**3. Modern serologic diagnostic**

The World Health Organization recommendations of screening for syphilis in a low prevalence population of blood donors using enzyme-linked immune-sorbent assay (ELISA) may be adopted for usage in transfusion services that have the facility of ELISA [63].

On the other hand, the current screening of deceased organ donors by RPR yields a significant number of false-positive results [64].

And vice versa, in patients with positive Lyme screening and negative confirmatory testing, the performance of lues serology should be considered [29, 65, 66].

Park et al. [67], Hoover and Radolf [68], Dassah et al. emphasized the importance of the improvement of the serologic diagnostic [69]. Overall, nontreponemal tests were less sensitive than treponema-specific tests [70].

Nah et al. investigated the efficacy of traditional and reverse syphilis diagnostic algorithms during general health checkups. In total, 1000 blood specimens were obtained from 908 men and 92 women. As a result, the reverse screening algorithm could detect the subjects with possible latent syphilis who were not detected by the traditional algorithm [71].

Rourk and Litwin investigated the recently FDA cleared BioPlex 2200 syphilis total screen and automated RPR assay for the detection of total (IgG/IgM) treponemal and nontreponemal antibodies in the reverse syphilis algorithm. They concluded that the addition of the detection of treponemal IgM antibodies to the IgG/IgM screen had not significantly affected the sensitivity and specificity compared to the original IgG screen. But the addition of the comparable BioPlex RPR assay to the instrumentation significantly reduced the overall labor of syphilis screening and confirmation [72].

Yen-Lieberman et al. noted that regardless of the method, laboratories should develop approaches to identify analytical false-positive results wherever possible [73].

The syphilis testing may be affected by different racial and environmental factors [46], which is necessary to keep in mind at the estimation of serologic results.

Zhou et al. marked a high correlation between electrochemiluminescence immunoassay analyzer and chemiluminescent magnetic microparticle immunoassay. Both had high sensitivity and specificity [74].

The appearance of β2-GPI-dependent anticardiolipin antibody and its association with blood coagulation have been investigated in subjects with classical biological false-positive syphilis reactions. Subjects with false-positive tests for syphilis appeared to be more prone to blood coagulation disorders than syphilis patients,

*False-Positive Serologic Reactions for Syphilis DOI: http://dx.doi.org/10.5772/intechopen.106370*

and these autoantibodies may impact the intrinsic coagulation cascade in cases of false-positive reactions, similar to presumed antiphospholipid antibody syndrome patients [75].

Considering the importance of the diagnosis of syphilis, antibodies to T. pallidum in serum samples should be retested by the improved ELISA method to avoid falsepositive results [76]. Different reverse syphilis testing algorithms were proposed [77].

While in screening populations, discrepancies between chemiluminescent microparticle immunoassay and treponema pallidum particle agglutination results are quite prevalent, confirmation by immunoblot assay may be useful [78]. The ARCHITECT syphilis treponema pallidum chemiluminescent immunoassay accurately diagnoses current or past syphilis in pregnancy [79].

The Elecsys immunoassay (Roche Diagnostics) yielded no false-negative results and fewer false-positive results, compared to the other tests [80]. However, Li et al. underlined that the Elecsys® syphilis assay might be confirmed by other treponemal immunoassays [81].

Enders et al. noted that the specificity of the Elecsys syphilis assay in patients with other infections had been 100%; no false-positive samples had been identified [82].

Simčič and Potočnik supported the European Center for Disease Prevention and Control algorithm in the serodiagnosis of syphilis in high-prevalence populations and the use of nontreponemal serology to monitor the response to treatment [83].

Song et al. evaluated diagnostic methods for revealing syphilis in children. False-positive tests for syphilis were higher in the children's group than in the infant's group. The high false-positive rate of enzyme-linked immuno-sorbent assay (ELISA) could be caused by hemolysis. The RPR had low sensitivity in suspected syphilis neonates, and the colloidal gold test (SYP) was suitable for emergency treatment. The treponema pallidum particle agglutination test (TPPA) was fit for the diagnosis of syphilis [84].

It is obvious that further investigations are necessary, and different forms of syphilis need a specific complex of serologic reactions.
