American Board of Internal Medicine (ABIM) Certification Practice Exam

In cases of primary infection of syphilis, how might the results of nonspecific tests typically appear?

1. Always negative

2. Typically positive

3. Negative initially then positive later

4. Positive at lower titers

The correct answer is: Always negative

In primary syphilis, the results of nonspecific serological tests, such as the rapid plasma reagin (RPR) or the Venereal Disease Research Laboratory (VDRL) tests, often are not sensitively reactive during the earliest stages of the infection. This means that these tests can appear negative initially, particularly because the body may not have developed enough antibodies to produce a positive result right after the initial infectious exposure. Unlike specific tests that directly identify Treponema pallidum, the causative agent of syphilis, nonspecific tests are more dependent on the immune response of the host. In many primary infections, it can take some time for the immune system to respond sufficiently to be detected by these nonspecific tests, which explains why they may initially show negative results. Over time, as the infection progresses, these nonspecific tests may become positive, reflecting the body’s developing immune response to the infection, but during the very early phase of primary syphilis, it is common for these tests to not identify the disease, leading to negative results.