This article was compiled by Dr. Wujian Ke based on the latest syphilis treatment guidelines released by the CDC on June 5, 2015, and is published with permission (). Guangdong Dermatology Hospital, Department of Venereology, Ke Wujian Dark-field microscopy method: Detection of syphilis spirochetes directly from lesion exudate or tissue by dark-field microscopy can confirm the diagnosis of early syphilis. Polymerase chain reaction (PCR) method: Although there is a lack of commercial syphilis spirochete DNA polymerase chain reaction (PCR) test kits, there are some laboratories that can provide syphilis spirochete PCR testing. Non-syphilis spirochete antibody tests : These include the venereal disease research laboratory [VDRL] test or the rapid plasma reactin [RPR] test. Syphilis spirochete antibody testing : including fluorescent dense spirochete antibody adsorption [FTA-ABS] test, syphilis spirochete particle agglutination [TPPA] test, various enzyme immunoassays [EIA], chemiluminescent immunoassay [CIA], immunoblotting test, rapid syphilis spirochete antibody test, etc. The use of only one serologic test for syphilis as a clinical diagnosis is not sufficient, as it may result in false-negative results in patients with stage I syphilis and false-positive results in those who are not infected with syphilis. False-positive results for non-syphilis spirochetal antibody tests can occur in many diseases or conditions unrelated to syphilis, such as HIV infection, autoimmune diseases, immunizations, pregnancy, injection drug use, and the elderly. Therefore, those who test positive for non-syphilis spirochetes need further confirmation with a syphilis spirochete antibody test. The antibody titer of the non-syphilis spirochete antibody test may correlate with disease activity and can be used for post-treatment follow-up, so the test results should be reported in quantitative form. A fourfold change in antibody titer using the same non-syphilis spirochete antibody serologic test is clinically significant, i.e., equivalent to two dilution changes (e.g., from 1:16 to 1:4, or from 1:8 to 1:32). Follow-up testing of patients on treatment needs to be performed in the same laboratory using the same test (VDRL or RPR). results for both VDRL and RPR are equally valid, and since RPR titers are often slightly higher than VDRL titers, the quantitative results of these two tests cannot be directly compared. Non-syphilis antibody test titers usually fall after treatment and may become negative over time; however, in some individuals, non-syphilis antibody titers can persist for a considerable period of time, a process known as “serum fixation”. Regardless of treatment or change in disease, the spirochete antibody test will remain positive for life in most patients, so spirochete antibody titers cannot assess the effectiveness of treatment. Approximately 15-25% of patients with early syphilis will have a negative serum spirochete test within 2-3 years after treatment. Individuals with a positive syphilis spirochete antibody screening test should receive a quantitative non-syphilis spirochete antibody test that can be used to guide the patient’s treatment. If the non-syphilis spirochete antibody test is negative, the laboratory should perform a different syphilis spirochete antibody test (choose a test that detects a different antigen than the original test) to confirm the initial test results. If the second syphilis spirochete antibody test is positive, no further treatment is required unless the sexual history indicates the possibility of reinfection and the patient has been treated previously. In this case, a repeat non-syphilis spirochete antibody test is recommended in 2-4 weeks to evaluate and rule out early syphilis infection. If the patient has not been previously treated for syphilis, treatment should be given. All patients with untreated syphilis are treated for late-stage latent syphilis unless the history or physical examination findings indicate recent syphilis infection. If the second syphilis spirochete test is negative and the epidemiologic risk and clinical probability of syphilis infection is low, no further evaluation or treatment is recommended. Two studies have shown that high values of quantitative indicators of syphilis spirochete antibody EIA / CIA tests are associated with positive TPPA; however, the range of variation in the optical density values of different syphilis spirochete antibody tests and their clinical significance deserve further investigation. This article is published with permission from Dr. Wujian Ke (). If you have any questions about this article, please visit my homepage ( )