Understanding the inflammatory processes of neurocysticercosis: a US-India partne

了解神经囊尾蚴病的炎症过程：美印合作伙伴

• 批准号: 8246179
• 负责人: Helene Carabin
• 金额: $ 19.46万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8246179
• 关键词: Accounting; Antibodies; Antigens; Applications Grants; Biochemistry; Bioinformatics; Biological Markers; Biology; Biometry; Bone Cysts; Brain; Calcified; Candidate Disease Gene; Caring; Central Nervous System Infections; Characteristics; Christian Science; Classification; Clinical; Clinical Services; Collaborations; Collection; Complement; Cyst; Cysticercosis; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic Imaging; Diagnostic Procedure; Disease; Educational workshop; Encephalitis; Epidemiology; Epilepsy; Evolution; Funding; Gene Expression Profile; Genes; Genetic Transcription; Gold; Health Sciences; Image; Immune response; India; Infection; Inflammatory; Knowledge; Lead; Lesion; Life; Medicine; Messenger RNA; Methods; Molecular Profiling; Monitor; Neurocysticercosis; Neurologic; Oklahoma; Parasitic infection; Pathology; Patients; Pattern; Peripheral; Phase; Process; Proteins; Public Health; Publishing; Recruitment Activity; Research; Research Personnel; Research Training; Resolution; Scientist; Seizures; Sensitivity and Specificity; Serum; Societies; Spectrometry, Mass, Electrospray Ionization; Staging; Taenia solium; Technology; Test Result; Testing; Training; Tuberculosis; Universities; Work; X-Ray Computed Tomography; base; college; computerized; cost; graduate student; innovation; mRNA Expression; medical schools; meetings; minimally invasive; molecular marker; monocyte; novel; novel diagnostics; small molecule; statistics; tool

DESCRIPTION (provided by applicant): Neurocysticercosis (NCC) is a parasitic infection of the brain that accounts for 34% of active epilepsy cases in Vellore district, India. New methods for diagnosing patients with NCC are badly needed. The cost of diagnostic imaging is beyond the means of most patients, and 34% of NCC patients are missed by the gold standard for antibody detection. Recent data suggest that host immune responses are important for determining manifestations of NCC infection. Thus, analyses of non-antibody host responses using state of the art methods present a novel and logical approach for advancing knowledge in detection of NCC. The long-term objective of this US-India proposal is to identify novel circulating biomarkers for diagnosis for NCC-associated epilepsy. The purposes of this proposal are to establish an effective collaboration among investigators from the Univ. of Oklahoma Health Sciences Center (OUHSC), USA, and the Christian Medical College (CMC), India, and to test the extent to which serum profiling by electrospray ionization mass spectrometry (ESI-MS) and analysis of mRNA expression in blood monocytes represent innovative tools for better detection of NCC and its manifestations. The Collaborative partnership aim brings together expertise in epidemiology/biostatistics, monocyte biology and biochemistry with clinical and immunological expertise in NCC. In Research Aim 1, we will test the extent to which serum profiling by ESI-MS can develop of panel of small molecular markers to distinguish patients with NCC-associated epilepsy identified at CMC from well-characterized controls. In Research Aim 2, we will analyze mRNA expression of blood monocytes to identify gene expression signatures characteristic of NCC patients among people with epilepsy. Research Aim 3 will compare a sequential na¿ve Bayes statistical classification approach to the traditional approach to classify patients using results from Aims 1 and 2. During an initial meeting in Vellore, India, opportunities for exchange of scientists and graduate students as well as needs in training will be assessed. A workshop on Bayesian statistics will be organized. The research component will include collection of blood and sera from patients attending the clinical services of Dept. of Neurological Sciences, CMC. Four groups of patients will be selected: 1) patients with NCC-associated active epilepsy/seizures; 2) NCC patients recovered for at least 2 years; 3) patients with active epilepsy/seizures without evidence of NCC or cysticercosis; 4) patients without NCC, cysticercosis, and a normal brain CT scan. Serum profiling will be conducted at OUHSC, whereas monocyte isolation and analysis of mRNA expression will be conducted at CMC. Results will be compared with gold-standard antibody and antigen detection methods. This research will allow us to determine if mRNA expression profiling of monocytes and ESI-MS can be used to 1) identify cases of epilepsy, 2) identify cases of NCC-associated epilepsy, 3) describe the evolution of the inflammatory process post resolution of the lesions and 4) differentiate between types of NCC lesions. PUBLIC HEALTH RELEVANCE: Neurocysticercosis (NCC) is a parasitic infection of the brain which occurs when the larval stage of Taenia solium develops in the brain. NCC represents an enormous burden to Indian society. For example, 34% of all patients with active epilepsy in the Vellore district, India have NCC lesions in their brain. Diagnosis of NCC- associated epilepsy relies on computerized tomographic imaging, a technology inaccessible to most people living in India. Moreover current antibody and antigen based tests are sub-optimal. Thus, there is great need to identify novel biomarkers that will complement and extend the ability to diagnose diverse disease states and that will be inexpensive and minimally invasive. Research results from this proposal could provide novel diagnostic methods for NCC, as well as for identifying the stage of NCC infection in the brain. Earlier and more accurate detection of NCC would be a tremendous benefit to public health. Methods in this proposal also could be applied towards developing new diagnostic methods for other central nervous system infections.

描述（由申请人提供）：神经囊虫病（NCC）是一种脑部寄生虫感染，占印度Vellore地区活动性癫痫病例的34%。迫切需要诊断非细胞癌患者的新方法。诊断成像的费用超出了大多数患者的承受能力，34%的NCC患者没有通过抗体检测的金标准。最近的数据表明，宿主免疫反应是确定NCC感染表现的重要因素。因此，使用最先进的方法分析非抗体宿主反应，为提高NCC检测知识提供了一种新颖而合乎逻辑的方法。这项美国-印度提案的长期目标是确定用于诊断ncc相关癫痫的新型循环生物标志物。本提案的目的是在美国俄克拉何马大学健康科学中心（OUHSC）和印度基督教医学院（CMC）的研究人员之间建立有效的合作，并测试通过电喷雾电离质谱（ESI-MS）和血液单核细胞mRNA表达分析的血清谱分析在多大程度上代表了更好地检测NCC及其表现的创新工具。该合作伙伴关系旨在将流行病学/生物统计学、单核细胞生物学和生物化学方面的专业知识与NCC的临床和免疫学专业知识结合起来。在研究目标1中，我们将测试ESI-MS血清谱分析在多大程度上可以开发一组小分子标记，以区分CMC鉴定的nc相关癫痫患者和特征良好的对照组。在研究目标2中，我们将分析血液单核细胞mRNA表达，以确定癫痫患者中NCC患者的基因表达特征。研究目标3将使用目标1和目标2的结果比较顺序朴素贝叶斯统计分类方法和对患者进行分类的传统方法。在印度Vellore举行的首次会议上，将评估科学家和研究生交流的机会以及培训方面的需求。将组织一个关于贝叶斯统计的研讨会。研究部分将包括从参加CMC神经科学系临床服务的患者收集血液和血清。将选择四组患者：1)与ncc相关的活动性癫痫/发作患者；2) NCC患者康复至少2年；3)无NCC或囊虫病证据的活动性癫痫/癫痫发作患者；4)无NCC、囊虫病，且脑CT扫描正常的患者。血清谱分析将在OUHSC进行，而单核细胞分离和mRNA表达分析将在CMC进行。结果将与金标准抗体和抗原检测方法进行比较。这项研究将使我们能够确定单核细胞mRNA表达谱和ESI-MS是否可以用于1)识别癫痫病例，2)识别NCC相关癫痫病例，3)描述病变消退后炎症过程的演变，以及4)区分NCC病变类型。