Advantages and limitations of current diagnostic laboratory approaches in syphilis and congenital syphilis

ABSTRACT

Introduction

The reemergence of syphilis, especially congenital syphilis, presents a significant public health threat. Accurate diagnosis of syphilis depends on recognition of a constellation of symptoms, review of medical and sexual history, and multiple laboratory tests. While reliable, current tests for syphilis can be difficult to interpret, which can lead to delays in treatment.

Area covered

This review summarizes the major advantages and limitations of available diagnostic laboratory methods for syphilis, provides an update on recent advances in laboratory tools, and highlights the urgent need for coordinated efforts to create new tools to halt the resurgence of syphilis.

Expert opinion

In syphilis, the wide variety of short-lived signs and symptoms followed by periods of latency create diagnostic challenges. Currently available laboratory tests, when positive, require additional information to interpret (prior testing, treatment, and sexual history). Point-of-care tests that can rapidly and accurately detect both treponemal and non-treponemal antibodies would be a huge step toward reducing test turnaround time and time to treatment. Incorporating biological insights and technology innovations to advance the development of direct detection assays is urgently needed. A comprehensive coordinated effort is critical to stem the tide of rising syphilis in the United States and globally.

KEYWORDS:

• Congenital syphilis
• molecular detection
• nontreponemal test
• serologic test
• syphilis
• syphilis screening
• treponema pallidum
• treponemal test

Article highlights

• The resurgence of syphilis poses a significant public health threat; current diagnostic laboratory approaches have limitations.

• The availability of direct detection methods including DFM and NAATs are limited. No FDA-cleared NAATs are available.

• Current serologic assays including rapid tests are insensitive in early infection and cannot distinguish newly acquired from previously treated syphilis infection.

• Biomedical interventions to develop novel, sensitive, readily accessible, point-of-care tests are urgently needed to reduce the burden of syphilis, prevent complications, and eliminate mother-to-child transmission.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

Listed authors have substantially contributed to the conception and design of the review article, the review of relevant literature, and the writing and revision of the article.

Acknowledgments

The authors appreciate input for this review from Mayur Shukla, PhD, Allan Pillay, PhD, and Yetunde Fakile, PhD, from the Division of STD Prevention at the Centers for Disease Control and Prevention. The review was developed from a lecture at ID Week 2022 with acknowledgement of input and guidance from Laura Bachmann, MD, MPH and Leandro Mena, MD, MPH.

Disclaimer

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the CDC.

Additional information

Funding

The study was funded by the CDC (Atlanta, Georgia, USA).