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CNS Infections pp 227-247 | Cite as

Neurosyphilis

  • Juan C. SalazarEmail author
Chapter

Abstract

Syphilis is a sexually transmitted infection caused by the spirochetal bacterium Treponema pallidum, subspecies pallidum. During early syphilis, the spirochete has the ability to disseminate into the central nervous system and cause both symptomatic and asymptomatic meningitis and in more severe cases vasculitis leading to thrombosis, ischemia, and even death. During tertiary syphilis, the chronic inflammatory responses to the spirochete can severely compromise the brain parenchyma and the spinal cord, leading to paresis and tabes dorsalis. In this chapter we will review the clinical presentation, diagnostic criteria, and treatment modalities for neurosyphilis.

Keywords

Treponema pallidum Neurosyphilis Meningitis Meningovascular syphilis Gumma Paresis Tabes dorsalis 

References

  1. 1.
    Radolf JD, Hazlett KRO, Lukehart SA. Pathogenesis of syphilis. In: Radolf JD, Lukehart SA, editors. Pathogenic treponemes: cellular and molecular biology. Norfolk: Caister Academic Press; 2006. p. 197–236.Google Scholar
  2. 2.
    Salazar JC, Hazlett KR, Radolf JD. The immune response to infection with Treponema pallidum, the stealth pathogen. Microbes Infect. 2002;4:1133–40.PubMedCrossRefGoogle Scholar
  3. 3.
    WHO. Global incidence and prevalence of selected curable sexually transmitted infections-2008. Geneva: World Health Organization; 2012.Google Scholar
  4. 4.
    Cruz AR, Ramirez LG, Zuluaga AV, et al. Immune evasion and recognition of the syphilis spirochete in blood and skin of secondary syphilis patients: two immunologically distinct compartments. PLoS Negl Trop Dis. 2012;6:e1717.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Merritt HH, Adams RD, Solomon HC. Neurosyphilis. New York: Oxford University Press; 1946.Google Scholar
  6. 6.
    Tramont EC. Treponema pallidum (syphilis). In: Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas and Bennett’s principles and practice of infectious diseases. Philadelphia: Churchill Livingstone Elsevier; 2010. p. 3035–53.CrossRefGoogle Scholar
  7. 7.
    Tramont EC, Boyajian SS. Learning from history: what the public health response to syphilis teaches us about HIV/AIDS. J Contemp Health Law Policy. 2010;26:253–99.PubMedGoogle Scholar
  8. 8.
    Norris SJ, Paster BJ, Moter A, G’bel UB. The genus treponema. In: Dworkin MS, Falkow S, Rosenberg E, Schliefer KH, Stackebrandt E, editors. The prokaryotes: an evolving electronic resource for the microbiological community. New York: Springer; 2001.Google Scholar
  9. 9.
    Izard J, Renken C, Hsieh CE, et al. Cryo-electron tomography elucidates the molecular architecture of Treponema pallidum, the syphilis spirochete. J Bacteriol. 2009;191:7566–80.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Fraser CM, Norris SJ, Weinstock GM, et al. Complete genome sequence of Treponema pallidum, the syphilis spirochete. Science. 1998;281:375–88.PubMedCrossRefGoogle Scholar
  11. 11.
    Cameron CE. The T, pallidum outer membrane and outer membrane proteins. In: Radolf JD, Lukehart SA, editors. Pathogenic Treponema: molecular and cellular biology. Norwich: Caister Academic Press; 2006. p. 237–66.Google Scholar
  12. 12.
    Cox DL, Luthra A, Dunham-Ems S, et al. Surface immunolabeling and consensus computational framework to identify candidate rare outer membrane proteins of Treponema pallidum. Infect Immun. 2010;78:5178–94.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Desrosiers DC, Anand A, Luthra A, et al. TP0326, a Treponema pallidum beta-barrel assembly machinery A (BamA) orthologue and rare outer membrane protein. Mol Microbiol. 2011;80:1496–515.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Fenton KA, Breban R, Vardavas R, et al. Infectious syphilis in high-income settings in the 21st century. Lancet Infect Dis. 2008;8:244–53.PubMedCrossRefGoogle Scholar
  15. 15.
    Sexually Transmitted Disease Surveillance 2011. U.S. Department of Health and Human Services. 2012. The online version of this report is available at http://www.cdc.gov/std/stats.
  16. 16.
    Mayer KH, Mimiaga MJ. Resurgent syphilis in the United States: urgent need to address an evolving epidemic. Ann Intern Med. 2011;155:192–3.PubMedCrossRefGoogle Scholar
  17. 17.
    French P, Gomberg M, Janier M, Schmidt B, van Voorst Vader P, Young H. IUSTI: 2008 European Guidelines on the Management of Syphilis. Int J STD AIDS. 2009;20:300–9.PubMedCrossRefGoogle Scholar
  18. 18.
    European Centre for Disease Prevention and Control. Sexually transmitted infections in Europe 1990–2010. Stockholm: ECDC; 2012. (http://www.ecdc.europa.eu/en/publications/publications/201206-sexually-transmitted-infections-europe-2010.pdf).
  19. 19.
    Scott CM, Flint SR. Oral syphilis–re-emergence of an old disease with oral manifestations. Int J Oral Maxillofac Surg. 2005;34:58–63.PubMedCrossRefGoogle Scholar
  20. 20.
    Tucker JD, Yin YP, Wang B, Chen XS, 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 Suppl 2:ii16–8.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Tucker JD, Cohen MS. China’s syphilis epidemic: epidemiology, proximate determinants of spread, and control responses. Curr Opin Infect Dis. 2011;24:50–5.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Hutchinson CM, Hook 3rd EW, Shepherd M, Verley J, Rompalo AM. Altered clinical presentation of early syphilis in patients with human immunodeficiency virus infection. Ann Intern Med. 1994;121:94–100.PubMedCrossRefGoogle Scholar
  23. 23.
    Ansell DA, Hu TC, Straus M, Cohen M, Sherer R. HIV and syphilis seroprevalence among clients with sexually transmitted diseases attending a walk-in clinic at Cook County Hospital. Sex Transm Dis. 1994;21:93–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Zetola NM, Klausner JD. Syphilis and HIV infection: an update. Clin Infect Dis. 2007;44:1222–8.PubMedCrossRefGoogle Scholar
  25. 25.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Wasserheit JN. Epidemiological synergy. Interrelationships between human immunodeficiency virus infection and other sexually transmitted diseases. Sex Transm Dis. 1992;19:61–77.PubMedCrossRefGoogle Scholar
  27. 27.
    Tosca A, Lehou J, Hatjivasiliou M, Varelzidis A, Stratigos JD. Infiltrate of syphilitic lesions before and after treatment. Genitourin Med. 1988;64:289–93.PubMedCentralPubMedGoogle Scholar
  28. 28.
    Van Voorhis WC, Barrett LK, Koelle DM, Nasio JM, Plummer FA, Lukehart SA. Primary and secondary syphilis lesions contain mRNA for Th1 cytokines. J Infect Dis. 1996;173:491–5.PubMedCrossRefGoogle Scholar
  29. 29.
    McBroom RL, Styles AR, Chiu MJ, Clegg C, Cockerell CJ, Radolf JD. Secondary syphilis in persons infected with and not infected with HIV-1: a comparative immunohistologic study. Am J Dermatopathol. 1999;21:432–41.PubMedCrossRefGoogle Scholar
  30. 30.
    Salazar JC, Cruz AR, Pope CD, et al. Treponema pallidum elicits innate and adaptive cellular immune responses in skin and blood during secondary syphilis: a flow-cytometric analysis. J Infect Dis. 2007;195:879–87.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Sheffield JS, Wendel Jr GD, McIntire DD, Norgard MV. Effect of genital ulcer disease on HIV-1 coreceptor expression in the female genital tract. J Infect Dis. 2007;196:1509–16.PubMedCrossRefGoogle Scholar
  32. 32.
    Theus SA, Harrich DA, Gaynor R, Radolf JD, Norgard MV. Treponema pallidum, lipoproteins, and synthetic lipoprotein analogues induce human immunodeficiency virus type 1 gene expression in monocytes via NF-κB activation. J Infect Dis. 1998;177:941–50.PubMedCrossRefGoogle Scholar
  33. 33.
    Jarzebowski W, Caumes E, Dupin N, et al. Effect of early syphilis infection on plasma viral load and CD4 cell count in human immunodeficiency virus-infected men: results from the FHDH-ANRS CO4 cohort. Arch Intern Med. 2012;172:1237–43.PubMedCrossRefGoogle Scholar
  34. 34.
    Moore JE. Asymptomatic neurosyphilis: a comparison of early and late asymptomatic neurosyphilis. Arch Derm Syphilol. 1928;18:99–108.CrossRefGoogle Scholar
  35. 35.
    Nagappa M, Sinha S, Taly AB, et al. Neurosyphilis: MRI features and their phenotypic correlation in a cohort of 35 patients from a tertiary care university hospital. Neuroradiology. 2013;55:379–88. doi:  10.1007/s00234-012-1017-9. Epub 2012 Dec 30.
  36. 36.
    Chesney AM, Kemp JE. Incidence of Spirochaeta pallidum in cerebrospinal fluid during early stages of syphilis. JAMA. 1924;22:1725–8.CrossRefGoogle Scholar
  37. 37.
    Stokes JH, Beerman H, Ingraham NR. Modern clinical syphilology. 3rd ed. Philadelphia: W.B. Saunders; 1944.Google Scholar
  38. 38.
    Hahn RD, Clark EG. Asymptomatic neurosyphilis; a review of the literature. Am J Syph Gonorrhea Vener Dis. 1946;30:305–16.PubMedGoogle Scholar
  39. 39.
    Lukehart SA, Hook 3rd EW, Baker-Zander 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;109:855–62.PubMedCrossRefGoogle Scholar
  40. 40.
    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. The Syphilis and HIV Study Group. N Engl J Med. 1997;337:307–14.PubMedCrossRefGoogle Scholar
  41. 41.
    Marra CM. Update on neurosyphilis. Curr Infect Dis Rep. 2009;11:127–34.PubMedCrossRefGoogle Scholar
  42. 42.
    Ghanem KG, Workowski KA. Management of adult syphilis. Clin Infect Dis. 2011;53 Suppl 3:S110–28.PubMedCrossRefGoogle Scholar
  43. 43.
    Collis TK, Celum CL. The clinical manifestations and treatment of sexually transmitted diseases in human immunodeficiency virus-positive men. Clin Infect Dis. 2001;32:611–22.PubMedCrossRefGoogle Scholar
  44. 44.
    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;189:369–76.PubMedCrossRefGoogle Scholar
  45. 45.
    Flood JM, Weinstock HS, Guroy ME, Bayne L, Simon RP, Bolan G. Neurosyphilis during the AIDS epidemic, San Francisco, 1985–1992. J Infect Dis. 1998;177:931–40.PubMedCrossRefGoogle Scholar
  46. 46.
    Ghanem KG, Moore RD, Rompalo AM, Erbelding EJ, Zenilman JM, Gebo KA. Lumbar puncture in HIV-infected patients with syphilis and no neurologic symptoms. Clin Infect Dis. 2009;48:816–21.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Merritt HH, Moore M. Acute syphilitic meningitis. Medicine. 1935;14:119–83.CrossRefGoogle Scholar
  48. 48.
    Feng W, Caplan M, Matheus MG, Papamitsakis NI. Meningovascular syphilis with fatal vertebrobasilar occlusion. Am J Med Sci. 2009;338:169–71.PubMedCrossRefGoogle Scholar
  49. 49.
    Chahine LM, Khoriaty RN, Tomford WJ, Hussain MS. The changing face of neurosyphilis. Int J Stroke. 2011;6:136–43.PubMedCrossRefGoogle Scholar
  50. 50.
    Kodama K, Okada S, Komatsu N, et al. Relationship between MRI findings and prognosis for patients with general paresis. J Neuropsychiatry Clin Neurosci. 2000;12:246–50.PubMedCrossRefGoogle Scholar
  51. 51.
    Berbel-Garcia A, Porta-Etessam J, Martinez-Salio A, et al. Magnetic resonance image-reversible findings in a patient with general paresis. Sex Transm Dis. 2004;31:350–2.PubMedCrossRefGoogle Scholar
  52. 52.
    Luo W, Ouyang Z, Xu H, Chen J, Ding M, Zhang B. The clinical analysis of general paresis with 5 cases. J Neuropsychiatry Clin Neurosci. 2008;20:490–3.PubMedCrossRefGoogle Scholar
  53. 53.
    Agayeva N, Karli-Oguz K, Saka E. Teaching neuroImages: a neurosyphilis case presenting with atypical neuroradiologic findings. Neurology. 2013;80:e119.PubMedCrossRefGoogle Scholar
  54. 54.
    Dewhurst K. The neurosyphilitic psychoses today. A survey of 91 cases. Br J Psychiatry. 1969;115:31–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Russouw HG, Roberts MC, Emsley RA, Truter R. Psychiatric manifestations and magnetic resonance imaging in HIV-negative neurosyphilis. Biol Psychiatry. 1997;41:467–73.PubMedCrossRefGoogle Scholar
  56. 56.
    Mehrabian S, Raycheva MR, Petrova EP, Tsankov NK, Traykov LD. Neurosyphilis presenting with dementia, chronic chorioretinitis and adverse reactions to treatment: a case report. Cases J. 2009;2:8334.PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Abdelerahman KT, Santamaria DD, Rakocevic G. Pearls & Oy-sters: neurosyphilis presenting as mesial temporal encephalitis. Neurology. 2012;79:e206–8.PubMedCrossRefGoogle Scholar
  58. 58.
    Denays R, Collier A, Rubinstein M, Atsama P. A 51-year-old woman with disorientation and amnesia. Lancet. 1999;354:1786.PubMedCrossRefGoogle Scholar
  59. 59.
    Bash S, Hathout GM, Cohen S. Mesiotemporal T2-weighted hyperintensity: neurosyphilis mimicking herpes encephalitis. AJNR Am J Neuroradiol. 2001;22:314–6.PubMedGoogle Scholar
  60. 60.
    Szilak I, Marty F, Helft J, Soeiro R. Neurosyphilis presenting as herpes simplex encephalitis. Clin Infect Dis. 2001;32:1108–9.PubMedCrossRefGoogle Scholar
  61. 61.
    Hahn RD. Tabes dorsalis with special reference to primary optic atrophy. Br J Vener Dis. 1957;33:139–48.PubMedCentralPubMedGoogle Scholar
  62. 62.
    Horowitz HW, Valsamis MP, Wicher V, et al. Brief report: cerebral syphilitic gumma confirmed by the polymerase chain reaction in a man with human immunodeficiency virus infection. N Engl J Med. 1994;331:1488–91.PubMedCrossRefGoogle Scholar
  63. 63.
    Seeley WW, Venna N. Neurosyphilis presenting with gummatous oculomotor nerve palsy. J Neurol Neurosurg Psychiatry. 2004;75:789.PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Fargen KM, Alvernia JE, Lin CS, Melgar M. Cerebral syphilitic gummata: a case presentation and analysis of 156 reported cases. Neurosurgery. 2009;64:568–75; discussion 75–6.PubMedCrossRefGoogle Scholar
  65. 65.
    Aldave AJ, King JA, Cunningham Jr ET. Ocular syphilis. Curr Opin Ophthalmol. 2001;12:433–41.PubMedCrossRefGoogle Scholar
  66. 66.
    Smith MM, Anderson JC. Neurosyphilis as a cause of facial and vestibulocochlear nerve dysfunction: MR imaging features. AJNR Am J Neuroradiol. 2000;21:1673–5.PubMedGoogle Scholar
  67. 67.
    Becker GD. Late syphilitic hearing loss: a diagnostic and therapeutic dilemma. Laryngoscope. 1979;89:1273–88.PubMedGoogle Scholar
  68. 68.
    Zoller M, Wilson WR, Nadol Jr JB, Girard KF. Detection of syphilitic hearing loss. Arch Otolaryngol. 1978;104:63–5.PubMedCrossRefGoogle Scholar
  69. 69.
    Pletcher SD, Cheung SW. Syphilis and otolaryngology. Otolaryngol Clin North Am. 2003;36:595–605, vi.PubMedCrossRefGoogle Scholar
  70. 70.
    Musher DM. Syphilis, neurosyphilis, penicillin, and AIDS. J Infect Dis. 1991;163:1201–6.PubMedCrossRefGoogle Scholar
  71. 71.
    Musher DM, Hamill RJ, Baughn RE. Effect of human immunodeficiency virus (HIV) infection on the course of syphilis and on the response to treatment. Ann Intern Med. 1990;113:872–81.PubMedCrossRefGoogle Scholar
  72. 72.
    Golden MR, Marra CM, Holmes KK. Update on syphilis: resurgence of an old problem. JAMA. 2003;290:1510–4.PubMedCrossRefGoogle Scholar
  73. 73.
    Farhi D, Dupin N. Management of syphilis in the HIV-infected patient: facts and controversies. Clin Dermatol. 2010;28:539–45.PubMedCrossRefGoogle Scholar
  74. 74.
    Poliseli R, Vidal JE, Penalva De Oliveira AC, Hernandez AV. Neurosyphilis in HIV-infected patients: clinical manifestations, serum venereal disease research laboratory titers, and associated factors to symptomatic neurosyphilis. Sex Transm Dis. 2008;35:425–9.PubMedCrossRefGoogle Scholar
  75. 75.
    Libois A, De Wit S, Poll B, et al. HIV and syphilis: when to perform a lumbar puncture. Sex Transm Dis. 2007;34:141–4.PubMedCrossRefGoogle Scholar
  76. 76.
    Workowski KA, Berman S. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010;59:1–110.PubMedGoogle Scholar
  77. 77.
    Guyure KA. Infections. In: Prayson RA, editor. Neuropathology. Philadelphia: Elsevier/Churchill Livingstone; 2005. p. 287–338.Google Scholar
  78. 78.
    Brown E, Gray F. Bacterial infections. In: Love S, Louis DN, Ellison DW, editors. Greenfield’s neuropathology. London: Hodder Arnold; 2008. p. 1391–445.Google Scholar
  79. 79.
    Jackman Jr JD, Radolf JD. Cardiovascular syphilis. Am J Med. 1989;87:425–33.PubMedCrossRefGoogle Scholar
  80. 80.
    Ghanem KG. Neurosyphilis: a historical perspective and review. CNS Neurosci Ther. 2010;16:e157–68.PubMedCrossRefGoogle Scholar
  81. 81.
    Larsen SA, Pope V, Johnson RE, Kennedy EJ. A manual of tests for syphilis. Washington, DC: American Public Health Association; 1998.Google Scholar
  82. 82.
    Larsen SA, Steiner BM, Rudolph AH. Laboratory diagnosis and interpretation of tests for syphilis. Clin Microbiol Rev. 1995;8:1–21.PubMedCentralPubMedGoogle Scholar
  83. 83.
    Belisle JT, Brandt ME, Radolf JD, Norgard MV. Fatty acids of Treponema pallidum and Borrelia burgdorferi lipoproteins. J Bacteriol. 1994;176:2151–7.PubMedCentralPubMedGoogle Scholar
  84. 84.
    Post JJ, Khor C, Furner V, Smith DE, Whybin LR, Robertson PW. Case report and evaluation of the frequency of the prozone phenomenon in syphilis serology – an infrequent but important laboratory phenomenon. Sex Health. 2012;9:488–90.PubMedCrossRefGoogle Scholar
  85. 85.
    Creegan L, Bauer HM, Samuel MC, Klausner J, Liska S, Bolan G. 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;34:1016–8.PubMedGoogle Scholar
  86. 86.
    Radolf JD, Pillay A, Cox DL. Treponema and Brachyspira, human host-associated spirochetes. In: Versalovic J, editor. Manual of clinical microbiology. 10th ed. Washington, D.C.: American Society for Microbiology; 2011. p. 941–63.Google Scholar
  87. 87.
    CDC. Discordant results from reverse sequence syphilis screening-five laboratories, United States, 2006–2010. MMWR Morb Mortal Wkly Rep. 2011;60:133–7.Google Scholar
  88. 88.
    Hernandez-Aguado I, Bolumar F, Moreno R, et al. False-positive tests for syphilis associated with human immunodeficiency virus and hepatitis B virus infection among intravenous drug abusers. Valencian Study Group on HIV Epidemiology. Eur J Clin Microbiol Infect Dis. 1998;17:784–7.PubMedCrossRefGoogle Scholar
  89. 89.
    Augenbraun MH, DeHovitz JA, Feldman J, Clarke L, Landesman S, Minkoff HM. Biological false-positive syphilis test results for women infected with human immunodeficiency virus. Clin Infect Dis. 1994;19:1040–4.PubMedCrossRefGoogle Scholar
  90. 90.
    Hutchinson CM, Rompalo AM, Reichart CA, Hook 3rd EW. Characteristics of patients with syphilis attending Baltimore STD clinics. Multiple high-risk subgroups and interactions with human immunodeficiency virus infection. Arch Intern Med. 1991;151:511–6.PubMedCrossRefGoogle Scholar
  91. 91.
    Geisler WM. The prozone phenomenon in syphilis testing. South Med J. 2004;97:327–8.PubMedCrossRefGoogle Scholar
  92. 92.
    Ghanem KG, Erbelding EJ, Wiener ZS, Rompalo AM. Serological response to syphilis treatment in HIV-positive and HIV-negative patients attending sexually transmitted diseases clinics. Sex Transm Infect. 2007;83:97–101.PubMedCentralPubMedCrossRefGoogle Scholar
  93. 93.
    Hicks CB, Benson PM, Lupton GP, Tramont EC. Seronegative secondary syphilis in a patient infected with the human immunodeficiency virus (HIV) with Kaposi sarcoma. A diagnostic dilemma. Ann Intern Med. 1987;107:492–5.PubMedCrossRefGoogle Scholar
  94. 94.
    Kingston AA, Vujevich J, Shapiro M, et al. Seronegative secondary syphilis in 2 patients coinfected with human immunodeficiency virus. Arch Dermatol. 2005;141:431–3.PubMedCrossRefGoogle Scholar
  95. 95.
    Marra CM, Tantalo LC, Maxwell CL, Ho EL, Sahi SK, Jones T. The rapid plasma reagin test cannot replace the venereal disease research laboratory test for neurosyphilis diagnosis. Sex Transm Dis. 2012;39:453–7.PubMedCentralPubMedCrossRefGoogle Scholar
  96. 96.
    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. J Clin Lab Anal. 2008;22:257–61.PubMedCrossRefGoogle Scholar
  97. 97.
    Jaffe HW, Larsen SA, Peters M, Jove DF, Lopez B, Schroeter AL. Tests for treponemal antibody in CSF. Arch Intern Med. 1978;138:252–5.PubMedCrossRefGoogle Scholar
  98. 98.
    Schroeter AL, Lucas JB, Price EV, Falcone VH. Treatment for early syphilis and reactivity of serologic tests. JAMA. 1972;221:471–6.PubMedCrossRefGoogle Scholar
  99. 99.
    Zenker PN, Rolfs RT. Treatment of syphilis, 1989. Rev Infect Dis. 1990;12 Suppl 6:S590–609.PubMedCrossRefGoogle Scholar
  100. 100.
    Ghanem KG, Erbelding EJ, Cheng WW, Rompalo AM. Doxycycline compared with benzathine penicillin for the treatment of early syphilis. Clin Infect Dis. 2006;42:e45–9.PubMedCrossRefGoogle Scholar
  101. 101.
    Wong T, Singh AE, De P. Primary syphilis: serological treatment response to doxycycline/tetracycline versus benzathine penicillin. Am J Med. 2008;121:903–8.PubMedCrossRefGoogle Scholar
  102. 102.
    Spornraft-Ragaller P, Abraham S, Lueck C, Meurer M. Response of HIV-infected patients with syphilis to therapy with penicillin or intravenous ceftriaxone. Eur J Med Res. 2011;16:47–51.PubMedCentralPubMedCrossRefGoogle Scholar
  103. 103.
    Long CM, Klausner JD, Leon S, et al. Syphilis treatment and HIV infection in a population-based study of persons at high risk for sexually transmitted disease/HIV infection in Lima, Peru. Sex Transm Dis. 2006;33:151–5.PubMedCrossRefGoogle Scholar
  104. 104.
    Shann S, Wilson J. Treatment of neurosyphilis with ceftriaxone. Sex Transm Infect. 2003;79:415–6.PubMedCentralPubMedCrossRefGoogle Scholar
  105. 105.
    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;30:540–4.PubMedCrossRefGoogle Scholar
  106. 106.
    Hook 3rd EW, Roddy RE, Handsfield HH. Ceftriaxone therapy for incubating and early syphilis. J Infect Dis. 1988;158:881–4.PubMedCrossRefGoogle Scholar
  107. 107.
    Ormerod LD, et al. Syphilitic posterior uveitis: correlative findings and significance. Clin Infect Dis. 2001;32(12):1661–73. doi: 10.1086/320766.

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© Springer-Verlag London 2014

Authors and Affiliations

  1. 1.Department of PediatricsConnecticut Children’s Medical CenterHartfordUSA

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