Review of current evidence and comparison of guidelines for effective syphilis treatment in Europe

International Journal of STD and AIDS

Volumn 15, Issue 2, 2004, Pages 73-88

  Parkes, R ^a   Renton, A ^b   Meheus, A ^c   Laukamm Josten, U ^d  

^a ST MARY S HOSPITAL   (United Kingdom)

^b IMPERIAL COLLEGE SCHOOL OF MEDICINE   (United Kingdom)

^c UNIVERSITY OF ANTWERP   (Belgium)

^d WHO REGIONAL OFFICE FOR EUROPE   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

AMOXICILLIN; AMPICILLIN; ARSENIC; AZITHROMYCIN; BENZATHINE PENICILLIN; BISMUTH; CEFTRIAXONE; DOXYCYCLINE; ERYTHROMYCIN; OXACILLIN; PENICILLIN DERIVATIVE; PENICILLIN G; PENICILLIN G SODIUM; PROBENECID; PROCAINE; PROCAINE PENICILLIN; TETRACYCLINE;

CONGENITAL SYPHILIS; DISEASE ASSOCIATION; DISEASE SEVERITY; DOSE TIME EFFECT RELATION; DRUG BLOOD LEVEL; DRUG CEREBROSPINAL FLUID LEVEL; DRUG EFFECT; EUROPE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; NEUROSYPHILIS; PENICILLIN ALLERGY; PRACTICE GUIDELINE; PREGNANCY; PRIORITY JOURNAL; REVIEW; SYPHILIS; TREATMENT OUTCOME; TREPONEMA PALLIDUM;

EUROPE; EVIDENCE-BASED MEDICINE; HUMANS; PENICILLINS; PRACTICE GUIDELINES; RUSSIA; SYPHILIS; UNITED STATES;

EID: 1242292332     PISSN: 09564624     EISSN: None     Source Type: Journal    
DOI: 10.1258/095646204322764253     Document Type: Review

References (118)

1. Eatough G. Fracastoro's Syphilis. Liverpool UK: Francis Cairns, 1984; Book II:63
2. Goh B, van Voorst Vader P. European guideline for the management of syphilis. Int J STD AIDS 2001;12(Suppl 3):14-26 www.iusti.org/
3. Goh B, Syphillis Guidelines Revision Group. UK national guidelines on the management of early syphilis 2002. www.mssvd.org.uk
4. French P, Syphilis Guidelines Revision Group. UK national guidelines for the management of late syphilis 2002. www.mssvd.org.uk
5. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2002. MMWR 2002;51:18-28 www.cdc.gov/std/ treatment/
6. Akovbian V, Filatova E. Management of syphilis infected patients in Russia. Country paper for WHO/EURO project. 2002 www.sti-taskforce.org/ documents.html 'STI: case management'
7. Rolfs R. Treatment of syphilis, 1993. Clin Infect Dis 1995;20(Suppl 1):S23-38
8. Global prevalence and incidence of selected curable sexually transmitted infections: overview and estimates. WHO/HIV_AIDS/2001.02;WHO/CDS/CSR/EDC/2001. 10. WHO: Geneva, 2001
9. Goldmeier D, Hay P. A review and update on adult syphilis, with particular reference to its treatment. Int J STD AIDS 1993;4:70-82
10. Gjestland T. An epidemiological investigation of the natural course of the syphilitic infection based on a restudy of the Boeck-Bruusgaard material. Acta Derm Venereol (Stockh) 1955;35(Suppl 34)
11. Neil EE. Comparative sensitivities of treponemes of syphilis, yaws and bejel to penicillin in vitro, with observations of factors affecting its treponemicidal actions. Am J Syph 1958;38:92-106
12. Norris SJ, Edmonson DG. In vitro culture systems to determine MICs and MBCs of antimicrobial agents against Treponema pallidum subspecies pallidum (Nichols strains). Antimicrob Agents Chemother 1988;32:68-7
13. Eagle H, Fleischman R, Musselman AD. The effective concentration of penicillin in vitro and in vivo for streptococcus, pneumococcus and Treponema pallidum. J Bacteriol 1950;59:625-43
14. Idsoe O, Guthe T, Willcox RR. Penicillin in the treatment of syphilis. The experience of three decades. Bull WHO 1972;47(Suppl):5-68
15. Cumberland MC, Turner TB. The rate of multiplication of Treponema pallidum in normal and immune rabbits. Am J Syph Gonorr Vener Dis 1949;33:201-12
16. Brockmeyer NH. Syphilis. In: Petzoldt D, Gross G, Eds. Diagnostik und Therapie sexuell Obertragbarer Krankheiten-Leitlinien 2001 der Deutschen STD Gesellschaft. Berlin: Springer Verlag, 2001:101-11
17. Martindale. 33rd edition. PhP. P157-60, 239-40
18. Augenbraun MH, Rolfs R. Treatment of syphilis, 1998: Non pregnant adults. Clin Infect Dis 1999;28:(Suppl 1):S21-8
19. Smith C, Kamp M, Olansky S, Price E. Benzathine penicillin G in the treatment of syphilis. Bull WHO 1956;15:1087-96
20. Kapur TR, Halder HR, Anand S, et al. Outcome of treated syphilis with various types of penicillin and broad-spectrum antibiotics among Indian Armed Forces personnel. Indian Med Gazette 1981;115:374-86
21. Rolfs RT, Joesoef RM, Hendershot EF, et al. A randomised trial of enhanced therapy for early syphilis in patients with and without HIV infection. N Engl J Med 1997;337:307-14
22. Hardy JB, Hardy PH, Oppenheimer EH, Ryan SJ, Sheff RN. Failure of penicillin in a newborn with congenital syphilis. JAMA 1970;212:1345-9
23. Jackson FR, Vanderstoep EM, Knox JM, Desmond MM, Moore MB Jr. Use of aqueous benzathine penicillin G in the treatment of syphilis in pregnant women. Am J Obstet Gynecol 1962;83:1389-92
24. Mascola L, Pelosi R, Alexander CE. Inadequate treatment of syphilis in pregnancy. Am J Obstet Gynecol 1984;150:945-7
25. Donder GGG, Desmyrer J, Hooft J, De Wet 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
26. Moskovitz BL, Klimek JJ, Goldman RL, Flumara NJ, Quinitiliani R. Meningovascular syphilis after 'appropriate' treatment of primary syphilis. Arch Intern Med 1982;142:139-40
27. Giles AJH, Lawrence AG. Treatment failure with penicillin in early syphilis. Br J Vener Dis 1979;55:62-4
28. Johns DR, Tierney M, Felefestein D. Alterations in the natural history of neurosyphilis by concurrent infection with the human immunodeficiency virus. N Engl J Med 1987;316:1569-72
29. Berry CD, Hooton TM, Collier AC, Lukehart SA. Neurological relapse after benzathine penicillin therapy for secondary syphilis in a patient with HIV infection. N Engl J Med 1987;316:1587-9
30. Tomberlin MG, Holton PD, Owens JL, et al Evaluation of neurosyphilis in human immunodeficiency virus-infected individuals. Clin Infect Dis 1994;18:288-94
31. Malone JL, Wallace MM, Hendrick BB, et al. Syphilis and neurosyphilis in a HIV type 1 seropositive population: evidence for frequent serological relapse after therapy. Am J Med 1995;99:55-63
32. Schofer H, Imhof M, Thoma-Greber E, et al. Active syphilis in HIV infection: a multicentre retrospective survey. The German AIDS study group. Genitourin Med 1996;72:176-81
33. McLeish WM, Pulido JS, Holland S, Culbertson WW, Winward K. The ocular manifestation of syphilis in human immunodeficiency virus type 1 infected host. Ophthalmology 1990;97:196-203
34. Gregory N, Sanchez M, Buchness MR. The spectrum of syphilis in patients with human immunodeficiency virus. J Am Acad Dermatol 1990;22:1061-7
35. Fiumara NJ. Treatment of primary and secondary syphilis. Serological response. J Am Arch Dermatol 1986;14:487-91
36. Perdrup A. Penicillin treatment of early syphilis. Acta Derm Venereol (Stockh) 1960;40:340-57
37. Weiner AL, Wilybackh CA, Ludlow CE. Ambulatory penicillin therapy of syphilis in a public health clinic - report on four hundred and two patients. Ohio State Med J 1951;47:720-30
38. Elliot W. Treatment of primary syphilis. J Am Vener Dis Assoc 1976;3:128-35
39. Brown ST, Zaidi A, Larsen SA, Reynolds GH. Serological response to syphilis treatment. A new analysis of old data. JAMA 1985;253:1296-9
40. Crowe G, Theodore C, Forster GE, et al. Acceptability and compliance with daily injections of procaine penicillin in the outpatient treatment of syphilis-treponemal infection. Sex Transm Dis 1997;245:127-30
41. Sonnichsen N, Tolzin M. Die hochdosierte Penicillin-Infusions-Therapie - eine alternative Behandlungsform der Syphillis. Dermatol Monatsschr 1985;171:698-703
42. Gomberg M, Losseva OK, Koubanova AA, Tikhonova LI. Personal correspondence
43. Kitayeva NJ. The long-term results of the treatment of early symptomatic syphilis and latent syphilis with penicillin preparations according to the duration of disease. Candidate dissertation for Medical Science, Moscow 2001;116 pp
44. Loseva O, Kitayeva N. Terms of seroconversion in patients with early syphilis forms of different duration of the infection, who had received treatment with various penicillin preparations. Sex Transm Infect 2001;4:9-13
45. Kiefer L, Rubin A, McCoy JB, Fultz EL. Placental transfer of erythromycin. Am J Obstet Gynecol 1955;69:174-7
46. Philipson A, Sabath LD, Charles D. Transplacental passage of erythromycin and clindamycin. N Engl J Med 1973;288:1219-21
47. Augenbraun MH. Treatment of syphilis 2001: Nonpregnant adults. Clin Infect Dis 2002;35(Suppl 2):187-90
48. Lukehart SA, Fohn MJ, Baker-Zander SA. Efficacy of azithromycin for therapy of active syphilis in the rabbit model. J Antimicrob Chemother 1990;25(Suppl A):91-9
49. Stamm LV, Parrish EA. In vitro activity of azithromycin and CP-63,956 against Treponema pallidum. J Antimicrob Chemother 1990;25(Suppl A):11-14
50. Verdon MS, Hansfield HH, Johnson RB. Pilot study of azithromycin for treatment of primary and secondary syphilis. Clin Infect Dis 1994;19:486-8
51. Hook EW, Stephens J, Ennis DM. Azithromycin compared with penicillin G benzathine for treatment of incubating syphilis. Ann Intern Med 1999;131:434-7
52. Mashkilleyson AL, Gomberg MA, Mashkilleyson N, Kutin SA. Treatment of syphilis with azithromycin. Int J STD AIDS 1996;7(Suppl 1):13-15
53. Gruber F, Kastelan M, Cabrijan L, Simonic E, Brajac I. Treatment of early syphilis with azithromycin. J Chemother 2000;12:240-3
54. Stamm LV, Stapleton JT, Bassford PJ. In vitro assay to demonstrate high level of erythromycin resistance of a clinical isolate of Treponema pallidum. Antimicrob Agents Chemother 1988;32:164-9
55. Parkes R. Audit project on refusal of parenteral treatment for syphilis. 2002. Unpublished data
56. Onada Y. Clinical evaluation of amoxycillin in the treatment of syphilis. J Int Med Res 1979;7:739-45
57. Goldman JN. Clinical experience with ampicillin and probenecid in the management of treponeme associated uveitis. Transact Acad Ophthalmol Otolaryngol 1970;74: 509-14
58. Collart P, Borel L-J, Durel P. Significance of spiral organisms found, after treatment, in rabbits and humans. Br J Vener Dis 1968;40:81-9
59. Yobs AR, Clark JW Jr, Mothershed SE, Bullard JC, Artley CW. Further observations on the persistence of Treponema pallidum after treatment in rabbits and humans. Br J Vener Dis 1968;44:116-30
60. Smith JL, Israel CW, McCrary JA, Harner RE. Recovery of Treponema pallidum from aqueous humour removed at cataract surgery in man by transfer to rabbit testes. Am J Ophthalmol 1968;65:242-7
61. Yogeswari L, Chako CW. Persistence of T. pallidum and its significance in penicillin treated late syphilis with persistent seroreactivity. WHO/DT/RES/72 1972;262:1-13
62. Tramont EC. Persistence of Treponema pallidum following penicillin G therapy. Report of 2 cases. JAMA 1976;236:2206-7
63. Musher D, Hamil R, Baughn R. Effect of human immunodeficiency virus on the course of syphilis and effect of treatment. Ann Intern Med 1990;113:872-81
64. Hellerstrom S, Skog E. Outcome of penicillin therapy of syphilis. Acta Dermato-Venereol 1962;42:179-91
65. Morrison RE, Harrison SM, Tramont EC. Oral amoxycillin, an alternative treatment for neurosyphilis. Genitourin Med 1985;61:359-62
66. Musher DM. Syphilis, neurosyphilis, penicillin and AIDS. J Infect Dis 1991;163:1201-6
67. Hahn RD, Cutler JC, Curtis AC, et al. Penicillin treatment of asymptomatic CNS syphilis I. Probability of progression to symptomatic neurosyphilis. Arch Dermatol 1956;74:355-66
68. Polnikorn N, Witoonpanich R, Vorachit M, Vejjajiva S, Vejjajiva A. Penicillin concentrations in the cerebrospinal fluid after different treatment regimens for syphilis. Br J Vener Dis 1980;56:363-7
69. Ducas J, Robson HG. Cerebrospinal fluid levels during treatment for latent syphilis. JAMA 1981;246:2583-4
70. Mohr J, Griffiths W, Jackson R, Saadah H, Bird P, Riddle J. Neurosyphilis and penicillin levels in the cerebrospinal fluid. JAMA 1976;236:2208-9
71. Lowhagen G-B, Brorson J-E, Kalijaser B. Penicillin concentration in cerebrospinal fluid and serum after intramuscular, intravenous, and oral administration to syphilitic patients. Acta Dermatovener (Stockh) 1983;63:53-7
72. Dunlop EMC, Al-Egaily AA, Houang ET. Production of treponemicidal concentration of penicillin in CSF. BMJ 1981;283:646
73. Hooshmand H, Escobar M, Koft S. Neurosyphilis: a study of 241 patients. JAMA 1972;219:726-9
74. Wilner E, Brody J. Prognosis of general paresis after treatment. Lancet 1968;2:1370-1
75. Van der Valk PGM, Kraai EJ, Van Voorst Vader PC, et al. Penicillin concentrations in CSF during repository treatment regimen for syphilis. Genitourin Med 1988;64:223-5
76. Yoder F. Penicillin treatment of neurosyphilis. Are recommended treatment doses enough? JAMA 1975;232: 270-3
77. Faber WR, Bos JD, Tietra PJGM, et al. Treponemicidal levels of amoxycillin in cerebrospinal fluid after oral administration. Sex Transm Dis 1983;10:148-50
78. Whiteside C, Flynn NM, Fitzgerald FT. Penetration of oral doxycycline into the cerebrospinal fluid of patients with latent or neurosyphilis. Antimicrob Agents Chemother 1985;28:347-8
79. Marra CM, Slatter V, Tartaglione TA, et al. Evaluation of aqueous penicillin G and ceftriaxone for experimental neurosyphilis. J Infect Dis 1992;165:396-7
80. Hook EW III, Baker-Sander SA, Moskovitz BL, Lukehart SA, Handfield HH. Ceftriaxone therapy for asymptomatic neurosyphilis: case report and western blot analysis of serum and CSF IgG response to therapy Sex Transm Dis 1986;13:185-8
81. Hook E, Roddy R, Hansfield H. Ceftriaxone for early and incubating syphilis. J Infect Dis 1988;158:881-4
82. Moorthy T, Lee C, Lim K, Tan T. Ceftriaxone for the treatment of primary syphilis in men: A preliminary study. Sex Transm Dis 1987;14:116-18
83. Dowell M, Ross P, Musher D, Cate T, Baughn R. Response of latent syphilis or neurosyphilis to ceftriaxone therapy in persons infected with human immunodeficiency virus. Am J Med 1992;93:481-8
84. Johns DR, Tierny M, Felsenstein D. Alteration in the natural history of neurosyphilis by concurrent infection with the human immunodeficiency virus. N Engl J Med 1987;316:1569-72
85. Hicks CB, Benson PM, Luptgon GP, Tramont EC. Seronegative secondary syphilis in a patient infected with the human immunodeficiency virus with Kaposi sarcoma. Ann Intern Med 1987;107:492-5
86. Tramont EC. Syphilis in the AIDS era. N Engl J Med 1987;316:1600-1
87. Centers for Disease Control. Recommendations for diagnosing and treating syphilis in HIV-infected patients. MMWR 1988;37:600-2, 607-8
88. Musher DM. How much penicillin cures early syphilis? Ann Intern Med 1988;109:849-51
89. Tramont EC. Controversies regarding the natural history and treatment of syphilis in HIV disease. AIDS Clin Rev 1991:97-107
90. Tramont EC. Syphilis from Beethoven to HIV. Mt Sinai J Med 1990;57:192-6
91. Hicks CB. Syphilis and HIV infection. Dermatol Clin 1991;9:493-501
92. Felmore YM. Recent developments in the diagnosis and management of sexually transmitted diseases: infectious syphilis and acquired immunodeficiency syndrome. Cutis 1989;44:288-90
93. Hook E III. Syphilis and HIV infection. J Infect Dis 1989;160:530-4
94. Fiumara N. Human immunodeficiency virus infection and syphilis. J Am Acad Dermatol 1989;21:141-2
95. Kinloch de Loes S, Radeff B, Saurat JH. AIDS meets syphilis: changing patterns of the syphilitic infection and its treatment. Dermatologica 1988;177:261-4
96. Hook E III. Management of syphilis in human immunodeficiency virus infected patients. Am J Med 1992;92:477-9
97. Engelkens HJ, van der Sluis JJ, Stolz E. Syphilis in the AIDS era. Int J Dermatol 1991;30:254-6
98. Goeman J, Kivuvu M, Nzila N, et al. Similar serologic response to conventional therapy for syphilis among HIV positive and HIV negative women. Genitourin Med 1995;71:275-9
99. Schofer H, Imhof M, Thoma-Greber E, et al. Active syphilis in HIV infection: A multicentre retrospective survey. Genitourin Med 1996;72:176-81
100. Walker GJ. Antibiotics for syphilis diagnosed during pregnancy. The Cochrane Library 2002: Issue 3
101. Singh R, McCloskey J. Syphilis in pregnancy. Venereology 2001;14:121-31
102. Nathan L, Bawdon RE, Sidawi JE, et al. Penicillin levels following the administration of benzathine penicillin G in pregnancy. Obstet Gynecol 1993;82:238-42
103. Watson-Jones D, Gumodoka B, Weiss H, et al. Syphilis in pregnancy in Tanzania II. The effectiveness of antenatal screening and single-doze benzathine penicillin treatment for the prevention of adverse pregnancy outcomes. J Infect Dis 2002;186:948-57
104. Alexander JM, Sheffield JS, Sanchez PJ, et al. Efficacy of treatment for syphilis in pregnancy. Obstet Gynecol 1999;93:5-8
105. Rawston SA, Bromberg K. Failure of recommended maternal therapy to prevent congenital syphilis. Sex Transm Infect 1991;18:102-6
106. Cavanee MR, Farris JR, Spalding TR, et al. Treatment of gonorrhoea in pregnancy. Obstet Gynecol 1993;81:33-8
107. Fenton LJ, Light IJ. Congenital syphilis after maternal treatment with erythromycin. Obstet Gynecol 1976;47:492-4
108. Chang SN, Chung KY, Lee MG, Lee GB. Seroconversion of the serological tests in the newborns to treated syphilitic mothers. Genitourin Med 1995;71:68-70
109. Harshan V, Jayakumar W. Doxycycline in early syphilis. A long term follow up. Indian J Dermatol 1982;27:119-24
110. Onoda Y. Therapeutic effect of oral doxycycline on syphilis. Br J Vener Dis 1979;55:110-15
111. Schroeter AL, Lucas JB, Price EV, et al. Treatment for early syphilis and reactivity of serological tests. JAMA 1972;221:471-6
112. Fernando WL. Erythromycin in early syphilis. Br J Vener Dis 1969;45:200
113. Katsambas A, Adoniou C, Katsarou A, Kerkidou A, Stratigos J. Comparative study of ceftriaxone and benzathine penicillin G in the treatment of primary and secondary syphilis. Chemioterapia 1987;6:549-50
114. Schofer H, Vogt HJ, Milbradt R. Ceftriaxone for the treatment of primary and secondary syphilis. Chemotherapy 1989;35:140-5
115. Tichonova L, Borisenko K, Ward H, Meheus A, Gromyko A, Renton A. Epidemics of syphilis in the Russian Federation: trends, origins and priorities for control. Lancet 1997;350:210-13
116. Renton AM, Borisenko KK, Meheus A, Gromyko A. Epidemics of syphilis in the newly independent states of the former Soviet Union. Sex Transm Infect 1998;74:165-8
117. Riedner G, Dehne KL, Gromyko A. Recent declines in reported syphilis rates in the former Soviet Union: are the epidemics over? Sex Transm Infect 2000;76:263-5
118. World Health Organization Europe STI Task Force. Overview of HIV/AIDS/ STI situation in the European Region. www.sti-taskforce.org