Syphilis (overview) A53.9

History: Syphilis first appeared in 1495 during the siege of Naples by the French King Charles VIII. Thereafter, within five years, a syphilis epidemic swept across Europe. The course of its spread can be seen from the names given to it by the different peoples, depending on where they thought the source of the infection was:

• Italy: French or Celtic disease.
• France: Italian or Neapolitan disease.
• Germany: French disease
• Japan: Chinese celestial disease.

According to the Columbus theory, syphilis was introduced by Christopher Columbus or his sailors when he returned to Europe in 1495 after discovering America. This theory has since been disproved. There is evidence that syphilis existed in a more harmless form, as a skin disease, as early as ancient Greece or pre-Columbian America. The name "syphilis" derives from a poem published in 1530 by the Venetian scholar Girolamo Fracastoro, which is the story of the infected shepherd Syphilus.

The pure cultivation of the syphilis pathogen was first achieved by the Japanese bacteriologist Noguchi Hideyo in 1911.

Worldwide spread infectious disease(venereal disease: in the FRG - non-named report directly to the RKI in case of laboratory detection), caused by Treponema pallidum.

A distinction is made according to the mode of infection, duration and organ manifestation:

• Congenital syphilis(Syphilis connata): only occasionally found in industrialised countries.
• Acquired syphilis (Syphilis acquisita)
  • Early sy philis (syphilis I and syphilis II)
  • Late syphilis (syphilis III - tertiary stage)
    • Neurosyphilis (late syphilis of the CNS)

Pathogen: Treponema pallidum (Spirochaeta pallida). A spirochaeta which, due to its sensitivity, is only transmitted in a warm and humid environment and thus almost exclusively via sexual intercourse.

Syphilis progresses in 3 stages with different clinical and disease activity, interrupted by latency phases.

• Early syphilis: the infectious phase of the disease (concerns the 1st year of untreated syphilis infection) is called early syphilis (primary and secondary stage).
• Late syphilis: the non-infectious stage is called tertiary stage (neurosyphillis). This stage is reached in industrialized countries only exceptionally.

In 2015, the nationwide incidence was 8.5 cases/100,000 inhabitants/year. In Berlin, the incidence was 31/100,000 inhabitants, in Hamburg 19.7/100,000. In 2014, the average incidence in Europe (29 countries) was 5.1 cases/100,000 inhabitants/year. The lowest incidence was found in Italy (0.6/100,000) and the highest in Malta (11.5/100,000 inhabitants/year).

The proportion of female syphilis cases reported in Germany was 6.2%.

Syphilis infections are more common in men who have sex with men ("men who have sex with men" MSM). The highest growth rates have been recorded in this group in recent years.

Up to 15% of those infected in Germany also suffer from an HIV infection, and up to 80% of those infected with HIV are TPHA-positive(no significant difference in the clinical course).

Note: For the Federal Republic of Germany, a non-named mediation with laboratory evidence directly to the RKI applies!

A distinction is made between search, confirmation and progress reactions:

• Search reactions: TPPA test, TPHA test, VDRL.
• Confirmation reactions: FTA test, FTA-Abs test (gold standard of confirmation test procedures), IgM/IgG-ELISA or IgG/IgM-Western blot.
• Activity control: Evaluation of the activity of the infection and titer determination can be performed by VDRL (Veneral Disease Research Laboratory) or Cardiolipin-KBR. The detection of IgM antibodies against Treponema pallidum can also be performed by IgM FTA-Abs test or by 19S IgM-FTA test.
• Follow-up: VDRL/RPR with the aim of a decrease of 3-4 titer levels within about one year after adequate therapy. 19-S-IgM-FTA-ABS in case of mainly re-infection, normal decrease after 3-24 months.

Clinically relevant test procedures:

• TPHA test (Treponema-Pallidum-Haemaglutination test): screening test with high specificity (0.2% false reactive findings). Detection of IgM and IgG antibodies. Reaction in all phases of the disease. Positive from the 3rd postinfection week. Low titers persist for life.
• FTA test (Flurescence Treponema Pallidum Antibody Absorption Test): High specificity and sensitivity (false reactive findings in 1%). With the 19S IgM FTA Abs Abs test, fresh infections can be diagnosed from the 2nd postinfection week.
• VDRL (= Venereal Disease Research Laboratory Test): Non-specific but quantitatively evaluable for activity and success assessment. Titres >1:4 are positive and indicate active syphilis. Positive reactions from the 5th week post infection. Time course and correlation with the clinic.
• Notice! In principle, non-specific and specific tests should be combined in the serological diagnosis of syphilis, such as the VDRL test and/or the TPHA test as a screening test in combination with the FTA-Abs test as a confirmatory test.

CSF serology for the assessment of neurosyphilis: Detection of syphilis-AK in the CSF. A negative result of the specific tests in CSF excludes neurosyphilis. The detection of IgG antibodies does not prove neurosyphilis, since these are liquor-permeable. The detection of IgM-AK in the cerebrospinal fluid secures the diagnosis.

Primary stage: 10-14 days after infection, mostly in the genital area (also extragential: lips, tongue, anal area, rectum, tonsils, fingers) development of a rich red, little aching nodule as a sign of primary infection. The nodule ulcerates (ulcus durum) between the 18th and 30th day after infection. Painless swelling of the regional lymph nodes.

Direct detection of spirochetes from the irritant serum by means of dark field technique possible(is only mastered by a few and therefore has no practical relevance anymore). TPHA test becomes positive 1 week after the ulcer develops.

Secondary stage: exanthema stage with the typical clinical changes. Detection of Treponema-pallidum-AK (VDRL >1:4, detection of IgG- and IgM-AK in the FTA-Abs and TPHA test)

Tertiary stage: Detection of Treponema-pallidum-AK

Neurosyphilis: Detection of IgM-AK in cerebrospinal fluid

See below syphilis early syphilis, late syphilis syphilis connata.

History of treatment methods: Until the beginning of the 20th century, syphilis was treated with highly toxic mercury, which was applied to large areas of the patient's body, usually resulting in the complete loss of body hair and all teeth and the rapid deterioration of all bodily functions. The South American natives had a combined syphilis therapy, which usually also cured them, as the disease was less severe in them than in Europeans. They used decoctions made from the wood or bark of the guaiac tree (Guaiacum officinale and G. sanctum) or sarsaparilla roots (Smilax regelii and other species) in combination with a sweat bath and a fasting cure. The sweat bath that the indigenous people of South America underwent after taking guaiac consisted of targeted hot steaming of the external genitals. Ulrich von Hutten tested this method himself and described it in his work 'De guajaci medicina et morbo gallico liber unus', published in 1519. The treatment did indeed lead to a temporary improvement. Around 1900 it was discovered that Treponema pallidum does not survive temperatures of > 41 °C. As a result, syphilis patients were infected with malaria. The high malaria fever attacks were often sufficient to kill the syphilis pathogen (malaria therapy). In 1909, Paul Ehrlich developed Salvarsan, a less toxic but effective arsenical remedy.

See also p. 10 and 11 of the current guidelines of the German STI Society(guidelines for syphilis)

Treatment of syphilis acquisita

History: Syphilis first appeared in 1495 during the siege of Naples by the French King Charles VIII. A syphilis epidemic then spread throughout Europe within five years. The course of its spread can be recognized by the names given to it by the various peoples, depending on where the source of the infection was thought to be:

• Italy: French or Celtic disease
• France: Italian or Neapolitan disease
• Spain: French disease
• England: French disease
• Scotland: English disease
• Germany: French disease
• Poland: German disease
• Hungary: French disease
• Russia: Polish disease
• Mongolia: Russian disease
• Japan: Chinese celestial cancer.

According to the Columbus theory, syphilis was introduced by Christopher Columbus or his sailors when he returned to Europe in 1495 after discovering America. The Columbus theory has since been challenged. There is evidence that syphilis already existed in a more harmless form, as a skin disease, in ancient Greece or in pre-Columbian America. The name syphilis goes back to a poem published in 1530 by the Venetian scholar Girolamo Fracastoro, which tells the story of the shepherd Syphilus, who suffered from this disease.

The Japanese bacteriologist Noguchi Hideyo was the first to succeed in cultivating the syphilis pathogen in 1911.

1. Adam B (2001) The punishment of Venus. A cultural history of venereal diseases. Orbis, Munich
2. Nenoff P et al (2017) Nonviral sexually transmitted infections-epidemiology, clinical manifestations,
   diagnostic workup, therapy: Part 3: Treponemes, Gardnerella and trichomonads. Dermatologist 68:136-148.