Q1 2024 Urgent Caring – The Silent Spread: Syphilis on the Rise

Cesar Mora Jaramillo, MD, FAAFP, FCUCM

Syphilis is one of the oldest known sexually transmitted infections. It was first recorded in the 1490s and known with different names, “the French disease”, “the Neapolitan disease” and “the Polish disease”. 

Once thought to be under control, syphilis has reemerged as a formidable public health challenge. Recent data shows a notable upswing in cases including newborn infections.  This so-called epidemic is occurring in the U.S., with sustained increases in primary and secondary syphilis. Unfortunately, the epidemic is driven by health disparities, particularly among certain populations – sexual and gender minorities and HIV and substance use disorders. 

But how can Urgent Care centers (UCCs) assist with the fight against this epidemic? UCCs play a pivotal role in early detection and intervention. Hence, protocols for screening, testing, and treatment within Urgent Care settings are crucial, and centers should emphasize their role in not only managing individual cases but also in stemming the tide of syphilis within our communities. In the context of health disparities, well-established protocols act as a leveling mechanism, ensuring that all individuals, irrespective of their socio-economic background, receive equitable and timely healthcare services. These protocols contribute to consistency in diagnosis, treatment, and follow-up, reducing variations in care that may contribute to disparities. UCCs can implement strategies to decrease disparities in their communities. These strategies should include:

  • Community Outreach and Education – Tailoring information to specific communities, allowing healthcare providers to address cultural and linguistic barriers that may contribute to disparities
  • Accessible Testing – Flexible hours, walk-in services, and mobile services particularly in underserved areas
  • Culturally Competent Care – Healthcare staff receive training to understand and respect diverse cultural backgrounds, thereby fostering trust and increasing patient engagement
  • Collaboration with Community Organizations and Local Health Departments – Facilitate communication, implement preventative measures, enhance surveillance, outreach, and follow-up care for syphilis cases

On Tuesday, January 30, 2024, the CDC reported syphilis cases had increased 80% in the United States between 2018 and 2022 (from 115,000 to more than 207,000), compounding a decades-long upward trend. The cases increased by 17% between 2021 and 2022 and surged by 32% between 2020 and 2021 to reach the highest number of reported incidences in 70 years. This has led the CDC to warn healthcare entities that this epidemic is showing no signs of slowing, and it has pointed to some “alarming” new trends driving this sudden spike in the disease.

If untreated, syphilis can seriously damage the heart and brain and can cause blindness, deafness, and paralysis.  When transmitted during pregnancy, it can cause miscarriage, lifelong medical issues, and infant death. 

Serologic response to infection with Treponema pallidum, the causative agent of syphilis: source CDC 

CDC is recommending action to stop the increase of newborn syphilis cases. New CDC data reveal that more than 3,700 babies were born with syphilis in 2022, which was more than 10 times the number in 2012. The increase in newborn syphilis follows rising syphilis cases among women of reproductive age combined with social and economic factors that create barriers to high-quality prenatal care and ongoing declines in the prevention resources. According to the CDC, almost 9 in 10 cases of newborn syphilis in 2022 might have been prevented with timely testing and treatment during pregnancy. They point out that more than half were among people who tested positive for syphilis during pregnancy but did not receive adequate or timely treatment. Nearly 40% were among mothers who were not in prenatal care.


On February 8t, 2024, the CDC reported new recommendations for tests that support a diagnosis of syphilis including serologic testing and methods for the identification of the causative agent Treponema pallidum

These tests can be divided into nontreponemal and treponemal tests (depending on whether they detect antibodies that react to lipoidal antigens shared by both host and T. pallidum or antibodies specific to T. pallidum respectively. Both types of tests must be used in conjunction to help distinguish between an untreated infection or a past infection that has been successfully treated. 

Newer serologic tests allow for laboratory automation but must be used in an algorithm, which also can involve older manual serologic tests. Direct detection of T. pallidum continues to evolve from microscopic examination of material from lesions for visualization of the organism. Limited point-of-care tests for syphilis are available in the U.S.; increased availability of point-of-care tests that are sensitive and specific could facilitate expansion of screening programs and reduce the time from test result to treatment. 

Here are some of the recommendations from CDC from February 8t, 2024: 

Algorithms that can be applied to screening for syphilis with serologic tests — CDC laboratory recommendations for syphilis testing in the United States, 2024.

Recommendation for syphilis serologic testing algorithm. Serologic tests that measure antibodies to both nontreponemal (lipoidal) and treponemal antigens related to syphilitic infections should be used in combination when the primary test is reactive to aid in the diagnosis of syphilis. Sole reliance on one reactive serologic test result can misclassify a patient’s syphilis status. Both the traditional syphilis screening algorithm (initial screening with nontreponemal assays) and the reverse syphilis screening algorithm (initial screening with treponemal immunoassays) are acceptable. The preferred algorithm should be based on laboratory resources, including staff, space and costs, test volume, and patient populations served.

Comment and evidence summary. Antibodies detected by nontreponemal and treponemal antigen tests vary by the stage of syphilis, treatment status, and past infection that was treated. Results from both types of serologic tests are required to help diagnose the stage of syphilis. Both traditional and reverse syphilis testing algorithms are used in the U.S. and have about 99% concurrence between the two approaches. The cost-effectiveness of the two algorithms might vary by laboratory setting and need to be considered by individual laboratories.

Recommendation for the direct detection of T. pallidum by dark field microscopy. Dark Field microscopy should be maintained if already in use or established in STD clinics where a POC test for primary or secondary syphilis diagnosis would be beneficial for timely patient treatment.

Comment and evidence summary. The sensitivity of darkfield microscopy in detecting T. pallidum from primary lesions ranges from 94% to 100% and 81% to 100% from secondary lesions when compared with NAATs (141,187191). Darkfield microscopy can be more sensitive than serologic tests at the primary stage and offers the advantage of timely detection and rapid treatment of primary syphilis (186). The procedure is classified as moderately complex by CLIA, and the settings implementing the darkfield microscopy will require CLIA certification for such a test.

Recommendation for direct detection of T. pallidum by immunohistochemistry and silver staining. IHC is preferred over silver staining for FFPE tissue sections regardless of anatomic site.

Comment and evidence summary. The sensitivity of IHC ranged from 64% to 94% whereas silver stain had a sensitivity of 0%–41%. 

Recommendation for serologic syphilis testing. Nontreponemal tests (e.g., RPR or VDRL) are not interchangeable when used to determine antibody titers; testing on follow-up samples must be performed with the same type of test. The TPPA test is the preferred manual treponemal test.

Comment and evidence summary. Sensitivity and specificity estimates of RPR and VDRL were similar but not exact in head-to-head studies and studies that used similar reference standards. When assessing changes in antibody titers using nontreponemal tests, it is critical that the same test be used because titers are used by clinicians to classify the infection status of a patient and follow treatment response. A recent study with 959 patients estimated the sensitivity of FTA-ABS and TPPA to be 78.2% and 94.5%, respectively, when testing specimens from patients with primary syphilis (115). Two studies that tested specimens from patients with secondary syphilis reported a sensitivity of 92.8%–95.0% compared with 100% for TPPA. Many automated treponemal immunoassays are similar in sensitivity, and certain ones are slightly less specific when compared with the manual TPPA, except for the Trep-Sure test which has inferior specificity. Among the other immunoassays, data are insufficient to recommend one assay based on test performance.

Only the Syphilis Health Check (Diagnostics Direct) and Dual Path Platform (DPP) HIV-Syphilis Assay (Chembio Diagnostics) are FDA cleared and CLIA waived for the detection of T. pallidum antibodies. Physician office laboratories and public health field-based screening programs that offer CLIA-waived tests are required to have and maintain a CLIA certificate of waiver that requires these tests to be quality assured and operated by trained personnel according to manufacturer instructions.

POC Tests

Despite years of study internationally, non-laboratory-based POC tests for syphilis are in their infancy in the United States, with only two FDA-cleared and CLIA-waived tests. Additional POC tests and data are needed to increase understanding of their performance in clinical and outreach settings. Additional areas needed for research include well-designed prospective studies on POC test performance in the context of screening algorithms, special patient populations, linkage to treatment and care, and cost-benefits so that recommendations can be made regarding performance and use in the U.S. Also needed are studies comparing POC tests with FDA-cleared, laboratory-based treponemal serologic tests, followed by programmatic recommendations for implementation to guide their appropriate use in syphilis testing algorithms.

Direct Detection Tests

Direct detection of T. pallidum has been based on microscopy but is being modernized with molecular methods for detection. No FDA-cleared molecular tests are marketed in the U.S., although certain laboratories offer such testing using in-house, laboratory-developed and validated tests. Molecular tests that are FDA cleared for T. pallidum would facilitate their uptake in laboratories. However, additional research is needed in determining optimal specimen types, including genital and extragenital specimens stratified by stage of syphilis, specimen transport and storage, and specimen adequacy; identifying molecular markers that could be used to monitor for the emergence of antimicrobial resistance and strain typing to better aid epidemiological investigations; evaluating the sensitivity of NAATs on whole blood or its components (serum and plasma); and assessing the cross-reactivity of NAATs with commensal Treponema spp.


Combating health disparities among syphilis cases in Urgent Care centers requires a multifaceted and inclusive approach. Protocols are not mere guidelines; they are powerful tools for dismantling health disparities. The implementation of tailored protocols, coupled with community engagement and cultural sensitivity, stands as a crucial step in addressing the unique challenges faced by diverse populations. As we strengthen our protocols, we move closer to fostering healthier communities.

It is imperative for Urgent Care centers to be cognizant of the interconnectedness of social determinants, economic factors, and cultural considerations that contribute to disparities in healthcare access and outcomes. Thus, we should incorporate initiatives to address the barriers to care services, proactively bridge gaps in care, and ensure that individuals from all backgrounds have equal access to timely and effective syphilis screening, testing, and treatment. 

As we advance towards a future with reduced health disparities, the integration of these strategies into acute care protocols becomes an indispensable part of a resilient and responsive healthcare system. Moreover, community focused strategies and collectively working towards this envisioned future, Urgent Care centers can become transformative agents in the pursuit of health equity and shape a healthcare landscape that is truly accessible, equitable, and responsive to the diverse needs of all individuals and communities.

Ultimately, the commitment to inclusivity in Urgent Care not only improves outcomes for individuals affected by syphilis but contributes to a broader vision of a more just and equitable healthcare system.


  1. Papp JR, Park IU, Fakile Y, Pereira L, Pillay A, Bolan GA. CDC Laboratory Recommendations for Syphilis Testing, United States, 2024. MMWR Recomm Rep 2024;73(No. RR-1):1–32. DOI: http://dx.doi.org/10.15585/mmwr.rr7301a1.
  2. 2022 U.S. syphilis cases reach highest numbers since the 1950s. Centers for Disease Control and Prevention. January 30, 2024. Accessed February 11, 2024. https://www.cdc.gov/nchhstp/newsroom/2024/STI-Surveillance-Report-2022.html. 
  3. S. syphilis cases in newborns continue to increase: A 10-times increase over a decade. Centers for Disease Control and Prevention. November 7, 2023. Accessed February 11, 2024. https://www.cdc.gov/nchhstp/newsroom/2023/syphilis-cases-in-newborns.html.