Rapid and Simple CSF Tests for Neurosyphillis Diagnosis

描述(申请人提供)：全球每年有1200万人感染梅毒，其中许多人合并感染艾滋病毒。有证据表明，感染艾滋病毒的人比未感染艾滋病毒的人更容易患上症状性神经梅毒。梅毒和艾滋病毒的负担最沉重地落在发展中国家身上，那里缺乏诊断神经梅毒的资源。在美国，脑脊液VDRL(脑脊液性病研究实验室)检测和基于实验室的脑脊液梅毒检测相结合被用来评估神经梅毒的可能性。脑脊液VDRL试验对神经梅毒的诊断具有特异性，但不敏感。相比之下，脑脊液梅毒螺旋体试验是敏感的，但不是特异的。在发展中国家，这两种检测要么无法获得，要么只能在遥远的实验室进行。因此，确诊症状性神经梅毒的机会非常有限，而且这种病例常常被遗漏。用于脑脊液的简单而快速的检测将有助于在世界各地的当地环境中诊断神经梅毒。快速血浆反应素(RPR)测试在发展中国家广泛使用，并用于对血清进行梅毒诊断。它比VDRL测试更容易执行。然而，这项测试还没有开发出来用于脑脊液。世界卫生组织(WHO)最近评估了6种价格低廉、操作简单的商业快速梅毒螺旋体血清检测方法。其中4个品种被推荐用于田间试验。我们的初步研究表明，快速梅毒试验或脑脊液RPR试验可能对神经梅毒的诊断具有特异性。该应用程序的目标是开发护理点式脑脊液测试，以便在资源匮乏的环境中快速而简单地诊断症状性神经梅毒。它利用了美国正在进行的一项关于神经梅毒的研究。其具体目标是：1)确定4种WHO评估的脑脊液梅毒快速检测方法诊断神经梅毒的敏感性和特异性，并确定用于AIMS 3和4的最佳检测方法；2)优化用于脑脊液的RPR，并确定其诊断神经梅毒的敏感性和特异性；3)确定脑脊液梅毒检测(在AIM 1中选择)和神经梅毒治疗后CSF-RPR恢复正常的时间；4)确定AIM 1中确定的最佳梅毒检测方法和CSF-RPR在美国门诊诊所实时诊断神经梅毒的能力。这项研究的结果将用于在最需要的地区设计实地试验。

DESCRIPTION (provided by applicant): Worldwide, 12 million people acquire syphilis every year, and many are co-infected with HIV. Evidence suggests that HIV-infected people are more likely than HIV-uninfected people to develop symptomatic neurosyphilis. The burden of syphilis and HIV falls most heavily on the developing world where the resources to diagnose neurosyphilis are lacking. In the US, a combination of the CSF-VDRL (cerebrospinal fluid Venereal Disease Research Laboratory) test and laboratory-based CSF treponemal tests are used to evaluate the possibility of neurosyphilis. The CSF-VDRL test is specific for the diagnosis of neurosyphilis, but is not sensitive. In contrast, the CSF treponemal tests are sensitive, but not specific. In the developing world, these 2 tests are not available or are performed only at distant laboratories. Thus there is very limited opportunity to establish the diagnosis of symptomatic neurosyphilis and such cases are often missed. Simple and rapid tests for use on CSF would facilitate the diagnosis of neurosyphilis in local settings throughout the world. The rapid plasma reagin (RPR) test is widely available in the developing world and is used on serum to establish a syphilis diagnosis. It is simpler to perform than the VDRL test. However, this test has not been developed for use on CSF. The World Health Organization (WHO) recently evaluated 6 commercial rapid, treponemal tests on serum that are inexpensive and simple to perform. 4 of them were recommended for field trials. Our preliminary studies suggest that the rapid treponemal tests or the RPR test on CSF may be specific for diagnosis of neurosyphilis. The goal of this application is to develop point-of-care CSF tests to , rapidly and simply diagnose symptomatic neurosyphilis in resource poor settings. It takes advantage of an ongoing study of neurosyphilis in the US. The specific aims are: 1) Determine the sensitivity and specificity of the 4 WHO-evaluated rapid treponemal tests on CSF for diagnosis of neurosyphilis and identify the best test for use in Aims 3 and 4; 2) Optimize the RPR for use on CSF and determine its sensitivity and specificity for diagnosis of neurosyphilis; 3) Determine the time to normalization of the CSF treponemal test (chosen in Aim 1) and of the CSF-RPR after neurosyphilis treatment; 4) Determine the ability of the best treponemal test identified in Aim 1 and of the CSF-RPR to diagnose neurosyphilis in real time in a US outpatient clinic. The results of this study will be used to design field trials in the areas of greatest need.