Serum Rapid Plasma Reagin Titers Research Articles

Syphilitic Uveitis and Alopecia

A 60-year-old man presented to the eye emergency room with one month of blurry vision, hearing loss, and polyarthralgia. Eye examination revealed panuveitis of both eyes. There was optic disc edema with a retinal flame hemorrhage in the right eye (Fig. 1A). Scalp exam revealed alopecia and papulosquamous eruption with crusted and eroded papules (Fig. 1B). Serum rapid plasma reagin titer (RPR) was 1:1,024 and cerebrospinal fluid was positive for the venereal disease research laboratory (VDRL) test.

Factors Associated With Neurosyphilis in Patients With Syphilis Treatment Failure: A Retrospective Study of 165 HIV-Negative Patients.

BackgroundIn recent years, the incidence of syphilis has increased year by year. Our study is to explore the risk factors for the development of neurosyphilis in patients who failed syphilis treatment.MethodsA total number of 165 patients with complete medical records and who agreed to undergo lumbar puncture were divided into 47 neurosyphilis cases and 118 non-neurosyphilis cases according to the diagnostic criteria of neurosyphilis, and the differences in clinical characteristics and laboratory features between the two groups were analyzed. Significant variables were entered into multivariable logistic regression models.Results(1) There were statistical differences (p < 0.05) between the neurosyphilis (NS) group and the non-neurosyphilis (NNS) group in terms of the higher proportion of male and serum rapid plasma reagin (RPR) > 1:32 and the elevated cerebrospinal fluid white blood cell (CSF WBC) and CSF protein in the neurosyphilis group compared with the non-neurosyphilis group. (2) Male gender, serum RPR titers >1:32 at lumbar puncture, CSF WBC >8 × 106/L were significantly associated with neurosyphilis.ConclusionFor patients who have failed syphilis treatment, lumbar puncture should be performed to exclude neurosyphilis, to enable early diagnosis and treatment, and to prevent irreversible damage of neurosyphilis, especially if the patient is male and has a serum RPR>1:32 and elevated CSF WBC at lumbar puncture, which are risk factors for neurosyphilis.

Clinical Features and Corrected Factors with Neurosyphilis in HIV/Syphilis Co-Infected Patients Based on Stage of Syphilis

Abstract Objective: Neurosyphilis is challenging to diagnose, especially in patients with human immunodeficiency virus (HIV)/syphilis co-infection. The aim of this study was to profile the clinical features of neurosyphilis and evaluate the correlation between neurosyphilis and clinical or laboratory factors among patients with HIV/syphilis co-infection. Methods: We retrospectively analyzed the data of 479 HIV/syphilis co-infected patients examined between August 2009 and September 2018. A multivariate logistic regression model was used to identify factors correlated with neurosyphilis. Results: The overall prevalence of neurosyphilis was 21.7%. The prevalence of neurosyphilis differed among patients with primary (11.1%), secondary (20.1%), and latent syphilis (29.1%). The prevalences of neurosyphilis in patients with serological non-response and serofast patients were 26.1% and 6.3%, respectively, while 12.5% of patients with serological relapse had neurosyphilis. Patients with secondary and latent syphilis had serum rapid plasma reagin (RPR) titers (per unit) of 1.44-fold [95% confidence interval (CI): 1.08–1.93, P = 0.014] and 2.73-fold (95% CI: 1.49–5.00, P = 0.001), respectively, which increased the risk of confirmed neurosyphilis. Among patients with latent syphilis, a serum RPR titer of ≥1:32 and peripheral blood CD4 cell count of ≤350/mL were significantly associated with neurosyphilis, with adjusted odds ratios of 9.45 (95% CI: 1.86–48.03, P = 0.007) and 3.75 (95% CI: 1.11–12.66, P = 0.033), respectively. Conclusion: A serum RPR titer of ≥1:32 and a peripheral blood CD4 cell count of ≤350/mL have predictive value in screening for neurosyphilis among HIV-positive patients with latent syphilis.

Detection of Treponema pallidum DNA in Oropharyngeal Swabs and Whole Blood for Syphilis Diagnosis.

Syphilis diagnosis relies on serological tests, which may be falsely nonreactive or may be reactive but not reflect current syphilis. Polymerase chain reaction for detection of T. pallidum DNA was performed on 123 oropharyngeal swabs, 120 whole bloods, and 46 lesion exudate swabs from 123 untreated individuals with syphilis (cases); oropharyngeal swabs from 148 at-risk controls without syphilis; and 73 oropharyngeal swabs and 36 whole bloods from 73 individuals recently treated for syphilis. Most (90.2%) cases had early syphilis. T. pallidum DNA was detected in 33 (26.8%) of 123 oropharyngeal swabs, 32 (26.7%) of 120 bloods, and 30 (65.2%) of 46 lesion exudate swabs. T. pallidum DNA was detected in 49 (40.8%) of 120 individuals in whom both oropharyngeal swabs and blood were tested. T. pallidum was more likely to be amplified from oropharyngeal swabs when it was amplified from blood than when it was not (15 of 32 [46.9%] vs. 17 of 88 [19.3%], P = 0.003). For each 2-fold increase in serum rapid plasma reagin titer, the odds of detection of T. pallidum DNA in oropharyngeal swabs increased by 1.44 (95% confidence interval, 1.14-1.82, P = 0.003). T. pallidum DNA was not detected in oropharyngeal samples from controls, but it was detected in 3 (8.3%) of 36 bloods from individuals recently treated for syphilis: 2 at 1 day and 1 at 5 days after initiation of syphilis treatment. Nucleic amplification tests can identify recent T. pallidum infection and may be particularly useful for diagnosis of very early or asymptomatic syphilis.

Identification of the factors associated with post-treatment asymptomatic neurosyphilis in HIV-negative patients with serological non-response syphilis: a retrospective study.

Some syphilis patients do not exhibit an appropriate serological response after treatment despite the absence of any clinical evidence of treatment failure or reinfection. This condition is called "serofast syphilis" or "serological non-response syphilis." This study explored the incidence of asymptomatic neurosyphilis (ANS) and related factors in 324 asymptomatic patients with serological non-response syphilis. We analyzed descriptive statistics stratified by the presence of asymptomatic neurosyphilis for the basic characteristics of samples. Bivariate analysis was conducted to assess correlations between outcomes and potential predictors. Variables significant in the bivariate analysis (p<0.1) were entered into multivariable logistic regression models. All p-values were two-sided with a significance threshold of p<0.05. The results indicated that 89 of 324 patients had ANS (incidence of 27.5%), and the greatest risk factors were a < fourfold decrease in serum rapid plasma reagin (RPR) titers after treatment and current serum RPR titers >1:32. Our findings suggest that ANS is common among syphilis patients, and patients with a fourfold decrease in serum RPR titers after treatment and current serum RPR titers >1:32 are more likely to develop ANS.

Utility of Treponemal Testing from Aqueous Fluid in the Diagnosis of Ocular Syphilis in Patients with HIV/AIDS

ABSTRACT Purpose Ocular syphilis is re-emerging globally especially in patients with human immunodeficiency virus (HIV). Atypical manifestations of ocular syphilis and/or other associated opportunistic infections often lead to a diagnostic dilemma. We evaluated the utility of aqueous humor (AH) Treponema pallidum hemagglutination assay (TPHA) titers in the diagnosis of ocular syphilis. Methods Retrospective case series of five HIV positive patients with positive syphilis serology in whom AH sampling was performed. All patients had ocular manifestations suspicious of infectious etiology. Results Panuveitis with/without retinitis was the commonest presentation. Along with blood investigations, polymerase chain reaction (PCR) testing from AH was done for Mycobacterium tuberculosis (MTB), Herpes Simplex Virus (HSV), Varicella Zoster Virus (VZV), Cytomegalovirus (CMV), and Toxoplasma gondii. In addition, serum antibody titers for Toxoplasma, rapid plasma reagin (RPR) and TPHA tests for syphilis were done. In patients with raised serum RPR/TPHA, aqueous TPHA titers were also assessed. Mean serum RPR titer was ≥ 1:32 and TPHA titer was ≥1:1280. Aqueous humor titers of TPHA was high in all patients (range ≥ 1:320 to ≥1:5120). Aqueous PCR was negative for all other infectious etiologies in four patients. In one patient, PCR-CMV was also positive, suggestive of a dual infection. Post-treatment with highly active antiretroviral therapy (HAART) and appropriate anti-syphilitic regime, complete resolution of lesions with corresponding fall in the serum RPR/TPHA titers were noted in all patients. Conclusions Ocular syphilis with atypical presentations is usually diagnosed based on a positive syphilis serology and by excluding other infectious causes. In the present study, we have shown an excellent correlation between raised AH TPHA titers with serological values and the clinical presentation. Considering the ease of collection of AH in contrast to vitreous fluids, the AH-TPHA assay could potentially be a valuable tool in the diagnosis of ocular syphilis.

The performance of rapid plasma reagin (RPR) titer in HIV-negative general paresis after neurosyphilis therapy

BackgroundRepeated nontreponemal serologic test for syphilis titers is recommended to evaluate treatment response. However, it is unknown whether serum rapid plasma reagin (RPR) titer can serve as a surrogate for determining the efficacy of treatment in general paresis (GP) remains unknown.MethodsWe retrospectively reviewed data from 105 GP patients, who were divided into two groups (62 CSF RPR+ patients and 43 CSF RPR- patients) according to reactive RPR test status in CSF. Clinical assessment included the Mini-Mental State Examination (MMSE) scores, CSF examinations (WBC count, protein concentration and RPR titer), and serum tests (RPR titer and TPPA). Among the 105 GP patients, 13 CSF RPR+ patients and 6 CSF RPR- patients had a 12 months follow-up of CSF, serum measures and MMSE.ResultsThe median serum RPR titer was significantly higher in CSF RPR+ patients than that in CSF RPR- GP patients, 1:8 [IQR 1:4–1:32] vs. 1:4 [IQR 1:4–1:8] (P < 0.001). The number of CSF RPR+ patients with serum RPR titer≥1:32 was significantly higher when compared with CSF RPR- patients (P = 0.001). For CSF RPR+ patients, the MMSE scores improved or remained constantly after penicillin treatment. For CSF RPR+ patients, the CSF RPR titer declined four-fold in 85% (11/13) of the patients, whereas the serum RPR titer declined four-fold in only 46% (6/13) of the patients, the odds ratio is 6.4 (95% confidence interval 1.0–41.2).ConclusionsA four-fold decline in CSF RPR titer is a good predictor for treatment efficacy in CSF RPR+ GP patients within 12 months after the completion of therapy.

Incidence of asymptomatic neurosyphilis in serofast Chinese syphilis patients

More new diagnosed syphilis cases were reported in china, the incidence and relevant factors of asymptomatic neurosyphilis (ANS) in serofast syphilis patients were unclear. Clinical and laboratory data of 402 Human Immunodeficiency Virus (HIV) negative, serofast syphilis patients, who underwent lumbar puncture at the Peking University Ditan Teaching Hospital between September 2008 and August 2016, were collected. Incidence of ANS was verified and the relevant factors were further analyzed. According to the ANS criteria, 139 (34.6%) patients had ANS. Of these, 40 (28.8%) had reactive cerebrospinal fluid (CSF), rapid plasma reagin (RPR) positive, 115 (82.7%) had CSF white blood cell (WBC) count > 5 × 106/L, 28 (20.1%) had CSF protein concentration > 45 mg/dL (without other neurological diseases). Patients aged 51–60 years, of non-Han ethnicity, with serum RPR titer 1:32 and ≥ 1:64 were 2.28-fold, 9.11-fold, 5.12-fold and 5.69-fold, respectively, more likely to have ANS. The incidence of ANS was 34.6% among Chinese serofast syphilis patients. Age, ethnicity and serum RPR titer were associated with high risk of ANS.

Serological Response Predicts Normalization of Cerebrospinal Fluid Abnormalities at Six Months after Treatment in HIV-Negative Neurosyphilis Patients

This study aimed to determine whether a serological response could predict the normalization of cerebrospinal fluid (CSF) abnormalities at 6 months after treatment in human immunodeficiency virus (HIV)-negative neurosyphilis patients. A total of 123 neurosyphilis patients were recruited at baseline, 58 of these patients undergoing treatment, repeated CSF examinations and serological tests for syphilis at 6 months after treatment were included in the follow-up study. Before treatment, the CSF rapid plasma reagin (RPR) titer, CSF Treponema pallidum particle agglutination (TPPA) titer, CSF leukocyte count, and CSF protein concentration were correlated with both serum RPR and TPPA titers. At 6 months after treatment, 28 and nine patients achieved serological responses of RPR and TPPA tests, respectively. The sensitivities of the serological response of RPR and TPPA tests for identifying the normalization of CSF abnormalities were 60.0∼83.3% and 17.1~22.2%, respectively; and 75.0∼91.3% of patients showing serological response of RPR test also achieved CSF normalization, suggesting that the serological response could predict CSF normalization to some degree. Particularly, in patients with ≥8-fold decreases in the serum RPR titer, the CSF RPR, CSF leukocyte count, and CSF protein concentration had normalized, and follow-up lumbar puncture could be reduced considering the resolution of neurological symptoms.

Novel predictors of neurosyphilis among HIV-negative syphilis patients with neurological symptoms: an observational study

BackgroundKnown predictors of neurosyphilis were mainly drawn from human immunodeficiency virus (HIV)-infected syphilis patients, which may not be applicable to HIV-negative populations as they have different characteristics, particularly those with neurological symptoms. This study aimed to identify novel predictors of HIV-negative symptomatic neurosyphilis (S-NS).MethodsFrom June 2005 to June 2015, 370 HIV-negative syphilis patients with neurological symptoms were recruited, consisting of 191 S-NS patients (including 123 confirmed neurosyphilis and 68 probable neurosyphilis patients) and 179 syphilis/non-neurosyphilis (N-NS) patients. Clinical and laboratory characteristics of S-NS were compared with N-NS to identify factors predictive of S-NS. Serum rapid plasma reagin (RPR), Treponema pallidum particle agglutination (TPPA), and their parallel testing format for screening S-NS were evaluated.ResultsThe likelihood of S-NS was positively associated with the serum RPR and TPPA titers. The serum TPPA titers performed better than the serum RPR titers in screening S-NS. The optimal cut-off points to recognize S-NS were serum RPR titer ≥1:4 and serum TPPA titer ≥1:2560 respectively. A parallel testing format of a serum RPR titer ≥1:2 and serum TPPA titer ≥1:1280 screened out 95.8% of S-NS and all confirmed cases of neurosyphilis. S-NS was independently associated with male sex, serum RPR titer ≥1:4, serum TPPA titer ≥1:2560, and elevated serum creatine kinase. Concurrence of these factors increased the likelihood of S-NS.ConclusionsQuantitation of serum TPPA is worthwhile and performs better than serum RPR in screening S-NS. Serum RPR, serum TPPA, male sex, and serum creatine kinase can predict S-NS. Moreover, patients with both a serum RPR titer <1:2 and a serum TPPA titer <1:1280 have a low probability of S-NS, suggesting that it is reasonable to reduce lumbar punctures in such individuals.

Reduced Treponema pallidum-Specific Opsonic Antibody Activity in HIV-Infected Patients With Syphilis.

Human immunodeficiency virus (HIV)-infected individuals may have poorer serological responses to syphilis treatment and may be more likely to experience neurosyphilis. Treponema pallidum is cleared from sites of infection by opsonization, ingestion, and killing by macrophages. Serum samples from 235 individuals with syphilis were tested for T. pallidum-specific opsonic activity. Blood T. pallidum concentrations were determined by real-time polymerase chain reaction amplification of the tp0574 gene, and T. pallidum was detected in cerebrospinal fluid (CSF) by reverse-transcriptase polymerase chain reaction of 16S ribosomal RNA. Opsonic activity was higher with higher serum rapid plasma reagin titers (P < .001), and in those treated for uncomplicated syphilis before serum collection (P < .001). Opsonic activity was lower in HIV-infected than in HIV-uninfected individuals even after the above factors were taken into account (P = .006). In participants in whom blood T. pallidum was detectable, those with the highest opsonic activity had lower blood T. pallidum concentrations. In multivariable analyses, there was not a significant relationship between opsonic activity and detection of T. pallidum in CSF or CSF-VDRL reactivity. Serum T. pallidum-specific opsonic activity is significantly lower in HIV-infected individuals. Impaired T. pallidum-specific immune responses could contribute to differences in the course of disease or treatment response.

Clinical and laboratory characteristics of ocular syphilis: a new face in the era of HIV co-infection.

BackgroundOcular syphilis is reemerging as an important cause of uveitis in the new era of common co-infection with HIV. This study will reveal the clinical and laboratory characteristics in the group of individuals co-infected with ocular syphilis and HIV compared with HIV-negative individuals. In this retrospective observational case series, medical records of patients diagnosed with ocular syphilis with serologic support from 2008 to 2014 were reviewed. Ocular and systemic manifestation and laboratory profiles were reviewed.ResultsTwenty-nine eyes of 16 consecutive patients (10 HIV-positive and 6 HIV-negative) were included. All patients were males, and mean age of onset for ocular syphilis was 43 (mean 42.65 ± 13.13). In both HIV-positive and HIV-negative groups, ocular manifestations of syphilis were variable including anterior uveitis (4 eyes), posterior uveitis (8 eyes), panuveitis (13 eyes), and isolated papillitis (4 eyes). In HIV-positive patients, panuveitis was the most common feature (12/18 eyes, 67 %) and serum rapid plasma reagin (RPR) titers were significantly higher (range 1:64–1:16,348; mean 1:768; p = 0.018) than in HIV-negative patients. Upon the diagnosis of ocular syphilis in HIV-positive patients, HIV-1 viral load was high (median 206,887 copies/ml) and CD4 cell count ranged from 127 to 535 cells/ml (mean 237 ± 142; median 137). Regardless of HIV status, cerebrospinal fluid (CSF) exam was frequently abnormal: positive CSF fluorescent treponemal antibody absorption (FTA-ABS) or Venereal Disease Research Laboratory (VDRL) test results in seven patients or either elevated CSF WBC count or elevated CSF protein in six patients.ConclusionsOur results reveal that the patients with ocular syphilis with high serum RPR titers may have concomitant HIV infection requiring further testing for HIV status and ocular syphilis is likely associated with the central nervous system involvement and therefore needs to be managed according to the treatment recommendations for neurosyphilis.

A clinical study of new cases of parenchymal neurosyphilis: has tabes dorsalis disappeared or been missed?

Tabes dorsalis (TD) was documented as the most common parenchymal neurosyphilis, but its incidence dramatically declined in the antibiotic era. Syphilis has resurged on the China mainland since the 1980s. In recent years, physicians have been reporting parenchymal neurosyphilis, and the overwhelming majority was general paresis, but this was not the case in the authors' hospital. To make clear the real situation of parenchymal neurosyphilis in the authors' hospital, a retrospective review was carried out of the records of patients during 2009-2012. Overrepresented clinical new cases of tabetic and paretic parenchymal neurosyphilis were collected. Clinical characteristics, neuroimaging, laboratory data, and responses to penicillin were analyzed in two groups. The efficiency of two current criteria based on CSF antibodies tests was inspected. In the 43 cases with positive serum rapid plasma reagin (RPR) and TPPA tests, 18 patients met the criteria of this study: 11 presented with symptoms of general paresis, and seven had typical presentations of TD. There were statistical differences in serum RPR titers, CSF RPR, white blood cell count, and TP between the paretic and tabetic groups. The response to penicillin was relatively poor in TD. The efficiency of two current criteria was lower in the diagnosis of TD. TD was not uncommon in our area. Its clinical features remained typical, but underdiagnosis with CSF-based criteria and a decreased response to penicillin were prominent issues.

Toll-like receptor polymorphisms are associated with increased neurosyphilis risk.

Single-nucleotide polymorphisms (SNPs) in toll-like receptors (TLR) 1, 2, and 6 impair cell signaling in response to spirochetal lipoproteins. We investigated whether common SNPs in TLR1, TLR2, or TLR6 were associated with laboratory- or clinically-defined neurosyphilis. Polymorphisms in the genes for TLR1 (a T→G mutation at position 1805), TLR2 (a G→A mutation at position 2258), and TLR6 (a C→T mutation at position 745) were sought in 456 white patients with syphilis. Laboratory-defined neurosyphilis included a reactive cerebrospinal fluid (CSF)-Venereal Disease Research Laboratory (VDRL) test. Clinically-defined neurosyphilis included new vision or hearing loss. Controls had CSF white blood cells of 5/μL or less, nonreactive CSF-Venereal Disease Research Laboratory, and no vision or hearing loss. Overall, 26.2% of patients had laboratory-defined and 36.2% had clinically-defined neurosyphilis. Compared with controls, patients with any of the 3 SNPs were more likely to have laboratory-defined neurosyphilis. Those with TLR2 or TLR6 SNPs were more likely to have clinically-defined neurosyphilis. These associations were independent of serum rapid plasma reagin titer. A common TLR1 polymorphism is associated with an increased risk of laboratory-defined neurosyphilis, and common TLR2 and TLR6 polymorphisms are associated with an increased risk of both laboratory- and clinically-defined neurosyphilis. These data suggest that host factors impact the natural history of syphilis.

Clinical Prediction and Diagnosis of Neurosyphilis in HIV-Infected Patients with Early Syphilis

The diagnosis of neurosyphilis (NS) is a challenge, especially in HIV-infected patients, and the criteria for deciding when to perform a lumbar puncture (LP) in HIV-infected patients with syphilis are controversial. We retrospectively reviewed demographic, clinical, and laboratory data from 122 cases of HIV-infected patients with documented early syphilis who underwent an LP to rule out NS, and we evaluated 3 laboratory-developed validated real-time PCR assays, the Treponema pallidum particle agglutination (TPPA) assay, the fluorescent treponemal antibody absorption (FTA-ABS) assay, and the line immunoassay INNO-LIA Syphilis, for the diagnosis of NS from cerebrospinal fluid (CSF) samples of these patients. NS was defined by a reactive CSF-VDRL test result and/or a CSF white blood cell (WBC) count of >20 cells/μl. Thirty of the 122 patients (24.6%) had early NS. Headache, visual symptoms, a CD4 cell count of <500 cells/μl, and viremia, as defined by an HIV-1 RNA count of ≥50 copies/ml, were associated with NS in multivariate analysis (P = <0.001 for each factor). Blood serum rapid plasma reagin (RPR) titers were not associated with early NS (P = 0.575). For the diagnosis of NS, the PCR, FTA-ABS, TPPA, and INNO-LIA assays had sensitivities of 58%, 100%, 68%, and 100%, specificities of 67%, 12%, 49%, and 13%, and negative predictive values of 85%, 100%, 84%, and 100%, respectively. Visual disturbances, headache, uncontrolled HIV-1 viremia, and a CD4 cell count of <500 cells/μl were predictors of NS in HIV-infected patients with early syphilis, while blood serum RPR titers were not; therefore, RPR titers should not be used as the sole criterion for deciding whether to perform an LP in early syphilis. When applied to CSF samples, the INNO-LIA Syphilis assay easily helped rule out NS.

Syphilis and neurosyphilis in human immunodeficiency virus-infected patients: A retrospective study at a teaching hospital in Taiwan

Some studies have reported that the risk factors for neurosyphilis in patients with human immunodeficiency virus (HIV) and syphilis co-infection, include CD4 cell counts ≤350cells/μL and rapid plasma reagin (RPR) titer ≥1:32. However, neurosyphils can develop even in patients with CD4 cell counts >350cells/μL or RPR titer <1:32. In this study, we evaluated the outcome of syphilis to treatment in HIV-infected patients, and analysed the predictors of neurosyphilis in this population. We retrospectively reviewed medical records of HIV-infected patients with syphilis who visited the China Medical University Hospital between January 2000 and December 2009. Neurosyphilis was defined by white blood cell (WBC) counts >20cells/μL in the cerebrospinal fluid (CSF) sample or elevated Venereal Disease Research Laboratory (VDRL) titers of the CSF samples. Treatment failure was defined as less than 4-fold decrease in the serum RPR titer at or beyond 12 months post-treatment in case of early syphilis, and, at or beyond 24 months in case of late syphilis. One hundred and twenty-one HIV-infected patients (average age, 32 years) with syphilis were included in this study. Of 63 patients who had follow-up of serologic responses, 30 (47.6%) failed to respond to treatment. CD4 cell counts ≤200cells/μL was the indicator for treatment failure (P=.029). Lumbar puncture was performed in 65 patients, and 14 patients were diagnosed with neurosyphilis. At the time of lumbar puncture, 31 and 19 of the 65 patients showed CD4 cell counts of >350cells/μL and RPR of <1:32, respectively. An HIV viral load (VL) ≥10000copies/mL was found to be associated with the development of neurosyphilis (P=.016). In HIV-infected patients with syphilis, RPR titer should be evaluated more frequently when CD4 count ≤200cell/μL is associated with treatment failure. Lumbar puncture for the diagnosis of neurosyphilis should be considered in patients with HIV and syphilis co-infection, even in patients with CD4 cell counts >350cells/μL, and particularly when the HIV VL ≥10000copies/mL.

Azithromycin Treatment Failure Among Primary and Secondary Syphilis Patients in Shanghai

Azithromycin has been used to treat primary and secondary syphilis and as prophylaxis for sexual partners. We evaluated syphilis treatment failure in patients who received azithromycin therapy. Patients who did not respond to azithromycin therapy were referred to Shanghai Skin Disease and sexually transmitted disease hospital. Treatment failure was defined as follows: (1) persistent ulcers or cutaneous or mucosal lesions 1 month after therapy; or (2) detection of spirochetes in dark-field microscopy examination of a lesion at least 1 week after treatment; or (3) failure of rapid plasma reagin titers to decrease 4-fold at 3 months after treatment. A total of 132 patients with primary and secondary syphilis who failed azithromycin therapy were referred to our hospital between January 2001 and October 2008. Of 132 patients, 42 (31.8%) had primary syphilis and 90 (68.2%) had secondary syphilis. Twenty-six patients with primary syphilis developed multiple lesions or secondary syphilis, or persistent ulcers despite using azithromycin. The skin or mucosal lesions did not resolve in 37 patients with secondary syphilis after azithromycin treatment. Ten patients had a positive dark-field examination for Treponema pallidum (T. pallidum) after treatment. The serum rapid plasma reagin titers studied in all cases had failed to decrease 4-fold at 3 months after therapy. The doses of azithromycin used for treatment ranged from 4 to 30 g. The failure of azithromycin to cure a substantial number of patients with primary and secondary syphilis in Shanghai suggests that azithromycin has limited therapeutic value in this setting.

One-Year Follow-Up of Relapse to Risky Behaviors and Incidence of Syphilis Among Patients Enrolled in the HIV Case Management Program

A longitudinal prospective study was conducted at an AIDS designated hospital in Taiwan. The study aimed to determine the incidence of syphilis and to identify risk factors predicting new onset syphilis and relapse into risky behaviors among 117 patients enrolled in the HIV case management program for 1 year. Having a new episode of syphilis was defined as patients had a fourfold increase of serum rapid plasma reagin titers from baseline to 12-month follow-up. After enrollment, 17% relapsed in unprotected sexual intercourse. New onset syphilis was noted in ten (10.4%) participants, and all were men having sex with men. The incidence of syphilis was 5.8 per 100 person-years. Predictors of a new episode of syphilis were higher CD4 cell counts [hazard ratio (HR), 1.003; 95% confidence interval (CI), 1.00-1.006], and recreational drug use (HR, 18.89; 95% CI, 2.78-128.15). Regular screening for syphilis among patients retaining in HIV care remains necessary.

Normalization of Serum Rapid Plasma Reagin Titer Predicts Normalization of Cerebrospinal Fluid and Clinical Abnormalities after Treatment of Neurosyphilis

Success of neurosyphilis treatment is defined by normalization of cerebrospinal fluid (CSF) and clinical abnormalities. The goal of this study was to determine whether normalization of serum rapid plasma reagin (RPR) titer could accurately predict treatment success. One hundred ten patients who were enrolled in a longitudinal study of CSF abnormalities in syphilis had asymptomatic syphilitic meningitis, symptomatic syphilitic meningitis, or syphilitic eye disease and were treated for neurosyphilis. At 4, 7, and 13 months after treatment, serum RPR titer and CSF and clinical abnormalities were analyzed for normalization. Odds ratios for normalization of each CSF and clinical abnormality when serum RPR titer had normalized and the positive predictive value of normalization of serum RPR titer for normalization of CSF and clinical abnormalities were determined. Serum RPR titer had normalized in 63 patients (57%) by 4 months after treatment, in 94 (85%) by 7 months, and in 97 (88%) by 13 months. Except for CSF protein concentration, normalization of serum RPR titer predicted normalization of other CSF and clinical abnormalities in >80% of patients at 4 months, >85% at 7 months, and >90% at 13 months. The odds of normalization of CSF and clinical abnormalities were 28-57-fold higher when serum RPR titer had normalized, compared with when it had not. Normalization of serum RPR titer was consistently less accurate in predicting treatment success in human immunodeficiency virus-infected patients who were not receiving antiretroviral therapy, compared with those who were receiving such therapy. In most instances, normalization of serum RPR titer correctly predicts success of treatment of neurosyphilis, and follow-up lumbar puncture can be avoided.

SPECT in Neurosyphilis

A 41-year-old woman had a mild confusional state after an assault. She reported a history of sexual promiscuity, and subsequent testing revealed a serum rapid plasma reagin titer of 1:64, a cerebral spinal fluid venereal disease research laboratory titer of 1:8, and fluorescent treponemal antibody absorption reactive in both serum and CSF. Neurobehavioral testing revealed only subtle deficits in attention. MRI (T1 and T2 weighted of the brain), and EEG were normal. SPECT showed areas of hypoperfusion in a patchy distribution involving the parietal lobes bilaterally. This pattern is suggestive of meningovasculitis