Diagnosis of gambiense HAT

冈比亚HAT的诊断

基本信息

批准号：
8239586
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
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-03 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8239586
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

项目摘要

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，在疾病的关键早期阶段未能用显微镜观察血涂片和/或脑脊液中的锥虫可能是导致这种情况的最重要因素。治疗失败。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 流行病的实用诊断方法。地区。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 将为 PCR 和其他现场使用的检测方法提供一种更简单、可能更特异的替代方案。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。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（1）

Loop-Mediated Isothermal Amplification for Detection of the 5.8S Ribosomal Ribonucleic Acid Internal Transcribed Spacer 2 Gene Found in Trypanosoma brucei gambiense.

用于检测布氏冈比亚锥虫中发现的 5.8S 核糖体核糖核酸内转录间隔区 2 基因的环介导等温扩增。

DOI：
10.4269/ajtmh.15-0288
发表时间：
2017
期刊：
The American journal of tropical medicine and hygiene
影响因子：
0
作者：
Nikolskaia,OlgaV;Thekisoe,OrielMM;Dumler,JStephen;Grab,DennisJ
通讯作者：
Grab,DennisJ

Using detergent to enhance detection sensitivity of African trypanosomes in human CSF and blood by loop-mediated isothermal amplification (LAMP).

DOI：
10.1371/journal.pntd.0001249
发表时间：
2011-08
期刊：
PLoS neglected tropical diseases
影响因子：
3.8
作者：
Grab DJ;Nikolskaia OV;Inoue N;Thekisoe OM;Morrison LJ;Gibson W;Dumler JS
通讯作者：
Dumler JS

Detection of pathogen-specific antibodies by loop-mediated isothermal amplification.

通过环介导的等温扩增检测病原体特异性抗体。

DOI：
10.1128/cvi.00811-14
发表时间：
2015
期刊：
Clinical and vaccine immunology : CVI
影响因子：
0
作者：
Burbulis,IanE;Yamaguchi,Kumiko;Nikolskaia,OlgaV;Prigge,SeanT;Magez,Stefan;Bisser,Sylvie;Reller,MeganE;Grab,DennisJ
通讯作者：
Grab,DennisJ