CDC Releases Recommendations to Address Rising Syphilis Cases

In an era of advanced modern medicine, syphilis should no longer be the feared disease it once was—but the US is currently experiencing a syphilis epidemic. Cases of infection reached a historic low in 2000/2001, but despite efforts to keep case numbers down, they have been climbing ever since.¹ According to a new report from the U.S. Centers for Disease Control and Prevention (CDC), over 203,000 syphilis cases were reported in 2022 in the US alone—a staggering 79 percent increase from 2018.¹ Now, the CDC has decided to step in to address the rising cases by releasing its first comprehensive set of recommendations for syphilis testing.²

The stages of syphilis infection

Caused by the bacterium Treponema pallidum, syphilis progresses through four distinct stages.³ During the primary stage, individuals develop painless sores that mostly go unnoticed, but the infection is easily transmitted to others. The secondary stage, months after the initial sores disappear, is accompanied by a rough, bumpy rash that can cover the entire body and by other symptoms such as fever, sore throat, swollen lymph nodes, and fatigue. If untreated, the infection will enter the asymptomatic latent phase, during which it can remain in the body for years. The tertiary and final phase occurs 10–30 years after the initial infection. Though most people do not progress to this stage, it can lead to severe organ damage and result in death if the infection continues to go undetected and untreated.

The laboratory’s role

Laboratory testing is crucial for keeping syphilis cases at bay, especially in the early stages of infection when diagnosis and treatment can prevent onward transmission and progression. However, syphilis is known as “the great imitator” because of its range of nonspecific symptoms,⁴ which may lead to delayed detection.

These missed opportunities for testing are highly prevalent in pregnant people,⁵ and an upward trend of syphilis in women of reproductive age has been linked to a 10-fold increase in congenital syphilis cases during the past decade.⁶ Screening pregnant people can lower the risk of vertical transmission, especially when caught early enough in the pregnancy. However, a lack of timely prenatal care and late identification of seroconversion are associated with the rising rates of congenital syphilis.⁴

“Syphilis is often asymptomatic and the physical exam findings of infection are often missed—not only by patients but also by providers,” says Irene Stafford, MS, MD, physician and associate professor at the University of Texas Health Science Center at Houston, Texas. “Testing is also not universally available, especially outside of the routine clinic environment—and often, patients may not have health insurance or resources to access traditional care and get tested.”

New recommendations from the CDC

Laboratory testing for syphilis has typically relied on serologic algorithms to test the immune response to T. pallidum; tests can be characterized as either treponemal or nontreponemal. The term “treponemal tests” still accurately reflects those that detect antibody responses to T. pallidum-specific antigens. However, “nontreponemal tests” is now considered a misnomer because the antigens detected by these tests are not exclusive to T. pallidum membranes.

Nontreponemal (lipoidal antigen) tests

Going forward, the CDC recommends the term “nontreponemal (lipoidal antigen) tests” to better describe their ability to detect lipoidal antigens associated with both T. pallidum and host membranes. Furthermore, rather than using the blanket term “nonspecific antibodies” when using nontreponemal (lipoidal antigen) tests, the CDC suggests it is more accurate to report antibody specificity and how that impacts overall test specificity.

The recommendations emphasize the importance of nontreponemal antibody titers for monitoring treatment response and guiding further management. However, results from different nontreponemal (lipoidal antigen) tests should not be used interchangeably due to incompatibilities between test methods and subjective interpretations of results between laboratories.

Treponemal tests

Treponemal tests are used to confirm reactive nontreponemal (lipoidal antigen) test results and assess patients presenting with signs of potential syphilis, especially during the primary stage of infection when nontreponemal (lipoidal antigen) tests may not yet be reactive. Unless the patient is treated early enough, antibodies detected with treponemal tests remain in the body for life; therefore, treponemal tests cannot be used to monitor treatment response because they will always be reactive, even after treatment. For this reason, the CDC recommends against using these tests to detect reinfection in patients with previously treated syphilis and reactive treponemal test results. Instead, patients should be assessed using nontreponemal (lipoidal antigen) testing titers in combination with their clinical history of syphilis, a physical examination, and a sexual risk assessment.

Meeting patients where they are

Point-of-care (POC) tests for syphilis are currently limited in the US and distinguishing current from past infections with them may prove difficult. However, the CDC suggests that wider availability of POC serologic antibody tests could reduce the time to treatment by identifying syphilis at the initial visit, rather than waiting up to five days for laboratory results and follow-up appointments.⁶

Hope for the future

Will the new recommendations help curb the decades-long rise of syphilis? Stafford is optimistic. “I believe they will be very impactful for the clinical side of syphilis management—they can help empower providers to feel confident about ordering appropriate tests for syphilis and learn more about what is available to them,” she says. By staying informed and implementing the CDC’s recommendations, clinical laboratory professionals will be pivotal in slowing the spread of syphilis and safeguarding public health. Stafford concludes, “Ultimately, the key thing to consider is how we can better serve patients through improved—and increased—application of these guidelines.”

References:

1. Sexually Transmitted Infections Surveillance, 2022. Centers for Disease Control and Prevention. January 30, 2024. https://www.cdc.gov/std/statistics/2022
2. Papp JR, et al. CDC Laboratory Recommendations for Syphilis Testing, United States, 2024. MMWR Recomm Rep. 2024;73(1):1–32. doi:10.15585/mmwr.rr7301a1.
3. Syphilis – CDC Basic Fact Sheet. Centers for Disease Control and Prevention. February 10, 2022. https://www.cdc.gov/std/syphilis/stdfact-syphilis.htm
4. Çakmak SK et al. Syphilis: A Great Imitator. Clin Dermatol. 2019;37(3):182–191. doi:10.1016/j.clindermatol.2019.01.007.
5. Kimball A et al. Missed opportunities for prevention of congenital syphilis – United States, 2018. MMWR Morb Mortal Wkly Rep. 2020;69(22):661–665. doi:10.15585/mmwr.mm6922a1.
6. Syphilis in Babies Reflects Health System Failures. Centers for Disease Control and Prevention. December 14, 2023. https://www.cdc.gov/vitalsigns/newborn-syphilis