SBIR Phase II: Broad-based Urine Test for the Diagnosis of Plasmodium falciparum and P. vivax Malaria In Febrile Patients

这项小企业创新研究（SBIR）二期项目将开发和验证一种基础广泛、无创、单步尿液疟疾检测（UMT-Pf/Pv），用于临床诊断恶性疟原虫（Pf）和间日疟原虫（Pv）疟疾，这两种疟疾每年导致约80万人死亡。由于疟疾死亡发生在症状出现后48小时内，如果能够在大多数病例发生的家庭或村庄环境中管理疟疾，将（一）促进迅速获得抗疟疾治疗，（二）有针对性地向需要治疗的人提供治疗，以及（三）降低疟疾死亡率。在本项目中，将利用热疟疾患者尿液中发现的新型多天冬酰胺蛋白片段的单克隆抗体（mab）来开发UMT-Pf/Pv试纸。这四个重叠的具体目标是：(1)对I期开发的单克隆抗体的诊断效用进行详细表征；(2)开发、测试和优化原型，以满足设计输入规范；(3)实施初步性能评价研究，以评估敏感性/特异性；(4)进行初步临床试验。作为血液检测的一种非侵入性替代方法，UMT-Pf/Pv可促进在疟疾流行的所有地理区域的环境中提供快速疟疾诊断，显著影响全世界诊断和治疗疟疾的方式。该项目的更广泛影响/商业潜力是开发一种基础广泛的一步尿液检测，用于在家庭或护理点诊断发烧患者的临床氟性和/或Pv疟疾。使用UMT-Pf/Pv量尺，操作人员需要执行的步骤数量大大减少，在初级保健环境中具有更高的实用性、便利性和可靠性。该测试还将促进将疟疾RDTs有效地纳入私营部门疟疾病例管理，并鼓励在流行地区，特别是在农村地区和经常发生混合感染的地方，更广泛地接受临床疟疾诊断。总体而言，该检测方法有可能显著影响95%以上的临床疟疾的诊断和治疗方式，并推动目前全球努力按照世界卫生组织的要求，在治疗所有发热病例之前进行家庭或护理点疟疾检测。由于该测试基于与当前rdt相同的平台，因此可以很容易地将其整合到当前的卫生保健结构中，从而为大多数流行国家的公共卫生提供重大益处。目前还没有这样的测试。

This Small Business Innovation Research (SBIR) Phase II project will develop and validate a broad-based non-invasive, single-step Urine Malaria Test (UMT-Pf/Pv) for the clinical diagnosis of Plasmodium falciparum (Pf) and P. vivax (Pv) malaria, which account for ~800,000 deaths a year. Since malaria deaths occur within 48 hours of onset of symptoms, the ability to manage malaria at home or in village settings where most cases occur would (i) facilitate prompt access to antimalarial treatment, (ii) target treatment to those who need it, and (iii) reduce malaria mortality. In this project, monoclonal antibodies (MAbs) to novel poly-asparagine protein fragments identified in the urine of febrile malaria patients will be used to develop a UMT-Pf/Pv dipstick. The four overlapping specific aims are to (1) perform a detailed characterization of the diagnostic utility of MAbs developed in Phase I; (2) develop, test and optimize a prototype to meet design input specifications; (3) implement preliminary performance evaluation studies to evaluate sensitivity/specificity, and; (4)undertake preliminary clinical testing. As a non-invasive alternative to blood-based tests, the UMT-Pf/Pv could facilitate the delivery of rapid malaria diagnosis in settings across all geographical areas where malaria is endemic, markedly impacting the way malaria is diagnosed and treated worldwide.The broader impact/commercial potential of this project is the development of a broad-based one-step urine test for the home-based or point-of-care diagnosis of clinical Pf and/or Pv malaria in persons with fever. With the UMT-Pf/Pv dipstick, the number of steps that the operator is required to perform is significantly reduced, permitting greater utility, convenience and reliability in primary care settings. The test will also facilitate the effective integration of malaria RDTs into private sector malaria case management and encourage wider acceptability of clinical malaria diagnosis in endemic regions, especially in rural areas and in places where mixed infections frequently occur. Overall, the test has the potential to markedly impact the way over 95% of all clinical malaria is diagnosed and treated, and drive current global efforts toward home-based or point-of-care testing for malaria prior to treatment in all cases of fever, as mandated by the World Health Organization. Since it is based on the same platform as current RDTs, this test can be easily integrated into current healthcare structures to provide significant benefits to public health in most endemic countries. No such test is currently available.