Clinical And Therapeutic Studies Of Human Filariasis and Related Diseases

我们已经开发了基于分子和重组抗原的方法来敏感和特异地诊断丝虫和STH感染，我们已经在世界各地使用这些诊断方法，其中许多方法正在商业化的过程中。 帮助确定点头综合征（NS）的原因，这是一种与O。扭转感染，一直是过去6年来HIS工作的一部分。以前，我们帮助证明了NS与O的存在的关联。肠扭转特异性抗体，并已表明这些抗体诱导自身反应性神经毒性反应，这可能是该综合征的原因。在过去的一年中，我们对这些交叉反应性自身抗体提供了新的见解，表明它们不是在中枢神经系统中本地产生的，并且在NIH未诊断疾病服务的一部分进行的扩展家族的全面家庭研究中，不是基于遗传的。在最近的研究中，我们已经证明，在NS患者的CSF中，不仅针对Leiomodin-1的自身抗体，而且针对DJ-1的自身抗体也明显较高。 如上所述，我们已经使用分子和生物信息学方法来鉴定许多寄生虫感染的诊断靶标。利用鉴定高度重复DNA短序列的方法，我们已经开发了新的分子方法，用于高灵敏度的寄生虫检测。loa，W. bancrofti，O. volvulus，A. cantonensis，广州拟步行虫A. lumbricoides、S. stercoralis、T.克氏血吸虫属（Schistotoma spp）（曼氏血吸虫（mansoni），埃及血吸虫（haematobium），intercalatum），利什曼原虫属（Leishmania spp.）其中许多检测方法可以检测血浆、CSF和/或尿液中作为无细胞循环DNA（cfcDNA）的寄生虫DNA。此外，我们已经开发了重组酶聚合酶测定法（RPA）的两个A。cantonensis和O.肠扭转

Having developed both molecular and recombinant antigen-based approaches to sensitive and specific diagnosis for filarial and STH infections, we have utilized these diagnostics around the world and many are in the throes of being commercialized. Helping define the cause of the Nodding Syndrome (NS), a devastating syndrome associated with O. volvulus infection, has been a part of the work of the HIS over the past 6 years. Previously, we helped demonstrate the association of NS with the presence of O. volvulus -specific antibodies and had shown that these antibodies induce an autoreactive neurotoxic response that may be responsible for the syndrome. Over the past year, we have provided new insights into these cross-reactive autoantibodies by showing that they are not locally produced in the CNS and that, in a comprehensive family study of an extended kindred performed as part of the Undiagnosed Disease Service at the NIH, was not genetically based. In more recent studies, we have demonstrated that autoantibodies not only to Leiomodin-1 but also to DJ-1 are markedly higher in the CSF of patients with NS. As has been mentioned above, we have used molecular and bioinformatic approaches to identify diagnostic targets for many parasitic infections. Using methodologies to identify highly repetitive DNA short sequences, we have developed new molecular approaches for highly sensitive parasite detection in L. loa, W. bancrofti, O. volvulus, A. cantonensis, A. lumbricoides, S. stercoralis, T. cruzi and Schistotoma spp (mansoni, haematobium, intercalatum), Leishmania spp. Many of these assays can detect the parasite DNA as cell free circulating DNA (cfcDNA) in plasma, CSF, and/or urine. Futhermore, we have developed recombinase polymerase assays (RPA) for both A. cantonensis and O. volvulus.