Diagnosis of gambiense HAT

冈比亚HAT的诊断

• 批准号: 7666449
• 负责人: JOHN STEPHEN Dumler
• 金额: $ 42.68万
• 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/7666449
• 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.

性状（由申请方提供）：冈比亚布氏锥虫和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。如果不治疗，HAT的死亡是不可避免的。最近，艾滋病毒/艾滋病已达到流行病的程度，非洲每年有4万多人死亡。虽然对有限药物治疗的耐药性可能是一个因素，但在患者通常可见的农村地区，在疾病的关键早期阶段未能在显微镜下观察到血涂片和/或CSF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，但是使用通常不可负担得起的“热循环仪”（其可能在高环境温度、湿度和/或多尘环境下不稳定地工作）否定了PCR作为HAT流行地区的实用诊断方法。我们提出了一种新的技术，我们认为这将是重要的寄生虫感染的检测，特别是在现场设置。环介导等温扩增（LAMP）是PCR的一种替代方法。该反应在等温条件下以高特异性、高效率和高速度扩增DNA，并允许容易地目视阳性鉴定靶DNA。我们建立了LAMP检测T. B. gambiense和T. B.罗得西亚语我们建议，LAMP将提供一个更容易，潜在的更具体的，替代PCR和其他检测方法在现场使用。在本申请中，我们建议验证基于LAMP的检测用于安哥拉HAT临床诊断的潜力，重点是2期HAT。成功完成本提案的具体目标将为非洲卫生保健中心和该领域适用的HAT早期检测提供新的诊断测试。由非洲锥虫（一种原生动物寄生虫）引起的非洲昏睡病每年在非洲造成4万多人死亡。这是因为在农村地区不存在诊断和分期昏睡病的良好测试。我们希望开发一种新的、简单的测试方法来早期诊断这种致命的疾病。