Syphilis

Testing for syphilis in pregnancy aims to detect women who have the infection so that they can be treated and transmission to their babies prevented.

36.1 Background

Syphilis is a sexually acquired infection caused by Treponema pallidum subs. pallidum. In pregnancy, it can result in spontaneous miscarriage or stillbirth or cause congenital syphilis infection. Syphilis in pregnancy can be safely treated with antibiotics, which can prevent these complications.

36.1.1 Syphilis in Australia

Rates of diagnosis of syphilis

Between 2013 and 2017, the notification rate of infectious syphilis increased 135% from 7.8 per 100,000 in 2013 to 18.3 per 100,000 in 2017, with an increase in both men (119%) and women (309%) Kirby Institute 2018a. ^[26] Rates among women in 2017 were highest in the 15–19 year (15.9 per 100,000), 20-24 year (15.1 per 100,000) and 25–29 year (13.7 per 100,000) age groups. The rate of notification for infectious syphilis among Aboriginal and Torres Strait Islander women was 40 times greater than among non-Indigenous women (97.4 vs 2.3 per 100,000) Kirby Institute 2018b. 

Geographical distribution

In 2017, infectious syphilis notification rates were higher in remote and very remote areas (62.9 per 100 000) than in major cities (17.8 per 100,000) Kirby Institute 2018a. Increases in notification rates occurred in all regions of residence between 2013 and 2017, with the greatest increase in remote areas (284% increase) and regional areas (271%), followed by major cities (127%). Rates of notification among Aboriginal and Torres Strait Islander people were highest in the Northern Territory (353.1 per 100,000) and Queensland (151.0 per 100,000) Kirby Institute 2018b, corresponding with regions in which there has been an outbreak of infectious syphilis (see below).

Congenital syphilis

Australia is a country of low prevalence for congenital syphilis. However, coinciding with peaks in infectious syphilis notifications, there have been peaks in cases of congenital syphilis (see below). Over the last 10 years (2008–2017), more than half (59%) of the 44 congenital syphilis notifications were in the Aboriginal and Torres Strait Islander population Kirby Institute 2018b.

Risk factors

Syphilis in Australia largely continues to be primarily among men having male-to-male sex in urban settings and of young heterosexual Aboriginal and Torres Strait Islander people in remote communities The Kirby Institute 2016. However, syphilis is increasing in some geographic areas and among some population groups Kirby Institute 2018b. A pregnant woman is at high risk of syphilis infection or reinfection when she: 

• (or her partner[s]) resides in a declared outbreak area (see Syphilis outbreak below) or an area of known high prevalence 
• is aged 15 to 29 years and resides in an area of high prevalence
• has a sexually transmitted infection in the current pregnancy or within the previous 12 months
• has previously had infectious syphilis in pregnancy
• engages in intravenous substance use during pregnancy.

Factors that increase the risk of syphilis infection or reinfection about which women may not be aware include when:

• she is a sexual contact of a person with infectious syphilis
• she has unprotected vaginal, oral or anal sex with a male partner at high risk of having syphilis
• she has a male sexual partner who has sex with men
• she and/or her partner(s) have sexual partners from high prevalence countries (eg countries in Africa and Asia, especially among refugees from these countries). 

An existing syphilis infection may be undetected among women who have had no or limited antenatal care.

Syphilis outbreak in Australia

In January 2011, an increase of infectious syphilis notifications among young Aboriginal and Torres Strait Islander people was identified in the North-West region of Queensland, which subsequently spread to other regions in north Queensland Bright & Dups 2016. Subsequent increases in notifications were reported in the Northern Territory and Western Australia in July 2013 and June 2014 respectively, following sustained periods of low notification rates. In March 2017, South Australia declared an outbreak in the Western and Eyre and Far North regions from November 2016 MJSO 2018. By 30 June 2018, there had been seven confirmed cases of congenital syphilis, six probable cases and six deaths from congenital syphilis (three confirmed and three probable) associated with the outbreak MJSO 2018. Surveillance reports on the outbreak are published online regularly by the Multijurisdictional Syphilis Outbreak Working Group. Outbreak management is discussed briefly in Section 36.5 and detailed in the Communicable Disease Network Australia (CDNA) Syphilis CDNA National Guidelines for Public Health Units Version 1.1 (see Section 36.7).

Notification

Syphilis is a notifiable disease under the public health acts of all states and territories, and nationally. Cases of reactive serology are reported by pathology laboratories to public health authorities CDNA 2018. In some jurisdictions, the health professional who diagnoses syphilis is also required to notify the jurisdictional public health authority. Probable or confirmed congenital syphilis must also be notified, including syphilis-related stillbirth CDNA 2018.

36.1.2 Risks associated with syphilis in pregnancy

Untreated syphilis during pregnancy is associated with stillbirth Arnesen et al 2015; Gomez et al 2013; Qin et al 2014 and fetal loss, preterm birth, neonatal death, low birthweight and congenital syphilis Gomez et al 2013; Qin et al 2014. Early treatment of maternal syphilis improves outcomes for the baby (see Section 36.4). 

A baby with congenital syphilis may be severely affected at birth (with hepatomegaly, ascites, hydrops, fetal anaemia) or more frequently, may appear unaffected CDNA 2015. If the diagnosis is not made then, the baby will present later with non-specific complaints (rhinitis, failure to thrive, pneumonia), nearly always within 3 months of birth. Neonates with severe disease have a poorer prognosis. 

36.2 Syphilis testing

There are two main classifications of serological tests for syphilis (T. pallidum) performed in medical testing laboratories (CDNA 2018): 

• treponemal tests, which detect specific treponemal antibodies and can be run on high throughput random access instruments — commonly used assays include EIAs and particle agglutination assays (eg T. pallidum particle agglutination [TPPA])
• non-treponemal tests, which detect non-specific antibodies and are performed manually — the assay most commonly used is the rapid plasma reagin (RPR).

In Australia, serum from blood specimens is usually screened with a treponemal assay and confirmed with an alternative treponemal assay using a different platform (ie screening with an EIA and confirmation with a TPPA). In people with prior treated syphilis, because the treponemal assays remain reactive for life, an RPR alone is sometimes used to detect reinfection or treatment success ASHA 2018.

Due to intralaboratory and interlaboratory variation, when a person has a changing non-treponemal antibody result, the current specimen should be tested in parallel with previous specimens.

Point-of-care tests are now available that present results within 15–20 minutes (see Section 36.2.3).
 

36.2.1 Universal testing

Given the severity of outcomes associated with syphilis during pregnancy (see Section 36.1.2) and the availability of effective treatment (see Section 36.4), routine testing for syphilis at the first antenatal contact is recommended. 

36.2.2 Repeat testing in women at high risk of infection or reinfection

Studies in the United States found that universal testing in the third trimester is not cost-effective when prevalence is low Albright et al 2015; Shiber & Todia 2014. However, testing and treatment early in the third trimester prevented 78% of cases of congenital syphilis in an area of very high prevalence Matthias et al 2017. 

Testing at additional time points is recommended in areas affected by an ongoing syphilis outbreak (see Section 36.5).

This recommendation provides the minimum time points for testing women at high risk of infection or reinfection. The testing schedule may be expanded based on local needs.

Monitoring changes in risk is also important for women at high risk of infection or reinfection.

36.2.3 Point-of-care testing

In Australia, the only syphilis point-of-care test registered by the Therapeutic Goods Administration is the Determine Syphilis TP™ manufactured by Alere, Abbott CDNA 2018.

Point-of-care tests for syphilis have sensitivity and specificity in the ranges of 0.70 to 0.92 and 0.93 to 0.99 for Determine™ Rogozinska et al 2017, 0.60 to 0.83 and 0.96 to 1.00 for SD Bioline Syphilis 3.0 Smit et al 2013; Rogozinska et al 2017, and 0.95 to 1.00 and 0.97 to 1.00 for SD Bioline HIV/Syphilis Duo Kit Omoding et al 2014; Bristow et al 2016; Shakya et al 201 (moderate to high certainty).

A systematic review Swartzendruber et al 2015 reported substantial increases in antenatal syphilis testing following introduction of point-of-care syphilis testing in low and middle income countries. Qualitative data revealed that women were highly satisfied with point-of-care syphilis testing. Adequate training for health care workers and supplies of commodities were cited as key implementation barriers. Another study noted the requirement for health professional training Smith et al 2015.

Studies into the cost-effectiveness of point-of-care testing conducted in developing countries highlighted that point-of-care tests were more cost-effective than RPR both in the field Sweeney et al 2014 and in the laboratory Mallma et al 2016. No cost-effective studies conducted in Australia were identified. 

More detailed information on the use and limitations of point-of-care tests in Australia, including the need for serological confirmation, their inability to distinguish between current and previous infection and the need for training of health professionals conducting point-of-care testing, is given in Syphilis CDNA National Guidelines for Public Health Units Version 1.1 (see Section 36.7).

36.3 Caring for women with a positive syphilis test result

All cases of syphilis in pregnancy should be discussed with a health professional with expertise in the area CDNA 2018. 

Women with infectious syphilis need to be informed of the infectious nature of the condition, even in the absence of visible lesions or symptoms, and to abstain from sexual activity for 5 days post-treatment or until symptoms have resolved, 5 days post treatment of their partners or until symptoms have completely resolved (whichever is longer). The risk of reinfection should be reinforced and the possible signs and symptoms of a new syphilis infection discussed. The importance of follow-up and repeat syphilis serology testing to monitor the response to treatment and detect reinfection should be emphasised and women assisted to access this follow-up (eg through recall systems). The woman should be informed that she is likely to continue to have positive treponemal specific tests for life, even after successful treatment.

Contact tracing and treatment for the woman’s partner(s) are critical to minimise the potential for re-infection as this represents a particular threat to the unborn baby CDNA 2018. Where possible, the interview should be conducted by someone known to and trusted by the woman and her partner CDNA 2018. Contacts should be treated presumptively without waiting for serology results.

36.4 Treatment for women with confirmed syphilis

While these Guidelines do not generally make recommendations on treatment, a recommendation on treatment for newly confirmed infectious syphilis is included here due to the current outbreak, deaths from congenital syphilis and rising prevalence nationally. This recommendation is consistent with advice from the CDNA.

Systematic reviews found that:

• treatment of syphilis in pregnancy with at least 1.8 g (2.4 MU) benzathine penicillin intramuscularly as a single dose reduces the incidence of congenital syphilis by 97% (95%CI 93 to 98%; 3 studies; moderate certainty), stillbirth by 82% (95%CI 67 to 90%; 8 studies; low certainty), preterm birth by 64% (95%CI 53 to 73%; 7 studies; low certainty) and neonatal deaths by 80% (95%CI 68 to 87%; 5 studies; low certainty) Blencowe et al 2011
• rates of adverse outcomes were higher among women receiving treatment in the third trimester compared to those treated in the first or second trimester (OR 2.24; 95%CI 1.28 to 3.93), although there was considerable heterogeneity (I2=78.3 to 81.7%) for outcomes other than congenital syphilis (odds ratio [OR] 2.92, 95%CI 0.66 to 12.87; I2=48.2%, p=0.165) (low certainty) Hawkes et al 2013
• based on the risk of adverse reactions to benzathine penicillin in the general population (pooled absolute risk 0.169%; 95%CI 0.073 to 0.265% I2 = 97%), risks from treatment among pregnant women are likely to be low (very low certainty) Galvao et al 2013.

Observational studies in settings of very high prevalence were consistent in finding treatment in the first trimester to be more effective than treatment in the third trimester Hong et al 2017; Zhang et al 2016. 

As treatment for syphilis varies depending on its duration, it is advisable to seek expert advice and arrange to see the woman again in one week as further treatment may be required.

Due to the high risk of mother-to-child transmission during pregnancy, particular care is required to conduct follow-up serology to monitor the response to treatment. Further details on monitoring and management of syphilis in pregnancy and postnatally, including treatment for women who are allergic to penicillin, and for congenital syphilis are given in the Syphilis CDNA National Guidelines for Public Health Units Version 1.1 (see Section 36.7). 

36.5 Outbreak management

This section is based on guidance from the CDNA (CDNA 2018). Local guidance about testing schedules and treatment should be sought in areas affected by an outbreak.

In the jurisdictions affected by an ongoing syphilis outbreak, syphilis serology testing five times around the pregnancy is recommended for women at risk of infection or re-infection within the outbreak areas: at the booking visit, again at 28 weeks, at 36 weeks, at birth, and 6 weeks post-partum CDNA 2018. As local guidelines within those areas may recommend different or additional times for testing, it is advisable to seek direction from local authorities CDNA 2018. In areas where point-of-care tests are used, serology confirmation of current infection or stages should be performed CDNA 2018. 

Women should be reassessed at every antenatal visit for symptoms of syphilis, and/or change in risk factors, and additional testing outside of the routine screening intervals should be considered based on clinical indication. Women at risk of inadequate antenatal care should be screened opportunistically, outside of the set interval where appropriate, whenever they present for care.

Women who present with symptoms consistent with infectious syphilis should be treated at the time of first presentation CDNA 2018. Women with infectious syphilis diagnosed on serology should be treated as soon as possible (and ideally within 2 days) of diagnosis CDNA 2018.

Contact tracing must be initiated immediately and support provided to ensure that current and previous contacts receive treatment. Women who are named as contacts of syphilis should also be treated at the time of initial presentation without waiting for serology results. Notification of confirmed or probable infectious syphilis in a pregnant woman is an urgent public health priority.
 

36.5.1 Notification of congenital syphilis 

One study found that 95% of babies in the Northern Territory meeting CDNA criteria for probable congenital syphilis were not notified between 2009 and 2014 and that improved education regarding CDNA criteria for notification of congenital syphilis is necessary for clinicians and public health staff. This study contributed to the release of new national case definitions for congenital syphilis in July 2015. 
 

36.6 Practice summary: syphilis testing

When

Early in antenatal care or at five key times in areas experiencing an outbreak (see Section 36.5)

Who

• Midwife
• GP
• obstetrician
• Aboriginal and Torres Strait Islander health worker
• multicultural health worker
• infectious diseases specialist
• public health unit staff.

What

• Discuss the reasons for syphilis testing
  Explain that it is important to find out whether a woman has syphilis because of the effects that infection can have on the pregnancy and the baby.
• Monitor changes in risk
  Discuss potential symptoms and changes in risk-factors at all antenatal visits, particularly in areas experiencing an outbreak.
• Document and follow-up
  Note the results of syphilis testing in the woman’s record, including whether the syphilis is newly diagnosed or was previously treated. Have a follow-up system in place so that women with confirmed syphilis receive timely treatment or referral. Any positive tests should be notified to the relevant public health authority.
• Take a holistic approach
  If a woman is found to be infected with syphilis, important considerations include counselling, contact tracing, partner testing, testing for other sexually transmitted infections (if this has not already been done) and follow-up.

36.7 Resources

• ASHA (2018) Australian STI Management Guidelines for Use in Primary Care. Australasian Sexual Health Alliance. 
• HIV Medicine">ASHM (2016) Australasian Contact Tracing Guidelines. Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine.
• CDNA (2018) Syphilis CDNA National Guidelines for Public Health Units Version 1.1. Canberra: Communicable Diseases Network Australia.
• MJSO (2018) Multijurisdictional Syphilis Outbreak Surveillance Reports. Multijurisdictional Syphilis Outbreak Working Group. 
• Palasanthiran P, Starr M, Jones C et al (2014) Management of perinatal infections. Sydney: Australasian Society for Infectious Diseases (ASID). 
• WHO (2017) WHO Guideline on Syphilis Screening and Treatment for Pregnant Women. Geneva: World Health Organization.