Screening for Syphilis Infection: Recommendation Statement

U.S. Preventive Services Task Force

Ann Fam Med. 2004;2(4) 

In This Article


In 2002, the reported nationwide incidence rate of primary and secondary cases of syphilis infection was 2.4 per 100,000 persons (state incidence rates ranged from 0-5.4 per 100,000 persons), and the rate of congenital syphilis infection nationwide was 11.1 per 100,000 live births (state incident rates ranged from 0-31.1 per 100,000 live births).[4] Rates of primary and secondary syphilis infection had been steadily decreasing during the 1990s; however, in 2001, the rate increased for the first time in a decade. This increase was evident only in men and was associated with outbreaks in several urban areas among men who have sex with men, high reported rates of HIV co-infection, and high-risk sexual behavior. The prevalence of syphilis infection differs by region (3.1 and 1.7 per 100,000 persons for the South and Northeast U.S., respectively) and by ethnicity (9.8, 2.7, and 1.2 per 100,000 persons for African Americans, Hispanics, and whites, respectively).[4] The median seropositivity has been reported as 2.1% to 12.2% in incarcerated women and 0.9% to 5.2% in incarcerated men.[4] Commercial sex workers and persons who exchange sex for drugs have a higher incidence of syphilis infection.[5,6] Late-stage syphilis includes gummatous, cardiovascular, and neurological complications that can lead to significant disability and premature death. Congenital syphilis infection results in fetal or perinatal death in 40% of affected pregnancies,[1] as well as disease complications in surviving newborns, including central nervous system abnormalities; deafness; multiple skin, bone, and joint deformities; and hematological disorders.[7]

The USPSTF examined the evidence from 1994 to 2003 to determine the efficacy of syphilis screening in decreasing syphilis-related morbidity and mortality in the general population, as well as in high-risk populations and in pregnant women.[3] The USPSTF found no direct evidence that screening for syphilis infection in the general population or in high-risk populations reduces morbidity or mortality. The USPSTF did find observational evidence that screening for syphilis infection in pregnant women and/or neonates reduces the prevalence of congenital syphilis infection in neonates.[8,9]

Traditionally, screening for syphilis infection is a 2-step process that involves an initial nontreponemal test (VDRL or RPR) followed by a confirmatory treponemal test (FTA-ABS or TP-PA). Sensitivity of the RPR and VDRL tests are estimated to be 78% to 86% for detecting primary syphilis infection, 100% for detecting secondary syphilis infection, and 95% to 98% for detecting latent syphilis infection. Specificity ranges from 85% to 99% and may be reduced in individuals who have preexisting conditions (ie, collagen vascular disease, pregnancy, intravenous drug use, advanced malignancy, tuberculosis, malaria, and viral and rickettsial diseases) that produce false-positive results. The FTA-ABS test has a sensitivity of 84% for detecting primary syphilis infection and almost 100% sensitivity for detecting syphilis infection in other stages, and a specificity of 96%.[10] Several new screening tests are currently being studied, including Immunochromatographic Strip (ICS), Line Immunoassay (LIA), Enzyme-linked Immunosorbent Assay (ELISA), RPR card, and Rapid Syphilis Test (RST).[3] New screening tests currently being studied for use in pregnant women and infants include: IgM immunoblotting and Polymerase Chain Reaction (PCR) assay of serum and cerebrospinal fluid for central nervous system infection in infants, placenta histopathology, and umbilical cord blood testing.[3]

The yield of screening using a two-step process (RPR followed by confirmatory FTA-ABS) can be estimated using test characteristics and the incidence of syphilis infection in a given population. For example, in the general population (assuming a prevalence of 5 per 100,000, an RPR sensitivity of 91% and specificity of 95%, and FTA-ABS sensitivity of 92% and specificity of 96%), one would have to screen more than 24,000 patients to detect a single case of syphilis infection (number needed to screen [NNS] = 24,000); 200 per 100,000 people screened would have false-positive test results. On the other hand, in a high-risk population of incarcerated women (assuming a prevalence of 12%, an RPR sensitivity of 91% and specificity of 95%, and FTA-ABS sensitivity of 92% and specificity of 96%), one would have to screen 10 patients to detect 1 case of syphilis infection (NNS = 10); almost 2,000 per 100,000 people screened would have false-negative test results.

Antibiotic therapy is highly effective in eliminating T. pallidum and in preventing congenital infection when administered early to pregnant women.[11] Penicillin G has long been an effective regimen for all stages of syphilis,[12] and new trials focus on antibiotics that are easier to administer or are alternatives for penicillin allergic individuals. A number of small poor-quality cohort and RCT studies on the use of oral azithromycin have been published and report comparable outcomes to penicillin treatment.[13,14,15,16] Little evidence is available to guide therapy in pregnancy.

No studies have directly looked at the harms of screening or treatment. Potential harms of screening may include opportunity costs to the clinician and patient (time, resources, etc.) and false-positive results which may lead to stress, labeling, and further work-up. Harms of treatment include adverse drug-related effects including anaphylaxis from penicillin allergy and the Jarisch-Herxheimer reaction (febrile reaction with headache, myalgia, and other symptoms) that may occur within the first 24 hours after any therapy for syphilis.

Seven cost studies done in different countries support continued universal testing during pregnancy.[7] In a study done in the UK, universal prenatal screening of pregnant women was about as cost-effective as targeted screening programs.[17]