RaDiCal: Rapid diagnosis of Calf Pneumonia

我们将开发一种快速、灵敏、具有成本效益的农场诊断检测方法，能够检测引起小牛肺炎的微生物，以告知牛群管理并减少不必要的抗生素使用。肺炎的早期诊断将使农民能够以适当和及时的方式进行治疗。犊牛肺炎是一种由多种病原体引起的复杂疾病。通常，临床疾病是由某些种类的细菌引起的，这些细菌通常不会对肺部造成不良影响，但当动物以某种方式受到损害时，例如特定的病毒感染与其他应激因素（如断奶、饲料变化、环境温度和湿度变化）相结合时，就会对肺部造成不良影响。据估计，一头小母牛患肺炎的终生经济成本为772英镑，这凸显了投资减少这种疾病影响的潜在回报。尽管小牛肺炎给英国养牛业带来了巨大的成本，但大多数农民更愿意降低疾病发生的可能性，或者依靠非特异性手段检测肺炎。这并不是说没有诊断测试，但测试的高成本和结果延迟的事实，因此不能为治疗决定提供信息，这可能是这些测试不被常规使用的原因。我们打算通过与农民、兽医和小牛饲养者的接触，在本项目中更详细地了解牲畜诊断测试使用的障碍。快速分子诊断的最新发展（许多是由项目团队开发的）提供了一种比现有商业测试更便宜、更快、更灵敏的测试的可能性，为将这种测试用于农场常规监测提供了机会。这将有助于早期干预和制定具体的治疗方案，从而减少抗生素耐药性并改善小牛福利。我们的项目位于政策变化、经济机遇、不断变化的实践、公众对行业的看法甚至抗生素管理之间的交叉点。我们是一个新的重点合作伙伴关系，结合了奶牛养殖的工作知识、兽医传染病的专业知识、诊断测试开发和利益相关者参与方法。该测试将基于使用简单的鼻道拭子同时检测与小牛肺炎相关的六种最常见感染中的任何一种，与目前针对COVID-19的侧流测试没有什么不同。拭子将放置在项目合作伙伴开发的新型装置中，该装置使用侧向流装置提供测试结果的简单最终读数。我们打算采用的技术已被证明可用于检测至少一些与小牛肺炎相关的病原体，并且其中三个合作伙伴具有使用该技术开发兽医重要病原体快速检测和人类呼吸道传染病检测（包括COVID-19）。然而，开发测试只是故事的一半，我们必须确保测试是与最终使用它的人共同开发的。其中一个合作伙伴是奶农，另一个是畜牧兽医，另外两个人在过去五年中与小牛饲养者一起工作，研究肺炎管理和抗生素耐药性。使用方法，如与小牛饲养者和兽医的访谈/研讨会，我们将询问以下问题：您目前如何控制肺炎，从开始到结果需要多快的测试，应该花费多少钱，哪种销售渠道最有吸引力，以及您将如何应对测试结果？这将是至关重要的信息，以确保我们开发的测试有最好的机会在农场使用，以造福动物健康和福利，GB养牛业，等等。

We shall develop a rapid, sensitive, cost-effective on-farm diagnostic test capable of detecting the organisms responsible for calf pneumonia to inform herd management and reduce the unnecessary use of antibiotics. Early diagnosis of pneumonia will allow the farmer to administer treatment in a proportionate and timely way. Calf pneumonia is a complex disease caused by a variety of infectious agents. Typically, the clinical disease is caused by certain species of bacteria that may normally cause no adverse effects to the lungs but do so when the animal is compromised in some way, such as a specific viral infection in combination with other stress factors, such as weaning, changes of feed, variation in ambient temperature and humidity. The estimated lifetime economic cost of a case of pneumonia in a dairy heifer is £772, highlighting the potential returns from investing in reducing the impact of this disease. Despite the substantial cost that calf pneumonia causes the UK cattle industry, most farmers prefer to reduce the likelihood of the disease occurring or rely on detecting pneumonia through non-specific means. That is not to say that diagnostic tests are not available, but the high cost of tests and the fact that the results are delayed and therefore cannot inform treatment decisions are likely reasons why these are not used routinely. We intend to understand the impediments to livestock diagnostic test use in more detail in this project through engagement with farmers, vets, and calf rearers.Recent developments in rapid molecular diagnostics (many by the project team) offer the possibility of delivering a test that is considerably cheaper, quicker and more sensitive than existing commercial tests, opening up the opportunity to use such a test for routine surveillance on-farm. This would enable early intervention and the development of specific treatment protocols, thus reducing antimicrobial resistance and improving calf welfare. Our project sits at the intersections between policy change, economic opportunity, changing practice, public perception of the industry, and even antibiotic stewardship.We are a new and focused partnership that combines working knowledge of dairy farming, expertise in veterinary infectious disease, diagnostic test development and stakeholder engagement methods. The test will be based on simultaneous detection of any of the six most common infections associated with calf pneumonia using a simple swab of the nasal passages, not unlike the current lateral flow tests for COVID-19. The swab will be placed in a novel device developed by the project partners that gives a simple final readout of the test result using a lateral flow device. Proof of principle has been demonstrated for the technology we intend to adopt for the detection of at least some of the pathogens associated with calf pneumonia, and three of the partners have experience of the development of rapid tests using this technology for pathogens of veterinary importance, and respiratory infectious disease testing in humans (incl. COVID-19). However, developing a test is only half the story, and we must ensure the test is co-developed with those who will ultimately use it. One of the partners is a dairy farmer, another a livestock veterinarian, and two others have worked with calf rearers for the last five years on pneumonia management and antibiotic resistance. Using methods, such as interviews/workshops with calf rearers and vets, we shall ask questions such as, how do you currently control pneumonia, how quick does the test need to be from start to result, how much should it cost, which sales channel is most attractive, and what will you do differently in response to the test result? This will be vital information to ensure the test we develop has the best chance of being used on farm to the benefit of animal health and welfare, the GB cattle industry, and beyond.