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Edward W. Hook, Editorial Commentary: A Syphilis Wish List: Better Data, Better Tests, Clinical Infectious Diseases, Volume 55, Issue 12, 15 December 2012, Pages 1623–1624, https://doi.org/10.1093/cid/cis766
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(See the Major Article by Kanute et al, on pages 1615–22.)
William Osler referred to syphilis as “The Great Imitator,” referring to the vast array of potential clinical presentations and morbidity associated with syphilis at the beginning of the 20th century. While the infection's varied presentations remain a continuing source of confusion for clinicians, the challenges of syphilis management do not stop with diagnosis. The absence of readily available culture or other direct microbiologic tests for syphilis diagnosis, and the resulting dependence upon serological testing to evaluate response to therapy, regularly creates questions for clinicians.
For better and for worse, serological testing for syphilis diagnosis and monitoring response to therapy has been a mainstay of syphilis management since soon after 1906 when Wassermann and colleagues developed the first serological tests for syphilis [1]. Since then however, evolution of tests, testing methods, reagents, and test formats has not resolved fundamental questions or limitations of currently available tests. Syphilis is no longer common enough to be easily studied at a single institution in the numbers needed to provide conclusive answers to important management questions but it is common enough that questions regularly arise in management of syphilis patients. In the United States, rates of primary and secondary syphilis have been <5 per 100 000 population for >15 years [2] and rates are still lower in Western Europe. Nonetheless, questions regarding serological test interpretation continue to vex clinicians at all stages of syphilis management—diagnosis, staging, and response to therapy. Furthermore, the close links between syphilis and human immunodeficiency virus infection add to concerns because of the theoretical potential for coexistence of the 2 infections to modify the manifestations and management of each other. Common questions include: How long should it take for effective therapy to result in changes of serological tests and titers? Does the response to syphilis vary in persons with human immunodeficiency virus (HIV)? What is the best test for serological follow-up of infection? and What is the clinical significance of test titers that do not change following therapy? Generation of reliable answers to these questions is a challenge. Further, newer assays such as enzyme immunoassays and tests for IgM antibodies to Treponema pallidum likewise [3, 4] are badly in need of study.
