The explosive increase in syphilis throughout China and Russia during the past several decades represents a global public health threat for several reasons. 1) Most cases are undertreated and thus collectively offer optimal conditions for the emergence of resistant strains of the syphilis spirochete, Treponema pallidum. No penicillin-resistant strains have been recognized to date, but strains resistant to the second line antibiotic agents are now common. 2) The recent discovery of plasmids in T. pallidumraises the likelihood of plasmid transfer from other bacteria of various resistance genes, especially those directed toward penicillin-type antibiotics, currently the drugs of choice for syphilis. 3) Compounding the public health threat is the absence of antibiotic successors to penicillin. The development new antibiotics would take more than a decade, hence the concern for interim measures to treat any emergent multi-resistant strains. Pre-antibiotic treatment of syphilis involved two mechanisms -- 1) agents which are directly toxic to T. pallidum, such as heavy metals and 2) fever induction in patients which reduces spirochetal survival, such as malariotherapy and bacterial pyrogens. The appearance of multi-drug resistant strains of syphilis in the absence of effective antibiotic therapy may require reviving and improving upon treatments used previously.
Ambrose, Charles T., "Pre-Antibiotic Therapy of Syphilis" (2016). Microbiology, Immunology, and Molecular Genetics Faculty Publications. 83.