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Potekaev N.N.

Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology;
The Russian National Research Medical University named after N.I. Pirogov

Frigo N.V.

Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology

Dmitriev G.A.

Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology

Kitaeva N.V.

Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology

Dolya O.V.

Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology;
Peoples’ Friendship University of Russia

Gushchin A.E.

Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology

Negasheva E.S.

Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology

Mardanly S.G.

Ecolab, CJCS;
State University of Humanities and Technology

Makhnovskaya T.S.

The Russian National Research Medical University named after N.I. Pirogov

Laboratory diagnosis of syphilis. Current approaches and perspectives. Part II. Indirect (serological) diagnostic methods

Authors:

Potekaev N.N., Frigo N.V., Dmitriev G.A., Kitaeva N.V., Dolya O.V., Gushchin A.E., Negasheva E.S., Mardanly S.G., Makhnovskaya T.S.

More about the authors

Journal: Russian Journal of Clinical Dermatology and Venereology. 2022;21(3): 271‑280

DOI: 10.17116/klinderma202221031271

Read: 6737 times

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Table of contents

LABORATORY DIAGNOSIS OF SYPHILIS. CURRENT APPROACHES AND PERSPECTIVES. PART II. INDIRECT (SEROLOGICAL) DIAGNOSTIC METHODS
LABORATORY DIAGNOSIS OF SYPHILIS. CURRENT APPROACHES AND PERSPECTIVES. PART II. INDIRECT (SEROLOGICAL) DIAGNOSTIC METHODS

To cite this article:

Potekaev NN, Frigo NV, Dmitriev GA, et al. Laboratory diagnosis of syphilis. Current approaches and perspectives. Part II. Indirect (serological) diagnostic methods. Russian Journal of Clinical Dermatology and Venereology. 2022;21(3):271‑280. (In Russ.)
https://doi.org/10.17116/klinderma202221031271

Подписка 2026 Клиническая дерматология и венерология (Russian Journal of Clinical Dermatology and Venereology)
МСФ на ЯМ
Использование инфографики авторами научных работ
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Recommended articles:
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Abstract:

BACKGROUND

Syphilis is a chronic systemic infection caused by T. pallidum. Despite efforts by health authorities to prevent the spread of syphilis, it continues to be reported in many countries around the world, including the Russian Federation. The disease may cause severe consequences such as visceral and congenital syphilis. The disease often has a latent course, which determines the high requirements for laboratory diagnosis.

OBJECTIVE

To address indirect, serologic methods in syphilis diagnosis.

RESULTS

Serological diagnosis of syphilis is still performed using non-treponemal and treponemal tests, which have both advantages and disadvantages. The development of serological diagnostic methods is aimed at automation, non-biased results evaluation, acceleration of laboratory cycles, miniaturizing of test formats, and development of multiplex systems based on recombinant T. pallidum proteins (immunochemiluminescence methods, immunoturbidometry, immunoblotting, flow multiplexing on microparticles, immunochips) with high sensitivity and specificity, as well as the search for new, highly immunogenic, «candidate» T. pallidum antigens and possibilities of noninvasive syphilis diagnosis.

Keywords:

syphilis
serological diagnostic methods
non-treponemal and treponemal tests

Authors:

Potekaev N.N.

Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology;
The Russian National Research Medical University named after N.I. Pirogov

Frigo N.V.

Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology

Dmitriev G.A.

Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology

Kitaeva N.V.

Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology

Dolya O.V.

Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology;
Peoples’ Friendship University of Russia

Gushchin A.E.

Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology

Negasheva E.S.

Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology

Mardanly S.G.

Ecolab, CJCS;
State University of Humanities and Technology

Makhnovskaya T.S.

The Russian National Research Medical University named after N.I. Pirogov

Received:

07.10.2021

Accepted:

28.03.2022

Close metadata

References:

  1. Wassermann A, Neisser A, Bruck C. Eine serodiagnostische reaktion bei Syphilis. Dtsch Med Wochenschr. 1906;32:745-746. 
  2. Harris A, Mahoney JF. Cardiolipin and Purified Lecithin as Reagents in Syphilis Serology. Am J Public Health Nations Health. 1947;37(8):997-1001.
  3. Cardiolipin antigens. Division of Laboratories and Research New York State Department of Health. Bull World Health Organ. 1951;4(2):151-200. 
  4. Shaw Sidney Evaluation of Cardiolipin Antigen in Routine Wassermann Reactions. Br J Vener Dis. 1955;31(2):86-88.  https://doi.org/10.1136/sti.31.2.86
  5. Prikaz Ministerstva zdravoohraneniya Rossijskoj Federacii ot 26.03.01 №87 «O sovershenstvovanii serologicheskoj diagnostiki sifilisa». (In Russ.).
  6. Forrestel Amy K, Kovarik Carrie L, Katz Kenneth A. Sexually Acquired Syphilis. Part 2: Laboratory diagnosis, management, and prevention (2019). Journal of the American Academy of Dermatology. 2020;82(1):17-28.  https://doi.org/10.1016/j.jaad.2019.02.074
  7. Linda Creegan, Heidi M Bauer, Michael C Samuel, Jeffrey Klausner, Sally Liska, Gail Bolan Creegan L. An evaluation of the relative sensitivities of the venereal disease research laboratory test and the Treponema pallidum particle agglutination test among patients diagnosed with primary syphilis. Sex Transm Dis. 2007;34:1016-1018.
  8. Wende RD, Mudd RL, Know JM, & Holder WR. The VDRL slide test in 322 cases of darkfield positive primary syphilis. South Med J. 1971;64,633-634.  https://doi.org/10.1097/00007611-197105000-00030
  9. Rosanna W Peeling, David Mabey, Mary L Kamb, Xiang-Sheng Chen, Justin D Radolf, Adele S Benzaken. Syphilis. Nat Rev Dis Primers. 2017;12; 3:17073. https://doi.org/10.1038/nrdp.2017.73
  10. Centers for Disease Control and Prevention. Syphilis treatment and care. 2015. https://www.cdc.gov/std/syphilis/treatment.htm
  11. Larsen SA, Johnson RE. A Manual of Tests for Syphilis: Diagnostic Tests 9th edn. 1998. https://www.cdc.gov/std/syphilis/manual-1998/chapt1.pdf
  12. Frigo NV. Modern aspects of differential diagnosis of true and false seropositivity of serological tests for syphilis. Vestnik dermatologii i venerologii. 2004; 2:51-54. (In Russ.).
  13. Davis LE, Schmitt JW. Clinical significance of cerebrospinal fluid tests for neurosyphilis. Annals of Neurology. 1989;25(1):50-55.  https://doi.org/10.1002/ana.410250108
  14. Castro R, Prieto ES, 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. Journal of Clinical Laboratory Analysis. 2008;22(4):257-261.  https://doi.org/10.1002/jcla.20254
  15. Kulyash GYu, Sabaev MI, Erko LV, Mardanly SG, Bahilina NV. On the effectiveness and prospects of using the test of the Research Laboratory of Venereal Diseases (VDRL) for the diagnosis of NS in the Russian Federation. Klinicheskaya laboratornaya diagnostika. 2013;3:30-33. (In Russ.).
  16. Geisler WM. The prozone phenomenon in syphilis testing. South Med J. 2004;97(4):327-328.  https://doi.org/10.1097/01.SMJ.0000092571.52330.13
  17. Li-Li Liu, Li-Rong Lin, Man-Li Tong https://doi.org/10.1093/cid/ciu325
  18. Özgür Appak, Mert Manyaslı, Meryem Merve Cengiz, Burak Deliloğlu, Hatice Karaoğlu Asrak, https://doi.org/10.5578/mb.68172
  19. Potekaev SN. Influence of HIV infection on clinical and serological manifestations of syphilis. Management tactics and methods of treatment of patients with HIV infection and syphilis. Medicinskaya pomoshch’. 1993;5:5-59. (In Russ.).
  20. Janier M, Chastang C, Spindler E, Strazzi S, Rabian C, Marcelli A, Morel P. A prospective study of the influence of HIV status on the seroreversion of serological tests for syphilis. Dermatology. 1999;198(4):362-369.  https://doi.org/10.1159/000018149
  21. Peeling RW, Holmes KK, Mabey D, & Ronald A. Rapid tests for sexually transmitted infections (STIs): the way forward. Sex Transm Infect. 2006; 82(5):1-6.  https://doi.org/10.1136/sti.2006.024265
  22. Janier M, Unemo M, Dupin N, Tiplica GS, Potocnik M, Patel R. European guideline on the management of syphilis. J Eur Acad Dermato. Venereol. 2020;35(3):574-588.  https://doi.org/10.1111/jdv.16946
  23. Workowski KA, Bolan GA. Centers for Disease Control & Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recommen. Rep. 2015;64(RR-03):1-137. 
  24. Centers for Disease Control & Prevention. Sexually Transmitted Infections Treatment Guidelines, 2021. https://www.cdc.gov/std/treatment-guidelines/toc.htm
  25. World Health Organisation. WHO guidelines for the treatment of Treponema pallidum (syphilis), 2016. WHO.  https://www.who.int/reproductivehealth/publications/rtis/syphilis-treatment-guidelines/en/
  26. Mardanly SG, Tugolukov AYe, Starovoytova TA, Avdonina VS, Kirdanovskaya OI, Vengerov YuYu. Video-digital system on the basis of «Expert-Lab» for automatic registration of the results of the immune blotting for the diagnosis of syphilis. Vestnik sovremennoy klinicheskoy meditsiny. 2013; 6(4):62-67. (In Russ.).
  27. Mardanly SG, Bahilina NV, Ermolaeva IA, Tugolukov AE, Sorokoletov SM, Starovojtova TA, Vengerov YuYu. Video digital recording of the results of the microprecipitation reaction in the diagnosis of syphilis. Vestnik sovremennoj klinicheskoj mediciny. 2013;6(5):80-83. (In Russ.).
  28. Seung Jun Choi, Yongjung Park, Eun Young Lee, Sinyoung Kim, Hyon-Suk Kim. Comparisons of fully automated syphilis tests with conventional VDRL and FTA-ABS tests. Clin Biochem. 2013;46(9):834-837.  https://doi.org/10.1016/j.clinbiochem.2013.02.008
  29. Osbak K, Abdellati S, Tsoumanis A, Van Esbroeck M, Kestens L, Crucitti T, Kenyon C. Evaluation of an automated quantitative latex immunoturbidimetric non-treponemal assay for diagnosis and follow-up of syphilis: a prospective cohort study. J Med Microbiol. 2017;66(8):1130-1139. https://doi.org/10.1099/jmm.0.000559
  30. Tsuboi M, Nishijima T, Aoki T, Teruya K, Kikuchi Y, Gatanaga H, Oka S. Usefulness of automated latex turbidimetric rapid plasma reagin test for diagnosis and evaluation of treatment response in syphilis in comparison with manual card test: a prospective cohort study. J Clin Microbiol. 2018;56(11): e01003-1018. https://doi.org/10.1128/JCM.01003-18
  31. Sanfilippo AM, Freeman K, Schmitz JL. Comparison of manual and fully automated AIX1000 Rapid Plasma Reagin assays for laboratory diagnosis of syphilis. J Clin Microbiol. 2018;56(8):e00214-18.  https://doi.org/10.1128/JCM.00214-18
  32. Arbefeville S, Lynch M, Ferrieri P. Evaluation of a multiplex fully automated treponemal and nontreponemal (Rapid Plasma Reagin) assay. Am J Clin Pathol. 2019;152:230-236.  https://doi.org/10.1093/ajcp/aqz034
  33. Rourk AR, Litwin CM. Evaluation of the BioPlex 2200 syphilis total screen (IgG/IgM) with reflex to an automated rapid plasma reagin test. J Clin Lab Anal. 2019;33(5):e22878. https://doi.org/10.1002/jcla.22878
  34. Alexander Pyden, Anthony D Kang, Sheryl Amato, Sanjucta Dutta, Gretchen Berg, Stefan Riedel. Evaluation of the Fully Automated AIX1000 Rapid Plasma Reagin System Compared to a Manual Plasma Reagin Testing Method for the Diagnosis of Syphilis. Diagn Microbiol Infect Dis. 2020;97(4): 115081. https://doi.org/10.1016/j.diagmicrobio.2020.115081
  35. Mardanly SG, Arsen’yeva VA. New test system «Line-Blot Syphilis-IgM» for the determination of IgM antibodies to Treponema pallidum by linear immunoblotting. Vestnik sluzhby krovi. 2014;1:44-47. (In Russ.).
  36. Osbak KK, Tsoumanis A, De Baetselier I, Van Esbroek V, Smet H, Kenion CR, Crucitti T. Role of IgM testing in the diagnosis and post-treatment follow-up of syphilis: a prospective cohort study. BMJ Open. 2020;21;10(9): e035838. https://doi.org/10.1136/bmjopen-2019-035838
  37. Young H, Moyes A, Ross JD. Markers of past syphilis in HIV infection comparing Captia Syphilis G anti-treponemal IgG enzyme immunoassay with other treponemal antigen tests. Int J STD AIDS. 1995;6(2):101-104.  https://doi.org/10.1177/095646249500600207
  38. Ballard R, Hook EW, 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. Geneva: World Health Organization (WHO). 2013;107-129. 
  39. Mardanly SG, Shershneva NN, Amelina, Rotanov SV. The significance of the immunofluorescence reaction in the algorithm of modern syphilis diagnosis. Meditsinskiy alfavit. Epidemiologiya i gigiyena. 2018;1(8):62-65. (In Russ.).
  40. Programmno-apparatnyj kompleks «Ekspert-Lab». (In Russ.). https://mma-expo.ru/lab/2016/visitors/presentations/2-2-15.pdf
  41. Biohimicheskij analizator CHEM-7. (In Russ.). https://medtehural.ru/images/ERBA_ERBArus_katalog.pdf
  42. Malm K, Andersson S, Fredlund H, Norrgren H, Biague A, Månsson F, Ballard R, Unemo M. Analytical evaluation of nine serological assays for diagnosis of syphilis. J Eur Acad Dermatol Venereol. 2015;29(12):2369-2376. https://doi.org/10.1111/jdv.13237
  43. Nobuyasu Yukimasa, Keisuke Miura, Yukiko Miyagawa, Kunihiko Fukuchi. Evaluation of new automated syphilis test reagents ‘IMMUNOTICLES AUTO3’ series: performance, biochemical reactivity, and clinical significance. J Infect Chemother. 2015;21(1):1-7.  https://doi.org/10.1016/j.jiac.2014.08.008
  44. Donkers A, Levy HR, Letens-van Vliet A. Syphilis detection using the Siemens ADVIA Centaur Syphilis treponemal assay. Clin Chim Acta. 2014; 433:84-87.  https://doi.org/10.1016/j.cca.2014.01.041
  45. Gomez E, Jespersen DJ, Harring JA, Binnicker MJ. Evaluation of the Bio-Rad BioPlex 2200 Syphilis Multiplex Flow Immunoassay for the Detection of IgM- and IgG-Class Antitreponemal Antibodies. Clinical and Vaccine Immunology. 2010;17(6):966-968.  https://doi.org/10.1128/CVI.00086-10
  46. Mardanly SG, Arsen’yeva VA, Frigo NV, Rotanov SV, Amelina YeA, Zakharov MV. Using the Line Blot Syphilis test system for diagnosing syphilis by the linear immunoblotting method. Vestnik dermatologii i venerologii. 2011;3:80-87. (In Russ.).
  47. Wong EH, Klausner JD, Caguin-Grygiel G, Madayag C, Barber KO, Qiu GC, Liska S, Pandori MW. Evaluation of an IgM/IgG sensitive enzyme immunoassay and the utility of index values for the screening of syphilis infection in a high-risk population. Sex Transm Dis. 2011;38(6):528-532.  https://doi.org/10.1097/OLQ.0b013e318205491a
  48. Chekanova TA, Markelov ML, Manzenyuk IN, Speranskaya AS, Shishova AV, Alekseeva YuA, Sudina AE, Braslavskaya SI, Shipulin GA. Development of an immunochip for separate detection of antibodies to hepatitis C virus. Klinicheskaya laboratornaya diagnostika. 2008;6:25-30. (In Russ.).
  49. Patent RF na izobretenie №2397178/20.08.10. Byul. №23. Markelov ML, CHekanova TA, SHipulin G.A. Diagnosticheskaya test-sistema v formate immunochipa i sposob serologicheskoj differencial’noj diagnostiki sifilisa. Accessed Oct 18, 2021. (In Russ.). https://www.freepatent.ru/patents/2397178
  50. Potekaev NN, Negasheva ES, Savinov GV, Stukolova OA, Karaseva IP, Sudina AE, Markelov ML, Shipulin GA, Dmitriev GA, Frigo NV. Effectiveness of modern methods of diagnosis of neurosyphilis. Opportunities and prospects for the use of VDRL and immunochips. Russian Journal of Clinical Dermatology and Venereology = Klinichaskaya dermatologiya i venerologiya. 2016;6(15):11-22. (In Russ.). https://doi.org/10.17116/klinderma201615611-21
  51. Huang NL, Ye L, Schneider ME, Du YX, Xu YH, Fan LB, Du WD. Development of a novel protein biochip enabling validation of immunological assays and detection of serum IgG and IgM antibodies against Treponema pallidum pathogens in the patients with syphilis. Biosens Bioelectron. 2016;75: 465-471.  https://doi.org/10.1016/j.bios.2015.08.036
  52. Van Voorhis WC, Barrett LK, Lukehart SA, Schmidt B, Schriefer M, Cameron CE. Serodiagnosis of syphilis: antibodies to recombinant Tp0453, Tp92, and Gpd proteins are sensitive and specific indicators of infection by Treponema pallidum. J Clin Microbiol. 2003;41(8):3668-3674. https://doi.org/10.1128/JCM.41.8.3668-3674.2003
  53. Xu M, Xie Y, Jiang C, Xiao Y, Kuang X, Zhao F, Zeng T, Liu S, Liang M, Wang C, Wu Y. A novel ELISA using a recombinant outer membrane protein, rTp0663, as the antigen for serological diagnosis of syphilis. Int J Infect Dis. 2016;43:51-57.  https://doi.org/10.1016/j.ijid.2015.12.013
  54. Long FQ, Zhang JP, Shang GD, Shang SX, Gong KL, Wang QQ. Seroreactivity and immunogenicity of Tp0965, a hypothetical membrane protein of Treponema pallidum. Chin Med J (Engl). 2012;125(11):1920-924. 
  55. Runina AV, Starovojtova AS, Deryabin DG, Gubanov AA. Recombinant protein Tr0965 Treponema pallidum as a candida antigen for serological diagnosis of syphilis. Vestn Ross Akad Nauk. 2016;2(71):109-113. (In Russ.). https://doi.org/10.15690/vramn653
  56. Chuanhao Jiang, Feijun Zhao, Jinhong Xiao,Tiebing Zeng, Jian Yu, Xiaohua Ma, Haiying Wu, Yimou Wu. Evaluation of the recombinant protein TpF1 of Treponema pallidum for serodiagnosis of syphilis. Clin Vaccine Immunol. 2013;20(10):1563-1568. https://doi.org/10.1128/CVI.00122-13
  57. Jiang C, Xiao J, Xie Y, Xiao Y, Wang C, Kuang X, Xu M, Li R, Zeng T, Liu S, Yu J, Zhao F, Wu Y. Evaluation of FlaB1, FlaB2, FlaB3, and Tp0463 of Treponema pallidum for serodiagnosis of syphilis. Diagn Microbiol Infect Dis. 2016;84(2):105-111.  https://doi.org/10.1016/j.diagmicrobio.2015.10.005
  58. Xie Y, Xu M, Wang C, Xiao J, Xiao Y, Jiang C, You X, Zhao F, Zeng T, Liu S, Kuang X, Wu Y. Diagnostic value of recombinant Tp0821 protein in serodiagnosis for syphilis. Lett Appl Microbiol. 2016;62(4):336-343.  https://doi.org/10.1111/lam.12554
  59. Wu N, Li N, Hu L, He J, Li J, Zhao F, Wu Y. Immunogenicity and immunoreactivity of Tp0821 recombinant protein from Treponema pallidum. Mol Med Rep. 2017;16(1):851-856.  https://doi.org/10.3892/mmr.2017.6675
  60. Kubanov A, Runina A, Deryabin D. Novel Treponema pallidum Recombinant Antigens for Syphilis Diagnostics: Current Status and Future Prospects. BioMed Res Int. 2017;2017:12.  https://doi.org/10.1155/2017/1436080
  61. Runina AV, Katunin GL, Filippova MA, Zatevalov AM, Kubanov AA, Deryabin DG. Immunochip for serological diagnosis of syphilis using an expanded panel of recombinant antigens Treponema pallidum. Byulleten’ eksperimental’noj biologii i mediciny. 2018;6:726-731. (In Russ.).
  62. Kara K Osbak, Geert A Van Raemdonck, Martin Dom, Candidate Treponema pallidum biomarkers uncovered in urine from individuals with syphilis using mass spectrometry. Future Microbiol. 2018;13(13):1497-1510. https://doi.org/10.2217/fmb-2018-0182
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