ICF: Development of a rapid diagnostic test to identify Crimean-Congo Haemorrhagic Fever at the point-of-care

克里米亚-刚果出血热（CCHF）是世界卫生组织（WHO）列出的优先疾病，因为它的死亡率高，缺乏疫苗和有效的治疗和诊断。CCHF患者的死亡率很高，并且只有一种抗病毒药物只有在疾病早期使用才有效。然而，目前用于CCHF诊断的测试结果的转变缓慢，延迟2-5天，导致治疗效果降低和患者恢复不良。开发用于快速诊断CCHF的快速诊断测试（RDTs）已被WHO确定为优先事项。该提案旨在满足这一需求，利物浦热带医学院（LSTM）与全球接入诊断公司（GADx）合作开发了第一个诊断CCHF的RDT原型，其灵敏度和特异性符合WHO对RDT的建议。LSTM与GADx合作将优化RDT，以在ISO认证的环境中改进灵敏度和特异性。GADx将扩大生产技术的规模，包括原液结合，并在其质量管理体系中使用质量控制系统，以确保RDT在批次之间以及以商业批量生产时保持其原始性能。我们将做一个市场范围界定工作，以确定客户和拉动通过机制，以市场为这一重要的RDT。我们将使用所有套件组件设计锁定产品以进行评估。首先，我们将与英国卫生安全局（UKHSA）对所有CCHF病毒谱系进行分析评价，然后我们将在土耳其卫生部（MoH）和伊拉克疾病控制和预防中心（CDC）评价库存样本中的RDT。此外，LSTM将与卫生部合作，在土耳其CCHF高流行地区的492名二级卫生诊所患者中开展临床试验，对RDT进行诊断评估。这些试验的数据将用于编写UKCA标记下的监管申报资料。

Crimean-Congo haemorrhagic fever (CCHF) is a World Health Organisation (WHO)-listed priority disease due to its high mortality and lack of vaccines and effective treatment and diagnostics. Patients with CCHF have a high mortality and there is only one antiviral used that may only be effective if given early in disease. However, the current turnaround of test results for CCHF diagnosis is slow with a 2-5-day delay causing reduced treatment efficacy and poor patient recovery. The development of rapid diagnostic tests (RDTs) for rapid diagnosis of CCHF has been identified as a priority by the WHO. This proposal seeks to address this need and the Liverpool School of Tropical Medicine (LSTM) in collaboration with Global Access Diagnostics (GADx) have achieved the development of the first RDT prototype to diagnose CCHF with a sensitivity and specificity that fulfils the recommendations from WHO for RDTs.LSTM in collaboration with GADx will optimise the RDT to refine sensitivity and specificity within an ISO-accredited environment. GADx will perform up-scale of manufacturing techniques including bulk conjugations and use quality control systems within their Quality Management System to ensure that the RDT preserves its original performance between batches and when manufactured at commercial volumes. We will do a market scoping exercise to identify the customers and pull through mechanisms to market for this important RDT. We will design-lock the product with all the kit components for evaluation. Firstly, we will perform analytical evaluations across all CCHF viral lineages with UK Health Security Agency (UKHSA) and following this we will evaluate the RDT in banked samples at the Ministry of Health (MoH) in Turkey and the Centers for Disease Control and Prevention (CDC) in Iraq. Also, in collaboration with the MoH, LSTM will set up clinical trials for diagnostic evaluation of the RDT among 492 patients attending secondary health clinics in CCHF hyperendemic regions in Turkey. Data from these trials will be used for preparation of regulatory submission under UKCA marking.