Clinical And Therapeutic Studies Of Human Filariasis and Related Diseases

人类丝虫病及相关疾病的临床和治疗研究

• 批准号: 7592152
• 负责人: Thomas B Nutman
• 金额: $ 43.68万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7592152
• 关键词: Acute; Affect; Angioneurotic Edema; Benign; Blood; Cells; Clinical; Clinical assessments; Condition; Diagnosis; Disease; Eosinophilia; Filarial Elephantiases; Filariasis; Goals; Human; Idiopathic Hypereosinophilic Syndromes; Individual; Infection; Inflammation; Inflammatory Response; Lesion; Loiasis; Lymphatic; Lymphedema; Lymphocyte; Malaria; Molecular; Onchocerciasis; Parasites; Pathogenesis; Pathway interactions; Patients; Population; Reverse Transcriptase Polymerase Chain Reaction; Site; Strongyloides; Strongyloidiasis; Therapeutic Studies; Tissues; Wolbachia; eosinophil; novel diagnostics; therapeutic target; trafficking

To understand better the pathogenesis of filarial infections (onchocerciasis, loiaisis, lymphatic filarasis) clinical assessments of patients with these and other related non-filarial (strongyloides, malaria) infections have been studied in detail. Moreover, the post-treatment inflammatory responses and the underlying mechanisms in their induction have been detailed. In particular, the control of eosinophil induction and cell trafficking to sites of post-treatment inflammation has been studied. The importance of the Wolbachia endosymbiont both as a therapeutic target and as a inducer of inflammation has been detailed as well. The pathogenesis of lymphedema in lymphatic filariasis has been shown to result (in part) from interdigital lesions that predispose to acute lymphangioadenitis. Understanding of the pathogenesis of eosinophil-related disorders has been a major focus of our clinically related studies. Multiple groups of hypereosinophilic patients (parasite-infected, familial hypereosinophilia, idiopathic hypereosinophilic syndrome, benign hypereosinophilia, episodic angioedema with eosinophilia) have been assessed clinically; moreover, lymphocytes (and their subsets) and eosinophils have been examined functionally and at the molecular level (human microarrays and RT-PCR) to identify the molecules and pathways involved in conditions associated with increased blood and tissue eosinophilia. New diagnostic approaches have been developed and utilized for the rapid and specific diagnosis of Strongyloidiasis, loiasis, and onchocerciasis.

为了更好地了解丝虫病(丝虫病、血吸虫病、淋巴丝虫病)的发病机制，对这些和其他相关非丝虫病(线虫病、疟疾)患者的临床评估进行了详细研究。此外，还详细介绍了治疗后的炎症反应及其诱导的潜在机制。特别是，控制嗜酸性粒细胞的诱导和细胞向治疗后炎症部位的运输已经被研究过。沃尔巴克氏菌内共生菌作为治疗靶标和炎症诱导剂的重要性也已详细介绍。 淋巴丝虫病淋巴水肿的发病机制已被证明是(部分)指间病变易患急性淋巴管炎的结果。 了解嗜酸性粒细胞相关疾病的发病机制一直是我们临床相关研究的主要焦点。临床上对多组高嗜酸性粒细胞增多症患者(寄生虫感染、家族性高嗜酸性粒细胞增多症、特发性高嗜酸性粒细胞综合征、良性高嗜酸性粒细胞增多、发作性血管水肿伴嗜酸性粒细胞增多)进行了临床评估；此外，还对淋巴细胞(及其亚群)和嗜酸性粒细胞进行了功能和分子水平的检测(人体微阵列和RT-PCR)，以确定与血液和组织嗜酸粒细胞增加相关的分子和途径。 已经开发并利用新的诊断方法来快速和特异地诊断弓形虫病、血吸虫病和盘尾丝虫病。