Can a liquid bandage be used as a new treatment for infectious causes of lameness in sheep and reduce antibiotic treatment?

绵羊的跛行是一个主要的福利问题，从2004年的数据来看，英格兰的羊瘸患病率为10.6%，脚步被确定为主要原因。Footrot的发病机制是复杂的、多因素的，其主要病理基础与结节双歧杆菌的细菌复制有关。严重程度增加是由于并发传染性绵羊指状皮炎(Codd)，这与密螺旋体感染有关。在英国的养羊场，Footrot和Codd病例都具有很高的传染性，很难控制。推荐将注射抗生素用于临床跛行的动物，占英国绵羊业使用的抗生素总量的三分之二。尽管如此，疾病管理的一个重要方面是需要迅速遏制感染细菌的任何绵羊的传播，这些绵羊确实出现了蹄疾或鳕鱼。在不求助于抗生素治疗的情况下实现这一点，将对绵羊的福利和可取的减少抗生素使用都有巨大的好处。Bastos等人(2020)最近报道了坚固的、快速固定的抗菌液体屏障(绷带)，并举例说明了它们在牛的蹄子上用于治愈数字皮炎。这些屏障是专门为遇到极端条件的损伤而设计的，如牧场、泥浆、水和泥浆，这些屏障不仅保护伤口不受环境的影响，而且通过接触杀死可能会突破屏障或在其上建立生物膜的细菌，从而保持其固有的无菌性质。这些材料只使用饲料级组件，即天然聚合物(虫胶)加上铜和锌，以帮助结构和提供抗菌活性。这项技术已经获得剑桥大学一家名为NoBACZ Healthcare的衍生公司的许可，NoBACZ Healthcare是这项应用的工业合作伙伴。假设以锌为基础的抗菌剂和快速形成的液体屏障可以封闭并治愈导致绵羊跛行的感染性病变，而不需要系统的抗生素治疗。与注射抗生素的绵羊相比，这种方法将减少羊脚上携带的AMR细菌的水平。目的和方法确定一种适合治疗绵羊跛行的液体绷带。这将以锌为基础，因为一些品种的绵羊对铜敏感。A.一系列锌基液体绷带配方将应用于屠宰场来源的羊脚，以确定最佳的应用、粘附性和耐用性。在使用液体绷带之前和之后都要用棉签拭子。(Y1，包括在NoBACZ的时间)。B.自然感染临床蹄和/或鳕鱼的绵羊将在严密的兽医监督下，用含铅液体绷带配方进行治疗。在绷带使用前和使用后的几种情况下，都要用棉签拭子。跛行程度将定期评分。绵羊福利将被放在首位。(Y2)2.研究液体绷带对绵羊脚上D结节杆菌水平的影响。从目标1中采集的拭子中：a.提取DNA，并用定量聚合酶链式反应(QPCR)检测真细菌和结节杆菌总数。(Y1-2)b.细菌将被培养在含有治疗绵羊跛行的常用抗生素的培养基上。耐药分离株将用纸片扩散法进一步鉴定。(Y1-3)3.调查利益相关者对用液体绷带代替抗生素注射治疗跛脚羊的适当性和实用性的意见。最初，这将集中在一名兽医密切监控的农场上，有一小部分值得信赖的牧羊人。在适当的情况下，将更广泛地从重点小组和/或更广泛地分发问卷中收集意见。(Y3，包括在NoBACZ的时间)

Lameness in sheep is a major welfare concern with a prevalence of 10.6% in England from 2004 figures, and footrot identified as the primary cause. The pathogenesis of footrot is complex and multifactorial with the primary pathology mostly related to the bacterial replication of Dichelobacter nodosus. Severity increases due to concurrent contagious ovine digital dermatitis (CODD) which is associated with treponeme infection. Footrot and CODD cases are both highly infectious and difficult to control on UK sheep farms. Injectable antibiotics are recommended for clinically lame animals accounting for two thirds of the total antibiotics used in the UK sheep industry. Notwithstanding, an important facet of disease management is the need to rapidly curtail the spread of infectious bacteria from any sheep that do develop either footrot or CODD. Achieving this without resorting to antibiotic therapy would be of enormous benefit to both the welfare of sheep and the desirable reduction of antibiotic usage. Robust, rapid-setting antibacterial liquid barriers (bandages) have recently been reported by Bastos et al (2020) and their use exemplified on the hooves of cattle to heal digital dermatitis. Designed, specifically, for lesions that encounter extreme conditions, such as pasture, mud, water and slurry, these barriers not only protect the wound from the environment but they retain their inherent sterile nature by contact killing bacteria that might otherwise breach the barrier or establish biofilms on it. These materials use feed grade components only, namely a natural polymer (shellac) plus copper and zinc to aid structure and provide antibacterial activity. The technology has been licensed by a spin out company of the University of Cambridge, called 'NoBACZ Healthcare'- the industrial partner for this application. Hypothesis Zinc-based, antimicrobial and rapid-setting liquid barriers can seal, and enable healing, of infectious lesions that lead to lameness in sheep, without the need for systemic antibiotic treatment. This approach will reduce the level of AMR bacteria carried on sheep feet compared to sheep treated with antibiotic injections. Aims and Methods Identification of an appropriate liquid bandage for the treatment of lameness in sheep. This will be based on zinc, as some breeds of sheep are copper sensitive. a. A range of zinc-based liquid bandage formulations will be applied to abattoir sourced sheep feet to identify optimum application, adherence and durability properties. Swabs will be taken before and after liquid bandage application. (Y1, includes time at NoBACZ). b. Sheep naturally infected with clinical footrot and/or CODD will be treated with the lead formulation of liquid bandage under close veterinary supervision. Swabs will be taken pre-application of the bandage and on several occasions post-application. Lameness levels will be scored at regular intervals. Sheep welfare will take priority. (Y2) 2. Investigation of the impact of a liquid bandage on levels of D nodosus on sheep feet. From swabs taken in Aim 1: a. DNA will be isolated and total eubacteria & D nodosus will be determined by qPCR. (Y1-2) b. Bacteria will be plated on media containing commonly used antibiotics to treat ovine lameness. Resistant isolates will be further characterized using disc diffusion assays. (Y1-3) 3. Investigation of stakeholder opinion as to the appropriateness and practicalities of treating lame sheep with a liquid bandage instead of an antibiotic injection. Initially this will be focused, with a small number of trusted shepherds, on farms that are closely monitored by a veterinarian. Where appropriate, opinion will be more widely gathered from focus groups and/or a more widely distributed questionnaire. (Y3, includes time at NoBACZ)