SYPHILIS

Last updated: 06 September 2004

1. Reason for surveillance

To monitor the epidemiology of the disease to inform prevention strategies.

2. Case definition

Syphilis is a complex sexually transmissible disease with a highly variable clinical course and requires knowledge of clinical history, past serology and past treatment.

Syphilis - Infectious (primary, secondary and early latent), less than 2 years duration
A confirmed case requires:

• Laboratory definitive evidence, or
• Laboratory suggestive evidence AND clinical evidence.

Laboratory definitive evidence

• Seroconversion in past two years: specific treponemal test (e.g., IgG EIA, TPHA, TPPA, TPI, or FTA-AbS) reactive when previous treponemal test non-reactive within past two years, or
• A fourfold or greater rise in non-specific treponemal antibody test (e.g., VDRL, RPR) antibody titre in the past two years, and a reactive specific treponemal test (e.g., IgG EIA, TPHA, TPPA, TPI, or FTA-AbS).

Laboratory suggestive evidence:

• Demonstration of Treponema pallidum by darkfield microscopy (not oral lesions), direct fluorescent antibody tests, equivalent microscopic methods (e.g., silver stains), or DNA methods (e.g., nucleic acid testing [NAT]), or
• Non-specific treponemal test (e.g., VDRL, RPR) reagin titre of greater than or equal to 1:8.

Clinical evidence:

• Presence of a primary chancre (or ulcer), or
• Clinical signs of secondary syphilis.

Epidemiological evidence:
Not applicable.

Syphilis - More than 2 years or unknown duration
A confirmed case requires that the case does not meet the criteria for a case of less than 2 years duration AND EITHER:

• Laboratory definitive evidence, or
• Laboratory suggestive evidence AND clinical evidence.

Laboratory definitive evidence:

• A reactive specific treponemal test (e.g. IgG EIA, TPHA, TPPA, TPI, FTA-AbS) which is confirmed either by a reactive non-specific treponemal test (e.g. VDRL, RPR) or by a different specific treponemal test if the nonspecific treponemal test is non-reactive, and
• The absence of a history of documented previous adequate treatment of syphilis, or endemic treponemal disease (e.g. yaws).

Laboratory suggestive evidence
Demonstration of Treponema pallidum by darkfield microscopy (not oral lesions), direct fluorescent antibody tests, equivalent microscopic methods (e.g. silver stains), or DNA methods (e.g. NAT).

Clinical evidence
Clinical signs of tertiary syphilis.

Epidemiological evidence
Not applicable.

Congenital syphilis
Confirmed case
A confirmed case requires either:

• Laboratory definitive evidence, or
• Laboratory suggestive evidence and clinical evidence.

Laboratory definitive evidence

• Treponemal-specific antibody titres (eg. TPHA, TPPA, FTA-ABS) in infant serum greater than four-fold higher than in maternal serum, or
• Treponemal specific antibody titres in infant serum comparable with those in maternal serum and specific treponemal IgM EIA or IFA positive, or
• Detection of T. pallidum DNA in normally sterile specimen from infant (CSF, tissue) by nucleic acid testing.

Laboratory suggestive evidence

• Dark field microscopy of infant lesion exudate or node aspirate smears (not oral lesions) to demonstrate characteristic morphology and motility of T. pallidum, or
• Demonstration of T. pallidum in infant tissues by special (e.g. silver) stains, or
• Detection of T. pallidum DNA from an infant non-sterile site by nucleic acid testing, or
• Reactive fluorescent treponemal absorbed-19SIgM antibody test or IgM enzyme-linked immunosorbent assay AND treponemal-non specific antibody titre (eg. RPR) in infant serum greater than four-fold higher than in maternal serum.

Clinical evidence

• Asymptomatic infection (in the infant of an infected mother), or
• Foetal death in utero, or
• Stillbirth, which is a foetal death that occurs after a 20-week gestation or in which the foetus weighs greater than 500 g and the mother is untreated or inadequately treated for syphilis at delivery. Inadequate treatment is a nonpenicillin regimen or penicillin treatment given less than thirty days prior to delivery, or
• Clinical evidence of congenital syphilis on examination:
  • Age <2 years: Hepatosplenomegaly, rash, condylomalata, snuffles, jaundice (non-viral hepatitis), pseudoparalysis, anaemia, oedema
  • Age >2 years: Interstitial keratitis, nerve deafness, anterior bowing of shins, frontal bossing, mulberry molar, hutchinson teeth, saddle nose, rhagades, or clutton joints
  • Evidence of congenital syphilis on long bone X-ray changes in the metaphysis and epiphysis are considered classic for congenitally acquired syphilis)
  • Evidence of congenital syphilis on CSF examination (even if the mother has been adequately treated). This could include an elevated CSF cell count or protein (without other cause) as well as a reactive CSF VDRL titre. This diagnosis should be made with paediatric input because the white cell count of neonates is normally elevated.

Probable case
A probable case requires either:

• An infant (regardless of clinical signs) whose mother has been inadequately treated for syphilis during pregnancy. Inadequate treatment is a non-penicillin regimen or penicillin treatment given less than thirty days prior to delivery, or
• An infant or child who has a reactive treponemal antibody 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 CSF VDRL titre
  • An elevated CSF cell count or protein (without other cause)
  • A reactive fluorescent treponemal antibody absorbed assay -- 19S-IgM antibody test or IgM enzyme-linked immunosorbent assay.

Factors to be considered in case identification
Darkfield examinations and direct fluorescent antibody tests of lesion exudate or tissue are the definitive methods for diagnosing early syphilis. Such tests require considerable expertise and have low sensitivity.

A presumptive diagnosis is possible with the use of two types of serologic tests for syphilis:

• Nontreponemal (e.g., VDRL and RPR) and
• Treponemal (e.g., fluorescent treponemal antibody absorbed {FTA-ABS} and microhemagglutination assay for antibody to T. pallidum {MHA-TP}).

The use of only one type of test is insufficient for diagnosis because false-positive nontreponemal test results occasionally occur secondary to various medical conditions.

Nontreponemal test antibody titres usually correlate with disease activity, and results should be reported quantitatively. A fourfold change in titre, usually is considered necessary to demonstrate a clinically significant difference between two nontreponemal test results that were obtained by using the same serologic test. Nontreponemal test will eventually become nonreactive after treatment; however, in some patients, nontreponemal antibodies can persist at a low titre for a long period, sometimes for the remainder of their lives.

Most patients who have reactive treponemal tests will have reactive tests for the remainder of their lives, regardless of treatment or disease activity. However, 15%-25% of patients treated during the primary stage might revert to being serologically nonreactive after 2-3 years. Treponemal test antibody titres correlate poorly with disease activity and should not be used to assess treatment response.

Sequential serologic tests should be performed by using the same testing method (e.g., VDRL or RPR), preferably by the same laboratory. The VDRL and RPR are equally valid, but quantitative results from the two tests cannot be compared directly because RPR titres often are slightly higher than VDRL titres.

HIV-Infected patients can have abnormal serologic test results (i.e., unusually high, unusually low, and fluctuating titres). For such patients with clinical syndromes suggestive of early syphilis, use of other tests (e.g., biopsy and direct microscopy) should be considered. However, for most HIV-infected patients, serologic tests appear to be accurate and reliable for the diagnosis of syphilis and for evaluation of treatment response.

No single test can be used to diagnose all cases of neurosyphilis. The diagnosis of neurosyphilis can be made based on various combinations of reactive serologic test results, abnormalities of cerebrospinal fluid (CSF) cell count or protein, or a reactive VDRL-CSF with or without clinical manifestations. The CSF leukocyte count usually is elevated (≥5 BCs/mm3)
when neurosyphilis is present, and it also is a sensitive measure of the effectiveness of therapy. The VDRL-CSF is the standard serologic test for CSF; when reactive in the absence of substantial contamination of CSF with blood, it is considered diagnostic of neurosyphilis. However, the VDRL-CSF may be nonreactive when neurosyphilis is present. Some experts recommend performing an FTA-ABS test on CSF. The CSF FTAABS is less specific (i.e., yields more false-positive results) for neurosyphilis than the VDRL-CSF. However, the test is believed to be highly sensitive, and some experts believe that a negative CSF FTA-ABS test excludes neurosyphilis. False positives are caused by blood contamination of CSF (through traumatic lumbar punctures). PCR on CSF is available at ICPMR for diagnosis of neurosyphilis.

PCR testing is still under development. It may be useful for diagnosing congenital syphilis, early primary syphilis and neurosyphilis, and in distinguishing between old and new infections.

T. pallidum cannot be grown using conventional culture techniques.

3. Notification criteria and procedure

Syphilis is to be notified by:

• Medical practitioners and hospital CEOs on clinical diagnosis (ideal reporting by routine mail)
• Laboratories on diagnosis (ideal reporting by routine mail).

Only new confirmed cases of syphilis acquired after birth, and confirmed and probable cases of congenital syphilis should be entered onto NDD. To assist in identification of previously reported cases, PHUs should enter old cases on NDD as Other (treated syphilis).

4. The disease

Infectious agent
The spirochaete Treponema pallidum.

Mode of transmission
Syphilis is transmitted by direct contact with infectious exudates from early lesions of skin and mucous membranes, or with body fluids or secretions during sexual contact with infected persons, but may rarely occur with non-sexual contact where mucous membrane or skin lesions are present.

Timeline
The typical incubation period is 10 to 90 days, but more commonly 20 days.

Syphilis is communicable for a variable and indefinite period, but more likely when skin lesions (apparent or inapparent) are present. Congenital syphilis is most probably acquired during early maternal syphilis, but can occur some years after initial infection. Adequate penicillin therapy usually ends infectivity within 24 to 48 hours.

Clinical presentation
Most cases of syphilis have no signs or symptoms at diagnosis and are detected by serology. However, the usual clinical presentation is a primary lesion (chancre), which appears about three weeks after exposure. In untreated cases this may be followed several weeks later by a generalised rash, which is often maculopapular and may involve the palms and soles, as well as generalised lymphadenopathy. Cardiovascular or neuro-syphilis may develop many years later. Neurosyphilis usually presents as meningovascular disease, paresis or tabes dorsalis.

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 long bone x-rays may help, since xray changes in the metaphysis and epiphysis are considered classic for congenitally acquired disease. The decision may ultimately be based on maternal history and clinical judgment. The possibility of sexual abuse should be considered. For reporting purposes, congenital syphilis includes cases of congenitally acquired syphilis among infants and children, as well as syphilitic stillbirths. Cord blood may be used for screening for congenital syphilis, but a positive result should be confirmed using the infant's serum.

5. Managing single notifications

Managing single notifications
Investigation
On same day of notification of a probable or confirmed case of congenital syphilis begin follow-up investigation. For all other cases, mail a follow up letter (that includes an offer to assist in case follow up and a Syphilis Questionnaire that seeks information on the stage of the case) to the treating doctor within 3 working days of notification. If no response is received from the doctor, send a follow up letter (or telephone the doctor) within 30 days of the initial notification.

Data entry
Within 3 working days of notification enter cases onto NDD.

Update case classification on NDD within 45 days of initial notification.

Response procedure
PHU staff should determine whether the case is infectious. Such information should be sought from the referring doctor, for example by telephone or using the sample letters and form.

Where a case is reported in a child <16 years old is reported, the PHU must send a letter to the caring doctor outlining his/her obligation to notify the Department of Community Services (see sample letter, Appendix 1).

Case management
Investigation and treatment
In general, the attending medical practitioner is responsible for treatment.

Refer to Therapeutic Guidelines: Antibiotic, and seek expert advice. The efficacy of treatment and detection of reinfection are determined by serial quantitative measurements of the non-treponemal tests. It is recommended that follow-up include:

• For primary, secondary or early latent syphilis, monthly RPR/VDRL testing at 3, 6, 12 and 24 months
• For all other stages of syphilis, evidence of effective treatment should continue to be sought for ≥2 years, emphasising documentary proof of adequate treatment.

Retreatment should be considered if:

• Signs or symptoms remain or recur, or
• Initial RPR or VDRL titres fail to show a 4-fold decrease within 6 months of treatment.

Education
In general, the case's doctor provides counselling and education. The medical practitioner should provide information for the case about the nature of the infection and the mode of transmission (i.e., sexually transmitted infection).

Contact management
Identification of contacts
Depends on sexual history and stage of infection.

Investigation and treatment
Contacts of the following case categories require investigation and treated as follows:

• Primary syphilis: all sexual contacts in the preceding 90 days should be investigated and treated
• Secondary syphilis: contacts during the previous 6 months should be investigated and treated presumptively if serology results cannot be obtained or if follow up is uncertain
• Early latent syphilis: contact tracing and investigation should cover the preceding year
• Latent syphilis, late and or unknown duration: sexual partners and children of infected mothers should be investigated
• Congenital syphilis: all members of the immediate family should be investigated. (Usually the mother and her partner, and other children if considered they are at risk).

In addition, neonates born to seropositive woman who had inadequately treated syphilis (i.e. non-penicillin therapy, or penicillin administered less than 30 days before delivery) or whose initial RPR or VDRL titres fail to show a 4-fold decrease within 6 months of treatment should be carefully investigated. No infant should leave the hospital of delivery without ensuring that the serological status of the infant's mother had been documented at least once during pregnancy. Serological testing also should be performed at delivery in groups at risk for congenital syphilis. Serological tests can be nonreactive among infants infected late during their mother's pregnancy.