Serological diagnosis of syphilis depends on assays that detect treponemal and nontreponemal antibodies. Laboratory certification and trained personnel are needed to perform most of these tests, while high costs and long turnaround time can hinder treatment initiation or linkage to care. A rapid treponemal syphilis test (RST) that is simple to perform, accessible, and inexpensive would be ideal. The Syphilis Health Check (SHC) assay is the only Food and Drug Administration (FDA)-cleared and Clinical Laboratory Improvement Amendments (CLIA)-waived RST in the United States. In this study, 1,406 archived human serum samples were tested using SHC and traditional treponemal and nontreponemal assays. Rapid test results were compared with treponemal data alone and with a laboratory test panel consensus defined as being reactive by both treponemal and nontreponemal assays for a given specimen, or nonreactive by both types of assays. The sensitivity and specificity of the SHC assay compared with treponemal tests alone were 88.7% (95% confidence interval [CI], 86.2 to 90.0%) and 93.1% (95% CI, 90.0 to 94.9%), respectively, while comparison with the laboratory test panel consensus showed 95.7% (95% CI, 93.6 to 97.2%) sensitivity and 93.2% (95% CI, 91.0 to 95.1%) specificity. The data were further stratified based on age, sex, pregnancy, and HIV status. The sensitivity and specificity of the SHC assay ranged from 66.7% (95% CI, 46.0 to 83.5%) to 91.7% (95% CI, 87.7 to 94.7%) and 88% (95% CI, 68.8 to 97.5%) to 100% (95% CI, 47.8 to 100%), respectively, across groups compared to traditional treponemal assays, generally increasing for all groups except the HIV-positive (HIV) population when factoring in the laboratory test panel consensus. These data contribute to current knowledge of the SHC assay performance for distinct populations and may guide use in various settings.

No abstract

ObjectivesSerological 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.MethodsCardiolipin 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.ResultsThe 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.ConclusionPreliminary 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.

No abstract

Methods We searched the medical literature for studies evaluating performance of dual syphilis/HIV RTs against laboratorybased reference tests for syphilis and HIV, and compared performance across studies. For the syphilis component of the RTs, we compared results using laboratory-based treponemal tests (TPPA or TPHA) as the reference and (when available) TPPA+/RPR+ as the reference, considering RPR titers>1:4 to represent active syphilis (vs. previously treated infections). Results We found 19 studies evaluating dual syphilis/HIV RT performance, of which 7 (37%) were field evaluations studying at least one of three diagnostics: SD Bioline HIV/Syphilis Duo Test (n=4); Chembio Dual Path Platform HIV-Syphilis Assay (n=2); or Medmira Multiplo Rapid TP/HIV Antibody Test (n=1). All used HIV EIA and TPPA or TPHA tests as reference standards; 6 also reported RPR titers. Study populations were pregnant women (n=3), female sex workers (n=1), high-risk men (n=2) and STD clients (n=1), representing a total of 13 915 persons (median study size, 415 participants; range 175-9983). Across studies, prevalence of HIV ranged from <1% to 78% (median, 25.3%), and of T. pallidum (TP) from <1% to 40.2% (median, 8.2%). RT sensitivity for HIV against EIA ranged from 93.8% to 100% (median, 99.1%), and specificity from 97% to 100% (median, 99.4%). RT sensitivity for TP against TPPA or TPHA ranged from 52.7% to 96.5% (median, 81%), and specificity from 89% to 100% (median, 98.8%), with better performance in study populations with higher TPPA/RPR+ prevalence. Using TPPA+/RPR +>1:4 as the standard, RT sensitivity ranged from 88.5% to 100% (median, 94.3%). Conclusion In the few published field evaluations of dual syphilis/HIV RTs, performance of the HIV component was high for all tests studied. Sensitivity of the syphilis component against TPPA was poorer, but was more accurate using probable active syphilis infection as the standard.