Reported Cases of Neurosyphilis Among Early Syphilis Cases-United States, 2009 to 2015.

The surveillance of neurosyphilis, an uncommon but severe consequence of syphilis, is complex; surveillance classification of neurosyphilis requires a lumbar puncture and cerebrospinal fluid analysis. We examined the prevalence of reported neurosyphilis among primary, secondary, and early latent syphilis cases reported in the United States from 2009 to 2015. Overall, the prevalence of reported neurosyphilis from 2009 to 2015 was low (0.84%); however, this is likely an underestimate of the true burden in the United States.

Prevalence Estimates of Complicated Syphilis.

We reviewed 68 cases of possible neurosyphilis among 573 syphilis cases in King County, WA, from 3rd January 2012 to 30th September 2013; 7.9% (95% confidence interval, 5.8%-10.5%) had vision or hearing changes, and 3.5% (95% confidence interval, 2.2%-5.4%) had both symptoms and objective confirmation of complicated syphilis with either abnormal cerebrospinal fluid or an abnormal ophthalmologic examination.

Detection of Treponema pallidum by semi-nested PCR in the cerebrospinal fluid of asymptomatic HIV-infected patients with latent syphilis.

BACKGROUND: Neurosyphilis diagnosis is frequently dependent upon the results of serological tests and cerebrospinal fluid abnormalities, but the reliability of findings in patients with HIV-1 infection has been questioned, especially in asymptomatic patients with latent syphilis. In this study, we present the data on the presence of T. pallidum DNA in CSF from asymptomatic HIV-infected patients with the diagnosis of syphilis. METHODS: CSF and serum samples were collected from 12 HIV-infected patients attending a tertiary care clinic located in southern Brazil, during the period 2012 to 2013. RESULTS: In CSF samples from five of 12 patients (40%), we detected T. pallidum DNA. Unexpectedly, in these patients, the CSF cell count, protein and glucose levels were normal. In addition, none of these 5 CSF samples presented a positive VDRL reaction. Serum VDRL titers were similar between patients with positive and negative CSF T. pallidum DNA. Most patients with detectable T. pallidum DNA presented low serum VDRL titers. A higher serum VDRL titer of 1:64 was observed in only one patient. CONCLUSIONS: Our results have shown that asymptomatic HIV-infected patients with evidence of latent syphilis and normal CSF might present detectable T. pallidum DNA in the CSF. The detection of T. pallidum DNA by our seminested PCR provides additional information beyond conventional CSF analysis for the diagnosis of neurosyphilis. The detection of T. pallidum DNA in CSF despite normal CSF findings in HIV-infected patients could also provide a different therapeutic approach including the use of intravenous aqueous crystalline penicillin.

Lumbar puncture for evaluation of latent syphilis in hospitalized patients. High prevalence of cerebrospinal fluid abnormalities unrelated to syphilis.

OBJECTIVE: To determine the prevalence of abnormal neurologic findings and cerebrospinal fluid abnormalities in hospitalized patients with serologic evidence of latent syphilis. DESIGN: Cross-sectional survey. METHODS: Consecutively admitted hospital inpatients from an inner-city population were screened for serologic evidence of syphilis with reactive plasma reagin and confirmatory fluorescent treponemal antibody absorption assays. In those with reactive tests, such clinical findings as a history of treatment for syphilis, neurologic abnormalities, presence of human immunodeficiency virus infection, and rapid plasma reagin titer were correlated with cerebrospinal fluid white blood cell count, protein level, and VDRL result. RESULTS: Of 490 consecutive patients, 52 (11%) had serologic evidence of syphilis. Forty-three (83%) of these underwent lumbar puncture. Of the 43, 31 (72%) were seronegative for human immunodeficiency virus and 12 (28%) were seropositive. No patient had a reactive cerebrospinal fluid VDRL test. Cerebrospinal fluid abnormalities were seen in 32% of human immunodeficiency virus-seronegative patients and in 67% of human immunodeficiency virus-seropositive patients. Cerebrospinal fluid abnormalities were not predicted by history of treatment for syphilis, abnormal neurologic findings, or an elevated rapid plasma reagin titer. Cerebrospinal fluid IgG indexes in patients with elevated cerebrospinal fluid protein levels suggested that the protein abnormalities were not caused by local antibody production. Nonreactive cerebrospinal fluid fluorescent treponemal antibody absorption tests suggest that the cerebrospinal fluid abnormalities were not the result of neurosyphilis. CONCLUSIONS: There was a high prevalence of cerebrospinal fluid abnormalities in hospitalized patients with latent syphilis detected by routine screening. Because of the nonspecificity of the cerebrospinal fluid findings, routine lumbar puncture for such patients appears to contribute little to the treatment of latent syphilis.

Treatment of syphilis, 1989.

With the introduction of penicillin after World War II, the incidence of syphilis in the United States decreased. Because of penicillin's great success, clinical trials stopped after an initial period of intensive investigation. Syphilis is a difficult disease to study; the natural history may span decades in an individual, and diagnosis and outcome are usually defined serologically, not clinically or bacteriologically. Although the recommended penicillin regimens changed, clinical trials were not repeated. Furthermore, because the early studies occurred before modern clinical-trial methodology was developed, interpretation of the results is difficult. As a result, while current regimens for syphilis therapy are effective, they may or may not be optimal. With the accumulation of reports of treatment failures and the recent appearance of human immunodeficiency virus, current regimens for the treatment of syphilis are being questioned. As background for a meeting at which treatment guidelines were reviewed, the available literature on syphilis therapy is summarized herein.

Use of the polymerase chain reaction to detect DNA sequences specific to pathogenic treponemes in cerebrospinal fluid.

The polymerase chain reaction was used to detect Treponema pallidum in specimens of cerebrospinal fluid (CSF), as a means of diagnosing syphilis. Segments of the TmpA and 4D genes were amplified to provide an estimated threshold sensitivity of approximately 65 organisms in 0.5 ml. A spectrum of pathogens known to cause meningitis, and several non-pathogenic treponemes were unreactive. Treponema pertenue, and only one of 30 control specimens of CSF were positive. In contrast, 10 of 19 CSFs from patients being evaluated for latent or tertiary syphilis were positive, as were 7 of 28 specimens from HIV-positive patients.

[Clinico-laboratory parallels in changes in the cerebrospinal fluid and the immune status of patients with early stages of syphilis]. / Kliniko-laboratornye paralleli izmenenii spinnomozgovoi zhidkosti i sostoianiia immunnogo statusa u bol'nykh rannimi stadiiami sifilisa.

A total of 135 patients with early syphilis were examined, 24 of these with primary seropositive, 31 with secondary new, 70 with secondary relapsing, and 10 with latent early condition. Abnormal shifts were revealed in the cerebrospinal fluid of 51 (37%) patients, in 28 of these Stages I-II shifts, Stages II-III shifts in 10, and Stages III-IV shifts in 13 patients. Clinically the patients with abnormal liquor developed multiple chancres, erosive papules, leukoderma, alopecia, neutrophilia; these patients had suffered from various diseases in the past. Immunologic examinations have detected manifest noncoordination of the immune system: increased counts of the T-lymphocytes and plasmacytes, reduced counts of B-lymphocytes, depressed primary immune response, disordered immunoglobulin ratio.

Evaluation of cerebrospinal fluid in asymptomatic late syphilis.

To help determine the role of lumbar puncture in evaluation of patients with asymptomatic late syphilis, we reviewed results of cerebrospinal fluid (CSF) testing of 47 asymptomatic patients with syphilis. Syphilis was of unknown duration (n = 27) or known duration of greater than one year (n = 20), and all patients had reactive rapid plasma reagin (RPR) tests and reactive fluorescent treponemal antibody absorption tests. Thirty-two per cent of subjects had abnormal CSF findings; these included elevated protein in nine (19%) of 47 and pleocytosis in six (13%) of 47. In most cases, the etiology of these abnormalities was uncertain. Asymptomatic neurosyphilis, diagnosed on the basis of a reactive Venereal Disease Research Laboratory (VDRL; Atlanta, GA) test of CSF, was present in three (6%) of 47 patients. Of the eight patients with RPR titers of greater than or equal to 1:128, three (38%) had neurosyphilis. These results suggest that lumbar puncture is indicated for patients with asymptomatic late syphilis or syphilis of unknown duration.

Lumbar puncture in asymptomatic late syphilis. An analysis of the benefits and risks.

We evaluated the treatment of asymptomatic patients with untreated syphilis of more than one year's duration (asymptomatic late syphilis) using a decision-analysis model. Two strategies were compared: treatment with 7.2 million units of penicillin G benzathine, or performing a lumbar puncture to test for asymptomatic neurosyphilis followed by penicillin and management based on cerebrospinal fluid analysis. Estimates of probabilities of disease prevalence, test sensitivity, and cure and complication rates were derived from published studies. Both strategies resulted in a cure rate of at least 99.7% using the best estimates. Although the strategy using lumbar puncture results in a 0.2% higher cure rate, its rate of complications (0.3%) exceeds its marginal benefit. We conclude that a lumbar puncture offers little additional benefit and may increase morbidity in patients with asymptomatic late syphilis.

[Visual and auditory evoked potentials in latent syphilis]. / Potenciales evocados visuales y auditivos en sífilis latente.

The evoked potentials visual and auditory are studied in 43 patients with latent syphilis without previous mucocutaneous lesions. Twenty nine of them had not received treatment, and 14 due to their positive serology were treated with benzathine penicillin. At the visual potential evoked there were no abnormalities but in 20 cases evoked auditive potential were abnormal. This findings suppose the existence of subclinical neurological indicates the existence of lesions in almost 50% of the cases of this period of syphilis. All these patients had positive circulate immune complexes and normal cerebro-spinal fluid. The neurological alteration consists in a lesion of the cerebral trunk. According to these results the auditory potential evoked test is very important. The authors doubt on the efficacity of the benzathine penicillin in this period of syphilis.

Cerebrospinal fluid penicillin levels during therapy for latent syphilis.

Cerebrospinal fluid and serum penicillin levels were determined in patients with latent syphilis. Mean serum concentration one week after the third weekly dose of 2.4 million units penicillin G benzathine was 0.32 units/mL. Concurrent administration of probenecid orally produced a mean serum penicillin level of 0.41 units/mL. Doubled penicillin doses without and with daily orally administered probenecid resulted in mean serum concentrations of 0.75 and 1.00 units/mL, respectively. Two of six patients in the last group had CSF penicillin concentrations greater than 0.03 units/mL.

Cerebrospinal fluid immunoglobulins in neurosyphilis.

Using the fluorescent treponemal antibody-absorption (FTA-ABS) test and the solid phase haemadsorption assay (SPHA) Treponema pallidum-specific IgA was found in the cerebrospinal fluid (CSF) of patients with neurosyphilis but not in those with late latent syphilis. The presence of T pallidum-specific IgA in the CSF may inhibit the antitreponemal activity of IgG and thus play some part in the pathogenesis of neurosyphilis.

Penetration of penicillin into the cerebrospinal fluid of patients with latent syphilis.

Eighteen patients with latent syphilis were treated with 360 mg, 720 mg, 1080 mg or 1440 mg intramuscular procaine penicillin daily for 14 days. Penicillin was assayed in serum and cerebrospinal fluid collected 3 hours after the second injection in each patient. Penicillin was present in all sera in concentrations greater than the generally accepted fully treponemacidal level, but none was detected in cerebrospinal fluid from 11 patients. The significance of these results is discussed, particularly with a view to changes in standard treatment regimens for latent syphilis.