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Analysis. Answers. Action. www.aphl.org
Overview of Syphilis Diagnostics:Background and History
Analysis. Answers. Action. www.aphl.org
Treponema pallidum
• Spirochete• Mechanism of
transmission– Sexually transmitted– Person to person
through direct contact with an infected ulcer
– Can be transmitted from mother to child (congenital syphilis)
Analysis. Answers. Action. www.aphl.org
History of Syphilis
Analysis. Answers. Action. www.aphl.org
1905 1906 1910 1940
Sefton, A.M (2001), J Appl Microb., Tampa M. et. Al. (2014) J Med Life.
History of Syphilis
Analysis. Answers. Action. www.aphl.org
Role of the Public Health Laboratory
• Syphilis reporting is mandated by state laws
• Information about syphilis cases is reported to CDC from all states and territories
• Syphilis surveillance provides data for planning, implementation and evaluation for public health programs and interventions
Analysis. Answers. Action. www.aphl.org
Syphilis Rates-Still not gone
Reported cases by Stage of Infection, US, 1941-2013
Analysis. Answers. Action. www.aphl.org
Highest Syphilis Rates Amongst Young Men
Primary and Secondary Syphilis – Rates of Reported Cases by Age and Sex, US, 2013
Analysis. Answers. Action. www.aphl.org
Syphilis Challenges
• Efforts to eliminate syphilis are falling short• Ease of treatment – penicillin works• Lack of knowledge – syphilis has been
eliminated?• Dependence on serologic tests to detect syphilis
– Indirect evidence– Requires normal immune response (HIV)– Non-specific (false positive) and false negative reactions
Analysis. Answers. Action. www.aphl.org
Diagnosis of Syphilis is Challenging
• Syphilis is the “great imitator”• Persons present without symptoms or signs
– Painless primary lesion can be in nonvisible locations and resolve without treatment
– Inapparent lesions– Latent infections
• Culture is not a diagnostic option • Direct detection of early infection limited
Analysis. Answers. Action. www.aphl.org
Syphilis Infection
Analysis. Answers. Action. www.aphl.org
Direct Detection
Serologic Detection of Treponemal Antibodies
Serologic Detection of Non-Trep Antibodies
Common patterns of serologic reactivity
Analysis. Answers. Action. www.aphl.org
Direct Detection• Ideally suited for early detection before antibodies are
generated• Available Tests (not FDA-cleared)
– Darkfield microscopy – Immunostaining-DFA– Nucleic Acid Amplification tests
• Challenges– Limited availability– False negatives– Expertise CLIA requirements
Analysis. Answers. Action. www.aphl.org
Serologic Diagnosis of Syphilis
Always requires detection of two types of antibodies– Non-Treponemal antibodies
• Directed against lipoidal antigens• Most common tests: RPR and VRDL
– Treponemal antibodies• Directed against T. pallidum• Most common tests: FTA-ABS, TP-PA, EIA, CIA and MBIA
– POC Testing• FDA-cleared: Syphilis HealthCheck (Treponemal Ab only)• Non FDA-cleared: Chembio: Treponemal and Non-
treponemal Ab
Analysis. Answers. Action. www.aphl.org
Syphilis Diagnosis
No testing algorithm can take the place of clinical judgment– Test results must be used in conjunction with
the patient’s clinical symptoms, medical and sexual history, and other clinical and/or laboratory findings to produce an overall clinical diagnosis.
Analysis. Answers. Action. www.aphl.org
ReferencesCortez, K. J., & Greenwald, M. A. (2014). Current trends in donor testing to detect syphilis infection. Curr Infec Dis Rep. 16 (9), 423. doi: 10.1007/s11908-014-0423-z
Peeling, R.W. & Ye, H. (2004). Diagnostic tools for preventing and managing maternal and congenital syphilis: an overview. Bulletin of the World Health Oragnization, 82(6), 439-446. Retrieved from http://www.who.int/bulletin/volumes/82/6/439.pdf?ua=1
Sefton, A.M. (2001) The Great Pox that was…syphilis. J Appl Microb. 91, 592-596. doi: 10.1046/j.1365-2672.2001.01494.x
Tampa, M. Sarbu, I., Matei, C., Benea, V., & Georgescu, S.R. (2014) Brief history of syphilis. J Med Life, 7(1), 4-10. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956094/?report=printable
Unemo, M., Ballard, R., Ison, C., Lewis, D., Ndowa, F., & Peeling, R. (Eds.). (2013). Laboratory diagnosis of sexually transmitted infections, including human immunodeficiency virus. World Health Organization. Retrieved from http://www.who.int/reproductivehealth/publications/rtis/9789241505840/en/
Analysis. Answers. Action. www.aphl.org
ResourcesImages• http://phil.cdc.gov/phil/home.asp• http://www.nlm.nih.gov/hmd/ihm/
General• CDC Sexually Transmitted Disease Surveillance 2013 • STD Treatment Guidelines 2015• Syphilis Fact Sheets• Laboratory Diagnostic Testing for Treponema pallidum,
Expert Consultation 2009• CDC Division of STD Prevention (DSTDP)• APHL STD Homepage