Syphilis: Screening and diagnostic testing
- Charles B Hicks, MD
Charles B Hicks, MD
- University of California, San Diego
- Meredith Clement, MD
Meredith Clement, MD
- Division of Infectious Diseases
- Duke University Medical Center
Syphilis is a sexually transmitted disease caused by the spirochete Treponema pallidum. The manifestations of this disease are notoriously protean, with different stages occurring over time in untreated infection [1-3]. Patients may seek evaluation for symptoms or signs of primary infection (eg, chancre), secondary infection (eg, diffuse rash), or tertiary infection (eg, symptoms of aortic insufficiency). Alternatively, patients may be completely asymptomatic and only identified on routine screening. The diagnosis of syphilis is most commonly made by serologic testing, a technique first described by Wasserman in 1906 .
The appropriate use and interpretation of diagnostic testing are important for optimal patient management. Testing for syphilis will be reviewed here. The pathophysiology, natural history, clinical manifestations, and treatment of this disorder, as well as the laboratory monitoring of patients undergoing therapy, are discussed elsewhere. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in HIV-uninfected patients" and "Syphilis: Treatment and monitoring".)
WHOM TO TEST
Diagnostic testing for syphilis should be performed on patients with signs or symptoms of infection. In addition, asymptomatic patients should be screened for syphilis if they are at high risk for having acquired disease or for transmitting disease to others. Serologic testing is generally used to make a diagnosis of syphilis. The approach to testing is described below. (See 'Approach to testing' below.)
All persons who are diagnosed with a new syphilis infection should be treated. In addition, they should be offered HIV testing, as well as screening for other sexually transmitted infections. (See "Syphilis: Treatment and monitoring" and "Screening for sexually transmitted infections".)
Symptomatic patients — Since syphilis can present with a wide range of signs and symptoms, the threshold for serologic testing should be low. We test the following groups of patients regardless of their apparent risk behaviors:To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Ghanem KG, Workowski KA. Management of adult syphilis. Clin Infect Dis 2011; 53 Suppl 3:S110.
- Miller BA and Hicks CB. Syphilis and HIV: The intersection of two epidemics. http://www.jwatch.org/ac201009030000001/2010/09/03/syphilis-and-hiv-intersection-two-epidemics (Accessed on October 15, 2014).
- Golden MR, Marra CM, Holmes KK. Update on syphilis: resurgence of an old problem. JAMA 2003; 290:1510.
- Wassermann A, et al. Eine serodiagnostische reaktion bei syphilis. Dtsch Med Wochenschr 1906; 32:745.
- Centers for Disease Control and Prevention. Primary and secondary syphilis – reported cases and rates of reported cases in counties and independent cities ranked by number of reported cases, United States, 2013. http://www.cdc.gov/std/stats13/tables/33.htm (Accessed on March 17, 2016).
- Centers for Disease Control and Prevention. Sexually transmitted disease surveillance 2014 http://www.cdc.gov/std/stats14/ (Accessed on February 06, 2017).
- Workowski KA and Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR June 5, 2015; 64:3. http://www.cdc.gov/std/tg2015/default.htm (Accessed on June 05, 2015).
- Cantor AG, Pappas M, Daeges M, Nelson HD. Screening for Syphilis: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA 2016; 315:2328.
- Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf (Accessed on July 10, 2017).
- Aberg JA, Gallant JE, Ghanem KG, et al. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2014; 58:1.
- http://hab.hrsa.gov/deliverhivaidscare/files/hepccoinfectguide2011.pdf (Accessed on October 16, 2014).
- Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015; 64:1.
- US Preventive Services Task Force (USPSTF), Bibbins-Domingo K, Grossman DC, et al. Screening for Syphilis Infection in Nonpregnant Adults and Adolescents: US Preventive Services Task Force Recommendation Statement. JAMA 2016; 315:2321.
- Seña AC, White BL, Sparling PF. Novel Treponema pallidum serologic tests: a paradigm shift in syphilis screening for the 21st century. Clin Infect Dis 2010; 51:700.
- Hart G. Syphilis tests in diagnostic and therapeutic decision making. Ann Intern Med 1986; 104:368.
- Larsen SA. Syphilis. Clin Lab Med 1989; 9:545.
- World Health Organization: The sexually transmitted diagnostics initiative (SDI): special programme for research and training in tropical diseases (TDR), Geneva: World Health Organization, 2003.
- Zarakolu P, Buchanan I, Tam M, et al. Preliminary evaluation of an immunochromatographic strip test for specific Treponema pallidum antibodies. J Clin Microbiol 2002; 40:3064.
- 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 Suppl 5:v7.
- Castro AR, Esfandiari J, Kumar S, et al. Novel point-of-care test for simultaneous detection of nontreponemal and treponemal antibodies in patients with syphilis. J Clin Microbiol 2010; 48:4615.
- 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.
- FDA News Release. “FDA grants CLIA waiver expanding availability of rapid screening test for syphilis.” 15 Dec 2014. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm426843.htm (Accessed on March 17, 2016).
- Matthias J, Dwiggins P, Totten Y, et al. Notes from the Field: Evaluation of the Sensitivity and Specificity of a Commercially Available Rapid Syphilis Test - Escambia County, Florida, 2016. MMWR Morb Mortal Wkly Rep 2016; 65:1174.
- Diagnostics direct. Syphillis health check test. 510(k) summary. August 1, 2011, Stone Harbor, NJ: Diagnostics Direct; 2011. http://www.accessdata.fda.gov/cdrh_docs/pdf10/k102400.pdf (Accessed on December 27, 2016).
- Jafari Y, Peeling RW, Shivkumar S, et al. Are Treponema pallidum specific rapid and point-of-care tests for syphilis accurate enough for screening in resource limited settings? Evidence from a meta-analysis. PLoS One 2013; 8:e54695.
- Causer LM, Kaldor JM, Conway DP, et al. An evaluation of a novel dual treponemal/nontreponemal point-of-care test for syphilis as a tool to distinguish active from past treated infection. Clin Infect Dis 2015; 61:184.
- Liu H, Rodes B, Chen CY, Steiner B. New tests for syphilis: rational design of a PCR method for detection of Treponema pallidum in clinical specimens using unique regions of the DNA polymerase I gene. J Clin Microbiol 2001; 39:1941.
- Leslie DE, Azzato F, Karapanagiotidis T, et al. Development of a real-time PCR assay to detect Treponema pallidum in clinical specimens and assessment of the assay's performance by comparison with serological testing. J Clin Microbiol 2007; 45:93.
- Grange PA, Gressier L, Dion PL, et al. Evaluation of a PCR test for detection of treponema pallidum in swabs and blood. J Clin Microbiol 2012; 50:546.
- Gayet-Ageron A, Sednaoui P, Lautenschlager S, et al. Use of Treponema pallidum PCR in testing of ulcers for diagnosis of primary syphilis. Emerg Infect Dis 2015; 21:127.
- Heymans R, van der Helm JJ, de Vries HJ, et al. Clinical value of Treponema pallidum real-time PCR for diagnosis of syphilis. J Clin Microbiol 2010; 48:497.
- Centers for Disease Control and Prevention (CDC). Syphilis testing algorithms using treponemal tests for initial screening--four laboratories, New York City, 2005-2006. MMWR Morb Mortal Wkly Rep 2008; 57:872.
- Gottlieb SL, Pope V, Sternberg MR, et al. Prevalence of syphilis seroreactivity in the United States: data from the National Health and Nutrition Examination Surveys (NHANES) 2001-2004. Sex Transm Dis 2008; 35:507.
- Sparling PF. Diagnosis of neurosyphilis: New tools. Sex Transm Dis 2010; 37:288.
- Vanhaecke C, Grange P, Benhaddou N, et al. Clinical and Biological Characteristics of 40 Patients With Neurosyphilis and Evaluation of Treponema pallidum Nested Polymerase Chain Reaction in Cerebrospinal Fluid Samples. Clin Infect Dis 2016; 63:1180.
- Ratnam S. The laboratory diagnosis of syphilis. Can J Infect Dis Med Microbiol 2005; 16:45.
- Ogilvie GS, Taylor DL, Moniruzzaman A, et al. A population-based study of infectious syphilis rediagnosis in British Columbia, 1995-2005. Clin Infect Dis 2009; 48:1554.
- Larsen SA, Steiner BM, Rudolph AH. Laboratory diagnosis and interpretation of tests for syphilis. Clin Microbiol Rev 1995; 8:1.
- Park IU, Chow JM, Bolan G, et al. Screening for syphilis with the treponemal immunoassay: analysis of discordant serology results and implications for clinical management. J Infect Dis 2011; 204:1297.
- Huber TW, Storms S, Young P, et al. Reactivity of microhemagglutination, fluorescent treponemal antibody absorption, Venereal Disease Research Laboratory, and rapid plasma reagin tests in primary syphilis. J Clin Microbiol 1983; 17:405.
- Castro R, Prieto ES, Santo I, et al. Evaluation of an enzyme immunoassay technique for detection of antibodies against Treponema pallidum. J Clin Microbiol 2003; 41:250.
- Lefevre JC, Bertrand MA, Bauriaud R. Evaluation of the Captia enzyme immunoassays for detection of immunoglobulins G and M to Treponema pallidum in syphilis. J Clin Microbiol 1990; 28:1704.
- Liu LL, Lin LR, Tong ML, et al. Incidence and risk factors for the prozone phenomenon in serologic testing for syphilis in a large cohort. Clin Infect Dis 2014; 59:384.
- 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.
- Tikjøb G, Russel M, Petersen CS, et al. Seronegative secondary syphilis in a patient with AIDS: identification of Treponema pallidum in biopsy specimen. J Am Acad Dermatol 1991; 24:506.
- WHOM TO TEST
- Symptomatic patients
- Asymptomatic patients
- DIAGNOSTIC TESTS
- Serologic tests
- - Nontreponemal tests
- - Treponemal tests
- - Rapid serologic tests
- Direct methods for diagnosis
- APPROACH TO TESTING
- Serologic testing algorithms
- Testing for neurosyphilis
- INTERPRETATION OF SEROLOGIC TESTING
- Positive nontreponemal/positive treponemal test
- - Patients without a history of syphilis
- - Patients with a history of treated syphilis
- Positive nontreponemal/negative treponemal
- Positive treponemal/negative nontreponemal test
- Negative nontreponemal test in early syphilis
- - Testing prior to antibody formation
- - Prozone reaction
- - Early treatment
- Negative nontreponemal test in late syphilis
- LATENT SYPHILIS
- Early latent
- Late latent
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS