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; 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
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; Sahi, Sharon K; Tantalo, Lauren C et al. (2010) Enhanced molecular typing of treponema pallidum: geographical distribution of strain types and association with neurosyphilis. J Infect Dis 202:1380-8
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
Li, Jonathan Z; Tucker, Joseph D; Lobo, Ann-Marie et al. (2010) Ocular syphilis among HIV-infected individuals. Clin Infect Dis 51:468-71
Marra, Christina M; Maxwell, Clare L; Tantalo, Lauren C et al. (2008) Normalization of serum rapid plasma reagin titer predicts normalization of cerebrospinal fluid and clinical abnormalities after treatment of neurosyphilis. Clin Infect Dis 47:893-9
Marra, Christina M; Colina, April P; Godornes, Charmie et al. (2006) Antibiotic selection may contribute to increases in macrolide-resistant Treponema pallidum. J Infect Dis 194:1771-3
Lukehart, Sheila A; Godornes, Charmie; Molini, Barbara J et al. (2004) Macrolide resistance in Treponema pallidum in the United States and Ireland. N Engl J Med 351:154-8
Marra, Christina M; Maxwell, Clare L; Smith, Stacy L et al. (2004) Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features. J Infect Dis 189:369-76

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