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Control Guideline

Last updated: 01 July 2012

1. Reason for surveillance

1. To facilitate control of transmission.
2. 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) titre >=1:4.

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 less than 2 years duration and has 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 non-specific 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.

3. 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.
Reinfection of syphilis should be considered in the event of a fourfold or greater rise in non-specific treponemal antibody test (e.g., VDRL, RPR) after successful treatment following a previous notification.
Non-specific treponemal antibody tests done at different laboratories should not be directly compared. If a notification is received for a patient for whom there has been a previous notification from a different laboratory, and there is evidence suggestive of infection, enhanced surveillance information should be sought as per the usual process for following up new notifications.
Follow up of doctors in a timely manner has been correlated with more accurate and complete data collection as evidenced from HIV and other STI surveillance systems.

4. Notification criteria and procedure

Syphilis should be notified by:

• Laboratories on diagnosis (reporting by phone or fax on day of positive result).
• Medical practitioners and hospital CEOs on clinical diagnosis (ideal reporting by routine mail).

5. 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.

6. Managing single notifications

Response time
Public health units that receive laboratory notifications of syphilis in persons residing in another area health service should forward the laboratory notification to the relevant PHU on the same day to enable a prompt response.

Investigation

1. For probable or confirmed cases of congenital syphilis begin the follow up investigation within one working day of notification.
2. For all new notifications or suspected re-infections in men aged under 60 years and women aged under 45 years where the requesting doctor is not known to have experience in the management of syphilis, refer notification details, enhanced syphilis questionnaire and evaluation form onto sexual health clinic within one working day of notification (template included as appendix). The sexual health clinic will contact the doctor to provide support as appropriate, complete and return the enhanced surveillance questionnaire and evaluation questions.
3. For all new notifications or suspected re-infections where the requesting doctor is known to have experience in the management of syphilis or the patient is aged over 60 years if male or over 45 years if female then send the Syphilis Questionnaire to the diagnosing doctor within 3 working days of notification, and if necessary, follow up by phone within 14 days of notification (unless special arrangements have been made as outlined below).

Response procedure
For cases diagnosed by a Sexual Health Service, or clinicians known to the PHU to have expertise in sexual health, the PHU may make special arrangements to facilitate efficient notification, for example, arranging for distribution or collection of completed forms on a regular basis (at least monthly). This may replace the follow up phone call.
Where infectious syphilis is reported in a pregnant woman the PHU/Sexual Health Service staff member should contact the diagnosing doctor to confirm the woman has returned for treatment or has been referred to specialist services, if appropriate.

Cases under 16 years

• Where a case of syphilis is reported in a child <16 years old, the PHU must send a letter to the doctor who requested the test to undertake an assessment of the risk of harm according to the mandatory reporting guidelines and obligations under the Children and Young Persons (Care and Protection) Act, 1998 and resources for clinical management (Therapeutic Guidelines).
• Where a case of syphilis is reported in a child aged 12 years or under, the PHU must also directly contact the doctor (eg by telephone) to ensure that mandatory reporting obligations have been addressed. If no contact can be made, the PHU should contact the Child Well Being Unit (1300 480 420) or make a direct report to the Department of Community Services.
• All actions should be documented in the NCIMS record.

Data entry
Within 3 working days of notification enter new notifications onto NCIMS. Enter these new notifications into as syphilis unspecified.
All new notifications should be checked for duplicates on NCIMS.
To assist in identifying suspected re-infections enter the non-specific treponemal antibody tests (e.g. VDRL, RPR) along with laboratory name in the clinical notes in NCIMS. A 4-fold rise in RPR suggests that the notification represents a re-infection and should be managed in the same way as the new infection response.

On completion of the enhanced surveillance update case classification on NCIMS to indicate that the patient either:

• does not have a new infection and the previous infection was adequately treated then amend the NCIMS case status to excluded.
• has primary, secondary or early latent syphilis amend the NCIMS classification to syphilis- infectious.
• has late latent, neurological or tertiary syphilis amend the NCIMS classification to syphilis >2yrs or unknown duration
• has been re-infected with syphilis then re-enter the case as syphilis- infectious.

This should be done within 28 days of initial notification.

Cross-checking data with local Sexual Health Service
To optimise data quality in NCIMS the PHU should arrange for the Sexual Health Service in the Area Health Service to regularly provide lists of all syphilis diagnoses seen at the clinic. This list should include the patient identifiers, date of birth and postcode of residence, stage of classification of disease, symptomatic status and Aboriginality status. This information will assist in checking the completeness of notifications received and enable an update to the NCIMS where necessary.

Case management
Congenital cases

The response to a notification will normally be carried out in collaboration with the case's health carers. But regardless of who does the follow-up, PHU staff should ensure that action has been taken to:

• Confirm results of relevant pathology tests and presence of symptoms for child and maternal serological test results to determine child meets case definition.
• Complete the congenital syphilis form and forward to Communicable Diseases Branch.
• Refer to appropriate specialist for management.

Non congenital cases
In general, the attending medical practitioner is responsible for patient management, although the sexual health service should assist when required.
Investigation and treatment
Refer to Therapeutic Guidelines: Antibiotic, and seek expert advice from your local Sexual Health Service.
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:

• Primary syphilis: all sexual contacts in the preceding 90 days
• Secondary syphilis: all sexual contacts during the previous 6 months
• Early latent syphilis: all sexual contacts during the preceding year
• More than 2 year duration or unknown duration: sexual partners and children of infected mothers.
• Congenital syphilis: all members of the immediate family (Usually the mother and her partner, and other children if considered they are at risk).

Investigation and treatment
Contact tracing is generally the responsibility of the treating doctor and patient, although the sexual health service should assist when required.
For primary syphilis, early latent syphilis and latent syphilis, late and or unknown duration, contact tracing should involve investigation and treatment of contacts as described above.
For secondary syphilis, contact tracing should involve investigation of contacts and presumptive treatment if serology results cannot be obtained or if follow up is uncertain.
All contacts of congenital syphilis cases should be investigated and treated as appropriate.
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. Serological tests can be nonreactive among infants infected late during their mother's pregnancy

TEMPLATE FOR SHARING INFORMATION WITH THE SEXUAL HEALTH CLINIC
(to go on fax coversheet or hand delivered)

Dear XX

The XX Public Health Unit is undertaking follow up into notifications of syphilis as part of NSW Health's role under the Public Health Act. The information is provided to you to assist the PHU in undertaking this role in addressing and assessing risk to the public.

Please return the attached Syphilis Questionnaire and Evaluation of Sexual Health Service Follow Up form to us on (insert fax details)

Many thanks

Forms

1. Syphilis questionnaire form
2. Congenital syphilis questionnaire form
3. Evaluation of sexual health service follow up form