Screening

Screening for syphilis is important for the following reasons:

  • Syphilis infection is often asymptomatic but highly transmissible

  • If untreated, it causes in-utero mortality and considerable morbidity many years after initial infection

  • Treatment of syphilis in the early stage of infection is curative and aims to halt disease progression and eliminate further transmission of infection

  • Syphilis is an important facilitator of HIV transmission.

Screening is undertaken in:

  • Asymptomatic patients who are at risk of syphilis infection[1][80]

  • Pregnant women[8][31][67][68]​​[69][70]

  • Blood donors.[81]

Screening tests

Many laboratories employ a 'reverse sequence screening algorithm' whereby a treponemal serology test is used as the initial screening test (usually the treponemal enzyme immunoassay).[80] A treponemal test will identify patients with an infection, but it cannot distinguish between an active infection (i.e., currently untreated or incompletely treated) and a past (treated) infection.[8][46]

False-negative results may occur in incubating and early primary syphilis. False-positive results may occur with other non-sexually transmitted treponemal infection (e.g., yaws, pinta, bejel).[49]

If the treponemal test is positive, a non-treponemal test, such as the Venereal Disease Research Laboratory (VDRL) or rapid plasma reagin (RPR) test, should be performed to confirm the diagnosis and provide evidence of active disease or re-infection.[36]​ These tests enable a quantitative value of disease activity (titre) to guide treatment. If the non-treponemal test is subsequently negative, then a different treponemal test - preferably a Treponema pallidum particle agglutination assay or treponemal assay based on different antigens than the original test - should be performed to confirm the results of the initial test.[8]

An alternative approach to screening is the use of a non-treponemal test (VDRL or RPR) as the initial test. Positive tests need to be confirmed by using a treponemal test because false-positive results can occur due to other medical conditions (e.g., pregnancy, autoimmune disorders, other infections).

In resource-limited countries and in non-clinical settings, rapid point-of-care tests (which are recommended by the World Health Organization [WHO]) may have an important role in the control of syphilis and the prevention of adverse outcomes associated with syphilis in pregnancy.[67][82][83]

Screening in STI clinic

All patients with an STI should have syphilis screening, as should patients at higher risk of STIs, irrespective of where they are seen.[80] This includes men who have sex with men (MSM), HIV-infected patients, people with multiple sexual partners, commercial sex workers, and people exchanging sex for drugs.[1]​​​​[80][84][85]​​ The World Health Organization recommends self-collection of samples for syphilis may be considered as an additional approach to deliver STI testing services, although this recommendation has a low certainty of evidence.[86]

Antenatal screening

Screening of all pregnant women for syphilis infection is recommended by the US Preventive Services Task Force, the US Centers for Disease Control and Prevention (CDC), the American College of Obstetricians and Gynecologists (ACOG), the WHO, and the UK National Screening Committee.[7][8][67][68]​[80]​​[87][88]​ NSC: the UK NSC recommendation on syphilis screening in pregnancy Opens in new window​​​

Syphilis serology should be performed on all pregnant women at the first antenatal visit, or as early as possible in pregnancy, and results interpreted in the same way as for non-pregnant individuals.[8][36]​[67]​​​​ Serology should be repeated again at 28 weeks’ gestation and at delivery for women at high risk of syphilis infection.[8] Women who had no antenatal care before delivery or were at high risk for syphilis infection during pregnancy should have their serological status determined before they or their babies are discharged from hospital. No mother or baby should be discharged from hospital without the maternal serological status being documented at least once during the pregnancy.[8] In the context of the rapidly increasing rates of congenital syphilis, ACOG recommends that all pregnant individuals should be screened serologically for syphilis at the first prenatal care visit, followed by universal rescreening during the third trimester and at birth, rather than a risk-based approach to testing.[68]​ Antenatal screening is cost-effective, even in areas of low prevalence.[89]

Any woman who delivers a stillborn infant after 20 weeks’ gestation should be tested for syphilis.

All pregnant women who have syphilis and all infants and children at risk for congenital syphilis should be tested for HIV; UK and US guidelines recommend testing for HIV as part of routine antenatal care.[8][69][70]

Antenatal screening detects syphilis infection in asymptomatic pregnant women, enabling treatment to prevent infection in newborns (congenital syphilis), and other associated risks such as miscarriage, stillbirth, or neonatal death.[72] Evidence strongly supports antenatal syphilis screening and early treatment as a measure for preventing congenital syphilis.[31][68][87][90][91][92][93][94]​​​​

Clinics that provide on-site rapid syphilis testing, and immediate treatment for positive cases and their partners, may reduce the rate of congenital syphilis in regions where lack of awareness of syphilis infection, and problematic access to antenatal syphilis screening services, are potential issues.[95]

Screening low-risk asymptomatic population

Screening is not recommended if the patient is asymptomatic and not at increased risk of syphilis infection. Given the low incidence of syphilis infection in the general population and the consequent low yield of screening, the potential harms (e.g., of false positives) of screening in a low-incidence population may outweigh the benefits.[80]

Screening for HIV and other STIs

All patients with syphilis should be screened for chlamydia, gonorrhoea, and blood-borne viruses such as hepatitis B and C. All patients with syphilis should be tested for HIV.[8] Syphilis is an important facilitator of HIV transmission.[19] Co-infection is disproportionately high among MSM, particularly those on antiretroviral therapy.[23][42] A high level of suspicion for the testing and treatment of syphilis in patients with HIV is advisable. In geographical areas in which the prevalence of HIV is high, patients who have syphilis should be re-tested for HIV after 3 months, even if the first HIV test result is negative, and be offered HIV pre-exposure prophylaxis (PrEP).[8] In patients with HIV, serological responses to infection may be atypical, with high, low, or fluctuating titres.

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