Syphilis: Laboratory Aspects

Abstract

The laboratory diagnosis of syphilis remains a challenge to physicians. The organism cannot be subcultured and dark‐field microscopy requires a skilled operator. Current routine assays rely on serological‐based techniques, which cannot distinguish syphilis from other treponemal infections such as yaws and pinta. False‐positive and false‐negative results can occur, as well as difficulties between differentiating between acute and chronic infection. Concomitant infection with human immunodeficiency virus (HIV) can also skew results. Molecular analysis with polymerase chain reaction (PCR) is promising but is still in its infancy and standardisation is required. Therefore in order to diagnose syphilis correlation with the history and clinical examination findings remain of paramount importance.

Key Concepts:

  • Models of the cyclical epidemics of syphilis, which have been proposed and the factors that influence their periodicity and size of recurrence.

  • Comparison with the Treponema species that infect man with those from primates points to the origin of the disease, whereas study of their molecular structure throws light on treponemal biology.

  • The role of serological tests in the diagnosis of syphilis is analysed. Rapid screening tests are contrasted with more sophisticated laboratory tests. An example of the latter is the place of confirmatory tests.

  • The reasons for the gradual introduction of molecular tests like PCR into the diagnostic armoury and their current shortcomings are evaluated.

  • The practical difficulties of manufacturing and introducing a syphilis ‘vaccine’ are addressed, despite the theoretical and experimental support for this approach.

Keywords: syphilis; serology; treponema; PCR; immunisation

References

Breban R, Supervie V, Okano JT, Vardavas R and Blowers S (2008) Is there any evidence that syphilis epidemics cycle? Lancet Infectious Diseases 9: 577–581.

Castro R, Prieto E, Aguas A et al. (2009) Molecular subtyping of Treponema pallidum subs pallidum in Lisbon, Portugal. Journal of Clinical Microbiology 47: 2510–2512.

Centurion‐Lara A, LaFond RE, Hevner K et al. (2004) Gene conversion: a mechanism for generation of heterogeneity in the tprK gene of Treponema pallidum during infection. Molecular Microbiology 52(6): 1579–1596.

Cullen PA and Cameron CE (2006) Progress towards an effective syphilis vaccine: the past, present and future. Expert Review of Vaccines 5(1): 67–80.

Desrosiers DC, Anand A, Luthra A et al. (2011) TP0326, a Treponema pallidum β‐barrel assembly machinery A (BamA) orthologue and rare outer membrane protein. Molecular Microbiology 80(6): 1496–1515.

Dracoby A (2003) Ethics and experiments on human subjects in mid‐nineteenth century France. The story of the 1859 syphilis experiment. Bulletin of the History of Medicine 77.2: 332–366.

Eames KTD and Keeling MJ (2004) Monogamous networks and the spread of sexually transmitted diseases. Mathematical Biosciences 189: 115–130.

Egglestone SI, Turner AJ and PHLS Serology Working Group (2000) Serological diagnosis of syphilis. Communicable Disease Public Health 3: 158–162.

Fraser CM, Norris ST, Weinstock GM et al. (1998) Complete genome sequence of Treponema pallidum, the syphilis spirochaete. Science 281: 375–388.

French P, Gomberg M, Janier M et al. IUSTI (2009) IUSTI 2008 European guidelines on the management of syphilis. International Journal of STD AIDS 20: 300–309.

Garnett GP, Aral SO, Hoyle DV, Cates W and Anderson RM (1997) The natural history of syphilis. Sexually Transmitted Diseases 24: 185–200.

Gesink Law DC, Bernstein KT, Serre ML et al. (2006) Modelling a syphilis outbreak through space and time using Baysian maximum entropy approach. Annals of Epidemiology 16: 797–804.

Giacani L, Molini BJ, Kim EY et al. (2010) Antigenic variation in Trponema pallidum: TprK sequence diversity accumulates in response to immune pressure during experimental syphilis. Journal of Immunology 184: 3822–3829.

Grassly NC, Fraser C and Garnett GP (2005) Host immunity and synchronised epidemics of syphilis across the United States. Nature 433: 417–421.

Heymans R, van der Helm JJ, de Vries HJC et al. (2010) Clinical value of Real Time PCR for the diagnosis of syphilis. Journal of Clinical Microbiology 48: 497–502.

Houston S, Hof R, Francescuti T et al. (2011) Bifunctional role of Treponema pallidum extracellular matrix binding adhesion TP0751. Infection and Immunity 79: 1386–1398.

Izard J, Renken C, Hsieh CE et al. (2009) Cryo‐electron tomography elucidates the molecular architecture of Treponema pallidum, the syphilis spirochete. Journal of Bacteriology 191: 7566–7580.

LaFond RE, Molini BJ, Van Voorhis WC and Lukehart SA (2006) Antigenic variation of TprK V regions abrogates specific antibody binding in syphilis. Infection and Immunity 74: 6244–6251.

Liu JB, Hong FC, Pan P et al. (2010) A risk model for congenital syphilis in infants born to mothers with syphilis treated in gestation: a prospective study. Sexually Transmitted Infections 86: 292–296.

MacGill MA, Edmondson DG, Carroll JA et al. (2010) Characterization and serologic analysis of the Treponema pallidum proteome. Infection and Immunity 78(6): 2631–2643.

Magnuson HJ, Thomas EW, Olansky S et al. (1956) Inoculation syphilis in human volunteers. Medicine 35: 33–82.

Marra CM, Tantalo LC, Sahi SK, Maxwell CL and Lukehart SA (2010) CXCL13 as a cerebrospinal fluid marker for neurosyphilis in HIV‐infected patients with syphilis. Sexually Transmitted Diseases 37: 283–287.

Mikalová L, Strouhal M, Čejková D et al. (2010) Genome analysis of Treponema pallidum subsp. pallidum and subsp. pertenue strains. Most of the genetic differences are localised to six regions. PLoS One 5: e15713. (Dec. 29).

Miller JN (1973) Immunity in experimental syphilis. VI. Successful inoculation of rabbits with Treponema pallidum, Nichols strain, attenuated by gamma‐irradiation. Immunology 110: 1206–1215.

Norris SJ, Cox DL and Weinstock GM (2001) Chapter 18. Biology of Treponema pallidum: correlation of functional activities with genome sequence data. In: Saier MH Jr and Garcia‐Lara J (eds) The Spirochetes: Molecular and Cellular Biology, pp. 171–200. Wymondham, Norfolk, UK: Horizon Press.

Norris SJ and Treponema pallidum Polypeptide Research Group (1993) Polypeptides of Treponema pallidum: progress toward understanding their structural, functional, and immunologic roles. Microbiological Reviews 57(3): 750–779.

Oxman GL, Smolkowski K and Noell J (1996) Mathematical modeling of epidemic syphilis transmission. Implication for control programs. Sexually Transmitted Diseases 23: 30–39.

Pillay A, Liu H, Ebrahim S et al. (2002) Molecular typing of Treponema pallidum in South Africa across sectional studies. Journal of Clinical Microbiology 40: 256–258.

Salazar JC, Cruz AR, Pope CD et al. (2007) Treponema pallidum elicits innate and adaptive cellular immune responses in skin and blood during secondary syphilis: a flow‐cytometric analysis. Journal of Infectious Diseases 195(6): 879–887.

Sena AC, White BL and Sparling PF (2010) Novel Treponemal pallidum serologic tests. A paradigm shift in syphilis testing for the 21st century. Clinical Infectious Diseases 51: 700–708.

Seshadri R, Myers GS, Tettelin H et al. (2004) Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes. Proceedings of the National Academy of Sciences of the USA 101: 5646–5651.

Setubal JC, Reis M, Matsunaga J and Haake DA (2006) Lipoprotein computational prediction in spirochetal genomes. Microbiology 152: 113–121.

Turner TB and Hollander DH (1957) Biology of the Treponematoses. Geneva: World Health Organization.

Voltz E and Meyer LA (2007) Susceptible‐infected recovered epidemics in dynamic contact networks. Proceedings of Biology and Science 274: 2925–2933.

Further Reading

Hart G (1986) Syphilis tests in diagnostic and therapeutic decision making. Annals of Internal Medicine 104: 368–376.

La Fond RE and Buckhurst SA (2006) Biological basis of syphilis. Clinical Microbiology 19: 24–49.

Peeling RW and Hooke EW (2006) Pathogenesis of syphilis. Journal of Pathology 208: 224–232.

Radolf JD and Lukehart SA (2006) Pathogenic Treponema: Molecular and Cellular Biology. Wymondham, Norfolk, UK: Caister Academic Press.

Sell S and Hsu P‐L (1993) Delayed hypersensitivity, immune deviation, antigen processing and T‐cell subset selection in syphilis pathogenesis and vaccine design. Immunology Today 14: 576–582.

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Wright, David J, Norris, Steven J, Dhillon, Rishi H‐P, and Edmondson, Diane G(Jan 2012) Syphilis: Laboratory Aspects. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0023925]