Unravelling the aetiology of contagious ovine digital dermatitis.

传染性绵羊指皮炎（CODD）是英国绵羊传染性跛行的一种极其严重和相对较新的原因，每年影响约35-53%的英国绵羊农场和300，000只绵羊。CODD的经济影响尚不清楚，但可能与另一种常见的跛行原因--蹄病相似，估计每年有2400万英镑。向英国政府报告农场动物福利问题的农场动物福利理事会认为，对这种新疾病的研究应该是优先事项。对蹄病的研究使农民和兽医在跛行这方面的建议得到了实质性的改善，并被羊业广泛采用。然而，许多农民正在努力控制鸡群中的CODD感染，需要大量的研究支持。申请人是目前唯一研究CODD的研究小组，通过英国兽医协会，HCC和EBLEX的资助，该研究小组正在推进我们对该疾病的流行病学，病理学和微生物学的理解，包括使用抗菌药物的控制策略的开发。这项工作的成果将为农业提供切实可行的解决方案。鉴于全球范围内抗菌剂使用的严重压力，可持续的非抗生素解决方案必须侧重于预防性方法，例如通过生物安全和通过接种疫苗提高绵羊抵抗感染的能力来阻止疾病进入幼稚羊群。这两种解决方案都需要比我们目前拥有的更多的关于引起疾病的物质的知识。我们已经证明了与牛指皮炎相同的特定可培养密螺旋体与CODD病变相关的证据，其他研究的数据表明结节性叉毛癣菌和坏死梭杆菌的作用。本研究建议i）进行大量的宏基因组学研究，（整个微生物群落）CODD病变的研究，以鉴定所涉及的关键微生物，和ii）鉴定宿主对所鉴定的微生物的免疫应答，并确定特定抗原是否可以允许保护性免疫应答，以支持未来的疫苗研究，和iii）使用宿主农场环境和粪便的额外宏基因组调查来检测相关微生物，这应该允许相关农民/兽医指引，以改善疾病控制。这项建议可确保我们更深入了解不同细菌在慢性阻塞性肺病发展中所扮演的角色。这些信息将是未来疫苗研究的关键，以便疫苗设计以正确的微生物为目标。在暴露于CODD后，监测本研究中使用的未处理绵羊群的特异性免疫力将允许评估感染过程的不同阶段。这不仅可以描述微生物感染的阶段，还可以确定某些动物是否能够产生有效的免疫应答，从而为随后的有效疫苗抗原发现提供依据。鉴定所考虑的致病微生物也将允许更适当的抗菌治疗，从而降低抗生素耐药性发展的风险。监测治疗后CODD病变的细菌种群应告知生物安全实践，即治疗动物是否导致细菌学治愈或成为无症状的CODD“携带者”。监测粪便和环境样本之前和之后的抗生素治疗也将允许最佳农场实践的发展，以尽量减少再感染的羊与CODD，从而防止失败/过度使用抗生素治疗在羊群level.Investigating CODD使用上述各种方法，应提高对疾病的理解，并有助于消除这种痛苦和昂贵的疾病。

Contagious ovine digital dermatitis (CODD) is an extremely severe and relatively recent cause of infectious lameness in sheep in the UK, affecting approximately 35-53% of UK sheep farms and 300,000 sheep annually. The economic impact of CODD is unknown but likely similar to that of footrot, another common cause of lameness which is estimated at £24million per year. The Farm Animal Welfare Council, who report to the UK government on farm animal welfare issues, identified that research into this new disease should be a priority. Research into footrot has led to substantial improvements for the evidenced based advice available to farmers and vets on this aspect of lameness, and has been widely taken up by the sheep industry. However many farmers are struggling to control CODD infection in their flocks and substantial research support is required here. The applicants are currently the only research group studying CODD and through funding from the British Veterinary Association, HCC and EBLEX, this research group is making advances in our understanding of the epidemiology, pathology and microbiology of the disease, including the development of control strategies using antimicrobial drugs. The outputs of this work will produce practical solutions for the farming industry. Given the severe pressure on antimicrobial usage world-wide, sustainable, non-antibiotic solutions to CODD must focus on preventative approaches such as stopping the introduction of disease into naïve flocks through biosecurity and improvement in the sheep's ability to resist infection through vaccination. Both these solutions require a greater knowledge of the agent(s) causing the disease than we currently possess. We have already demonstrated evidence that specific culturable treponemes identical to those from bovine digital dermatitis have an association with CODD lesions and data from other studies has suggested a role for Dichelobacter nodosus and Fusobacterium necrophorum. This study proposes to i) carry out substantial metagenomic (entire microbial community) investigations of CODD lesions to identify the key microbes involved and ii)to characterise the host immune response to the identified microbes and determine whether specific antigens may allow a protective immune response to underpin future vaccine studies and iii) to use additional metagenomic surveys of the host farm environment and faeces to detect the relevant microbes which should allow for relevant farmer / veterinary guidelines to improve disease control.This proposal would ensure we obtain a greater understanding of the role of different bacteria in CODD development. This information will be key to future vaccine studies so that the correct microorganisms are targeted for vaccine design. Monitoring specific immunity in the naive sheep flock to be used in this study after exposure to CODD will allow assessment of the different stages of the infective process. This will not only describe stages of microbial infections but may also identify whether some animals are able to produce an effective immune response allowing for subsequent antigen discovery for effective vaccines. Identification of the considered causal microorganisms will also allow for more appropriate antimicrobial treatments thus reducing the risk of antibiotic resistance developing. Monitoring bacterial populations of CODD lesions post treatment should inform biosecurity practices i.e. whether treated animals result in bacteriological cure or become asymptomatic CODD "carriers". Monitoring faeces and environmental samples prior and post antibiotic treatment will also allow for development of best farm practices to minimise reinfection of sheep with CODD thus preventing failure / overuse of antibiotic treatment at the flock level.Investigating CODD using the various methods described above, should improve understanding of the disease and contribute towards the eradication of this painful and expensive disease.