2014 European guideline on the management of syphilis

Journal of the European Academy of Dermatology and Venereology

Volumn 28, Issue 12, 2014, Pages 1581-1593

  Janier, M ^a   Hegyi, V ^b   Dupin, N ^c   Unemo, M ^d   Tiplica, G S ^e   Potocnik M ^f   French, P ^g   Patel, R ^h  

^a SAINT JOSEPH HOSPITAL   (France)

^b Faculty of Natural Sciences   (Slovakia)

^c Institut Cochin   (France)

^d ÖREBRO UNIVERSITY HOSPITAL   (Sweden)

^e CAROL DAVILA UNIVERSITY OF MEDICINE AND PHARMACY   (Romania)

^f UNIVERSITY MEDICAL CENTRE LJUBLJANA   (Slovenia)

^g UNIVERSITY COLLEGE LONDON   (United Kingdom)

^h ROYAL SOUTH HANTS HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; AZITHROMYCIN; BENZATHINE PENICILLIN; CEFTRIAXONE; DOXYCYCLINE; PENICILLIN G; PROCAINE; PROCAINE PENICILLIN;

ANAPHYLACTIC SHOCK; ARTICLE; BLEEDING DISORDER; CONGENITAL SYPHILIS; CONTACT EXAMINATION; EUROPE; FALSE NEGATIVE RESULT; FOLLOW UP; HERXHEIMER REACTION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOHISTOCHEMISTRY; LABORATORY DIAGNOSIS; LABORATORY TEST; NEUROSYPHILIS; PARENTERAL DRUG ADMINISTRATION; PENICILLIN ALLERGY; PRACTICE GUIDELINE; PREGNANCY; SCREENING TEST; SECONDARY SYPHILIS; SEROLOGY; SEXUALITY; SUDDEN DEAFNESS; SYPHILIS; SYPHILIS SEROLOGY; TREATMENT DURATION; TREATMENT REFUSAL; TREPONEMA PALLIDUM; HOSPITAL INFORMATION SYSTEM; ISOLATION AND PURIFICATION; POLYMERASE CHAIN REACTION;

ANTI-BACTERIAL AGENTS; EUROPE; HUMANS; PENICILLIN G BENZATHINE; POINT-OF-CARE SYSTEMS; POLYMERASE CHAIN REACTION; PRACTICE GUIDELINES AS TOPIC; SYPHILIS; TREPONEMA PALLIDUM;

EID: 84911926573     PISSN: 09269959     EISSN: 14683083     Source Type: Journal    
DOI: 10.1111/jdv.12734     Document Type: Article

References (101)

1. European Union. European Centre for Disease Prevention and Control. http://www.ecdc.europa.eu/
2. World Health Organisation. Sexually transmitted infections management guidelines 1999. http://www.who.int/HIV-AIDS
3. French P, Gomberg M, Janier M, Schmidt B, van Voorst Vader P, Young H,. IUSTI: 2008 European guideline on the management of syphilis. Int J STD AIDS 2009; 20: 300-309.
4. Rompalo AM, Lawlor J, Seaman P, Quinn TC, Zenilman JM, Hook EW,. Modification of syphilitic genital ulcer manifestations by coexistent HIV infection. Sex Transm Dis 2001; 28: 448-454.
5. Rompalo AM, Joesoef MR, O'Donnell JA, et al,. Clinical manifestations of early syphilis by HIV status and gender. Results of the Syphilis and HIV study. Sex Transm Dis 1997; 28: 158-165.
6. Hope-Rapp E, Anyfantakis V, Fouéré S, et al,. Etiology of genital ulcer disease. A prospective study of 278 cases seen in an STD clinic in Paris. Sex Transm Dis 2010; 37: 153-158.
7. Farhi D, Benhaddou N, Grange P, et al,. Clinical and serologic baseline and follow up features of syphilis according to HIV status in the post HAART era. Medicine 2009; 88: 331-340.
8. Parc CE, Chahed S, Patel SV, Salmon-Ceron D,. Manifestations and treatment of ocular syphilis during an epidemic in France. Sex Transm Dis 2007; 34: 553-556.
9. Villanueva AV, Sahouri MJ, Ormerod LD, Puklin JE, Reyes MP,. Posterior uveitis in patients with positive serology for syphilis. Clin Infect Dis 2000; 30: 479-485.
10. Mishra S, Walmsley SL, Loutfy MR, Kaul R, Logue KJ, Gold WL,. Otosyphilis in HIV-coinfected individuals: a case series from Toronto, Canada. AIDS Patient Care STDS 2008; 22: 213-219.
11. Ghanem KG, Moore RD, Rompalo AM, Erbelding EJ, Zenilman JM, Gebo KA,. Neurosyphilis in a cohort of HIV-1 infected patients. AIDS 2008; 22: 1145-1151.
12. MMWR: CDC case definitions for public health surveillance. Oct 19,1990/vol.39/No.RR-13.
13. Wheeler HL, Agarwal S, Goh BT,. Dark ground microscopy and treponemal serological tests in the diagnosis of early syphilis. Sex Transm Infect 2004; 80: 411-414.
14. 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. World Health Organization (WHO), Geneva, Switzerland, 2013: 107-129.
15. Grange PA, Gressier L, Dion PL, et al,. Evaluation of a PCR test for detection of Treponema pallidum in swabs and blood. J Clin Microbiol 2012; 50: 546-552.
16. 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: 264-269.
17. Gayet-Ageron A, Lautenschlager S, Ninet B, Perneger TV, Combescure C,. Sensitivity, specificity and likelihood ratios of PCR in the diagnosis of syphilis: a systematic review and meta-analysis. Sex Transm Infect 2013; 89: 251-256.
18. Shields M, Guy RJ, Jeoffreys NJ, Finlayson RJ, Donovan B,. A longitudinal evaluation of Treponema pallidum PCR testing in early syphilis. BMC Infect Dis 2012; 12: 353.
19. Buffet M, Grange PA, Gerhardt P, et al,. Diagnosing Treponema pallidum in secondary syphilis by PCR and immunohistochemistry. J Invest Dermatol 2007; 127: 2345-2350.
20. Müller H, Eisendle K, Bräuninger W, Kutzner H, Cerroni L, Zelger B,. Comparative analysis of immuno-histochemistry, 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: 50-60.
21. Grange PA, Allix-Beguec C, Chanal J, et al,. Molecular subtyping of Treponema pallidum in Paris, France. Sex Transm Dis 2013; 40: 641-644.
22. Peng RR, Wang AL, Li J, Tucker JD, Yin YP, Chen XS,. Molecular typing of Treponema pallidum: a systematic review and meta-analysis. PLoS Negl Trop Dis 2011; 5: e1273.
23. Ho EL, Lukehart SA,. Syphilis: using modern approaches to understand an old disease. J Clin Invest 2011; 121: 4584-4592.
24. Cole MJ, Chisholm SA, Palmer HM, Wallace LA, Ison CA,. Molecular epidemiology of syphilis in Scotland. Sex Transm Infect 2009; 85: 447-451.
25. Larsen SA, Steiner BM, Rudolph AH,. Laboratory diagnosis and interpretation of tests for syphilis. Clin Microbiol Rev 1995; 8: 1-21.
26. Nandwani R, Evans DTP,. Are you sure it's syphilis?. A review of false positive serology Int J STD AIDS 1995; 6: 241-248.
27. Young H,. Guidelines for serological testing for syphilis. Sex Transm Infect 2000; 76: 403-405.
28. Hunter M, Robertson PW, Post JJ,. Significance of isolated reactive treponemal chemiluminescence immunoassay results. J Infect Dis 2013; 207: 1416-1423.
29. Cole MJ, Perry KR, Parry JV,. Comparative evaluation of 15 serological assays for the detection of syphilis infection. Eur J Clin Microbiol Infect Dis 2007; 26: 705-713.
30. Binnicker MJ, Jespersen DJ, Rollins LO,. Treponema-specific tests for serodiagnosis of syphilis: comparative evaluation of seven assays. J Clin Microbiol 2011; 49: 1313-1317.
31. Wong EH, Klausner JD, Caguin-Grygiel G, et al,. 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: 528-532.
32. Busse C, Navid MH, Strubel A, Schnitzler P,. Evaluation of a new recombinant antigen-based Virotech Treponema pallidum screen ELISA for diagnosis of syphilis. Clin Lab 2013; 59: 523-529.
33. Marangoni A, Nardini P, Foschi C, et al,. Evaluation of the BioPlex 2200 syphilis system as a first-line method of reverse-sequence screening for syphilis diagnosis. Clin Vaccine Immunol 2013; 20: 1084-1088.
34. 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: e003347.
35. st century. Clin Infect Dis 2010; 51: 700-708.
36. Park IU, Chow JM, Bolan G, Stanley M, Shieh J, Schapiro JM,. Screening for syphilis with the treponemal immunoassay: analysis of discordant serology results and implications for clinical management. J Infect Dis 2011; 204: 1297-1304.
37. Centers for Disease Control and Prevention (CDC). Discordant results from reverse sequence syphilis screening-five laboratories, United States, 2006-2010. MMWR Morb Mortal Wkly Rep 2011; 60: 133-137.
38. Pillay A, Chen CY, Reynolds MG, et al,. Laboratory-confirmed case of yaws in a 10-year-old boy from the Republic of the Congo. J Clin Microbiol 2011; 49: 4013-4015.
39. Herring AJ, Ballard RC, Pope V, et al,. A multi-centre evaluation of nine rapid, point-of-care syphilis tests using archived sera. Sex Transm Infect 2006; 82 (Suppl 5): v7-v12.
40. Castro AR, Esfandiari J, Kumar S, et al,. Novel point-of-care test for simultaneous detection of nontreponemal and treponemal antibodies in patients with syphilis. J Clin Microbiol 2010; 48: 4615-4619.
41. Yin YP, Chen XS, Wei WH, et al,. A dual point-of-care test shows good performance in simultaneously detecting nontreponemal and treponemal antibodies in patients with syphilis: a multisite evaluation study in China. Clin Infect Dis 2013; 56: 659-665.
42. Owusu-Edusei K, Gift TL, Ballard RC,. Cost-effectiveness of a dual non-treponemal/treponemal syphilis point of care test to prevent adverse pregnancy outcomes in Sub-Saharan Africa. Sex Transm Dis 2011; 38: 997-1003.
43. Owusu-Edusei K, Koski KA, Ballard RC,. The tale of two serologic tests to screen for syphilis-treponemal and non-treponemal: does the order matter? Sex Transm Dis 2011; 38: 448-456.
44. Owusu-Edusei K, Peterman TA, Ballard RC,. Serologic testing for syphilis in the United States: a cost-effectiveness analysis of two screening algorithms. Sex Transm Dis 2011; 38: 1-7.
45. Stoner B,. Current controversies in the management of adult syphilis. Clin Infect Dis 2007; 44 (Suppl 3): S130-S146.
46. Workowski KA, Berman S, Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep 2010; 59: 1-110.
47. Wöhrl S, Geusau A,. Neurosyphilis is unlikely in patients with late latent syphilis and a negative blood VDRL test. Acta Derm Venereol 2006; 86: 335-339.
48. Geusau A, Kittler H, Hein U, Dangl-Erlach E, Stingl G, Tschachler E,. Biological false-positive tests comprise a high proportion of Venereal Disease Research Laboratory reactions in an analysis of 300 000 sera. Int J STD AIDS 2005; 16: 722-726.
49. Hooshmand H, Escobar MR, Kopf SW,. Neurosyphilis; a study of 241 patients. JAMA 1972; 219: 726-729.
50. Löwhagen GB, Andersson M, Blomstrand C, Roupe G,. Central nervous system involvement in early syphilis. Part I. Intrathecal immunoglobulin production. Acta Derm Venereol 1983; 63: 409-417.
51. Wiesel J, Rose DN, Silver AL, Sacks HS, Bernstein RH,. Lumbar puncture in asymptomatic late syphilis. Arch Intern Med 1985; 145: 465-468.
52. Lukehart SA, Hook EW III, Bakerzander SA, Collier AC, Critchlow CW, Handsfield HH,. Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment. Ann Intern Med 1988; 109: 855-862.
53. Wolters EC, Hische EAH, Tutuarima JA, et al,. Central nervous system involvement in early and late syphilis: the problem of asymptomatic neurosyphilis. J Neurol Sciences 1988; 88: 229-239.
54. van Voorst Vader PC,. Syphilis management and treatment. Dermatol Clin 1998; 16: 699-711.
55. Luger AF, Schmidt BL, Kaulich M,. Significance of laboratory findings for the diagnosis of neurosyphilis. Int J STD AIDS 2000; 11: 224-234.
56. Marra CM, Maxwell CL, Smith SL, et al,. Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features. J Infect Dis 2004; 189: 369-376.
57. Centers for Disease Control and Prevention (CDC). Symptomatic early neurosyphilis among HIV-positive men who have sex with men-four cities, United States, January 2002-June 2004. MMWR Morb Mortal Wkly Rep 2007; 56: 625-628.
58. Libois A, De Wit S, Poll B, et al,. HIV and syphilis: when to perform a lumbar puncture. Sex Transm Dis 2007; 34: 141-144.
59. Harding AS, Ghanem KG,. The performance of cerebrospinal fluid treponemal-specific antibody tests in neurosyphilis: a systematic review. Sex Transm Dis 2012; 39: 291-297.
60. Dabis R, Radcliffe K,. What is the role of a full physical examination in the management of asymptomatic patients with late syphilis? Int J STD AIDS 2012; 23: 901-902.
61. 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.
62. Dabis R, Radcliffe K,. Is it useful to perform a chest X-ray in asymptomatic patients with late latent syphilis? Int J STD AIDS 2011; 22: 105-106.
63. Rolfs RT,. Treatment of syphilis, 1993. Clin Infect Dis 1995; 20 (Suppl 1): S23-S38.
64. Dunlop EMC,. Survival of treponemes after treatment, comments, clinical conclusions and recommendations. Genitourin Med 1985; 61: 293-301.
65. Löwhagen GB, Brorson J-E, Kaijser B,. Penicillin concentrations in cerebrospinal fluid and serum after intramuscular, intravenous and oral administration to syphilitic patients. Acta Derm Venereol 1983; 63: 53-57.
66. Goh BT, Smith GW, Samarasinghe L, Singh V, Lim KS,. Penicillin concentrations in serum and cerebrospinal fluid after intramuscular injection of aqueous procaine penicillin 0.6 MU with and without oral probenecid. Br J Venereol Dis 1984; 60: 371-373.
67. Van der Valk PGM, Kraai EJ, van Voorst Vader PC, Haaxma-Reiche H, Snijder JAM,. Penicillin concentrations in cerebrospinal fluid (CSF) during repository treatment regimen for syphilis. Genitourin Med 1988; 64: 223-224.
68. Schoth PEM, Wolters EC,. Penicillin concentrations in serum and CSF during high-dose intravenous treatment for neurosyphilis. Neurology 1987; 37: 1214-1216.
69. Faber WR, Bos JD, Tietra PJGM, Fass H, van Ejk RTW,. Treponemicidal level of amoxycillin in cerebrospinal fluid after oral administration. Sex Transm Dis 1983; 10: 148-150.
70. Ghanem KG, Erbelding EJ, Cheng WW, Rompalo AM,. Doxycycline compared with benzathine penicillin for the treatment of syphilis. Clin Infect Dis 2006; 42: e45-e49.
71. Marra CM, Boutin P, McArthur JC, et al,. A pilot study evaluating ceftriaxone and penicillin G as treatment agents for neurosyphilis in human immunodeficiency virus-infected individuals. Clin Infect Dis 2000; 30: 540-544.
72. Dowell ME, Ross PG, Musher DM, Cate TR, Baughn RE,. Response of latent syphilis or neurosyphilis to ceftriaxone therapy in persons infected with human immunodeficiency virus. Am J Med 1992; 93: 481-488.
73. Smith NH, Musher DM, Huang DB, et al,. Response of HIV infected patients with asymptomatic syphilis to intensive intramuscular therapy with ceftriaxone or procaine penicillin. Int J STD AIDS 2004; 15: 328-332.
74. Riedner G, Rusizoka M, Todd J, et al,. Single dose azithromycin versus penicillin G benzathine for the treatment of early syphilis. N Engl J Med 2005; 353: 1236-1244.
75. Hook EW, Behets F, Van Damme K, et al,. A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis. J Infect Dis 2010; 201: 1729-1735.
76. Lukehart SA, Godornes C, Molini BJ, et al,. Macrolide resistance in Treponema pallidum in the United States and Ireland. N Engl J Med 2004; 351: 154-158.
77. Stamm LV,. Global challenge of antibiotic resistant Treponema pallidum. Antimicrob Agents Chemother 2010; 54: 583-589.
78. Zhou P, Li K, Lu H, et al,. Azithromycin treatment failure among primary and secondary syphilis patients in Shanghai. Sex Transm Dis 2010; 37: 726-729.
79. Chen XS, Yin YP, Wei WH, et al,. High prevalence of azithromycin resistance to Treponema pallidum in geographically different areas in China. Clin Microbiol Infect 2013; 19: 975-979.
80. Gjestland T,. The Oslo study of untreated syphilis; an epidemiologic investigation of the natural course of the syphilitic infection based upon a re-study of the Boeck-Bruusgaard material. Acta Derm Venereol Suppl (Stockh) 1955; 35 (Suppl 34): 3-368; Annex I-LVI.
81. Amir J, Ginat S, Cohen YH, Marcus TE, Keller N, Varsano I,. Lidocaine as a diluent for administration of benzathine penicillin G. Pediatr Infect Dis 1998; 17: 890-893.
82. Crowe G, Theodore C, Forster GE, Goh BT,. Acceptability and compliance with daily injections of procaine penicillin in the treatment of syphilis-treponemal infection. Sex Transm Dis 1997; 24: 127-130.
83. Wong T, Singh AE, De P,. Primary syphilis treatment response to doxycycline/tetracycline versus benzathine penicillin. Am J Med 2008; 121: 903-908.
84. Janier M, Libar E, Bonnet A, et al,. Treatment of late syphilis with 2.4 million units Benzathine Penicillin G (BPG): tolerance of single versus divided doses. Sex Transm Dis 2012; 39: 359-360.
85. Boot JM, Oranje AP, De Groot R, Tan G, Stolz E,. Congenital syphilis. Int J STD AIDS 1992; 3: 161-167.
86. Kamb ML, Newman LM, Riley PL, et al,. A road map for the global elimination of congenital syphilis. Obstet Gynecol Int 2010; 2010: 312798.
87. Peterman TA, Newman DR, Davis D, Su JR,. Do women with persistently negative nontreponemal test results transmit syphilis during pregnancy? Sex Transm Dis 2013; 40: 311-315.
88. Wendel GD, Sheffield JS, Hollier LM, Hill JB, Ramsay PS, Sanchez PJ,. Treatment of syphilis in pregnancy and prevention of congenital syphilis. Clin Infect Dis 2010; 35: S200-S209.
89. Donders GG, Desmyter J, Hooft J, DeWet H,. Apparent failure of one injection of benzathine penicillin G for syphilis during pregnancy in HIV-seronegative African women. Sex Transm Dis 1997; 24: 94-101.
90. Walker GJA,. Antibiotics for syphilis diagnosed during pregnancy. Cochrane Database Syst Rev 2001, 3, Art No: CD 001143. DOI: 10.1002/14651858.CD001143
91. Herremans T, Kortbeek L, Notermans DW,. A review of diagnostic tests for congenital syphilis in newborns. Eur J Clin Microbiol Infect Dis 2010; 29: 495-501.
92. Blank LJ, Rompalo AM, Erbelding EJ, Zenilman JM, Ghaem KG,. Treatment of syphilis in HIV-infected subjects: a systematic review of the literature. Sex Transm Infect 2011; 87: 9-16.
93. Janier M, Chastang C, Spindler E, et al,. A prospective study of the influence of HIV status on the seroreversion of serological tests for syphilis. Dermatology 1999; 198: 362-369.
94. Seña AC, Wolff M, Martin DH, et al,. Predictors of serological cure and serofast state after treatment in HIV-negative persons with early syphilis. Clin Infect Dis 2011; 53: 1092-1099.
95. Ghanem KG, Erbelding EJ, Wiener ZS, Rompalo AM,. Serological response to syphilis treatment in HIV-positive and HIV-negative patients attending sexually transmitted disease clinics. Sex Transm Infect 2007; 83: 97-101.
96. Fröhlich-Knaute D, Graf N, Lautenschlager S, Weber R, Bosshard PP,. Serological response to treatment of syphilis according to disease stage and HIV status. Clin Infect Dis 2012; 55: 1615-1622.
97. Gonzalez-Lopez JJ, Fernandez-Guerrero ML, Lujan R, Fernandez-Tostado S, de Gorgolas M, Requena L,. Factors determining serologic response to treatment in patients with syphilis. Clin Infect Dis 2009; 49: 1505-1511.
98. Cortes NJ, Afzali B, MacLean D, et al,. Transmission of syphilis by solid organ transplantation. Am J Transplant 2006; 6: 2497-2499.
99. Gudjonsson H, Skog E,. The effect of prednisolone on the Jarisch-Herxheimer reaction. Acta Dermatol Venereol 1968; 48: 15-18.
100. Katz KA, Lee MA, Gray T, Marcus JL, Pierce EF,. Repeat syphilis among men who have sex with men-San Diego county, 2004-2009. Sex Transm Dis 2011; 38: 349-352.
101. Marra CM, Maxwell CL, Tantalo L, et al,. Normalization of cerebrospinal fluid abnormalities after neurosyphilis therapy: does HIV status matter. Clin Infect Dis 2004; 38: 1001-1006.