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HIV/AIDS患者中常见的严重机会性感染。在许多资源有限的地区，如拉丁美洲，艾滋病毒/艾滋病的发病率可能超过20%，病例死亡率超过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的床旁（POC）诊断测试。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，昂贵，并且需要训练有素的人员。另一种诊断方法是检测体液如血液或尿液中的脱落真菌抗原。免疫测定是诊断广谱感染性疾病的真菌和微生物感染的成熟手段。重要的是，使用平台技术如侧流测定（LFA），免疫测定容易适应于POC形式。在标题为“Point-of-care immunoassay for diagnosis of histoplasmosis in HIV/AIDS”的I期STTR Grant#1 5 R41 AI 096945 -02中，开发了针对组织胞浆菌多糖的单克隆抗体，并用于开发准确检测感染患者尿液中组织胞浆菌抗原存在的LFA。该II期项目的目标是进一步开发和验证组织胞浆菌LFA，用于南美洲HIV/AIDS感染患者尿液中组织胞浆菌病的明确诊断。该II期SBIR提案成功的标准是生成数据以支持诊断检测的510 k应用，该诊断检测将明确检测感染患者尿液中是否存在组织胞浆菌，这最终可能导致与该疾病相关的死亡率大幅降低。

 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.