Antimicrobials and improved diagnostics towards integrated control of CBPP

CBPP是非洲牛的一种细菌性肺炎，给受影响国家的畜牧农民和国家政府造成重大经济损失。这主要是由于受感染的牛的死亡和存活下来的牛的生产力下降。这种疾病的一个特点是，牛在明显康复后的一段不同时期内继续传播病原体。这些动物被称为携带动物，正因为如此，动物运动在疾病的传播中起着重要作用。因此，CBPP在一个国家的存在往往会对畜产品施加贸易壁垒。因此，各国政府投入了大量资源，试图控制或根除这种疾病。控制CBPP通常是国家兽医部门的责任，并依赖于使用减毒活疫苗，而个体农民无法获得这种疫苗。每年或在疫情爆发时部署这些措施。然而，现有疫苗的效力有限，而且由于国家兽医服务往往资源不足，因此很少实现必要的疫苗覆盖。因此，农民通常会重新使用抗生素来治疗他们认为被感染的牛。不幸的是，关于抗生素治疗感染CBPP的牛的疗效的信息很少，一些研究表明这些干预措施没有任何益处。此外，面对CBPP使用抗生素一直存在争议，因为人们认为抗生素会促进载体状态的建立。事实上，在大多数受影响的国家，不鼓励或禁止使用抗生素治疗CBPP。尽管如此，基于疫苗的控制战略未能限制CBPP在非洲的传播，这导致人们呼吁重新评估抗微生物药物在控制其方面的作用。此外，数学模型研究预测，如果与现有疫苗结合使用，有效的抗菌剂将很有可能成功地从受感染的畜群中根除这种疾病。本项目将采用先进的药理学方法评估三种抗菌化合物对CBPP细菌的功效，并制定合理的剂量策略，以便在现场作为控制工具部署。该项目还将开发一种诊断测试，能够在感染的早期阶段识别牛，使用适用于碾压侧或护理点的格式，为治疗决策提供信息。

CBPP is a bacterial pneumonia of cattle in Africa that causes major economic losses to livestock farmers and national governments in affected countries. These arise chiefly from the death of infected cattle and the reduced productivity of those that survive. A feature of the disease is that cattle continue to shed the pathogen for a variable period after they have apparently recovered. These are known as carrier animals and, because of them, animal movement plays a major role in the spread of the disease. As a result, the presence of the CBPP in a country often imposes trade barriers on livestock products. Considerable resources are therefore invested by national governments in attempts to control or eradicate the disease. Control of CBPP is generally the responsibility of the state veterinary services and relies on the use of live attenuated vaccines, which are not available to individual farmers. These are deployed either annually or in the face of outbreaks. However, available vaccines have limited efficacy, and because state veterinary services are often under-resourced, the necessary vaccine coverage is rarely achieved. Farmers therefore often revert to the use of antibiotics to treat cattle that they believe are infected. Unfortunately, there is little information on the efficacy of antibiotics for treatment of CBPP infected cattle and some studies suggest that these interventions have no benefit. In addition, the use of antibiotics in the face of CBPP has been controversial because of the belief that it promotes establishment of the carrier state. Indeed, use of antibiotics for treatment of CBPP is discouraged or banned in most affected countries. Notwithstanding this, the failure of vaccine-based control strategies to limit the spread of CBPP in Africa has led to calls for a re-evaluation of the role of antimicrobials in its control. In addition, mathematical modeling studies have predicted that, used in conjunction with available vaccines, effective antimicrobials would have a high chance of success in eradicating the disease from infected herds. This project will apply advanced pharmacological methods to evaluate three antimicrobial compounds for their efficacy against the CBPP bacterium and develop rational dosage strategies for their deployment as control tools in the field. The project will also develop a diagnostic test capable of recognising cattle in the early stages of infection, using a format applicable at the crush side or point-of-care, to inform decisions to treat.