Syphilis in the AIDS era: diagnostic dilemma and therapeutic challenge.

This review argues that syphilis has been underdiagnosed and undertreated, a problem that goes back to the beginning of the Wassermann era, and indeed long before. Non-treponemal tests do not detect the larger pool of persons with latent syphilis, the immunological consequences of which have not been systematically investigated in the context of HIV infection and progression to AIDS. Recent efforts to confirm the prevalence of syphilis in high-risk patients by reverse sequence screening, i.e. using a treponemal test first, as the screening test, have revealed untreated syphilis at higher rates than expected. Further testing using PCR discovered even more previously undetected cases. We suggest that latent syphilis is a chronic active immunological condition that drives the AIDS process and cannot be managed with the older Wassermann-based algorithm, and that non-treponemal tests have failed to associate syphilis with immune suppression since this screening concept was developed in 1906. In light of the overwhelming association between a past history of syphilis and HIV seroconversion, more sensitive tools, including recombinant antigen-based immunological tests and direct detection (PCR) technology, are needed to adequately assess the role of latent syphilis in persons with HIV/AIDS. Repeating older syphilis reinoculation studies may help establish a successful animal model for AIDS, and resolve many paradoxes in HIV science.