Designated Medical Practitioner Handbook

Appendix XI: Laboratory Diagnosis of Syphilis

Appendix XI is excerpted from Canadian Guidelines on Sexually Transmitted Infections, 2006 Edition, which is available in full online at www.phac-aspc.gc.ca/std-mts/sti_2006/sti_intro2006_e.html.

Serology

Serological diagnosis involves the initial screening of sera by non-treponemal tests such as the Venereal Disease Research Laboratory (VDRL), rapid plasma reagin (RPR), toluidine red unheated serum test (TRUST) or reagin screening test (RST). These tests normally become positive one to four weeks after the appearance of a primary chancre, approximately six weeks after infection.

Sera positive in non-treponemal tests are retested by treponemal assays such as the Treponema pallidum particle agglutination (TP-PA) test, flourescent treponemal antibody absorption (FTA-ABS) test and microhemagglutination for Treponema pallidum (MHA-TP).

Treponemal tests (for example, FTA-ABS, MHA-TP and EIA) usually remain reactive for life regardless of treatment, although 15–25% will serorevert if the patient is treated during the primary stage. These tests are highly sensitive, and possible false-positive syphilis tests should be kept in mind in individuals from areas of the world where pinta, yaws and bejel are prevalent.

The introduction of treponemal tests for IgG/IgM antibodies, such as the treponemal enzyme immunosassay (EIA), may provide a more sensitive screening test for syphilis. Although EIA is highly sensitive, the test can lack specificity. Therefore, if the treponemal-specific ELISA is positive, confirmation by a second treponemal-specific test is required (for example, TP-PA, MHA-TP, FTA-ABS).

Guide to interpretation of serologic tests for syphilis
(R=Reactive; NR=Nonreactive)

Test results on blood or serum Most likely condition
Non-treponemal test:
RPR/VDRL
Treponemal
test: TP-PA
Treponemal
test:
FTA-ABS
 
NR NR R Primary syphilis with compatible history/clinical findings
R
(dilutions
can vary)
R R Infectious syphilis (primary, secondary, early latent), especially if titre >1:8
OR
Old treated syphilis (especially if titre <1:8)
OR
Follow-up of treated syphilis
OR
In persons from endemic countries, yaws (e.g., Caribbean), pinta (e.g., Central America) or bejel
NR R R Usually treated syphilis
OR
Early infection (early primary syphilis)
OR
Late latent syphilis
OR
In persons from endemic countries, yaws (e.g., Caribbean), pinta (e.g., Central America) or bejel
OR
Lyme Disease
R NR NR Biological false positive
(repeat in 3–4 weeks)

Treatment

Stage Preferred treatment Alternative treatment for penicillin-allergic patients
All non-pregnant adults
• Primary
• Secondary
• Early latent
(<1 year duration)
Benzathine penicillin G 2.4 million units IM as a single dose • Doxycycline 100 mg PO bid for 14 days
All non-pregnant adults
• Late latent syphilis
• Latent syphilis of unknown duration
• Cardiovascular syphilis and other tertiary syphilis not involving the central nervous system
Benzathine penicillin G 2.4 million units IM weekly for 3 doses • Consider penicillin desensitization
• Doxycycline 100 mg PO bid for 28 days
All adults
Neurosyphilis
Penicillin G 3–4 million units IV q 4 h (16–24 million units/day) for 10–14 days • Strongly consider penicillin desensitization followed by treatment with penicillin
• Ceftriaxone 2 g IV/IM qd x 10–14 days
Epidemiological treatment of sexual contacts in the preceding 90 days to primary, secondary and early latent syphilis Benzathine penicillin G 2.4 million units IM as a single dose  
Pregnant women
• Primary
• Secondary
• Early latent
(<1 year duration)
Benzathine penicillin G 2.4 million units IM weekly for 3 doses • There is no satisfactory alternative to penicillin for the treatment of syphilis in pregnancy
• Strongly consider penicillin desensitization followed by treatment with penicillin
Pregnant women
• Late latent syphilis
• Latent syphilis of unknown duration
• Cardiovascular syphilis and other tertiary syphilis not involving the central nervous system
Benzathine penicillin G 2.4 million units IM weekly for 3 doses • There is no satisfactory alternative to penicillin for the treatment of syphilis in pregnancy
• Strongly consider penicillin desensitization followed by treatment with penicillin

Notes: Occasionally, there is inappropriate use of short-acting benzylpenicillin (Penicillin G) (IM) for the treatment of infectious syphilis rather than long-acting benzathine penicillin G (Bicillin-LA). DMPs should be aware of the similar names of these two products to prevent and avoid inappropriate and inadequate treatment. Long-acting benzathine penicillin achieves detectable serum levels of penicillin for two to four weeks in non-pregnant adults and is required to treat infectious syphilis adequately; short-acting penicillin agents are not adequate for achieving cure.

Special Considerations

HIV infection

Persons co-infected with HIV and syphilis may require a longer course of treatment, as well as closer and longer follow-up.

Pregnancy

All women newly diagnosed with syphilis during pregnancy should receive treatment appropriate to their stage of disease, with the exception of secondary syphilis in late pregnancy, where despite the administration of the recommended penicillin regimen, as many as 14% will have a fetal death or deliver infants with clinical evidence of congenital syphilis.

Retreatment during pregnancy is not necessary unless there is clinical or serologic evidence of new infection (four-fold rise in a non-treponemal test titre), or history of recent sexual contact with early syphilis.

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