Published on March 14, 2008
Guidance on antimicrobials and risk assessment:The OIE perspective: Guidance on antimicrobials and risk assessment: The OIE perspective Jacques Acar M.D Emeritus Professor of Microbiology Slide2: Since the Swann report 1969… The contribution of the use of antibiotics in animals to resistant bacteria in humans, was debated 1987: Vancomycin resistance in human isolates of Enterococci (after more than 20 years of use) 1993: Animal isolates resistant to avoparcin 1997: Ban of avoparcin animal use (EU) 1997–2004: Experiences of restriction of antibiotic use in animals; expert consultations; guidelines, codes of practice: national and international organisations Global ‘Authority’Reports/Recommendations (few examples): Global ‘Authority’ Reports/Recommendations (few examples) OIE (AR recommendations) FAO/Codex WHO (Berlin, FQ, Global Principles of Containment, Use Monitoring) Europe (CVMP, EU SSC, UK CMSF, UK H. Lords, Microbial Threat, etc.) Australia (JETACAR) US (NRC, CDC, CVM, GAO, IOM, etc.) Canada (Adv. Com. Report, CCAR) Japan Slide4: World Organisation for Animal Health created in 1924 in Paris Americas: 29 – Africa: 50 – Europe: 49 – Middle East: 13 – Asia: 26 OIE 167 Member Countries Objectives: Objectives To ensure transparency in the global animal disease and zoonosis situation To collect, analyse and disseminate scientific veterinary information Within its mandate under the WTO SPS Agreement, to safeguard world trade by publishing health standards for international trade in animals and animal products To provide a better guarantee of the safety of food of animal origin and to promote animal welfare through a science-based approach To provide expertise and encourage international solidarity in the control of animal diseases . To improve the legal framework and resources of national Veterinary Services Early investigation in Member Countries: Early investigation in Member Countries Evaluation of veterinary services surveillance and monitoring Establish a baseline of information on animal health necessary for a science-based approach to measure the risk of antimicrobial resistant zoonotic bacteria to human health (monitoring of quantities of antibiotics used in animals, surveillance programmes for antimicrobial resistance in food animals, guidelines on prudent use of antimicrobials) Develop risk analysis methodology for adressing the problem of the impact on humans and animals of antimicrobial resistant bacteria caused by the use of antimicrobials in food animals OIE Approach: OIE Approach Terrestrial Animal Health Code 2004 Guidelines for the harmonisation of antimicrobial resistance surveillance and monitoring programmes Guidelines for the monitoring of the quantities of antimicrobials used in animal husbandry Guidelines for the responsible and prudent use of antimicrobial agents in veterinary medicine Objectives of antimicrobial resistance surveillance and monitoring programmes: Follow trends in antimicrobial resistance in bacteria Integration to human surveillance date Help detection of emergence of new antimicrobial resistance (new antibiotic – new mechanism) Provide a basis for policy recommendations for animal and public health Provide information for prudent use recommendations and better efficacy of prescription Provide data for conducting risk analysis Objectives of antimicrobial resistance surveillance and monitoring programmes Objectives of monitoring the quantitiesof antimicrobial used in animal husbandry: Objectives of monitoring the quantities of antimicrobial used in animal husbandry Quantitative information on usage patterns, including potency and type of use. These data can be used for: Interpreting surveillance data on resistance Targeted response to problems of antimicrobial resistance Evaluating the effectiveness of prudent use guidelines Conducting Risk Analysis and planning Application of risk analysis process(Covello and Merkhofer system) to antimicrobial resistance – Code 2005: Hazard Identification Risk Assessment Risk Management Risk Communication Application of risk analysis process (Covello and Merkhofer system) to antimicrobial resistance – Code 2005 Hazard identification: Hazard identification The process of identifying the determinant that emerges as a result of the use of a specific antimicrobial in animals: the resistance determinant may be or in a specific zoonotic bacteria, or may be passed from one species of bacteria to another The hazard might produce adverse consequences through any scenario that could expose HUMANS, or ANIMALS, to the resistant pathogens Analysis of risks from antimicrobial resistant bacteria from animal origin should be applied :: Analysis of risks from antimicrobial resistant bacteria from animal origin should be applied : To human health As well to animal health The Risk Assessment: The Risk Assessment Release assessment: describes and quantifies the process linking the use of a specific antimicrobial in animals and the direct or indirect emergence of the resistant pathogen (Bacterial species; animal species; genetic mechanism of the resistance; dosage and administration of a particular antibiotic) Exposure assessment: describes the pathways by which the resistant bacteria colonise/infect a human population or an animal population (cycling of resistant bacteria; microbial load…) The Risk Assessment (2): The Risk Assessment (2) Consequence assessment: adverse health and/or environmental consequences (wide range incompletely explored; loss of efficacy of antimicrobials; number of ill people; severity of disease; economic costs) Risk estimation: integrate the results of the previous steps (scale consequences to allow weighted summation) Risk Management: Risk Management Risk management policy – a framework for monitoring, measuring, assessing and managing the risk involved in the use of antimicrobials in food-producing animals. The risk management policy should be established at the beginning of the process of risk analysis. Risk management components: Risk evaluation Options/evaluation Process of implementation Monitoring and review programme When data are insufficient or inadequate to answer the risk question, the risk decision is temporary Risk Communication: Risk Communication Interactive exchange of information on risk among risk assessors, risk managers, and other interested parties (stakeholders) Programme to establish EARLY from the intention to perform a risk analysis to the implementation of the risk management decisions Risk Communication (2): Risk Communication (2) Promote awareness and understanding of the specific issues Promote consistency and transparency in implementing risk management decisions Provide sound basis for understanding the risk management decisions implemented Improve effectiveness/efficiency of the process Strengthen working relationships among participants Promote appropriate involvement of stakeholders Exchange information concerning the risk at hand OIE Recommendations: OIE Recommendations Risk assessment should be objective and defensible Process should be transparent and consistent Risk management and risk assessment functions should be separate to ensure independence of decision making and evaluation of the risk Risk management should be conducted using a policy framework that sets the domain of the regulator and range of risk reduction actions to consider OIE Recommendations (2): OIE Recommendations (2) Risk assessment should be based on sound science and conducted according to a strategy developed with managers and assessors Qualitative risk assessment should be undertaken and provide information on whether full quantitative or semi-quantitative risk assessment is feasible or necessary Help developing countries develop/access skills required for risk assessment – Harmonisation effort Communication among managers, assessors and stakeholders is essential Slide20: Developping science, fairly new Different methods: farm to fork – top-down approach Different models to describe bio-pathways: differents variables: antibiotic to resistance marker (bacteria) resistant strains from animals to human colonisation and infection Broad range of human health impacts and animal health impact Qualitative, semiquantitative, quantitative studies Risk analysis applied to antimicrobial resistant bacteria Slide21: CVM FDA guidance (based on OIE guidelines) – possible use of qualitative approach and possible development In USA, Europe and Australia: 2 qualitative studies 3 quantitative studies 2 semiquantative studies Identification of problems, or special factors to be considered: Identification of problems, or special factors to be considered Resistance determinant – Microorganism: clonal spread vs horizontal and clonal spread Microbial population Density ; Load Mixture of resistant and susceptible subpopulations Bacterial variability (serotypes, phenotypes…) affect uncertainty (duration of the study) Identification of problems, or special factors to be considered (contd): Identification of problems, or special factors to be considered (contd) Complexity of resistance mechanisms: More than one for an antibiotic Cross resistance Co-resistance Linkage of resistance determinant to fitness, to virulence… Relation between commensals and pathogens Complex pathways (methods for risk attribution) Environmental factors Transmission (animals, farmers, humans, environmental) in both direction Food processing; preparation… Other sources of contamination than food Other origin of contamination (travel) Slide24: Choose the most appropriate type of study according available data (identification of key data needs for further development. Methods and models will evolve as more adequate information will become available Importance to recognize essential antibiotics for humans as well for animals – Threshold of resistance (alert) Optimize the use of existing surveillance systems (bacteria; antimicrobial resistance; infections; outcome of treatment…) in humans and animals Give chance for risk assessors, microbiologists and risk managers to work more closely together Slide25: Not as Mark Twain once said: “Researchers have already cast much darkness on this subject. If they continue their investigations we shall soon know nothing at all”.