Tripartite M&E Animal Use Consultation – September 2017

Tripartite Monitoring and Evaluation Framework Consultation – Animal Use of Antibiotics

We appreciate the opportunity to share this input for the public consultation on the Tripartite Monitoring and Evaluation (M&E) to the Global Action Plan on Antimicrobial Resistance. To ensure a One Health approach to tackling AMR, the indicators for M&E must similarly benchmark progress on the use of antibiotics in the agricultural sector and capture the effect of antibiotic discharge into the environment. Data should be collected in a way whereby the impact of interventions on reducing antibiotic use and reduced resistance can be tracked. Several members of the Antibiotic Resistance Coalition (ARC) have worked together to offer a civil society perspective on the proposed indicators relating to the non-human use of antibiotics.

 

Disparate impact across differently resourced countries

Countries differ in the size of their livestock industry, their level of exports or imports of food animal products, the availability of a trained veterinary workforce, the presence of indigenous pharmaceutical production facilities, and their resources to implement regulatory efforts. So the same rules applied to these differing circumstances can result in disparate impact across these various settings. This local context will influence the level of technical and financial resources required for meeting targeted benchmarks for monitoring and evaluation.

The indicators themselves can be designed with these differences among countries in mind. Rather than a “one size fits all” approach, indicators might be tiered, taking into account the country’s stage of development or level of resources. A tiered approach could lay out a series of steppingstones, with expectations growing as local infrastructure and capacity do and as external technical and financial support is received. By tiering indicators, lower-resourced countries might participate in the global reporting system at an earlier stage. To be clear, we are not suggesting that a tiered approach should enable some countries to delay or even not to commit to targets of eliminating routine preventative use.

The country context also plays an important role. If the country has a major livestock or aquaculture industry, its potential contribution to the global burden of AMR may be commensurately greater. Similarly, if the country is a major pharmaceutical producer, the manufacturing of active pharmaceutical ingredients (APIs) could pose a significant source of environmental discharge of antibiotics. Nonetheless, wastewater discharge from manufacturing plants is a fraction of what goes into the downstream use of antibiotics. So environmental measures need to go beyond API manufacturing plants and consider point source pollution from hospitals and agricultural run-off from factory farms.

The time horizon for these monitoring indicators also is of consequence. A dearth of technical and/or financial resources might make it difficult for a country to comply with a global monitoring system. The Tripartite agencies might also specify what subset of proposed indicators would be critical for report back within the differing time horizons for NAPs, the three-year mandate for the IACG and its report back to the UNGA, and general timeframe of 5-10 years. With the three-year mandate for the IACG and its report back to the UNGA, some near-term indicators should be included to demonstrate momentum and early milestones achieved in tackling AMR globally.

 

Accountability

In curbing the use of antibiotics in food animal production, several strategic approaches exist: 1) requiring veterinary oversight and prescription; 2) restricting the use of antibiotics for certain indications, such as growth promotion, routine preventative use, and routine metaphylaxis use; and 3) reducing or removing the use in agriculture of antibiotics that are critically important antibiotics for human medicine.

Requiring veterinary oversight and prescription affords some assurances that trained personnel would oversee the use of antibiotics in food animal production, and accordingly, serve as a check on unnecessary use of these drugs. However, where there are few veterinarians, this may not be a practical step. Means to extend the reach of available veterinarians, either by enabling those available to work with other paraprofessionals or a tele-veterinary network, might need to be piloted. Where veterinarians are employed or are employed by companies in the food production system, the independence of their judgment also may need to be verified.

A serious obstacle to ensuring accountability is the failure to include routine preventative use of antibiotics as part of non-therapeutic use of antibiotics in animal husbandry and aquaculture. The WHO Global Action Plan calls for “research to identify alternatives to nontherapeutic uses of antimicrobial agents in agriculture and aquaculture, including their use for growth promotion and crop protection”.[1] Under Member State action, it describes the need for “policies on use of antimicrobial agents in terrestrial and aquatic animals and agriculture, including: implementation of Codex Alimentarius and OIE international standards and guidelines as well as WHO/OIE guidance on the use of critically important antibiotics; phasing out of use of antibiotics for animal growth promotion and crop protection in the absence of risk analysis; and reduction in nontherapeutic use of antimicrobial medicines in animal health.”[2] This definition of therapeutic use as limited to “treating an animal(s) with a clinically diagnosed infectious disease or illness” is part of Codex Alimentarius’ Code of Practice to Minimize and Contain Antimicrobial Resistance.[3] 74% of countries have already banned antibiotics for growth promotion. Given the European experience, expanding that list of countries curbing growth promotion would not alone make a significant difference. In the Netherlands, growth promoters were banned according to the EU timetable, that is, avoparcin in April 1997, seven more growth promoters banned on 1 July 1999 and the remaining four on 1 January 2006. This action did not lead to very significant reductions in use, and in fact by 2006 and 2007, antibiotic usage was around the same level as it had been in 1998 or 1999. In 2006, the Dutch Minister for Agriculture discussed fining veterinarians that prescribed preventatively, presumably off-label at that time. Only in 2011 were indications for preventative group treatments removed from Dutch farm antibiotic products. This proved to be the key to reducing overall use: between 2007 and 2015, total use of antibiotics for food animal production in the Netherlands fell from 590 to 207 tonnes. Five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) and the Netherlands have all ended routine preventative group treatments with antibiotics, and these countries have lower than average use of these drugs compared to European countries still permitting preventative group treatments. We need a consistent definition of non-therapeutic use of antibiotics that includes preventative group treatments. By contrast, OIE defines all preventative use as therapeutic. This needs to be corrected and made consistent with the European experience. Moreover, the current M&E document does not discuss curbing or eliminating non-therapeutic use that includes preventative use of antibiotics in food animal production, and clearly curbing growth promotion alone will be insufficient.

Collecting farm and veterinary prescription data on antibiotic use, sales, and resistance patterns, by livestock species and country, would be critical in monitoring effectively global progress on meeting One Health goals in tackling AMR. These data must not only be collected, but they also must be made transparent to policymakers and the public. OIE has received data from 89 countries,[4] but complete data have not been published.[5] As has been seen with colistin—a last-line defense against drug-resistant infections in human medicine—the OIE has received multiple Voluntary National Reports confirming its continued use, yet the identity of these countries has not been publicly released.[6] The concern is that countries may be reluctant to share such data in a global reporting system if these findings were made public. The value of such monitoring is not alone in its data collection, but in how its public reporting drives policy change. By adopting a measure that captures a country’s transparency in releasing such data, we might begin to encourage the sharing of such data more rapidly. This is a key steppingstone to ensuring greater accountability.

Several indicators capture the growing conditions that predispose to greater or more inappropriate use of antibiotics. Indicators of intensive farming should distinguish between internal biosecurity (that is, how disease spreads within the farm) and external biosecurity (that is, how disease spreads between farms and between farms and the environment) concerns. Open grazing of cattle, for example, might raise more external biosecurity concerns, but fewer internal biosecurity issues. Dense growing conditions can raise internal biosecurity concerns prompting mass medication of the herd. Consideration should be given, within the relevant indicators, to the relationship between livestock rearing practices or systems and the need for antibiotic administration – particularly in relation to husbandry methods which encourage the development of good immune systems in farm animals. The testing of antibiotic residues in food animal products is important to gauge whether withdrawal periods are not being respected. The data capture of drug-resistant pathogens also complements this picture. The route of administration is also a useful, complementary measure. The OIE recommends that antibiotics critically important in both human and animal medicine “Not to be used as preventive treatment applied by feed or water in the absence of clinical signs in the animal(s) to be treated.” [7]



Need for Regulation, not Recommendations

Similarly, curbing the use of antibiotics critically important to human medicine is an important goal. But recommendations may not go far enough. Regulation is needed, and so one measure might focus on the presence of such legally enforced regulation. The U.S. FDA prohibits the “extralabel” or unapproved use of the highest priority critically important antibiotic class cephalosporins in cattle, swine, chickens and turkey for both growth promotion and disease prevention, but allows their use for disease treatment and control.[8]Much more might be done. The British Veterinary Association published guidelines that recommended restricted use of certain antibiotic classes in 2009,[9] yet in the following and subsequent years, the highest ever use of these antibiotics were reported.[10] In contrast, the introduction of legislation in the Netherlands has had a major impact in reducing the use of the critically important antibiotics. Since January 2013, an EMA/EFSA report notes that in the Netherlands “veterinarians have been obliged by legislation to perform bacteriological and susceptibility testing before prescribing 3rd– and 4th– generation cephalosporins and fluoroquinolones. Various quality assurance systems anticipated this by restricting or prohibiting the use of these substances: the pig sector voluntarily restricted use of 3rd– and 4th– generation cephalosporins and fluoroquinolones and the dairy sector banned the use of 3rd– and 4th-generation cephalosporins for dry cow treatment (see PUAVM Guidelines).”[11] This legislative action, the knowledge that this was forthcoming, and some binding restrictions since 2011 led to huge declines in the use of critically important antibiotics.[12]Dutch sales data saw total veterinary use of fluoroquinolones fall by 78% since 2011, and the total use of 3rdand 4th generation cephalosporins fell by 99.8% in that time period as well.[13] Reducing sales volumes of medically important antibiotics should be included in the goals for the next five years.

The removal of antibiotics critically important to human medicine from food animal production still may overlook concerns over co-selection, whereby the use of an antibiotic selects for resistance to antibiotics not only in its family, but also in other families. So the overarching aim should not be just to curb the use of antibiotics critically important to human medicine, but to reduce the use of all antibiotics.

 

Innovation

There are targeted areas where R&D into alternatives to antibiotics, including more sustainable agricultural practices, would be welcomed and should be measured. In particular, such R&D should capture the best practices that enable livestock farming capable of ensuring both high greater welfare for animals and lower use of antibiotics. Implementation research should work to encourage uptake of such practices, and the speed of such uptake could also be a measurable indicator. However, implementing what we already know about sustainable agricultural practices, less reliant on antibiotic use, also requires implementation research.

 

Topline Indicators

We would highlight several areas for priority indicator development on the food animal production side:

  • How many countries have effective controls on use of antimicrobials (either licensing or import controls that limit imports antibiotics consistent with international guidance, that is, not for growth promotion and not administered for disease prevention in feed or water)? Is there also effective enforcement in place? Are there differences between production for export and for domestic consumption?
  • What countries have eliminated all use of medically important antibiotics for growth promotion, not just some use? This should be distinguished from not authorizing for use to accurately report countries that do not require authorization for antibiotic use. For countries that still allow the use of antibiotics for growth promotion, reporting what drugs are used and whether they are of importance in human medicine is important.
  • What countries have taken concrete steps to reduce other non-therapeutic use, that is, for routine disease prevention? What specific steps have been taken to accomplish this (prohibit all use, restrict extra-label use, prohibit use for certain classes such as the critically important)? Which countries have banned preventative group treatments?
  • What steps have country governments taken to regulate the mass administration of antibiotics in medicated feed or aqueous solution? The availability and use of antibiotics in medicated feed or in aqueous solution for mass administration often signals the use of such antibiotics for growth promotion or routine preventative use, both non-therapeutic indications. Two indicators that would enable policymakers to assess this problem would be 1) the availability of antibiotics premixed in feed or aqueous solution on the local market and 2) legal or regulatory statutes that prevent the import, production, or sale of antibiotics premixed in feed or aqueous solution for purposes of growth promotion or routine preventative use.
  • What have countries done to address highest priority, critically important antimicrobials (prohibit use, prohibit extra/off label and preventive use, set targets for reduction)? Countries should provide information on steps taken for all included classes. The WHO CIA list was created to guide risk management, and the Codex Alimentarius has created a document describing how countries should manage risk in the food chain.[xiv] Since these are two of the major documents laying out the international response to AMR, there should be monitoring of their adoption.
  • How many countries have set up integrated surveillance systems for both use and resistance, and of these, how many have included making data public to civil society? This should include monitoring of zoonosis. The document only mentions Salmonella at the global monitoring level and only mentions specifically monitoring coli and select animal pathogens at the country level. It does not mention colistin anywhere.  At the least, the extent to which countries should monitor for resistance to highest priority antibiotics in organisms likely to be transferred from animals to humans. (Salmonella, Campylobacter, E. coli, and Enterococci) should be measured. The extent to which countries use and for what purposes (treatment, control, prevention, and growth promotion) of the highest priority critically important antibiotics should also be reported.
  • Complementing the surveillance system for drug-resistant pathogens, what steps have country governments taken to collect data on antibiotic use and indication, by livestock type and by farming operation and veterinarian? The Yellow Card system in Denmark demonstrates how such profiling data on individual farm operations and veterinarians can be used by governments to target outliers in the level of antibiotic usage and help support corrective steps to minimize the excessive use of antibiotics in food animal production. The corresponding indicator would be to determine whether the government does or does not collect such profiling data on farming operations and veterinarians in the country.

 

Supported by:

Alliance to Save Our Antibiotics (Coilin Nunan)

Centre for Science and Environment (Amit Khurana)

Food Animal Concerns Trust (Steve Roach)

Heath Care Without Harm (Anja Leetz)

Sustainable Food Trust (Richard Young)

ReAct:

ReAct Africa Node (Mirfin Mpundu)

ReAct Asia Pacific (Sujith Chandy)

ReAct Europe (Anna Zorzet)

ReAct Latin America (Arturo Quizhpe)

ReAct North America/Strategic Policy Program (Anthony So)

 

 

[1] WHO, GLOBAL ACTION PLAN ON ANTIMICROBIAL RESISTANCE, 2015. Page 9. Available at: http://apps.who.int/iris/bitstream/10665/193736/1/9789241509763_eng.pdf?ua=1

[2] WHO, GLOBAL ACTION PLAN ON ANTIMICROBIAL RESISTANCE, 2015. Page 18. Available at: http://apps.who.int/iris/bitstream/10665/193736/1/9789241509763_eng.pdf?ua=1

[3] Codex Alimentarius. Code of Practice to Minimize and Contain Antimicrobial Resistance, CAC/RCP 61-2005. Available at: www.fao.org/input/download/standards/10213/CXP_061e.pdf

[4] OIE, Outcomes from the OIE’s questionnaire on antimicrobial use in animals in 2015, 2016. Page 3. Available at: http://www.oie.int/fileadmin/Home/eng/Our_scientific_expertise/docs/pdf/AMR/A_Bull_2016-3_Moulin.pdf

[5] OIE, OIE Annual report on the use of antimicrobial agents in animals BETTER UNDERSTANDING OF THE GLOBAL SITUATION, 2016. Available at: http://www.oie.int/fileadmin/Home/fr/Our_scientific_expertise/docs/pdf/AMR/Survey_on_monitoring_antimicrobial_agents_Dec2016.pdf

[6] OIE, Outcomes from the OIE’s questionnaire on antimicrobial use in animals in 2015, 2016. Page 3. Available at: http://www.oie.int/fileadmin/Home/eng/Our_scientific_expertise/docs/pdf/AMR/A_Bull_2016-3_Moulin.pdf

[7] OIE, LIST OF ANTIMICROBIAL AGENTS OF VETERINARY IMPORTANCE, May 2015. Page 4. Available at: http://www.oie.int/fileadmin/Home/eng/Our_scientific_expertise/docs/pdf/Eng_OIE_List_antimicrobials_May2015.pdf

[8] Food and Drug Administration, Cephalosporin Order of Prohibition Questions and Answers, 2014. Available at: https://www.fda.gov/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/ucm421538.htm

[9] British Veterinarian Association RESPONSIBLE USE OF ANTIMICROBIALS IN VETERINARY PRACTICE: THE 8-POINT PLAN, 2009. Available at: http://www.fve.org/veterinary/pdf/medicines/National%20initiatives/UK/bva_antimicrobials_poster.pdf

[10] UK Veterinary Antibiotic Resistance and Sales Surveillance, 2015. Available at:  https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/477788/Optimised_version_-_VARSS_Report_2014__Sales___Resistance_.pdf

[11] European Medicines Agency. MA and EFSA Joint Scientific Opinion on measures to reduce the need to use antimicrobial agents in animal husbandry in the European Union, and the resulting impacts on food safety (RONAFA), 2016. Page 67. Available at: http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2017.4666/epdf

[12] European Medicines Agency. MA and EFSA Joint Scientific Opinion on measures to reduce the need to use antimicrobial agents in animal husbandry in the European Union, and the resulting impacts on food safety (RONAFA), 2016. Page 14-15 & 67. Available at: http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2017.4666/epdf

[13] MARAN 2017 Monitoring of Antimicrobial Resistance and Antibiotic Usage in Animals in the Netherlands in 2016. Page15-16. Available at: https://www.wur.nl/upload_mm/b/0/1/74ce6009-b112-428d-aeb7-99b95063aab6_Maran%20report%202017.pdf

[xiv] Guidelines for Risk Analysis of Foodborne Antimicrobial Resistance, CAC/GL 77-2011. Available at: www.fao.org/input/download/standards/11776/CXG_077e.pdf

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