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  • • Serologic tests for syphilis are the most common means for diagnosis of syphilis and the best currently available tool for evaluating response to therapy.
  • • Serologic diagnosis of past or present syphilis infection is based on the results of two tests: a reactive nontreponemal serologic test for syphilis, confirmed by a test for syphilis based on unrelated treponemal antigens.
  • • Testing may be complicated by atypical immunologic responses by cross-reactive antibodies leading to false-positive test results, and by difficulties in distinguishing current from past infection.

Syphilis is a chronic sexually transmitted disease (STD) with worldwide prevalence. From the time of acquisition of infection until diagnosis, the course of untreated infection may span decades. At any point in its natural history, a diagnosis of untreated syphilis warrants treatment. Although the causative organism, Treponema pallidum, may be demonstrated using darkfield microscopy during its earliest (primary and secondary) stages, this test is not useful for diagnosis except in the early stages of disease. Equally important, darkfield microscopy is often not performed even when lesions are present because a microscope equipped with a darkfield condenser is rarely available in the settings where patients with syphilis are seen. As a result, most syphilis diagnosis, as well as follow-up to ascertain response to therapy, is carried out using serologic tests for syphilis. The practical utility of serologic testing may be complicated by atypical immunologic responses by cross-reactive antibodies leading to false-positive test results, and by difficulties in distinguishing current from past infection.

Serologic tests for syphilis become reactive early in the course of untreated infection as infected individuals begin to produce antibodies to T pallidum. It is estimated that up to 10% of patients with syphilitic chancres of primary syphilis will have nonreactive serologic tests for syphilis, most of which occur in the first few days following appearance of the lesion. After primary lesions have been present for several days, the likelihood of nonreactive serologic tests declines markedly. Over the course of untreated infection, serologic titers tend to rise and then may fall, reflecting disease activity and duration of infection. Nearly all patients with untreated secondary or early latent syphilis will have reactive serologic tests. With continuing infection and production of anti—T pallidum antibodies, serologic titers tend to increase. Thus, patients with primary syphilis tend to have somewhat lower serologic titers than those with secondary or early latent infection.

After rising over the first few years of untreated infection (ie, from primary through secondary and into the latent stage), serologic titers peak and then may decline gradually over time. Although serologic titers may roughly reflect duration of infection, there is far too much person-to-person variation in antitreponemal antibody production to allow currently available serologic test titers to be considered as precise reflections of duration of infection. Studies done more than 50 years ago suggested that a small (but poorly quantified) proportion of individuals with untreated late latent or late syphilis will have ...

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