Assessment of Two Rapid Assays for Diagnostic Capability to Accurately Identify Infection by Treponema pallidum

Abstract

Background: Rapid, point-of-care tests that accurately identify syphilis are gaining popularity and offer several advantages over classic tests. Methods: The SD Bioline Syphilis 3.0 and the Chembio DPP Syphilis Screen and Confirm Assay (CB) were assessed using 1283 samples that had been characterized by reference tests. The challenge samples included 5 commercial panels (seroconversion, mixed-titer), archived samples, fresh samples, and a dilution series. Both tests detect specific anti-treponemal antibodies, and the CB additionally detects antibodies to a non-treponemal (NT) component. The evaluation was used to determine performance indices and compare with those cited by the manufacturers. Results: When assessing reactivity to treponemal, the sensitivities for the 2 tests were 98.3% and 93.2%, with specificities of 100% and 99.4%, respectively. For both tests, precision, whole blood testing, and high-temperature testing produced perfect results, and there were no invalid results. Comparisons of 2 different lots of each test indicated excellent concordance (100% and 99.5%), and reproducibility was 100% and 98.0%, respectively. For the CB, the sensitivity for the NT component was between 65.3% and 80.9%, but increased to 98.5% with samples having a rapid plasma regain (RPR) titer of ≥8. The specificity for NT was found to be 100%, and the reading of results visually and when using a battery-operated reader indicated a concordance for all challenges of 95%-100%. Conclusions: Both rapid tests produced impressive results for the detection of antibodies to treponemal for all challenges and exceeded, met, or closely approached the performance characteristics as cited by the manufacturers. IMPACT STATEMENT The use of these rapid tests can assist patients in a variety of care venues, including in resource-limited countries, in physicians' offices so that positive patients are immediately connected to care, for pregnant women to improve infant morbidity, for transfusions to protect recipients, and for the timely treatment of syphilis. The information provided will inform potential users of the performance characteristics of the two tests being considered for adoption and provides a comparison with what the manufacturers state. The results contribute to the field by providing a comparative analysis of two tests that are used in many countries.

Laboratory Evaluation of the DPP Syphilis Screen & Confirm Assay

“…Additionally, highly trained staff members performed reference comparator tests and DPP Syphilis Screen & Confirm assay test procedures and thus the high level of concordance between operator and microreader results may be an overestimate; however, the microreader could perform better in a field trial with less-well-trained staff members. Finally, our results for the performance of the DPP Syphilis Screen & Confirm assay were somewhat lower than previously reported by other investigators and might be influenced by the study population or the manufacturing lot included in our analysis ( 20 ). Despite these limitations, the Chembio DPP Syphilis Screen & Confirm assay used with the microreader complies with REASSURED criteria for POC syphilis tests, which establish a sensitivity of at least 75% and a specificity of 92% for treponemal antibody detection; however, there are no criteria for nontreponemal POC tests ( 26 ).…”

“…In that study, the investigators used several biological samples and obtained sensitivity values between 57% and 64% for treponemal antibodies in serum. On the other hand, our results show a performance for the treponemal antibody component closer to that found by Causer et al ( 18 ), who reported a sensitivity of 89%, but lower than values reported by other authors ( 12 , 19 , 20 ).…”

“…When stratified by RPR titer, we found that the sensitivity of the DPP Syphilis Screen & Confirm assay nontreponemal component performed very well on sera with RPR titers of ≥1:8. Other studies reported similar findings when assessing samples with high RPR titers ( 18 , 20 , 21 ). Castro et al reported that the majority of false-negative samples with the DPP Syphilis Screen & Confirm assay had RPR titers up to 1:2, but the sensitivity improved when those were excluded ( 16 ).…”

“…The Chembio electronic microreader reported qualitative results (cutoff of 9.0) equivalent to operator results; furthermore, microreader device numerical results showed good correlation with RPR titers. Good microreader performance was reported for this syphilis assay ( 20 ) and other dual tests ( 24 ). The electronic reader demonstrated performance equivalent to that of laboratory-trained staff members, and this could mean that the Chembio microreader might be used for active syphilis case detection and treatment monitoring when a conventional RPR test is unavailable or DPP Syphilis Screen & Confirm assay testing is performed by nonlaboratory health professionals.…”

Improving the coverage and accuracy of syphilis testing: The development of a novel rapid, point-of-care test for confirmatory testing of active syphilis infection and its early evaluation in China and South Africa

“…A laboratory evaluation in Australia [7] reported that 49¢8% (105/211) presumptive past treated serum samples were misclassified as active syphilis by the DPP test, whereas a field evaluation among pregnant women in Burkina Faso [8] showed 48¢4% (44/91) women with active syphilis would be undiagnosed had the DPP test been used. The difference in test performance can be partly explained by the lot-to-lot variation as a laboratory study in the United States [9] showed a significant difference in the sensitivity for the non-treponemal component of the DPP in two different lots studied -65¢3% (95%CI: 60¢5À69¢8) and 80¢9% (95%CI: 72¢6À87¢2) respectively.…”