Lumbar Puncture and Syphilis Outcome

腰椎穿刺和梅毒结果

• 批准号: 8828818
• 负责人: Christina M Marra
• 金额: $ 72.16万
• 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 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8828818
• 关键词: Area; Attention; Bacteria; Benzathine Penicillin; Blindness; Brain; CD4 Lymphocyte Count; Cerebrospinal Fluid; Cognition; Cognitive; Dementia; Diagnosis; Disease; Evaluation; Germ; HIV; Health; Impaired cognition; Individual; Invaded; Liquid substance; Morbidity - disease rate; Neuraxis; Neurologic; Neuropsychological Tests; Neurosyphilis; Outcome; Patients; Penicillins; Performance; Pharmaceutical Preparations; Plasma; Randomized; Reagins; Research; Research Infrastructure; Risk; Role; Serological; Serum; Spinal Puncture; Stroke; Symptomatic Neurosyphilis; Symptoms; Syphilis; Testing; Treatment Failure; Treponema pallidum; Uncertainty; Wit; base; cognitive function; functional disability; functional outcomes; hearing impairment; high risk; killings; peripheral blood; 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(LP)在梅毒治疗中的作用是有争议的，尤其是对HIV感染的患者。梅毒螺旋体在疾病的早期就会侵入中枢神经系统(CNS)，而推荐用于治疗非复杂梅毒的苄星青霉素G(BPG)并没有达到杀灭梅毒的脑脊液药物水平。血清学确定的治疗失败在HIV感染的梅毒患者中很常见，可能是由于未治疗的神经梅毒(NS)。根据血清快速血浆反应素(RPR)滴度和外周血CD4计数，可以确定NS的最高风险患者。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不太清楚。一些专家认为，即时LP的策略将避免神经疾病的发生。其他人则认为，在BPG和LP之后，症状性NS并不常见，可以保留给那些治疗失败的人。在这项提案中，我们将检验这样一种假设，即立即对LP I高危患者采取策略，然后基于脑脊液(CSF)检查进行治疗，可以在HIV感染的梅毒患者中产生更好的血清学结果。第二个不确定的领域是，神经入侵是否会影响原本可能被认为是“神经学上没有症状”的个体的认知。我们发现，有梅毒病史的HIV感染患者，尤其是那些脑脊液异常与NS一致的患者，认知功能受损。我们将测试这一假设，即梅毒螺旋体感染中枢神经系统具有认知和功能后果，并且在高危个体中立即进行LP策略，然后进行基于治疗的脑脊液检查，可以在HIV感染的梅毒患者中产生更好的认知和功能结果。我们的研究计划利用已建立的专业知识和基础设施，研究艾滋病毒感染患者的梅毒、NS和认知功能。我们将根据血清RPR E1：32或CD4d350/ul将患有NS的高危HIV感染患者随机分为两组：LP(根据脑脊液评估指导治疗：确诊NS[接受BPG治疗]或无NS[接受BPG治疗])和非LP(非CSF评估指导治疗：均接受BPG治疗)。具体目标是：1)确定立即LP的策略是否会在HIV感染的梅毒患者中产生更好的血清学结果。假设：无LP组，包括未诊断和未治疗的NS患者，其血清学治疗反应将比LP组差；2)在诊断为梅毒时，确定HIV感染患者的认知和功能障碍。假设：确诊的NS患者的认知和功能表现将比未确诊的NS患者差。由于No LP组包括未确诊的NS患者，他们的表现将比No NS患者更差；3)确定立即LP策略是否会在HIV感染的梅毒患者中带来更好的认知和功能结果。假设：非LP组，包括未诊断和未治疗的NS患者，在治疗后认知和功能的改善将低于LP组。