• non-treponemal antibody
• point-of-care test
• rapid plasma reagin
• rapid test
• serum
• signal/cutoff ratio
• syphilis
• treponemal antibody

• Uveitis/complications
• Uveitis/diagnosis
• Uveitis/therapy
• Syphilis/complications
• Syphilis/diagnosis
• Syphilis/therapy
• Taiwan
• Humans
• Ophthalmology/standards

• atypical stroke
• cerebro-vascular accident (stroke)
• meningovascular neurosyphilis
• tertiary syphilis
• vascular neurology

• diagnostic performance
• neurosyphilis
• nontreponemal tests
• serological assays
• treponemal tests

Immunoassays are widely used as screening tests for HIV and syphilis in clinical, public health, and research settings. For syphilis, immunoassays are used in 'reverse syphilis algorithms' that start with treponemal tests such as syphilis IgG or syphilis total antibodies for the initial screen. Many screening immunoassays for HIV and syphilis use signal-to-cutoff (S/CO) values for determining positivity, with a cutoff value such as 1.0 differentiating positive from negative. Published literature indicates that the S/CO value often correlates with the likelihood of subsequent confirmation of HIV and syphilis infections, with low S/CO values barely exceeding the cutoff more likely to represent false positive screens. The data in this article present results from the Roche Diagnostics Elecsys HIV combi PT Assay and the Elecsys Syphilis Assay. The data include 19,368 syphilis total antibody screening results on 15,764 unique patients and 28,952 HIV screening results on 24,556 unique patients, S/CO values, clinical area where testing was ordered, sex, and age. For samples with positive syphilis total antibody screens, the data also include results of RPR (the immediate next step in the reverse algorithm), Treponema pallidum particle agglutination (TP-PA; for those samples in which RPR was non-reactive in the testing cascade), and clinical information and other testing related to diagnosis of syphilis. For positive HIV screens, the data also include HIV antibody differentiation results, HIV-1 PCR or HIV-2 results results (if performed), and clinical information related to diagnosis of HIV. The distributions of S/CO values relative to confirmation status were analyzed.

• False positive reaction
• HIV-1
• Treponema pallidum
• immunoassay
• syphilis
• viral load

• Reverse algorithm
• Treponema pallidum
• serodiagnosis
• syphilis

• Ocular syphilis
• Sexually transmitted infections
• Syphilis
• Syphilitic uveitis
• Uveitis

Rising rates of syphilis (T. pallidum; Tp) requires rapid diagnosis and treatment to manage the growing epidemic. Syphilis serology is imperfect and requires interpretation of multiple tests while molecular diagnostics allows for potential yes-no identification of highly infective, primary anogenital lesions. Accuracy of this testing modality has thus far been limited to small, highly selective studies. Therefore, we retrospectively assessed a large, adult population of patients with anogenital lesions seen at Sexually Transmitted Infection (STI) clinics in Alberta, Canada who were screened for syphilis and herpes simplex (HSV) 1/2 using PCR to evaluate Tp-PCR versus serology to diagnose primary syphilis. 114 (3.1%) of the 3,600 adult patients had at least one Tp-PCR+ anogenital lesion with 99 (2.8%) patients having newly positive syphilis serology (new INNO-LIA positive or 4-fold RPR increase). Tp-PCR had a sensitivity of 49.3% (95% CI 42.6-56.1) and specificity of 99.9% (99.7-100.0). Positive predictive values and negative predictive values in the study population or when corrected for provincial prevalence were 97.4% (92.5-99.5) or 0.4% (0.4-1.2) and 96.7% (96.1-97.3) or 100.0% (100.0-100.0), respectively. Positive and negative likelihood ratios were estimated at 555 (178-1733) and 0.5 (0.4-0.6), respectively. Review of all Tp-PCR performed with or without exclusion of HSV-positive lesions resulted in no significant change in Tp-PCR characteristics. Interestingly, 12 of the Tp-PCR+ samples had negative serology at time of lesion sampling but became positive within our 28-day testing window. Overall, this study further supports the use of Tp-PCR as an accurate assay to rapidly identify, treat, and prevent the spread of primary syphilis.

• anogenital lesions
• molecular diagnostic
• serology diagnostic
• sexually transmitted diseases (STDs)
• sexually transmitted infections
• syphilis
• treponema pallidum

• appropriate use
• lumbar puncture
• neoplastic meningitis
• non-treponemal
• syphilis

Early neurosyphilis can occur in an immunocompromised host. It has a widely varied presentation. Isolated CN6 as presenting symptom has not been described.

• HIV
• infectious disease
• neurology
• neurosyphilis
• syphilis

• Bacterial Proteins/immunology
• Cross Reactions
• Recombinant Proteins/immunology
• Serologic Tests
• Syphilis/diagnosis
• Syphilis/immunology
• Treponema pallidum/immunology

• Coordination of Superior Level Staff Improvement - Brazil
• Brazilian National Council for Scientific and Technological Development (CNPq)
• Bahia State Research Support Foundation (FAPESB)

• AIX1000
• Laboratory automation
• RPR
• Syphilis

Serological tests of non-treponemal and treponemal types are the most frequently used for syphilis diagnosis. Treponemal tests are available in wide variety of assay formats; however, limited advances have been made for the improvement of conventional non-treponemal tests. The objective of this work was to develop a novel non-treponemal magnetic particle-based agglutination assay (NT-MAA) and evaluate its feasibility for syphilis testing.

Cardiolipin was modified and coupled to magnetic microbeads. Serum diluted in phosphate-buffered saline was mixed with cardiolipin-coupled beads and incubated in a round bottom microplate for 90–120 min followed by visual inspection. A panel of reported syphilis (n=127) and non-reactive (n=244) specimens was prepared to evaluate the NT-MAA performance in comparison to conventional rapid plasma reagin (RPR). Treponema pallidum particle agglutination (TP-PA) assay and enzyme immunoassay (EIA) were included. Analytical sensitivity and reproducibility of NT-MAA were also determined.

The non-treponemal NT-MAA and RPR showed sensitivity of 90.6% and 88.2% and specificity of 96.7% and 100%, respectively. The treponemal TP-PA and EIA yielded sensitivity of 100% and 99.2%, respectively, and 100% specificity by both assays. The per cent agreement between NT-MAA and RPR was 97% (kappa=0.931, 95% CI 0.891 to 0.971). Analytical sensitivity determined with IgM anticardiolipin antibody (ACA) was 2.6 µg/mL for both NT-MAA and RPR, while IgG ACA yielded 0.9 µg/mL and 1.7 µg/mL for NT-MAA and RPR, respectively. Qualitative results of intra-assay and interassay reproducibility revealed 100% consistency for NT-MAA.

Preliminary evaluation of the novel NT-MAA validated proof of concept using laboratory-characterised syphilis sera and demonstrated performance comparable to RPR. Further validation of NT-MAA using additional specimens with better clinical staging may broaden the scope of developed test for syphilis diagnosis.

• antibodies
• diagnostics
• immunology
• syphilis
• testing

• Automation
• Rapid plasma reagin (RPR)
• Syphilis antibody testing

• algorithm
• diagnosis
• nontreponemal test
• syphilis
• treponemal test

To synthesize lessons from comparison of results obtained from the immuno-chromatographic SD Bioline testing method and the chemiluminescent micro-particle immunoassay Architect in the diagnosis of syphilis at Livingstone Central hospital laboratory.

The specificity and sensitivity of SD Bioline syphilis 3.0 against the chemiluminescent immunoassay using the Architect syphilis Treponema pallidum (TP) was 85.3% and 91.3% respectively with substantial agreement between the two test methods (88%, ĸ  = 0.76; p < 0.0005). We recommend further comprehensive study with a larger sample size and clinical details to ascertain the validity of our findings. We also recommend using a non-treponemal test with the current treponemal tests being used to aid diagnosis.

• Architect syphilis
• Immunoassay
• SD Bioline
• Treponema pallidum

• Algorithm
• Screening
• Syphilis
• Treponema pallidum latex agglutination

• Early onset dementia
• Infective etiology
• Neglected diagnosis
• Neurosyphilis
• Psychiatric manifestations

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Algorithms
• Cross-Sectional Studies
• HIV Infections/complications
• Humans
• Male
• Mass Screening/methods
• Middle Aged
• Seroepidemiologic Studies
• Serologic Tests/methods
• Syphilis/diagnosis
• Syphilis/epidemiology
• Tertiary Care Centers
• Treponema pallidum/immunology
• Young Adult

• Mega-Project for National Science and Technology Development under the “12th, Five-Year Plan of China”

• CNS
• Case report
• Diagnosis
• HIV
• Neurosyphilis

An increasing number of institutions are transitioning from the traditional syphilis testing algorithm (initial screening with nontreponemal tests) to the ‘reverse’ algorithm (initial screening with treponemal tests such as syphilis IgG). The aim of this study was to evaluate the switch in syphilis algorithm at an academic medical center with a population with low syphilis prevalence.

We performed a six-year retrospective study at the University of Iowa Hospitals and Clinics, an academic medical center, comparing the traditional algorithm (n=12,612) with the reverse algorithm (n=10,453). False positives were considered to be positive screens with negative confirmatory testing.

Using the traditional algorithm, 93 samples (0.7% of total) screened positive with RPR, with 40 of these samples having negative TP-PA testing (43% of positive screens, 0.3% of total). Using the reverse algorithm, 110 screened positive with syphilis IgG (1.1% of total), and 33 of these samples had both negative RPR and TP-PA (30% of positive screens, 0.3% of total). In both algorithms, higher RPR titers and syphilis IgG values were associated with increased probability of positive confirmation.

In this study at an academic medical center, the reverse algorithm had significantly more total positive screens than the traditional algorithm. Both algorithms produced equivalent rates of active infection. The quantitative difference in positives between the two algorithms are the category of patients who are syphilis IgG positive, RPR non-reactive, and TP-PA reactive. Specimens with higher RPR titers and syphilis IgG values are more likely to confirm positive.

• False positive reactions
• Laboratory automation
• Obstetrics
• Serologic tests
• Sexually transmitted diseases

• Reverse testing algorithm
• Serology
• Syphilis
• Treponema pallidum

Automated Mediace Treponema pallidum latex agglutination (TPLA) and Mediace rapid plasma reagin (RPR) assays are used by many laboratories for syphilis diagnosis. This study compared the results of the traditional syphilis screening algorithm and a reverse algorithm using automated Mediace RPR or Mediace TPLA as first-line screening assays in subjects undergoing a health checkup.

Samples from 24,681 persons were included in this study. We routinely performed Mediace RPR and Mediace TPLA simultaneously. Results were analyzed according to both the traditional algorithm and reverse algorithm. Samples with discordant results on the reverse algorithm (e.g., positive Mediace TPLA, negative Mediace RPR) were tested with Treponema pallidum particle agglutination (TPPA).

Among the 24,681 samples, 30 (0.1%) were found positive by traditional screening, and 190 (0.8%) by reverse screening. The identified syphilis rate and overall false-positive rate according to the traditional algorithm were lower than those according to the reverse algorithm (0.07% and 0.05% vs. 0.64% and 0.13%, respectively). A total of 173 discordant samples were tested with TPPA by using the reverse algorithm, of which 140 (80.9%) were TPPA positive.

Despite the increased false-positive results in populations with a low prevalence of syphilis, the reverse algorithm detected 140 samples with treponemal antibody that went undetected by the traditional algorithm. The reverse algorithm using Mediace TPLA as a screening test is more sensitive for the detection of syphilis.

• Automated RPR
• Automated TPLA
• Reverse algorithm
• Syphilis
• Syphilis screening algorithm

• Human immunodeficiency virus (HIV)
• MSM
• coinfection
• prevention
• syphilis

• Inpatient
• Serologic Test
• Syphilis
• Treponema pallidum

The methods and strategies used to screen for syphilis and to confirm initially reactive results can vary significantly across clinical laboratories. While the performance characteristics of these different approaches have been evaluated by multiple studies, there is not, as of yet, a single, universally recommended algorithm for syphilis testing. To clarify the currently available options for syphilis testing, this update will summarize the clinical challenges to diagnosis, review the specific performance characteristics of treponemal and non-treponemal tests, and finally, summarize select studies published over the past decade which have evaluated these approaches. Specifically, this review will discuss the traditional and reverse sequence syphilis screening algorithms commonly used in the United States, alongside a discussion of the European Centre for Disease Prevention and Control syphilis algorithm. Ultimately, in the United States, the decision of which algorithm to use is largely dependent on laboratory resources, the local incidence of syphilis and patient demographics.

• Syphilis
• Treponemal infection
• Immunoassay
• Reverse sequence screening
• Rapid plasma regain
• Treponema pallidum particle agglutination test
• Automation
• Algorithm
• Primary infection
• Late latent infection

Recent efforts in transfusion medicine are focused on improving blood safety as well as establishing effective and efficient diagnostic algorithms for donor screening. To date, syphilis is a transfusion-transmitted infection re-emerged in many countries as a public health threat especially among populations at specific risk. This task requires new diagnostic tools and hemovigilance programs. The current diagnostic methodologies are debated, since presenting limitations and unresolved issues with special regard to the clinical interpretation of serological patterns, especially in asymptomatic patients and in blood donors. Furthermore, the switch from the traditional to alternative diagnostic algorithms underlines the lack of a gold standard, which has not been supported by shared guidelines. Besides, a lot of ongoing clinical trials on the performance of diagnostic assays, on the serological response associated with different pharmacological treatments, as well as on the prevention programs are currently under investigation. Here, we review the recent literature about the diagnosis of syphilis especially for low-risk populations proposing the adoption of an algorithm for blood donor screening that should satisfy the need of increasing safety for transfusion-transmitted infections in the modern blood transfusion centers.

• Blood donors
• confirmatory testing
• diagnostic tests syphilis
• serology

• Syphilis
• Treponema pallidum
• immunoassays
• non-treponemal antibodies
• screening algorithms
• treponemal antibodies

• Chlamydia trachomatis
• Neisseria gonorrhoeae
• New Caledonia
• Socio-demographic risk factors
• Treponema pallidum

• Adolescent
• Adult
• Chlamydia Infections/epidemiology
• Chlamydia Infections/etiology
• Cross-Sectional Studies
• Female
• Gonorrhea/epidemiology
• Gonorrhea/etiology
• Health Surveys
• Humans
• Logistic Models
• Male
• Middle Aged
• New Caledonia/epidemiology
• Prevalence
• Risk Factors
• Socioeconomic Factors
• Syphilis/epidemiology
• Syphilis/etiology
• Young Adult

• Algorithms
• Automation, Laboratory/methods
• Global Health
• Humans
• Point-of-Care Systems
• Serologic Tests/methods
• Serologic Tests/trends
• Syphilis/diagnosis

• VDRL tests
• antenatal care
• congenital syphilis management
• treponema screening

• IMMUNOLOGY

• Adult
• Aged
• Antibodies, Bacterial/blood
• Female
• Hemagglutination Tests
• Humans
• Immunoenzyme Techniques
• Male
• Middle Aged
• Reagent Kits, Diagnostic/standards
• Reagins/blood
• Sensitivity and Specificity
• Syphilis/diagnosis
• Syphilis Serodiagnosis/methods
• Treponema pallidum/immunology

New rapid point-of-care (POC) tests are being developed that would offer the opportunity to increase screening and treatment of several infections, including syphilis. This study evaluated three of these new rapid POC tests at a site in Southern California.

Participants were recruited from a testing center in Long Beach, California. A whole blood specimen was used to evaluate the performance of the Dual Path Platform (DPP) Syphilis Screen & Confirm, DPP HIV-Syphilis, and DPP HIV-HCV-Syphilis rapid tests. The gold-standard comparisons were Treponema pallidum passive particle agglutination (TPPA), rapid plasma reagin (RPR), HCV enzyme immunoassay (EIA), and HIV-1/2 EIA.

A total of 948 whole blood specimens were analyzed in this study. The sensitivity of the HIV tests ranged from 95.7–100% and the specificity was 99.7–100%. The sensitivity and specificity of the HCV test were 91.8% and 99.3%, respectively. The treponemal-test sensitivity when compared to TPPA ranged from 44.0–52.7% and specificity was 98.7–99.6%. The non-treponemal test sensitivity and specificity when compared to RPR was 47.8% and 98.9%, respectively. The sensitivity of the Screen & Confirm test improved to 90.0% when cases who were both treponemal and nontreponemal positive were compared to TPPA+/RPR ≥1∶8.

The HIV and HCV on the multi-infection tests showed good performance, but the treponemal and nontreponemal tests had low sensitivity. These results could be due to a low prevalence of active syphilis in the sample population because the sensitivity improved when the gold standard was limited to those more likely to be active cases. Further evaluation of the new syphilis POC tests is required before implementation into testing programs.

• Female
• HIV Infections/blood
• HIV Infections/diagnosis
• Hepatitis C/blood
• Hepatitis C/diagnosis
• Humans
• Immunoenzyme Techniques
• Male
• Point-of-Care Systems
• Sensitivity and Specificity
• Syphilis/blood
• Syphilis/diagnosis
• Syphilis Serodiagnosis/methods
• Treponema pallidum

• P20 MD003942 NIMHD NIH HHS
• R01 DA030234 NIDA NIH HHS
• R01DA030234 NIDA NIH HHS
• P20MD003942 NIMHD NIH HHS