Throughout the world, 12 million people acquire syphilis every year. About one-third reside in sub-Saharan Africa, where the proportion of individuals with syphilis is 2-3 times higher in those who are HIV-infected compared to those who are not. In the US, compared to all patients with primary and secondary syphilis, rates of primary and secondary syphilis are 80 times higher in patients who are HIV-infected. Development of early neurosyphilis is more common in HIV-infected individuals than in those who are not HIV infected. Early neurosyphilis causes substantial morbidity, including symptomatic meningitis, hearing loss, vertigo, and visual loss. Neurosyphilis begins with asymptomatic meningitis. Untreated, asymptomatic neurosyphilis can lead to symptomatic neurosyphilis. Identification and treatment of the ~25% of HIV-infected patients with asymptomatic neurosyphilis would prevent them from progressing to symptomatic disease. However, there is currently no sensitive and specific test to identify these individuals. One approach to this problem would be to perform a lumbar puncture on all HIV-infected patients with syphilis. However this approach is impractical in many settings and potentially wastes resources. In this application, we build upon our previous work in a cohort of 556 HIV-infected subjects with syphilis to develop and validate algorithms to 1) determine which HIV- infected patients with syphilis should undergo lumbar puncture and 2) interpret CSF abnormalities. These algorithms will be constructed using a novel statistical method called classification and regression tree (CART) analysis. Further, we will determine the impact of concomitant antiretroviral therapy, and of particular antiretroviral agents within a regimen, on response to neurosyphilis therapy. Our study is unique. It is the only study of neurosyphilis conducted in the HIV era. Neurosyphilis carries significant morbidity in HIV-infected patients. The studies proposed in this application will yield the necessary tools for clinicians to optimally evaluate, treat and manage HIV-infected patients with syphilis and neurosyphilis. Syphilis, a disease that many thought was more or less controlled, is enjoying a major come back in the developed world and remains endemic in the developing world. Many of those infected also have HIV, and they are at increased risk of a complication called neurosyphilis, which can cause blindness, deafness and stroke within weeks after syphilis infection. Our proposed research builds on our previous work and will lead to ways to better diagnose and treat neurosyphilis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS034235-16
Application #
8269682
Study Section
NeuroAIDS and other End-Organ Diseases Study Section (NAED)
Program Officer
Wong, May
Project Start
1996-07-01
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2014-05-31
Support Year
16
Fiscal Year
2012
Total Cost
$382,200
Indirect Cost
$137,200
Name
University of Washington
Department
Neurology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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
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
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
Ho, Emily L; Marra, Christina M (2012) Treponemal tests for neurosyphilis--less accurate than what we thought? Sex Transm Dis 39:298-9
Grimes, Matthew; Sahi, Sharon K; Godornes, B Charmie et al. (2012) Two mutations associated with macrolide resistance in Treponema pallidum: increasing prevalence and correlation with molecular strain type in Seattle, Washington. Sex Transm Dis 39:954-8
Marra, Christina M; Tantalo, Lauren C; Maxwell, Clare L et al. (2012) The rapid plasma reagin test cannot replace the venereal disease research laboratory test for neurosyphilis diagnosis. Sex Transm Dis 39:453-7
Bucher, Joy B; Golden, Matthew R; Heald, Alison E et al. (2011) Stroke in a patient with human immunodeficiency virus and syphilis treated with penicillin and antiretroviral therapy. Sex Transm Dis 38:442-4
Marra, Christina M; Tantalo, Lauren C; Sahi, Sharon K et al. (2010) CXCL13 as a cerebrospinal fluid marker for neurosyphilis in HIV-infected patients with syphilis. Sex Transm Dis 37:283-7

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