Background: Serologic tests for syphilis results at the time of diagnosis are the basis for evaluating response to syphilis therapy. After treatment, however, serologic tests for syphilis titers may continue to increase for several weeks. We evaluated rapid plasma reagin (RPR) titer variation during the 14 days after therapy using data from a recent large, prospective randomized controlled trial.
Methods: Prospectively enrolled participants in North America and Madagascar with primary, secondary, or early latent syphilis were randomly assigned to penicillin, doxycycline (in the case of penicillin allergy), or azithromycin treatment. Blood for RPR analysis was drawn at days 0, 7, and 14 posttreatment. All RPR titers were determined simultaneously at a central laboratory.
Results: Four hundred and seventy patients had data available for at least 2 of 3 RPR measurements. Overall, 20% of patients showed a titer increase of at least 1 dilution in the 14 days after therapy. The greatest proportion of titer increases following therapy was observed in patients with primary syphilis. Comparing outcome of therapy using the initial (day 0) RPR titer versus the maximal RPR titer (during 14 days) resulted in outcome reclassification in 2.98% of participants.
Conclusions: Despite the fact that about 20% of early syphilis patients had increases in RPR titers immediately after treatment, these changes rarely influenced assessment of therapeutic outcome. Only 3% of patients treated would have been reclassified.
From the *Department of Quality Management, Birmingham VA Medical Center, Birmingham, AL; †Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL; ‡Emmes Corporation, Rockville, MD; §Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC; ¶Division of Infectious Diseases, Department of Medicine, Louisiana State University, Baton Rouge, LA; ‖Departments of Medicine and Epidemiology, University of North Carolina at Madagascar, Antananarivo, Madagascar; and **Family Health International, Research Triangle Park, NC
The authors acknowledge the following: Carolyn Deal, PhD, Nancy Padian, PhD, and Peter Wolff, MHA, Sexually Transmitted Infections Clinical Trials Group Executive Committee; Willard Cates, MD, MPH, Myron Cohen, MD, and Walter E. Stamm, MD, Sexually Transmitted Diseases Clinical Trials Unit Executive Committee; Emil Gotschlich, MD, Kenyon Burke, EdD, Helen Lee, PhD, Larry Moulton, PhD, and Peter Rice, MD, Data Safety and Monitoring Board; Lihan Yan, Melinda Tibbals, Robin Cessna, Carol Smith, and Jamie Winestone, EMMES Corporation; Nincoshka Acevedo, BS, Florence Carayon, MA, and Jill Stanton, BA, Family Health International; Carol Langley, MD, Janet N. Arno, MD, IN University School of Medicine; Tomay Mroczkowski, MD, Stephanie Taylor, MD, Barbara Smith, RN, LA State University; Carolyn Deal, PhD, Penny Hitchcock, DVM, Barbara Saverese, RN, Peter Wolff, MHA, National Institutes of Allergy and Infectious Disease; Joan Stephens, RN, Anna Lee Hughes, RN, Tracey Burkett, CRNP, Connie Lenderman, MT (ASCP), MBA, Paula B. Dixon, Grace Daniels, and Sharron Hagy, University of Alabama at Birmingham/Jefferson County Department of Health; Heidi Swygard, MD, Karen Lau, FNP, Christopher Bernart, PA, University of North Carolina at Chapel Hill; Bodo Sahondra Randrianasolo, MD, Mbolatiana Soanirina, MD, Michèle Raharinivo, Felasoa Noroseheno Ramiandrisoa, MD, Ny Lovaniaina Rabenja, MD, Herinjaka Andrianasolo, Roméo Rakotomanga, Tahiana Rasolomahefa, Norbert Ratsimbazafy, MD, Zo Fanantenana Raharimanana, MD, Verolanto Ramaniraka, MD, Marina Rakotonirina, Tiana Ravelohanitra, Andrianiseta Rakotomihanta, Jacqueline Hortensia Rajaonarison, Lucienne Rasoamanana, Elyse Rasoanijanahary, Charlotte Razanasolonambinina, Olivier Claret Raoelina, MD, Naina Ranaivo, MD, Angele Zanatsoa, Claire Fety, Cynthai Mamy, Bruno Raoelina, Esther Solovavy, Justine, Julienne Rasoamarovavy, Diana Ratsiambakaina, MD, Agnè Ramaroson, MD, Theodosie Tombo, David Noelimanana, Florence Raeliarisoa, Gilbert Razaka Sadiry, Bacar Soumaely, Bernard, Justin Ranjalahy Rasolofomanana, Lala Rakotondramasy, Falimanantsoa Sylvain Ramandiarivony, Hobitiana Rakotoarimanan, Lucie Razanamiandrisoa, University of North Carolina-Madagascar; Jocelyne Andriamiadana, MD, USAID Madagascar; and Institut Pasteur de Madagascar, The Ministry of Health, Madagascar.
Supported by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (grant number N01 A1 75329, Myron Cohen, MD, PI) and the STI Clinical Trials Group (grant number HHSN 26620040073C, Edward W. Hook, III, MD, PI).
Potential Conflicts of Interest: K.H., M.W., A.S., F.B., K.V.D, L.M., and M.G. declare no conflict of interest. D.M. is a share holder in Merck and has been a consultant to Cempra Pharma. P.L. has received research funding from GSK, Abbott Diagnostics, Norvartis and Trinity Diagnostics and has been on the speakers' bureaus for GSK, Norvartis and Abbott Diagnostics. E.W. has received research funding from GenProbe, Becton-Dickinson, Roche Molecular Diagnostics, Siemens Diagnostics, and has been on the speakers' bureaus for GSK, Norvartis and Abbott Diagnostics.
Correspondence: Katherine M. Holman, MD, Division of Infectious Diseases, University of Alabama at Birmingham, 1900 University Blvd THT 229, Birmingham, AL 35294. E-mail: email@example.com; or Edward Hook, III, MD, Division of Infectious Diseases, University of Alabama at Birmingham, 1900 University Blvd THT 229, Birmingham, AL 35294. E-mail: firstname.lastname@example.org.
Received for publication January 9, 2012, and accepted February 29, 2012.