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Before the advent of serological tests for syphilis, the disease was difficult to diagnose. When Wasserman, Hinton, and others developed their serological tests, the diagnostic problem was simplified. With the development of Reiter protein complement fixation (RPCF), fluorescent treponemal antibody (FTA), Treponema pallidum immobilization (TPI), and fluorescent treponemal antibodyabsorption (FTA-ABS) tests, both the specificity and sensitivity have been greatly improved. What is most conclusive, however, is the demonstration of Treponema pallidum, not only during the early stages but also at the late stage of the disease. With the advent of penicillin, treatment of syphilis has become a simple matter. Nowadays, syphilis is considered as just another infectious disease, no longer taught separately as "syphilology."
Nonetheless, in this book, J. L. Smith takes the opposite view: syphilis is now both hard to diagnose and hard to treat.
Section 1 of the book reviews the problem of late seronegative (by reaginic tests)
Chang T. Spirochetes in Late Seronegative Syphilis, Penicillin Notwithstanding.. Arch Intern Med. 1970;126(3):534. doi:10.1001/archinte.1970.00310090164041