Lateral Flow Assay for Diagnosis of Histoplasmosis

 描述(由申请人提供)：进行性播散性组织胞浆菌病是艾滋病毒/艾滋病患者中一种常见且严重的机会性感染。在许多资源有限的地区，如拉丁美洲，艾滋病毒/艾滋病的发病率可达20%，病例死亡率为30%。艾滋病患者组织胞浆菌病的成功治疗需要早期诊断和治疗。因此，迫切需要一种快速、有效和低成本的组织胞浆菌病诊断方法。目前，组织胞浆菌病的诊断依赖于通过组织病理学或培养在临床标本中证实真菌。这种方法灵敏度低，耗时长，价格昂贵，需要训练有素的人员。另一种诊断方法是检测血液或尿液等体液中的脱落真菌抗原。免疫分析是诊断各种传染病的真菌和微生物感染的一种行之有效的方法。重要的是，免疫分析很容易适应使用平台技术的POC格式，例如侧向流动分析(LFA)。在第一阶段STTR赠款#1 5R41AI096945-02中，开发了一种针对组织胞浆多糖的单抗，并将其用于开发一种能够准确检测感染患者尿液中组织胞浆抗原存在的LFA。这一第二阶段项目的目标是进一步开发和验证组织胞浆LFA，以明确诊断南美洲艾滋病毒/艾滋病患者尿液中的组织胞浆菌病。这项第二阶段SBIR建议的成功标准将是生成数据，以支持510K诊断试验的应用，该诊断试验将明确检测感染患者尿液中组织胞浆的存在，这最终可能导致与这种疾病相关的死亡率大幅下降。

 DESCRIPTION (provided by applicant): Progressive disseminated histoplasmosis is a common and serious opportunistic infection among individuals with HIV/AIDS. In many resource-limited areas, such as Latin America, incidence rates in HIV/AIDS can be >20%, with mortality rates among cases >30%. Successful treatment of histoplasmosis in patients with AIDS requires early diagnosis and treatment. As a consequence, there is a critical need for a rapid, effective and low-cost point-of-care (POC) diagnostic test for histoplasmosis. Currently, diagnosis of histoplasmosis relies on demonstration of the fungus in clinical specimens by histopathology or culture. Such methods have a low sensitivity, are time consuming, are expensive, and require trained personnel. An alternative approach to diagnosis is detection of shed fungal antigens in body fluids such as blood or urine. Immunoassays are a well-established means to diagnose fungal and microbial infections for a broad spectrum of infectious diseases. Importantly, immunoassays are readily adaptable to a POC format using platform technologies such as a lateral flow assay (LFA). In the Phase I STTR Grant #1 5R41AI096945-02 entitled "Point-of-care immunoassay for diagnosis of histoplasmosis in HIV/AIDS" a monoclonal antibody to a Histoplasma polysaccharide was developed and used to develop an LFA that accurately detects the presence of Histoplasma antigen in the urine of infected patients. The goal of this Phase II project is to further develop and validate the Histoplasma LFA for definitive diagnosis of histoplasmosis in the urine of HIV/AIDS infected patients in South America. Criteria for success of this Phase II SBIR proposal would be the generation of data to support a 510k application of a diagnostic assay that would definitively detect the presence of Histoplasma in the urine of infected patients, which could ultimately result in a dramatic decrease in the mortality associated with this disease.