FARMS-SAFE: Future-proofing Antibacterial resistance Risk Management Surveillance and Stewardship in the Argentinian Farming Environment

Antibacterial drug resistance (ABR) is a global threat to health and development and a problem that is getting steadily
worse. Within Latin America, Argentina has been tracking levels of ABR in human infections since 1986. Argentina was
also the first country in the region to develop a national strategy for the control of ABR. This national Strategy takes a
starting assumption that the use of antibacterial drugs (ABs) in livestock agriculture is in part responsible for the threat
of ABR in humans. The use of ABs on farms can potentially result in ABR human infections via 3 main pathways: (1)
ABR bacteria selected in the farm environment infect humans, or at least the mobile ABR genes carried within them
are transmitted to bacteria that infect humans; (2) Agricultural AB residues in food are ingested by humans, selecting
for ABR in human bacteria; (3) Agricultural ABs contaminate the non-farm environment, selecting ABR in bacteria
there, which then infect humans. In Argentina, data are extremely limited for the amount of ABR bacteria on farms
and in the near-farm environment. Furthermore, whilst AB residues are monitored in foodstuffs entering the formal
market, there is a significant informal market, and AB levels in the environment are not routinely measured. One
potential response to the rising threat of ABR is regulation, and both international organizations - led by the WHO -
and individual countries have sought to formulate, for example, new regulatory frameworks to address the and use of
ABs in farming, as well as the management of farm waste. As the O'Neill report recognises, however, developing
countries "...will need extra support and additional time to train veterinarians, develop regulations, build surveillance
capacity and improve farming practices". The premise of this project - FARMS-SAFE - is that as well as providing better
surveillance information for ABR and AB usage, extra support for Argentina and other Latin American countries should
encompass a risk-based approach to the design of regulation as well as to the strengthening of enforcement capacities;
their weakness is another source of risk.

FARMS-SAFE will address this issue by reference to four key risk areas via an UK/Argentinian research consortium:

1. Animal disease as a driver of ABR risk - We will identify why farmers use ABs in the context of animal disease.

2. Animal husbandry practice as a driver of ABR risk - We will identify what farm management practices are being
employed that influence the usage of ABs and will perform surveillance of the usage of ABs on farms in Argentina.

3. Farm waste management as a driver of ABR risk. We will perform surveillance of ABR bacteria with clear
potential to affect human health on farms in the near farm environment and will measure the levels of ABs and
other chemicals in the near-farm environment. We will correlate ABR with AB usage and will identify management risk
factors for ABR and AB contamination in the environment.

4. Regulatory capacity as a driver of ABR risk. We will identify the key individuals and organisations involved in
regulation of ABR and work with them to develop tools that can be used to regulate in a way that is informed by the
risks that drive ABR.

This work will lead to significant new understanding of the prevalence and causes of ABR in Argentinian farming
systems, how this influences the near-farm environment (and so potentially influences human health) and will inform
policy making within Argentina, Latin America and the wider world. We will also create a surveillance structure and
trained researchers who can continue to monitor ABR, AB usage and environmental contamination with ABs and ABR
into the future, and who can measure success and failure of strategies employed to reduce this risk.

WS1: We will design and implement a nationwide telephone survey administered to farms. We will explore respondents' views about ABR, what ABs are being used on farms, how they are sourced, what diseases they are used to prevent or treat and how farmers view their use. A combination of qualitative and quantitative analyses will be used to examine differences in reported farmer perceptions and behaviours according to predictor variables.

WS2: We will undertake an in-depth social science analysis of how farmers deal with animal health, ABs and the risk of ABR. In-depth semi-structured interviews, ethnographic farms visits and participant observation at agro-shops will be used. Qualitative data will be thematically analysed using Quirkos qualitative text analysis software.

WS3: We will develop survey methodologies for AB, metal and biocide use using veterinary prescription and on-farm records, validated using bin audits. Evaluation of farm risk factors associated with ABU will be carried out using multilevel, multivariable regression modelling with variables identified in WSs 1 and 2.

WS4: We will establish surveillance protocols for ABR bacteria on farms. We will monitor prevalence and mechanism of ABR in Enterococci, Escherichia coli, Salmonella and Campylobacter using whole genome sequencing to link bacteria and ABR mechanisms between and within farms and near-farm environments. We will measure AB, metal and biocide contamination on farms and in near-farm environments and associate this with on-farm ABU, ABR and management practices using multilevel, multivariable linear regression modelling.

WS5: We will map regulatory actors for ABU and ABR, developing a heuristic model to summarise the major ABR risk factors for each livestock sector identified in WS1-4 in ways that are clear, understandable and actionable by regulators. We will produce policy briefing and best practice position papers to be shared with stakeholders in Argentina and the region.

Health and welfare of Argentinian people and animals, along with those across Latin America
There is a significant burden of disease and economic cost of antibacterial drug resistance (ABR) in Argentina. Since
ABR is rising, inevitably the health and well-being cost of ABR will also rise, and probably moreso in developing areas
like those of Latin America, which are likely to have higher death tolls (of both humans and animals) than other regions.
Our aim is to develop an holistic picture of ABU and ABR in livestock systems in Argentina and to uncover their impact
on the environment as well as to identify potential interventions that can reduce ABU and so ABR. What we learn will
be transferable to other countries, particularly neighbouring countries in Latin America where ABR is also a significant
burden. In order to meet this challenge and improve human health, we need to have impact in policy engagement as
well as public engagement at all levels - from our study site to the entire Latin American region. One major advantage
of the timing of our proposed work is that it is contemporaneous with the implementation and review of Argentina's
Strategy to Control ABR, which is specifically focussed on reducing ABU and ABR in humans and animals. Our work will
synergise and expand current surveillance work ongoing in Argentina, and this synthesis will be extremely valuable
both in benchmarking success and informing modification of the Strategy for Argentina and her neighbours.

Policy makers and other stakeholders in Argentina and Latin America
Our project will provide timely information on key actions and resolutions for better control and traceability of ABs in
livestock farming and will identify the realities of compliance in these areas in ways that policy makers are currently
unable to fully assess. Findings of our study will be developed into policy briefings and disseminated through our
excellent policy partners and links in Argentina and throughout Latin America, impacting policy in the region directly.
Our work will also be presented at sub-national meetings within Argentina and meetings across Latin America as well
as internationally so that it can be applied to developing policy concurrently and subsequent to the work being
completed.

Industry (farming and veterinary)
Overuse of ABs, biocides and metals in Argentinian agriculture may reduce the economic efficiency of the agricultural
industries. Better farm management practices would not only reduce the reliance on medicines and chemicals, but
would improve yields in livestock agriculture, thereby improving overall economic growth. The risk factor analysis in
this project - combined with social science work - will uncover farm management practices and potential leverage
points that can be used to encourage more efficient practices across livestock agriculture. Many of these will reduce
ABR but all will lead to more responsible use of ABs. This project also addresses the impact that the farming industries
and veterinary profession might have on human health through animal-mediated contamination of publicly accessible
land and waterways with ABR bacteria. Understanding risk factors for acquisition of ABR in livestock and possible ways
to mitigate these will assist the livestock industries as they react to growing public concern about ABR and possible
legislation in an informed way. Directly involving stakeholders from these sectors in our project will allow them to
advocate for our findings in their own industries. For example, provision of first-hand evidence on the positive effect
of reducing ABU on ABR levels on the farms in our study may stimulate a peer-led process to encourage others to
reduce levels further. Limiting the rise of ABR will make farming in Argentina productive (via less untreatable disease)
and more economically successful, and will provide a model for tackling ABR elsewhere in the world.