Syphilis is caused by the spirochete Treponema pallidum and is most often acquired by sexual contact. It is rarely transmitted by transfusion. Although numerous cases of transfusion-transmitted syphilis were reported before World War II, no cases have been reported in the United States in more than 40 years.

Donor screening for syphilis has been performed for almost 80 years. Most reactive donor test results reflect either biologic false-positive results or persistent antibody in previously treated individuals and do not represent infectious syphilis. In the past, donors were initially screened by nontreponemal serologic tests that detect antibody to cardiolipin [eg, rapid plasma reagin (RPR)]. In recent years, tests that detect specific antibodies to T. pallidum have largely replaced the RPR because these tests can be performed with automated testing instruments.