CLINICAL AND THERAPEUTIC STUDIES OF HUMAN FILARIASIS

临床研究和发病机制盘尾丝虫病-由于与伊维菌素治疗盘尾丝虫病相关的不良反应（尽管比以前可用的药物，乙胺嗪轻微）可能是严重的，全身性的和使人衰弱的（几乎总是涉及皮肤），这种治疗后反应的介质已经被确定和量化。已发现IL-5和GM-CSF均介导治疗后观察到的嗜酸性粒细胞增多，并且IL-6和TNF-α已被认为是治疗后观察到的全身不良反应的主要介质。趋化因子RANTES也已被鉴定为接受治疗的患者皮肤中的主要嗜酸性粒细胞趋化剂之一，为了确定盘尾丝虫病患者伊维菌素治疗后的反应是否与伊维菌素治疗后的反应有相似的病因，对于较老的药物（DEC），最近在加纳完成了对接受伊维菌素的盘尾丝虫病患者的仔细临床和实验室研究，以及对治疗后反应期间血液细胞因子水平的实验室评价。淋巴丝虫病：影响暴露于W.目前正在库克群岛和印度人口中进行广泛的家庭研究，以评估班氏杆菌感染。虽然这些研究仍在进行中，但已经认识到，在印度钦奈的40名热带肺嗜酸性粒细胞增多症（TPE）综合征患者中，有两对受影响的兄弟。对这些患者的家系进行了深入分析，结合这些家系的临床和免疫学HLA研究，继续进行同胞对分析，评估了维持（3年）微丝蚴血症清除的患者和那些在确定性治疗后未能清除微丝蚴血症的患者之间的临床和免疫学差异。这些数据表明，在免疫学和临床上，在治疗后保持无微丝蚴的那些人和长期存在微丝蚴血症的那些人之间没有明显的差异（除了存在微丝蚴血症）。诊断技术Loa loa-开发了一种基于多重PCR的评估方法，最初使用4个靶序列，用于Loa的确定性诊断。经过改进，使用2个靶序列的系统已被证明是最灵敏和特异的。使用这种基于PCR和ELISA的检测系统，我们已经开发出一种检测感染的方法，该方法具有100%的灵敏度和98%的特异性。随着最佳灵敏度和特异性的条件已经设定，目前正在通过筛选在西非收集的全血样本和转介给NIH的患者中建立这种基于PCR的测定在诊断活动性感染中的效用。Stongyloides stercoralis -已经建立了用于检测粪便中Strongyloides stercoralis的基于PCR的诊断。治疗试验在过去一年中，治疗丝虫感染的治疗方法取得了重大进展，证明了阿苯达唑治疗DEC难治性丝虫病的实用性。- 丝虫病、盘尾丝虫病、类圆线虫病、阿苯达唑、细胞因子-人类受试者

Clinical studies and pathogenesisOnchocerciasis - Because the adverse reactions associated with treatment of onchocerciasis with ivermectin (although milder than with the previous available drug, diethycarbamazine) can be severe, systemic, and debilitating (and almost always involve the skin), the mediators of this posttreatment reaction have been identified and quantified. Both IL-5 and GM-CSF have been found to mediate the post-treatment eosinophilia seen, and IL-6 and TNF-alpha have been implicated as the major mediators of the systemic adverse reactions seen post-treatment. The chemokine, RANTES, has also been identified as one of the major eosinophil chemoattractants in the skin of patients undergoing treatment, and serial skin biopsies have been obtained from these patients for immunocytochemical analysis to understand the mechanism of the skin inflammatory response seen.To determine whether the posttreatment reactions following ivermectin therapy of patients with onchocerciasis share a similar etiology with those following treatment with the older drug (DEC), a careful clinical and laboratory study of onchocerciasis patients receiving ivermectin has recently been completed in Ghana and the laboratory evaluation of blood cytokine levels during the posttreatment reactions. Lymphatic filariasis - Possible factors affecting the clinical outcome of exposure to W. bancrofti infection are being evaluated by extensive family studies in both the Cook Islands and Indian populations. While these studies are still ongoing, already it has been recognized that among 40 patients from Chennai, India, with the tropical pulmonary eosinophilia (TPE) syndrome there are two pairs of affected brothers. Intense analysis of the family trees of these patients, in conjunction with clinical, immunological HLA studies of these families, sib pair analysis continues.The clinical and immunological differences between patients who maintain (for three years) clearance of microfilaremia and those who fail to do so following definitive treatment has been assessed. The data suggest that both immunologically and clinically there are no obvious differences (save for the presence of microfilaremia) between those who remain microfilaria- free and those who are microfilaremic long term after therapy. Diagnostic techniquesLoa loa- A multiplex PCR-based assessment method, initially using 4 target sequences, was developed for the definitive diagnosis of loiasis. With refinements, a system using 2 target sequences has been shown to be the most sensitive and specific. Using this system of PCR and ELISA-based detection, we have developed a method for detection of infection that is 100% sensitive and 98% specific. With the conditions for optimal sensitivity and specificity having now been set, the utility of such a PCR-based assay in the diagnosis of active infection is currently being established by screening whole blood samples collected in West Africa and among patients referred to the NIH.Stongyloides stercoralis - A PCR-based diagnostic for the detection of Strongyloides stercoralis in the stool has been established. Therapeutic trials The major advance in the therapeutic approach to the treatment of filarial infections that has come about over the past year is the demonstration of the utility of albendazole for the treatment of DEC-refractory loiasis. - Filarial, loiasis, filariasis, onchocerciasis, strongyloidiasis, albendazole, cytokines - Human Subjects