22-ICRAD Call 2 - Improving the diagnosis of tuberculosis in domestic ruminants through the use of new antigens and test platforms

22-ICRAD 呼吁 2 - 通过使用新抗原和测试平台改善家养反刍动物结核病的诊断

• 批准号: BB/Y000927/1
• 负责人: Gareth Jones
• 金额: $ 21.37万
• 依托单位: ANIMAL AND PLANT HEALTH AGENCY
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FY000927%2F1
• 关键词: 22; ICRAD; Call; Improving; diagnosis

Bovine tuberculosis (BTB) presents a significant challenge to animal and public health globally. BTB is also a significant cause of zoonotic TB (zTB), mainly in developing/low and middle income countries (LMIC) as highlighted in the recently published roadmap to zTB eradication jointly produced by WHO, WOAH and the International Union against TB & Lung Disease (UTLD). Their One Health approach acknowledged that TB eradication in animals will impact zTB in humans. Eradication could be accelerated by improved diagnostic tests that overcome limitations associated with Purified Protein Derivative (PPD) tuberculin: limited performance, standardisation, vaccine-interference. These could be overcome by defined antigens. PPDs are used both in tuberculin skin tests and blood interferon-gamma release assays (IGRA). More sensitive blood test platforms that complement the IGRA test could further enhance diagnostic performance. BTB tests primarily targetcellular immunity, yet serological tests can also be useful for additional case detection. Thus, our proposal aims to address these constraints to optimise test performance in an inter-connected manner. We will conduct field validation for test sensitivity and specificity of the defined antigen formulation DST-F (fusion protein of ESAT6, CFP10, Rv3615c) in domestic ruminants (cattle, goats, buffalos) in different epidemiological settings (WP1, skin test, IGRA). Environmental exposure to mycobacteria in the farms will be also evaluated. We will develop a multi-cytokine platform (MCP) to enhance test performance beyond the current IGRA, (WP2) and also develop novel antigen capture and lateral flow assays (WP3). The performance of these innovative tests will be assessed with samples generated in WP1. WP4 will critically assess data generated in WP1-3 and provide recommendations for the optimal combinations of test platforms to accelerate BTB eradication.

牛结核病（BTB）是全球动物和公共卫生面临的重大挑战。BTB也是人畜共患结核病（zTB）的一个重要原因，主要发生在发展中/低收入和中等收入国家（LMIC），这在最近公布的由世卫组织、世界卫生组织和国际结核病和肺病防治联盟（UTB）联合制定的消灭zTB路线图中得到了强调。他们的“一个健康”方法承认，在动物中根除结核病将影响人类的zTB。通过改进诊断试验，克服与纯化蛋白衍生物（PPD）结核菌素相关的局限性（性能有限、标准化、疫苗干扰），可以加速根除。这些可以通过确定的抗原来克服。PPD用于结核菌素皮肤试验和血液干扰素-γ释放试验（IGRA）。补充IGRA测试的更灵敏的血液测试平台可以进一步提高诊断性能。BTB检测主要针对细胞免疫，但血清学检测也可用于其他病例检测。因此，我们的提案旨在解决这些限制，以相互关联的方式优化测试性能。我们将在不同流行病学环境（WP 1、皮肤试验、IGRA）下，对确定的抗原制剂DST-F（ESAT 6、CFP 10、Rv 3615 c的融合蛋白）在家养反刍动物（牛、山羊、水牛）中的试验灵敏度和特异性进行田间验证。还将评估农场中分枝杆菌的环境暴露。我们将开发一个多细胞因子平台（MCP），以提高测试性能，超越目前的IGRA，（WP 2），并开发新的抗原捕获和侧流测定（WP 3）。这些创新测试的性能将使用WP 1中生成的样本进行评估。WP 4将严格评估WP 1 -3中生成的数据，并为加速BTB根除的测试平台的最佳组合提供建议。