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

蹄疾步使羊一瘸一拐。这种令人衰弱的疾病会导致绵羊体重减轻，产奶量减少，从而导致羊羔生长缓慢。蹄疾在英国非常普遍，影响了98%的羊群，每年大约有300万只羊变得跛脚。蹄疾是由结节双歧杆菌引起的，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，损伤非常严重，以至于蹄角从脚内的活组织中分离出来，暴露出这块肉(严重脚步，SFR)。这是一种在绵羊之间传播的传染病，绵羊可能会因为免疫力差而反复跛行。因此，蹄踏是导致绵羊生产力下降和福利低下的一个重要原因。蹄疾每年给英国的养羊业造成8000万GB的损失，是全球养羊业中代价最高的疾病之一。虽然我们知道结节孢子虫会引起蹄疾，但我们也知道它存在于健康的脚上，因此并不总是导致疾病。一些节瘤金线虫菌株比其他菌株更能引起严重疾病。在实验室中，由于细菌中的遗传标记，菌株被标记为剧毒(可导致SFR)或良性(不能引起SFR)，然而，这是一种与我们在绵羊身上看到的疾病不匹配的分类。Footrot在英国的大多数地区全年都存在(地方性)，全年都以一系列小型流行病的形式出现。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脚步。在英国很难做到这一点，因为狐步舞存在于如此多的羊群中，持续存在于我们的温带气候中，并通过羊群之间的羊群之间的移动传播，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。这可以通过分离患病的绵羊、及时治疗绵羊以防止疾病传播、预防性地使用消毒剂和疫苗(尽管目前获得许可的疫苗单独使用是无效的)来实现。这些并不能预防疾病。对健康足部、炎症足部和患病足部的所有结节螺旋体的研究表明，发炎皮肤上结节螺旋体数量的增加与发展成严重疾病的风险增加有关。在这里，我们建议，要发生疾病，必须至少存在一种毒力强的节点螺旋体，并在一只脚上有足够数量的节点螺旋体，反之，可以通过减少节瘤螺旋体的数量和减少节点螺旋体种群中的毒力因子的数量来获得控制。为了测试这些想法，我们将调查没有脚步的羊群中的结节圆线虫的数量，这些羊群正在从患病状态转变为非患病状态，以及作为临床试验的一部分，通过实施各种新的管理措施来减少跛行。总共将采集约11,000个脚部拭子样本进行分析。这项分析将使用现代分子技术来确定健康鸡群中是否存在结节螺旋体，是否在疾病进展的不同时间点存在不同的结节螺旋体菌株，以及足部结节螺旋体的数量是否与足部疾病状态有关。然后，我们将使用这些数据来模拟脚部、绵羊和羊群中发生的情况，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疾病进展中最重要的因素，并使用强大的数学来确定这些因素是如何导致疾病传播和持续的。这个项目包括致力于了解微生物群落如何在时间和空间上变化的科学家，与兽医流行病学家一起工作，他们调查牲畜疾病如何传播并可以被控制，以及建模人员，他们确定我们今天收集的数据如何被用于最有效地治疗并有望在未来预防疾病。

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.