Performance Assessment of Treponemal and Nontreponemal Tests for the Diagnosis of Acquired Syphilis.

There are a variety of nontreponemal test (NTT) and treponemal test (TT) kits for the serologic diagnosis of syphilis. Because of the complexity of the infection (multiple clinical stages) and the different antigens used in these kits, a systematic evaluation of the accuracy of the currently available commercial tests is warranted. Our objective was to evaluate the performance of commercially available tests for the diagnosis of syphilis infection. In this study, we analyzed one NTT (Venereal Disease Research Laboratory [VDRL] test, Wiener Laboratories, Rosario, Argentina) and two TTs (fluorescent treponemal antibody absorption [FTA-ABS] test, Euroimmun, Lübeck, Germany, and syphilis recombinant ELISA v. 4.0 test [ELISA], Wiener Laboratories, Rosario, Argentina) using a panel of 187 samples, including serum samples from 31 individuals with primary syphilis, 77 with secondary syphilis, and 79 with latent syphilis. An additional 192 samples from uninfected individuals and 323 serum samples from individuals with other diseases were included. The sensitivities of the VDRL, ELISA, and FTA-ABS tests were 97.9%, 100%, and 96.3%, respectively. The VDRL and ELISA tests showed a specificity of 100%, and the FTA-ABS test showed a specificity of 99.5%. Accuracy was 98.9% for the VDRL test, 100% for the ELISA, and 97.9% for the FTA-ABS test. For primary, secondary, and latent syphilis, the ELISA achieved a diagnostic performance of 100%, whereas the sensitivity for the VDRL and FTA-ABS tests ranged from 96.8% to 98.7% and 93.7% to 98.7%, respectively. No difference was observed when the tests were used as traditional or reverse algorithms. In general, all three tests are able to discriminate positive and negative samples for syphilis, regardless of the diagnostic algorithm.

Prevalence of Traditional and Reverse-Algorithm Syphilis Screening in Laboratory Practice: A Survey of Participants in the College of American Pathologists Syphilis Serology Proficiency Testing Program.

CONTEXT: -Syphilis serology screening in laboratory practice is evolving. Traditionally, the syphilis screening algorithm begins with a nontreponemal immunoassay, which is manually performed by a laboratory technologist. In contrast, the reverse algorithm begins with a treponemal immunoassay, which can be automated. The Centers for Disease Control and Prevention has recognized both approaches, but little is known about the current state of laboratory practice, which could impact test utilization and interpretation. OBJECTIVE: -To assess the current state of laboratory practice for syphilis serologic screening. DESIGN: -In August 2015, a voluntary questionnaire was sent to the 2360 laboratories that subscribe to the College of American Pathologists syphilis serology proficiency survey. RESULTS: -Of the laboratories surveyed, 98% (2316 of 2360) returned the questionnaire, and about 83% (1911 of 2316) responded to at least some questions. Twenty-eight percent (378 of 1364) reported revision of their syphilis screening algorithm within the past 2 years, and 9% (170 of 1905) of laboratories anticipated changing their screening algorithm in the coming year. Sixty-three percent (1205 of 1911) reported using the traditional algorithm, 16% (304 of 1911) reported using the reverse algorithm, and 2.5% (47 of 1911) reported using both algorithms, whereas 9% (169 of 1911) reported not performing a reflex confirmation test. Of those performing the reverse algorithm, 74% (282 of 380) implemented a new testing platform when introducing the new algorithm. CONCLUSION: -The majority of laboratories still perform the traditional algorithm, but a significant minority have implemented the reverse-screening algorithm. Although the nontreponemal immunologic response typically wanes after cure and becomes undetectable, treponemal immunoassays typically remain positive for life, and it is important for laboratorians and clinicians to consider these assay differences when implementing, using, and interpreting serologic syphilis screening algorithms.

[Current status of external quality assessment of syphilis test in Korea].

BACKGROUND: Current status of external quality assessment (EQA) of laboratory tests for syphilis in Korea was analyzed to find out the problems that should be improved in the future. METHODS: Based on the data from the external quality assessment program performed twice a year by the Immunoserology Subcommittee of the Korean Association of Quality Assurance for Clinical Laboratory from the year 2004 to 2006, discordance rates were analyzed according to the test method and commercial kit used. RESULTS: Among the laboratories participating in the EQA program for syphilis test, about 90% of them used non-treponemal tests and about 55% treponemal tests. The non-treponemal tests included RPR (rapid plasma reagin) and VDRL tests used in 88% (363/412) and 11% (45/412), respectively, of the laboratories. The discordance rates were 2.2% for RPR test and 3.6% for VDRL. For the treponemal tests, Treponema pallidum hemagglutination assay (TPHA) was used in 60-76% and Immunochromatography assay (ICA) in about 30% of the laboratories in 2006. A high discordance rate of over 10% was reported in both TPHA and in ICA methods, possibly due to a low titer (1:1 in VDRL) of EQA samples in 2005. Analysis of the accumulated data from year 2004 to 2006 showed that the discordance rates of TPHA, ICA, and FTA-ABS were 4.6%, 3.7%, and 2.7%, respectively. CONCLUSIONS: For syphilis tests, RPR test, TPHA, and ICA are mainly used in Korea. A high discordance rate is still reported in TPHA and ICA, especially when testing samples with a low titer. Further analysis of data and education of laboratory personnel are needed for the improvement of the EQA program.

Field evaluation of the performance and testing costs of a rapid point-of-care test for syphilis in a red-light district of Manaus, Brazil.

OBJECTIVES: To assess the performance, usefulness and cost of a rapid treponemal antibody assay (VisiTect Syphilis) to detect syphilis in high risk populations. METHODS: People who attended STI clinics in Manaus, Brazil, were screened for syphilis using the fluorescent treponemal antibody absorption (FTA-Abs) test and a non-treponemal test (Venereal Diseases Research Laboratory (VDRL)), and for HIV. Finger prick blood samples were tested with VisiTect Syphilis. The rapid test was evaluated against the reference FTA-Abs and for its usefulness in detecting active syphilis (FTA-Abs and VDRL positive). Operational performance was assessed through providers' and patients' interviews. An economic evaluation was conducted from the provider's perspective. RESULTS: 510 patients (60% men) were enrolled, of whom 13 (2.5%) were HIV-1 seropositive. Syphilis prevalence (FTA-Abs) was 18% and active syphilis prevalence was 7.5%. 11% (57/506) of samples were positive by VisiTect. The sensitivity, specificity, positive and negative predictive values of VisiTect Syphilis were 57% (95% CI 45.8 to 66.7), 99% (95% CI 97.0 to 99.6), 91% (95% CI 80.0 to 96.7) and 91% (95% CI 88.0 to 93.5), respectively. VisiTect Syphilis identified 79% (30/38) of active syphilis cases. The cost per case of syphilis was $16.8 for VDRL, $33.2 for low cost and $56.3 for high cost VisiTect Syphilis; the cost per case of active syphilis was $21.3, $57.5 and $97.6, respectively. Patients identified finger prick pain and preference for venous blood collection as minor barriers to test use. CONCLUSION: VisiTect Syphilis had low sensitivity in field use and was less cost effective than conventional VDRL. However, rapid and correct identification of a high proportion of active syphilis cases combined with operational characteristics suggest a role in high risk populations.

Comparative evaluation of 15 serological assays for the detection of syphilis infection.

Fifteen commercial syphilis kits were assessed against the same moderately sized specimen panel that included 114 serum and plasma specimens from syphilis cases and 249 specimens from unselected blood donors. The 114 specimens from syphilis cases comprised 40 from cases of primary syphilis, 43 from cases of secondary syphilis, 19 from cases of early latent syphilis, and 12 from cases of late latent syphilis. Of the 15 kits, ten were enzyme immunoassays, four were Treponema pallidum haemagglutination assays, and one was a T. pallidum particle agglutination assay. Thirteen of the 15 kits gave final specificities of 100%; the other two kits were repeatedly reactive with one to two specimens. Initial sensitivities ranged from 93.9 to 99.1%. Most variation between kits was observed in results for the groups with untreated primary and treated late latent disease, although the differences were not statistically significant. The comparative data on kit performance derived from this study is useful for examining syphilis testing guidelines and for making informed purchasing decisions.

Cost-effectiveness of on-site antenatal screening to prevent congenital syphilis in rural eastern Cape Province, Republic of South Africa.

OBJECTIVES: On-site screening and same-day treatment of maternal syphilis in underresourced settings can avert greater numbers of congenital syphilis cases, but health outcomes and associated costs must be evaluated jointly. METHODS: We used decision analysis to estimate the incremental cost-effectiveness of two on-site antenatal syphilis screening strategies to avert congenital infections-qualitative RPR (on-site RPR) and treponemal immunochromatographic strip assay (on-site ICS)-compared to the current practice (off-site RPR/TPHA). FINDINGS: With antenatal active syphilis prevalence of 6.3%, the incremental cost-effectiveness of on-site ICS in averting congenital infections was estimated to be USD104, averting 82% of cases expected in absence of a program. The incremental cost-effectiveness of off-site RPR/TPHA was USD82 but would avert only 55% of congenital syphilis cases. On-site RPR was dominated by the other screening strategies. CONCLUSIONS: In settings of high maternal syphilis prevalence, on-site antenatal screening with ICS is a cost-effective approach to reduce the incidence of congenital syphilis.

Modelling the cost-effectiveness of introducing rapid syphilis tests into an antenatal syphilis screening programme in Mwanza, Tanzania.

OBJECTIVES: A study found screening (with rapid plasma reagin (RPR)) pregnant women for maternal syphilis was cost-effective in Mwanza, Tanzania. Recently, four rapid point-of-care (POC) syphilis tests were evaluated in Mwanza, and found to have reasonable sensitivity/specificity. This analysis estimates the relative cost-effectiveness of using these POC tests in the Mwanza syphilis screening intervention. METHODS: Empirical cost and epidemiological data were used to model the potential benefit of using POC tests instead of RPR. Reductions in costs relating to training, supplies, and equipment were estimated, and any changes in impact due to test sensitivity were included. Additional modelling explored how the results vary with prevalence of past infection, misclassified RPR results, and if not all women return for treatment. RESULTS: The cost-effectiveness of using POC tests is mainly dependent on their cost and sensitivity for high titre active syphilis (HTAS). Savings due to reductions in training and equipment are small. Current POC tests may save more disability-adjusted life years (DALYs) than the RPR test in Mwanza, but the test cost needs to be <0.63 US dollars to be as cost-effective as RPR. However, the cost-effectiveness of the RPR test worsens by 15% if its HTAS sensitivity had been 75% instead of 86%, and by 25-65% if 20-40% of women had not returned for treatment. In such settings, POC tests could improve cost-effectiveness. Lastly, the cost-effectiveness of POC tests is affected little by the prevalence of syphilis, false RPR-positives, and past infections. DISCUSSION: Although the price of most POC tests needs to be reduced to make them as cost-effective as RPR, their simplicity and limited requirements for electricity/equipment suggest their use could improve the coverage of antenatal syphilis screening in developing countries.

Effectiveness and cost-benefit of enhancements to a syphilis screening and treatment program at a county jail.

BACKGROUND: High rates of syphilis are found in inmates of county jails. Treatment of this infected transient population necessitated the development of a rapid protocol. GOAL: To evaluate a rapid screening and treatment protocol for syphilis in a county jail. STUDY DESIGN: Over a 2-year period 18,442 inmates were screened for syphilis with a nontreponemal test and record search for treatment history. Confirmatory test results were reviewed following treatment. Cost was defined as deflated marginal outlays. Benefit was calculated as the discounted expected cost of treatment of congenital, late, and neurosyphilis. RESULTS: The sensitivity, specificity, and positive predictive value of the protocol were 99.6%, 80.8%, and 79.3%, respectively. Of 257 confirmed cases, 183 were offered treatment in jail. The percentage of short-term inmates treated increased following implementation. The cost-benefit ratio was 9.14:1. CONCLUSIONS: The protocol was highly effective in patient identification and treatment delivery, and cost-effective as well.

Bayes' theorem-based assessment of VDRL syphilis screening miss rates.

BACKGROUND AND OBJECTIVES: Interlaboratory differences (and conflicting practices) in syphilis screening strategies (serial versus parallel test combinations) prompted us to determine an estimate of the diagnostic miss rate in the detection of (1) infected persons and (2) infected but untreated persons potentially affected by late active syphilis. GOAL: We set out to establish the most efficient syphilis screening strategy for two routine tests (VDRL and Treponema pallidum hemagglutination assay [TPHA]) with regard to our tested public health population (average VDRL+ TPHA+ and VDRL- TPHA+ reactor ages being 59.9 years and 50.5 years, respectively. STUDY DESIGN: Retrospective analysis covered the results of a routine parallel VDRL and TPHA testing on 24,863 persons done in four public health laboratories. Nosologic sensitivity of the VDRL test (18.32%) was determined using the TPHA test as reference. The percentage of VDRL nonreactors among infected persons (TPHA reactors) was considered as the VDRL false negative rate (81.68%). We estimated the proportion of persons infected but untreated with potential late active syphilis using our own Bayes theorem-based procedure. RESULTS: The Bayes theorem-based estimate showed a significantly higher value for persons at risk of active late syphilis than the number of suspected cases obtained using the classical approach (25.1% versus 18.32%, or 83 persons versus 61 of the 330 infected). CONCLUSION: In screening an older population, the VDRL test alone (or as the first of a series with TPHA as a confirmation test) may produce a diagnostic miss rate higher than the syphilis detection rate. Another miss in such a population is detected by the Bayes theorem-based method.

Unreliability of current screening tests for syphilis in chronic psychiatric patients.

OBJECTIVE: This study examined whether psychiatrists perform adequate diagnostic screening for syphilis in patients with chronic mental illness. METHOD: Two hundred patients with chronic mental illness underwent testing for syphilis with the commonly used RPR test and the microhemagglutination assay for Treponema pallidum (MHA-TP). Sensitivities of the two tests were compared. RESULTS: A substantial number of patients with negative results on RPR tests had reactive MHA-TPs and would have not been identified as having had syphilis with the use of RPR testing alone. CONCLUSIONS: Nontreponemal tests such as the RPR test are less likely than treponemal tests to detect syphilis appropriately in chronically mentally ill patients, and specific treponemal tests such as the MHA-TP should be considered.

Valoración de un Nuevo Método de Serodiagnóstico para Sífilis (ELISA. IgG)

Se realizó un estudio descriptivo prospectivo en el que se valoró la técnica de ELISA (Captia Syphilis G, Mercia Diagnostic, Guilford, England) para detectar anticuerpos anti-Treponema pallidum de la clase inmunoglobulina G. El antígeno utilizado fue extracto protéico de T. pallidum perteneciente a la cepa Nichols. Para comparar la ELISA Captia Syphilis G se utilizó la técnica de inmunofluorescencia indirecta FTA-Abs. Se evaluaron 100 sueros de pacientes cuya distribución fue: 60 sueros de pacientes enfermos de sifilis, 20 sueros de paciente sanos sin enfermedades de trasmisión sexual conocida, 15 sueros de pacientes con enfermedades del colágeno y 5 sueros de pacientes con tuberculosis. La sensibilidad de ELISA Captia Syphilis G fue del 98.4 por ciento mientras que FTA-Abs fue del 100 por ciento. La especificidad de ELISA Captia Syphilis fue del 100 por ciento y del FTA-Abs del 97.3 por ciento. Esta técnica podría ser incluida en Colombia como prueba confirmatoria para el diagnóstico de sífilis por su alta sensibilidad y especificidad, sumado a la facilidad de su realización, sencillez del procedimiento y economía, que ofrece resultados objetivos y confiables

Screening to control infectious diseases: evaluation of control programs for gonorrhea and syphilis.

Gonorrhea and syphilis serve as models for the definition of criteria for the evaluation of screening programs for detection of disease. Mass screening and selective screening are distinguished from individual screening (case finding). Important characteristics of screening tests are sensitivity, specificity, efficiency, precision, accuracy, and acceptability. Program evaluation includes process evaluation and outcome evaluation. Major criteria to consider in the evaluation of mass screening programs are prevalence and incidence of disease, predictive value of tests used, yield, available screening tests, acceptance, follow-up services, costs and benefits, and control over the spread of infection. All forms of screening programs should be evaluated by available methods so that they will operate with maximal efficiency and so that nonproductive programs can be discarded.