007 Feb 2011) The project enhanced and reinforced the existing Community Reference Laboratory and National Reference Laboratory network for avian influenza within the European Union Member States. FLURESIST (Mar 2007 Feb 2010) Collection of data on trade in treated and fresh poultry commodities and litter. The data collected and parameters calculated could be of value to inform future risk assessment and possibly also provide some baseline information for surveillance. FLUTEST (Feb 2007 Jan 2011) Mathematical models have been developed that can serve as a blueprint for the design of a surveillance program for HPAI as well as for LPAI. Moreover, a risk assessment model has been developed. 3 www.epi-interactive.com
EU-funded projects NEW FLUBIRD (Jan 2007 Dec 2010) An early warning and risk assessment system for the threat posed to animal and human health by avian influenza viruses in migratory birds has been established. RISKSUR (Nov 2012 Oct 2015) The overall aim of RISKSUR is to develop and validate conceptual and decision support frameworks and associated tools for designing efficient risk-based animal health surveillance systems. Case study diseases have been selected such as early detection of HPAI in poultry in UK and measuring (endemic) prevalence in poultry in Vietnam. ConFluTech (Feb 2007 Jan 2011) The main objective of the project was capacity building in target INCO countries with a particular emphasis on those countries which border the EU. 4 www.epi-interactive.com
EU-funded projects EPIZONE (Feb 2007 Jan 2011) The project established a network of excellence on epizootic viral diseases including avian influenza. For avian influenza viruses EU surveillance programmes were improved and harmonised. Also a sequence database 'FLUZONE' for avian influenza was developed, which will provide some baseline data. ESNIP2 / ESNIP 3 (Jan 2006 Oct 2013) Presented by Kristien Van Reeth FLURISK (Dec 2012 Oct 2013) Presented by Giovanni Cattoli and Sophie Von Dobschuetz 5 www.epi-interactive.com
ESNIP 2: European Surveillance Network for Influenza in Pigs 2 (2006-08) Co-ordination action, 11 partners FLUPIG: Pathogenesis and transmission of influenza in pigs (2010-14) Research project, 10 partners Prof. Kristien Van Reeth, Ghent University, Belgium
Review of influenza A virus in swine worldwide Zoonoses and Public Health 2013, Amy Vincent and members of the OFFLU SN group
Review of influenza A virus in swine worldwide Zoonoses and Public Health 2013, Amy Vincent and Concurrent circulation of H1N1, H3N2, H1N2, multiple lineages members of the OFFLU SN group Distinct SIV lineages in North America, Europe, Asia, regional differences Human and avian viruses repeatedly transmit to pigs, adaptation to pigs by reassortment/mutations Pigs as reservoirs for older human (and avian) virus genes
ESNIP2 Aims Virological and serological surveillance Expand knowledge on the epidemiology and evolution of SIVs in Europe with the purpose to improve the control and diagnosis of SI Antigenic characterization Update of classical diagnostic techniques and develop a rapid test for detection and subtyping Expansion of the virus bank, electronic database and website Serological screening of swine for avian influenza viruses Interaction between swine, avian and human influenza surveillance networks To gain insights into the public health risks of influenza in swine
Achievements Standard protocols and ring trials A virus bank with 54 isolates from 11 countries Genetic and antigenic characterization of isolates Data about (sero)prevalence of various SIV subtypes in Belgium, France, Italy, Spain and UK Challenges Voluntary participation of swine producers and veterinarians Serological surveillance needs careful design and interpretation Limited government support for non-reportable diseases
Swine-adapted viruses only occasionally infect people: Incidence unknown Mostly dead-end 2009 pandemic H1N1 virus is an exception: Human-to-human transmission Underlying mechanisms largely unknown AIM OF FLUPIG Gain insights into the role of pigs in the overall influenza ecology and specifically in the generation of human pandemic viruses
Q1. What makes avian influenza virus adapted to pigs? Q2. between pigs? What determines transmissibility? Q3. from pigs to other relevant species? Q4. between humans (ferret as a model)?
Some lessons from the FLUPIG project Mutations in avian virus (10-25 serial passages) or reassortment made it more adapted to pigs but were insufficient for fully adapted virus A change in receptor specificity alone doesn t make an avian virus swine adapted Pigs made avian virus more human-like in terms of receptorspecificity, less human-like in terms of fusion Pigs don t select for same mutations as humans Avian viruses replicate better in ferret than in pig Adaptation of an avian virus to pigs may make it less adapted to birds A challenge to study virus adaptation and transmission in an experimental setting
The FLURISK Project Sophie von Dobschuetz, Gwenaelle Dauphin EMPRES-Animal Health Food and Agriculture Organization (FAO) Rome, Italy Marco De Nardi, Giovanni Cattoli IZSVe, Padova, Italy Animal Influenza Workshop at EFSA: 8-9 January 2015, Parma
Outline Overview of the FLURISK project: Overall Objective of FLURISK Central Questions External Advisors / Invited Experts Project Structure Work Packages 1-4 and Related Activities FAO Proposal Integration of the FLURISK IRAF with FAO Databases External Evaluation of Influenza Risk Assessment Tools
Outline Overview of the FLURISK project: Overall Objective of FLURISK Central Questions FLURISK Project Consortium External Advisors / Invited Experts Project Structure Work Packages 1-4 and Related Activities FAO Proposal Integration of the FLURISK IRAF with FAO Databases External Evaluation of Influenza Risk Assessment Tools
Overall Objective of FLURISK Several meetings in 2010 and 2011: One Health approach One Flu Strategic Retreat in Castelbrando, Italy Operationalizing One Health Meeting in Stone Mountain, Georgia FAO/OIE/WHO Joint Scientific Consultation in Verona, Italy Recommendations: a greater understanding of influenza viruses is needed in order to improve the ability to systematically assess a potential public health threat In 2011 EFSA called for the development and validation of an influenza risk assessment framework (IRAF) to rank animal influenza A strains in their potential to cross the species barrier and cause human infection EFSA encouraged the consortium to develop a general methodological framework enabling the assessment of the zoonotic potential of ANY animal influenza virus
Central Questions What is the current knowledge on the influenza virus etiology and epidemiology in pigs, birds and other animals (i.e. cats, dogs, horses)? What are the scientific community and institutional stakeholders doing in terms of influenza virus surveillance, monitoring and control? What are the scientific gaps still present to be addressed? What are the characteristics which an animal influenza A virus must possess to be potentially pandemic? How can we grade the pandemic risk posed by a given animal influenza A virus?
External Advisors / Invited Experts: Food and Agriculture Organization of the United Nations (FAO) Influenza Division of the Centers for Disease Control and Prevention (CDC) European Food Safety Authority (EFSA) European Centers for Disease Control (ECDC) World Organization for Animal Health (OIE), World Health Organization (WHO) OIE/FAO Network of expertise on Animal Influenza (OFFLU)
FLURISK Project Structure WP1: Data collection and validation WP2: Building the model WP3: Gap analysis WP4: Coordination
p i = Farm Incidence E and I = chicken population densities (extensive vs intensive) w = contact ratios R i = Likelihood of more than one human infection V i = Virus score URF = underreporting factor = Epidemiological component of probability of effective contact Poisson risk model for a defined spatial area domestic chicken only
Outline Overview of the FLURISK project: Overall Objective of FLURISK Central Questions FLURISK Project Consortium External Advisors / Invited Experts Project Structure Work Packages 1-4 and Related Activities FAO s Proposal Integration of the FLURISK IRAF with FAO Databases External Evaluation of Influenza Risk Assessment Tools
Integration of the FLURISK IRAF with FAO Databases FAO, as external advisor to the project, was involved in the IRAF development from the very beginning. FAO data were utilized to parameterize the IRAF: animal influenza outbreak data, including genetic information, from EMPRES-i animal species population density by production systems from the EPT+ project survey on influenza surveillance systems in animals FAO offered to host the IRAF tool and maintain, further validate and make it available to the international community.
Integration of the FLURISK IRAF with Formal endorsement of FAO s offer by EFSA and the FLURISK consortium Funding required for human resources IRAF integration with FAO databases user interface and access restriction FAO Databases coordination of future data flow and interaction between partners; define responsibilities development of standard operating procedures for the use of the tool and communication of results External evaluation of the tool guided by the OFFLU applied epidemiological group; this could include other influenza RA tools
External Evaluation of Influenza Risk Assessment Tools FLURISK: Influenza Risk Assessment Framework (IRAF) to rank viruses according to their (relative) ability to cross the species barrier and infect at least 1 human CDC: Influenza Risk Assessment Tool (IRAT) to assess the potential pandemic risk posed by influenza A viruses that currently circulate in animals but not in humans, based on two different scenarios: emergence and public health impact FAO/USAID: Emerging Pandemic Threats Plus (EPT+) to identify drivers of influenza emergence at the livestock-wildlife-human interface, with one outcome being a real-time risk model
FLURISK Project Consortium Coordinator: Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe) ITALY P1: Animal Health and Veterinary Laboratory Agency (AHVLA) UNITED KINGDOM P2: Royal Veterinary College (RVC) UNITED KINGDOM Kick Off meeting Legnaro, February 2012 Thank You! P3: National Institute for Public Health and the Environment (RIVM) NETHERLANDS P4: Pasteur Institute (IP)- FRANCE P5: Ghent University (UGent) BELGIUM
State of the art Integration much needed The overarching theme Integration across all animal species One Health approach Integration across the transmission continuum Data sharing Integrated risk assessment & integrated epidemiological analysis (epidemiological, molecular, animal and human health data ) 31 www.epi-interactive.com
State of the art Surveillance The ability to identify and characterize Influenza A viruses circulating in animals is a prerequisite for preparedness. Surveillance in animals is mostly driven by the objective of safeguarding production animal health and international trade. Surveillance activities therefore currently mainly target known viruses notifiable to the World Organisation for Animal Health (OIE). For an influenza surveillance system to detect the emergence of a potentially zoonotic virus in a timely way, it should be anticipatory rather an reactive. Need for prioritisation / risk-based approaches Furthermore any surveillance activity should be placed, coupled with timely communication of results, including genetic sequence data, to national and international stakeholders. 32 www.epi-interactive.com
State of the art Risk assessment and epidemiology Specific risk assessment tools have been developed which in a next step could be further validated and integrated with existing surveillance systems. >> FLURISK / Influenza Risk Assessment Tool (IRAT) Many data gaps for risk assessment on AI still exist. Much of our understanding of risk factors for spread of influenza viruses within animal populations and transmission of virus from animals to humans is restricted to H5N1 HPAI in poultry populations. Molecular epidemiology increasingly used to bring together phylogenetic data with information on space, time and host species. Increased use of models (transmission, control ) 33 www.epi-interactive.com
Knowledge and data gaps key findings of previous research There is a need for: efficient sampling methods rapid detection of emerging new strains identifying high pathogenic influenza virus in animals and influenza viruses with zoonotic infection and/or pandemic potential. Assure support from stakeholders for monitoring or surveillance activities (social science) Infrastructure funding necessary Open data use Scope beyond EU for research projects, global approach needed for research projects Virus bank in combination with database must be maintained 34 www.epi-interactive.com
Knowledge and data gaps key findings of previous research A permanent need to monitor and report virus evolution in different species: A permanent system is needed to regularly analyze and report results of sequencing efforts on a single gene or whole virus genome level to monitor virus evolution in avian, swine and equine populations. Integrated, permanent worldwide interoperable database needed, e.g. mirroring NIH database Routine testing is required to screen for potentially pandemic viruses and data should be reported timely. Need to characterize viruses from new outbreaks and collect detailed epidemiological, genomic, antigenic and phenotypic information. Strengthen collaboration between public health and veterinary services (One Health approach). 35 www.epi-interactive.com
Knowledge and data gaps key findings of previous research Further development of methodologies to analyze virus evolution, estimate risks and simulate possible scenarios and to inform decision making: Standardization of definitions, data collection and data storage at global level. Continuation of databases across & beyond projects Need for (systematic) application of molecular epidemiology by combining time, geographic location and phylogenetic data, linked with diagnostics and bioinformatics. Integration and validation of risk assessment frameworks. Further develop modeling approaches to simulate possible scenarios to inform policy decisions. Fill most important data gaps that impair decision making, e.g. link between experimental and surveillance data with specific respect to viral and host determinants adaptation 36 www.epi-interactive.com
DAY 2 37 www.epi-interactive.com
Possible research topics based on previous initiatives (OFFLU/STAR-IDAZ workshop April 2014) Short-term applied research priorities: Develop effective systems for monitoring influenza viruses in animals and in people at the animal-human interface. Understand the viral, environmental and socioeconomic factors associated with zoonotic and interspecies transmission. 38 www.epi-interactive.com
Possible research topics based on previous initiatives (OFFLU/STAR-IDAZ workshop April 2014) Longer-term applied research priorities: Generate real time data on subtypes and strains of circulating influenza viruses and their prevalence, to guide disease prevention and control. Identify the risk factors associated with international travel that increase virus shedding by vaccinated horses. Establish complete data on influenza virus strains that are circulating globally and determine their impact on animal health and welfare in different populations of equidae including working animals in developing countries. Obtain a complete global picture (including data about genotype and phenotype) of influenza viruses circulating in swine through improved coordination in approaches to surveillance and sharing of data. www.epi-interactive.com 39
Possible research topics based on previous initiatives (OFFLU/STAR-IDAZ workshop April 2014) Longer-term applied research priorities: Determine the processes involved in transmission of influenza viruses within human and swine populations, between human and swine populations (bidirectional), and the adaptation of influenza viruses to either species. Comprehensive integration and data mining of laboratory and field data (pathogenesis, virus sequence, field metadata, production data) with coordinated analysis that will provide digested information to allow more effective risk and source attribution, surveillance, prevention and control of avian influenza. Identify and model risk factors for influenza transmission between wild birds and poultry in different ecological settings, including the socioeconomic and human cultural aspects that contribute to or reduce such transmission. www.epi-interactive.com 40
Possible research topics based on previous initiatives (OFFLU/STAR-IDAZ workshop April 2014) Priority basic research: Identify viral determinants that influence interspecies transmission, and introduce surveillance at the interfaces between species. Analyze and describe the ecology and evolution of animal influenza viruses in all species. Identify the determinants of key phenotypes of animal influenza viruses including the virulence and pathogenicity to different animals, receptor specificity, antigenic properties, transmissibility in different animals, host range. Develop a predictive understanding of the link between genetic sequence data and all other available metadata (epidemiological, pathological, structural, etc.) as the basis for genetic sequence-based risk assessment. 41 www.epi-interactive.com
Possible additional research topics based on review of previous EU initiatives Many additional topics of interest were identified by previous research. The next slides show a selection as a basis for further discussion in the breakout groups. 42 www.epi-interactive.com
Possible additional research topics based on review of previous EU initiatives Molecular-level (stratified) assessment of risk factors for transmission as well as zoonotic and pandemic potential. Targeted / sentinel / risk-based activities where background risk is high or to elucidate certain aspects of transmission and virus evolution on a finer scale. Development of truly integrated surveillance systems (multi country, multispecies, epidemiological metadata combined with sequence data) with sufficient analytical and reporting/early warning capacity. 43 www.epi-interactive.com
Possible additional research topics based on review of previous EU initiatives Conduct epidemiological surveys at regular intervals in densely populated animals and human areas to determine swine influenza virus prevalence and different subtypes circulation patterns. Conduct targeted surveillance in animal populations to monitor evolution and circulation of potentially novel viruses with yet unknown public health risks, to be prepared for a potentially emerging influenza virus of animal origin in humans. Conduct active surveillance at the human-animal interface, targeting groups of people amongst the general population that are at higher risk of being infected with animal influenza viruses. 44 www.epi-interactive.com
Possible additional research topics based on review of previous EU initiatives Toolset of epidemiological analyses, risk assessment and modelling methodologies that specifically integrate virus- or molecular-level information (including WGS). Development of virus-level screening tools for human-pathogenicity when zoonotic potential is suspected (incl. possible extension of FLURISK triage approach). This could also include a systematic approach to review and select those characteristics (e.g. genetic similarity, host/species specificity, time and place, pathogenicity) that define an influenza strain in the first place. There is a need to provide useful scientific information from animal influenza surveillance systems to determine the significance of virus evolution and identification of viruses with epizootic and/or pandemic potential. 45 www.epi-interactive.com
Possible additional research topics based on review of previous EU initiatives There is a need to develop predictive tools for rapid identification and appropriate response to emerging animal influenza virus strains. A permanent system is needed to regularly analyze and report results of sequencing efforts on a single gene or whole virus genome level to monitor virus evolution. A permanent system is needed to regularly evaluate the antigenic consequences of genetic diversity and making recommendations for vaccine strain composition. 46 www.epi-interactive.com