Diagnosis of gambiense HAT

冈比亚HAT的诊断

• 批准号: 8044779
• 负责人: Dennis John Grab
• 金额: $ 32.15万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-03 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8044779
• 关键词: Abbreviations; Acute; Africa; African; African Trypanosomiasis; Agglutination Tests; Angola; Anions; Archives; Area; Bacillus (bacterium); Biological Assay; Blood; Blood Circulation; Cessation of life; Characteristics; Chronic; Clinical; Clinical Sensitivity; Communicable Diseases; DNA; Demyelinations; Detection; Diagnosis; Diagnostic Procedure; Diagnostic tests; Disease; Disease Progression; Drowsiness; Drug toxicity; Early Diagnosis; Environment; Epidemic; Failure; Fluorescent Antibody Technique; Genes; Healthcare; Human; Humidity; Incubators; Individual; Infection; Invaded; Lead; Left; Malaria; Mediating; Meningoencephalitis; Methods; Morbidity - disease rate; Mus; Myelin P0 Protein; Names; Neuraxis; Neurologic; Parasitemia; Parasites; Parasitic Diseases; Patients; Pharmacotherapy; Phase; Plague; Polymerase Chain Reaction; Proteins; Reaction; Relapse; Resistance; Rural; Sampling; Sensitivity and Specificity; Serum; Signs and Symptoms; Sleep disturbances; Sleeplessness; Specificity; Speed; Spinal Puncture; Staging; Sudan; Symptoms; Syndrome; Techniques; Technology; Temperature; Testing; Translational Research; Treatment Failure; Treatment Protocols; Trypanosoma; Trypanosoma brucei brucei; Trypanosoma brucei gambiense; Trypanosoma brucei rhodesiense; Trypanosomiasis; Uganda; Viral; Visual; Work; base; clinical Diagnosis; cost effective; design; high risk; killings; magnesium pyrophosphate; mortality; novel diagnostics; pathogen; response; retinal rods; rural area; success; tripolyphosphate; working group

DESCRIPTION (provided by applicant): Trypanosoma brucei gambiense and T. b. rhodesiense are pathogens responsible for human African trypanosomiasis (HAT or sleeping sickness). Death from HAT is inevitable if untreated. Recently, HAT has reached epidemic proportions with over 40,000 people dying every year in Africa. While resistance to the limited drug therapies may be a factor, in the rural areas where patients are typically seen, failure to microscopically observe trypanosomes in blood smears and/or CSF in the critical early stages of the disease is probably the single most important factor in failed treatment. While early detection of HAT using PCR-based methods is possible, the use of often non- affordable "thermal cyclers" that may work erratically at high ambient temperatures, humidity and/or dusty environments, negates PCR as a practical diagnostic method in HAT endemic areas. We propose a recent technology that we believe will be important for the detection of parasite infections, particularly in the field setting. It is an alternative to PCR called loop-mediated isothermal amplification (LAMP). This reaction amplifies DNA with high specificity, efficiency and speed under isothermal conditions and allows for easy visual positive identification of the target DNA. We have developed LAMP for the detection HAT caused by T. b. gambiense and T. b. rhodesiense. We propose that LAMP will provide an easier, potentially more specific, alternative to PCR and other detection methods for use in the field. In this application we propose to validate the potential of LAMP-based tests for the clinical diagnosis of HAT in Angola with an emphasis on Stage 2 HAT. Success in the completion of the Specific Aims of this proposal will provide novel diagnostic tests for the early detection of HAT applicable in African health care centers and in the field. African sleeping sickness, caused by African trypanosomes (a protozoan parasite), kills over 40,000 people each year in Africa. This is because good tests for diagnosis and staging of sleeping sickness in rural areas do not exist. We want to develop a new and easy test for early diagnosis of this deadly disease.

描述（由申请人提供）：Trypanosoma brucei gambiense 和 T. b.罗得西亚锥虫是导致人类非洲锥虫病（HAT 或昏睡病）的病原体。如果不及时治疗，HAT 导致的死亡是不可避免的。最近，HAT 已达到流行病的程度，非洲每年有超过 40,000 人死亡。虽然对有限药物治疗的耐药性可能是一个因素，但在患者经常出现的农村地区，未能在疾病关键的早期阶段用显微镜观察血涂片和/或脑脊液中的锥虫可能是治疗失败的最重要因素。虽然使用基于 PCR 的方法早期检测 HAT 是可能的，但使用通常价格昂贵的“热循环仪”可能在高环境温度、湿度和/或多尘环境下工作不稳定，从而否定了 PCR 作为 HAT 流行地区的实用诊断方法。我们提出了一项最新技术，我们相信该技术对于检测寄生虫感染非常重要，特别是在现场环境中。它是 PCR 的替代方案，称为环介导等温扩增 (LAMP)。该反应在等温条件下以高特异性、高效率和高速度扩增 DNA，并可轻松直观地对目标 DNA 进行阳性识别。我们开发了 LAMP 用于检测 T. b. 引起的 HAT。冈比亚和 T. b.罗德西亚。我们建议 LAMP 将提供一种更简单、可能更特异的 PCR 和其他检测方法的替代方案，供现场使用。在此应用中，我们建议验证基于 LAMP 的测试在安哥拉 HAT 临床诊断的潜力，重点是 2 期 HAT。成功完成该提案的具体目标将为早期检测 HAT 提供新颖的诊断测试，适用于非洲卫生保健中心和实地。由非洲锥虫（一种原生寄生虫）引起的非洲昏睡病每年导致非洲 40,000 多人死亡。这是因为农村地区不存在用于诊断和分期昏睡病的良好测试。我们希望开发一种新的、简单的测试来早期诊断这种致命疾病。