Syphilis, Late With Clinical Manifestations (Including Late Benign Syphilis and Cardiovascular Syphilis)
2014 Case Definition

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.

Syphilis is a complex sexually transmitted disease that has a highly variable clinical course. Adherence to the following surveillance case definitions will facilitate understanding the epidemiology of this disease across the U.S.

Comments

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. If no other stage is appropriate, the case should be staged as "late, with clinical manifestations".

Neurosyphilis can apply to all stages of infection of syphilis on this page, including: primary syphilis, secondary syphilis, early latent syphilis, late latent syphilis, and late syphilis with clinical manifestations.

Neurosyphilis Surveillance Case Definition:

Clinical description

Infection of the central nervous system with T. pallidum, as evidenced by manifestations including syphilitic meningitis, meningovascular syphilis, optical involvement including interstitial keratitis and uveitis¹, general paresis, including dementia, and tabes dorsalis.

Laboratory criteria for diagnosis

• A reactive VDRL in cerebrospinal fluid (CSF) AND either 1.) a reactive treponemal serologic test for syphilis (e.g., FTA-ABS, TP-PA, EIA, CIA, or equivalent serologic methods) OR 2.) a reactive nontreponemal serologic test for syphilis (VDRL, RPR, or equivalent serologic method).

Case classification

Probable:

Syphilis of any stage with a negative VDRL test in CSF specimen and either 1) a reactive treponemal serologic test for syphilis (e.g., FTA-ABS, TP-PA, EIA, CIA, or equivalent serologic methods) OR 2) a reactive non-treponemal serologic test for syphilis (VDRL, RPR, or equivalent serologic method), AND both the following:

• Elevated CSF protein† or leukocyte count† in the absence of other known causes of these abnormalities, AND
• Clinical symptoms or signs consistent with neurosyphilis without other known causes for these clinical abnormalities

†CSF protein >50 mg/dL², >5 white blood cells/cubic millimeter CSF³; in HIV-positive individuals, these parameters are less specific

Confirmed:

Syphilis of any stage that meets the laboratory criteria for neurosyphilis.

Clinical Description

A stage of infection with Treponema pallidum characterized by one or more ulcerative lesions (e.g. chancre), which might differ considerably in clinical appearance.

Laboratory Criteria For Diagnosis

Demonstration of T. pallidum in clinical specimens by darkfield microscopy, or by polymerase chain reaction (PCR) or equivalent direct molecular methods.

Probable

A case that meets the clinical description of primary syphilis with a reactive serologic test (nontreponemal: Venereal Disease Research Laboratory [VDRL], rapid plasma reagin [RPR], or equivalent serologic methods; treponemal: fluorescent treponemal antibody absorbed [FTA-ABS], T. pallidum particle agglutination [TP-PA], enzyme immunoassay [EIA], chemiluminescence immunoassay [CIA], or equivalent serologic methods). These treponemal tests supersede older testing technologies, including microhemagglutination assay for antibody to T. pallidum [MHA-TP].

Confirmed

A case that meets the clinical description of primary syphilis that is laboratory confirmed

Comments

For cases with neurological manifestations, please refer to the Comment field about neurosyphilis at the bottom of this page

Clinical Description

A stage of infection caused by T. pallidum characterized by localized or diffuse mucocutaneous lesions (e.g., rash — such as non-pruritic macular, maculopapular, papular, or pustular lesions), often with generalized lymphadenopathy. Other symptoms can include mucous patches, condyloma lata, and alopecia. The primary ulcerative lesion may still be present. Because of the wide array of symptoms possibly indicating secondary syphilis, serologic tests for syphilis and a thorough sexual history and physical examination are crucial to determining if a case should be classified as secondary syphilis.

Laboratory Criteria For Diagnosis

Demonstration of T. pallidum in clinical specimens by darkfield microscopy, or by polymerase chain reaction (PCR) or equivalent direct molecular methods.

Probable

A case that meets the clinical description of secondary syphilis with a nontreponemal (VDRL, RPR, or equivalent serologic methods) titer ≥4 AND a reactive treponemal test (FTA-ABS, TP-PA, EIA, CIA, or equivalent serologic methods

Confirmed

A case that meets the clinical description of secondary syphilis (with at least one sign or symptom) that is laboratory confirmed

Comments

For cases with neurological manifestations, please refer to the Comment field about neurosyphilis at the bottom of this page

Clinical Description

A subcategory of latent syphilis (a stage of infection caused by T. pallidum in which organisms persist in the body of the infected person without causing symptoms or signs) when initial infection has occurred within the previous 12 months.

Probable

A person with no clinical signs or symptoms of syphilis who has one of the following:

• No past diagnosis of syphilis, AND a reactive nontreponemal test (e.g., VDRL, RPR, or equivalent serologic methods), AND a reactive treponemal test (e.g., FTA-ABS, TP-PA, EIA, CIA, or equivalent serologic methods),

OR

• A current nontreponemal test titer demonstrating fourfold or greater increase from the last nontreponemal test titer.

AND evidence of having acquired the infection within the previous 12 months based on one or more of the following criteria:

• Documented seroconversion or fourfold or greater increase in titer of a nontreponemal test during the previous 12 months
• Documented seroconversion of a treponemal test during the previous 12 months
• A history of symptoms consistent with primary or secondary syphilis during the previous 12 months
• A history of sexual exposure to a partner within the previous 12 months who had primary, secondary, or early latent syphilis (documented independently as duration < 12 months)
• Only sexual contact was within the last 12 months (sexual debut)

There is no confirmed case classification for early latent syphilis.

Comments

For cases with neurological manifestations, please refer to the Comment field about neurosyphilis at the bottom of this page

Clinical Description

A subcategory of latent syphilis (a stage of infection caused by T. pallidum in which organisms persist in the body of the infected person without causing symptoms or signs) when initial infection has occurred >12 months previously.

Probable

A person with no clinical signs or symptoms of syphilis who has one of the following:

• No past diagnosis of syphilis, AND a reactive nontreponemal test (e.g., VDRL, RPR, or equivalent serologic methods), AND a reactive treponemal test (e.g., FTA-ABS, TP-PA, EIA, CIA, or equivalent serologic methods),

OR

• A past history of syphilis therapy and a current nontreponemal test titer demonstrating fourfold or greater increase from the last nontreponemal test titer.

AND who has no evidence of having acquired the disease within the preceding 12 months (see Syphilis, early latent).
There is no confirmed case classification for early latent syphilis.

Comments

For cases with neurological manifestations, please refer to the Comment field about neurosyphilis at the bottom of this page

Clinical Description

A fetal death that occurs after a 20-week gestation or in which the fetus weighs greater than 500 g and the mother had untreated or inadequately treated* syphilis at delivery

Comments

For reporting purposes, syphilitic stillbirths should be reported as cases of congenital syphilis.

*Inadequate treatment consists of any non-penicillin therapy or penicillin given less than 30 days before delivery.

Clinical Description

A condition caused by infection in utero with Treponema pallidum. A wide spectrum of severity exists, and only severe cases are clinically apparent at birth. An infant or child (aged less than 2 years) may have signs such as hepatosplenomegaly, rash, condyloma lata, snuffles, jaundice (nonviral hepatitis), pseudoparalysis, anemia, or edema (nephrotic syndrome and/or malnutrition). An older child may have stigmata (e.g., interstitial keratitis, nerve deafness, anterior bowing of shins, frontal bossing, mulberry molars, Hutchinson teeth, saddle nose, rhagades, or Clutton joints).

Laboratory Criteria For Diagnosis

Demonstration of T. pallidum by darkfield microscopy, fluorescent antibody, or other specific stains in specimens from lesions, placenta, umbilical cord, or autopsy material.

Probable

A condition affecting an infant whose mother had untreated or inadequately treated* syphilis at delivery, regardless of signs in the infant, or an infant or child who has a reactive treponemal test for syphilis and any one of the following:

• Any evidence of congenital syphilis on physical examination
• Any evidence of congenital syphilis on radiographs of long bones
• A reactive cerebrospinal fluid (CSF) venereal disease research laboratory (VDRL)
• An elevated CSF cell count or protein (without other cause)
• A reactive fluorescent treponemal antibody absorbed--19S-IgM antibody test or IgM enzyme-linked immunosorbent assay

Confirmed

A case that is laboratory confirmed.

Comments

Congenital and acquired syphilis may be difficult to distinguish when a child is seropositive after infancy. Signs of congenital syphilis may not be obvious, and stigmata may not yet have developed. Abnormal values for CSF VDRL, cell count, and protein, as well as IgM antibodies, may be found in either congenital or acquired syphilis. Findings on radiographs of long bones may help because radiographic changes in the metaphysis and epiphysis are considered classic signs of congenitally acquired syphilis. The decision may ultimately be based on maternal history and clinical judgment. In a young child, the possibility of sexual abuse should be considered as a cause of acquired rather than congenital syphilis, depending on the clinical picture. For reporting purposes, congenital syphilis includes cases of congenitally acquired syphilis among infants and children as well as syphilitic stillbirths.

*Inadequate treatment consists of any non-penicillin therapy or penicillin given less than 30 days before delivery.