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

绵羊跛行是一个主要的福利问题，从2004年的数据来看，英国的跛行率为10.6%，而脚跑被确定为主要原因。小脚的发病机制是复杂的，多因素的，主要病理与结节双杆菌的细菌复制有关。严重程度增加，由于并发传染性羊数字性皮炎（CODD），这是与螺旋体感染有关。在英国的绵羊养殖场，足疾和CODD病例都具有高度传染性，难以控制。注射抗生素被推荐用于临床跛行的动物，占英国绵羊行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来自任何确实出现足癣或CODD的羊的传染性细菌的传播。在不诉诸抗生素治疗的情况下实现这一目标，将对绵羊的福利和减少抗生素的使用都有巨大的好处。巴斯托斯等人（2020）最近报道了坚固、快速设置的抗菌液体屏障（绷带），并在牛蹄子上使用它们来治疗数字皮炎。这些屏障是专门为遇到极端条件的损伤而设计的，例如牧场、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破坏屏障或在其上建立生物膜的细菌，它们保持了固有的无菌性质。这些材料仅使用饲料级成分，即天然聚合物（虫胶）加上铜和锌来辅助结构并提供抗菌活性。这项技术已获得剑桥大学附属公司“NoBACZ医疗保健”的许可，该公司是这项应用的工业合作伙伴。假设基于锌的抗微生物和快速凝固液体屏障可以密封并使导致绵羊跛行的感染性病变愈合，而无需全身抗生素治疗。与接受抗生素注射的羊相比，这种方法将降低羊脚上携带的抗菌素耐药性细菌的水平。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，因为某些品种的羊对铜敏感。a.一系列锌基液体绷带配方将应用于屠宰场采购的羊脚，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取拭子。（Y1，包括在NoBACZ的时间）。b.自然感染临床足癣和/或CODD的羊将在兽医的密切监督下使用含铅配方的液体绷带进行治疗。在使用绷带前和在使用绷带后的几次使用棉签。跛行程度将定期评分。羊的福利将优先考虑。(Y2) 2。液体绷带对羊足结节病水平影响的研究。从目标1:a中采集的拭子中分离DNA，并通过qPCR确定真菌体和结节菌总数。（1-2） b.细菌将被镀在含有治疗羊跛行的常用抗生素的培养基上。耐药菌株将采用圆盘扩散法进一步鉴定。(Y1-3) 3。利益相关者意见的适当性和实用性的调查用液体绷带代替抗生素注射治疗跛羊。最初，这将集中在由兽医密切监测的农场上，有少数值得信赖的牧羊人。在适当情况下，将更广泛地从焦点小组收集意见和/或更广泛地分发调查表。（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)