One Health Drivers of Antibacterial Resistance in Thailand

抗菌药物耐药性（ABR）是海外发展援助（ODA）国家死亡率过高的一个重要原因，对福祉和经济发展构成了日益严重的重大威胁。据估计，2010年，抗菌素耐药性（AMR），主要是ABR，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测，泰国已被用作官方发展援助国家ABR特征的典范。ABR在人类、环境和动物细菌分离株中很常见。然而，ABR大多是在离散部门（例如医院病人或家禽）单独研究的。由于ABR的选择和传播源于人类、动物和环境之间的相互作用，因此无法以这种方式确定与人类健康相关的ABR的关键驱动因素。需要对这一问题采取“同一个健康”办法。在这个联合项目中，我们将研究存在于人类和动物肠道中的肠杆菌科细菌肺炎克雷伯菌（Kp）和大肠杆菌（Ec），它们在被粪便污染的环境中很常见，被认为是对泰国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），这些药物通常用于严重感染。耐碳青霉烯肠杆菌科（CRE）也被世卫组织认定为全球最优先的病原体之一，迫切需要新的抗体。Ec和Kp在住院患者中引起一系列感染（如手术部位、腹内、肺炎、败血症）和严重的社区获得性感染（如并发症尿路感染、化脓性肝脓肿、脑膜炎）。泰国人类感染中3GCR Kp和Ec的流行率从1999年的不到10%增加到2016年的50%，碳青霉烯类耐药Kp的流行率从2010年之前的零增加到2016年的10%-20%。我们联盟的愿景是全面了解泰国ABR的驱动因素，利用这些信息造福泰国人民，并为其他官方发展援助国家树立榜样。术语“驱动因素”可指：1)物质条件或物质，如化学品（如抗生素），在特定浓度下，选择ABR细菌的增加流行；2)一种行为，例如通过服用抗生素使细菌暴露于该化学物质；或3)解释该行为的社会经济条件或环境（例如，面对疾病继续工作的经济必要性）。充分了解各个层面的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，这个跨学科的联盟将对它们进行调查。我们的研究区域是泰国中部和西部的Mae Klong-Ta Chin盆地，面积为80x80公里。这是湄龙河和塔钦河沿着泰缅边境（湄龙河）和泰国中上游（塔钦河）从山区源头流向泰国湾的地区。研究区域包括分布在五个省的地区（Karnchanaburi, Ratchaburi, Samut Songkram， Samut Sakorn和Nakornprathom）。两条河流都进入研究地点，流经有许多工厂、动物农场、稻田、果园和社区的地区，这使得我们的工作可以考虑多个可能的驱动因素。我们的工作将与泰国的抗微生物药物耐药性国家战略计划同时进行，这将为我们提供一个绝佳的机会，将我们的发现纳入战略计划的年度审查，从而影响政策，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活动也将促进我们的研究结果在同一全球地区的其他国家传播，并与全球其他项目进行比较将产生附加价值。

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.