Syphilis ( IPA : ˈzyːfilɪs , ), also Lues (venerea) ( IPA : ˈluːɛs , ), hard chancre and Schaudinn's disease or Schaudinn's disease , is a chronic infectious disease that belongs to the group of sexually transmitted Diseases heard. The causative agent of syphilis is the bacterium Treponema pallidum subspecies pallidum . Syphilis is mainly caused by Sexual intercourse is transmitted through contact with the mucous membranes and only from person to person. During pregnancy and childbirth an infected mother can give her child infect ( Congenital syphilis ).
The appearance of the disease is diverse. A typical start with painless ulcers of the mucous membrane and swelling of the lymph nodes. Some of the infected people develop a chronic course, which is characterized by diverse skin and organ involvement. In the final stage, the central nervous system is destroyed . Diagnosis is mainly made by the detection of antibodies . Syphilis can be cured by administering antibiotics , including penicillin . The discovery and subsequent availability of antibiotics in sufficient quantities led to a significant decline in syphilis in the 20th century. Since the 1990s, however, there has been an increase in the number of recognized diseases.
Since 2010 there have been 3 to 6 new infections per 100,000 inhabitants in Germany per year. The direct or indirect detection of the pathogen Treponema pallidum does not have to be reported by name in Germany. There is a reporting obligation for pathogens and diseases in Switzerland and a limited reporting obligation for the disease in Austria.
Syphilidology is the study of syphilitic diseases.
Etymology and names
The first documented syphilis outbreak in Europe occurred in 1494 or 1495 in Naples, Italy , during the French invasion of the Italian War of 1494-98 . At the time, it was believed that the disease was spread by the French troops, which is why the disease first came to be known as the French disease .
The word syphilis is found for the first time in 1530 in the title of a poem by the Veronese doctor Girolamo Fracastoro (1483 [?] - 1553), with the name syphilis, sive Morbus Gallicus (syphilis, or the French disease) . It tells the story of the shepherd Syphilus , who was punished for blasphemy (he erected forbidden altars) with a new disease, syphilis. The name Syphilus is the Latinized form of the ancient Greek name Σύφιλος Sýphilos , which can be translated as "loving pigs" ( σῦς sŷs , German 'pig' , φιλεῖν phileîn , German 'love' ). Fracastoro probably borrowed the name Syphilus from ancient mythology. In Ovid 's second son is called Niobe Sipylus . Why he chose this name is unknown.
The Latin word luēs means "plague", " calamity "; venereus comes from humanistic Latin , derives from venus , love lust, love enjoyment 'and means "relating to sexual intercourse". The French doctor Jacques de Béthencourt coined the name Morbus veneris (“Disease of Venus”) in 1526 with the intention of giving the disease a neutral name instead of the term "French disease", which was denigrating the French . Syphilis was often referred to as the epidemic of lust .
In addition, several hundred other names for syphilis have come down to us from history. These relate to the external appearance ( Morbus pustulatus ), to fallen body parts, to saints ( Job , Rochus and others), to alleged causes ( Lues venera , Lues aphrodisiaca ) or to the supposed country of origin. Syphilis has been named in various European languages as Neapolitan , Italian , French , Spanish , Castilian , English , Scottish or Polish disease, depending on the country from which the disease was supposedly introduced into the respective language area. In popular parlance, syphilis was also known as "large leaves" and with similar terms.
Treponema pallidum subspecies pallidum is a gram-negative bacterium of the genus Treponema in the family of Spirochaetaceae . Treponema pallidum (formerly called Spirochaeta pallida ) is spirally wound. In the dark field microscope , which is also used for detection, it shows rotations around the longitudinal axis and flexion movements, but no independent movement. The replication time is about 36 hours.
The only reservoir host is the human for whom it is obligately pathogenic , i.e. H. healthy immunocompetent people also fall ill. T. pallidum only survives outside the body for a short time; reduced oxygen concentration extends survival ( microaerophilic bacterium). An in vitro culture of Treponema pallidum is not possible because it requires nutrients from the human organism that it cannot produce itself. Cultivation is only successful in rabbit testicles.
In addition to Treponema pallidum , the genus Treponema includes other (harmful) pathogens that are pathogenic to humans: T. pallidum subspecies endemicum causes the endemic disease Bejel , also called non- venereal or extragenital syphilis, in Africa and the Middle East (see below). T. pallidum subspecies pertenue causes in Africa, Asia and Latin America, yaws , a lengthy infectious disease (-manifestationen) with skin and bone changes associated. Treponema carateum caused in Central and South America, the Pinta . This is a skin disease with recurrent hyperpigmented lesions, predominantly on the arms and legs, which heal with scarring. T. vincentii can cause Plaut-Vincent angina as part of a mixed infection .
Non-pathogenic Treponema species are T. denticola, T. minutum, T. refringens and T. phagedenis that in normal resident flora of the mouth, digestive tract and the reproductive organs can be found. If the pathogen is microscopic, they can lead to confusion.
Treponema pallidum is usually transmitted through direct sexual contact . It penetrates the body through the smallest lesions in the vaginal , oral or anal mucous membrane or skin. The pathogen can also be transmitted through injuries and skin contact. The liquid that escapes from the highly infectious ulcers is extremely contagious if it comes into direct contact with the skin. While syphilis in stages I and II (see below: stages ) is contagious to highly contagious, the infectiousness is much lower in the later stages.
Another important route of transmission is diaplacental transmission, i.e. the transfer of bacteria via the placenta to the unborn child ( fetus ). Diaplacental transmission is possible from the fourth month of pregnancy up to and including birth and can lead to abortion , intrauterine fetal death, stillbirth or damage to the child. In Germany, the examinations required by the maternity guidelines detect almost all untreated cases of syphilis in pregnant women and prevent transmission.
Infections caused by non- sterile acupuncture needles, injection cannulas or blood transfusions play a minor role, since all blood donors are tested for the disease. The highly infectious ulcers and papules that occur in stages I and II can , however, lead to infection without sexual contact.
Syphilis is an infectious disease that is widespread around the world. The WHO estimates the number of new cases worldwide at around twelve million cases annually, over 90% of them in developing countries, as of 1999. After the development of penicillin, the number of cases declined significantly in the course of the 20th century, which was severely affected by treatment programs of the WHO Regions since the 1950s.
In industrialized countries , the focus is on the big cities; homosexual men are particularly affected. 84 percent of all information on the probable route of infection (given in 71.5% of the 3,698 cases in 2011) related to such sexual contacts. The proportion of men among those affected has risen from 60% in the middle of the 20th century to over 85%. The number of cases in women and heterosexually infected men, however, has remained stable.
In Germany , new diagnoses registered by the Robert Koch Institute for 2019 are 7889, for 2018 with 7332, for 2017 with 7476, for 2016 with 7178, for 2015 with 6834, for 2014 with 5722, for 2013 with 5017, for 2009 with 2742 , for 2004 given as 3352. The number of infections in Germany has increased significantly in recent years. The incidence in women is only 1.1; for men, however, 18.1 cases per 100,000 inhabitants and year. The cities with the highest incidence are Cologne (57.8), Berlin (39.7) and Munich (30.2) per 100,000 inhabitants and year for 2019. The stage of the cases reported to the RKI in 2019 was as follows:
- 26.5% primary syphilis
- 15.5% secondary syphilis
- 2.1% tertiary syphilis
- 24.5% early latency
- 1.1% late latency
- 3 cases of congenital syphilis
The incidence was thus 3 to 6 new infections per 100,000 inhabitants per year. It is not uncommon for syphilis to appear as a co-infection in people infected with HIV . The situation is comparable in other industrialized countries.
The rate of congenital infections ( congenital syphilis ) is very low, with a few cases per year.
In Germany, the direct or indirect detection of the Treponema pallidum pathogen is not subject to notification by name according to (3) of the Infection Protection Act (IfSG). Laboratories etc. are required to report ( IfSG). According to the law of Saxony, according to the ordinance of the Saxon State Ministry for Social Affairs and Consumer Protection on the expansion of the reporting obligation for communicable diseases and pathogens according to the Infection Protection Act, there is a reporting obligation by name with regard to illness and death from congenital syphilis .
According to the Austrian Venereal Diseases Act, the disease syphilis has to be reported to a limited extent ( in conjunction with Venereal Diseases Act).
In Switzerland, the positive laboratory analysis findings at the request of the cantonal doctor or to report the case to the cantonal physician, or the start of antibiotic treatment of syphilis is a notifiable disease . In addition, positive laboratory analysis results for Treponema pallidum must be reported. Both the Epidemics Act (EpG) in conjunction with the Epidemics Ordinance and or the Ordinance of the FDHA on the reporting of observations of communicable diseases in humans .
Primary stage, primary syphilis, syphilis I
Three to four weeks after infection, a small painless or painless, nodular ulcer appears at the point where the bacteria have penetrated the skin or mucous membrane , the edge of which is hardened. That is why the ulcer, which has become the size of a coin after about a week, is also referred to as a hard chancre ( ulcus durum ). So it is initially a local infection . This primary effect occurs during vaginal intercourse on the penis , on the labia or in the vagina . It can also be found in the mouth or throat during oral intercourse and in the rectum during anal intercourse . The ulcer is red and secretes a colorless liquid. This contains many pathogens, so it is extremely contagious. One to two weeks later, the neighboring lymph nodes swell and pain in the joints, muscles, and bones can occur. From this point on, the disease can be detected with the TPHA test. Even if left untreated, the ulcers heal on their own after 4–6 weeks, which is why the disease is often ignored or not recognized.
Hard chancre on the underside of the penis .
Chancre on the shaft of the penis due to a Treponema pallidum infection (primary stage of syphilis).
Secondary stage, secondary syphilis, syphilis II
Eight to nine weeks after infection, flu-like symptoms such as fever, fatigue or headache and body aches often occur. The lymph nodes all over the body are swollen (generalized lymphadenopathy , polyscleradenitis). The disease has now passed into a generalized stage. After ten weeks, most of the patients develop a rash ( exanthem ). Initially, there are only light pink spots that turn into copper-colored nodules ( papules ). Broad papules, which occur especially in skin folds, are called condylomata lata . If these rise and wet, the leaking liquid is highly infectious. Changes in the mucous membrane in the mouth ( enanthemum , plaques muqueuses ) and on the genitals are also less common . Eye infections can also occur. Some patients lose their hair ( alopecia specifica ). All skin symptoms (syphilids) heal after about four months, so that some patients notice little of their infection. If left untreated, they come back at various intervals. Typically, there is little to no itching for all skin manifestations of syphilis .
In about 30% of untreated syphilis, spontaneous healing occurs over the course of years. In the case of untreated early syphilis that has not healed spontaneously, the disease can come to a standstill in those affected in the following latency period , although the pathogens are still in the body. After months or years, latent syphilis can develop into late syphilis . The infected person is contagious, even if this risk decreases the longer the patient remains symptom-free.
The term Babinski-Vaques syndrome was previously used for a form of late syphilis with Robertson's pupil , aortitis and weakened reflexes of the thigh and lower leg muscles as well as chronic meningoencephalitis .
Tertiary stage, tertiary syphilis, syphilis III
Three to five years later, it is not only the portal of entry, lymph nodes and skin that are affected. The pathogens have spread throughout the body and also attacked internal organs such as blood and airways , throat , esophagus , stomach , liver , bones and muscles . Knots are formed that are often rubbery and hardened ( gums , in the singular gumma ). Histologically, gums appear as monocyte-destructive, plasma-cell-containing granulomas . They occur in particular on the skin, mucous membrane and bones. They sometimes form large ulcers on the skin and a perforation to the nasal cavity may appear on the palate. A syphilitic nodule on the main artery ( aorta ) caused by an inflammation in the middle and outer wall layers of the same ( mesaortitis luetica ) is particularly dangerous . About 30 years after the infection, such a lump can lead to a late complication of an easily tearable aortic sac ( aortic aneurysm ). Should this bulge tear, the affected person will bleed to death internally. The central nervous system can also be affected.
Quaternary stage (neurolues, neurosyphilis), syphilis IV
While the severe neurological disorders that occur in around 20% of those affected ten to twenty years after the onset of the disease were originally assigned to the tertiary stage, the more recent literature also speaks of an independent quaternary stage (Lues IV). A quarter of untreated patients develop chronic brain inflammation ( syphilis cerebrospinalis ), which leads to dementia . In some cases, a significant short-term increase in the cognitive mental abilities of the infected is also reported. The progressive paralysis of neurosyphilis manifests itself by the increasing loss of intellectual faculties, an ataxia and speech disorders. In addition, the spinal cord and its exiting nerves are so damaged that the patient initially feels pain, then no longer perceives pain and temperature ( tabes dorsalis ). Walking and control of the bladder and bowel are disturbed. In the end, the patients are paralyzed. The optic nerve can also be involved, with subsequent deterioration in vision, including blindness. There are also circulatory, bone and joint damage ( Charcot joints). This course is rarely observed in Western countries thanks to adequate antibiotic therapy. Exceptional sensitive or psychological changes in this phase have been described in many places, but never systematized, such as the excessive increase in libido and various types of changes in perception .
Congenital syphilis (Lues connata, congenital syphilis)
In the fourth to fifth month of pregnancy (i.e. after developing its own immune system), a fetus can develop syphilis. As a result, there can be stillbirth, miscarriage or premature birth , births of seriously ill children with congenital syphilis, syphilis , or births of apparently healthy children in whom no symptoms are noticeable. The Lues connata is roughly divided into two forms, although this assessment can only be made retrospectively in part.
In the congenital syphilis praecox (also Congenital syphilis praecox - early congenital syphilis) are the main symptoms as follows: bloody coryza (runny nose), maculopapular rash (patchy, marked to the hair approaches by small nodules rash) and pseudoparalysis . In addition, it can lead to blistered skin changes ( pemphigus ), enlargement of the liver and spleen ( hepatosplenomegaly ) and osteochondritis (inflammatory cartilage / bone diseases), which affect later growth and appearance.
In the case of symptoms that appear a little later and are visible beyond the second year of life, on the other hand, one speaks of syphilis connata tarda (congenital delayed syphilis). This is classically associated with a Hutchinson triad: inflammation of the cornea of the eye ( keratitis ), inner ear hearing loss and barrel-shaped incisors. In addition, the destruction of the cartilage and bones of the nasal septum and the bridge of the nose can create a so-called saddle nose . These characteristics typical of congenital syphilis are also called stigmata . Preventive examinations and early therapy can almost rule out both manifestations of congenital syphilis.
Extra genital syphilis
The extragenital or endemic syphilis is caused by Treponema pallidum ssp. endemicum (see above). It occurs in Africa and the Middle East , where it is called Bejel . In contrast to Treponema Pallidum, it is also transmitted through objects of daily use; the portal of entry is often the oral mucosa. The skin and mucous membrane symptoms are practically indistinguishable from venereal syphilis, but organs are rarely affected. The serological syphilis tests are positive. As with venereal syphilis, treatment consists of the administration of benzylpenicillin .
In addition to the observation of typical symptoms (anamnesis and clinical examination), there are various direct and indirect methods of detection of syphilis infection. The direct detection of the pathogen occurs through dark field microscopy or silver staining of secretions. The immunofluorescence test is very sensitive. In individual cases, a PCR detection is also possible, but not the cultivation of the pathogen. If the time of infection is unknown, the cerebrospinal fluid must be examined for possible neurolues ( lumbar puncture ). The indirect methods, which are usually used for diagnosis, are based on the serological detection of syphilis antibodies in the patient's blood:
The TPHA (Treponema pallidum haemagglutination assay) is a screening test (search test) for the syphilis pathogen: the patient's blood serum is diluted with Treponema-marked sheep blood cells; if antibodies against the pathogen are present, the blood clumps together (see titer determination ). A variant of this test, in which latex particles are used instead of sheep blood cells, is called TPPA (Treponema pallidum particle agglutination test). The TPHA test is positive no earlier than four to six weeks after infection.
The FTA-Abs test (Treponema pallidum antibody fluorescence test) is a confirmatory test for positive TPHA: the serum is combined with so-called Reiter spirochetes (non-pathogenic treponemas). Cross-reacting antibodies that lead to a false positive result are removed. Hence the ABS in the name of the test: the "wrong" (cross-reacting) antibodies are absorbed. In the next step, a glass plate coated with dead treponemes is brought together with the patient's "absorbed" serum. The binding of the antibodies from the patient's serum to the treponemas on the glass plate is then made visible in fluorescence microscopy using a color-coded antibody. A variant of this test that only detects IgM antibodies is called FTA-ABS-19S-IgM.
The VDRL test (Venereal Disease Research Laboratory) serves as a test for progress control, activity assessment and assessment of the need for treatment: In this test, antibodies against cardiolipin are detected that are not specific for syphilis, but also occur in other diseases (especially antiphospholipid) Syndrome ). It is also known as the CMT (cardiolipin microflocculation test).
Since Treponema pallidum has not developed any resistance to penicillins even after 80 years , these agents are of choice for the treatment of syphilis in all stages of the disease, especially penicillin G and benzylpenicillin-benzathine . Since the treponemas replicate slowly, a treatment duration of at least 10-14 days is necessary - apart from early syphilis - in late stages and for neurolues of 14-21 days. In the primary / secondary stage, a single, higher-dose administration is alternatively possible. While an intramuscular injection is sufficient in the early stages , in the case of a neurolues it is not possible to build up a sufficient effective level in the brain in this way. In these cases, intravenous administration over a period of three weeks is necessary as part of an inpatient hospital stay . Penicillins are also indicated for the treatment of syphilis connata and diseases during pregnancy and in the case of HIV infection.
In the case of allergies, other antibiotics such as tetracyclines , macrolides or cephalosporins are used. The selection is made depending on the stage of the disease and accompanying circumstances. When using cephalosporins, cross allergies must be expected in around 5–10% of cases.
A side effect of antibiotic therapy for syphilis is the Jarisch-Herxheimer reaction , which occurs particularly in older patients or in long-standing syphilis, mostly in the early stages, only rarely in neurolues. The rapid disintegration of the treponemes in the presence of numerous pathogens leads to the release of toxins . Fever , headache , muscle pain and hypotension can result, usually 2–8 hours after the start of therapy. The Jarisch-Herxheimer reaction can be treated with cortisone derivatives. A prophylaxis is possible.
If the therapy is successful, there is a clear decrease in antibodies . Therapy controls should initially be carried out quarterly, later annually by means of VDRL and TPHA tests, and if the brain is affected, also by means of the CSF diagnostics, which have been used for a long time . Monthly checkups are recommended during pregnancy.
However, once syphilis has been overcome, it does not protect against renewed infection, as the disease does not produce any lasting antibodies against the pathogen and thus no immunity is developed.
There is no vaccination against syphilis . The use of condoms during sexual intercourse can significantly reduce the likelihood of transmission of syphilis and other sexually transmitted diseases . Because of the same path of infection, a syphilis disease often occurs together with an HIV infection, so if a sexually transmitted disease is present, others should always be checked and excluded. The notification and serological examination of the partner of the sick person is called partner tracing .
Transmission of syphilis is also possible during oral sex .
Origin of syphilis
For a long time there was disagreement about the origin of syphilis. Due to early descriptions by the participants of Columbus ' second trip to America and near the time of the trips, it was assumed that the syphilis had been introduced from America (cf. Columbian Exchange ) and was previously completely unknown in other continents. Later research suggests that - presumably less dangerous - forms of syphilis were known in Europe at least in ancient times. Presumably, however, a South American tribe was newly introduced by the Spanish voyages of discovery to which the European population had no adaptation (see below ).
In the 16th century, the word syphilis may have been used to refer to the disease caused by Treponema pallidum as well as other treponematoses such as yaws and pinta . The gonorrhea was sometimes not distinguished from syphilis. Confusion with leprosy (“leprosy”) at the time cannot be ruled out in some cases.
Spread at the end of the 15th century
From 1493, when Christopher Columbus returned from his first expedition to America, cases of a disease that seemed novel at the time were noticed in Spanish port cities such as Barcelona . The Spanish doctor Ruy Díaz de Isla claimed to have identified the first cases among the 1496 participants who returned from Columbus' second voyage.
The disease spread quickly in the port cities of the western and central Mediterranean, including Naples, which at that time belonged to the Crown of Aragon and thus had a direct personal exchange with Barcelona. In 1494, the French King Charles VIII set out for Italy with a ragged army consisting mostly of mercenaries recruited in Burgundy to assert his inheritance claims to the Kingdom of Naples . After a brief siege, Naples was captured on February 22nd, 1495. In the early summer of 1495, however, Charles VIII gave up Naples again because he feared being encircled by his opponents. During the occupation of Naples there was a first major syphilis outbreak among the troops of Charles, which after the withdrawal from October 1495 spread to central and northern Italy as well as the countries of origin of the mercenary troops. The Italian doctors subsequently called the disease, which was particularly noticeable through ulcers, the French disease, the French doctors spoke of an Italian disease. The high virulence of the pathogen was remarkable . As a result of the syphilis outbreak in Naples, a syphilis epidemic swept the Old World within fifty years . For example, the city of Strasbourg, which has around 20,000 inhabitants, was attacked by it in 1496 (the preacher Johann Geiler von Kaysersberg referred to the disease as "peeling" ). The epidemic then weakened significantly as a result of a loss of virulence and has continued at different levels to the present day.
The miasma theory was widespread in Germany in the early modern period . It was believed that the rare conjunction of the planets Saturn and Jupiter on November 25, 1484 under the sign of Scorpio and the House of Mars was the cause of the epidemic. "Good Jupiter succumbed to the evil planets Saturn and Mars and the sign of Scorpio, to which the genitals are subordinate, explains why the genitals were the first point of attack for the new diseases."
Paracelsus believed in the genesis of the sexual act of a leprous man with a woman with gonorrhea . Ultimately, a religious and socially critical explanation of syphilis was that this disease was God's scourge for the notorious sins of the world.
The Austrian doctor Leonhardus Schmaus concluded in 1518 from the fact that syphilis is cured by American guaiac wood that the disease must have originated in America. The Spanish doctor Ruy Díaz de Isla wrote a report between 1510 and 1520 that was not published until 1539. In it he described that in 1493 he had treated some members of Columbus' ship 's crew for syphilitic ulcers after their return from Central America. He had never seen this type of ulcer in his practice before. He concluded that this new disease had been imported into Europe from Hispaniola (island of Haiti). Also Gonzalo Fernández de Oviedo , who until 1556 eight crossed from 1514 the Atlantic Ocean and spent 42 years in Central America, wrote in his Historia general y natural de las Indias Occidentales ... it was certain that the disease from the West Indies tribe and by sailors of Columbus was brought to Europe. Bartolomé de las Casas , an opponent of Oviedo in relation to his position on the treatment of the Indians, nevertheless expressly testified to Oviedo's thesis of the American origin of syphilis. Even Jean Astruc reiterated the Columbus theory in his first 1736 published extensive treatise on venereal diseases, which lasted until well into the 19th century as a reference work.
The Italian humanist Niccolò Leoniceno had already declared in 1497 that the description of ulcerating diseases of the penis by ancient authors led to the conclusion that syphilis was a very old European disease. With reference to Leoniceno, the Portuguese doctor António Nunes Ribeiro Sanches (1752) and the German doctor Philipp Gabriel Hensler (1790) argued against the Columbus theory in the late 18th century.
The Englishman Simon Mays based an initially heavily controversial pre-Columbian theory on bone finds that were dated to the period from 1296 to 1445. In his opinion, specific changes in the bones indicate an infection with syphilis with great certainty. The most significant finds of this type come from Riverhall , Essex , in England . Accordingly, syphilis first appeared in England much earlier than in 1495.
Furthermore, in the area of the church of a destroyed monastery in the English port city of Kingston upon Hull, three skeletons were found which, according to the experts, show clear traces of an advanced syphilis disease. These findings motivated research to look more intensively in Europe for further traces of syphilis from the time before 1495. In southern Italy, archaeologists discovered during excavations in Metapont , a Greek settlement from the 6th century BC. BC, many bones with the classic signs of syphilis. For the first time in Europe, a transverse furrow caused only by syphilis was detected in a child's skeleton on the associated teeth. Such traces of teeth only appear if a child was infected with the syphilis pathogen by its mother during pregnancy or during childbirth. The search for signs of this disease in Pompeii and bone finds from the 13th century in Turkey were also found. These finds seem to prove that the severe form of syphilis was found in Europe long before the 15th century and that it was not first introduced by the conquistadors from Latin America. Upon closer inspection of the publications of up to then 54 cases of assumed syphilis infection in the Old World before Columbus, other researchers came to the conclusion that either the diagnostic criteria of tertiary syphilis were not met when strictly tested, or that in the cases with actual Fulfillment of the criteria, the radiocarbon dating was falsified by the so-called reservoir effect.
During excavations at Domplatz in St. Pölten , researchers from the Department of Forensic Medicine and the Center for Anatomy and Cell Biology (bone laboratory) at MedUni Vienna were able to morphologically (structurally) prove several cases of likely congenital syphilis from the period between 1320 and 1390 , with changes in the dentition of skeletons from the 14th century served as the basis. "We were able to detect the so-called Hutchinson teeth with central notches and converging edges as well as the mulberry or bud shape in molars, which are characteristic of syphilis," explain the study authors Kanz and Großschmidt (Department of Cell and Developmental Biology). In the next step, the morphological evidence is to be substantiated both in terms of molecular biology and with the help of proteomics . The scientists expect further conclusions to be drawn from the proteomic investigation in particular, since the DNA of syphilis disintegrates very quickly.
The approach that the syphilis pathogen existed in different pathogenic strains both in the Old and in the New World before Columbus was followed. Research results obtained through molecular biological investigation techniques indicate that the ship crews of the Spanish explorers introduced a South American strain of the Treponema pallidum bacterium to Europe for the first time . This then spread very quickly because the European population showed no adaptation to this strain.
There are also indications that syphilis already existed in a more harmless form, than a skin disease, in ancient Greece or in pre-Columbian America, and the scientists suspect that the pathogen, in the course of the early development of mankind and civilization, with increasing use of personal hygiene ( hygiene ) mutated in different cultures around the world to form the form of syphilis that is so dangerous for humans . A new study confirms this theory.
Descriptions of syphilis in the late 15th century
In the late 15th century, syphilis was repeatedly described in printed tracts . The first printed medical text dates from 1495. The first ten treatises on syphilis (also referred to as the French disease in German-language texts ) date back to the last five years of the 15th century. Printing locations were the first areas of spread of the new epidemic : Italy , Germany and Spain . The first French treatise followed in 1501.
Konrad Schellig's Consilium in 1495 or 1496 was the beginning. This was followed by Grünpeck's Tractatus de pestilentia scorra of 1496. The important humanist and doctor Niccolò Leoniceno from Vicenza addressed the epidemic in his lectures at the University of Ferrara from 1495 . In 1497 he published the first scientific treatise on the disease in Venice , which he called Morbus gallicus ("Gallic disease"). Leoniceno recommended topical application of mercury salts because he believed that the skin was diseased. The recommendation of the use of mercury for skin diseases was taken from Arabic sources. The Tractatus de pustulis by the Swabian personal physician Johannes Widmann and De morbo quem Gallicum nuncupant by Corradino Gilino were published in 1497 . In 1498 this was followed by Bartholomäus Steber's A malafranzos, morbo Gallorum, praeservatio et cura , Natale Montesauros De dispositionibus, quas vulgares mal franzoso appellant , Antonio Scanaroli's Disputatio utilis de morbo Gallico and the Spanish court doctor Francisco López de Villalobo's extensive monograph conobre unario de la medicodina las pestiferas bubas on syphilis. López de Villalobos reported the sexual transmission route already suspected in 1495, the skin manifestations and the late complications of the disease. He also recommends topical application of mercury salts.
As a second common remedy against syphilis, guaiac resin (see below) was added to mercury in the 16th century .
On February 25, 1500, Valentin Krauss (called Crusius), a doctor, senator and city judge from Kronstadt in Transylvania described the first cases of syphilis in Kronstadt in a letter to Conrad Celtis (he wrote "Gallus apud nos primum incipit saevire atrociter").
Differentiation from gonorrhea
The Scottish surgeon and anatomist John Hunter (1728–1793) tried in 1767 in a sensational self- experiment to prove syphilis and gonorrhea as different forms of a single disease by introducing pus from the urethra of a gonorrhea patient with a scalpel into his own penis. Due to a methodological error (the donor was infected with both diseases), Hunter, who developed typical syphilitic symptoms, believed to have proven the common origin. The error was not discovered until fifty years later, but in the 19th century, patients affected by various kinds of venereal diseases were referred to as "syphilitic". Hunter died in 1793 of the late effects of his experiment.
The fact that syphilis and gonorrhea are different diseases and that gonorrhea is an independent disease was first demonstrated in 1837 by the French doctor Philippe Ricord and published in 1838. Up to this point in time, both diseases were grouped together as venereus disease (or “lust epidemic”). The assistant doctor Albert Neisser , employed at the University of Breslau, first discovered the gonococci in a patient's urethral swab in 1879.
Recent history of the disease
Diagnostic procedures and pathogen detection
Fritz Schaudinn and Erich Hoffmann achieved the first microscopic detection of treponemas in 1905, the pure cultivation of the syphilis pathogen Treponema pallidum for the first time in 1911 by the Japanese bacteriologist Noguchi Hideyo . It was also the Japanese who, two years later, was able to establish a connection between the infection with Treponema pallidum and progressive paralysis and tabes dorsalis for the first time, as he had detected the treponemas in the brain and in the bone marrow.
In 1906 , August von Wassermann et al. Developed a detection method (Wassermann test) based on the work of Jules Bordet , in which antibodies (reagins) occurring in the blood or cerebrospinal fluid in syphilis reacted with cardiolipin obtained from bovine hearts . The test is a modification of the complement fixation reaction developed by Jules Bordet and Octave Gengou . For the first time, a serological possibility was available to diagnose a syphilis infection at an early stage. However, the detection with this method is relatively unspecific and produced many false-positive results. In the 1930s, William Augustus Hinton developed the Hinton test , which is based on flocculation and which was somewhat more specific. Both tests have now been replaced by more modern methods.
Development of treatment methods
Until the beginning of the 20th century, syphilis was mainly treated with the toxic mercury , which was used to coat the patient's body over a large area, which, along with other undesirable effects, usually led to a complete loss of body hair and all teeth and the rapid deterioration of all body functions initiated (see also mercury poisoning ), or with the pastille Pilula hydrargyri , also known as “blue mass” in English, a drug based on mercury in the 17th to 19th centuries . As early as 1783 and again in 1811, the physician Franz Joseph von Besnard (1749–1814), personal physician to the King of Bavaria, published warnings about this dangerous therapy.
In addition to treatment with substances such as mercury and calomel , solutions of mercury (II) chloride were even injected into the skin ( subcutaneously ) for syphilis therapy from the 1880s onwards .
Mercury had already been used several centuries earlier as a more or less effective therapeutic agent against leprosy and various other skin diseases. Konrad Schilling (1448–1508) was the first to report on external mercury therapy for syphilis in his work Consilium in morbum gallicum (around 1488–1496). Thereafter, other doctors, such as Antonio Benivieni (1440-1502), who had found out in Florence that syphilis can be transmitted from mother to child, Hieronymus Fracastorius (1478-1553), Pedro Pintor (1423-1503) and Johannes Widmann (1440–1524), wrote about the successful use of mercury as external medicine. Later, bathers and quacks also carried out this form of therapy. The application of mercury was mostly carried out in the form of rubbing in (for example with the gray mercury ointment and other mercury-containing ointments), through oral ingestion and also through inhalation of the incenses with mercury .
The South American Indians had a combined syphilis therapy, which usually also cured them, because the disease was less severe with them than with Europeans. They used decoctions from the wood or the bark of the guaiac tree ( Guaiacum officinale and G. sanctum ) or the sarsaparilla root ( Smilax regulii and others) in combination with a sweat bath and a fasting cure. The sweat bath, which the Indians underwent after taking guaiac, consisted of targeted hot steaming of the external genitals . The humanist Ulrich von Hutten tried this method out on himself and described it in his work De guajaci medicina et morbo gallico liber unus (“On the drug guaiac and the Gallic disease”) , published in 1519 . In fact, there was a temporary improvement with the treatment.
In 1892 Albert Neisser caused one of the first German medical scandals by infecting hospital patients with syphilis while looking for serum therapy . As early as 1844, Joseph-Alexandre Auzias-Turenne (1812–1870), a Pertuis- born assistant to Philippe Ricord in Paris, reported on his animal experiments on the transmission of syphilis, from which he derived a theory of prophylactic "syphilization". Until his death he believed in the effectiveness of this false hypothesis, the practical application of which he was forbidden in French hospitals.
The Austrian dermatologist Eduard Lang (1841–1916) summarized the status of therapeutic options at the end of the 19th century. Attempts with arsenic preparations such as atoxyl and arsacetin as well as the only successful animal preparation "preparation 418" (arsenophenylglycine), which had been developed and tested by Paul Uhlenhuth and Paul Ehrlich in 1907/1908 , failed mainly because of the serious side effects. In 1909 Sahachiro Hata and Paul Ehrlich developed the organic arsenic compound arsphenamine ( Salvarsan ), with which a targeted chemotherapeutic treatment of syphilis was attempted for the first time. In the following years, derivatives of the substance were developed with the aim of better tolerability, for example Neosalvarsan and Solusalvarsan as well as Spirotrypan . Another arsenic compound that was temporarily used in the United States to treat neurosyphilis was tryparsamide, developed by Walter Abraham Jacobs and Michael Heidelberger at the Rockefeller Institute for Medical Research . Another derivative of Salvarsan was the arsenic compound Neo-Arsoluin . In the middle of the 20th century, arsenic preparations were largely replaced by modern antibiotics such as penicillin , which is still the basis for treating syphilis to this day.
Ehrlich was specifically looking for a drug and first developed a theory about its effectiveness. The core of his theory was that the cells responsible for immune defense had certain receptors to which poisons or pathogens should dock, which ultimately triggers the production of antibodies. The pathogen and receptor fit together like a key in the lock. Ehrlich's idea was to reverse this principle and use it to combat the pathogen. It was necessary to track down the pathogen's receptors, to which drugs, rather than antibodies, were supposed to dock in order to smuggle their deadly poisonous load into the bacterium. The pathogen would now be treated with chemical substances, and at the same time the body's own cells should be affected as little as possible.
On the basis of this theoretical concept, Ehrlich and his assistant tested over 600 arsenic compounds for the required properties until they achieved the decisive breakthrough in September 1909. The compound with the chemical name m-diamino-p-dioxyarsenobenzene dichlorohydrate achieved amazing results in animal experiments. For the first time it seemed possible to effectively treat syphilis. It soon turned out that the drug Salvarsan caused severe side effects. In addition, it became toxic if stored incorrectly. Ehrlich optimized the drug. In 1911 it was possible to produce a salvarsan preparation that only contained 20% arsenic, but was also weaker than the old salvarsan in its effect. Between 1914 and 1930 (for example by Carl Voegtlin in 1923) the relevance of the animal experiments from the Speyer House was doubted and Salvarsan was classified by various authors as toxic and fundamentally dangerous for humans.
At the beginning of the 20th century it was found that Treponema pallidum could not survive temperatures above 41 ° C. In 1917 the Austrian Julius Wagner-Jauregg , director of the Lower Austrian State Healing and Nursing Institution for the Nervous and Mentally Ill in Vienna, vaccinated nine patients with progressive paralysis with the blood of a malaria patient. He observed an effect that was considerably more favorable than with all previously used therapy methods, and worked out a procedure combined with arsphenamine ( malaria therapy ), for the discovery of which he was awarded the Nobel Prize for Medicine in 1927 .
The effectiveness of the treatment of syphilis with penicillin was first demonstrated in 1943 by John F. Mahoney in the USA; as early as 1944, treatment was standard therapy in the US armed forces.
Tuskegee Syphilis Study
In Tuskegee , USA , a long-term study was carried out from 1932 to 1972 , in which the long-term effects of untreated infection were to be observed in around 400 black and, at the same time, mostly poor and illiterate residents with known syphilis. Even after the widespread introduction of penicillin therapy from 1947, this was deliberately withheld from the test persons; the people observed were neither informed about the study itself nor that an effective treatment option had been available in the meantime. After the press reported on the experiment in July 1972, the study was judged to be ethically unjustified by a specially appointed commission and terminated in the autumn of the same year. In 2010, another human syphilis experiment became known, which had been funded and carried out by the USA in Guatemala from 1946 to 1948.
Politicization of the concept of syphilis
From the 19th century, especially under National Socialism , the term syphilis was given an anti-Semitic , anti-feminist and racist charge. Syphilis became the code for developments in civilization that were perceived as " decadent ". The "syphilization" or "syphilization" became the anti-Semitic code of an assumed "poisoning" of the "people's body". This linguistic usage was used, for example, in Nazi propaganda material and was also taken up several times by Hitler himself. Syphilis was combined with a modern lifestyle that was opposed to a "German culture" and was accordingly rejected. In particular, connections were made to a libertarian sex life in large cities. In the discourse atlas Antifeminism this is summarized as follows: "Both in the warning against (early) sexualization and against artistic" degeneration ", the metaphor of" intellectual / cultural syphilis "describes" Jewish cultural Bolshevism ", which refers to a" decadent Decay "of the" German high culture "work towards."
Nowadays there is a resumption of this idea in the use of the right-wing fighting term "left-winged" or "left-green winged". This was initially shaped by the racist portal PI-News and later, among other things. Taken from the right author Akif Pirinnci and the right blog The Axis of the Good . This term was also used by the federal chairman of the AfD, Jörg Meuthen , in a speech in 2016.
Syphilis in art
The confrontation with syphilis arose with many authors, starting with Hutten simply from the motive of self-concern.
- Fracastoro's didactic poem from the 16th century ranks among comparable didactic writings of the Renaissance .
- As an independent, recurring literary motif, syphilis first appeared in the picaresque novels of baroque literature in the 17th century . B. at Grimmelshausen , who makes his Courasche fall ill with syphilis. (Simplicius, on the other hand, does not get syphilis, but smallpox.)
- The most successful depiction in the 18th century is the figure of Pangloss in Voltaire's Candide . To this end, Voltaire invents a complete chain of infections since Columbus as a satire on aristocratic family trees. Pangloss even develops a justification for syphilis in the best of all worlds.
- In his drama Ghosts (1881), Henrik Ibsen tells the story of Mrs. Alving, widow of a captain and chamberlain, who died of syphilis. Although the family he infected went through great suffering, the widow kept the actual circumstances of his death a secret.
- Oskar Panizza , who also reported on syphilis cases at the papal court in 1894, resorted to the late medieval conception of syphilis as a punishment from God in his heavenly tragedy The Love Council in the same year and was punished for alleged blasphemy .
- In his novel Doctor Faustus (1947), Thomas Mann consciously lets a composer become infected with syphilis for the sake of the ingenious inspiration that he expects from the syphilitic brain affection. This increase also occurs in the novel. After that, the genius who is so genius will fall into mental derangement for the rest of his life.
- In her Berlin novel Die Passion (1925), the naturalistic writer Clara Viebig deals with the life of young Eva, who was born with syphilis. In addition to the presentation of the course of the disease, the main motif is the social exclusion that the girl experiences because her environment cannot deal with the disreputable disease. Her will to live is soon broken by permanent discrimination, and Eva eventually dies of heart failure at the age of 18.
- In his novel Die Hitzkammer (also published as Hexenkammer ), Wolf Serno describes in detail the twenty-day treatment of a syphilis sufferer with a combination of sweating cure, fasting and large-scale external application of a mercury-containing ointment.
- In the debut movie The Libertine by Laurence Dunmore suffering the protagonist John Wilmot ( Johnny Depp ) from syphilis.
- In the film The Silent Duel (original title: Shizukanaru Ketto) by Akira Kurosawa, the protagonist Dr. Kyoji Fujisaki ( Toshirō Mifune ) with syphilis.
- Marianne Abele-Horn: Antimicrobial Therapy. Decision support for the treatment and prophylaxis of infectious diseases. With the collaboration of Werner Heinz, Hartwig Klinker, Johann Schurz and August Stich. 2nd, revised and expanded edition, Wiehl, Marburg 2009, ISBN 978-3-927219-14-4 , p. 233 f.
- Birgit Adam : The punishment of Venus. A cultural history of venereal diseases. Orbis, Munich 2001, ISBN 3-572-01268-6 , in particular pp. 17-21 and 28-111.
- Ernst Bäumler: Cupid's poisoned arrow. Cultural history of a secret illness. Hoffmann & Campe, Hamburg 1976, ISBN 3-455-08962-3 ; Reprinted there in 1997.
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- Klaus-Dieter Linsmeier: Epidemics. Charity in times of syphilis. In: Medicine in the Middle Ages. Between empirical knowledge, magic and religion (= spectrum of sciences. Special: Archeology, History, Culture. Volume 2.19), 2019, p. 74 f.
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Johann Karl Proksch
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- This is how Hans Henny Jahnn writes in his novel The Writing of Gustav Anias Horn after he was forty-nine years old. Europäische Verlagsanstalt, Frankfurt am Main 1959, p. 7 f .: “ And those suffering from syphilis, who experience a violent upswing in their mental powers, as if an inexhaustible fountain had opened up in them. They are violent, overflowing. The masters of this world. There are those who praise sickness as holy. There is no obstructive reason between them and their straight path to the goals. They are able to add the hours of the nights to those of the days without falling into deep fatigue. Fleeting thoughts are good enough for them to create a truth out of them. You only know half the doubt and the whole conviction. - Until the stutter comes over her, the twilight that blurs the high flight of her skill. "
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- Birgit Adam: The punishment of Venus. A cultural history of venereal diseases. 2001, p. 40.
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- Iwan Bloch : Origin of Syphilis. Fischer, Jena, 1901/11.
- treatise De morbo Gallico of Benedict Rinius; quoted from Ludwik Fleck: Origin and development of a scientific fact. Suhrkamp, Frankfurt am Main 1980 [first 1935], p. 4 f .: "... ut affirmant Astronomi, ex coniunctione Saturni et Iovis in tertia scorpionis facie in 23 gradu transacta 1484 ..."
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- Also Karl Sudhoff : A new disease, "die nuwe krenckte", in June 1494 in Düsseldorf. In: Sudhoff's archive . Volume 7, 1914, pp. 43-45.
- Volker Zimmermann: The two Harburg syphilis tracts. In: Würzburg medical history reports. Volume 7, 1989, p. 77 f.
- Historic dispute: Did syphilis originate in the New World. In: Scienclarified. Volume 2, 2008.
- Tract from the origin of the Evil Franzos With dedication preface by the author to the mayor and council of the city of Augsburg, November 11, 1496 . Digitized version of the Bavarian State Library.
- Niccolò Leoniceno. Libellus de Epidemia, quam vulgo Morbum Gallicum vocant. Aldus Manutius , Venice June 1497 (digitized version)
- Gundolf Keil : Plagues of the Middle Ages. In: Bernd Herrmann (Ed.): People and the environment in the Middle Ages. Stuttgart 1986, pp. 109-128; here: pp. 118–122.
- Birgit Adam: The punishment of Venus. A cultural history of venereal diseases. 2001, pp. 98-103 ( Mercury and Guaiac ).
- Robert Offner: Kronstadt, the city doctor Paulus Kyr and Ferrara. In: Robert Offner (Ed.): Paulus Kyr , Health is a delicious thing. A reprint of the health textbook of the Kronstadt doctor Paulus Kyr, translated into German, Romanian and Hungarian and provided with contemporary images, with comments: Sanitatis studium ad imitationem aphorismorum compositum item alimentorum uires breuiter et ordine alphabetico positae Autore Paulo Kyr medico. Imprint in Inclyta Transylvaniae Corona anno 1551. Schiller Verlag, Hermannstadt / Bonn 2010, ISBN 978-3-941271-33-3 , pp. 9-20, here: p. 10.
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- Ricord: Traité pratique des maladies vénériennes. 1838, p. 104 f.
- Hendrik Christian Voss: The representation of syphilis in literary works around 1900. Impact of scientific concepts and social ideas. Medical dissertation, Lübeck 2004, p. 9; zhb.uni-luebeck.de (PDF).
- Julius Rosenbaum: History of the lust epidemic in antiquity [...] . Hall 1839; 7th edition, H. Barsdorf, Berlin 1904
- Philippe Ricord: Lexicon of natural scientists . Spectrum, Heidelberg 2000.
- Stefan Winkle: Cultural history of epidemics . Komet, Düsseldorf / Zurich 1997, ISBN 3-933366-54-2 .
- Fritz Richard Schaudinn, Erich Hoffmann: Preliminary report on the occurrence of spirochaetes in syphilitic disease products and in papillomas. In: Work from the Imperial Health Department (Berlin). Volume 22, 1905, pp. 527-534.
- Hideyo Noguchi: The Establishment of Treponema pallidum as the causative agent of Syphilis, and the cultural Differentiation between this organism and certain morphologically allied Spirochaetae. In: Can Med Assoc J. Vol. 2, No. 4, April 1912, pp. 269-276.
- R. RULLIERE: Japanese medicine. In: R. Toellner: Illustrated history of medicine. Volume 2, Andreas, Salzburg 1992, ISBN 3-86070-204-1 .
- Bernard Zalc: Some comments on Fleck's Interpretation of the Bordet-Wassermann Reaction in view of present biochemical knowledge. In: Robert S. Cohen, Thomas Schnelle (Ed.): Cognition and Fact. Materials on Ludwik Fleck. Dordrecht 1986, pp. 399-406.
- R. Gregorzyk: Reagin and antibody titers in salvarsan and penicillin-treated late lues. Negotiations of the German Dermatological Society. 26th conference in association with the Swiss Society for Dermatology and Venereology held in Zurich from 17. – 20. April 1964. In: Arch. Klin. exp. Dermatol. Volume 219, 1964, pp. 261-264.
- August von Wassermann, Albert Neisser, Carl Bruck: A serodiagnostic reaction in syphilis . In: German Medical Weekly. 1906, No. 48, pp. 745-746.
- Felix Plaut: The theoretical justification of the Wassermann reaction. In: Munich medical weekly. Volume 78, 1931, pp. 1461-1463.
- See for example Heinrich E. Schmidt: About the meaning of Wassermann's reaction in general and in particular for the treatment of syphilitic soldiers. In: Berlin clinical weekly. Volume 53, 1916, pp. 589 f.
- J. Caspary: About chronic mercury treatment of syphilis. In: Quarterly magazine for dermatology and syphilis . 1887, Vol. 19, No. 1, pp. 3-35; link.springer.com (PDF).
- Emil Stern: About the mercury chloride-chlorine sodium and its subcutaneous use. In: Berlin clinical weekly. Volume 15, 1878, pp. 59-64.
- Gottfried Schramm: On the history of subcutaneous injections and injectables in the second half of the 19th century with special consideration of mercury therapy. Stuttgart 1987, pp. 60 and 70.
- Florian G. Mildenberger : No salvation through arsenic? The salvarsand debate and its consequences. In: Specialized prose research - Crossing borders. Volume 8/9, 2012/2013, pp. 327-390, here: pp. 329 f.
- Barbara I. Tshisuaka: Benivieni, Antonio. In: Werner E. Gerabek , Bernhard D. Haage, Gundolf Keil , Wolfgang Wegner (Eds.): Enzyklopädie Medizingeschichte. De Gruyter, Berlin / New York 2005, ISBN 3-11-015714-4 , p. 164 f.
- Eduard Lang: Prophylaxis and Therapy of Syphilis in Twelve Lectures. Wiesbaden 1896, p. 807.
- Siegmund Somogyi: To the knowledge of the effect of the antisyphilitica. In: Arch. Dermatol. Syph. Volume 126, 1926, pp. 660-663.
- Lobelia Syphilitica. Blue Lobelia . (John Uri Lloyd, Curtis G. Lloyd: Drugs and medicines of North America. Volume 2, JU & CG Lloyd, Cincinnati (JU) 1884-1887.) At: henriettes-herb.com ; accessed on September 8, 2020.
- Lutz Sauerteig: Illness, Sexuality, Society: Venereal Diseases and Health Policy in Germany in the 19th and Early 20th Century. Supplement 12 of Medicine, Society and History. Steiner, Stuttgart 1999, p. 35f.
- D. Beyer Perett: Ethics and error. The dispute between Ricord and Auzias-Turenne over syphilization 1845–70. Stanford, CA, 1977.
- Werner E. Gerabek : Auzias-Turenne, Joseph Alexandre. In: Werner E. Gerabek et al. (Ed.): Encyclopedia Medical History. De Gruyter, Berlin / New York 2005, ISBN 3-11-015714-4 , p. 124.
- Eduard Lang: Prophylaxis and Therapy of Syphilis in Twelve Lectures. Wiesbaden 1896.
- Florian G. Mildenberger: No salvation through arsenic? The salvarsand debate and its consequences. 2012/2013, p. 332 f.
- Egon Tomasczewski: Summary overview of the Salvarsan treatment of syphilis. Berlin / Vienna 1911.
- See also Konrad Alt: The newest Ehrlich-Hatapreparat against syphilis. In: Münchner medical Wochenschrift. Volume 57, 1910, pp. 561-564.
- Werner Höfer: Clinical experience with Neo-Arsoluin in syphilis treatment. In: German health system. Volume 6, 1951, pp. 1343-1347.
- Paul Ehrlich - From Immunology to Salvarsan . In: Pharmaceutical newspaper . No. 11/2004.
- Stefan Winkle: Cultural history of epidemics . Komet, Düsseldorf / Zurich 1997, ISBN 3-933366-54-2 , p. 599-602 .
- John Parascandola: Carl Voegtlin and the "Arsenic receptor" in chemotherapy. In: Journal of the History of Medicine and Allied Sciences. (J. Hist. Med. All. Sci.) Volume 32, 1977, pp. 151-171, here: p. 166.
- Florian G. Mildenberger: In a losing position. The lonely fight of Heinrich Dreuw against syphilis and Salvarsan.- In: Würzburger medical-historical messages. Volume 30, 2011, pp. 218-258.
- Florian G. Mildenberger: No salvation through arsenic? The salvarsand debate and its consequences. 2012/2013, pp. 327-390.
- See also Robert Bernhardt: Indications and contraindications of the Salvarsan treatment of syphilis. In: Archives for Dermatology and Syphilis. (Arch. Dermatol. Syphilis.) Volume 173, 1936, pp. 291-301.
- Julius Wagner-Jauregg: The Treatment of Dementia Paralytica by Malaria Inoculation. Nobel Lecture 1927.
- John F. Mahoney: Some of the early phases of penicillin therapy against syphilis. In: American Medical Association: Archives of Dermatology. 1956, Vol. 73, No. 5, pp. 485-488.
- JF Mahoney, RC Arnold, A. Harris: Penicillin treatment in early syphilis. In: American Journal of Public Health . 1943, Volume 43, pp. 1387-1391.
- Thomas G. Benedek: The "Tuskegee study" of syphilis. Analysis of moral versus methodological aspect. In: Journal of Chronical Diseases. Volume 31, 1978, pp. 35-50.
- The Centers for Disease Control and Prevention for the Tuskegee Study . On: cdc.gov ; accessed in June 2019.
- Guatemala 1946–1948 - US doctors infected hundreds with syphilis . On: Welt Online from October 1, 2010; Retrieved September 2, 2011.
- Klaus Theweleit: Male fantasies . Complete new edition with an epilogue, first edition. Matthes & Seitz, Berlin 2019, ISBN 978-3-95757-759-7 .
- Rotgrün-Versifft - Discourse Atlas. Retrieved August 11, 2021 .
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- Oskar Panizza: German theses against the Pope and his dark men.  With a preface by MG Conrad . New edition (selection from the “666 theses and quotations”). Nordland-Verlag, Berlin 1940, pp. 174-176.
- Oskar Panizza: The Love Council, a heavenly tragedy in five acts. Schabelitz, Zurich 1894.
- Wolf Serno: The heat chamber. Droemer, Munich 2004, ISBN 3-426-19594-1 .