Developing a conceptual framework to improve understanding of AMR in livestock systems: translating research into policy and practice

据估计，到2050年，AMR感染将成为全球死亡的主要原因，总经济成本为100万亿美元，其中LMIC承担了压倒性的负担（奥尼尔报告，2016）。家畜中的抗菌药物使用（AMU）已被证明是动物抗菌药物耐药性（AMR）的重要驱动因素，并与临床环境中的耐药性相关，最近的一项综述将人类24%的AMR归因于动物中的AMU。对更广泛环境的影响以及人类接触和传播的可能性也有充分的记录;尽管后者在牲畜饲养情景中的量化程度很低。农业在全球抗生素消费中所占的份额很高，而且随着对动物蛋白的需求增加，特别是在低收入和中等收入国家，这一份额还在上升。如果不考虑养殖和自然环境在增加AMR感染的总体负担方面所起的重要作用，并采取措施减少环境AMR，其他部门的努力可能无法阻止威胁现代医学的后抗生素时代。我们将使用DPSEEA框架（驱动因素-压力-状态-暴露-效应-行动）来考虑AMR问题。这个框架的目的是让复杂的问题被分解成逻辑组件，它还允许动作和关键控制点被识别，这有助于控制理论建模方法的应用。我们将为综合监测、分析、解释、建模和政策翻译方法制定“蓝图”，该方法可用于任何LMIC的任何畜牧系统，以促进决策、实施激励措施，并为减少AMU、AMR和人类健康风险的干预措施提供新政策。这将减少AMR的经济和社会负担，同时确保考虑干预措施的相关经济成本。我们没有试图在尽可能多的牲畜饲养系统中，在尽可能多的管理策略下产生尽可能多的监测数据，而是采取跨学科的方法来研究饲养场生产对肉牛抗菌剂使用和AMR的影响以及饲养场影响的环境。其基本原理是，我们可以详细研究这个单一的牲畜系统，作为一个范例，包括牛育种和饲养系统与特定干预措施相结合的影响，包括减少使用抗生素作为生长促进剂，停止在饲养场招募时的过敏反应和疫苗接种作为额外的干预措施。由于奶牛场抗菌剂使用量（AMU）增加，还将研究使用乳牛作为额外风险因素。在拉丁美洲和世界其他地区，包括拉丁美洲和其他地区的中低收入国家，越来越多地使用饲养场肉牛生产代替草地生产。具有讽刺意味的是，随着国际社会解决AMR问题的努力增加（例如，根据粮农组织、世界动物卫生组织和世卫组织于2018年5月30日签署的谅解备忘录，剩余的大规模、低AMU畜牧系统之一正在向集约化、高AMU生产系统发展。这一影响将在中低收入国家感受最强烈，这些国家对负担得起的动物蛋白的需求日益迅速。

It is estimated that by 2050 AMR infections will be the leading cause of death globally with a total economic cost of $100 trillion, with the overwhelming burden placed on LMICs (O'Neill report, 2016). Antimicrobial usage (AMU) in livestock has been shown to be an important driver of antimicrobial resistance (AMR) in animals and is associated with resistance in the clinical setting, with a recent review attributing 24% of AMR in humans to AMU in animals. Impacts on the wider environment are also well documented as is the potential for human exposure and transmission; although the latter are poorly quantified for livestock rearing scenarios. Agriculture's share of global antibiotic consumption is high and rising, as the demand for animal protein increases, especially in low and middle-income countries. Without considering the important role that the farmed and natural environment plays in contributing to the overall burden of AMR infection, and taking steps to reduce environmental AMR, efforts in other sectors may not prevent the post-antibiotic era that threatens modern medicine. We will consider the issue of AMR using a DPSEEA framework (Drivers-Pressure-State- Exposure-Effect-Action). This framework was designed to allow complex problems to be broken down into logical components, it also allows Actions and critical control points to be identified which lends itself to the application of control theory modelling approaches. We will produce a "blueprint" for an integrated surveillance, analysis, interpretation, modelling and policy translation approach that can be utilised for any livestock system in any LMIC to facilitate decision making, implementation of incentives and informing new policy around interventions to reduce AMU, AMR and risk to human health. This will reduce the economic and societal burden of AMR whilst ensuring associated economic costs of interventions are considered. Rather than trying to generate as much surveillance data, in as many livestock rearing systems, under as many management strategies as possible, we have instead taken an interdisciplinary approach to studying the impacts of feedlot production on antimicrobial usage and AMR in beef cattle as well as feedlot impacted environments. The rationale being that we can investigate this single livestock system, as an exemplar, in detail, including the impacts of cattle breeding and rearing systems combined with specific interventions including reduction of use of antibiotics as growth promoters, cessation of metaphylaxis at the point of recruitment to the feedlot and vaccination as an additional intervention. The use of dairy sourced calves as an additional risk factor due to increased antimicrobial usage (AMU) on dairy farms will also be investigated. Feedlot beef production is increasingly used instead of grassland production in much of Latin America and other parts of the world including LMICs in Latin America and beyond. It is ironic that as international efforts to tackle AMR increase (eg. the FAO, OIE and WHO Memorandum of Understanding, signed on the 30 May 2018) one of the remaining largely extensive, low AMU livestock systems is moving towards intensive, high AMU production systems. The impacts of this will be felt most keenly in LMICs where demand is increasingly most rapidly for affordable animal protein.