Syphilis

  • 1  Morton RS. Sexual Freedom and Venereal Disease. London: Peter Owen, 1971.
  • 2  Mattei PL, Beachkofsky TM, Gilson RT, Wisco OJ. Syphilis: a re‐emerging infection. Am Fam Phys 2012;85(5):433–40.
  • 3  World Health Organization. Global incidence and prevalence of selected curable sexually transmitted infections – 2008. Geneva: WHO Press, 2012. http://www.who.int/reproductivehealth/publications/rtis/stisestimates/en/ (last accessed June 2014).
  • 4  World Health Organization. Global strategy for the prevention and control of sexually transmitted infections: 2006–2015. Breaking the chain of transmission. Geneva: WHO Press; 2007 http://www.who.int/reproductivehealth/publications/rtis/9789241563475/en/ (last accessed June 2014).
  • 5  Guthe T. The treponematoses as a world problem. Br J Vener Dis 1960;36:67–77. Pubmed link
  • 6  Idsøe O, Guthe T. The rise and fall of the treponematoses. Br J Vener Dis 1967;43:227–43. Pubmed link
  • 7  Knudson EA. A clinical study on 29 cases of debatable STS and TPI seroreactions in Greenland. Acta Derm Venereol (Stockh) 1974;54:311–16.
  • 8  Ministry of Health Report for England and Wales. Venereal diseases in England and Wales. Br J Vener Dis 1966;42:50–7. Pubmed link
  • 9  Schamberg IL. Syphilis and sisyphus. Br J Vener Dis 1963;39:87–97. Pubmed link
  • 10  Tucker JD, Cohen MS. China's syphilis epidemic: epidemiology, proximate determinants of spread, and control responses. Curr Opin Infect Dis. 2011;24(1):50–5. Cross Ref link Pubmed link
  • 11  Tucker JD, Yue‐Ping Yin, Baoxi Wang, Xiang‐Sheng Chen, Cohen MS. An expanding syphilis epidemic in China: epidemiology, behavioural risk and control strategies with a focus on low‐tier female sex workers and men who have sex with men. Sex Transm Infect 2011;87:ii16.
  • 12  Lingolf T. Rapid increase of syphilis and gonorrhea in parts of the former USSR. Sex Transm Dis 1995;22:160–1. Cross Ref link Pubmed link
  • 13  Rubins A, Rubins S, Jakabsone I. Syphilis and gonorrhea in the Baltic countries. Sex Transm Infect 2000;76:214. Cross Ref link Pubmed link
  • 14  Public Health England. Recent Epidemiology of Infectious Syphilis and Congenital Syphilis. Health Protection Report, Vol. 7, No. 44. London: Public Health England, 2013.
  • 15  Savage EJ, Hughes G, Ison C, Lowndes CM, the European Surveillance of Sexually Transmitted Infections (ESSTI) network. Syphilis and gonorrhoea in men who have sex with men: a European overview. Eurosurveillance 2009;14(47):pii=19417. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19417 (last accessed June 2014).
  • 16  Centers for Disease Control and Prevention. Sexually transmitted disease surveillance 2011. Atlanta: US Department of Health and Human Services, 2012. http://www.cdc.gov/std/stats11/Surv2011.pdf (last accessed June 2014).
  • 17  World Health Organization (WHO). Treponemal Infections. Technical Report Series No. 674. Geneva: WHO, 1982.
  • 18  Thirumoorthy T, Lee CT, Lim KB. Epidemiology of infectious syphilis in Singapore. Genitourin Med 1986;62:75–7. Pubmed link
  • 19  Mitchell SJ, Engelman J, Kent CK, Lukehart SA, Godornes C, Klausner JD. Azithromycin‐resistant syphilis infection: San Francisco, California, 2000–2004. Clin Infect Dis 2006;42(3):337–45. Cross Ref link Pubmed link
  • 20  Ho EL, Lukehart SA. Syphilis: using modern approaches to understand an old disease. J Clin Invest 2011;121(2):4584–92. Cross Ref link Pubmed link
  • 21  LaFond RE, Molini BJ, Van Voorhis WC, Lukehart SA. Antigenic variation of TprK V regions abrogates specific antibody binding in syphilis. Infect Immun 2006;74:6244–51. Cross Ref link Pubmed link
  • 22  Radolf JD. Treponema pallidum and the quest for outer membrane proteins. Mol Microbiol 1995;16:1067–73. Cross Ref link Pubmed link
  • 23  Yobs AR, Brown L, Hunter EF. Fluorescent antibody technique in early syphilis. Arch Pathol 1964;77:220–9. Pubmed link
  • 24  Edwards EA. Detecting Treponema pallidum in primary lesions by the fluorescent antibody technique. Public Health Rep 1962;77:427–43. Pubmed link
  • 25  Jue R, Puffer J, Wood RM, et al. Comparison of the fluorescent and conventional dark field methods for the detection of Treponema pallidum in syphilitic lesions. Am J Clin Pathol 1967;47:809–11.
  • 26  Kellogg OS, Deacon WE. A new rapid immunofluorescent staining technique for identification of Treponema pallidum and Neisseria gonorrhoeae. Proc Soc Exp Biol Med 1964;115:963–5. Cross Ref link Pubmed link
  • 27  Norris SJ, Cox DL, Weinstock GM. Biology of Treponema pallidum: correlation of functional activities with genome sequence data. J Mol Microbiol Biotechnol 2001;3:37–62. Pubmed link
  • 28  Van Voorhis WC, Barrett LK, Koelle DM, et al. Primary and secondary syphilis lesions contain mRNA for Th1 cytokines. J Infect Dis 1996;173:491–5. Cross Ref link Pubmed link
  • 29  Riley BS, Oppenheimer‐Marks N, Radolf JD, Norgard MV. Virulent Treponema pallidum promotes adhesion of leukocytes to human vascular endothelial cells. Infect Immun 1994;62:4622–5. Pubmed link
  • 30  Fitzgerald TJ. The Th1/Th2‐like switch in syphilitic infection: is it detrimental? Infect Immun 1992;60:3475–9. Pubmed link
  • 31  Pope V, Larsen SA, Rice RJ, et al. Flow cytometric analysis of peripheral blood lymphocyte immunophenotypes in persons infected with Treponema pallidum. Clin Diagn Lab Immunol 1994;1:121–4. Pubmed link
  • 32  Gjestland T. The Oslo study of untreated syphilis. Acta Derm Venereol (Stockh) 1955;35(Suppl. 34):3–368.
  • 33  Talbot MD, Morton RS. The Tuskegee study of untreated syphilis. Eur J STD 1984;1:125–32.
  • 34  Dunlop EMC. Some aspects of infectious syphilis today. Public Health 1964;78:259–67. Cross Ref link Pubmed link
  • 35  Don PC, Rubinstein R, Christie S. Malignant syphilis (lues maligna) and concurrent infection with HIV. Int J Dermatol 1995;34:403–7. Cross Ref link Pubmed link
  • 36  Van der Ploeg DE, Stagnone JJ. Eyebrow alopecia in secondary syphilis. Arch Dermatol 1982;90:172–3.
  • 37  Van der Willigen AH, Peereboom‐Wynia JDR. Hair studies in patients with primary and secondary syphilis. Acta Derm Venereol (Stockh) 1987;67:250–4.
  • 38  Margo CE, Hamed LM. Ocular syphilis. Surv Ophthalmol 1992;37:203–5. Cross Ref link Pubmed link
  • 39  Laird SM. Yaws in Manchester. Br J Vener Dis 1955;31:30–2. Pubmed link
  • 40  Wray PM. Bejel in Sheffield. Br J Vener Dis 1966;42:25–7. Pubmed link
  • 41  Mackenzie H, Mahmalji W, Raza A. The gumma and the gonad: syphilitic orchitis, a rare presentation of testicular swelling. Int J STD AIDS 2011;22(9):531–3. Cross Ref link Pubmed link
  • 42  Johnson RA, White M. Syphilis in the 1990s: cutaneous and neurologic manifestations. Semin Neurol 1992;12:287–98. Cross Ref link Pubmed link
  • 43  Scheck DN, Hook EW, III. Neurosyphilis. Infect Dis Clin North Am 1994;8:769–85. Pubmed link
  • 44  Morrison AW. On syphilis and the ear – an otologist's view. Genitourin Med 1992;68:420–2. Pubmed link
  • 45  Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect 1999;75:3–17. Cross Ref link Pubmed link
  • 46  Zetola NM, Klausner JD. Syphilis and HIV infection: an update. Clin Infect Dis 2007;44:1222–8. Cross Ref link Pubmed link
  • 47  Cousins DE, Taylor N, Lee V. The outcome of treatment of early syphilis with different benzathine penicillin regimens in HIV‐infected and uninfected patients. Int J STD AIDS 2012;23(9):632–4. Cross Ref link Pubmed link
  • 48  Yinnon AM, Coury‐Doniger P, Polito R, Richman RC. Serologic response to treatment of syphilis in patients with HIV infection. Arch Intern Med 1996;156:321–5. Cross Ref link Pubmed link
  • 49  Hutchinson CM, Hook EW, III, Shepherd M, et al. Altered clinical presentation of early syphilis in patients with human immunodeficiency virus infection. Ann Intern Med 1994;121:94–100. Cross Ref link Pubmed link
  • 50  Brightbill TC, Ihmeidan IH, Post MJ, et al. Neurosyphilis in HIV‐positive and HIV‐negative patients: neuroimaging findings. Am J Neuroradiol 1995;16:703–11. Pubmed link
  • 51  Malone JL, Wallace MR, Hendrick BB, et al. Syphilis and neurosyphilis in a human immunodeficiency virus type‐1 seropositive population: evidence for frequent serologic relapse after therapy. Am J Med 1995;99:55–63. Cross Ref link Pubmed link
  • 52  Kinghorn GR, Hafiz S, McEntergart MG. Pathogenic microbiological flora of genital ulcers in Sheffield with particular reference to herpes simplex virus and Haemophilus ducreyi. Br J Vener Dis 1982;58:377–80. Pubmed link
  • 53  Evans AJ, Summerly R. Pseudo‐chancre redux with negative serology. Br J Vener Dis 1964;40:222–4. Pubmed link
  • 54  Lannigan‐O'Keefe FM. Pseudo‐chancre redux. BMJ 1964;ii:212.
  • 55  Gallup DG, Cowherd DW. Syphilitic cervicitis. A report on a case. Obstet Gynecol 1978;52(Suppl. 1):125–45. Pubmed link
  • 56  Lamb CA, Lamb EM, Mansfield, Sankar KN. Sexually transmitted infections manifesting as proctitis. Frontline Gastroenterol 2013;4(1):32–40. Cross Ref link Pubmed link
  • 57  Masterton G. Oro‐genital aphthosis. Br J Vener Dis 1965;41:282–96.
  • 58  Minicucci E, Vieira R, Oliveira D, Marques S. Oral manifestations of secondary syphilis in the elderly – a timely reminder for dentists. Aust Dent J 2013;58:368–70. Cross Ref link Pubmed link
  • 59  Larsen SA, Steiner BM, Rudolph AH. Laboratory diagnosis and interpretation of tests for syphilis. Clin Microbiol Rev 1995;8:1–21. Pubmed link
  • 60  Grange PA, Grressier L, Dion PL, et al. Evaluation of a PCR test for detection of Treponema pallidum in swabs and blood. J Clin Microbiol 2012;50(3):546–52.. Cross Ref link Pubmed link
  • 61  Kouznetsov AV, Prinz JC. Molecular diagnosis of syphilis: the Schaudinn–Hofmann lymph‐node biopsy. Lancet 2002;360:388–9. Cross Ref link Pubmed link
  • 62  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;89:251–6. Cross Ref link Pubmed link
  • 63  Sena AC, White BL, Sparling PF. Novel treponemal pallidum serologic tests: a paradigm shift in syphilis screening for the 21st century. Clin Infect Dis 2010;51:700–8. Cross Ref link Pubmed link
  • 64  Nelson RA, Mayer MM. Immobilization of Treponema pallidum in vitro by antibody produced in syphilitic infection. J Exp Med 1949;89:369–93. Cross Ref link Pubmed link
  • 65  Laurell AB, Hederstedt B. Fractionation of TPI antibodies and Wassermann reagins. Acta Pathol Microbiol Scand 1958;44:88–91. Cross Ref link Pubmed link
  • 66  Wilkinson AE. Studies on the treponemal immobilization test. Br J Vener Dis 1954;30:144–55. Pubmed link
  • 67  Deacon WE, Falcone VH, Harris AD. A fluorescent test for treponemal antibodies. Proc Soc Exp Biol Med 1957;96:477–80. Cross Ref link Pubmed link
  • 68  Nielsen HA, Idsøe O. Evaluation of the fluorescent treponemal antibody test (FTA). Acta Pathol Microbiol Scand 1963;57:331–47. Cross Ref link Pubmed link
  • 69  Deacon WE, Lucas JB, Price EV. Fluorescent treponemal antibody absorption (FTA/ABS) test for syphilis. JAMA 1966;198:624–8. Cross Ref link Pubmed link
  • 70  Rathlev T. Haemagglutination test utilizing pathogenic Treponema pallidum for the sero‐diagnosis of syphilis. Br J Vener Dis 1967;43:181–5. Pubmed link
  • 71  Sequiera PJL, Eldridge AE. Treponema haemagglutination test. Br J Vener Dis 1973;49:242–8. Pubmed link
  • 72  O'Neil P, Warner RW, Nicol CS. Treponema pallidum haemagglutination assay in the routine serodiagnosis of treponemal disease. Br J Vener Dis 1973;49: 427–31. Pubmed link
  • 73  Robertson DHH, McMillan A, Young H, et al. Clinical value of the Treponema pallidum haemagglutination test. Br J Vener Dis 1975;51:79–82. Pubmed link
  • 74  Eggelston SI, Turner AJL, for the PHLS Syphilis Serology Working Group. Serological testing for syphilis. Commun Dis Public Health 2000;3:158–62. Pubmed link
  • 75  Byrne RE, Laska S, Bell M, et al. Evaluation of a Treponema pallidum Western immunoblot assay as a confirmatory test for syphilis. J Clin Microbiol 1992;30:115–22. Pubmed link
  • 76  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:v7–12. Cross Ref link Pubmed link
  • 77  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(5):659–65. Cross Ref link Pubmed link
  • 78  Forster WD, Kerchan LLO. Biologically false positive Wassermann reactions in Uganda. Br J Vener Dis 1966;42:272–5. Pubmed link
  • 79  Garner MR, Backhouse JL, Collins CA, et al. Serological tests for treponemal infection in leprosy patients. Br J Vener Dis 1969;45:19–22. Pubmed link
  • 80  British Co‐operative Clinical Group. An examination of the treponemal immobilization test in the investigation of positive serological tests for syphilis in pregnancy. Br J Vener Dis 1959;35:162–8. Pubmed link
  • 81  Catterall RD. Collagen disease and the chronic biological false positive phenomenon. Q J Med 1961;30:41–55. Pubmed link
  • 82  Moore JE, Mohr CF. Biologically false positive serologic tests for syphilis. JAMA 1951;150:467–73. Cross Ref link
  • 83  Gibowski M, Neumann E. Non‐specific test results to syphilis in dermatological diseases. Br J Vener Dis 1980;56:17–19. Pubmed link
  • 84  Kraus SJ, Haserick JR, Lantz MA. Atypical FTA‐ABS test fluorescence in lupus erythematous patients. JAMA 1970;211:2140–1. Cross Ref link Pubmed link
  • 85  McKenna CH, Schroeter AL, Kierland RR, et al. The fluorescent treponemal antibody absorbed (FTA‐ABS) test beading phenomenon in connective tissue diseases. Mayo Clin Proc 1973;48:545–8. Pubmed link
  • 86  Shore RN, Faricelli JA. Borderline and reactive FTA‐ABS results in lupus erythematous. Arch Dermatol 1977;113:37–41. Cross Ref link Pubmed link
  • 87  Hunter EF, Russel S, Farshy CE, et al. Evaluation of sera from patients with Lyme disease by FTA/ABS test for syphilis. Sex Transm Dis 1986;13:232–6. Cross Ref link Pubmed link
  • 88  Kingston M, French P, Goh B, et al. UK National Guidelines on the Management of Syphilis 2008. Int J STD AIDS 2008;19:729–40. Cross Ref link Pubmed link
  • 89  Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010. MMWR 2010;59(RR‐12):1–115. http://www.cdc.gov/std/treatment/2010/STD‐Treatment‐2010‐RR5912.pdf (last accessed June 2014).
  • 90  Hook EW, III, Martin DH, Stephens J, et al. A randomized, comparative pilot study of azithromycin versus benzathine penicillin G for treatment of early syphilis. Sex Transm Dis 2002;29:486–90. Cross Ref link Pubmed link
  • 91  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;15:328–32. Cross Ref link Pubmed link
  • 92  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;353:1236–44. Cross Ref link Pubmed link
  • 93  Bai ZG, Wang B, Yang K, et al. Azithromycin versus penicillin G benzathine for early syphilis. Cochrane Database Syst Rev 2012;Issue 6. Pubmed link
  • 94  Spornraft‐Ragaller P, Abraham S, Lueck C, Meurer M. Response of HIV‐infected patients with syphilis to therapy with penicillin or IV ceftriaxone. Eur J Med Res 2011;16:47–51. Cross Ref link Pubmed link
  • 95  Ronald AR, Silverman M, McCutchan JA, et al. Evaluation of new anti‐infective drugs for the treatment of syphilis. Clin Infect Dis 1992;15(Suppl. 1):140–7. Cross Ref link
  • 96  Gordon SM, Eaton ME, George R, et al. The response of symptomatic neurosyphilis to high‐dose intravenous penicillin G in patients with human immunodeficiency virus infection. N Engl J Med 1994;331:1469–73. Cross Ref link Pubmed link
  • 97  Tipple C, McClure MO, Taylor GP. High prevalence of macrolide resistant Treponema pallidum strains in a London centre. Sex Transm Infect 2011;87(6):486–8. Cross Ref link Pubmed link
  • 98  Grimes M, Sahi SK, Godornes BC, et al. Two mutations associated with macrolide resistance in Treponema pallidum: increasing prevalence and correlation with molecular strain type in Seattle, Washington. Sex Transm Dis 2012;39(12):954–8. Cross Ref link Pubmed link

Congenital syphilis

  • 99  World Health Organization (WHO). Baseline Report on Global Sexually Transmitted Infection Surveillance 2012. Geneva: WHO.
  • 100  Blencowe H, Cousens S, Kamb M, Berman S, Lawn JE. Lives Saved Tool supplement detection and treatment of syphilis in pregnancy to reduce syphilis related stillbirths and neonatal mortality. BMC Public Health 2011;11(Suppl. 3):S9. Cross Ref link Pubmed link
  • 101  Peterman TA, Newman DR, Davis D, Su JR. Do women with persistently negative non‐treponemal test results transmit syphilis during pregnancy? Sex Transm Dis 2013:40(4):311–15. Cross Ref link Pubmed link
  • 102  Gomes GB, Kamb ML, Newman LM, Mark J, Broutet N, Hawkes SJ. Untreated maternal syphilis and adverse outcomes of pregnancy: a systematic review and meta‐analysis Bull World Health Organ 2013;91(3):217–26. Cross Ref link Pubmed link
  • 103  Kamb ML, Newman LM, Riley PL, et al. A road map for the global elimination of congenital syphilis. Obstet Gynecol Int 2010;2010:ID312798. Cross Ref link
  • 104  Centers for Disease Control and Prevention. Sexually transmitted disease surveillance 2011. Atlanta: US Department of Health and Human Services, 2012. http://www.cdc.gov/std/stats11/Surv2011.pdf (last accessed June 2014).
  • 105  Simms I, Royal College of Paediatrics and Child Health. Congenital syphilis in children under two. http://www.rcpch.ac.uk/what‐we‐do/bpsu/current‐studies/congenital‐syphilis/congenital‐syphilis (last accessed June 2014).
  • 106  Froberg MK, Fitzgerald TJ, Hamilton TR, Hamilton B, Zarabi M. Pathology of congenital syphilis in rabbits. Infect Immun 1993;61(11):4743–9. Pubmed link
  • 107  Holmes KK, Sparling PF, Stamm WE, et al., eds. Sexually Transmitted Diseases, 4th edn. New York: McGraw Hill, 2008.
  • 108  Schwartz DA, Larsen SA, Beck‐Sangue C, et al. Pathology of the umbilical cord in congenital syphilis: analysis of 25 specimens using histochemistry and immunofluorescent antibody to Treponema pallidum. Hum Pathol 1995;26:784–91. Cross Ref link Pubmed link
  • 109  Hirø SK, Bhat GJ, Patel JB, et al. Early congenital syphilis: clinico‐radiological features in 202 patients. Sex Transm Dis 1985;12:177–83. Cross Ref link Pubmed link
  • 110  Freiman I, Super M. Thrombocytopenia and congenital syphilis in South African Bantu infants. Arch Dis Child 1966;41:87–90. Cross Ref link Pubmed link
  • 111  Dunlop EMC, Zwink RB. Incidence of corneal changes in congenital syphilis Br J Vener Dis 1954;30: 201–9. Pubmed link
  • 112  Robinson RCV. Congenital syphilis. Arch Dermatol 1969;99:599–610. Cross Ref link Pubmed link
  • 113  Britten MJA, Palmer CAL. Glaucoma and inactive syphilitic interstitial keratitis. Br J Ophthalmol 1964;48:181–90. Cross Ref link Pubmed link
  • 114  Horne GO. Topical cortisone in syphilitic interstitial keratitis. Br J Vener Dis 1955;31:9–24. Pubmed link
  • 115  Borella L, Goobar JE, Clark GM. Synovitis of the knee joints in late congenital syphilis. JAMA 1962;180:190–2. Cross Ref link Pubmed link
  • 116  Morrison AW. Management of severe deafness in adults. Proc R Soc Med 1969;62:959–67. Pubmed link
  • 117  Bonugli FS. Involvement of aortic valve and ascending aorta in congenital syphilis. Br J Vener Dis 1961;37:257–67. Pubmed link
  • 118  White RJ. Aortic incompetence associated with congenital syphilis. Br J Vener Dis 1965;41:149. Pubmed link
  • 119  Bradlaw RV. The dental stigmata of prenatal syphilis. Oral Med Oral Pathol 1953;6:147–58. Cross Ref link
  • 120  Parish JL. Treponemal infections in the pediatric population. Clin Dermatol 2000;18:687–700. Cross Ref link Pubmed link
  • 121  Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2010. MMWR 2010;59(RR‐12):36–9. http://www.cdc.gov/std/treatment/2010/STD‐Treatment‐2010‐RR5912.pdf (last accessed June 2014).
  • 122  Kingston M, French P, Goh B, et al. UK national guidelines on early and late syphilis 2008. Int J STD AIDS 2008;19:729–40. Cross Ref link Pubmed link
  • 123  French P, Gomberg M, Janier M, et al. European guidelines on the management of syphilis. Int J STD AIDS 2009;20:300–9. Cross Ref link Pubmed link