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

据估计，到2050年，抗菌药耐药性感染将成为全球死亡的主要原因，总经济成本将达到100万亿美元，中低收入国家将承担巨大负担（O’neill报告，2016年）。牲畜的抗菌素使用（AMU）已被证明是动物抗菌素耐药性（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%的抗菌素耐药性归因于动物的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；尽管后者对牲畜饲养情景的量化很差。随着对动物蛋白需求的增加，特别是在低收入和中等收入国家，农业在全球抗生素消费中所占的份额很高，而且还在上升。如果不考虑养殖环境和自然环境在造成抗菌素耐药性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抗菌素耐药性，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-影响-行动）来考虑AMR问题。该框架旨在允许将复杂问题分解为逻辑组件，它还允许识别动作和关键控制点，这有助于控制理论建模方法的应用。我们将制定一个综合监测、分析、解释、建模和政策翻译方法的“蓝图”，可用于任何低收入和中等收入国家的任何牲畜系统，以促进决策、实施激励措施，并为围绕减少抗菌素、抗菌素耐药性和人类健康风险的干预措施制定新政策提供信息。这将减少抗菌素耐药性的经济和社会负担，同时确保考虑到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，而是采取了跨学科的方法来研究饲养场生产对肉牛抗菌药物使用和抗生素耐药性的影响，以及饲养场受影响的环境。其基本原理是，我们可以详细调查这种单一的牲畜系统，作为一个范例，包括牛的繁殖和饲养系统的影响，结合具体的干预措施，包括减少使用抗生素作为生长促进剂，在饲养场招募时停止过敏反应，以及作为额外干预的疫苗接种。由于奶牛场抗菌素使用量增加（AMU），使用奶牛场来源的小牛作为一个额外的风险因素也将进行调查。在拉丁美洲大部分地区和世界其他地区，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牛肉生产来代替草地生产。具有讽刺意味的是，随着应对抗生素耐药性的国际努力的增加(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（mou），仅剩的大量粗制滥造、低AMU畜牧系统之一正在向集约化、高AMU生产系统迈进。这种影响在中低收入国家最为明显，因为这些国家对负担得起的动物蛋白的需求增长最为迅速。

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.