Is multistrain infection by Dichelobacter nodosus important in the severity of footrot and in the management of disease?

蹄病导致羊跛行。这种使人衰弱的疾病会导致绵羊体重减轻，产奶量减少，从而使羔羊生长缓慢。蹄病在英国非常常见，影响>98%的羊群，每年约有300万只羊跛脚。蹄病是由结节性双螯菌（Dichelobacteriumnodosus）引起的，这是一种厌氧细菌，会导致羊脚皮肤发炎：这会导致跛行。在某些情况下，损伤是如此严重，蹄角与脚内的活组织分离，并暴露出这些肉（严重的蹄，SFR）。它是一种在羊之间传播的传染病，羊会因为免疫力差而反复跛行。因此，蹄病是绵羊生产力降低和福利差的重要原因。蹄病每年给英国羊业造成约8000万英镑的损失，是全球养羊业中最昂贵的疾病之一。结节虫引起足炎我们也知道它存在于健康的脚上，因此并不总是引起疾病。一些D。结节菌菌株比其它菌株更能引起严重的疾病。在实验室中，由于细菌中的遗传标记，菌株被标记为毒性（可以导致SFR）或良性（不能导致SFR），然而，这一分类与我们在绵羊中看到的疾病不匹配。蹄病在英国大部分地区全年存在（地方性），全年出现一系列小型流行病。然而，在世界上的一些地方，农民已经从他们的羊群中根除了蹄病。这在英国是困难的，因为蹄病存在于如此多的羊群中，在我们的温带气候中持续存在，并且通过羊在农场之间的移动在羊群之间传播，这在英国很常见。因此，对英国来说，控制是一个更可行的选择。这可以通过隔离患病的羊，及时治疗羊以防止疾病传播，预防性地用消毒剂洗脚和接种疫苗（尽管目前许可的疫苗如果单独使用无效）来实现。这些并不能预防疾病。在健康、发炎和患病足上的结节状足表明，越来越多的D.发炎皮肤上的结节状芽孢杆菌与严重疾病发展的风险增加有关。足上必须有足够数量的节足虫，相反，通过减少节足虫的数量可以获得控制。nodosus的毒力因子，减少了毒力因子的数量。结节状的为了验证这些想法，我们将调查D。来自没有蹄病的羊群、从患病状态转变为非患病状态的羊群以及作为通过实施各种新管理来减少跛行的临床试验的一部分的羊群的羊脚上的结节病。总共将收集约11,000个足部拭子样本进行分析。分析将使用现代分子技术来确定是否有D。nodosus是否存在于健康鸡群中，是否存在不同的D.结节状芽孢杆菌（恶性和良性）在疾病进展的不同阶段存在，以及是否存在结节状芽孢杆菌的数量。脚上的结节与脚的疾病状态有关。然后，我们将使用这些数据来模拟脚上、羊身上和羊群中发生的事情，以了解疾病如何传播和持续，以及如何预防。这些模型将使用复杂的统计数据来确定哪些因素在疾病进展中最重要，并使用强大的数学来确定这些因素如何导致疾病传播和持续。该项目包括科学家致力于了解微生物群落如何在时间和空间中变化，兽医流行病学家，他们研究牲畜疾病如何传播和控制，建模者确定我们今天收集的数据如何用于最有效地治疗和预防疾病，未来

Footrot causes lameness in sheep. This debilitating disease causes sheep to lose weight and produce less milk so that their lambs grow slowly. Footrot is very common in the UK, affecting >98% of sheep flocks, with ~3 million sheep becoming lame/year. Footrot is caused by Dichelobacter nodosus, an anaerobic bacterium, that causes inflammation of the skin in a sheep's foot: this causes lameness. In some cases damage is so severe that the hoof horn separates from the living tissue inside the foot and exposes this flesh (severe footrot, SFR). It is an infectious disease that spreads between sheep, and sheep can become lame repeatedly because immunity is poor. Consequently footrot is an important cause of reduced productivity and poor welfare in sheep. Footrot costs the UK industry ~£80 million/year and is one of the most costly diseases in sheep farming globally.Whilst we know D. nodosus causes footrot we also know that it is present on healthy feet and so does not always cause disease. Some D. nodosus strains are more able to cause severe disease than others. In the laboratory strains are labelled virulent (can cause SFR) or benign (cannot cause SFR) because of genetic markers in the bacteria, however, this is classification does not match disease that we see in sheep.Footrot is present all year round (endemic) in most areas of the UK, appearing as a series of mini-epidemics throughout the year. Yet, in some parts of the world farmers have eradicated footrot from their flock. This is difficult in the UK because footrot is present in so many flocks, persists in our temperate climate and is spread between flocks by movement of sheep between farms, which is common in the UK. Control is therefore a more feasible option for the UK. This can be done by separating diseased sheep, treating sheep promptly to prevent disease spread, by preventive footbathing in disinfectant and by vaccines (although the currently licensed vaccine is not effective if used alone). These do not prevent disease.Studies of all strains of D. nodosus on the feet of on healthy, inflamed and diseased feet show that increasing numbers of D. nodosus on inflamed skin is linked to increasing risk of the development of severe disease.Here we propose that for disease to occur at least one virulent D. nodosus must be present and in sufficient numbers on a foot and conversely that control can be gained by reducing the number of D. nodosus and reducing the number of virulence factors in the population of D. nodosus. To test these ideas we will investigate the population of D. nodosus on the feet of sheep from flocks that are free from footrot, sheep that are changing from the diseased to non-diseased state and in flocks that are part of a clinical trial to reduce lameness by implementing a variety of new managements. In total ~11,000 swab samples of feet will be collected for analysis.The analysis will use modern molecular techniques to determine whether D. nodosus is present in healthy flocks, whether different strains of D. nodosus (both virulent and benign) are present at different points in the progression of disease and whether the number of D. nodosus that are present on feet is linked to the disease state of the foot. We will then use these data to model what is happening on the feet, on sheep and within a flock to understand how the disease spreads and persists and how this might be prevented. The models will use sophisticated statistics to determine what factors are most important in disease progression and powerful mathematics to determine how these lead to disease spread and persistence.This project includes scientists working to understand how communities of microbes change in time and space, with veterinary epidemiologists, who investigate how livestock diseases spread and can be controlled and modellers who determine how data we collect today can be used to most effectively treat and hopefully prevent disease in the future.