Syphilis has returned as a pressing public health concern. Infections in the U.S. have climbed to levels not seen since the 1950s, and congenital cases reached more than 3,700 in 2022—a year-over-year increase of over 30 percent. These numbers highlight a simple truth: too many infections are being missed or caught too late.
Recent data shows a shift in this trend. The pace of new early-stage cases slowed in 2023, and congenital infections increased only slightly after years of steep annual rises. Behind those numbers lies the growing impact of clinical labs. Better protocols, faster assays, and alignment with modern guidelines are helping labs move the response from delayed detection to timely intervention.
Why older workflows fall short
For decades, syphilis testing began with non-treponemal assays such as the rapid plasma reagin (RPR) or venereal disease research laboratory (VDRL) test. These tests detect reagin antibodies against lipoidal antigens released during infection, but the response is not unique to syphilis. Other conditions can trigger the same antibodies, leading to false positives. At the same time, very early or latent infections may not produce a detectable response, causing missed cases. Equivocal results are common and often require repeat testing.1
The reverse sequence algorithm takes a different path. Testing begins with a treponemal assay that detects antibodies specific to Treponema pallidum, the bacterium that causes syphilis. If that result is positive, the sample is reflexed to a non-treponemal test to assess disease activity. Discordant cases—where the treponemal result is positive but the non-treponemal result is negative—are then resolved with a second treponemal assay.
The 2024 CDC laboratory recommendations recognize both the traditional and reverse sequence approaches, but note that treponemal-first testing is gaining ground in high-volume labs. The agency provides detailed guidance for handling discordant results to ensure accuracy across different patient populations.
A treponemal assay designed for confidence
The Elecsys® Syphilis assay from Roche helps labs implement the reverse algorithm with reliability. Using a double-antigen sandwich format, it detects both IgM and IgG antibodies against T. pallidum. That design enhances sensitivity in cases where antibody levels may be low, such as early infection or asymptomatic carriers.
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Independent evaluations and Roche’s own studies report sensitivity and specificity close to 100 percent across diverse populations, including high-risk groups, pregnant women, and patients with HIV² ³. That level of accuracy reduces equivocal results, shortens time to diagnosis, and gives laboratories greater certainty in clinical decision-making.
The assay also supports efficiency. Results are available in 18 minutes from as little as 10 µL of sample. Its electrochemiluminescence readout generates strong signals from very small antibody concentrations, enabling both low sample use and high throughput in routine workflows.
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Automation that scales with demand
As syphilis testing volumes rise, labs need systems that deliver accuracy at scale. Roche’s cobas® immunoassay analyzers automate the process from sample load to final report, maintaining throughput without adding manual steps.
The platform’s built-in reflex logic runs treponemal testing and non-treponemal confirmation within the same workflow. Positives are flagged automatically, negatives cleared without delay. This design reduces hands-on work, lowers the risk of error, and keeps results consistent across shifts.
Labs also gain efficiency through the platform’s consistency. Standardized assay response times (18 or 27 minutes, depending on the test), broad onboard stability of up to 112 days, and minimal sample volumes all contribute to reproducible, cost-effective operations.
Evidence of impact
A hospital case study³ shows the effect of moving from the traditional algorithm to treponemal-first testing. In the first year, the lab confirmed 57 additional infections that would have been missed under the older workflow. The positivity rate more than doubled, rising from 2.7 percent to 6.3 percent.
Automation removed the need for manual RPRs, cutting hands-on time and night-shift dependence. Around-the-clock availability of the Elecsys® Syphilis assay improved turnaround and reduced costs by keeping testing in-house.
Supporting implementation
Changing a diagnostic algorithm requires more than swapping out an assay. Labs need confidence in validation, workflow design, and staff training. Roche supports these transitions with technical guidance, resources for verification, and collaborative planning. That support reflects its broader Core Lab focus on science, simplicity, and partnership.
Standardization is part of the equation. When treponemal and non-treponemal tests are both run on cobas platforms, shared calibrators and controls reduce QC overhead, and results move through a single reporting system. That creates cleaner datasets for clinical teams and public health programs, while giving labs a firmer base for quality management as testing volumes rise.
Beyond syphilis: integrated infectious disease diagnostics
Patients at risk for syphilis are often at risk for other silent infections, including HIV and hepatitis C. Clinical guidelines call for broader testing, but running each test on separate systems creates unnecessary steps and slows reporting.
Running Elecsys® Syphilis, Elecsys® Anti-HCV II, and Elecsys® HIV Duo on a single cobas analyzer streamlines that work. The syphilis assay detects both IgM and IgG for early cases, the HCV assay targets multiple viral antigens to reduce false positives, and the HIV Duo assay measures p24 antigen as well as antibodies to shorten the diagnostic window. Together they allow labs to expand coverage in one workflow, keeping turnaround fast and demands on staff low.
Conclusion
Adopting a treponemal-first strategy has practical effects: more true positives, fewer redraws, and workflows that fit modern automation. The obstacles—interpretation of discordant results and cost considerations—remain, but laboratories that define reflex policies and train staff accordingly are seeing the benefits. In a period of resurging infection, this algorithm offers a framework that balances accuracy with efficiency.
References
1. CDC. Laboratory Recommendations for Syphilis Testing, United States, 2024 (MMWR). https://www.cdc.gov/mmwr/volumes/73/rr/rr7301a1.htm
2. Elecsys Syphilis method sheet, 2024-06, V 3.0 English
3. MCMC Syphilis reverse algorithm case study, 2019. Data on file.