Rapid and Simple CSF Tests for Neurosyphillis Diagnosis

描述（由申请人提供）：全世界每年有1200万人感染梅毒，许多人同时感染艾滋病毒。有证据表明，艾滋病毒感染者比未感染艾滋病毒的人更有可能发展为有症状的神经梅毒。梅毒和艾滋病福尔斯的负担最沉重地落在发展中国家，那里缺乏诊断神经梅毒的资源。在美国，CSF-VDRL（脑脊液性病研究实验室）测试和基于实验室的CSF密螺旋体测试的组合用于评估神经梅毒的可能性。CSF-VDRL试验对神经梅毒的诊断具有特异性，但不敏感。相比之下，CSF密螺旋体试验是敏感的，但不特异。在发展中国家，这两种测试是不可用的，或者只能在遥远的实验室进行。因此，有症状的神经梅毒的诊断机会非常有限，这类病例往往被漏诊。简单和快速的测试用于CSF将有助于诊断神经梅毒在世界各地的地方设置。快速血浆反应素（RPR）检测在发展中国家广泛使用，用于血清建立梅毒诊断。它比VDRL测试更容易执行。然而，该测试尚未开发用于CSF。世界卫生组织（WHO）最近评估了6种商业快速血清密螺旋体检测方法，这些方法价格低廉，操作简单。其中4个推荐用于田间试验。我们的初步研究表明，梅毒螺旋体快速试验或脑脊液RPR试验对神经梅毒的诊断可能具有特异性。该应用程序的目标是开发即时CSF检测，以在资源匮乏的环境中快速简单地诊断症状性神经梅毒。它利用了美国正在进行的神经梅毒研究。具体目标是：1）确定4种WHO评估的CSF快速梅毒螺旋体检测用于诊断神经梅毒的灵敏度和特异性，并确定用于目标3和4的最佳检测; 2）优化用于CSF的RPR，并确定其诊断神经梅毒的灵敏度和特异性; 3）确定CSF密螺旋体试验正常化的时间（目标1中选择的）和神经梅毒治疗后CSF-RPR; 4）确定目标1中确定的最佳密螺旋体试验和CSF-RPR在美国门诊中真实的时间诊断神经梅毒的能力。这项研究的结果将用于在最需要的领域设计田间试验。

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.