Preventing contagious ovine digital dermatitis: Characterisation of bacterial pathogens and development of disease control measures to prevent transmi

传染性羊指性皮炎（CODD）是绵羊跛行的严重原因。它影响了大约一半的英国羊群，并且正在全球范围内出现。由于其严重程度，CODD对羊的福利产生了实质性和非常明显的影响。经济后果以及与疾病控制相关的大量抗生素使用对可持续性产生负面影响。在2021年反刍动物健康与福利组织对英国畜牧农民的调查中，CODD是畜牧业最优先考虑的地方病；而最近的调查发现，提高对疾病传播和预防方法的了解是农民和兽医CODD研究的首要重点。本研究的目的是为预防CODD在农场之间和农场内部的传播提供信息和制定生物安全方案。目的1：比较、鉴定和定位野外病例的病原菌群。来自实验研究的证据表明，CODD的发生是由于先前存在的足部病变与三种密螺旋体细菌重复感染的结果；中密螺旋体、噬菌体密螺旋体和足螺旋体（DD密螺旋体）。为了向农场的疾病预防提供信息，这需要现场验证。因此，我们将采用16s宏基因组分析和定量PCR技术比较CODD和foottrot野外病例中这些DD密螺旋体细菌的微生物组、存在度、丰度和毒力特征。病原负荷和定位将利用荧光原位杂交技术进行研究。目的2：对牛、羊手指性皮炎皮损中、噬菌体、足弓形虫分离株进行全基因组测序。长期以来，人们一直担心DD密螺旋体起源于牛数字性皮炎（BDD），并且物种之间的传播通过农场环境发生。这有可能将疾病引入naïve农场，并可能成为地方性感染农场的感染源。我们将通过对感染BDD和CODD的农场中分离出的中型t .、噬菌体t .和足形t .的全基因组分型来研究这一假设。我们还将研究它们的细菌多样性和毒力因素。目的3：评价消除羊脚CODD病原体的消毒方案。随着CODD的继续传播，目前的生物安全建议显然是不够的。我们将开展农场随机对照试验，以调查消毒方案对消除羊脚上CODD病原体的效果。该方案将基于从当前研究和试点体内和体外疗效数据收集的证据。采用临床检查、细菌培养和qPCR评价疗效。

Contagious ovine digital dermatitis (CODD) is a severe cause of sheep lameness. It affects approximately half of UK sheep flocks, and is emerging globally. Due to its' severity, CODD has a substantial and highly visible impact on sheep welfare. The economic consequences, and high levels of antibiotic use associated with disease control, negatively affect sustainability. In the 2021 Ruminant Health and Welfare Group survey of UK livestock farmers, CODD was a top priority endemic disease for the livestock industry; whilst recent surveys identified that improved understanding of disease transmission and prevention methods were farmers and vets top CODD research priorities. The aim of this study is to inform and devise biosecurity protocols for prevention of between and within farm transmission of CODD. Objective 1: Comparison, characterisation and localisation of pathogenic bacterial populations from field cases of footrot and CODD. Evidence from experimental studies demonstrated that CODD occurs as a result of superinfection of pre-existing footrot lesions with three treponeme bacteria; Treponema medium, Treponema phagedenis and Treponema pedis (DD treponemes). To inform disease prevention on farms, this requires field validation. Therefore, we will compare the microbiomes, the presence, abundance and virulence characteristics of these DD treponeme bacteria from field cases of CODD and footrot using 16 S metagenomic analysis and quantitative PCR. Pathogen load and localisation will be studied using fluorescence in situ hybridisation.Objective 2: Whole genome sequencing of T.medium, T.phagedenis, T.pedis isolates from cattle and sheep digital dermatitis lesions.It is a long-held concern that the DD treponemes originated from bovine digital dermatitis (BDD), and that transmission between species occurs through the farm environment. This risks introduction of disease to naïve farms and maybe a source of infection in endemically affected farms. We will investigate this hypothesis using whole genome typing of T.medium, T.phagedenis and T.pedis isolates from farms affected by both BDD and CODD. We will also investigate their bacterial diversity and virulence factors. Objective 3: Evaluate disinfection protocols for the elimination of CODD pathogens from sheep's feet. As CODD continues to spread it is evident that current biosecurity advice is inadequate. We will conduct farm RCT trials to investigate the efficacy of disinfection protocols for the elimination of the CODD pathogens from sheep's feet. The protocols will be based on evidence gathered from the current study and pilot in vivo and in vitro efficacy data. Clinical examination, bacterial culture and qPCR will be used to assess efficacy.