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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)

25-ID-08

Subtype(s)

  • Syphilis, primary
  • Syphilis, secondary
  • Syphilis, early non-primary non-secondary
  • Syphilis, unknown duration or late
  • Syphilis, congenital

Background

Acquired syphilis is a sexually transmitted infection (STI) caused by the bacterium Treponema pallidum that typically progresses through multiple stages, alternating between symptomatic periods and periods of latency when no signs or symptoms of infection are present. T. pallidum is most commonly transmitted from person to person during vaginal, anal, or oral sex through direct contact with syphilitic lesions that occur during the primary (e.g., chancres) or secondary (e.g., condylomata lata, mucous patches) stages of infection. Although transmission typically occurs from persons with syphilitic lesions, many of these lesions are undetected. Thus, transmission may occur from persons who are unaware of their infection. Further, if untreated or inadequately treated, persons who are infected are at risk for severe sequelae, such as neurologic, ocular, and otic manifestations, at any stage of syphilitic infection. Those who remain untreated or inadequately treated may even develop late clinical manifestations (i.e., tertiary syphilis) 10 to 30 years after infection.

During pregnancy, T. pallidum can be transmitted across the placenta to the fetus at any stage of syphilitic infection and cause congenital syphilis. Likewise, during vaginal delivery, T. pallidum can be transmitted to the infant through direct contact with syphilitic lesions. Syphilis exposure to a fetus during pregnancy or an infant during vaginal delivery can lead to a wide variety of outcomes. Severe pregnancy complications may include miscarriage, stillbirth, or preterm delivery; while no clinical signs or symptoms may be apparent in an infant at birth, negative health effects in infants may occur, including perinatal death or multiple clinical manifestations. Even with adequate treatment, infants with congenital syphilis may experience lifelong physical and neurologic effects due to their infection.

Clinical and surveillance approaches and goals are different for the identification and staging of syphilis. The goal of clinical staging of syphilis is to ensure that a patient receives appropriate stage-specific treatment. The clinical approach typically focuses on identifying and treating all likely cases of syphilis using the information available at the time of clinical care. For this reason, clinicians apply criteria that have a high level of sensitivity, meaning that there are few false-negative results and thus fewer infections are missed.

Conversely, the goal of syphilis surveillance staging is to consistently monitor the burden of disease and identify cases for disease intervention. Surveillance staff typically leverage all available information captured over time (i.e., health department record searches, patient interviews by public health staff, and provider reports) to ensure that surveillance staging is accurate. Surveillance case definitions for acquired syphilis tend to be more specific (i.e., narrow) than clinical acquired syphilis staging determinations, thus generating fewer false positive results and improving accurate case ascertainment. By contrast, because congenital syphilis represents a failure of both the healthcare and the public health systems, it is important to capture as many cases as possible. Therefore, the surveillance case definition for congenital syphilis aims to maximize sensitivity. While clinical and surveillance staging are the same most of the time, they may not always align. It is important to remember that 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 or treatment needs.

Syphilis has been a nationally notifiable condition since 1944. The burden of syphilis has been high in recent years with over 200,000 cases of total syphilis reported in the United States for 2023, including more than 3,800 cases of congenital syphilis. Additionally, severe complications of acquired syphilis, including neurologic, ocular, and otic manifestations, continue to occur, often following trends in acquired syphilis.

Subtype(s) Case Definition

Other Criteria

Guidance for sub-classifying acquired syphilis cases

The following provides guidance for health departments to use for the classification and notification of acquired syphilis cases with neurologic, ocular, otic, and/or late clinical manifestations of syphilis. Cases should be reported to the CDC through voluntary notification according to stage of acquired syphilitic infection, as defined above (i.e., primary syphilis, secondary syphilis, early non-primary non-secondary syphilis, or unknown duration or late syphilis) and, if identified, should include the clinical manifestations in the case data, as defined below. These manifestations do not apply to congenital syphilis cases.

Neurologic Manifestations

Background

Neurologic manifestations (neurosyphilis) can occur at any stage of syphilitic infection. If neurologic manifestations of syphilis are present in a previously unreported case of syphilis, the case should be reported with the appropriate stage of infection, and neurologic manifestations should be included with the case data.

Neurologic Clinical Criteria

Has clinical signs or symptoms consistent with infection of the central nervous system with T. pallidum, as evidenced by manifestations including syphilitic meningitis, meningovascular syphilis, general paresis, or tabes dorsalis, without other clear causes for these clinical abnormalities.

Neurologic Laboratory Criteria

  • A reactive CSF VDRL or CSF RPR test in the absence of visibly blood-contaminated CSF†††, OR
  • Direct detection of T. pallidum in CSF by nucleic acid amplification test (e.g., PCR, LAMP) or diagnostically equivalent molecular method.

†††For the purposes of the syphilis surveillance case definition, visibly blood-contaminated CSF is defined as a CSF red blood cell (RBC) count of greater than or equal to 500 RBCs/µL or, in the absence of an available CSF RBC count, CSF that is described as bloody in appearance in a medical record.

Neurologic Sub-classifications

Verified:

  • Meets the surveillance case definition for primary, secondary, or early non-primary non-secondary syphilis AND meets neurologic clinical criteria AND meets neurologic laboratory criteria, OR
  • Has a reactive blood-based treponemal antibody test result AND has a current (i.e., a test performed in the context of this index presentation) reactive blood-based nontreponemal antibody test result# AND meets neurologic clinical criteria AND meets neurologic laboratory criteria.

Likely:

  • Meets the surveillance case definition for primary, secondary, or early non-primary non-secondary syphilis AND meets neurologic clinical criteria AND a diagnosis of neurosyphilis was made by a clinical provider, OR
  • Has a reactive blood-based treponemal antibody test result AND has a current (i.e., a test performed in the context of this index presentation) reactive blood-based nontreponemal antibody test result# AND meets neurologic clinical criteria AND a diagnosis of neurosyphilis was made by a clinical provider, OR
  • Meets the surveillance case definition for primary, secondary, or early non-primary non-secondary syphilis AND meets neurologic clinical criteria AND treatment for neurosyphilis was advised, ordered, or initiated by a clinical provider, OR
  • Has a reactive blood-based treponemal antibody test result AND has a current (i.e., a test performed in the context of this index presentation) reactive blood-based nontreponemal antibody test result# AND meets neurologic clinical criteria AND treatment for neurosyphilis was advised, ordered, or initiated by a clinical provider.

# See case definition for syphilis, unknown duration or late.

Current or historical reactive treponemal antibody tests can be used to satisfy this criterion.


Ocular Manifestations

Background

Ocular manifestations (ocular syphilis) can occur at any stage of syphilitic infection. If ocular manifestations of syphilis are present in a previously unreported case of syphilis, the case should be reported with the appropriate stage of infection, and ocular manifestations should be included with the case data.

Ocular Clinical Criteria

Has clinical signs or symptoms consistent with infection of any eye structure with T. pallidum, as evidenced by manifestations including posterior uveitis, panuveitis, anterior uveitis, conjunctivitis, optic neuropathy, retinal vasculitis, and interstitial keratitis, without other clear causes for these clinical abnormalities. Ocular syphilis may lead to permanent decreases in visual acuity, including permanent blindness.

Ocular Laboratory Criteria

Direct detection of T. pallidum in aqueous or vitreous fluid by nucleic acid amplification test (e.g., PCR, LAMP) or diagnostically equivalent molecular method.

Ocular Sub-classifications

Verified:

  • Meets the surveillance case definition for primary, secondary, or early non-primary non-secondary syphilis AND meets ocular clinical criteria AND meets ocular laboratory criteria, OR
  • Has a reactive blood-based treponemal antibody test result AND has a current (i.e., a test performed in the context of this index presentation) reactive blood-based nontreponemal antibody test result# AND meets ocular clinical criteria AND meets ocular laboratory criteria.

Likely:

  • Meets the surveillance case definition for primary, secondary, or early non-primary non-secondary syphilis AND meets ocular clinical criteria AND a diagnosis of ocular syphilis was made by a clinical provider, OR
  • Has a reactive blood-based treponemal antibody test result AND has a current (i.e., a test performed in the context of this index presentation) reactive blood-based nontreponemal antibody test result# AND meets ocular clinical criteria AND a diagnosis of ocular syphilis was made by a clinical provider, OR
  • Meets the surveillance case definition for primary, secondary, or early non-primary non-secondary syphilis AND meets ocular clinical criteria AND treatment for ocular syphilis was advised, ordered, or initiated by a clinical provider, OR
  • Has a reactive blood-based treponemal antibody test result AND has a current (i.e., a test performed in the context of this index presentation) reactive blood-based nontreponemal antibody test result# AND meets ocular clinical criteria AND treatment for ocular syphilis was advised, ordered, or initiated by a clinical provider.

# See case definition for syphilis, unknown duration or late.

Current or historical reactive treponemal antibody tests can be used to satisfy this criterion.


Otic Manifestations

Background

Otic manifestations (otosyphilis) can occur at any stage of syphilitic infection. If otic manifestations of syphilis are present in a previously unreported case of syphilis, the case should be reported with the appropriate stage of infection, and otic manifestations should be included with the case data.

Otic Clinical Criteria

Has clinical signs or symptoms consistent with infection of the cochleovestibular system with T. pallidum, as evidenced by manifestations including tinnitus, vertigo, and sensorineural or conductive hearing loss that can be permanent, without other clear causes for these clinical abnormalities.

Otic Laboratory Criteria

Direct detection of T. pallidum in inner ear fluid by nucleic acid amplification test (e.g., PCR, LAMP) or diagnostically equivalent molecular method.

Otic Sub-classifications

Verified:

  • Meets the surveillance case definition for primary, secondary, or early non-primary non-secondary syphilis AND meets otic clinical criteria AND meets otic laboratory criteria, OR
  • Has a reactive blood-based treponemal antibody test result AND has a current (i.e., a test performed in the context of this index presentation) reactive blood-based nontreponemal antibody test result# AND meets otic clinical criteria AND meets otic laboratory criteria.

Likely:

  • Meets the surveillance case definition for primary, secondary, or early non-primary non-secondary syphilis AND meets otic clinical criteria AND a diagnosis of otosyphilis was made by a clinical provider, OR
  • Has a reactive blood-based treponemal antibody test result AND has a current (i.e., a test performed in the context of this index presentation) reactive blood-based nontreponemal antibody test result# AND meets otic clinical criteria AND a diagnosis of otosyphilis was made by a clinical provider, OR
  • Meets the surveillance case definition for primary, secondary, or early non-primary non-secondary syphilis AND meets otic clinical criteria AND treatment for otosyphilis was advised, ordered, or initiated by a clinical provider, OR
  • Has a reactive blood-based treponemal antibody test result AND has a current (i.e., a test performed in the context of this index presentation) reactive blood-based nontreponemal antibody test result# AND meets otic clinical criteria AND treatment for otosyphilis was advised, ordered, or initiated by a clinical provider.

# See case definition for syphilis, unknown duration or late.

Current or historical reactive treponemal antibody tests can be used to satisfy this criterion.


Late Clinical Manifestations

Background

Late clinical manifestations of syphilis (tertiary syphilis) usually develop after a period of 10 or more years of untreated syphilitic infection. Therefore, if late clinical manifestations of syphilis are present in a previously unreported case of syphilis, the case should be reported as syphilis, unknown duration or late and late clinical manifestations should be included with the case data.

Late Clinical Criteria

In the absence of other clear causes for the clinical abnormalities,

  • Characteristic abnormalities or inflammatory lesions of the cardiovascular system (e.g., aortitis, coronary vessel disease), skin (e.g., gummatous lesions), bone (e.g., osteitis), or other tissues/structures (e.g., upper and lower respiratory tracts, mouth, eye, abdominal organs, reproductive organs, lymph nodes, central nervous system, and skeletal muscle).

Late Clinical Laboratory Criteria

  • Direct detection of T. pallidum by IHC staining in a specimen from a late lesion that was both not obtained from the oropharynx and not potentially contaminated by stool, OR
  • Direct detection of T. pallidum by nucleic acid amplification test (e.g., PCR, LAMP) or a diagnostically equivalent molecular method in any specimen from a late lesion, OR
  • Demonstration of pathologic changes that are consistent with T. pallidum infection on histologic examination of late lesions.

Late Clinical Sub-classifications

Verified#:

  • Has a current (i.e., a test performed in the context of this index presentation) reactive blood-based treponemal antibody test result AND meets late clinical criteria AND meets late clinical laboratory criteria, OR
  • Clinical signs and symptoms consistent with late neurologic manifestations of syphilis (i.e., general paresis or tabes dorsalis) in a case that meets the sub-classification criteria for verified neurologic manifestations of syphilis.

Likely#:

  • Has a current (i.e., a test performed in the context of this index presentation) reactive blood-based treponemal antibody test result AND meets late clinical criteria AND a diagnosis of late clinical manifestations was made by a clinical provider, OR
  • Has a current (i.e., a test performed in the context of this index presentation) reactive blood-based treponemal antibody test result AND meets late clinical criteria AND treatment for late clinical manifestations was advised, ordered, or initiated by a clinical provider, OR
  • Clinical signs and symptoms consistent with late neurologic manifestations of syphilis (i.e., general paresis or tabes dorsalis) in a case that meets the sub-classification criteria for likely neurologic manifestations of syphilis.

# See case definition for syphilis, unknown duration or late.