Background Syphilis management has traditionally been based on non-treponemal tests (NTT). However, investigations over 3 decades have revealed serious issues with the sensitivity of NTT.

Methods Beginning in the late 1980s, our group in Toronto and Budapest investigated the sensitivity of NTT in over 5000 high-risk gay men, and in an additional 800 men where we could control for HIV status and AIDS. Besides the use of quantified treponemal tests (TT), IgM/IgG screening (in Mardx SDS-PAGE blots), and experimental PCR were employed.

Results The main findings of accelerated screening were undetected and untreated latent cases, not old treated cases as traditionally believed. NTT only detected about 30 percent of cases. Investigators in Houston detected TT IgM in most HIV cases with no NTT reactions, possibly representing latent and chronic cases. Investigators in Vienna showed that aggressive therapy reversed the IgM marker. In Toronto, 557 high risk men were screened with EIA TT and 27 possible latent cases were detected, with negative NTT. 24/27 of these patients had IgM or IgG directed against the main T. pallidum proteins. In the 800 men screened sequentially, TT often dropped in titre or reverted to negative *only* in HIV cases - titres in other routine tests did not drop. Syphilis PCR found that 13/183 gay men screened in Hungary had latent syphilis. The PCR found 9 cases negative in both NTT and TT, and identified the four TPHA (+) treated men.

Conclusion NTT is historically unreliable in relapse or reinfection. Syphilis management should always include TT. Syphilis and HIV have an overwhelming association, yet syphilis is never opportunistic. Latent syphilis may be chronically active in many HIV persons. Th-1 --≥ Th-2 immunoregulation is the norm in untreated syphilis - many longstanding syphilitics have cutaneous anergy to TB and mitogens. We suggest a syphilis IGRA be developed.

Disclosure No significant relationships.