One Health Drivers of Antibacterial Resistance in Thailand

抗菌素耐药性是海外发展援助国家超额死亡率的一个重要来源，并对福祉和经济发展构成日益严重的威胁。2010年，抗菌素耐药性(AMR)，主要是ABR，估计已在泰国造成3.8万人死亡和12亿美元的经济损失。由于良好的记录保存和监督，泰国已成为官方发展援助国家ABR特征的典范。ABR在人类、环境和动物的细菌分离株中很常见。然而，ABR大多是在离散的部门(例如医院患者或家禽)中单独研究的。与人类健康相关的ABR的关键驱动因素不能以这种方式精确定位，因为ABR的选择和传播是人、动物和环境之间相互作用的结果。在这个联盟的项目中，我们将研究肠杆菌科细菌肺炎克雷伯氏菌(Klebsiella Penoniae)和大肠杆菌(EC)，它们存在于人和动物的肠道中，在被粪便污染的环境中很常见，在泰国被认为是对人类健康的重大威胁。它们通常是碳青霉烯类和/或第三代头孢菌素耐药(3GCR)，这是通常用于严重感染的药物。耐碳青霉烯类肠杆菌科细菌(CRE)也被世卫组织确认为全球最优先的病原体之一，迫切需要新的ABS。EC和KP可引起住院患者的一系列感染(如手术部位、腹内感染、肺炎、败血症)和严重的社区获得性感染(如复杂性尿路感染、化脓性肝脓肿、脑膜炎)。在泰国，3GCR KP和EC在人类感染中的流行率一直在上升，从1999年的不到10%上升到2016年的50%，碳青霉烯耐药KP的流行率从2010年之前的零上升到2016年的10%-20%。我们联盟的愿景是建立泰国ABR驱动因素的整体图景，并利用这些信息造福泰国人民，并作为其他官方发展援助国家的榜样。“驱动因素”一词可指：1)物质条件或物质，如化学物质(如抗生素)，在特定浓度下，导致ABR细菌的流行增加；2)一种行动，如通过服用抗生素使细菌暴露在该化学物质中；或3)造成该行动的社会经济条件或环境(如，面对疾病继续工作的经济必要性)。充分了解每个层面的ABR驱动因素，对于设计有效和适当的干预措施以限制ABR非常重要。因此，这个跨学科联合体将对所有这些进行调查。我们的研究区域将是泰国中西部80x80公里的Mae Klong-Ta Chin盆地。湄公河和大金河发源于泰缅边境(Mae Klong河)和泰国中部上游(大钦河)，一直流经泰国湾。研究区域包括五个省(Karnchanaburi、Ratchaburi、Samut Songkram、Samut Sakorn和NakornPrathom)的地区。这两条河流都进入研究现场，流经有许多工厂、畜牧场、稻田、果园和社区的地区，允许在我们的工作中考虑多种可能的驱动因素。我们的工作将与泰国关于AMR的国家战略计划一起进行，使我们有一个完美的机会，将我们的发现嵌入到战略计划的年度审查中，影响泰国的政策，并对泰国的人类健康产生相对短期和直接的影响。我们的参与和利益相关者的活动还将促进将我们的调查结果传播到同一全球区域内的其他国家，与全球其他项目进行比较将产生附加值。

Antibacterial Resistance (ABR) is a significant source of excess mortality in Overseas Development Assistance (ODA) countries and constitutes a major, increasing threat to wellbeing and economic development. Antimicrobial Resistance (AMR), predominantly ABR, is estimated to have caused 38,000 deaths and an economic loss of 1.2 billion US$ in Thailand in 2010. Because of good record keeping and surveillance, Thailand has been used as an exemplar for characteristics of ABR in ODA countries. ABR is common in human, environmental and animal bacterial isolates. However, ABR has mostly been studied separately in discrete sectors (e.g. hospital patients or poultry). The key drivers of ABR relevant to human health cannot be pinpointed in this way because the selection and transmission of ABR results from interactions between humans, animals, and the environment. A "One Health" approach to the problem is required.During this consortium project, we will study the Enterobacteriaceae family bacteria Klebsiella pneumoniae (Kp) and Escherichia coli (Ec), which reside in the human and animal gut, are common in environments contaminated with faeces, are are considered a significant threat to human health in Thailand. They are commonly carbapenem- and/or 3rd-generation cephalosporin-resistant (3GCR), which are drugs commonly used for serious infections. Carbapenem-resistant Enterobacteriaceae (CRE) are also recognised by WHO as one of the highest priority pathogens globally for which new ABs are urgently needed. Ec and Kp cause a range of infections in hospitalized patients (e.g. surgical site, intra-abdominal, pneumonia, sepsis) and serious community-acquired infections (e.g. complicated urinary tract infection, pyogenic liver abscess, meningitis). The prevalence of 3GCR Kp and Ec in human infections in Thailand has been increasing from less than 10% in 1999 to 50% in 2016, and of carbapenem-resistant Kp from none prior to 2010 to 10%-20% in 2016.Our consortium's vision is to build a holistic picture of the drivers of ABR in Thailand and to use this information to benefit the Thai people, and as an exemplar for other ODA countries. The term "driver" may refer to: 1) a material condition or substance, such as a chemical (e.g. an Antibiotic), which, at a particular concentration, selects for the increased prevalence of ABR bacteria; 2) an action, such as exposing bacteria to that chemical by taking an antibiotic; or 3) a socioeconomic condition or circumstance which accounts for that action (e.g. the economic necessity to keep working in the face of illness). A full understanding of ABR drivers at every level is important for the design of effective and appropriate interventions to limit ABR. Hence, this interdisciplinary consortium will investigate them all.Our study area will be the Mae Klong-Ta Chin Basin, which covers an area of 80x80 km in the central and western part of Thailand. This is the area where the Mae Klong and Ta Chin rivers run from their mountain sources along the Thai-Myanmar border (Mae Klong river) and upper central Thailand (Ta Chin river) down to the Gulf of Thailand. The study area includes districts spread over five provinces (Karnchanaburi, Ratchaburi, Samut Songkram, Samut Sakorn and Nakornprathom). Both rivers enter the study site and run through areas where there are numerous factories, animal farms, rice fields, fruit orchards and communities, allowing multiple possible drivers to be considered in our work.Our work will run alongside Thailand's National Strategic Plan on AMR, giving us a perfect opportunity to embed our findings in annual reviews of the Strategic Plan, influencing policy and having a relatively short term and direct impact on human health in Thailand. Our engagement and stakeholder activities will also facilitate dissemination of our findings into other countries within the same global region, and comparisons with other projects across the globe will yield added value.