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      The Rapid Plasma Reagin Test Cannot Replace the Venereal Disease Research Laboratory Test for Neurosyphilis Diagnosis

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          The cerebrospinal fluid (CSF) Venereal Disease Research Laboratory (VDRL) test is a mainstay for neurosyphilis diagnosis, but it lacks diagnostic sensitivity and is logistically complicated. The rapid plasma reagin (RPR) test is easier to perform, but its appropriateness for use on CSF is controversial. RPR reactivity was determined for CSF from 149 individuals with syphilis using 2 methods. The CSF-RPR was performed according to the method for serum. The CSF-RPR-V was performed using the method recommended for the CSF-VDRL. Laboratory-defined neurosyphilis included reactive CSF-fluorescent treponemal antibody absorption test and CSF white blood cells >20/uL. Symptomatic neurosyphilis was defined as vision loss or hearing loss. CSF-VDRL was reactive in 45 (30.2%) patients. Of these, 29 (64.4%) were CSF-RPR reactive and 37 (82.2%) were CSF-RPR-V reactive. There were no instances where the CSF-VDRL was nonreactive but the CSF-RPR or CSF-RPR-V was reactive. Among the 28 samples that were reactive in all 3 tests, CSF-VDRL titers (median [IQR], 1:4 [1:4-1:16]) were significantly higher than CSF-RPR (1:2 [1:1-1:4], P = 0.0002) and CSF-RPR-V titers (1:4 [1:2-1:8], P = 0.01). The CSF RPR and the CSF-RPR-V tests had lower sensitivities than the CSF-VDRL: 56.4% and 59.0% versus 71.8% for laboratory-diagnosed neurosyphilis and 51.5% and 57.6% versus 66.7% for symptomatic neurosyphilis. Compared with the CSF-VDRL, the CSF-RPR has a high false-negative rate, thus not improving upon this known limitation of the CSF-VDRL for neurosyphilis diagnosis. Adapting the RPR procedure to mimic the CSF-VDRL decreased, but did not eliminate, the number of false negatives and did not avoid all the logistical complications of the CSF-VDRL.

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          Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features.

          To define clinical and laboratory features that identify patients with neurosyphilis. Subjects (n=326) with syphilis but no previous neurosyphilis who met 1993 Centers for Disease Control and Prevention criteria for lumbar puncture underwent standardized history, neurological examination, venipuncture, and lumbar puncture. Neurosyphilis was defined as a cerebrospinal fluid (CSF) white blood cell count >20 cells/ microL or reactive CSF Venereal Disease Research Laboratory (VDRL) test result. Sixty-five subjects (20.1%) had neurosyphilis. Early syphilis increased the odds of neurosyphilis in univariate but not multivariate analyses. In multivariate analyses, serum rapid plasma reagin (RPR) titer > or =1 : 32 increased the odds of neurosyphilis 10.85-fold in human immunodeficiency virus (HIV)-uninfected subjects and 5.98-fold in HIV-infected subjects. A peripheral blood CD4+ T cell count < or =350 cells/ microL conferred 3.10-fold increased odds of neurosyphilis in HIV-infected subjects. Similar results were obtained when neurosyphilis was more stringently defined as a reactive CSF VDRL test result. Serum RPR titer helps predict the likelihood of neurosyphilis. HIV-induced immune impairment may increase the risk of neurosyphilis.
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            Neurosyphilis in a clinical cohort of HIV-1-infected patients.

            To describe the risk factors, clinical presentation, and long-term follow up of patients enrolled in a clinical cohort of HIV-infected patients who were diagnosed and treated for neurosyphilis. Comprehensive demographic, clinical, and therapeutic data were collected prospectively on all patients between 1990 and 2006. Patients were diagnosed with neurosyphilis if they had positive syphilis serologies and any of the following: (a) one or more cerebrospinal fluid abnormalities on lumbar puncture [white blood cells >10/microl; protein >50 mg/dl; reactive venereal diseases research laboratory], (b) an otherwise unexplained neurological finding. Of 231 newly diagnosed syphilis cases, 41 neurosyphilis cases met entry criteria (median age 38.6 years, 79.1% male). Risk factors for neurosyphilis included a CD4 cell count of less than 350 cells/ml at the time of syphilis diagnosis (odds ratio: 2.87; 95% confidence interval: 1.18-7.02), a rapid plasma regain titer >1: 128 (2.83; 1.11-7.26), and male sex (2.46; 1.06-5.70). Use of any highly active antiretroviral therapy before syphilis infection reduced the odds of neurosyphilis by 65% (0.35; 0.14-0.91). Sixty-three percent of cases presented with early neurosyphilis and the median time to neurosyphilis diagnosis was 9 months. Symptomatic patients had more cerebrospinal fluid abnormalities on initial lumbar puncture than asymptomatic patients (P = 0.01). Follow-up lumbar puncture within 12 months revealed that only 38% had resolution of all cerebrospinal fluid abnormalities. At 1 year, 38% had persistence of their major symptom despite adequate treatment for neurosyphilis. Twelve of 41 (29%) patients were retreated for syphilis. Early neurosyphilis was common in this cohort. Highly active antiretroviral therapy to reverse immunosuppression may help mitigate neurological complications of syphilis.
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              Laboratory diagnosis and interpretation of tests for syphilis.

              The lack of a method for demonstrating the presence of Treponema pallidum by growth necessitates the use of alternative methods. Traditionally, these methods are divided into direct detection methods (animal inoculation, dark-field microscopy, etc.) and serologic tests for the presence of patient antibody against T. pallidum. Serologic methods are further divided into two classes. One class, the nontreponemal tests, detects antibodies to lipoidal antigens present in either the host or T. pallidum; examples are the Venereal Disease Research Laboratory and rapid plasma reagin and tests. Reactivity in these tests generally indicates host tissue damage that may not be specific for syphilis. Because these tests are easy and inexpensive to perform, they are commonly used for screening, and with proper clinical signs they are suggestive of syphilis. The other class of test, the treponemal tests, uses specific treponemal antigens. Confirmation of infection requires a reactive treponemal test. Examples of the treponemal tests are the microhemagglutination assay for antibodies to T. pallidum and the fluorescent treponemal antibody absorption test. These tests are more expensive and complicated to perform than the nontreponemal tests. On the horizon are a number of direct antigen, enzyme-linked immunosorbent assay, and PCR techniques. Several of these techniques have shown promise in clinical trials for the diagnosis of congenital syphilis and neurosyphilis that are presently difficult to diagnose.

                Author and article information

                Sexually Transmitted Diseases
                Ovid Technologies (Wolters Kluwer Health)
                June 2012
                : 39
                : 6
                : 453-457
                © 2012


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