- A large U.S. study found an increase in neurologic symptoms of syphilis between 2019 and 2022
- Neurosyphilis is more common in late-stage syphilis, but also increased in the early stage
- Researchers recommended neurologic screening for people with syphilis to prevent injury
Rates of new syphilis diagnoses have been increasing in the past 20 years. As a result, there is now an epidemic of syphilis across Canada. The initial symptoms of syphilis—a sore or chancre on or inside the genitals, mouth or other parts of the body—may be painless or go unnoticed. The germs that cause syphilis (called treponemes) quickly spread from the site of first contact. These germs can attack nerves, eventually causing problems in the ears (hearing loss) and eyes (loss of vision). What’s more, if left untreated, over time syphilis can cause injury to vital organs, including the brain, bones, heart and circulatory system, liver and kidneys. Syphilis during pregnancy can harm the fetus and baby; this is called congenital syphilis. Symptoms of syphilis can mimic many other diseases; however, syphilis can be easily diagnosed with a simple blood test. Most people can recover with a single course of antibiotic therapy.
In the U.S.
According to researchers at the U.S. Centers for Disease Control and Prevention (CDC), rates of syphilis are resurgent, reaching levels “not seen since the 1960s.” As a result, the CDC is concerned that neurologic complications may be occurring more frequently in people with syphilis.
Syphilis affecting the brain, eyes and ears
According to the CDC, “without treatment, syphilis can spread to the brain and nervous system (neurosyphilis), the eye (ocular syphilis) or the ear (otosyphilis). This can happen during any of the stages [of syphilis].”
The CDC has summarized signs and symptoms of syphilis affecting different organs/systems as follows:
Signs and symptoms of neurosyphilis can include:
- severe headache
- muscle weakness and/or trouble with muscle movements
- changes to your mental state (trouble focusing, confusion, personality change) and/or dementia (problems with memory, thinking and/or decision making)
Signs and symptoms of ocular syphilis can include:
- eye pain and/or redness
- changes in your vision or even blindness
Signs and symptoms of otosyphilis may include:
- hearing loss
- ringing, buzzing, roaring or hissing in the ears (tinnitus)
- dizziness or vertigo (feeling like you or your surroundings are moving or spinning)
Study details
A team of researchers reviewed reports of syphilis sent to the CDC between 2019 and 2022. They focused on 171,855 cases of syphilis among people aged 15 and older sent from 12 jurisdictions in the U.S. This represents 27% of cases of syphilis reported to the CDC.
Results
The research team’s analysis found that “neurologic manifestations were infrequently reported but increased.” This increase occurred in people with late-stage syphilis and even among people with early-stage syphilis.
Early syphilis
- 2019 – 141 cases of neurosyphilis out of 22,855 cases of early syphilis
- 2022 – 313 cases of neurosyphilis out of 32,603 cases of early syphilis
Late syphilis
- 2019 – 146 cases of neurosyphilis out of 11,120 cases of late syphilis
- 2022 – 391 cases of neurosyphilis out of 22,037 cases of late syphilis
Secondary vs. late syphilis
The researchers found that neurologic signs and symptoms “were four times as prevalent among persons with secondary syphilis and five times as prevalent among persons with unknown duration of late syphilis compared to primary syphilis.”
Rates of neurosyphilis by different characteristics
Age
People who were aged 65 and older and who had early syphilis were seven times more likely to have neurosyphilis than people aged 15 to 24 who also had early syphilis.
People who were aged 65 and older and who had late syphilis were 20 times more likely to have neurosyphilis than people aged 15 to 24 who also had late syphilis.
Ethno-racial groups
According to the researchers, people who were White or multiracial were more likely to have signs/symptoms of neurosyphilis than people who were Black (regardless of whether they had early or late syphilis).
Sex and sexuality
Researchers found that neurologic signs/symptoms were more common among females (1.1%) than males (0.7%) who had early syphilis. However, this difference was not seen in people who had late syphilis.
Gay, bisexual and other men who have sex with men (gbMSM) were less likely to have signs/symptoms of neurosyphilis (1.5%) than men who had sex only with women (2%).
HIV
The researchers found that people with HIV who had either early or late syphilis were more likely to have neurological signs/symptoms of syphilis compared to people without HIV.
Bear in mind
Although cases of neurosyphilis increased over the course of the study, the rise was modest in the face of what the researchers called a “period of substantial [overall] increase in syphilis.” However, they noted that when syphilis attacks the nerves and brain, it can increase the risk of illness and even death. The financial cost of managing neurosyphilis is greater than the cost of managing uncomplicated syphilis.
Part of the reason that rates of neurosyphilis were lower in different populations may have to do with screening practices. For instance, the researchers state that since frequent screening of syphilis is encouraged for gbMSM by sexually transmitted infection guidelines, it is likely that syphilis in this population is, on average, diagnosed and treated earlier than in other populations.
The researchers state that people with HIV may undergo more screening for syphilis and neurosyphilis (compared to people without HIV) and this could have skewed their analysis. The researchers suggest that future analyses of data from people with HIV include information such as “disease severity, antiretroviral therapy use, and timing of HIV diagnosis,” as this could help scientists and doctors better understand the risk of neurosyphilis in people with HIV.
Caution needed
The researchers caution that their findings “likely represent a minimum burden of neurologic manifestations [arising from neurosyphilis] ….” They advanced several reasons for this, including the following:
- late syphilis, considered non-infectious, may not be prioritized in non-pregnant persons for investigation by health departments
- neurologic signs/symptoms may not be reported by patients
- neurologic screening and evaluation practices may vary among healthcare providers
- insufficient lab data because samples of cerebrospinal fluid (CSF) were not collected for analysis
Recommendations arising from this research
As the CDC scientists found neurologic manifestations of syphilis in different stages and “across every age group, sex, race/ethnicity and HIV status,” they made the following statement:
“Healthcare providers should evaluate all patients with syphilis for evidence of neurologic signs/symptoms, with collection of CSF for analysis if clinical evidence of neurological involvement is observed. Early detection and treatment is crucial to prevent potential long-term neurological [injury] from syphilis.”
—Sean R. Hosein
Resources
Winnipeg researchers warn about rising cases of syphilis-related stillbirths – CATIE News
Combatting the rise in congenital syphilis: How service providers can support prevention, testing and treatment – Prevention in Focus
Views from the front lines: Congenital syphilis – CATIE
Congenital syphilis – NCCID
Early access to syphilis screening and treatment needed to prevent stillbirths – CATIE News
Rapid combined syphilis-HIV testing found accurate and useful in an Alberta study – CATIE News
Alberta study underscores the importance of syphilis testing in people who use stimulants – CATIE News
New HIV infections in Manitoba intersect with housing and methamphetamine use – CATIE News
Understanding the impact of the antibiotic doxycycline on the sexual well-being of users – CATIE News
REFERENCE:
Wondmeneh S, McDonald R, Quilter LAS, et al. Reported neurologic manifestations among persons with syphilis by stage of infection – 12 states, 2019-2022. Clinical Infectious Diseases. 2025; in press.