Syphilis

Outbreak Training Website

Clinical management | Testing and treating

Detailed protocols regarding syphilis testing and clinical management are available from:

Jurisdictional guidelines for syphilis testing and clinical management protocols
Jurisdiction	Title of Guideline (including website link)
National	Syphilis Series of National Guidelines (SoNG), Developed by CDNA and updated in August 2018, provides nationally consistent guidelines for public health units in responding to syphilis.
	Pregnancy care guidelines within SoNG: Syphilis Chapter of the Pregnancy Care Guidelines In addition, the updated in 2019, includes strengthened recommendations for testing females during pregnancy.
	Australian STI Management Guidelines for Primary Care.
	STI/HIV Testing Guidelines for MSM
Western Australia	The Silver Book
Northern Territory	CARPA Standard Treatment Manual Women's Business Manual NT Guidelines for the Management of Sexually Transmitted Infections in the Primary Health Care setting
Queensland	Communicable Diseases Control Guidance and Information : A-Z Primary Clinical Care Manual (PCCM) Syphilis in Pregnancy (SiP) Guidelines
South Australia	South Australian STI Guidelines Aboriginal Health Council of South Australia STI BBV handbook

While not replicating the above guidelines, the following information aims to highlight some of the key information regarding the natural history, testing, and management of syphilis.

Why Testing for Syphilis is Important

Prompt and appropriate testing and management of syphilis is essential to:

Prevent the ongoing transmission to sexual partners
Prevent the transmission from mother to baby and subsequent poor outcomes such as miscarriage, stillbirth, and congenital syphilis
Prevent illness caused by syphilis, including secondary and tertiary syphilis
Reduce transmission of HIV and other STIs and blood-borne viruses (BBVs), which cause genital sores or inflammation of the mucous membranes

Who and When to Test for Syphilis

Health practitioners (Aboriginal and Torres Strait Islander Health Workers and Practitioners, midwives, doctors and nurses) should consider the need for syphilis testing as much as possible and provide treatment for people presenting with any signs or symptoms that could be due to syphilis or other STIs and BBVs.

Syphilis testing should be repeated frequently for those at highest risk.

Refer to the Syphilis Series of National Guidelines (SoNG) for Public Health Units for a list of high-risk groups and the STI/HIV Testing Guidelines for MSM (STIGMA) for additional information.

Priority populations for syphilis testing
Testing for syphilis should always be included when conducting a check-up for STIs and BBVs and when any other STI or BBV has been detected as co-infections are common.
Men who have sex with men (MSM)	See STI/HIV Testing Guidelines for MSM
Priority populations defined by age, sexual orientation and/or location	During an outbreak situation screen at least 6 monthly Priority populations: remote areas, young Aboriginal and Torres Strait Islander people aged 15–40 years, women of childbearing age Note: age groups and frequency depend on the jurisdiction and local guidelines should be used
People who are pregnant	Recommend testing at:* first antenatal visit, 28 weeks, 36 weeks, time of birth and 6 weeks after the birth *See local guidelines for further information, particularly in an outbreak declared area, as recommendations for repeat testing vary. If there is a clinical suspicion of syphilis or exposure to syphilis, refer to syphilis guidelines and seek urgent specialist advice.
HIV positive people	Tested up to 4 times a year for syphilis Routine CD4⁺ and viral load testing should be done at the same time if clinically appropriate
People who have previously been treated for syphilis	Once reactive, the syphilis antibody screening test will remain positive for life, but this does not protect against re-infection of syphilis. Syphilis serology should continue to be tested as per local/state/national epidemiology and guidelines
Symptomatic presentation Test for syphilis when someone of any age presents with any signs and symptoms possibly due to syphilis or other STIs and BBVs such as:	Genital chancres, ulcers, sores or lumps can be painless or painful (due to secondary infections) Rashes/lesions in anal and genital areas Unexplained rashes anywhere on the body and rashes involving palms and soles Patchy hair loss in the scalp or eyebrows Unexplained headache, fevers, muscle aches and pains or lymphadenopathy When any STI or BBV is detected
Asymptomatic Screening Asymptomatic screening for syphilis should be done routinely in the following circumstances:	All 15- 40-year-olds Note: exact age groups and frequency depends on the jurisdiction and local guidelines should be used New or change of partner/multiple partners At follow up when any STI or BBV is detected, if not tested at the initial presentation A contact of a person with any STI or BBV The client requests a sexual health check up During a 715-health check Opportunistically – during ANY consult at which your clients present!

Syphilis in pregnancy

Infectious syphilis in pregnancy requires an urgent response and treatment and follow up commenced as soon as possible and within 24 hours.

Seek advice from an expert in sexual health or infectious diseases regarding the care of females who test positive and their partners.
In areas affected by an outbreak, treat females with symptoms of syphilis or a new positive PoCT as soon as possible without waiting for confirmatory testing, particularly if there is a risk of loss to follow-up.
For females with newly confirmed infectious syphilis, give intramuscular 2,400,000 units (given as two 1,200,000 units injections) benzathine penicillin as soon as possible, ensuring that females receive treatment at least 30 days before the estimated date of birth to ensure adequate treatment before the birth.

Ensure contact tracing (including offering testing and treatment to identified contacts) is carried out. Involve an expert in contact tracing if required or seek advice from a sexual health or other relevant expert.

For people with penicillin hypersensitivity (allergies to penicillin), there are two alternative therapies for treatment:

Desensitisation to penicillin: only penicillin is effective in pregnancy, those allergic should be desensitised then treated with penicillin. Seek specialist advice.
Non-penicillin regimes: while there is less evidence than penicillin, doxycycline has been shown to be effective; seek specialist advice.

Testing for syphilis: treponemal and non-treponemal testing

There are two types of syphilis testing. Treponemal tests are specific to syphilis but only tell us if someone has ever had syphilis (including an old infection that has already been treated). Non-treponemal tests tell us information about how infectious the person is and how recent the infection is likely to be. We use both types of testing to screen and diagnosis syphilis.

Treponemal tests detect specific treponemal antibodies and are used as a screening test to identify whether someone has been exposed to syphilis or not. Most laboratories currently use a treponemal test that is reported as reactive or non-reactive.

Treponemal tests:

have a small false positive rate (report a positive result, when the person is actually negative i.e., does not have syphilis); therefore, these tests require a second reactive treponemal test to confirm a true positive result
that return a non-reactive test indicates that the person has never been exposed to syphilis, however it should be repeated if exposure to infection was within 3 weeks
that returns a reactive result, indicates the person has been infected with syphilis – however, does not indicate:
- How long ago the person was infected OR
- Whether they have been treated in the past OR
- Whether they currently require treatment.
following exposure to syphilis, treponemal tests will become reactive by three months if infected.

Screening treponemal tests include:

enzyme immunoassay (EIA),
immunoglobulin M (IgM) and immunoglobulin G (IgG),
fluorescent treponemal antibody absorption (FTA Abs),
Point-of-Care (PoC) tests (see further information below).

Positive treponemal screening tests (above) are confirmed by a confirmatory treponemal test such as:

treponema pallidum particle agglutination assay (TPPA),
treponema pallidum haemagglutination assay (TPHA).

Syphilis PoC tests can be a useful addition to laboratory testing and can lead to a reduction in the time interval between testing and treatment.

In settings where PoC tests will be used, staff should:

Be appropriately trained and comply with certification; this includes training to conduct testing, interpret results, record results and report test results accurately to the client,
Be provided with PoC test user manuals,
Ensure quality control and assurance testing are regularly conducted,
Comply with surveillance, monitoring and notification requirements.

Check with your local PHU or Sexual Health and Blood-Borne Virus Program for updated information.

Syphilis Point-of-Care Testing (PoCT) - Determine™ Syphilis TP

Test type

Sample required

Main use

Considerations*

Treponemal test:

identify syphilis specific Treponemal antibodies

Whole-blood samples:

finger-prick or venepuncture

Screening in:

· priority populations

· people with no known syphilis history,

· in outbreak regions

Training required.

For positive PoCT, laboratory testing MUST also be conducted

See further considerations below

*Considerations (continued):

The Determine™ syphilis PoC test does not replace syphilis tests conducted in the laboratory:
- If a PoCT is non-reactive, venous blood does not need to be sent to the laboratory for syphilis screening unless there is concern about very recently acquired syphilis or symptoms suggestive of syphilis
- If a PoCT is reactive, venous blood MUST be sent to the laboratory for RPR
A reactive PoCT indicates exposure only and does not indicate when the person was infected, if they have been treated or require treatment
As with all treponemal tests, once reactive it will remain reactive for life and should not be repeated
If client has tested positive in the past, send away for serology testing immediately (i.e. not point in doing a PoC test)

Indications for use:

A PoC test should only be used on people who have never had a reactive treponemal or screening test (including those who have never been tested).
Use of PoC should be directed to those within priority populations for syphilis:
- pregnant people,
- 15- to 34-year-olds,
- men who have sex with men (MSM) and
- individuals at high risk

Limitations to use:

It should not be used on people who have EVER had a reactive treponemal test as it may return a reactive result therefore it has no value in this context
In remote areas with previous endemic syphilis, a significant number of people aged over 40 years will return a reactive result, the majority of whom have been adequately treated in the past 2. In these regions, laboratory syphilis testing should be done for people requiring a syphilis test.

ALL PoCT results (both reactive and non-reactive) need to be recorded in the client’s medical record and relayed to the regional Public Health Unit (PHU) as per local protocols.

When to treat using PoCT testing:

If PoCT and/or clinical signs and symptoms identify a likely new infection (see below):

Take venous blood and send to the laboratory for syphilis testing
Commence treatment
Take a full sexual history
Conduct an examination as appropriate
Test for other STIs and BBVs
Initiate contact tracing
Advise client not to have sex, until contact(s) have been treated (refer to guidelines for the number of days to abstain)
Complete a notification form and send to the regional PHU (this may vary amongst jurisdictions)
Contact the PHU/syphilis register in your jurisdiction for advice.

Identifying a likely new infection:

If a client’s last documented syphilis PoCT was non-reactive, a reactive PoCT indicates a new infection acquired since the last non-reactive screening test:

commence treatment as a new infection and
send venous blood to the laboratory for syphilis testing – laboratory testing will inform the treatment regime required.

If there is no previous testing history and the PoCT is reactive, this indicates the client has been infected with syphilis but does not tell you when:

Contact the PHU/syphilis register to check if they have ever had a previous screening tests and treatment
Commence treatment on the spot if they have any symptoms, are a contact or are at high risk of syphilis.

References:

1Miller P, Skov S, Knox J. How to Interpret Syphilis Results: a Manual for Nursing and Medical Staff in Remote Communities. 2nd edn. Nganampa Health Council Inc., 1999. Available from: http://www.nganampahealth.com.au/
2Government of Western Australia Department of Health and KAMSC, 2009–2013. Clinical audits conducted at various ACCHS by J Knox. Internal WA Department of Health report. Unpublished.

Non-treponemal tests detect non-specific antibodies. Non-treponemal antibody tests are done in the laboratory, if one of the treponemal screening tests (see above) is reactive. Rapid Antigen Reagin (RPR) testing is the most common confirmatory non-treponemal test, used in the diagnosis of a syphilis infection.

Rapid Antigen Reagin (RPR) testing
Test type	Sample required	Main use	Considerations
Non-treponemal antibody test: detects non-specific antibodies	Venous blood, sent to laboratory* *Refer to your regular lab requirements for sending samples	Confirmatory laboratory tests, with or after treponemal screening test	Interpretation of titre changes can be difficult MUST use SAME laboratory for all serial testing
RPR testing: is performed manually in a laboratory, where reactivity is measured by serial dilutions used to monitor treatment efficacy (if treatment is/is not working) and identify re-infections does not tell you whether someone has been treated, but can give an indication of infectivity results are reported as a titre: titre changes occur over the course of an infection and in response to treatment (as shown in graph below) *Graph: Variation in RPR results over time and with treatment* 1
RPR Results interpretation (also see examples below): A two titre or four-fold fall in the RPR (e.g., 1:32 to 1:8) within 6 months following treatment of infectious syphilis usually indicates adequate response to treatment The RPR is unlikely to fall if the baseline titre is very low (as in latent syphilis) and therefore cannot be used in this context to monitor treatment response but can be used to identify new infections. A two titre or four-fold rise from a previous RPR result can indicate a new infection (e.g., 1:2 to 1:8). Testing and logistics: Blood tests for syphilis provide a baseline against which to measure future testing, response to treatment and re-infections. Blood tests should always be taken if syphilis is suspected and an RPR taken again at the time of commencement of treatment to provide a baseline to measure response to treatment. If a PoC test has been conducted and is reactive, venous blood must also be sent to the laboratory for syphilis testing as outlined. The lack of regular transportation to the laboratory is not a reason not to take blood tests. Check specific storage and transportation requirements with the local laboratory but in general, specimens that are to be sent some days later can be centrifuged and kept in the fridge and should be transported at 2-8C.

VDRL (Venereal Disease Research Laboratory) test

VDRL (Venereal Disease Research Laboratory) test is a non-treponemal test which is currently only used in Australia for testing cerebrospinal fluid (CSF).

Syphilis Nucleic Acid Amplification Test (NAAT/PCR)

A swab should be taken for Syphilis NAAT/PCR test directly from any sore or lesion possibly due to primary or secondary syphilis. A reactive NAAT/PCR test from a lesion confirms infectious syphilis. Indicate on the pathology form where the swab has been taken from (e.g., genital/mouth/peri-anal ulcer) and request ‘syphilis and herpes PCR’; it may be appropriate to include ‘donovanosis PCR’ depending on local epidemiology and guidelines.

A blood test should always be taken at the same time for laboratory testing if infectious syphilis is suspected.

Syphilis testing: false positive test result

A false positive is when the test results come back as positive, but the patient is actually negative for the infection.

False positive test results can occur with:

both treponemal and RPR tests.
False positive treponemal tests may be identified in the laboratory as an unclear or indeterminate test result but confirmatory tests are usually conducted with another treponemal test before the result is reported as reactive or non-reactive.

The RPR test is read manually and therefore results may vary slightly among specimens taken at different times or processed at different laboratories. Biological false positive results can also occur with the RPR for a number of reasons including acute infections, inflammation, injecting drug use and pregnancy. False positive RPR results should only cause a low titre reading (usually <1:8) while laboratory errors or variations are generally only within 1 titre of each other. Reactive RPR results should always be considered as true positives among people at risk and an increase in RPR of two titres from the previous RPR considered a likely new infection.

Syphilis testing: false negative test result

A false negative is when the test results come back as negative, but the patient is actually positive for the infection.

False negative test results can occur among people who have:

Very early syphilis and are tested before the test is measurable in the blood
A prozone reaction where a large antibody (immune) response can make the test falsely negative
Immune-suppression due to HIV or other causes.

If there are any concerns about possible false positive results among people at low risk of infection, or false negative results among people likely to have syphilis always contact the regional PHU or appropriate specialists for advice and repeat testing.

Clinical Management | Follow-up and other considerations

Clinical management recommendations during an outbreak

To improve treatment of infectious syphilis, the Syphilis SoNG emphasises the importance of prompt and appropriate management of cases and contacts which support the existing state and national STI management guidelines and include the following recommendations:

Treatment should be given at the time of presentation to people presenting with signs or symptoms of primary or secondary syphilis.
Treatment of infectious syphilis identified on serology should be given as soon as possible and ideally within 2 days.
A serum specimen for syphilis serology RPR should be taken to give a baseline on the day of treatment (even if most recent test was the day before)
The RPR on the day of treatment is necessary to show the RPR falling at 3-6 months and 12 months (or in accordance with local guidelines) demonstrating that treatment is working.
Follow-up RPR testing should be done by the same laboratory as the RPR done on the day of treatment.
Increased follow-up in an outbreak situation is helpful to look for re-infection where contact tracing has not been possible by the patient not disclosing their partners, or re-infection in a much higher prevalence situation.
Jarisch-Herxheimer reaction is a common reaction to treatment in patients with primary and secondary syphilis. It occurs six to 12 hours after commencing treatment and is an unpleasant reaction of varying severity with fever, headache, general feeling of being unwell, body shakes and joint pains, which can last for several hours. Symptoms are controlled with pain medicines and rest. Patients should be made aware that this reaction may occur and reassured accordingly.

Follow up

Follow up serology to check for response to treatment should be done at 3, 6 and 12 months. A two titre (four-fold) drop indicates an adequate response to treatment at 6 months. Local guidelines should be used to ensure frequency is correct according to the jurisdiction.
Once reactive, the syphilis antibody PoCT test will remain positive for life, but this does not protect against re-infection of syphilis. Syphilis serology should continue to be tested as per sexual risk factors and local epidemiology and guidelines.

Follow up chart: https://ww2.health.wa.gov.au/Silver-book/Notifiable-infections/Syphilis

WA clinicians please note

Structured Administration and Supply Arrangement’s (SASA’s)

The Structured Administration and Supply Arrangements (SASAs) for Treatment of Syphilis Infection by Registered Nurses and Aboriginal Health Practitioners enable the administration of antibiotics for treatment of syphilis in WA. The SASA’s, and associated Conditions for administering treatment, were developed in consultation with public health physicians from WA Department of Health, WA Country Health Service and Aboriginal Community Controlled Health Organisations, and consultant sexual health physicians.

Please click on the links below to read the relevant SASA:

SASA - Treatment of Syphilis Infection by Aboriginal Health Practitioners
SASA - Treatment of Syphilis Infection by Registered Nurses

Other STI and HIV testing

As STIs and BBVs are often acquired together, it is important to check these when testing for syphilis. The tests required will depend on your patient’s gender, symptoms and whether there are any abnormal findings on physical examination. Refer to your local guidelines for more information.