Although the probability of OS may be higher, numbers are small and it is unclear whether this observation is confounded by the lack of objective measures to diagnose OS. Acknowledgments The authors would like to thank Dr David Thiemann and the Center for Clinical Data Analysis at the Johns Hopkins University School of Medicine for providing the data. Footnotes Conflict of interest: None declared.. of detectable antibodies or with the prozone phenomenon) or in individuals with untreated late syphilis who have a decline in nontreponemal antibody titers over time. In the antibiotic era, in which patients routinely receive -lactams and other antibiotics with activity against syphilis for a variety of nonCsyphilis-related indications, the detection of serodiscordant test results in persons without a documented history of syphilis treatment raises several important clinical and public health questions: What are the public health risks of sexual transmission and vertical transmission of syphilis in these individuals? What is the risk that they either currently have or will progress to tertiary syphilis in the future? Studies from the pre-antibiotic era suggest that there is a low risk of sexual transmission in persons with late syphilis,2 and recent studies suggest that vertical transmission is rare.3 Determining the risk of progression to tertiary syphilis in the future would involve a protracted and logistically RELA difficult follow-up. In this study, we sought to further characterize the probability of neurosyphilis (NS) or ophthalmic syphilis (OS) at the time of a serodiscordant test result. We conducted a 2-step retrospective review using the Johns Hopkins Patient Database of all inpatient and outpatient visits from 1994 to 2012. Of note, Johns Hopkins initiated reverse sequence syphilis testing in 2011. Before that, the traditional algorithm was used. First, we searched pertinent (codes 090.0 through 097.9, or equivalent) relating to NS and OS. Second, we searched all records for patients who were seropositive for syphilis (defined as a positive serum treponemal test result) and who underwent a lumbar puncture for any reason. Patients who qualified under one or both of our search criteria were included in our study. We abstracted nontreponemal antibody titers, specifically RPR, and confirmatory treponemal antibody test results. We reviewed discharge summaries, clinic notes, progress notes, and laboratory data for symptoms, signs, HIV antibody testing, CD4 count, HIV RNA, cerebrospinal fluid (CSF) abnormalities, and treatment in the subset of MB-7133 patients who were serodiscordant. We defined definite NS as a positive CSF Venereal Disease Research Laboratory (VDRL) and suspected NS as a positive serum treponemal test result and a CSF white blood cell count (WBC) MB-7133 greater than 5 cells/mL or a CSF protein greater than 50 mg/dL. Ophthalmic syphilis was defined as compatible ocular findings in a person with a seroreactive treponemal antibody test independent of CSF abnormalities. This analysis was granted approval by the institutional review board of the Johns Hopkins Medical Institutions. Of 2,685,977 patient encounters in the Johns Hopkins Clinical Database, we identified 470 which met the above or laboratory criteria. Of these, 48, or 10.2%, were serodiscordant. Thirteen of the 48 were identified under the reverse sequence algorithm. None of these had a positive CSF VDRL result, although no CSF VDRL was done for 8 of the 48 patients. Of the 48 serodiscordant patients, 4 (8.3%) were treated for NS or OS. All of these patients had a negative CSF VDRL result. The clinical course for these serodiscordant patients MB-7133 is summarized in Table 1. TABLE 1 Clinical Course of Serodiscordant Patients Treated for Ophthalmic and NS codes for NS and OS to try to ensure that we captured all patients who were treated for either condition. Because this was a retrospective chart review, we had to rely on clinician judgment and documentation of diagnostic and therapeutic decisions. A CSF examination was performed for nonCsyphilis-related reasons in many patients. Finally, although we investigated the occurrence of NS or OS at the time of serodiscordant tests, the risk of progression to tertiary syphilis MB-7133 in the future for these patients remains unknown. Both the lack of a gold standard test to diagnose OS and NS and our limited understanding of the relationship between serum nontreponemal titers and underlying disease activity have made it difficult to define.
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