Lumbar Puncture and Syphilis Outcome

腰椎穿刺和梅毒结果

• 批准号: 9244858
• 负责人: Christina M Marra
• 金额: $ 68.68万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9244858
• 关键词: Area; Attention; Bacteria; Benzathine Penicillin; Blindness; Brain; CD4 Lymphocyte Count; Cerebrospinal Fluid; Cognition; Cognitive; Dementia; Diagnosis; Disease; Evaluation; Germ; HIV; Impaired cognition; Individual; Invaded; Liquid substance; Morbidity - disease rate; Neuraxis; Neurologic; Neurologic Symptoms; Neuropsychological Tests; Neurosyphilis; Outcome; Patients; Penicillin G; Penicillins; Performance; Pharmaceutical Preparations; Plasma; Randomized; Reagins; Research; Research Infrastructure; Risk; Role; Serological; Serum; Spinal Puncture; Stroke; Syphilis; Testing; Treatment Failure; Treponema pallidum; Uncertainty; Wit; base; cognitive function; functional disability; functional outcomes; hearing impairment; high risk; peripheral blood; public health relevance; treatment response

DESCRIPTION (provided by applicant): The role of lumbar puncture (LP) in syphilis is controversial, particularly in HIV-infected patient. Treponema pallidum invades the central nervous system (CNS) early in disease, and benzathine penicillin G (BPG), the recommended treatment for uncomplicated syphilis, does not achieve treponemacidal CSF drug levels. Serologically defined treatment failure is common in HIV-infected syphilis patients, perhaps due to untreated neurosyphilis (NS). Patients at highest risk for NS can be identified based on serum Rapid Plasma Reagin (RPR) titer and peripheral blood CD4 count. While most experts agree that patients with syphilis who have neurological symptoms should undergo LP, the approach to patients without neurological complaints is less clear. Some experts argue that a strategy of immediate LP will avert neurological morbidity. Others argue that symptomatic NS is uncommon after BPG and LP can be reserved for those who fail treatment. In this proposal, we will test the hypothesis that a strategy of immediate LP i high-risk individuals, followed by therapy based on cerebrospinal fluid (CSF) examination, results in better serological outcomes in HIV-infected syphilis patients. A second area of uncertainty is whether neuroinvasion impacts cognition in individuals who might otherwise be considered "neurologically asymptomatic." We show that HIV-infected patients with previous syphilis, especially those with CSF abnormalities consistent with NS, are cognitively impaired. We will test the hypothesis that CNS involvement by T. pallidum has cognitive and functional consequences, and that a strategy of immediate LP in high-risk individuals, followed by therapy based CSF examination, results in better cognitive and functional outcomes in HIV-infected syphilis patients. Our research plan takes advantage of established expertise and infrastructure for study of syphilis, NS and cognitive function in HIV-infected patients. We will randomize HIV-infected patients at high risk for NS based on serum RPR e1:32 or CD4 d350/ul into two groups: LP (treatment guided by CSF evaluation: Confirmed NS [treated for NS] or No NS [treated with BPG]) and No LP (treatment not guided by CSF evaluation: all receive BPG). The Specific Aims are: 1) Determine if a strategy of immediate LP results in better serological outcomes in HIV-infected patients with syphilis. Hypothesis: the No LP group, which includes undiagnosed and untreated NS patients, will have a poorer serological treatment response than the LP group; 2) Identify cognitive and functional impairment in HIV-infected patients at diagnosis of syphilis. Hypothesis: cognitive and functional performance will be poorer in the Confirmed NS patients compared to the No NS patients. Because the No LP group includes individuals with undiagnosed NS, they will perform more poorly than the No NS patients; 3) Determine if a strategy of immediate LP results in better cognitive and functional outcomes in HIV-infected patients with syphilis. Hypothesis: the No LP group, which includes undiagnosed and untreated NS patients, will have less improvement in cognition and function after therapy than the LP group.

描述（由申请人提供）： 腰椎穿刺术在梅毒诊断中的作用是有争议的，特别是在HIV感染患者中。梅毒螺旋体在疾病早期侵入中枢神经系统（CNS），苄星青霉素G（BPG），推荐用于无并发症梅毒的治疗，不能达到杀螺旋体的CSF药物水平。血清学定义的治疗失败在HIV感染的梅毒患者中很常见，可能是由于未经治疗的神经梅毒（NS）。可根据血清快速血浆反应素（RPR）滴度和外周血CD4计数确定NS最高风险患者。虽然大多数专家同意有神经系统症状的梅毒患者应该接受LP，但对没有神经系统症状的患者的方法尚不清楚。一些专家认为，立即LP的策略将避免神经系统疾病。其他人认为，症状性NS是罕见的后BPG和LP可以保留那些谁治疗失败。在这项建议中，我们将测试的假设，即立即LP i高危人群的策略，然后根据脑脊液（CSF）检查的治疗，结果在HIV感染的梅毒患者更好的血清学结果。第二个不确定的领域是神经侵袭是否会影响那些可能被认为是"神经学上无症状"的个体的认知。“我们发现，既往有梅毒史的HIV感染患者，特别是那些CSF异常与NS一致的患者，认知功能受损。我们将检验T.梅毒有认知和功能的后果，并立即LP的策略，在高危人群中，随后治疗为基础的CSF检查，结果在HIV感染的梅毒患者更好的认知和功能的结果。我们的研究计划利用现有的专业知识和基础设施来研究艾滋病毒感染者的梅毒、NS和认知功能。我们将根据血清RPR e1：32或CD4 d350/ul将NS高风险的HIV感染患者随机分为两组：LP（CSF评价指导的治疗：确诊NS [接受NS治疗]或无NS [接受BPG治疗]）和无LP（CSF评价未指导的治疗：均接受BPG）。具体目的是：1）确定立即LP策略是否能在HIV感染的梅毒患者中获得更好的血清学结局。假设：无LP组（包括未诊断和未经治疗的NS患者）的血清学治疗反应比LP组更差; 2）在诊断梅毒时识别艾滋病毒感染患者的认知和功能障碍。假设：与非NS患者相比，确诊NS患者的认知和功能表现较差。由于无LP组包括未确诊NS的个体，他们的表现将比无NS患者更差; 3）确定立即LP策略是否会导致HIV感染梅毒患者的认知和功能结局更好。假设：无LP组包括未确诊和未治疗的NS患者，治疗后认知和功能的改善低于LP组。