Syphilis screening

Two answers, depending on whether you are pregnant.

Not pregnant: screening is for people at increased risk, and no body recommends routine testing of average-risk nonpregnant adults. USPSTF (2022) grades screening A for persons at increased risk and lists where prevalence is higher: men, men who have sex with men, persons with HIV infection, young adults, and persons with a history of incarceration, sex work, or military service; it adds that a substantial percentage of heterosexual transmission occurs among persons who use illicit drugs, particularly methamphetamine, and that diagnosis of another STI may signal condomless sex. CDC's screening table (reviewed March 2024) conditions its rows for women and for men who have sex with women on being at increased risk, and names history of incarceration or transactional sex work, geography and race/ethnicity, adding being a male younger than 29 years in the men's row. Both bodies make geography part of the answer: CDC lists it as a risk factor, and USPSTF tells clinicians to consult state and local health department data and CDC surveillance for their area.

For people not at increased risk, USPSTF gives its reason for not extending the recommendation rather than issuing a separate grade: the yield of screening is likely low, and screening in this population may result in high false-positive rates and overtreatment.

Pregnant: everyone, as early as possible, on all three bodies' positions. USPSTF (2025) says this applies to all adolescents and adults who are pregnant, whether or not risk factors for syphilis are present, and that if early testing is not done, testing should occur at the first opportunity, which could be as late as at admission for delivery. Where the bodies part is on testing again later in pregnancy, which is the disagreement below.

One blood draw, then two tests in sequence. Under the traditional algorithm the laboratory screens with a nontreponemal test (VDRL or RPR) and, if it is reactive, confirms with a treponemal test such as TP-PA. Under the reverse sequence algorithm it screens with an automated treponemal immunoassay and follows a reactive result with a quantitative nontreponemal test. If those two disagree, CDC has the laboratory run a second, different treponemal test, TP-PA preferred, to adjudicate. CDC's 2024 laboratory recommendations accept both algorithms; it notes the traditional one might be less sensitive for early or late latent syphilis, while the reverse one might produce more false positives in low-prevalence populations.

A reactive nontreponemal test on its own is not a diagnosis. CDC lists the conditions that produce false positives: other infections including HIV, autoimmune conditions, vaccinations, injecting drug use, pregnancy, and older age. That is why the confirmatory step exists, and why USPSTF's pregnancy statement says a 2-step process is used because of high false-positive rates associated with nontreponemal tests alone, especially in pregnancy.

Rapid point-of-care tests exist and typically return a result in 5 to 30 minutes, but USPSTF (2022) reports that initial real-world data show sensitivity may be low, and its 2025 pregnancy statement says it is unclear how results from at-home fingerstick tests alone, without confirmatory testing, should guide treatment. Treat a rapid or home result as the first step, not the answer.

A confirmed infection is treated with penicillin, and the dose depends on the stage. CDC's 2021 regimen for primary, secondary and early latent syphilis is benzathine penicillin G 2.4 million units by intramuscular injection in a single dose; for late latent syphilis it is 7.2 million units total, given as three doses of 2.4 million units at 1-week intervals. CDC adds that extra doses or other antibiotics do not improve on the single-dose regimen for primary and secondary disease, and that azithromycin should not be used. In pregnancy, penicillin G is the only therapy with documented efficacy; a pregnant patient with a penicillin allergy is desensitized and then treated with penicillin. Supply is constrained: CDC's guideline pages carry a notice that Bicillin L-A availability is limited and that on March 6, 2026, the FDA announced it is allowing temporary importation of Lentocilin.

Expect three things alongside the injection. An HIV test: CDC says everyone with primary or secondary syphilis should be tested for HIV at diagnosis, and offered PrEP if negative. A possible reaction in the first 24 hours, the Jarisch-Herxheimer reaction, with fever, headache and muscle aches; CDC states it is a reaction to treatment and not a penicillin allergy. And partner notification: CDC's rule is that anyone who had sexual contact with a person diagnosed with primary, secondary or early latent syphilis within the 90 days before the diagnosis is treated presumptively, even with negative tests, and partners are confidentially notified going back 3 months plus the duration of symptoms for primary, 6 months plus the duration of symptoms for secondary, and 1 year for early latent syphilis.

Follow-up is by nontreponemal titer, and the meaningful change is fourfold, two dilutions, measured with the same test type, preferably at the same laboratory. CDC's benchmark is a fourfold fall within 12 months after treatment for primary or secondary syphilis, while noting that 10% to 20% of people treated with the recommended therapy will not reach it in that time. A treponemal test that stays positive after treatment is expected; CDC says a person with a history of treatment and a reactive treponemal test needs no further management unless their sexual history indicates a reexposure.