Syphilis guide: Screening and diagnostic testing

On this page

• Screening
  • Sexually active adults and adolescents
  • High prevalence groups and communities
  • Pregnant People
  • Other STBBIs
• Diagnostic Testing
  • Serologic testing
  • Syphilis serodiagnostic interpretation
  • Direct tests (Non-serological)
  • Lesions samples
  • Cerebrospinal fluid (CSF)
• References

Screening

For the purpose of PHAC's STBBI guides, screening is defined as testing asymptomatic individuals.

Screening for syphilis is an essential part of routine medical care for sexually active individuals, particularly in light of ongoing outbreaks of infectious and congenital syphilis in various jurisdictions across Canada^{Footnote 1}. Screening is effective for detecting and treating asymptomatic infections as well as preventing complications, transmission, and reinfection.

Health care providers should follow local public health recommendations and laboratory screening protocols during a syphilis outbreak.

Sexually active adults and adolescents

Screen all sexually active persons with a new or multiple partners, and/or upon request of the individual. Screening every 3 to 6 months is recommended in individuals with multiple partners.

High prevalence groups and communities

Due to stigma and prior negative experiences with the healthcare system, patients may not be fully transparent when discussing their sexual health. Health care providers should consider implementing an "opt-out" approach to screening to remove the need for an in-depth discussion on the person's sexual history. These programs have experienced greater success compared to "opt-in" programs in certain settings. Applying opt-out programs normalize STBBI screening and can help reduce stigma related to sexual health.

Targeted "opt-out" screening programs should be considered as frequently as every 3 months when serving population groups and/or communities experiencing high prevalence of syphilis (and other STBBI), such as:

• Gay, bisexual, and other men who have sex with men
• People living with HIV
• Person who is or has been incarcerated
• People who use substances and/or access addiction services
• Some Indigenous communities

It is important to consider aligning screening with other health services ("opportunistic screening") for individuals living with HIV and other individuals at increased risk accessing care services. Opportunistic screening is defined as offering screening when an individual is accessing non-emergency health services and has not undergone recent STBBI testing.

Consider local epidemiology when determining which groups/communities to target and for a specific individual, travel history and patient risk factors need to be considered^{Footnote 2}.

Pregnant people

Screening is of particular importance in pregnancy for the prevention of congenital syphilis and its impact on pregnancy outcomes.

Universal screening is recommended for pregnant people during the first trimester or at first prenatal visit.

Repeat screening at 28-32 weeks of pregnancy (or as close to this interval as possible) and again at delivery in the following circumstances:

• In areas with outbreaks or
• For pregnant people at ongoing risk of infection or reinfection

Consider more frequent screening for pregnant people at high risk.

Screen all people who deliver a stillborn infant after 20 weeks gestation.

Other STBBIs

STBBI screening varies by age, gender, sex, medical, and sexual history. Any person with STBBI risk factors should be screened for STBBIs and treated appropriately to prevent transmission and reinfection.

Syphilis increases the risk of acquisition and transmission of HIV^{Footnote 3}.

People being evaluated or treated for a syphilis infection should be screened for:

• Chlamydia
• Gonorrhea
• HIV, as per the recommendations in the HIV Screening and Testing Guide

Diagnostic testing

Consider a diagnosis of syphilis in anyone with signs or symptoms compatible with syphilis. Depending on the stage and clinical presentation, diagnostic testing may be done on blood, lesions and/or samples of cerebrospinal fluid.

Pregnant people diagnosed with infectious syphilis should be managed in consultation with an obstetric/maternal-fetal specialist. Assessment for possible congenital syphilis should be done:

• At 20 weeks gestation with a detailed obstetrical ultrasound^{Footnote 4,Footnote 5,Footnote 6,Footnote 7}
• In infancy

Test infants presenting with signs or symptoms compatible with early congenital syphilis even if their mother was seronegative at delivery because they may have become infected near term.

Refer to the following article by the Canadian Paediatric Society for information about how to manage infants born to mothers with reactive treponemal tests (TTs) during pregnancy : Congenital syphilis: No longer just of historical interest.

Serologic testing

Serologic testing should always be done regardless of suspected stage. Two (2) types of serologic screening algorithms are used in Canada^{Footnote 8}. Most provinces and territories use the reverse algorithm. Consult your local laboratory regarding testing protocols.

The traditional algorithm uses a non-treponemal test (NTT) - typically a rapid plasma reagin (RPR) test - to screen sera, followed by one (1) or two (2) TTs on the positive samples. An alternative approach is to use a reverse sequence algorithm, which uses a TT to screen and a quantitative NTT to confirm the positives. A second confirmatory TT may be done in some laboratories.

TTs such as the treponemal-specific enzyme immunoassay (EIA) are more sensitive tests for syphilis. Several commercial EIAs have been developed to detect IgG or IgM to specific T. pallidum antigens. Although EIA is highly sensitive, it may lack specificity; therefore if the EIA screen is positive, a second treponemal-specific test [e.g. T. pallidum particle agglutination (TP-PA), microhemagglutination assay for T. pallidum (MHA-TP), fluorescent treponemal antibody absorption(FTA-ABS), or INNO-LIA™ (if available)] can confirm the diagnosis.

Once reactive, TTs usually remain reactive for life regardless of treatment, although 15% to 25% of people will serorevert if treated during the primary stage^{Footnote 9}. False positive serologic tests for syphilis may occur with certain conditions such as collagen-vascular disease, pregnancy, injection drug use, Lyme Disease or a condition inherent to the test or testing technique.

NTT antibody titres usually correlate with disease activity and can help stage infection, monitor response to treatment and detect re-infection. The NTT may be non-reactive in cases of early primary, late latent syphilis or tertiary syphilis. If these diagnoses are suspected, it is appropriate to add a TT to the initial screen or, in the case of primary syphilis, to repeat both the TT and NTT after two (2) to four (4) weeks, when testing may have been done before seroconversion(incubation period).

Refer to the follow-up section for recommendations related to monitoring of NTT results post treatment.

Syphilis serodiagnostic interpretation

Note: The following information is provided for general guidance. Health care professionals should consider yaws, pinta, bejel and Lyme disease in the differential diagnosis when NTT and/or TT are positive. Interpret syphilis serology results in consultation with an experienced colleague. People with reactive syphilis serology should be tested for HIV, as HIV infection may affect treatment and recommended follow-up.

Traditional algorithm

Initial screen with NTT RPR	First TT TP-PA	Second TT FTA-ABS	Possible interpretation
Non-reactive	Non-reactive	Reactive	Primary syphilis with compatible history/clinical findings
Reactive (dilutions can vary)	Reactive	Reactive	Syphilis, any stageFootnote * Previously treated syphilis
Non-Reactive	Reactive	Reactive	Previously treated syphilis Early primary syphilis Late latent/tertiary syphilis
Reactive	Non-reactive	Non-reactive	False positive
Table 1 - Footnote * Note: RPR titre ≥ 8 are more likely to be infectious syphilis. Return to Table 1 - Footnote * referrer

Reverse algorithm

Initial screen with TT: EIA	NTT: RPR	Second TT: TP-PA, FTA-ABS or INNO-LA	Possible interpretation
Negative	Not done	Not done	Not a case. Repeat serology if at risk for syphilis
Borderline/ indeterminate	Non-reactive	Non-reactive or indeterminate	Repeat serology as seroconversion may not have occurred yet (incubation period) If repeat serology remains unchanged, it is not a case of syphilis
Borderline/ indeterminate	Non-reactive	Reactive	Early primary syphilis Late latent/tertiary syphilis Previously treated syphilis If laboratory does not do the confirmatory test, repeat serology to determine if the person is seroconverting If repeat serology remains unchanged it is not a case of syphilis
Positive	Reactive or non-reactive	Non-reactive	False positive EIA without 2nd TT: Early primary syphilis Late latent/tertiary syphilis Previously treated syphilis
Positive	Reactive or non-reactive	Indeterminate	Repeat serology to determine if it is early primary, late latent/tertiary or previously treated syphilis If repeat serology is unchanged this is likely to be a false positive EIA without 2nd TT: Syphilis, any stage, except with non-reactive NTT, then all but secondary stageFootnote * Previously treated syphilis
Positive	Non-reactive	Reactive	Early primary syphilis Late latent/tertiary syphilis Previously treated syphilis
Positive	Reactive	Reactive	Syphilis, any stageFootnote * Previously treated syphilis
Table 2 - Footnote * Note: RPR titre ≥ 8 are more likely to be infectious. Return to Table 2 - Footnote * referrer

Direct tests (Non-serological)

Non-serological tests are done on primary and secondary lesions. Contact your laboratory to determine the type and availability of direct tests for syphilis from suspect lesions (e.g. chancres, condylomata lata).

When latent or tertiary syphilis are suspected, conduct a physical and neurologic examination to evaluate for the presence of signs of tertiary syphilis. Chest radiographs for the evaluation of cardiovascular syphilis in asymptomatic people is not routinely recommended^{Footnote 10}.

Additional investigation, including long bone x-ray and lumbar puncture may be indicated when congenital syphilis is suspected. Work with a paediatric specialist to evaluate and test.

Lesions samples

Nucleic Acid Amplification Tests (NAAT) are very sensitive and specific. They can be used to detect T. pallidum in mucosa and skin from lesions of suspected primary and secondary syphilis and may be an option for oral/rectal lesions.

Dark-field microscopy is an older test that can detect the characteristic morphology and movement of T. pallidum spirochetes from genital lesions of early syphilis.

Note: Very few laboratories continue to offer dark-field microscopy in Canada.

The direct fluorescent antibody test (DFA) is another older test that can detect T. pallidum from genital lesions: it is not reliable for oral or rectal lesions as they may cross-react with specimens of non-pathogenic treponemes.

When ulcers are present, consider herpes simplex virus and (if epidemiologically appropriate) chancroid and/or lymphogranuloma venereum in the differential diagnosis.

Cerebrospinal fluid (CSF)

A diagnosis of neurosyphilis is usually based on a combination of reactive serologic results, abnormalities of CSF cell count or protein or a reactive CSF-VDRL with or without clinical manifestations^{Footnote 11}.

Indications for CSF examination in all people (including those who are HIV-positive) with suspected or confirmed syphilis, include:

• Presence of neurologic (including ocular and otic/auditory) symptoms or signs
• Failure to achieve an adequate serologic response to treatment
• Tertiary syphilis^{Footnote 12}
• Congenital syphilis

Some experts also recommend CSF examination in HIV-positive persons with infectious syphilis and a CD4 ≤ 350 cells/µL and VDRL/RPR ≥ 1:32 dilutions^{Footnote 13, Footnote 14}. CSF abnormalities in people with HIV-positive (e.g. elevated WBC and elevated protein) are common in persons with HIV, even without syphilis. It is unclear whether these findings are significant in people without neurologic symptoms.

While some studies have reported CSF abnormalities in people with CD4 ≤ 350 cells/µL and VDRL/RPR ≥ 1:32 dilutions^{Footnote 14}, CSF examination has not been associated with improved outcomes if the neurologic evaluation is normal.

CSF for cell count and differential, protein, VDRL and/or FTA-ABS^{Footnote 12} tests should be performed. CSF-VDRL is highly specific but not sensitive. The CSF FTA-ABS is highly sensitive but non-specific for neurosyphilis.

Note: A negative CSF FTA-ABS result may help to exclude a diagnosis of neurosyphilis^{Footnote 12}.

CSF examination is not recommended in late latent syphilis unless other criteria for CSF examination are met. In asymptomatic adults and youth co-infected with HIV, a detailed neurological evaluation^{Footnote 14}, close serologic and clinical follow-up post treatment is recommended.

References