The US and Europe are currently experiencing outbreaks of syphilis in men who have sex with men, many of whom are HIV-infected. This is of particular concern because neurosyphilis may be more common in HIV-infected individuals. Our neurosyphilis studies began in 1996. The overall goal of our original proposal was to test the hypothesis that HIV infection impairs clearance of Treponema pallidum from the cerebrospinal fluid (CSF). The results of our studies support this hypothesis. Specifically, individuals with more pronounced HIV-mediated immunosuppression are more likely to have neurosyphilis, and normalization of CSF-Venereal Disease Research Laboratory (VDRL) reactivity after treatment for neurosyphilis is significantly less likely in HIV-infected individuals, particularly those with advanced immunosuppression. In our competing renewal, we focused on predicting neurosyphilis and its treatment response. In the last 15 months, we have made substantial progress in addressing our previous Aims. We have shown that the CSF cellular phenotype can be used to support a diagnosis of neurosyphilis in HIV-infected patients, have additional preliminary data in support of the association between greater genetic diversity of blood T. pallidum and neurosyphilis, and have identified new markers of neurosyphilis treatment response. As of Dec 1,2003, we have enrolled and obtained CSF from 470 subjects with syphilis, and 91 have had at least one follow-up lumbar puncture after neurosyphilis treatment. Approximately three-quarters of our subjects are also HIV-infected. In this competing renewal application, we continue to focus on clinically and pathogenetically important questions regarding neurosyphilis and HIV.
The Specific Aims are: 1) Identify measures that predict a high likelihood of neurosyphilis in HIV-infected and -uninfected individuals; 2) Distinguish CSF pleocytosis due to T. pallidum infection from CSF pleocytosis due to HIV infection; 3) Determine factors associated with response to neurosyphilis therapy in HIV-infected and -uninfected individuals. Our ongoing study is the largest investigation of neurosyphilis in many decades, and is the only study with sufficient power to address the effect of concomitant HIV infection on development of neurosyphilis and the response to neurosyphilis therapy in both HIV-infected and -uninfected individuals. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS034235-10
Application #
7073315
Study Section
NeuroAIDS and other End-Organ Diseases Study Section (NAED)
Program Officer
Nunn, Michael
Project Start
1996-07-01
Project End
2008-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
10
Fiscal Year
2006
Total Cost
$342,337
Indirect Cost
Name
University of Washington
Department
Neurology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Edmondson, Diane G; Hu, Bo; Norris, Steven J (2018) Long-Term In Vitro Culture of the Syphilis Spirochete Treponema pallidum subsp. pallidum. MBio 9:
Davis, Arielle P; Stern, Joshua; Tantalo, Lauren et al. (2018) How Well Do Neurologic Symptoms Identify Individuals With Neurosyphilis? Clin Infect Dis 66:363-367
Marra, Christina M; Maxwell, Clare L; Dunaway, Shelia B et al. (2017) Cerebrospinal Fluid Treponema pallidum Particle Agglutination Assay for Neurosyphilis Diagnosis. J Clin Microbiol 55:1865-1870
Ho, Emily L; Maxwell, Clare L; Dunaway, Shelia B et al. (2017) Neurosyphilis Increases Human Immunodeficiency Virus (HIV)-associated Central Nervous System Inflammation but Does Not Explain Cognitive Impairment in HIV-infected Individuals With Syphilis. Clin Infect Dis 65:943-948
Obermeit, Lisa C; Beltran, Jessica; Casaletto, Kaitlin B et al. (2017) Evaluating the accuracy of self-report for the diagnosis of HIV-associated neurocognitive disorder (HAND): defining ""symptomatic"" versus ""asymptomatic"" HAND. J Neurovirol 23:67-78
Molini, Barbara J; Tantalo, Lauren C; Sahi, Sharon K et al. (2016) Macrolide Resistance in Treponema pallidum Correlates With 23S rDNA Mutations in Recently Isolated Clinical Strains. Sex Transm Dis 43:579-83
Marra, Christina M; Tantalo, Lauren C; Sahi, Sharon K et al. (2016) Reduced Treponema pallidum-Specific Opsonic Antibody Activity in HIV-Infected Patients With Syphilis. J Infect Dis 213:1348-54
Ho, Emily L; Tantalo, Lauren C; Jones, Trudy et al. (2015) Point-of-care treponemal tests for neurosyphilis diagnosis. Sex Transm Dis 42:48-52
Marra, Christina M; Sahi, Sharon K; Tantalo, Lauren C et al. (2014) Toll-like receptor polymorphisms are associated with increased neurosyphilis risk. Sex Transm Dis 41:440-6
Marra, C M; Deutsch, R; Collier, A C et al. (2013) Neurocognitive impairment in HIV-infected individuals with previous syphilis. Int J STD AIDS 24:351-5

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