Dr. med. Dirk Manski

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Syphilis: Diagnosis and Treatment

Diagnosis of Syphilis


Treponema pallidum can be diagnosed in fluids from skin lesions of primary and secondary syphilis with dark field microscopy or by immunohistochemistry. Corkscrew movements of spirochetes can be seen in wet mount specimens. False-positive results are possible by non-pathological spirochetes, but the sensitivity of microscopy is high.

NAAT swab test:

The NAAT swab test detects treponema DNA from the skin lesions, oral cavity or rectum, an option in early syphilis.

Serologic Testing for Syphilis

TPHA, TPPA or an immunoassay is used as a screening test (initial diagnosis), but these only become positive three weeks after first symptoms. If a screening test is positive, an alternative screening test is used as a confirmatory test or the FTA-Abs is used as a highly specific confirmatory test. Disease activity at initial diagnosis and follow-up is measured with the VDRL/RPR and IgM immunoassay:


The treponema pallidum hemagglutination or particle agglutination test enables a specific syphilis diagnosis. Patient serum is incubated with treponemas bound to erythrocytes or particles and agglutination is recorded semi-quantitatively at various dilution levels (titre).


Recombinant treponema antigens are incubated with patient serum and bound IgG and IgM are quantified. Depending on the test procedure, IgM and IgG are detected together (polyvalent screening tests) or the antibodies are quantified separately. Modern laboratories use immunoassays, since they are automated available.


The Fluorescent Treponemal Antibody Absorption test enables a highly specific syphilis diagnosis. Treponema pallidum is fixed on slides and incubated with patient serum. The patient's specific syphilis antibodies are detected with fluorescent anti-human antibodies.


The Venereal Disease Research Laboratory test or Rapid Plasma Reagin test are non-specific and measure disease activity by detecting anti-cardiolipin antibodies. VDRL and RPR are also positive in rheumatic diseases, pregnancy, leprosy and other infections.


Modern point-of-care tests simultaneously measure antibodies against cardiolipin (RPR) and syphilis antibodies (immunoassay) and allow a rapid diagnosis.

Further Diagnostic Studies

An HIV test and further examinations for sexually transmitted diseases are advisable. A detailed partner history and examination of all sexual partners is necessary.

Notifiable disease:

Syphilis is a notifiable disease in many countries.

Treatment of Syphilis

Treatment regims differ between early syphilis (primary syphilis, secondary syphilis and early latent syphilis) and late syphilis (late latent syphilis and tertiary syphilis).

Treatment of Early Syphilis:

First choice to treat early syphilis is benzathine penicillin G 2.4 million IU i.m. once, given as two gluteal injections with 1.2 million IU left and right.

Alternative Therapy (allergy to penicilline): ceftriaxone 1–2 g i.m. or i.v. for 10 days or doxycycline 100 mg p.o. 1-0-1 for 14 days.

Treatment of Late Syphilis:

First choice to treat late syphilis is Benzathine penicillin G 2.4 million IU i.m. at day 1, 8 and 15, the daily dose is given as two gluteal injections with 1.2 million IU left and right.

Alternative Therapy (allergy to penicilline): ceftriaxone 1–2 g i.m. or i.v. for 14 days or doxycycline 100 mg p.o. 1-0-1 for 28 days.

Treatment of Neurosyphilis:

Neurosyphilis is treated with penicillin G 3–4 million IU i.v. every 4 h for 14 days.

Alternative Therapy (allergy to penicilline): Ceftriaxone 2 g i.v. for 14 days or doxycycline 100 mg p.o. 1-0-1 for 28 days.

Treatment of Congenital Syphilis

Vertical transmission is likely prevented if treatment of the mother is started before the 16th week of pregnancy. The pregnant mother should be treated with Benzathine penicilline, see above mentioned recommendations. Newborns with congenital syphilis are treated with penicilline G i.v.

Jarisch-Herxheimer reaction

Jarisch-Herxheimer reaction is a systemic reaction due to massive bacterial antigen release after starting antibiotic therapy. Symptoms: fever, muscle pain, headache, skin rash. The Jarisch-Herxheimer reaction occurs most often in patients with secondary syphilis. For prophylaxis (1 h before antibiotic administration) or symptomatic therapy, 1 mg/kgKG prednisolone p.o. is prescribed.

Prophylaxis of Syphilis

Sexual abstinence, use of condoms, avoidance of risky sexual behaviour, post-exposure prophylaxis with doxycyclin in high-risk groups (trials ongoing).

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Deutsche STI-Gesellschaft (DSTIG): Diagnostik und Therapie der Syphilis. 2021. https://register.awmf.org/assets/guidelines/059-002l_S2k_Diagnostik_Therapie_Syphilis_2021_06.pdf

Center for Disease Control and Prevention: “Sexually Transmitted Infections (STI) Treatment Guidelines,” 2021. [Online]. Available: https://www.cdc.gov/std/treatment-guidelines/STI-Guidelines-2021.pdf

IUSTI, European guidelines on the management of syphilis. https://iusti.org/wp-content/uploads/2020/11/2020-Syphilis-guideline.pdf

Robert-Koch-Institut: RKI-Ratgeber Syphilis. https://www.rki.de/DE/Content/Infekt/EpidBull/Merkblaetter/Ratgeber_Syphilis.html

  Deutsche Version: Diagnose und Therapie der Syphilis (Lues)