NOTE: A surveillance case definition is a set of uniform criteria used to define a disease for public health surveillance. Surveillance case definitions enable public health officials to classify and count cases consistently across reporting jurisdictions. Surveillance case definitions are not intended to be used by healthcare providers for making a clinical diagnosis or determining how to meet an individual patient’s health needs.

CSTE Position Statement(s)

  • 17-ID-11

Subtype(s)

  • Syphilis, primary
  • Syphilis, secondary
  • Syphilis, early non-primary non-secondary
  • Syphilis, unknown duration or late
  • Syphilis, Congenital
  • Syphilitic Stillbirth

Background

Syphilis is a sexually transmitted disease (STD) caused by the bacterium Treponema pallidum. Syphilis is passed from person to person through direct contact with a syphilitic chancre. Chancres occur mainly on the external genitals, vagina, anus, or in the rectum but can also occur on the lips and in the mouth. Transmission of the organism occurs during vaginal, anal, or oral sex. Pregnant women with the disease can transmit it through the placenta to the fetus or at birth to the neonate. Many people infected with syphilis do not have any symptoms for years, yet remain at risk for late complications if they are not treated. Although transmission occurs from persons with chancres who are in the primary or secondary stage, many of these chancres are unrecognized. Thus, transmission may occur from persons who are unaware of their infection.

In the United States, testing for syphilis is currently being done using two algorithms. The traditional one has consisted of initial screening with an inexpensive nontreponemal test, followed by retesting reactive specimens with a more specific treponemal test. Quantitative nontreponemal tests are used to monitor responses to treatment or to indicate new infections. In the last 5–10 years, there has been an increase in the adoption of automated treponemal tests by laboratories which has resulted in the syphilis testing algorithm being reversed. Many laboratories now use an automated treponemal test as the initial screening test followed by a nontreponemal test. While this algorithm is more timely and cost effective for laboratories, it does have a ~14–40% false-positive rate with a second treponemal test often being used to help determine what clinical action should be taken.

Syphilis infections have continued to increase since their nadir in 2000–2001. Primary and secondary syphilis (the most infectious forms) had a rate of 2.1/100,000 (6,103 cases) in 2001; in 2015, this rate was 7.5/100,000 (23,872), the highest reported since 1994. While cases continue to occur primarily among males with men having sex with men being the primary risk factor, cases among women have also increased. Along with these dramatic increases in adult syphilis, congenital syphilis cases have also been increasing since 2012 with 487 cases reported in 2015 (12.4/100,000 live births). In addition, multiple jurisdictions have observed increases in ocular syphilis, a clinical manifestation that can occur at any stage of syphilis. However, at present, data on severe clinical manifestations such as ocular syphilis are not sufficiently captured in national syphilis case report data. Preliminary data for 2016 indicates an increase in syphilis infections of all stages, including congenital syphilis.

Subtype(s) Case Definition

Comments

Additional information to be collected on clinical manifestations of reported syphilis cases

Syphilis is a systemic infection that, if untreated, can cause a variety of clinical manifestations, including:

  • Signs and symptoms of primary and secondary syphilis (see above case definitions)
  • Latent infections (i.e., those lacking any signs or symptoms)
  • Neurologic, ocular, or otic manifestations (neurosyphilis, ocular syphilis, or otosyphilis), which can occur at any stage of syphilis
  • Late clinical manifestations (tertiary syphilis), which generally occur after 15–30 years of untreated infection

The following provides guidance for reporting neurologic, ocular, otic, and late clinical manifestations of syphilis. Cases should be reported according to stage of infection, as defined above (e.g., primary syphilis; secondary syphilis; early non-primary, non-secondary syphilis; or unknown duration or late syphilis) and the clinical manifestations should be reported in the case report data, as defined below.

Neurologic Manifestations:

Neurologic manifestations (neurosyphilis) can occur at any stage of syphilis. If the patient has neurologic manifestations of syphilis, the case should be reported with the appropriate stage of infection (as if neurologic manifestations were not present) and neurologic manifestations should be noted in the case report data.

Clinical description

Infection of the central nervous system with T. pallidum, as evidenced by manifestations including syphilitic meningitis, meningovascular syphilis, general paresis, including dementia, and tabes dorsalis.

Classification of neurologic manifestations (neurosyphilis)

Possible:

A person with a reactive nontreponemal test (e.g., VDRL, RPR, or equivalent serologic methods) and a reactive treponemal test (e.g., TP-PA, EIA, CIA or equivalent serologic methods) and clinical symptoms or signs that are consistent with neurosyphilis without other known causes for these clinical abnormalities.

Likely:

A person with a reactive nontreponemal test (e.g., VDRL, RPR, or equivalent serologic methods) and a reactive treponemal test (e.g., TP-PA, EIA, CIA or equivalent serologic methods) with both of the following:

  • Clinical symptoms or signs that are consistent with neurosyphilis without other known causes for these clinical abnormalities, AND
  • Elevated cerebrospinal fluid (CSF) protein (>50 mg/dL2) or leukocyte count (>5 white blood cells/cubic millimeter CSF) in the absence of other known causes of these abnormalities.

Verified:

A person with a reactive nontreponemal test (e.g., VDRL, RPR, or equivalent serologic methods) and a reactive treponemal test (e.g., TP-PA, EIA, CIA or equivalent serologic methods) with both of the following:

  • Clinical symptoms or signs that are consistent with neurosyphilis without other known causes for these clinical abnormalities, AND
  • A reactive VDRL in CSF in the absence of grossly bloody contamination of the CSF.

Ocular Manifestations:

Ocular manifestations (ocular syphilis) can occur at any stage of syphilis. If the patient has ocular manifestations of syphilis, the case should be reported with the appropriate stage of infection (as if ocular manifestations were not present) and ocular manifestations should be noted in the case report data.

Clinical description

Infection of any eye structure with T. pallidum, as evidenced by manifestations including posterior uveitis, panuveitis, anterior uveitis, optic neuropathy, and retinal vasculitis. Ocular syphilis may lead to decreased visual acuity including permanent blindness.

Classification of ocular manifestations (ocular syphilis)

Possible:

A person with a reactive nontreponemal test (e.g., VDRL, RPR, or equivalent serologic methods) and a reactive treponemal test (e.g., TP-PA, EIA, CIA or equivalent serologic methods) and clinical symptoms or signs consistent with ocular syphilis without other known causes for these clinical abnormalities.

Likely:

A person with a reactive nontreponemal test (e.g., VDRL, RPR, or equivalent serologic methods) and a reactive treponemal test (e.g., TP-PA, EIA, CIA or equivalent serologic methods) and both of the following:

  • Clinical symptoms or signs consistent with ocular syphilis without other known causes for these clinical abnormalities, AND
  • Findings on exam by an ophthalmologist that are consistent with ocular syphilis in the absence of other known causes for these abnormalities

Verified:

A person with a reactive nontreponemal test (e.g., VDRL, RPR, or equivalent serologic methods) and a reactive treponemal test (e.g., TP-PA, EIA, CIA or equivalent serologic methods) and both of the following:

  • Clinical symptoms or signs consistent with ocular syphilis without other known causes for these clinical abnormalities, AND
  • Demonstration of T. pallidum in aqueous or vitreous fluid by darkfield microscopy, or by polymerase chain reaction (PCR) or equivalent direct molecular methods.

Otic Manifestations:

Otic manifestations can occur at any stage of syphilis. If the patient has otic manifestations of syphilis, the case should be reported with the appropriate stage of infection (as if otic manifestations were not present) and otic manifestations should be noted in the case report data.

Clinical description

Infection of the cochleovestibular system with T. pallidum, as evidenced by manifestations including sensorineural hearing loss, tinnitus, and vertigo.

Classification of otic manifestations (otosyphilis)

Possible:

A person with a reactive nontreponemal test (e.g., VDRL, RPR, or equivalent serologic methods) and a reactive treponemal test (e.g., TP-PA, EIA, CIA or equivalent serologic methods) and clinical symptoms or signs consistent with otosyphilis without other known causes for these clinical abnormalities.

Likely:

A person with a reactive nontreponemal test (e.g., VDRL, RPR, or equivalent serologic methods) and a reactive treponemal test (e.g., TP-PA, EIA, CIA or equivalent serologic methods) and both of the following:

  • Clinical symptoms or signs consistent with otosyphilis without other known causes for these clinical abnormalities, AND
  • Findings on exam by an otolaryngologist that are consistent with otosyphilis in the absence of other known causes for these abnormalities

Verified:

A person with a reactive nontreponemal test (e.g., VDRL, RPR, or equivalent serologic methods) and a reactive treponemal test (e.g., TP-PA, EIA, CIA or equivalent serologic methods) and both of the following:

  • Clinical symptoms or signs consistent with otosyphilis without other known causes for these clinical abnormalities, AND
  • Demonstration of T. pallidum in inner ear fluid by darkfield microscopy, or by polymerase chain reaction (PCR) or equivalent direct molecular detection methods.

Late Clinical Manifestations:

Late clinical manifestations of syphilis usually develop only after a period of 15–30 years of untreated infection. Therefore, if the patient has late clinical manifestations of syphilis, the case should be reported with the appropriate stage of infection (for the vast majority of cases, unknown duration or late syphilis) and late clinical manifestations should be noted in the case report data.

Clinical description

Late clinical manifestations of syphilis (tertiary syphilis) may include inflammatory lesions of the cardiovascular system (e.g., aortitis, coronary vessel disease), skin (e.g., gummatous lesions), bone (e.g., osteitis), or other tissue. Rarely, other structures (e.g., the upper and lower respiratory tracts, mouth, eye, abdominal organs, reproductive organs, lymph nodes, and skeletal muscle) may be involved. In addition, certain neurologic manifestations (e.g., general paresis and tabes dorsalis) are also late clinical manifestations of syphilis.

Classification of late clinical manifestations of syphilis (tertiary syphilis)

Likely:

A person with a reactive nontreponemal test (e.g., VDRL, RPR, or equivalent serologic methods) and a reactive treponemal test (e.g., TP-PA, EIA, CIA or equivalent serologic methods) with either of the following:
  • Characteristic abnormalities or lesions of the cardiovascular system (e.g., aortitis, coronary vessel disease), skin (e.g., gummatous lesions), bone (e.g., osteitis), or other tissue, in the absence of other known causes of these abnormalities, OR
  • Clinical signs and symptoms consistent with late neurologic manifestations of syphilis (e.g., general paresis, including dementia, or tabes dorsalis) in a case that meets the criteria for likely neurologic manifestations of syphilis (see above)

Verified:

A person with a reactive nontreponemal test (e.g., VDRL, RPR, or equivalent serologic methods) and a reactive treponemal test (e.g., TP-PA, EIA, CIA or equivalent serologic methods) and either of the following:

  • Characteristic abnormalities or lesions of the cardiovascular system (e.g., aortitis, coronary vessel disease), skin (e.g., gummatous lesions), bone (e.g., osteitis), or other tissue in the absence of other known causes of these abnormalities, in combination with either demonstration of T. pallidum in late lesions by special stains or equivalent methods, or by polymerase chain reaction (PCR) or equivalent direct molecular methods, or demonstration of pathologic changes that are consistent with T. pallidum infection on histologic examination of late lesions, OR
  • Clinical signs and symptoms consistent with late neurologic manifestations of syphilis (e.g., general paresis, including dementia, or tabes dorsalis) in a case that meets the criteria for verified neurologic manifestations of syphilis (see above).

References

  1. Doris JP, Saha K, Jones NP, Sukthankar A. Ocular syphilis: the new epidemic. Eye (Lond). 2006 Jun;20(6):703-5. Epub 2005 Jun 3.
  2. Sparling, PF, Swartz, MN, Musher, DM, Healy, BP. Clinical Manifestations of Syphilis. In Holmes, KK, Sparling, PF, Stamm, WE, Piot, P, Wasserheit, J, Corey, L, Cohen, MS, Watts, DH (eds). Sexually Transmitted Diseases (4th ed). McGraw Medical: New York City, NY (2008), pp. 661–684.
  3. Tramont, EC. Treponema pallidum (Syphilis). In Mandell, GL, Bennett, JE, Dolin, R (eds). Principles and Practice of Infectious Diseases (5th ed). Churchill Livingstone: Philadelphia, PA (2000), pp. 2474–2490.

Related Case Definition(s)

Page last reviewed: April 16, 2021