Syphilis testing, typing, and treatment follow-up: A new era for an old disease

Current Opinion in Infectious Diseases

Volumn 28, Issue 1, 2015, Pages 53-60

  Tipple, Craig ^a   Taylor, Graham P ^b  

^a ST MARY S HOSPITAL   (United Kingdom)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

Syphilis; Testing; Treatment; Treponema pallidum; Typing

Indexed keywords

ANTIBIOTIC AGENT; MACROLIDE; ANTIINFECTIVE AGENT; BACTERIAL DNA;

ANTIBIOTIC RESISTANCE; FOLLOW UP; GENOTYPE; HUMAN; META ANALYSIS (TOPIC); MOLECULAR DIAGNOSTICS; MOLECULAR TYPING; NONHUMAN; PHENOTYPE; POINT OF CARE TESTING; POLYMERASE CHAIN REACTION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SCREENING TEST; SYPHILIS; SYPHILIS SEROLOGY; SYSTEMATIC REVIEW (TOPIC); TREPONEMA PALLIDUM; DRUG EFFECTS; GENETICS; HOSPITAL INFORMATION SYSTEM; ISOLATION AND PURIFICATION; MASS SCREENING;

ANTI-BACTERIAL AGENTS; DNA, BACTERIAL; DRUG RESISTANCE, BACTERIAL; FOLLOW-UP STUDIES; GENOTYPE; MACROLIDES; MASS SCREENING; MOLECULAR TYPING; POINT-OF-CARE SYSTEMS; POLYMERASE CHAIN REACTION; SYPHILIS; SYPHILIS SERODIAGNOSIS; TREPONEMA PALLIDUM;

EID: 84920920228     PISSN: 09517375     EISSN: 14736527     Source Type: Journal    
DOI: 10.1097/QCO.0000000000000124     Document Type: Review

References (67)

1. Schaudinn F, Hoffmann E. Bericht Über das Vorkommen von Spirochaeten in syphilitischen Krankheitsprodukten und bei Papilloten. Arb Kaiserl Gesurndheisamte 1905; 22:527-532.
2. Ho EL, Lukehart SA. Syphilis: using modern approaches to understand an old disease. J Clin Invest 2011; 121:4584-4592.
3. Binnicker MJ. Which algorithm should be used to screen for syphilis? Curr Opin Infect Dis 2012; 25:79-85.
4. Peng RR, Wang AL, Li J, et al. Molecular typing of Treponema pallidum: a systematic review and meta-analysis. PLoS Negl Trop Dis 2011; 5:e1273.
5. 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; 337:307-314.
6. Hook EW, Behets F, Van Damme K, et al. A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis. J Infect Dis 2010; 201:1729-1735.
7. Larsen S, Steiner B, Rudolph A. Laboratory diagnosis and interpretation of tests for syphilis. Clin Microbiol Rev 1995; 8:1-21.
8. Workowski KA, Berman S. (CDC) CfDCaP. Sexually transmitted diseases treatment guidelines 2010. MMWR Recomm Rep 2010; 59 ((RR-12)):1-110.
9. Owusu-Edusei K, Peterman TA, Ballard RC. Serologic testing for syphilis in the United States: a cost-effectiveness analysis of two screening algorithms. Sex Transm Dis 2011; 38:1-7.
10. Centres for Disease Control and, Prevention. Discordant results from reverse sequence syphilis screening: five laboratories, United States. MMWR Morb Mortal Wkly Rep 2011; 60:133-137.
11. Mishra S, Boily MC, Ng V, et al. The laboratory impact of changing syphilis screening from the rapid-plasma reagin to a treponemal enzyme immunoassay: a case-study from the Greater Toronto Area. Sex Transm Dis 2011; 38:190-196.
12. Binnicker MJ, Jespersen DJ, Rollins LO. Treponema-specific tests for serodiagnosis of syphilis: comparative evaluation of seven assays. J Clin Microbiol 2011; 49:1313-1317.
13. Jost H, Castro A, Cox D, et al. A comparison of the analytical level of agreement of nine treponemal assays for syphilis and possible implications for screening algorithms. Br Med J Open 2013; 3:e003347.
14. French P, Gomberg M, Janier M, et al. IUSTI: 2008 European Guidelines on the Management of Syphilis. Int J STD AIDS 2009; 20:300-309.
15. Tong ML, Lin LR, Liu LL, et al. Analysis of 3 algorithms for syphilis serodiagnosis and implications for clinical management. Clin Infect Dis 2014; 58:1116-1124.
16. Gaydos C, Hardick J. Point of care diagnostics for sexually transmitted infections: perspectives and advances. Expert Rev Anti Infect Ther 2014; 12:657-672.
17. Tucker JD, Bu J, Brown LB, et al. Accelerating worldwide syphilis screening through rapid testing: a systematic review. Lancet Infect Dis 2010; 10:381-386.
18. 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; 56:659-665.
19. Hay P, Clarke J, Strugnell R, et al. Use of the polymerase chain reaction to detect DNA sequences specific to pathogenic treponemes in cerebrospinal fluid. FEMS Microbiol Lett 1990; 56:233-238.
20. Wicher K, Noordhoek GT, Abbruscato F, Wicher V. Detection of Treponema pallidum in early syphilis by DNA amplification. J Clin Microbiol 1992; 30:497-500.
21. Orle K, Gates C, Martin D, et al. Simultaneous PCR detection of Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus types 1 and 2 from genital ulcers. J Clin Microbiol 1996; 34:49-54.
22. Kouznetsov A, Weisenseel P, Trommler P, et al. Detection of the 47-kilodalton membrane immunogen gene of Treponema pallidum in various tissue sources of patients with syphilis. Diagn Microbiol Infect Dis 2005; 51:143-145.
23. Gayet-Ageron A, Ninet B, Toutous-Trellu L, et al. Assessment of a real-time PCR test to diagnose syphilis from diverse biological samples. Sex Transm Infect 2009; 85:264-269.
24. Gayet-Ageron A, Lautenschlager S, Ninet B, et al. Sensitivity, specificity and likelihood ratios of PCR in the diagnosis of syphilis: a systematic review and meta-analysis. Sex Transm Infect 2013; 89:251-256.
25. Tipple C, Hanna MO, Hill S, et al. Getting the measure of syphilis: qPCR to better understand early infection. Sex Transm Infect 2011; 87:479-485.
26. Casal C, Araújo EaC, Corvelo TC. Risk factors and pregnancy outcomes in women with syphilis diagnosed using a molecular approach. Sex Transm Infect 2013; 89:257-261.
27. Shields M, Guy RJ, Jeoffreys NJ, et al. A longitudinal evaluation of Treponema pallidum PCR testing in early syphilis. BMC Infect Dis 2012; 12:353; Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541217/pdf/1471-2334-12-353.pdf [Accessed 24 November 2014]
28. Scott LJ, Gunson RN, Carman WF, Winter AJ. A new multiplex real-time PCR test for HSV1/2 and syphilis: an evaluation of its impact in the laboratory and clinical setting. Sex Transm Infect 2010; 86:537-539.
29. Pillay A, Liu H, Chen CY, et al. Molecular subtyping of Treponema pallidum subspecies pallidum. Sex Transm Dis 1998; 25:408-414.
30. Marra CM, Sahi SK, Tantalo LC, et al. Enhanced molecular typing of Treponema pallidum: geographical distribution of strain types and association with neurosyphilis. J Infect Dis 2010; 202:1380-1388.
31. Katz KA, Pillay A, Ahrens K, et al. Molecular epidemiology of syphilis: San Francisco. Sex Transm Dis 2010; 37:660-663.
32. Flasarová M, Pospíšilová P, Mikalová L, et al. Sequencing-based molecular typing of Treponema pallidum strains in the Czech Republic: all identified genotypes are related to the sequence of the SS14 strain. Acta Derm Venereol 2012; 92:669-674.
33. Peng RR, Yin YP, Wei WH, et al. Molecular typing of Treponema pallidum causing early syphilis in China: a cross-sectional study. Sex Transm Dis 2012; 39:42-45.
34. Tian H, Li Z, Hou J, et al. Molecular typing of Treponema pallidum: identification of a new sequence of tp0548 gene in Shandong, China. Sex Transm Dis 2014; 41:551.
35. Tipple C, McClure MO, Taylor GP. High prevalence of macrolide resistant Treponema pallidum strains in a London centre. Sex Transm Infect 2011; 87:486-488.
36. Grange PA, Allix-Beguec C, Chanal J, et al. Molecular subtyping of Treponema pallidum in Paris, France. Sex Transm Dis 2013; 40:641-644.
37. Dai T, Li K, Lu H, et al. Molecular typing of Treponema pallidum: a 5-year surveillance in Shanghai, China. J Clin Microbiol 2012; 50:3674-3677.
38. Wu H, Chang SY, Lee NY, et al. Evaluation of macrolide resistance and enhanced molecular typing of Treponema pallidum in patients with syphilis in Taiwan: a prospective multicenter study. J Clin Microbiol 2012; 50:2299-2304.
39. Mikalová L, Pospíšilová P, Woznicová V, et al. Comparison of CDC and sequence-based molecular typing of syphilis treponemes: tpr and arp loci are variable in multiple samples from the same patient. BMC Microbiol 2013; 13:178.
40. Harper KN, Liu H, Ocampo PS, et al. The sequence of the acidic repeat protein (arp) gene differentiates venereal from nonvenereal Treponema pallidum subspecies, and the gene has evolved under strong positive selection in the subspecies that causes syphilis. FEMS Immunol Med Microbiol 2008; 53:322-332.
41. Giacani L, Molini B, Godornes C, et al. Quantitative analysis of tpr gene expression in Treponema pallidum isolates: differences among isolates and correlation with T-cell responsiveness in experimental syphilis. Infect Immun 2007; 75:104-112.
42. Giacani L, Brandt SL, Puray-Chavez M, et al. Comparative investigation of the genomic regions involved in antigenic variation of the TprK antigen among treponemal species, subspecies, and strains. J Bacteriol 2012; 194:4208-4225.
43. Giacani L, Chattopadhyay S, Centurion-Lara A, et al. Footprint of positive selection in Treponema pallidum subsp. pallidum genome sequences suggests adaptive microevolution of the syphilis pathogen. PLoS Negl Trop Dis 2012; 6:e1698.
44. Mikalová L, Strouhal M, Čejková D, et al. Genome analysis of Treponema pallidum subsp. pallidum and subsp. pertenue strains: most of the genetic differences are localized in six regions. PLoS One 2010; 5:e15713.
45. Lukehart S, Godornes C, Molini B, et al. Macrolide resistance in Treponema pallidum in the United States and Ireland. N Engl J Med 2004; 351:154-158.
46. Matejková P, Flasarová M, Zákoucká H, et al. Macrolide treatment failure in a case of secondary syphilis: a novel A2059G mutation in the 23S rRNA gene of Treponema pallidum subsp. pallidum. J Med Microbiol 2009; 58 (Pt 6): 832-836.
47. Stamm LV. Global challenge of antibiotic-resistant Treponema pallidum. Antimicrob Agents Chemother 2010; 54:583-589.
48. Read P, Jeoffreys N, Tagg K, et al. Azithromycin-resistant syphilis-causing strains in Sydney, Australia: prevalence and risk factors. J Clin Microbiol 2014; 52:2776-2781.
49. 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; 39:954-958.
50. Muldoon EG, Walsh A, Crowley B, Mulcahy F. Treponema pallidum azithromycin resistance in Dublin, Ireland. Sex Transm Dis 2012; 39:784-786.
51. Grillová L, Pě trošová H, Mikalová L, et al. Molecular typing of Treponema pallidum in the Czech Republic during 2011-2013: increased prevalence of identified genotypes and of isolates encoding macrolide resistance. J Clin Microbiol 2014; 52:3693-3700.
52. Martin IE, Tsang RS, Sutherland K, et al. Molecular typing of Treponema pallidum strains in western Canada: predominance of 14d subtypes. Sex Transm Dis 2010; 37:544-548.
53. Martin IE, Gu W, Yang Y, Tsang RS. Macrolide resistance and molecular types of Treponema pallidum causing primary syphilis in Shanghai, China. Clin Infect Dis 2009; 49:515-521.
54. Van Damme K, Behets F, Ravelomanana N, et al. Evaluation of azithromycin resistance in Treponema pallidum specimens from Madagascar. Sex Transm Dis 2009; 36:775-776.
55. Mitchell SJ, Engelman J, Kent CK, et al. Azithromycin-resistant syphilis infection: San Francisco, California 2000-2004. Clin Infect Dis 2006; 42:337-345.
56. Morshed MG, Jones HD. Treponema pallidum macrolide resistance in BC. CMAJ 2006; 174:349.
57. Chen XS, Yin YP, Wei WH, et al. High prevalence of azithromycin resistance to Treponema pallidum in geographically different areas in China. Clin Microbiol Infect 2013; 19:975-979.
58. Müller EE, Paz-Bailey G, Lewis DA. Macrolide resistance testing and molecular subtyping of Treponema pallidum strains from southern Africa. Sex Transm Infect 2012; 88:470-474.
59. Chen CY, Chi KH, Pillay A, et al. Detection of the A2058G and A2059G 23S rRNA gene point mutations associated with azithromycin resistance in Treponema pallidum by use of a TaqMan real-time multiplex PCR assay. J Clin Microbiol 2013; 51:908-913.
60. Kingston M, French P, Goh B, et al. UK national guidelines on the management of syphilis. Int J STD AIDS 2008; 19:729-740.
61. Blank LJ, Rompalo AM, Erbelding EJ, et al. Treatment of syphilis in HIVinfected subjects: a systematic review of the literature. Sex Transm Infect 2011; 87:9-16.
62. Jinno S, Anker B, Kaur P, et al. Predictors of serological failure after treatment in HIV-infected patients with early syphilis in the emerging era of universal antiretroviral therapy use. BMC Infect Dis 2013; 13:605.
63. Seña AC, Wolff M, Martin DH, et al. Predictors of serological cure and Serofast State after treatment in HIV-negative persons with early syphilis. Clin Infect Dis 2011; 53:1092-1099.
64. Seña AC, Wolff M, Behets F, et al. Response to therapy following retreatment of serofast early syphilis patients with benzathine penicillin. Clin Infect Dis 2013; 56:420-422.
65. Tong ML, Lin LR, Liu GL, et al. Factors associated with serological cure and the serofast state of HIV-negative patients with primary, secondary, latent, and tertiary syphilis. PLoS One 2013; 8:e70102.
66. Wu BR, Tsai MS, Yang CJ, et al. Spirochetemia due to Treponema pallidum using polymerase-chain-reaction assays in patients with early syphilis: prevalence, associated factors and treatment response. Clin Microbiol Infect 2014; 20:O524-O527.
67. Tipple C, Hodson L, Jones R, et al. O05.2 measuring syphilis: quantitative PCR can be used to monitor treatment response. Abstract presented at a conference of the International Society for STD Research, Vienna, 2012.