Current standards for diagnosis of syphilis: comparing the russian and foreign guidelines (part I)

Cover Page

Cite item


Despite the abundance of existing laboratory methods the diagnosis of syphilis still faces many challenges. Though direct detection of T. pallidum plays an important role in early manifest forms of the disease, serological tests remain the mainstay of diagnosis. Traditional syphilis screening algorithm based on nontreponemal tests with subsequent confirmation using treponemal tests is a standard worldwide. Recently, the ability to automate the treponemal tests promotes the increasingly widespread implementation of reverse algorithm when these tests are used for syphilis screening. None of the current serological algorithms are able to reliably differentiate between active and previously treated syphilis, which causes uncertainty in the management of patients. There is no «gold standard» for the diagnosis of neurosyphilis, ocular, auricular and visceral syphilis. The interpretation of serological tests in children born to seropositive mothers is also complicated. Diagnosis of congenital syphilis in newborns and, consequently, the prescription of antibiotic therapy often depends on assessment of the adequacy of maternal treatment during pregnancy, which leads to subjective decisions. This article provides a comparative analysis of the «Federal guidelines for the management of patients with syphilis» and their foreign analogues, discusses significant peculiarities of these guidelines and reviews current concerns and controversies in syphilis diagnosis.

About the authors

T. V. Krasnoselskikh

First Pavlov State Medical University

Author for correspondence.
Russian Federation

E. V. Sokolovskiy

First Pavlov State Medical University

Russian Federation


  1. Федеральные клинические рекомендации по ведению больных сифилисом. М., 2013. 40.
  2. French P., Gomberg M., Janier M. at al. IUSTI: 2008 European Guidelines on the Management of Syphilis. Int J. STD AIDS, 2009; 20 (5): 300-309.
  3. Workowski K.A., Berman S. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recommendations and Reports, 2010; 59 (RR-12).
  4. Janier M., Hegyi V., Dupin N. et al. 2014 European guideline on the management of syphilis. J. Eur Acad Dermatol Venereol, 2014; 28 (12): 1581-1593.
  5. Draft for Public Comment Version: Sexually Transmitted Diseases Treatment Guidelines, 2014. Centers for Disease Control and Prevention [Official website]. Access mode:
  6. Wheeler H.L., Agarwal S., Goh B.T. Dark ground microscopy and treponemal serological tests in the diagnosis of early syphilis. Sex Transm Infect, 2004; 80 (5): 411-414.
  7. Grange P.A., Gressier L., Dion P.L. et al. Evaluation of a PCR test for detection of Treponema pallidum in swabs and blood. J. Clin Microbiol, 2012; 50 (3): 546-552.
  8. Гущин А.Е., Фриго Н.В., Дударева Л.А. и др. Перспективы применения полимеразной цепной реакции в диагностике ранних форм сифилиса. Вестн. дерматол. венерол., 2009; (1): 46-51.
  9. Ballard R., Hook E.W. III. Syphilis. In: Unemo M., Ballard R., Ison C., Lewis D., Ndowa F., Peeling R., eds. Laboratory diagnosis of sexually transmitted infections, including human immunodeficiency virus. World Health Organization (WHO), Geneva, Switzerland, 2013: 107-129.
  10. Liu H., Rodes B., Chen C.Y., Steiner B. New tests for syphilis: rational design of a PCR method for detection of Treponema pallidum in clinical specimens using unique regions of the DNA polymerase I gene. J Clin Microbiol, 2001, 39 (5): 1941-1946.
  11. Gayet-Ageron A., Ninet B., Toutous-Trellu L. et al. Assessment of a real time PCR to diagnose syphilis from diverse biological samples. Sex Transm Infect, 2009; 85 (4): 264-269.
  12. Gayet-Ageron A., Lautenschlager S., Ninet B. et al. Sensitivity, specificity and likelihood ratios of PCR in the diagnosis of syphilis: a systematic review and meta-analysis. Sex Transm Infect, 2013; 89 (3): 251-256.
  13. Buffet M., Grange P.A., Gerhardt P. et al. Diagnosing Treponema pallidum in secondary syphilis by PCR and immunohistochemistry. J Invest Dermatol, 2007; 127 (10): 2345-2350.
  14. Müller H., Eisendle K., Brauninger W. et al. Comparative analysis of immunohistochemistry, polymerase chain reaction and focus-floating microscopy for the detection of Treponema pallidum in mucocutaneous lesions of primary, secondary and tertiary syphilis. Br J Dermatol, 2011; 165 (1): 50-60.
  15. Родионова Е.Н., Гущин А.Е., Шипулин Г.А. и др. Выявление ДНК и РНК T. pallidum в клиническом материале у пациентов с различными стадиями сифилиса. Журн. микробиол. эпидемиол. иммунобиол., 2003; (3): 43-50
  16. Фриго Н.В., Лесная И.Н., Кубанов А.А. и др. Основные направления развития диагностических технологий в дерматовенерологии. Вестн. дерматол. венерол., 2010; (5): 35-44
  17. Hoang M.P., High W.A., Molberg K.H. Secondary syphilis: a histologic and immunohistochemical evaluation. J Cutan Pathol, 2004; 31 (9): 595-599.
  18. Hook E.W. 3rd, Roddy R.E., Lukehart S.A. et al. Detection of Treponema pallidum in lesion exudate with a pathogen-specific monoclonal antibody. J Clin Microbiol, 1985; 22 (2): 241-244.
  19. Peng R.R., Wang A.L., Li J. et al. Molecular typing of Treponema pallidum: a systematic review and meta-analysis. PLoS Negl Trop Dis, 2011; 5 (11): e1273.
  20. Ho E.L., Lukehart S.A. Syphilis: using modern approaches to understand an old disease. J Clin Invest, 2011; 121 (12): 4584-4592.
  21. Сидоренко С.В., Соломка В.С., Кожушная О.С., Фриго Н.В. Методы типирования возбудителей инфекций, передаваемых половым путем (N. gonorrhoeae, C. trachomatis, T. pallidum). Вестн. дерматол. венерол., 2010; (3): 12-21
  22. Marra C.M., Sahi S.K., Tantalo L.C. et al. Enhanced molecular typing of Treponema pallidum: geographical distribution of strain types and association with neurosyphilis. J Infect Dis, 2010; 202 (9): 1380-1388
  23. Фриго Н.В., Ротанов С.В., Манукьян Т.В. и др. Лабораторная диагностика сифилиса: вчера, сегодня, завтра. Вестн. дерматол. венерол., 2012; (4): 16-23
  24. Ratnam S. The laboratory diagnosis of syphilis. Can J Infect Dis Med Microbiol, 2005; 16 (1): 45-51. 22 к № 2, 2015
  25. Кубанова А.А., Фриго Н.В., Ротанов С.В. и др. Современные направления и перспективы развития лабораторной диагностики инфекций, передаваемых половым путем. Вестн. дерматол. венерол., 2011; (5): 54-6
  26. Castro A., Jost H., Cox D. et al. A comparison of the analytical level of agreement of nine treponemal assays for syphilis and possible implications for screening algorithms. BMJ Open, 2013; 3 (9): e003347
  27. Фриго Н.В., Манукьян Т.Е., Ротанов С.В., Катунин Г.Л. Диагностика ранних форм сифилиса методом иммунохемилюминесценции. Вестн. дерматол. венерол., 2013; (6): 66-72
  28. Кубанова А.А., Фриго Н.В., Ротанов С.В. и др. Опыт использования метода иммуноблоттинга для диагностики сифилиса. Вестн. дерматол. венерол., 2006; (2): 4-11
  29. Марданлы Cl., Арсеньева В.А., Фриго Н.В. и др. Применение тест-системы «Лайн-Блот Сифилис» в диагностике сифилиса методом линейного иммуноблоттинга. Вестн. дерматол. венерол., 2011; (3): 80-87
  30. Paris-Hamelin A., Debruyne M., Fustec-Isarboure S. Immunoblotting for the serodiagnosis syphilis. A candidate to replace the Nelson-Mayer test. Ann Pharm Fr, 1999; 57 (1): 68-75
  31. Sambri V., Marangoni A., Eyer C. et al. Western immunoblotting with five Treponema pallidum recombinant antigens for serologic diagnosis of syphilis. Clin Diagnost Lab Immunol, 2001; 8 (3): 534-539
  32. Ротанов С.В., Эрматова Ф.А. Информативность трепонемоспецифических антител класса M при диагностике сифилиса. Вестн. дерматол. венерол., 2013; (3): 48-55
  33. Schmid G.P., Stoner B.P., Hawkes S., Broutet N. The need and plan for global elimination of congenital syphilis. Sex Transm Dis, 2007; 34 (7 Suppl): S5-10.
  34. Herring A.J., Ballard R.C., Pope V. et al. A multicentre evaluation of nine rapid, point-of-care syphilis tests using archived sera. Sex Transm Infect, 2006; 82 (Suppl 5): v7-12.
  35. Ротанов С.В., Османова С.Р. Иммунохроматографические методы определения антител к антигенам Treponema pallidum. Вестн. дерматол. венерол., 2011; (4): 20-24
  36. Binnicker M.J., Jespersen D.J., Rollins L.O. Direct Comparison of the traditional and reverse syphilis screening algorithms in a population with a low prevalence of syphilis. J Clin Microbiol, 2012; 50 (1): 148-150.
  37. Sena A.C., White B.L., Sparling P.F. Novel Treponema pallidum serologic tests: a paradigm shift in syphilis screening for the 21st century. Clin Infect Dis, 2010; 51 (6): 700-708.
  38. Rolfs R.T., Joesoef M.R., Hendershot E.F. 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 (5): 307-314.
  39. Marra C.M., Maxwell C.L., Smith S.L. et al. Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features. J Infect Dis, 2004; 189 (3): 369-376.
  40. Luger A.F., Schmidt B.L., Kaulich M. Significance of laboratory findings for the diagnosis of neurosyphilis. Int J STD AIDS, 2000; 11 (4): 224-234.
  41. Hooshmand H., Escobar M.R., Kopf S.W. Neurosyphilis. A study of 241 patients. JAMA, 1972; 219 (6): 726-729.
  42. Castro R., Prieto E.S., da Luz Martins Pereira F. Nontreponemal tests in the diagnosis of neurosyphilis: an evaluation of the Venereal Disease Research Laboratory (VDRL) and the Rapid Plasma Reagin (RPR) tests. J Clin Lab Anal, 2008; 22 (4): 257-261.
  43. Ghanem K.G., Moore R.D., Rompalo A.M. et al. Neurosyphilis in a clinical cohort of HIV 1 infected patients. AIDS, 2008; 22 (10): 1145-1151
  44. Levchik N., Ponomareva M., Surganova V. et al. Criteria for the diagnosis of neurosyphilis in cerebrospinal fluid: relationships with intrathecal immunoglobulin synthesis and blood-cerebrospinal fluid barrier dysfunction. Sex Transm Dis, 2013; 40 (12): 917-922.
  45. Rawstron S.A., Mehta S., Marcellino L. et al. Congenital syphilis and fluorescent treponemal antibody test reactivity after the age of 1 year. Sex Transm Dis, 2001; 28 (7): 412-416.
  46. Herremans M., Notermans D.W., Mommers M., Kortbeek L.M. Comparison of a Treponema pallidum IgM immunoblot with a 19S fluorescent treponemal antibody absorption test for the diagnosis of congenital syphilis. Diagn Microbiol Infect Dis, 2007; 59 (1): 61-66.
  47. Peeling R.W., Ye H. Diagnostic tools for preventing and managing maternal and congenital syphilis: an overview. Bull World Health Organ, 2004; 82 (6): 439-446.
  48. Bromberg K., Rawstron S., Tannis G. Diagnosis of congenital syphilis by combining Treponema pallidum-specific IgM detection with immunofluorescent antigen detection for T. pallidum. J Inf Dis, 1993, 168 (1): 238-242.

Copyright (c) 2015 Krasnoselskikh T.V., Sokolovskiy E.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 60448 от 30.12.2014.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies