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

Abstract

Background: Current point-of-care tests (POCT) for syphilis, based on the detection of Treponema pallidum (TP) total antibodies, have limited capacity in distinguishing between active and past/treated syphilis. We report the development and early evaluation of a new prototype POCT based on the detection of TP-IgA antibodies, a novel biomarker for active syphilis. Methods: The TP-IgA POCT (index test) was developed in response to the World Health Organisation (WHO) target product profile (TPP) for a POCT for confirmatory syphilis testing. Two sub-studies were conducted consecutively using 458 pre-characterised stored plasma samples in China (sub-study one, addressing the criteria for the WHO TPP), and 503 venous blood samples collected from pregnant/postpartum women in South Africa (sub-study two, addressing potential clinical utility). Performance of the index test was assessed against standard laboratory-based serology using a combination of treponemal (TPHA) and non-treponemal (rapid plasma reagin [RPR]) tests. Findings: In sub-study one, the index test demonstrated 96¢1% (95%CI=91¢7%-98¢5%) sensitivity and 84¢7% (95%CI=80¢15À88¢6%) specificity for identification of active syphilis (TPHA positive, RPR positive). It correctly identified 71% (107/150) samples of past-treated syphilis (TPHA positive, RPR negative). In sub-study two, the index test achieved 100% (95%CI=59%-100%) sensitivity for active syphilis and correctly identified all nine women with past syphilis. Interpretation: The TP-IgA POCT has met the WHO TPP for a POCT for diagnosis of active syphilis and demonstrated its potential utility in a clinical setting. Future studies are warranted to evaluate field performance of the final manufactured test. Funding: Saving Lives at Birth: Grand Challenge for Development, Thrasher Research Fund, and the Victorian Government Operational Infrastructure Scheme.

Expanding syphilis test uptake using rapid dual self-testing for syphilis and HIV among men who have sex with men in China: A multiarm randomized controlled trial

“…Fourth, we have data from treponemal test results because these test kits are commercially available, accurate, and field tested. The addition of nontreponemal tests [ 42 ] will be important for differentiating previous and new infections. Fifth, we used dual self-testing for syphilis and HIV in this study, which might raise the concern that the increase in the proportion of testing uptake is due to participants interested in the HIV testing.…”

Point-of-Care Diagnostics for Diagnosis of Active Syphilis Infection: Needs, Challenges and the Way Forward

“…Although the potential of a new POC assay (Syphilis IgA Confirmatory test, Burnet Institute, Melbourne, Australia) to distinguish between active and past/treated syphilis has been demonstrated in a low-risk population (pregnant women) [53], further research is needed to examine test performance in diverse clinical settings, and in populations with a high background prevalence of past episodes of syphilis infection, such as MSM. Other POC tests which can differentiate active from past/treated syphilis infections include an immune-filtration device [54] for simultaneous detection of treponemal and nontreponemal antibodies (Span Diagnostics, Surat, India) and a Smartphone dongle triplex test [55] which can detect HIV, treponemal and non-treponemal antibodies (Columbia University, New York, NY, USA).…”

“…Point-of-care tests for syphilis with sensitivities and specificities from published evaluation studies[44,[51][52][53][54][55][56][57][58].…”

Improved rapid diagnostic tests to detect syphilis and yaws: a systematic review and meta-analysis

“… 9 The Burnet Institute (Melbourne, Australia) also developed an RDT for syphilis using a treponemal IgA-specific assay. 10 11 Furthermore, a new smartphone dongle triplex test targeting HIV, treponemal antibodies and anti-cardiolipin antibodies as the non-treponemal marker has been developed. 12 Of these novel RDTs, the only commercially available test currently is the DPP Screen and Confirm Assay which is accessible in Europe and the USA.…”

“…More recently, some novel RDTs have included both treponemal and non-treponemal test components in the same device, such as the Dual Path Platform (DPP) Syphilis Screen and Confirm Assay (Chembio Diagnostic Systems, New York, USA), which will be referred to as the DPP-RDT 9. The Burnet Institute (Melbourne, Australia) also developed an RDT for syphilis using a treponemal IgA-specific assay 10 11. Furthermore, a new smartphone dongle triplex test targeting HIV, treponemal antibodies and anti-cardiolipin antibodies as the non-treponemal marker has been developed 12.…”