Correspondence
Treatment of Early Syphilis
N Engl J Med 1997; 337:1697-1698December 4, 1997
- Article
To the Editor:
Rolfs and coworkers (July 31 issue)1 convincingly demonstrated that Treponema pallidum invades the central nervous system in at least one fourth of persons with early syphilis regardless of their status with respect to human immunodeficiency virus (HIV) infection. In addition, they adequately demonstrated that serologically defined treatment failure did not reflect early clinically defined treatment failure. Their study did not, however, address the long-term neurologic sequelae, which usually take from 15 to 25 years to occur.2 The purpose of using a treatment regimen such as amoxicillin and probenecid is not to increase the likelihood that acute symptoms will resolve with or without serologic resolution, an outcome that multiple studies have shown occurs with or without therapy.3 Rather, the purpose of penetrating the central nervous system with an appropriate antibiotic is to prevent long-term neurologic sequelae that, even in HIV-infected patients, cannot be predicted in a study with only a one-year follow-up period. The most valid way to compare the efficacy of penicillin G benzathine with that of any other antibiotic would be to employ a much longer follow-up period. An alternative would be to follow the decay of T. pallidum in the central nervous system, as could have been done for the four patients in this study who continued to have evidence of residual T. pallidum in their central nervous systems after treatment.
3 ReferencesLori Fantry, M.D., M.P.H.
Edmund C. Tramont, M.D.
University of Maryland Medical Center, Baltimore, MD 212011
Rolfs RT ,Joesoef MR ,Hendershot EF , et al. A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. N Engl J Med 1997;337:307-314
Full Text | Web of Science | Medline2
Hook EW ,Marra CM . Acquired syphilis in adults. N Engl J Med 1992;326:1060-1069
Full Text | Web of Science | Medline3
Hart G . Syphilis tests in diagnostic and therapeutic decision making. Ann Intern Med 1986;104:368-376
Web of Science | Medline
To the Editor:
In the study by Rolfs et al., 40 patients received incidental antibiotics effective against T. pallidum after the study therapy for early syphilis. Serologically defined treatment failure was less likely to occur and the mean decrease in the rapid plasma reagin titer was greater in those who received incidental antibiotics. In contrast, serologically defined treatment failure was no more likely to occur among patients who had T. pallidum detected in their pretreatment cerebrospinal fluid samples. T. pallidum was detected more commonly when the white-cell count in the cerebrospinal fluid was elevated but not when the protein content was elevated or when the Venereal Disease Research Laboratory test on the cerebrospinal fluid was reactive. Although study investigators may not have had access to the results of tests in which T. pallidum was detected in cerebrospinal fluid, they did have access to the results of conventional cerebrospinal fluid analyses. How many subjects were treated for neurosyphilis on the basis of cerebrospinal fluid abnormalities? Specifically, was there an association between these abnormalities, including the presence of T. pallidum in the cerebrospinal fluid, and incidental antibiotic use? Such an association might confound the assessment of the relation between the detection of T. pallidum in cerebrospinal fluid and the outcome of treatment in this study.
Christina M. Marra, M.D.
University of Washington, Seattle, WA 98104-2499Author/Editor Response
The authors reply:
To the Editor: We agree with Drs. Fantry and Tramont that the effect on late neurologic sequelae of the enhanced amoxicillin regimen used in our study cannot be adequately evaluated on the basis of one year of follow-up. That was not the primary goal of our study, however. The study was prompted primarily by reported complications of syphilis — in particular, early manifestations of neurosyphilis. The implication of those reports was that neurologic complications occurred within a few months after treatment for early syphilis in HIV-infected patients.1-3 Our study was designed primarily to identify the risks of those complications and assess the effectiveness of the enhanced regimen for preventing them. The absence of those early complications in this study population suggests that they are not common.
Our study also provided evidence that the enhanced regimen we studied will not produce better outcomes than those obtained with usual therapy. Differences in serologic response were found between HIV-infected and HIV-uninfected patients but not between the two treatment regimens. We also found evidence of T. pallidum in cerebrospinal fluid after therapy both in patients who had received the usual therapy and in those who had received the enhanced therapy (and in HIV-infected and uninfected patients). The presence of T. pallidum in cerebrospinal fluid after therapy might indicate the patients who are at greatest risk for the later development of neurosyphilis. As suggested, however, longer follow-up would be needed to determine the clinical relevance of that finding. The small number of subjects, the difficulty of maintaining contact with them, and the clinical decisions to provide additional treatment all limited our ability to address that issue.
In response to Dr. Marra's question, incidental antibiotics were not more commonly received by patients in whom T. pallidum had been detected or in those who had abnormal results on usual cerebrospinal fluid tests before treatment. The incidental receipt of antibiotics did not confound the relation between the detection of T. pallidum and the treatment outcomes.
3 ReferencesRobert T. Rolfs, M.D.
Utah Department of Health, Salt Lake City, UT 84114-2875Justin D. Radolf, M.D.
University of Texas Southwestern Medical Center, Dallas, TX 75235Michael H. Augenbraun, M.D.
State University of New York Health Science Center at Brooklyn, Brooklyn, NY 11203M. Riduan Joesoef, M.D., Ph.D.
Centers for Disease Control and Prevention, Atlanta, GA 303331
Musher DM . Syphilis, neurosyphilis, penicillin, and AIDS. J Infect Dis 1991;163:1201-1206
CrossRef | Web of Science | Medline2
Katz DA ,Berger JR . Neurosyphilis in acquired immunodeficiency syndrome. Arch Neurol 1989;46:895-898
Web of Science | Medline3
Bayne LL ,Schmidley JW ,Goodin DS . Acute syphilitic meningitis: its occurrence after clinical and serologic cure of secondary syphilis with penicillin G. Arch Neurol 1986;43:137-138
Web of Science | Medline
