Besides, they are not suitable for blood donors.[12,13] Serological tests: Serological tests are still considered the most useful approach for the diagnosis.[12,14,15] The serological diagnosis is based on the detection of two distinct antibodies, the nontreponemal antibody (reagin), which binds to cardiolipin released from damaged host cells and the treponemal antibody directed against specific antigens. The nontreponemal tests are rapid plasma reagin (RPR) and venereal disease research laboratory test (VDRL), derived from the first available laboratory test, the Wassermann reaction for cardiolipin. for transfusion-transmitted infections in the modern blood transfusion centers. is a noncultivable bacterium, the diagnosis of syphilis is based on direct identification of the pathogen in the lesion and the identification of a specific immunological response. Dark-field microscopy and/or polymerase chain reaction (PCR)[10,11] are useful in acute primary infection when spirochete can be detected directly. In particular, dark-field microscopy allows an immediate diagnosis of syphilis with a prompt start and a follow-up of the therapy. A principal limitation of this technique consists of the requirement for a great experience of each operators; moreover, the presence of nonpathogenic spirochetes can limit its use. Recently, PCR appears quite promising, but its routine use cannot yet be proposed.[10,11] It is known that molecular tests for syphilis are too expensive for many clinical laboratories and cannot replace the serology. Besides, they are not suitable for blood donors.[12,13] Serological tests: Serological tests are still considered the most useful approach for the diagnosis.[12,14,15] The serological diagnosis is based on the detection of two distinct antibodies, the nontreponemal antibody (reagin), which binds to cardiolipin released from damaged host cells and Geraniin the treponemal antibody directed against specific antigens. The nontreponemal tests are rapid plasma reagin (RPR) and venereal disease research laboratory test (VDRL), derived Geraniin from the first available laboratory test, the Wassermann reaction for cardiolipin. These tests are cheap and simple to perform and have a sensitivity of approximately 70-85%, which approaches 100% only in the secondary stage when, the infection is still active. Since RPR/VDRL takes 30 min, it can be performed in emergency departments and it is particularly suited for patients with a strong clinical suspicion of syphilis.[16] Nontreponemal antibodies become Geraniin detectable in the early infection (7-10 days after the appearance of the primary lesion) or a few weeks after the infection. They are indicative of active infection and important for monitoring treatment; indeed, a reduction of their titer shows the efficacy of the antibiotic treatment while an increase shows a relapse or re-infection.[17] When the incidence and prevalence of syphilis in blood donors appear elevated, it might be necessary to consider the use of a nontreponemal assay to identify those donors with Geraniin the evidence of recent infections. However, one of the major disadvantages of nontreponemal checks are the biological false-positive reactions since nontreponemal antibodies can also be present in additional diseases such as other spirochetal infections, mononucleosis, varicella, measles, malaria, leprosy, connective cells diseases such TEF2 as systemic lupus erythematosus and malignancy.[1,17,18] Since nontreponemal checks are not-specific, treponemal specific assays have been developed and improved. Treponemal checks use native or recombinant antigens and allow the detection of specific anti-treponemal antibodies; anti-treponemal IgM are detectable within approximately 2 weeks postinfection, Geraniin while anti-treponemal IgG appear at about 4 weeks after the postinfection.[19] Anti-treponemal IgM and nontreponemal antibodies decrease following treatment of early syphilis, while anti-treponemal IgG antibodies persist longer and are usually detectable for many years after the disease has been thought to be eradicated.[19,20] The treponemal tests evaluate the antibody reactivity against specific antigens and are based on different agglutination reactions: hemagglutination assay (TPHA) uses reddish blood cells, and the particle agglutination assay (TPPA), or the microhemagglutination assay for use gelatin particles. Higher titers of these checks are correlated to an active illness while they decrease in the latent phase. Clinically, TPHA reactivity may be detectable round the 4th week of illness with an overall level of sensitivity in the untreated main stage in the 70-80% range by increasing to about 100% in the secondary stage. TPPA is generally superior to TPHA for the detection of main syphilis.[21] Treponemal assays meet the requirements for use in blood center and contribute importantly to optimizing workflow and efficiency; on the other hand, they are theoretically difficult to perform and more expensive than nontreponemal checks and false positive reactions can occur.[16,18] Automated immunoassay: In the last.