Clinical development and performance of the First to Know Syphilis Self-Test for over-the-counter usage: a de novo rapid test for treponemal antibody.

UNLABELLED: The resurgence of syphilis in the USA and globally has hastened the need for widely available syphilis testing. Early detection of syphilis is crucial for avoiding serious clinical complications and preventing the spread of infection. Self-tests enhance access to testing and promote timely treatment for positive cases. Herein, we describe the performance of First to Know Syphilis Test (FTK), the first over-the-counter (OTC) treponemal test. A prospective multi-site clinical study with 1,270 subjects was conducted, where subjects self-collected fingerstick capillary blood and self-tested without assistance. FTK test results were compared with a composite reference standard to evaluate the diagnostic performance. The FTK test exhibited an overall sensitivity of 93.4% (95% CI, 87.0% to 96.8%) and specificity of 99.5% (95% CI, 98.9% to 99.8%) and accuracy of 99%. The overall agreement was 98.9%, with Cohen's Kappa (ⱪ) value 0.93 (95% CI, 0.90 to 0.97) showing excellent agreement between the reference standard and FTK results. In addition, the test was validated in a panel of 125 clinically staged syphilis patient samples, and the results showed 100% agreement in detecting anti-treponemal antibodies in all the samples. These data show excellent performance of the FTK Test, demonstrating its utility in the screening and diagnosis of syphilis. The availability of this OTC test and its excellent performance will have a profound impact on syphilis detection and prevention strategies and could reduce comorbidities such as HIV and transmission of other STIs.

IMPORTANCE: The resurgence of syphilis in the USA and globally underscores the urgent need for rapid, accessible testing. The First To Know Syphilis Test, as the first at-home, over-the-counter (OTC) test for syphilis, represents a significant breakthrough in rapid diagnostics for increased access to testing and support early diagnosis and treatment. The FTK test demonstrated excellent overall clinical performance, with 93.4% sensitivity and 99.5% specificity, confirming its reliability for syphilis detection. This novel, easy-to-use OTC syphilis test allows individuals to privately test at home and can promote testing among those hesitant or unable to seek traditional healthcare, reducing barriers like stigma and limited access. The availability of this OTC test will have a significant impact on syphilis detection and prevention strategies and reduction of comorbidities such as HIV.