In the early stages, discharge from open sores is examined to see if syphilis bacteria are present. In later stages, a blood test also can be done to check for antibodies to the bacteria.

The definitive method for diagnosing syphilis is visualizing the Treponema pallidum bacterium via darkfield microscopy. This technique is rarely performed today. Diagnoses are thus more commonly made using blood tests.Cdc-pdfExternal There are two types of blood tests available for syphilis: 1) nontreponemal tests and 2) treponemal tests. Both types of tests are needed to confirm a diagnosis of syphilis.

Nontreponemal tests (e.g., VDRL and RPR) are simple, inexpensive, and are often used for screening. However, they are not specific for syphilis, can produce false-positive results, and, by themselves, are insufficient for diagnosis. VDRL and RPR should each have their antibody titer results reported quantitatively. Persons with a reactive nontreponemal test should always receive a treponemal test to confirm a syphilis diagnosis. This sequence of testing (nontreponemal, then treponemal test) is considered the “classical” testing algorithm.

Treponemal tests (e.g., FTA-ABS, TP-PA, various EIAs, chemiluminescence immunoassays, immunoblots, and rapid treponemal assays) detect antibodies that are specific for syphilis. Treponemal antibodies appear earlier than nontreponemal antibodies and usually remain detectable for life, even after successful treatment. If a treponemal test is used for screening and the results are positive, a nontreponemal test with titer should be performed to confirm diagnosis and guide patient management decisions. Based on the results, further treponemal testing may be indicated. For further guidance, please refer to the 2015 STD Treatment Guidelines. 3 This sequence of testing (treponemal, then nontreponemal, test) is considered the “reverse” sequence testing algorithm.Reverse sequence testing can be more convenient for laboratories, but its clinical interpretation is problematic, as this testing sequence can identify persons previously treated for syphilis, those with untreated or incompletely treated syphilis, and persons with false-positive results that can occur with a low likelihood of infection.5

Special note: Because untreated syphilis in a pregnant woman can infect and possibly kill her developing baby, every pregnant woman should have a blood test for syphilis. All women should be screened at their first prenatal visit. For patients who belong to communities and populations with high prevalence of syphilis and for patients at high risk, blood tests should also be performed during the third trimester (at 28–32 weeks) and at delivery. For further information on screening guidelines, please refer to the 2015 STD Treatment Guidelines. 3

All infants born to mothers who have reactive nontreponemal and treponemal test results should be evaluated for congenital syphilis. A quantitative nontreponemal test should be performed on infant serum and, if reactive, the infant should be examined thoroughly for evidence of congenital syphilis. Suspicious lesions, body fluids, or tissues (e.g., umbilical cord, placenta) should be examined by darkfield microscopy, PCR testing, and/or special stains. Other recommended evaluations may include analysis of cerebrospinal fluid by VDRL, cell count and protein, CBC with differential and platelet count, and long-bone radiographs. For further guidance on evaluation of infants for congenital syphilis, please refer to the 2015 STD Treatment Guidelines. 3