overview of syphilis diagnostics background and history · • syphilis reporting is mandated by...

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Overview of Syphilis Diagnostics:Background and History


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)


History of Syphilis


1905 1906 1910 1940

Sefton, A.M (2001), J Appl Microb., Tampa M. et. Al. (2014) J Med Life.

History of Syphilis


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


Syphilis Rates-Still not gone

Reported cases by Stage of Infection, US, 1941-2013

http://www.cdc.gov/std/stats13/figures/30.htm


Highest Syphilis Rates Amongst Young Men

Primary and Secondary Syphilis – Rates of Reported Cases by Age and Sex, US, 2013

http://www.cdc.gov/std/stats13/figures/36.htm


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


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


Syphilis Infection


Direct Detection

Serologic Detection of Treponemal Antibodies

Serologic Detection of Non-Trep Antibodies

Common patterns of serologic reactivity


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


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


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.


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/

http://www.who.int/bulletin/volumes/82/6/439.pdf?ua=1

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956094/?report=printable

http://www.who.int/reproductivehealth/publications/rtis/9789241505840/en/


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

http://phil.cdc.gov/phil/home.asp

http://www.nlm.nih.gov/hmd/ihm/

http://www.cdc.gov/std/stats13/default.htm

http://www.cdc.gov/std/tg2015/default.htm

http://www.cdc.gov/std/syphilis/stdfact-syphilis.htm

http://dev.mindandmedia.com/aphl/background-history/story.htmlhttp:/www.aphl.org/aphlprograms/infectious/std/Documents/ID_2009Jan_Laboratory-Guidelines-Treponema-pallidum-Meeting-Report.pdf

http://www.cdc.gov/std/dstdp/

http://www.aphl.org/aphlprograms/infectious/std/pages/default.aspx