The Resurgence of Maternal Syphilis—A Public Health Wake-Up Call

How did we go from nearly eliminating syphilis in the US to the current situation? The plan to eliminate syphilis was finalized in the late 1990s, when rates in the US were the lowest in decades and syphilis was geographically contained to a relatively few areas.1 The plan required public health personnel such as disease intervention specialists to engage in community-based contact tracing and treatment. Although syphilis rates remained relatively low in the early 2000s, rates began to increase dramatically starting around 2011. Very recent data suggest that these annual increases in syphilis rates in the US may have peaked in 2022 and started to decline in 2023 and 2024.4 However, these same data suggest that women have been left behind; although there were decreases in syphilis rates overall and in men, rates of congenital syphilis and in women with syphilis diagnosed at later stages continued to increase in 2024.3,4

The factors contributing to the steady increases of syphilis in pregnant women are likely different than those in men. In the analysis by Staneva and colleagues,2 the women with maternal syphilis tended to be younger than 25 years, unmarried (90.1%), Black, and living in the Southeastern US—all of which are risk factors associated with sexually transmitted infections in US women in general. Delayed access to prenatal care was also associated with maternal syphilis, as more than one-third of the women did not have a perinatal visit in the first trimester.2 Nationally, maternal syphilis is associated with a range of syndemic factors, including substance abuse, incarceration, and lack of health insurance, each of which may impact access to prenatal care.5 Recent budget and personnel cuts at the Centers for Disease Control and Prevention and other public health infrastructure may further impact access to accurate public health data needed to track the epidemic and the ability to hire the public health workers needed to reverse the course of the current syphilis epidemic. To further complicate matters, in 2025 the US is experiencing a national shortage of injectable penicillin G benzathine, which is the only medication approved to treat syphilis in pregnant women.6

Several new initiatives are taking place that could impact the syphilis epidemic, including initiatives emerging from public health agencies and state policymakers. In the early 2020s, doxycycline postexposure prophylaxis began to be offered to men at increased risk for syphilis, and recent data suggest this strategy has been effective in reducing syphilis rates in men.7 However, doxycycline is not safe for use in pregnant women, and doxycycline postexposure prophylaxis is generally not yet recommended for women. Several influential professional organizations, including the US Preventive Services Task Force and the American College of Obstetrics and Gynecology, recently updated their guidelines to recommend testing of pregnant women for syphilis at up to 3 time points (initiation of obstetrical care, during the third trimester, and at the time they present for delivery), regardless of their real or perceived risk factors.8,9 Although the guidelines provide clinical recommendations, they are not requirements. Therefore, nearly all US states have passed and/or updated legislation to require syphilis testing during pregnancy, including at least 10 states (Alabama, Arizona, Colorado, Georgia, Maryland, Mississippi, Missouri, North Carolina, Tennessee, and Texas) that now require syphilis testing at all 3 recommended time points.10 Also with the current shortage of injectable penicillin G benzathine, numerous state, county, and city public health departments have sent out practitioner alerts or Dear Colleague letters to help increase awareness of the shortage and of the recommendations to limit use injectable penicillin G benzathine to treat syphilis in pregnant women, since it is the only available treatment for pregnant women, during the current shortage.

Increased testing for syphilis during pregnancy may contribute to the observed increase in rates of detected infections in pregnant women. Maternal syphilis can be treated, and maternal treatment can prevent consequences in both mother and infant. The data from Staneva and colleagues2 come from birth certificate data that do not provide information about whether the mothers received treatment or about the neonatal outcomes. Future data collection on similar topics should seek to report whether women who receive a diagnosis of syphilis during pregnancy received treatment and whether their offspring ended up with congenital syphilis or not. Such information will be very informative to fully understand the scope of the problem related to maternal diagnoses.

Overall, the data from maternal syphilis in Mississippi should serve as wake-up call across the US. It is encouraging to see that the syphilis epidemic appears to be decreasing among men in the US, and perhaps the rates of syphilis in women will soon follow. Even if rates in women begin to follow the trend and start to decrease, the current rates of maternal syphilis and congenital syphilis are among the highest ever in the US.3 Thus, the US health care system and public health authorities have an ongoing need for trustworthy and accurate data regarding syphilis rates in different subgroups of people. It is encouraging to see that screening guidelines and state legislative initiatives are being updated, but new public health interventions and policies will continue to be needed in the US and worldwide to reduce adverse outcomes related to syphilis and other sexually transmitted infections during pregnancy. Similarly, there is an ongoing need in the US to strengthen strategies to increase access to obstetrical care, including strategies to reduce stigma related to being pregnant and unmarried, substance use, incarceration, lack of private health insurance, and other social determinants of health.5 The combination of these interventions and policies will hopefully get back to the point where elimination of syphilis in the US is not only possible, it is doable.

Published: December 30, 2025. doi:10.1001/jamanetworkopen.2025.46723

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2025 Cook RL. JAMA Network Open.

Corresponding Author: Robert L. Cook, MD, MPH, Department of Epidemiology, University of Florida, PO Box 100231, Gainesville, FL 32610 (cookrl@ufl.edu).

Conflict of Interest Disclosures: Dr Cook reported receiving grants from the National Institutes of Health and Merck, paid to his university, outside the submitted work. No other disclosures were reported.