Changes in the Syphilis Rapid Plasma Reagin Titer Between Diagnosis and Treatment.

BACKGROUND: We compared the rapid plasma reagin (RPR) titer on the day of initial presentation with that on the day of syphilis treatment to inform clinical practice as to whether a repeated RPR test should be recommended. METHODS: We undertook a retrospective study between 1 March 2011 and 31 December 2020 at the Melbourne Sexual Health Centre in Australia among individuals who underwent syphilis serology on the day of initial presentation and the day of treatment, if the latter were within 14 days after initial presentation. We calculated the percentage of individuals with a ≥4-fold change in RPR titer, stratified by the time between initial presentation and treatment and by syphilis stage. RESULTS: Among the 766 included syphilis cases, the median duration between initial presentation and treatment was 6 days (interquartile range, 5-7 days). Of these cases, 14.8% (n = 113) had a ≥4-fold increase or decrease during this interval. The number of cases with a ≥4-fold increase or decrease in RPR titer increased with increasing time between initial presentation and treatment, from 5.7% (n = 6) 1-3 days after initial presentation to 26.2% (n = 27) at 10-14 days (Ptrend < .001). There was no significant difference in the number of cases with a ≥4-fold increase or decrease in RPR titer between syphilis stages (P = .66). CONCLUSIONS: Our data support the recommendation of repeating the RPR titer if the day of initial presentation and the day of treatment are different, even when treatment is within a few days after initial presentation.

Evaluation of Three Automated Nontreponemal Rapid Plasma Reagin (RPR) Tests for the Laboratory Diagnosis of Syphilis.

Automated nontreponemal rapid plasma reagin (RPR) tests were recently introduced in the United States for syphilis testing and limited performance data are available. In collaboration with the Association of Public Health Laboratories, three public health laboratories (PHL) were chosen through a competitive selection process to evaluate the performance of three FDA-cleared automated RPR test systems: BioPlex 2200 Syphilis Total & RPR assay (Bio-Rad Laboratories), AIX 1000 (Gold Standard Diagnostics), and ASI Evolution (Arlington Scientific). Panels prepared at the CDC included: a qualitative panel comprised of 734 syphilis reactive/nonreactive sera; a quantitative panel of 50 syphilis reactive sera (RPR titer 1:64 to 1:1,024); and a reproducibility panel of 15 nonreactive and reactive sera (RPR titer 1:1 to 1:64). Panels were shipped frozen to the PHL and tested on the automated RPR systems following manufacturers' instructions. Prior test results were blinded to all laboratories. When compared to manual RPR (Arlington Scientific) performed at the CDC as a reference test, the qualitative panel results demonstrated an overall concordance of 95.9% for AIX 1000, 94.6% for ASI Evolution, and 92.6% for Bioplex RPR; quantitative panel showed within range titer of 2-fold for 94% of specimens for AIX 1000, 68% for ASI Evolution, and 64% for BioPlex RPR, and the reproducibility testing panel demonstrated point estimates ranging from 69 to 95%. Automated RPR instruments could reduce turnaround time and minimize interpretation errors. However, additional evaluations with more specimens could assist laboratories with implementing automated RPR tests and understanding their limitations.

Evaluation of the AIX1000 Automated Rapid Plasma Reagin Assay in a High-Prevalence Setting.

BACKGROUND: Manually performed nontreponemal assays, such as rapid plasma reagin (RPR), are labor intensive and time consuming. Recently, commercial automated RPR assays gained attention. The aim of this study was to compare the qualitative and quantitative performance of the AIX1000 (RPR-A; Gold Standard Diagnostics) to a manual RPR test (RPR-M; Becton Dickinson Macrovue) within a high-prevalence setting. METHODS: A retrospective panel of 223 samples was selected for comparison between RPR-A and RPR-M, including 24 samples from patients with known syphilis stages and 57 samples from 11 patients in follow-up. In addition, 127 samples obtained during routine syphilis diagnosis with RPR-M were analyzed prospectively with AIX1000. RESULTS: Overall qualitative concordance (percent agreement) between both assays was 92.0% in the retrospective and 89.0% in the prospective panel. Of 32 discordances, 28 were explained by a treated syphilis infection still positive in one assay and already negative in the other. One sample was false positive with RPR-A, 1 infection remained undetected by RPR-M, and 2 remained undetected by RPR-A. A hook effect was apparent on the AIX1000 at RPR-A titers from 1:32 onward; however, no infections were missed. Accepting a ±1 titer difference, quantitative concordance between both assays reached 73.1% and 98.4% for the retrospective and prospective panels, respectively, with an upper limit of reactivity for RPR-A at 1:256. CONCLUSIONS: The AIX1000 showed a similar performance to Macrovue RPR with the exception of a negative deviation for high-titer samples. Within the reverse algorithm used in our high-prevalence setting, AIX1000's main advantage is automation.

High Number of Positive Rapid Plasma Reagin With Low Titers Using the Automated AIX 1000 RPR System.

ABSTRACT: This study evaluated the performance of manual rapid plasma reagin (RPR) and automated AIX1000 RPR tests for the diagnosis of syphilis. Manual RPR showed a 3% reactive result compared with 5.8% for the automated test mainly because of RPR reactive results with low titers not confirmed by Treponema pallidum particle agglutination.

A Case of Congenital Syphilis-Focus on Histopathology and Literature Review.

ABSTRACT: Although a rare disease, the incidence of congenital syphilis is on the rise in the US. We report a case of early congenital syphilis in a 1-day-old premature boy with positive Rapid plasma reagin titer, respiratory insufficiency, disseminated intravascular coagulation, and encephalopathy, born to a mother with known syphilis infection. Skin examination showed diffuse truncal petechiae, desquamation of the distal extremities, and violaceous, retiform plaques on the buttocks and lower extremities. A biopsy was performed to rule out an infectious etiology or vasculitis. Histopathologic examination revealed irregular epidermal acanthosis with orthokeratosis and parakeratosis. There were foci of neutrophilic infiltrate forming rare pustules within the stratum corneum and focal intraepidermal eosinophils, neutrophils, and rare dyskeratotic keratinocytes. In the dermis, there was some minimal endothelial swelling with a perivascular, interstitial, and periadnexal infiltrate of lymphocytes, eosinophils, and rare plasma cells. A Treponema pallidum immunostain highlighted spirochetes present within the epidermis and within the eccrine ducts. Penicillin G therapy was administered for 10 days. The infant's Rapid plasma reagin titer trended downward until it was negative 6 months after birth. Literature review reveals 8 case reports within the last 20 years describing the histopathology of rashes in congenital syphilis. Herein we summarize the reported histopathology of rashes in congenital syphilis and compare it to the histopathology of rashes in secondary syphilis in adults.

Evaluation of BioPlex 2200 Syphilis Total With Automated Rapid Plasma Reagin: Experience From a Tertiary Medical Center.

BACKGROUND: Treponema-specific assays are widely adopted in the first step of the reverse algorithm of serologic syphilis screening. The new BioPlex 2200 Syphilis Total and rapid plasma reagin (RPR) test is designed to perform the first 2 steps of the algorithm simultaneously. However, limited data regarding the BioPlex Syphilis Total and RPR in clinical practice exist. METHODS: A total of 293 random samples at a tertiary medical center were tested by BioPlex Syphilis Total and RPR, BioPlex Syphilis IgG, Architect Syphilis TP, and BD Macro-Vue RPR card. Treponema pallidum particle agglutination (TP-PA) assay and clinical chart review were used to resolve discrepancies. Comparisons were performed among treponemal-specific assays and between 2 RPR tests. RESULTS: Good overall agreements (>91%) were achieved between BioPlex Syphilis Total, BioPlex Syphilis IgG, and Architect Syphilis TP. Overall agreement between BioPlex RPR and BD RPR was 86.8% with positive percent agreement of 66.7% and negative percent agreement of 96.3%. There were 37 discordant samples including 30 with BD RPR+/BioPlex RPR- and 7 with BD RPR-/BioPlex RPR+. Negative BioPlex RPR results were observed in samples with reactive BD RPR: 10 (91%) of 11 for BD RPR 1:1, 13 (65%) of 20 for BD RPR 1:2, 6 (35%) of 17 for BD RPR 1:4, and 1 (7%) of 14 for BD RPR 1:8. The discordant samples were predominantly from patients with high-risk of syphilis reinfection and included 9 patients with an early reinfection. CONCLUSIONS: Our results demonstrated that BioPlex Syphilis Total and Architect Syphilis TP performed similarly. The BioPlex RPR missed a small number of early syphilis reinfections, and its implementation should depend on the patient population that the laboratory serves.

Utility of rapid plasmin reagin titres in assessing treatment response and re-infection for infectious syphilis.

Background The rapid plasma reagin (RPR) assay is commonly used as a surrogate marker of infectious syphilis, but is non-specific, slow to change and variable in its rate of decline post treatment. METHODS: Within an urban sexual health service testing predominantly men who have sex with men, a file review of RPR changes was undertaken in all subjects who had a dilution level of ≥1:4, between January 2015 to the end of December 2018. RESULTS: Overall, 248 cases of infectious syphilis were identified in 215 subjects (165 HIV seropositive, 50 HIV seronegative). Among unique-subject cases with follow-up RPR recorded, seroreversion to a non-reactive titre was achieved in only 42.3% (71/168) cases at a median of 235 days (interquartile range: 138-348 days) and was significantly less likely if patients had HIV infection (P = 0.02), late latent syphilis (P = 0.003) or a subsequent syphilis infection (P < 0.0001). Having HIV infection (P = 0.03) or a subsequent episode of syphilis (P = 0.01) were associated with a lower likelihood of documented cure. CONCLUSIONS: The slow decay in RPR titres post therapy and the inability of a significant number of subjects to achieve a non-reactive result over time makes RPR a poor test for assessing the adequacy of treatment or in diagnosing re-infection, especially in populations having repeated and frequent risk exposures. As the number of syphilis cases continue to climb, better tests that accurately assess pathogen presence are urgently needed.

Clinical Performance of the BioPlex 2200 Syphilis Total & RPR Assay at a Tertiary Medical Center with a High Rate of Syphilis.

Manual treponemal and nontreponemal serologic testing has historically been used for the diagnosis of syphilis. This approach is simple and reproducible but labor intensive. Recently, the FDA cleared the fully automated BioPlex 2200 Syphilis Total & RPR assay for the detection of treponemal and nontreponemal antibodies. We evaluated the clinical performance of this assay at a tertiary medical center with a high syphilis prevalence. Prospective consecutively collected (n = 400) and known RPR-positive (n = 100) specimens were compared using predicate manual rapid plasma reagin (RPR) and fluorescent treponemal antibody absorption (FTA) methods and the BioPlex 2200 Syphilis Total & RPR assay. Positive and negative percent agreements (PPA and NPA, respectively) between the assays were calculated. The PPA and NPA between the manual and BioPlex 2200 RPR results for the prospective population were 85% (17/20; 95% confidence interval [CI], 69% to 100%) and 98% (373/380; 95% CI, 97% to 99%), respectively. The PPA for the manual RPR-positive population was 88% (88/100; 95% CI, 82% to 94%). Overall, the manual and BioPlex 2200 RPR titers demonstrated 78% (99/127) concordance within ±1 dilution and 94% (120/127) within ±2 dilutions. An interpretation of the syphilis serologic profile using the traditional algorithm showed a concordance of 99.5% in the prospective population and 85% in the manual RPR-positive cohort. The performance of the BioPlex 2200 Syphilis Total & RPR assay is comparable to those of manual methods. The high NPA of this assay combined with the ability to automate a historically labor-intensive assay is an appealing attribute for syphilis screening in a high-volume laboratory.

Risk of neurosyphilis in HIV-infected persons with syphilis lacking signs or symptoms of central nervous system infection.

OBJECTIVES: People living with HIV (PLWH) are at increased risk of asymptomatic neurosyphilis; thus, it has been common practice to perform a lumbar puncture (LP) in all PLWH presenting with syphilis regardless of stage, signs or symptoms. However, this practice varies widely among clinicians. Our objective was to elucidate the number of LPs required to diagnose a single case of asymptomatic neurosyphilis. METHODS: We performed an electronic health record (EHR) review of PLWH who were diagnosed with syphilis of any stage over a 10-year period. EHRs were reviewed to determine the number of subjects who had an LP performed, what proportion had neurological signs or symptoms, and whether a diagnosis of neurosyphilis was made at presentation or follow-up. RESULTS: In 261 separate episodes of syphilis in 230 subjects, we found the major risk factors for asymptomatic neurosyphilis to be low CD4 T-cell count (P = 0.0007), high rapid plasma reagin (RPR) titre (P = 0.019) and lack of HIV virological suppression (P = 0.003). The majority of our subjects (78%) with neurosyphilis presented with central nervous system (CNS) symptoms. We estimate, if standard practice is to perform LP in all patients, that the number needed to test (NNTT) = 38. CONCLUSIONS: This large number of potentially unnecessary LPs, along with heterogeneity of presentation, and the never-nil risk of asymptomatic neurosyphilis should be incorporated into clinical decision-making. The majority of PLWH presenting with a serological diagnosis of syphilis, but no neurological signs or symptoms, do not necessarily require an LP for an evaluation of asymptomatic neurosyphilis.

Rapid Syphilis Testing for Men Who Have Sex With Men in Outreach Settings: Evaluation of Test Performance and Impact on Time to Treatment.

BACKGROUND: Rapid syphilis tests (RST) may shorten time to syphilis diagnosis and treatment while enhancing access to testing in outreach settings. There are limited data on the performance of RST in outreach settings in the US. METHODS: We offered RST (Syphilis Health Check) at 6 outreach sites to men who reported having sex with men and no prior history of syphilis. Clients accepting RST were also tested with laboratory-based rapid plasma reagin (RPR) and reflex Treponema pallidum particle agglutination (TPPA) assay when RPR or RST were positive. Clients with positive RST were immediately referred to a sexually transmitted infection clinic. Those declining RST were screened with RPR and reflex TPPA only. The validity of the RST-based algorithm was compared with the RPR-based algorithm among participants receiving both. Time to treatment for those accepting RST was compared with those declining RST and to a historical control group screened in outreach settings with RPR and reflex TPPA before the availability of RST. RESULTS: Rapid syphilis test was accepted by 690 (64%) of 1081 eligible clients. Compared with RPR-based algorithm, RST sensitivity was 90%; specificity, 98.5%; positive predictive value, 47.4%; and negative predictive value, 98.5. The single false-negative case by RST was determined to be a late latent case by RPR/TPPA. Median time to treatment was 1 day (range, 0-6 days) for 9 of 690 accepting RST, compared to 9 days (range, 7-13 days) for 3 of 391 declining RST, and 9 days (range, 6-21 days) for 25 of 1229 historical controls (P < 0.0001). CONCLUSION: Compared with an RPR-based algorithm, RST identified all early syphilis cases. Although RST had high specificity and negative predictive value, the low positive predictive value resulted in additional assessments in a sexually transmitted infection clinic for some patients. However, RST use in outreach settings significantly decreased time to treatment for new syphilis cases.

Evaluation of a Rapid Syphilis Test in an Emergency Department Setting in Detroit, Michigan.

BACKGROUND: Syphilis transmission can be prevented by prompt diagnosis and treatment of primary and secondary infection. We evaluated the performance of a point-of-care rapid syphilis treponemal (RST) test in an emergency department (ED) setting. METHODS: Between June 2015 and April 2016, men aged 18 to 34 years seeking services in a Detroit ED, and with no history of syphilis, were screened for syphilis with the RST test, rapid plasma reagin (RPR) test, and Treponema pallidum particle agglutination assay (TP-PA). A positive reference standard was both a reactive RPR and a reactive TP-PA. We compared test results in self-reported men who have sex with men (MSM) to non-MSM. RESULTS: Among 965 participants, 10.9% of RST tests were reactive in MSM and only 1.5% in non-MSM (P < 0.001). Sensitivity of the RST test was 76.9% and specificity was 99.0% (positive predictive value, 50.0%) compared with the positive reference standard. Three discordant specimens found negative with the RST test but positive with the reference standard had an RPR titer of 1:1, compared with 10 specimens with concordant positive results that had a median RPR titer of 1:16. The RST sensitivity was 50.0% (positive predictive value, 68.4%) compared to the TP-PA test alone. Among men seeking care in an ED, the RST detected 76.9% of participants with a reactive RPR and TP-PA. CONCLUSIONS: The RST test detected all of the participants with an RPR titer ≥1:2 but less than 20% of participants with a positive TP-PA and negative RPR. The RST test was useful to detect a high proportion of participants with an active syphilis in an urban ED.

Increasing Syphilis Detection Among Patients Assigned Male at Birth Screened at a Boston Community Health Center Specializing in Sexual and Gender Minority Health, 2005-2015.

BACKGROUND: United States syphilis rates have increased to levels last seen in the 1990s. We examined syphilis epidemiology of patients attending a Boston community health center specializing in sexual and gender minority health. METHODS: We performed a retrospective cohort study of all patients assigned male at birth screened with rapid plasma reagin from 2005 through 2015. We developed an algorithm to identify new infections and used repeat cross-sectional analysis to assess temporal trends in syphilis diagnoses. We also performed longitudinal analysis to calculate syphilis incidence using a Cox proportional hazards model that accounts for multiple infections over time. RESULTS: Eighteen thousand two hundred eighty-two patients had a total of 57,080 rapid plasma reagins, 1170 (2.0%) tests met criteria for syphilis. Adjusted syphilis diagnoses increased from 1.2% to 1.9%, recurrent syphilis diagnoses increased from 0.04% to 0.3% during the study period. Black and Hispanic/Latinx patients, patients aged 35 to 44 years, gay/bisexual patients, cisgender men, and human immunodeficiency virus (HIV)-infected patients and those who became HIV-infected during the study period were more likely to test positive for syphilitic infection in repeat cross-sectional analysis. Among 6199 patients screened more than 1 time over 21,745 person-years, there were 661 new syphilis cases (3.0% annual incidence; 95% confidence interval [CI], 2.8% to 3.2%). Compared with those aged 14 to 24 years, patients 45 years or older were less likely to experience syphilis. New HIV infection was associated with increased risk of incident syphilis (adjusted hazard ratio, 2.87; 95% CI, 1.61-5.13). Virally suppressed HIV-infected patients were less likely to experience incident syphilis (adjusted hazard ratio, 0.69; 95% CI, 0.55-0.87). CONCLUSIONS: The high incidence of syphilis among patients assigned male at birth disproportionately affected young patients, black and Hispanic/Latinx patients, gay/bisexual patients, cisgender men, and those with new or chronic HIV infection. Syphilitic reinfection rates increased over time.

Evaluation of the BioPlex 2200 syphilis total screen (IgG/IgM) with reflex to an automated rapid plasma reagin test.

BACKGROUND: We evaluated the recently FDA cleared BioPlex 2200 Syphilis Total Screen and automated rapid plasma reagin (RPR) assay for the detection of total (IgG/IgM) treponemal and non-treponemal antibodies in the reverse syphilis algorithm. METHODS: Prospectively submitted samples (n = 885) were assayed by both the IgG/IgM BioPlex Syphilis Screen and the original IgG BioPlex Syphilis Screen. The IgG screen reactive samples were reflexed to traditional RPR, and IgG/IgM screen reactive samples were reflexed to the automated RPR. Nonreactive RPR samples were tested by the Treponemal Pallidum Particle Agglutination test (TP-PA). Additional samples were collected (n = 404 total samples) to directly compare the automated and traditional RPR assays with each other. RESULTS: The sensitivity and specificity of the IgG/IgM screen with automated RPR was 95.6% (95% confidence interval [CI] 87.0-99.1) and 99.6% (CI 99.2-99.8) while the sensitivity and specificity of the BioPlex IgG screen with traditional RPR was 97.8% (CI 89.1-99.9) and 99.3% (CI 98.8-99.4). The sensitivity and specificity of the BioPlex RPR compared with traditional RPR was 95.8% (CI 93.9-97.0) and 94.1% (CI 89.4-91.1) and 95.3% (CI 92.6-97.1). The mean of the titer differences between the BioPlex RPR and the traditional RPR was 1.0 ± 0.9 SD titers. CONCLUSION: The addition of the detection of treponemal IgM antibodies to the IgG/IgM screen did not significantly affect the sensitivity and specificity compared to the original IgG screen. However, the addition of the comparable BioPlex RPR assay to the instrumentation significantly reduces the overall labor of syphilis screening and confirmation.

Trends and Predictors of Syphilis Prevalence in the General Population: Global Pooled Analyses of 1103 Prevalence Measures Including 136 Million Syphilis Tests.

Background: This study assessed levels, trends, and associations of observed syphilis prevalence in the general adult population using global pooled analyses. Methods: A standardized database of syphilis prevalence was compiled by pooling systematically gathered data. Random-effects meta-analyses and meta-regressions were conducted using data from the period 1990-2016 to estimate pooled measures and assess predictors and trends. Countries were classified by World Health Organization region. Sensitivity analyses were conducted. Results: The database included 1103 prevalence measures from 136 million syphilis tests across 154 countries (85% from women in antenatal care). Global pooled mean prevalence (weighted by region population size) was 1.11% (95% confidence interval [CI], .99-1.22). Prevalence predictors were region, diagnostic assay, sample size, and calendar year interacting with region. Compared to the African Region, the adjusted odds ratio (AOR) was 0.42 (95% CI, .33-.54) for the Region of the Americas, 0.13 (95% CI, .09-.19) for the Eastern Mediterranean Region, 0.05 (95% CI, .03-.07) for the European Region, 0.21 (95% CI, .16-.28) for the South-East Asia Region, and 0.41 (95% CI, .32-.53) for the Western Pacific Region. Treponema pallidum hemagglutination assay (TPHA) only or rapid plasma reagin (RPR) only, compared with dual RPR/TPHA diagnosis, produced higher prevalence (AOR >1.26), as did smaller sample-size studies (<500 persons) (AOR >2.16). Prevalence declined in all regions; the annual AORs ranged from 0.84 (95% CI, .79-.90) in the Eastern Mediterranean to 0.97 (95% CI, .97-1.01) in the Western Pacific. The pooled mean male-to-female prevalence ratio was 1.00 (95% CI, .89-1.13). Sensitivity analyses confirmed robustness of results. Conclusions: Syphilis prevalence has declined globally over the past 3 decades. Large differences in prevalence persist among regions, with the African Region consistently the most affected.

Comparison of Manual and Fully Automated AIX1000 Rapid Plasma Reagin Assays for Laboratory Diagnosis of Syphilis.

The analytical performance of the AIX1000 system, a fully automated and recently FDA-cleared rapid plasma reagin (RPR) system, was evaluated by comparison to a manual RPR test in a traditional syphilis testing algorithm. A total of 1,028 consecutive serum samples submitted for syphilis testing to the University of North Carolina Hospitals Clinical Immunology Laboratory were tested per each manufacturer's instructions. Among those samples, 996 were nonreactive and 20 were reactive using both the ASI RPR card system and the AIX1000 system. Of the 12 discrepant specimens, 11 were AIX1000 reactive and ASI card nonreactive whereas 1 specimen was ASI card reactive and AIX1000 nonreactive. The sensitivity and specificity of the manual ASI card were 76.0% and 99.8%, respectively, while the sensitivity and specificity of the AIX100 were 100.0% and 99.4%, respectively (sensitivity P = 0.03). Among the 20 concordant reactive specimens, 68.4% of the titers agreed within ±1 dilution between methods. Reproducibility testing of the AIX1000 system demonstrated qualitative and semiquantitative (within ±1 dilution) agreement between specimens tested on different days of 96.0% and 76.0%, respectively, and 100.0% agreement between replicates within the same run. One of 24 samples analyzed under other disease conditions was reactive on both the AIX1000 system and the ASI card. Overall, the fully automated AIX1000 system demonstrated significantly enhanced sensitivity and specificity similar to that of the manual ASI RPR card test, making the AIX1000 system suitable for the laboratory diagnosis of syphilis in a clinical laboratory setting.

Usefulness of Automated Latex Turbidimetric Rapid Plasma Reagin Test for Diagnosis and Evaluation of Treatment Response in Syphilis in Comparison with Manual Card Test: a Prospective Cohort Study.

The usefulness of an automated latex turbidimetric rapid plasma reagin (RPR) assay, compared to the conventional manual card test (serial 2-fold dilution method), for the diagnosis of syphilis and evaluation of treatment response remains unknown. We conducted (i) a cross-sectional study and (ii) a prospective cohort study to elucidate the correlation between automated and manual tests and whether a 4-fold decrement is a feasible criterion for successful treatment with the automated test, respectively, in HIV-infected patients, from October 2015 to November 2017. Study i included 518 patients. The results showed strong correlation between the two tests (r = 0.931; P < 0.001). With a manual test titer of ≥1:8 plus a positive Treponema pallidum particle agglutination (TPPA) test as the reference standard for diagnosis, the optimal cutoff value for the automated test was 6.0 RPR units (area under the curve [AUC], 0.998), with positive predictive value (PPV) of 92.5% and negative predictive value (NPV) of 99.4%. Study ii enrolled 66 men with syphilis. Their RPR values were followed up until after 12 months of treatment. At 12 months, 77.3% and 78.8% of the patients achieved a 4-fold decrement in RPR titer by the automated and manual test, respectively. The optimal decrement rate in RPR titer by the automated test for a 4-fold decrement by manual card test was 76.54% (AUC, 0.96) (PPV, 96.1%; NPV, 80.0%). The automated RPR test is a good alternative to the manual test for the diagnosis of syphilis and evaluation of treatment response and is more rapid and can handle more specimens than the manual test without interpersonal variation in interpretation.

Serological response to therapy following retreatment of serofast early syphilis patients with benzathine penicillin.

Background: Some syphilitic patients remain in a serologically positive state after the recommended therapy. Although we often retreat patients in clinical practice, the optimal treatment protocol remains uncertain due to the paucity of data regarding serological response to retreatment and long-term outcomes. Methods: We examined rapid plasma reagin serological test results of 70 serofast early syphilis cases who were retreated with 2.4 million units of benzathine penicillin weekly for 3 weeks. Serological retreatment success was defined as a minimum 4-fold decrease in baseline rapid plasma reagin test antibody titre within 6 months. Results: Thirty-four (48.6%) of the patients who failed to achieve serological cure at 6 months after initial therapy achieved serological cure at 12 months. Patients who had higher non-treponemal titres at baseline and at 6 months were more likely to exhibit serological cure after retreatment than those with lower titres. Conclusions: Our results suggest that the incremental benefit of retreating serofast patients with early syphilis is moderate, considering the almost 1:1 ratio of serological response to serofast state at follow-up.

Repeat syphilis has a different immune response compared with initial syphilis: an analysis of biomarker kinetics in two cohorts.

OBJECTIVE: We aimed to asses if there are differences in the clinical presentation and immune response of repeat as compared with initial syphilis. METHODS: Prospective study: we prospectively recruited all patients with a new diagnosis of syphilis and tested their plasma for a range of cytochemokines and rapid plasma reagin (RPR) at baseline pretreatment and 6 months following therapy. Retrospective study: we compared RPR assay response kinetics between initial and repeat syphilis in persons attending our HIV/STI clinic from 1993 to 2016. RESULTS: Prospective study: a total of 91 individuals, 36 with initial syphilis and 55 with repeat syphilis, were included in the study. At baseline visit, those with initial syphilis were more likely to be symptomatic and have higher levels of interleukin-10 than repeaters. At baseline, median RPR titres were higher in the repeat than the initial infection groups. Repeaters were less likely than those with initial infections to serorevert to a negative RPR and be serofast (<4-fold RPR titre decline) at 6 months.Retrospective study: syphilis was diagnosed in 1027/43 870 individuals tested. At diagnosis, repeaters had higher RPR titres and a stepwise increase in RPR titre with number of syphilis episodes. They had a different RPR test response kinetic: they were less likely to be serofast and to serorevert than initial syphilis at 6 and 12 months. No individuals with four or more previous episodes of syphilis seroreverted. CONCLUSION: Repeat syphilis has a different clinical presentation and immunological response to initial infection.

Unique manifestations and risk factors of Jarisch-Herxheimer reaction during treatment of child congenital syphilis.

OBJECTIVES: The objective of this retrospective study was to summarise the clinical manifestations of, and to analyse the incidence and risk factors of, Jarisch-Herxheimer reaction (JHR) during the treatment of children with symptomatic congenital syphilis. METHODS: Clinical data of 60 children with clinically and laboratory diagnosed congenital syphilis, hospitalised in Beijing Ditan Hospital between January 2010 and November 2015, were collected and analysed. RESULTS: A total of 11 patients with congenital syphilis (11/60, 18.3%) developed JHR. JHR occurred in 1-6 hour after the first dose of penicillin. Common clinical manifestations included fever (11/11, 100%), irritability (11/11, 100%), rapid pulse and breathing (11/11, 100%), exacerbation of existing rash (5/11, 45.6%) and chills (3/11, 27.3%). Of the 11 patients who developed JHR, 9 patients (9/11, 81.8%) had bone syphilis, 10 (10/11, 90.9%) had more than three organs affected by syphilis and 10 (10/11, 90.9%) had a high plasma concentration of rapid plasma reagin (RPR) (≥1:256); these percentages were significantly higher than in patients who had not developed JHR (p<0.05), suggesting that the occurrence of JHR was related to bone syphilis, having more than three organs affected by syphilis and a high plasma concentration of RPR. CONCLUSIONS: Clinicians should be familiar with the risk factors for this reaction and its common clinical manifestations.

A Web Application to Facilitate Syphilis Reactor Grid Evaluations.

BACKGROUND: Many health departments use a "reactor grid" to determine which laboratory-reported syphilis serologic test results require investigation. We developed a Web-based tool, the Syphilis Reactor Grid Evaluator (SRGE), to facilitate health department reactor grid evaluations and test the tool using data from Seattle & King County, Washington. METHODS: We developed SRGE using the R Shiny Web application framework. When populated with a data set including titer results and final disposition codes, SRGE displays the percent of verified early syphilis cases by serologic titer result and patient age in each cell of the grid. The results can be optionally stratified by sex, test type, and previous rapid plasma reagin titer. The impact of closing laboratory results without investigation in cells selected by the user is dynamically computed. The SRGE calculates the percent of all laboratory reports closed ("efficiency gained"), the proportion of all early syphilis cases closed without investigation ("case finding loss"), and the ratio of percent of cases identified for investigation to percent of all laboratory reports investigated ("efficiency ratio"). After defining algorithms, users can compare them side-by-side, combine subgroup-specific algorithms, and export results. We used SRGE to compare the current Public Health-Seattle & King County (PHSKC) reactor grid to 5 alternate algorithms. RESULTS: Of 13,504 rapid plasma reagin results reported to PHSKC from January 1, 2006, to December 31, 2015, 1565 were linked to verified early syphilis cases. Updating PHSKC's current reactor grid could result in an efficiency gain of 4.8% to 25.2% (653-3403 laboratory reports) and case finding loss of 1% to 8.4% (10-99 fewer cases investigated). CONCLUSIONS: The Syphilis Reactor Grid Evaluator can be used to rapidly evaluate alternative approaches to optimizing the reactor grid. Changing the reactor grid in King County to close more laboratory results without investigation could improve efficiency with minimal impact on syphilis case finding.