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Use of Treponema pallidum PCR in Testing of Ulcers for Diagnosis of Primary Syphilis1 - Volume 21, Number 1—January 2015 - Emerging Infectious Disease journal - CDC

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Use of Treponema pallidum PCR in Testing of Ulcers for Diagnosis of Primary Syphilis1 - Volume 21, Number 1—January 2015 - Emerging Infectious Disease journal - CDC


Volume 21, Number 1—January 2015


Use of Treponema pallidum PCR in Testing of Ulcers for Diagnosis of Primary Syphilis1

Angèle Gayet-AgeronComments to Author , Patrice Sednaoui, Stephan Lautenschlager, Tristan Ferry, Laurence Toutous-Trellu, Matthias Cavassini, Fatima Yassir, Begoña Martinez de Tejada, Stéphane Emonet, Christophe Combescure, Jacques Schrenzel, and Thomas Perneger
Author affiliations: University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland (A. Gayet-Ageron, L. Toutous-Trellu, B. Martinez de Tejada, S. Emonet, C. Combescure, J. Schrenzel, T. Perneger)Institut Alfred Fournier, Paris, France (P. Sednaoui)Triemlispital, Zurich, Switzerland (S. Lautenschlager)Hospices civils de Lyon, Lyon, France (T. Ferry, F. Yassir)Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland (M. Cavassini)


Treponema pallidum PCR (Tp-PCR) has been noted as a valid method for diagnosing syphilis. We comparedTp-PCR to a combination of darkfield microscopy (DFM), the reference method, and serologic testing in a cohort of 273 patients from France and Switzerland and found the diagnostic accuracy of Tp-PCR was higher than that for DFM.
Incidence of syphilis, caused by Treponema pallidum, has increased steadily worldwide since the early 2000s, especially in at-risk populations (1). The US Centers for Disease Control and Prevention (CDC) recently updated the definitions for confirmed cases of primary and secondary syphilis and now considers Treponema pallidumPCR (Tp-PCR) to be a valid diagnostic method along with darkfield microscopy (DFM) (2), which is still considered the reference test (although it remains imperfect) (3). In diagnosis of sexually transmitted ulcerative disease, a positive DFM result confirms syphilis because other T. pallidum subspecies are not sexually transmitted and have a different geographic distribution. However, the meaning of a negative DFM result is more uncertain. Samples from up to 20% of case-patients with syphilis may show negative DFM results when the test is performed by technicians who are not fully trained or when it is performed in suboptimal conditions (3). Tp-PCR is clinically useful for testing of ulcers or skin lesions in areas where syphilis prevalence is high (4), but uncertainties remain because of the variability in the reference tests used in the different diagnostic studies. Moreover, the risk for misclassification by DFM diminishes the apparent value of Tp-PCR when DFM is the reference test because samples from syphilis patients that yield a negative DFM result, but a positive Tp-PCR result, are currently considered false-positive.
We conducted a multicenter study in France and Switzerland to evaluate the accuracy of Tp-PCR compared with DFM and serologic testing. To resolve the difficulty of assessing a new diagnostic test against an imperfect standard, in addition to the standard DFM diagnostics, we used an enhanced definition for the diagnosis of syphilis that combines clinical information with DFM, serologic testing, or both, to enable a fair assessment to be made of the diagnostic performance of Tp-PCR.

Dr. Gayet-Ageron is a medical doctor and researcher in the Division of Clinical Epidemiology and Infection Control Program of the University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland. Her primary research interest is epidemiology and clinical research in the field of infectious diseases.


We thank Rosemary Sudan for editorial assistance; Gisela Getaz-Jimenez and Manuela Tangomo for performing the Tp-PCR; Deolinda Alves, Nadia Mzoughi, and Chrystelle Chapolard for help with data collection; and Bernard Hirschel and Béatrice Ninet for their advice concerning the study design. We also thank Fatiha Abed, Juan Ambrosioni, Caroline Barde, Philippe Brossard, Alexandra Calmy, Laura Ciaffi, Basile Darbellay, Donato Ferrara, Telma Maria Fok Lee Da Silva, Emmanuelle Grau, Caroline Huber, Olivier Julen, Emmanuel Laffitte, Marthe Thanh Lecompte, Damjan Nikolic, Frédéric Poffet, Sandrine Quenan, Maral Sahil, Manuel Schibler, Florence Theintz, Béatrice Trigona, Diem-Lan Vu-Cantero, Nasstasja Wassilew, C. Chapuis-Taillard, Olivier Clerc, François-Régis Duss, Laurence Feldmeyer, Stefano Giulieri, Manuel Joccallaz, I. Luchsinger, R. Kasper, Vera König, D. Reinhardt, and M. Sigg for their voluntary support regarding the recruitment of patients or their help in study implementation.
Financial support for this study was provided by the Research and Development Fund of the University of Geneva Hospitals (4-2012-II).


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Technical Appendix

Suggested citation for this article: Gayet-Ageron A, Sednaoui P, Lautenschlager S, Ferry T, Toutous-Trellu L, Cavassini M, et al. Use of Treponema pallidumPCR in testing of ulcers for diagnosis of primary syphilis. Emerg Infect Dis [Internet]. 2015 Jan [date cited]. http://dx.doi.org/10.3201/eid2101.140790
DOI: 10.3201/eid2101.140790
1Preliminary results from this study were presented at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy, September 10–13, 2013, Denver, Colorado, USA.

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