US Syphilis Cases Surging: What You Need to Know

Syphilis and congenital syphilis cases have been surging nationwide, with an 80% increase in total syphilis cases between 2018 and 2022.¹ Per the US Centers for Disease Control and Prevention (CDC), the rate of reported congenital syphilis in the United States has increased 10-fold between 2012 and 2022.²

Testing

• Serologic testing is the primary means of diagnosing, staging, and managing syphilis.
• Testing should be done for any sexually active patient where syphilis is suspected or who has new, unexplained symptoms.
• Prompt diagnosis and treatment of syphilis can prevent systemic complications, including ocular involvement and permanent blindness.
• All pregnant individuals should be tested for syphilis.

Pregnancy

• Syphilis during pregnancy can lead to stillbirth, miscarriage, or infant death. Infants who survive and do not receive adequate treatment can develop blindness, deafness, developmental delay, or skeletal abnormalities.³
• All pregnant individuals should be tested for syphilis at the first prenatal visit or as soon as possible thereafter.
• Depending on risk factors, some patients should be tested again, for example, at the start of the first trimester and when the baby is born.⁴
• Among all congenital syphilis cases reported in 2022, the birth parent of most patients received either no or nontimely testing or no or nondocumented or inadequate treatment during pregnancy.²
• In about 5% of congenital syphilis cases, syphilis was diagnosed late in pregnancy, after earlier nonreactive testing.²

Drug Shortage

Amid rising syphilis infections in the United States and a continuing shortage of the benzathine penicillin G injectable suspension Bicillin, the US Food and Drug Administration (FDA) has temporarily allowed importation of the benzathine benzylpenicillin powder and diluent Extencilline (requires reconstitution), which is not FDA approved, to be used in its place. The FDA notes that Extencilline contains soy, which may cause allergic reactions in patients with a sensitivity. The Bicillin shortage is anticipated to be resolved in mid-2024.

Transmission of Syphilis

Syphilis is a sexually transmitted infection (STI) caused by the spirochete bacterium Treponema pallidum. It is characterized by a chronic intermittent clinical course.

Treponema pallidum is transmitted person to person via direct contact with a syphilis ulcer during vaginal, anal, or oral sex and may enter through skin or mucous membranes. Hence, the locations for syphilitic ulcers include the vagina, cervix, penis, anus, rectum, lips, hands, and inside of the mouth.

Syphilis may also be transmitted perinatally from an infected birth parent, resulting in congenital syphilis. This can occur in utero via the placenta or, less commonly, at delivery through exposure to syphilitic genital lesions. Transmission can occur during any stage of pregnancy.

Disease Course of Syphilis

The signs and symptoms of syphilis can resemble those of many different diseases, or the infection may be asymptomatic or unrecognized. That is why it is important to test any sexually active patient where syphilis is suspected or who has new, unexplained symptoms.

There are 4 main stages of syphilis: primary, secondary, latent, and tertiary. Active infection stages include primary, secondary, and early latency. Tertiary syphilis has a later onset in patients who never received initial treatment.

Once a patient is infected, it usually takes 18-21 days for a painless ulceration, or chancre, to appear, usually on the genitals. It’s easy to miss the chancre in women because of its location in the vagina or on the cervix. A chancre will usually last 3-6 weeks and then heal spontaneously. This is primary syphilis.

The secondary syphilis phase begins about 3-10 weeks after the chancre heals. Patients present with a rash that includes palms and soles, and there may sometimes be mucosal lesions as well. Other symptoms might include malaise, appetite loss, fever, headache, stiff neck, myalgias, lacrimation, photophobia, red and painful eyes, back pain, arthralgias, pharyngitis, flu-like symptoms, pruritus (more common in immunocompromised patients), lymphadenopathy, splenomegaly, bursitis, and tenosynovitis. The variety of possible symptoms can make it difficult to recognize secondary syphilis or distinguish it from other conditions.

The latent stage of syphilis, also called the hidden stage, is defined as seroreactivity without other evidence of primary, secondary, or tertiary disease.⁵ Persons who have latent syphilis and who acquired syphilis during the preceding year are classified as having early latent syphilis. The latent stage can last for years. Without treatment, however, the disease can lead to long-term complications. Pregnant patients with latent syphilis can transmit the infection vertically to their fetus. Therefore, individuals with latent syphilis, both pregnant and nonpregnant, should be treated.

If left untreated, tertiary syphilis can develop months or years after the initial infection. Tertiary syphilis can include cardiac or neurologic manifestations known as neurosyphilis. Tertiary syphilis can also affect the bones and skin.

Syphilitic uveitis or other ocular syphilis manifestations (eg, neuroretinitis or optic neuritis) can occur at any stage of syphilis, including early-stage syphilis, and can be isolated abnormalities or associated with neurosyphilis.

What Can Health Care Professionals Do?

The CDC and other health organizations have made suggestions about how to raise awareness of syphilis and prevent its spread:

• Have an open and honest dialogue with patients about their sexual history and practices.
• Test any sexually active patient where syphilis is suspected or who has new, unexplained symptoms.
• Test pregnant patients at their first prenatal visit and treat, if necessary. Test again at delivery. If a patient is determined to be at risk, one or more additional tests can be completed throughout the pregnancy.
• Educate patients about syphilis, its symptoms, how it is spread, and possible short- and long-term health effects.
• Encourage safe sex using condoms.
• Recommend frequent testing, as often as every 3 months, for those at risk for syphilis and other STIs.
• Report new cases and track down partners that may also be infected so they can be treated.

Improved awareness and timely testing and treatment can reduce the spread of syphilis, complications of syphilis during pregnancy, and the incidence of congenital syphilis.

References

1. National Center for HIV, Viral Hepatitis, STD, and TB Prevention Newsroom. 2022 U.S. Syphilis Cases Reach Highest Numbers Since the 1950s. Centers for Disease Control and Prevention. Last reviewed January 30, 2024. Accessed April 5, 2024. https://www.cdc.gov/nchhstp/newsroom/2024/STI-Surveillance-Report-2022.html.
2. McDonald R, O’Callaghan K, Torrone E, et al. Vital Signs: Missed Opportunities for Preventing Congenital Syphilis – United States, 2022. MMWR Morb Mortal Wkly Rep. 2023;72(46):1269-1274. Published 2023 Nov 17. https://www.cdc.gov/mmwr/volumes/72/wr/mm7246e1.htm?s_cid=mm7246e1_w.
3. Cooper JM, Sánchez PJ. Congenital syphilis. Semin Perinatol. 2018;42:176–84. https://pubmed.ncbi.nlm.nih.gov/29627075/.
4. Sexually Transmitted Diseases (STDs): Congenital Syphilis – CDC Fact Sheet. Centers for Disease Control and Prevention. Last reviewed January 30, 2024. Accessed April 5, 2024. https://www.cdc.gov/std/syphilis/stdfact-congenital-syphilis.htm.
5. Sexually Transmitted Infections Treatment Guidelines, 2021. Latent Syphilis. Centers for Disease Control and Prevention. Last reviewed July 22, 2021. Accessed April 5, 2024. https://www.cdc.gov/std/treatment-guidelines/latent-syphilis.htm.