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Biology and Natural History of Syphilis

  • Attila Horváth
Chapter

Abstract

Syphilis continues to have great public health importance because it increases the risk of human immunodeficiency virus (HIV) infection significantly; furthermore, statistical studies suggest that there are no chances of eradicating it in the foreseeable future. The T. pallidumGenome Sequencing Project also confirmed what had already been suggested by ongoing experimental efforts: this bacterium is a fastidious, microaerophilic, obligate parasite of humans. T. pallidumderives most essential macromolecules from the host, using interconversion pathways to generate others. The course of untreated syphilis consists of intermittent stages with sequential symptomatic and asymptomatic (latency) periods. This regular choreography, however, may be disturbed if the immunological competence of the host organism is severely compromised (HIV infection) by inappropriately administered prevention or antimicrobial therapy for another disease.

Keywords

Human Immunodeficiency Virus Infection Obligate Parasite Congenital Syphilis Secondary Syphilis Early Syphilis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1.  1.
    Baker-Zander, S.A., Hook III, E.W., Bonin, P., Handsfield, H.H., Lukehart, S.A.: Antigens of Treponema pallidum recognized by IgG and IgM antibodies during syphilis in humans. J. Infect. Dis. 151, 264–272 (1985)PubMedCrossRefGoogle Scholar
  2.  2.
    Baughn, R.E., Musher, D.M.: Secondary syphilitic lesions. Clin. Microbiol. Rev. 18, 205–216 (2005)PubMedCrossRefGoogle Scholar
  3.  3.
    Bauer, T.J., Price, E.V., Cutler, J.C.: Spinal fluid examinations among patients with primary or secondary syphilis. Am. J. Syph. 36, 309–318 (1952)PubMedGoogle Scholar
  4.  4.
    Benoit, S., Posey, J.E., Chenoweth, M.R., Gherardini, F.C.: Treponema pallidum 3-phosphoglycerate mutase is a heat-labile enzyme that may limit the maximum growth temperature for the spirochete. J. Bacteriol. 183, 4702–4708 (2001)PubMedCrossRefGoogle Scholar
  5.  5.
    Blanco, D.R., Champion, C.I., Miller, J.N., Lovett, M.A.: Antigenic and structural characterization of Treponema pallidum (Nichols strain) endoflagella. Infect. Immun. 56, 168–175 (1988)PubMedGoogle Scholar
  6.  6.
    Blanco, D.R., Champion, C.I., Exner, M.M., Shang, E.S., Skare, J.T., Hancock, R.E., Miller, J.N., Lovett, M.A.: Recombinant Treponema pallidum rare outer membrane protein 1 (Tromp1) expressed in Escherichia coli has porin activity and surface antigenic exposure. J. Bacteriol. 178, 6685–6692 (1996)PubMedGoogle Scholar
  7.  7.
    Bos, J.D., Hamerlinck, F., Cormane, R.H.: Immunoglobulin-bearing polymorphonuclear leucocytes in primary syphilis. Br. J. Vener. Dis. 56, 218–220 (1980)PubMedGoogle Scholar
  8.  8.
    Centurion-Lara, A., Castro, C., Castillo, R., Shaffer, J.M., Van Voorhis, W.C., Lukehart, S.A.: The flanking region sequences of the 15-kDa lipoprotein gene differentiate pathogenic treponemes. J. Infect. Dis. 177, 1036–1040 (1998)PubMedGoogle Scholar
  9.  9.
    Cox, D.L., Chang, P., McDowall, A.W., Radolf, J.D.: The outer membrane, not a coat of host proteins, limits antigenicity of virulent Treponema pallidum. Infect. Immun. 60, 1076–1083 (1992)PubMedGoogle Scholar
  10. 10.
    Cumberland, M.C., Turner, T.B.: The rate of mutiplicatio of Treponema pallidum in normal and immune rabbits. Am.J.Syph. Gonorrhea Vener. Dis. 33, 201 (1949)PubMedGoogle Scholar
  11. 11.
    Deka, R.K., Lee, Y.H., Hagman, K.E., Shevchenko, D., Lingwood, C.A., Hasemann, C.A., Norgard, M.V., Radolf, J.D.: Physicochemical evidence that Treponema pallidum TroA is a zinc-containing metalloprotein that lacks porin-like structure. J. Bacteriol. 181, 4420–4423 (1999)PubMedGoogle Scholar
  12. 12.
    Deka, R.K., Neil, L., Hagman, K.E., Machius, M., Tomchick, D.R., Brautigam, C.A., Norgard, M.V.: Structural evidence that the 32-kilodalton lipoprotein (Tp32) of Treponema pallidum is an L-methionine-binding protein. J. Biol. Chem. 279, 55644–55650 (2004)PubMedCrossRefGoogle Scholar
  13. 13.
    Feher, J., Somogyi, T., Timmer, M., Jozsa, L.: Early syphilitic hepatitis. Lancet ii, 896–899 (1975)CrossRefGoogle Scholar
  14. 14.
    Fieldsteel, A.H., et al.: Cultivation of virulent Treponema pallidum in tissue culture. Infect. Immun. 32, 908 (1981)PubMedGoogle Scholar
  15. 15.
    Fieldsteel, A.H.: Genetics. In: Schell, R.F., Musher, D.M. (eds.) Pathogenesis and Immunology of Treponemal Infection, pp. 39–54. Dekker, New York (1983)Google Scholar
  16. 16.
    Fitzgerald, T.J., Johnson, R.C., Miller, J.N., Sykes, J.A.: Characterization of the attachment of Treponema pallidum (Nichols strain) to cultured mammalian cells and the potential relationship of attachment to pathogenicity. Infect. Immun. 18, 467–478 (1977)PubMedGoogle Scholar
  17. 17.
    Fitzgerald, T.J., Repesh, L.A., Oakes, S.G.: Morphological destruction of cultured cells by the attachment of Treponema pallidum. Br. J. Vener. Dis. 58, 1–11 (1982). 104PubMedGoogle Scholar
  18. 18.
    Fraser, C.M., Norris, S.J., Weinstock, G.M., White, O., Sutton, G.G., Dodson, R., Gwinn, M., Hickey, E.K., Clayton, R., Ketchum, K.A., Sodergren, E., Hardham, J.M., McLeod, M.P., Salzberg, S., Peterson, J., Khalak, H., Richardson, D., Howell, J.K., Chidambaram, M., Utterback, T., McDonald, L., Artiach, P., Bowman, C., Cotton, M.D., Fujii, C., Garland, S., Hatch, B., Horst, K., Roberts, K., Sandusky, M., Weidman, J., Smith, H.O., Venter, J.C.: Complete genome sequence of Treponema pallidum, the syphilis spirochete. Science 281(5375), 324–325 (1998)CrossRefGoogle Scholar
  19. 19.
    Gjestland T.: The Oslo study of untreated syphilis: an epidemiologic investigation of the natural course of syphilitic inection based on a restudy of the Boeck-Bruusgaard material. Acta. Derm. Venereal 35(I Suppl [Stockh]34):1 (1955)Google Scholar
  20. 20.
    Greene, S.R., Stamm, L.V., Hardham, J.M., Young, N.R., Frye, J.G.: Identification, sequences, and expression of Treponema pallidum chemotaxis genes. DNA Seq. 7, 267–284 (1997)PubMedGoogle Scholar
  21. 21.
    Greene, S.R., Stamm, L.V.: Molecular characterization of Treponema pallidum mcp2, a putative chemotaxis protein gene. Infect. Immun. 66, 2999–3002 (1998)PubMedGoogle Scholar
  22. 22.
    Hagman, K.E., Porcella, S.F., Popova, T.G., Norgard, M.V.: Evidence for a methyl-accepting chemotaxis protein gene (mcp1) that encodes a putative sensory transducer in virulent Treponema pallidum. Infect. Immun. 65, 1701–1709 (1997)PubMedGoogle Scholar
  23. 23.
    Hazlett, K.R., Cox, D.L., Sikkink, R.A., Auch’ere, F., Rusnak, F., Radolf, J.D.: Contribution of neelaredoxin to oxygen tolerance by Treponema pallidum. Methods Enzymol. 353, 140–156 (2002)PubMedCrossRefGoogle Scholar
  24. 24.
    Hazlett, K.R., Rusnak, F., Kehres, D.G., Bearden, S.W., La Vake, C.J., La Vake, M.E., Maguire, M.E., Perry, R.D., Radolf, J.D.: The Treponema pallidum tro operon encodes a multiple metal transporter, a zinc-dependent transcriptional repressor, and a semi-autonomously expressed phosphoglycerate mutase. J. Biol. Chem. 278, 20687–20694 (2003)PubMedCrossRefGoogle Scholar
  25. 25.
    Hayes, N.S., Muse, K.E., Collier, A.M., Baseman, J.B.: Parasitism by virulent reponema pallidum of host cell surfaces. Infect. Immun. 17, 174–186 (1977)PubMedGoogle Scholar
  26. 26.
    Jenkin, H.: Cultivation of treponemes. In: Schell, R.F., Musher, D.M. (eds.) Pathogenesis and Immunology of Treponemal Infection. Dekker, New York (1982)Google Scholar
  27. 27.
    Jepsen, O.B., Hougen, K.H., Birch-Andersen, A.: Electron microscopy of Treponema pallidum Nichols. Acta Pathol. Microbiol. Scand. 74, 241–258 (1968)PubMedCrossRefGoogle Scholar
  28. 28.
    Jones, S.A., Marchitto, K.S., Miller, J.N., Norgard, M.V.: Monoclonal antibody with hemagglutination, immobilization, and neutralization activities defines an immunodominant, 47, 000 mol wt, surface-exposed immunogen of Treponema pallidum (Nichols). J. Exp. Med. 160, 1404–1420 (1984)PubMedCrossRefGoogle Scholar
  29. 29.
    Kumar, B., Muralidhar, S.: Malignant syphilis: a review. AIDS Patient Care STDs 12, 921–925 (1998)PubMedCrossRefGoogle Scholar
  30. 30.
    La Fond, R.E., Lukehart, S.A.: Biological Basis of Syphilis. Clin. Microbiol. Rev. 19, 29–49 (2006)CrossRefGoogle Scholar
  31. 31.
    Lee, K.H., Choi, H.J., Lee, M.G., Lee, J.B.: Virulent Treponema pallidum 47 kDa antigen regulates the expression of cell adhesion molecules and binding of T-lymphocytes to cultured human dermal microvascular endothelial cells. Yonsei Med. J. 41, 623–633 (2000)PubMedGoogle Scholar
  32. 32.
    Lee, J.H., Choi, H.J., Jung, J., Lee, M.G., Lee, J.B., Lee, K.H.: Receptors for Treponema pallidum attachment to the surface and matrix proteins of cultured human dermal microvascular endothelial cells. Yonsei Med. J. 44, 371–378 (2003)PubMedGoogle Scholar
  33. 33.
    Lee, R.V., Thornton, G.F., Conn, H.O.: Liver disease associated with secondary syphilis. N Engl J. Med. 284, 1423–1425 (1971)PubMedCrossRefGoogle Scholar
  34. 34.
    Lien, E., Sellati, T.J., Yoshimura, A., Flo, T.H., Rawadi, G., Finberg, R.W., Carroll, J.D., Espevik, T., Ingalls, R.R., Radolf, J.D., Golenbock, D.T.: Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products. J. Biol. Chem. 274, 33419–33425 (1999)PubMedCrossRefGoogle Scholar
  35. 35.
    Lukehart, S.A., Hook III, E.W., Baker-Zander, S.A., Collier, A.C., Critchlow, C.W., Handsfield, H.H.: Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment. Ann. Intern. Med. 109, 855–862 (1988)PubMedGoogle Scholar
  36. 36.
    Magnuson, H.J., Eagle, H., Fleischmann, R.: The minimal infectious inoculum of Spirochaeta pallida (Nichols strain), and a consideration of its rate of multiplication in vivo. Am. J. Syph. Gonorrhea Vener. Dis. 32, 1–18 (1948)PubMedGoogle Scholar
  37. 37.
    Magnuson, H.J., Thomas, E.W., Olansky, S., Kaplan, B.I., DeMello, L., Cutler, J.C.: Inoculation syphilis in human volunteers. Medicine 35, 33–82 (1956)PubMedCrossRefGoogle Scholar
  38. 38.
    Mahoney, J.F., Bryant, K.K.: The time element in the penetration of the genital mucosa of the rabbit by the Treponema pallidum. J. Vener. Dis. Inf. 15, 1–5 (1934)Google Scholar
  39. 39.
    Maio, R.M., Fieldsteel, A.H.: Genetic relationship between Treponema pallidum and Treponema pertenue, two noncultivable human pathogens. J. Bacteriol. 141, 427–429 (1980)Google Scholar
  40. 40.
    Marra, C.M., Maxwell, C.L., Smith, S.L., Lukehart, S.A., Rompalo, A.M., Eaton, M., Stoner, B.P., Augenbraun, M., Barker, D.E., Corbett, J.J., Zajackowski, M., Raines, C., Nerad, J., Kee, R., Barnett, S.H.: Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features. J. Infect. Dis. 189, 369–376 (2004)PubMedCrossRefGoogle Scholar
  41. 41.
    Mascola, L., Pelosi, R., Blount, J.H., Alexander, C.E., Cates Jr., W.: Congenital syphilis revisited. Am. J. Dis. Child. 139, 575–580 (1985)PubMedGoogle Scholar
  42. 42.
    Metzger, M., Hardy Jr., P.H., Nell, E.E.: Influence of lysozyme upon the treponeme immobilization reaction. Am. J. Hyg. 73, 236–244 (1961)PubMedGoogle Scholar
  43. 43.
    Mullick, C.J., Liappis, A.P., Benator, D.A., Roberts, A.D., Parenti, D.M., Simon, G.L.: Syphilitic hepatitis in HIV-infected patients: a report of 7 cases and review of the literature. Clin. Infect. Dis. 39, 100–105 (2004)CrossRefGoogle Scholar
  44. 44.
    Nichols, H.J., Hough, W.H.: Demonstration of Spirochaeta pallida in the cerebrospinal fluid. JAMA 60, 108 (1913)Google Scholar
  45. 45.
    Nichols, J.C., Baseman, J.B.: Carbon sources utilized by virulent Treponema pallidum. Infect. Immun. 12, 1044–1050 (1975)PubMedGoogle Scholar
  46. 46.
    Norris, S.J., Sell, S.: Antigenic complexity of Treponema pallidum: antigenicity and surface localization of major polypeptides. J. Immunol. 133, 2686–2692 (1984)PubMedGoogle Scholar
  47. 47.
    O’Regan, S., Fong, J.S., de Chadarevian, J.P., Rishikof, J.R., Drummond, K.N.: Treponemal antigens in congenital and acquired syphilitic nephritis: demonstration by immunofluorescence studies. Ann. Intern. Med. 85, 325–327 (1976)PubMedGoogle Scholar
  48. 48.
    Penn, C.W., Rhodes, J.G.: Surface-associated antigens of Treponema pallidum concealed by an inert outer layer. Immunology 46, 9–16 (1982)PubMedGoogle Scholar
  49. 49.
    Purcell, B.K., Chamberlain, N.R., Goldberg, M.S., Andrews, L.P., Robinson, E.J., Norgard, M.V., Radolf, J.D.: Molecular cloning and characterization of the 15-kilodalton major immunogen of Treponema pallidum. Infect. Immun. 57, 3708–3714 (1989)PubMedGoogle Scholar
  50. 50.
    Radolf, J.D., Norgard, M.V., Schulz, W.W.: Outer membrane ultrastructure explains the limited antigenicity of virulent Treponema pallidum. Proc. Natl Acad. Sci. USA 86, 2051–2055 (1989)PubMedCrossRefGoogle Scholar
  51. 51.
    Ricord, P.: A Practical Treatise on Venereal Diseases. Rouvier et le Bouvier, Paris (1838)Google Scholar
  52. 52.
    Riley, B.S., Oppenheimer-Marks, N., Hansen, E.J., Radolf, J.D., Norgard, M.V.: Virulent Treponema pallidum activates human vascular endothelial cells. J. Infect. Dis. 165, 484–493 (1992)PubMedCrossRefGoogle Scholar
  53. 53.
    Riley, B.S., Oppenheimer-Marks, N., Radolf, J.D., Norgard, M.V.: Virulent Treponema pallidum promotes adhesion of leukocytes to human vascular endothelial cells. Infect. Immun. 62, 4622–4625 (1994)PubMedGoogle Scholar
  54. 54.
    Romero-Jimenez, M.J., Suarez, L.I., Fajardo, P.J.M., Baron, F.B.: Malignant syphilis in patient with human immunodeficiency virus (HIV); case report and literature review. Ann. Med. Intern. 20, 373–376 (2003)Google Scholar
  55. 55.
    Rompalo, A.M., Joesoef, M.R., O’Donnell, J.A., Augenbraun, M., Brady, W., Radolf, J.D., Johnson, R., Rolfs, R.T.: Clinical manifestations of early syphilis by HIV status and gender: results of the syphilis and HIV study. Sex. Transm. Dis. 28, 158–165 (2001)PubMedCrossRefGoogle Scholar
  56. 56.
    Rosahn, P.D.: Autopsy studies in syphilis. J. Vener. Dis. Inf. 649, 1–67 (1947)Google Scholar
  57. 57.
    Salazar, J.C., Hazlett, K.R., Radolf, J.D.: The immune response to infection with Treponema pallidum, the stealth pathogen. Microbes Infect. 4, 1133–1140 (2002)PubMedCrossRefGoogle Scholar
  58. 58.
    Schaudinn, F.N.: Vorlaufiger bericht über das vorkommen von spirochaeten in syphilitischen krankheitsprodukten und bei papillomen. Arbeiten K. Gesundheits 22, 527–534 (1905)Google Scholar
  59. 59.
    Schouls, L.M.: Recombinant DNA technology in syphilis research. In: Wright, D.J.M., Archard, L. (eds.) Molecular Biology of Sexually Transmitted Diseases. Chapman & Hall, London (1992)Google Scholar
  60. 60.
    Schroeter, A.L., Turner, R.H., Lucas, J.B., Brown, W.J.: Therapy for incubating syphilis. Effectiveness of gonorrhea treatment. JAMA 218, 711–713 (1971)PubMedCrossRefGoogle Scholar
  61. 61.
    Sheffield, J.S., Sanchez, P.J., Morris, G., Maberry, M., Zeray, F., McIntire, D.D., and Wendel Jr., G.D.: Congenital syphilis after maternal treatment for syphilis during pregnancy. Am. J. Obstet. Gynecol. 186, 569–573 (2002)PubMedCrossRefGoogle Scholar
  62. 62.
    Smibert, R.M.: Genus III: Treponema Schaudinn 1905, 1728AL. In: Kreig, N.R., Holt, J.G. (eds.) Bergey’s Manual of Systematic Bacteriology, vol. 1, pp. 49–57. Williams & Wilkins, Baltimore (1984)Google Scholar
  63. 63.
    van der Sluis, J.J., Koehorst, J.A., Boer, A.M.: Factors that inhibit adherence of Treponema pallidum (Nichols strain) to a human fibroblastic cell line: development in serum of patients with syphilis. Genitourin. Med. 63, 71–76 (1987)PubMedGoogle Scholar
  64. 64.
    Stamm, L.V., Hodinka, R.L., Wyrick, P.B., Bassford Jr., P.J.: Changes in the cell surface properties of Treponema pallidum that occur during in vitro incubation of freshly extracted organisms. Infect. Immun. 55, 2255–2261 (1987)PubMedGoogle Scholar
  65. 65.
    Stamm, L.V., Gherardini, F.C., Parrish, E.A., Moomaw, C.R.: Heat shock response of spirochetes. Infect. Immun. 59, 1572–1575 (1991)PubMedGoogle Scholar
  66. 66.
    Strugnell, R., Cockayne, A., Penn, C.W.: Molecular and antigenic analysis of treponemes. Crit. Rev. Microbiol. 17, 231–250 (1990)PubMedCrossRefGoogle Scholar
  67. 67.
    Swancutt, M.A., Riley, B.S., Radolf, J.D., Norgard, M.V.: Molecular characterization of the pathogen-specific, 34-kilodalton membrane immunogen of Treponema pallidum. Infect. Immun. 57, 3314–3323 (1989)PubMedGoogle Scholar
  68. 68.
    Thomas, D.D., Navab, M., Haake, D.A., Fogelman, A.M., Miller, J.N., Lovett, M.A.: Treponema pallidum invades intercellular junctions of endothelial cell monolayers. Proc. Natl Acad. Sci. USA 85, 3608–3612 (1988)PubMedCrossRefGoogle Scholar
  69. 69.
    Wagner von Jauregg, J.: Uber die Einwirkung der Malaria auf die progressive Paralyse. Psychiatr. Neurol. Wochenschr. 20, 132 (1918)Google Scholar
  70. 70.
    Walker, E.M., Zampighi, G.A., Blanco, D.R., Miller, J.N., Lovett, M.A.: Demonstration of rare protein in the outer membrane of Treponema pallidum susp. Pallidum by freez-fracture analysis. J. Bacteriol. 171, 5005–5011 (1989)PubMedGoogle Scholar
  71. 71.
    Zhang, Z., Feige, J.N., Chang, A.B., Anderson, I.J., Brodianski, V.M., Vitreschak, A.G., Gelfand, M.S., Saier Jr., M.H.: A transporter of Escherichia colispecific for L- and D-methionine is the prototype for a new family within the ABC superfamily. Arch. Microbiol. 180, 88–100 (2003)PubMedCrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.BudapestHungary

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