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

该小型企业创新研究（SBIR）第二阶段项目将开发和验证一种基础广泛的非侵入性单步尿疟疾检测（UMT-Pf/Pv），用于恶性疟原虫（Pf）和间日疟原虫（Pv）疟疾的临床诊断，每年约有80万人死亡。由于疟疾死亡发生在症状出现后48小时内，因此，如果能够在家中或在大多数病例发生的村庄环境中管理疟疾，将有助于（i）迅速获得抗疟治疗，（ii）有针对性地为有需要的人提供治疗，（iii）降低疟疾死亡率。在这个项目中，单克隆抗体（单克隆抗体）的新的聚天冬酰胺蛋白片段中确定的发热疟疾患者的尿液将被用来开发UMT-Pf/Pv试纸。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，以满足设计输入质量标准;（3）实施初步性能评价研究，以评价灵敏度/特异性;（4）进行初步临床试验。UMT-Pf/Pv作为血液检测的一种非侵入性替代方法，可以促进在疟疾流行的所有地理区域提供快速疟疾诊断，显着影响了全球疟疾的诊断和治疗方式。该项目更广泛的影响/商业潜力是开发一种广泛的一步尿液检测，用于临床Pf和/或Pv疟疾。使用UMT-Pf/Pv试纸，操作员需要执行的步骤数量显著减少，从而在初级保健环境中实现更大的实用性、便利性和可靠性。该测试还将促进将疟疾快速诊断测试有效纳入私营部门疟疾病例管理，并鼓励疟疾流行地区，特别是农村地区和经常发生混合感染的地方更广泛地接受疟疾临床诊断。 总体而言，该测试有可能显著影响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在所有发热病例治疗前进行基于家庭或护理点的疟疾测试，这是世界卫生组织的要求。由于它基于与当前RDT相同的平台，因此该测试可以轻松集成到当前的医疗保健结构中，为大多数流行国家的公共卫生提供显着益处。目前尚无此类测试。

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.