History of syphilis

Last updated

Syphilitic Man, Albrecht Durer, 1496, with "1484" appearing Broadsheet; text and wood cut of a syphilitic. Wellcome L0014503EB.jpg
Syphilitic Man , Albrecht Dürer, 1496, with "1484" appearing
Illustration of people with syphilis, Vienna, 1498 400Behandlung der Syphilis.jpg
Illustration of people with syphilis, Vienna, 1498
Syphilitic sores depicted in Yuzuan yizong jinjian (China, 1742) Chinese C18 woodcut; External medicine - syphilitic sores Wellcome L0039895.jpg
Syphilitic sores depicted in Yuzuan yizong jinjian (China, 1742)

The first recorded outbreak of syphilis in Europe occurred in 1494/1495 in Naples, Italy, during a French invasion. [1] [2] Because it was spread geographically by French troops returning from that campaign, the disease was known as "French disease", and it was not until 1530 that the term "syphilis" was first applied by the Italian physician and poet Girolamo Fracastoro. [2] The causative organism, Treponema pallidum , was first identified by Fritz Schaudinn and Erich Hoffmann in 1905 at the Charité Clinic in Berlin. [2] The first effective treatment, Salvarsan, was developed in 1910 by Sahachiro Hata in the laboratory of Paul Ehrlich. It was followed by the introduction of penicillin in 1943. [2]

Contents

Many well-known figures, including Scott Joplin, Franz Schubert, Friedrich Nietzsche, Al Capone, and Édouard Manet are believed to have contracted the disease. [2]

Origin

The history of syphilis has been well studied, but the exact origin of the disease remains unknown. [3] It appears to have originated in both Africa and America. [4] [5] As such, there are two primary hypotheses: one proposes that syphilis was carried to Europe from the Americas by the crew(s) of Christopher Columbus as a byproduct of the Columbian exchange, while the other proposes that syphilis previously existed in Europe but went unrecognized. [1] There has been a recent skeletal discovery in the Yucatan Peninsula dating over 9,900 years ago of a 30 year old woman who had Treponema peritonitis, a disease related to syphilis. [6] "There is also evidence for a possible trepanomal bacterial disease that caused severe alteration of the posterior parietal and occipital bones of the cranium." [7] News of it spread quickly and widely, and documentation is abundant. For the time, it was "front page news" that was widely known among the literate. It is also the first disease to be widely recognized as a sexually transmitted disease, and it was taken as indicative of the moral state (sexual behavior) of the peoples in which it was found. Its geographic origin and moral significance were debated as had never been the case with any other illness. European countries blamed it on each other. Somewhat later, when the significance of the Western Hemisphere was perceived, it has been used in both pro- and anti-colonial discourse.[ citation needed ]

Debate over European origins

The deadliest of the four diseases that constitute treponematosis is syphilis, a sexually transmitted disease of adults. The others are bejel, yaws, and pinta, endemic childhood diseases that are usually not fatal, if still unpleasant and disfiguring. [8] Throughout human history, confusion has reigned about the presence of syphilis in various populations around the world. It was often confused not only with the other treponematoses, but also with completely different diseases that produced similar symptoms. These included leprosy (Hansen's disease), elephantiasis, and scabies, among many others. [9] [10] [5] For this reason syphilis came to be called "the great imitator", and in many places for long stretches of time it did not even have its own name. [11] As a result of the difficulty of identifying syphilis in any given population, historians and paleopathologists have engaged in a long debate over its origins in Europe, where it famously ravaged the population in the late fifteenth and early sixteenth centuries. Two primary hypotheses emerged. One proposed that syphilis was carried to Europe from the Americas by the men who sailed with Christopher Columbus as a byproduct of the Columbian exchange. The other held that it previously existed in Europe but went unrecognized. These are referred to as the "Columbian" and "pre-Columbian" hypotheses. [5]

There is no doubt that treponematosis existed in the Americas long before contact with the Europe and Afro-Eurasia. For decades scholars of North and South American prehistory have agreed that the evidence from bones and teeth is clear. [5] [12] The situation in the Old World has been murkier, with fewer specimens clearly pointing to treponematosis rather than some other disease. Added to this conundrum, there was no documentary record on syphilis, a particularly horrible disease that should have elicited commentary from priests, scholars, and/or kings in Medieval Europe.

A lack of written evidence for the existence of syphilis in Europe, combined with an explosion of sources attesting to the appearance of a virulent new disease following exploration of the Caribbean islands, led some historians to accept the opinions of contemporary medical writers that Columbus and his men had brought the disease to Spain from America. From there it spread rapidly. [13] In particular, the reliance of King Charles VIII of France on mercenary troops (some of them Spanish) at the time of his attack on Naples in the winter of 1495 had led, most historians believed, to the dissemination of the highly contagious "French pox" throughout Europe when those troops returned home to their own countries. This epidemic, perhaps the result of a more transmissible or deadlier variant of treponematosis, although that is not yet known, led to significant confusion beginning in the eighteenth century and exemplified most recently in the work of Kristin N. Harper and colleagues. [14] Yet all this time some scholars believed that evidence from skeletal remains and documentary accounts did point to the existence of syphilis in Afro-Eurasia beginning in ancient times, even if it were rare. Foremost among them was Ellis Herndon Hudson, a clinician who published extensively about the prevalence of treponematosis, including syphilis, in times past. [15] [16] [9] [17]

Discoveries in paleopathology

In 2020, a group of leading paleopathologists concluded that enough evidence had been collected from bones and teeth to prove that treponemal disease existed in Europe prior to the voyages of Columbus. [18] At least fifteen cases of acquired treponematosis based on evidence from bones, and six examples of congenital treponematosis based on evidence from teeth, are now widely accepted as ancient or medieval. In several of the twenty-one cases the evidence may also indicate syphilis specifically. Highlights of this important literature include:

While the absolute number of cases is still small, they keep turning up, most recently in 2015 in London and St. Pölten, Austria. [23] Yet there is an outstanding issue. Damaged teeth and bones seem to hold proof of pre-Columbian syphilis, but there is a possibility that they point to an endemic form of treponematosis instead. Some researchers have expressed skepticism regarding whether the cases from Metaponto, Apple Down and Turkey even represent treponemal diseases at all. [14]

Discoveries in ancient DNA studies

As syphilis, bejel, and yaws vary considerably in mortality rates and the level of human disgust they elicit, it is important to know which one is under discussion in any given case, but it remains difficult for paleopathologists to distinguish among them. (Pinta is a skin disease and therefore unrecoverable through paleopathology.) Ancient DNA (aDNA) holds the answer, because just as only aDNA suffices to distinguish between syphilis and other diseases that produce similar symptoms in the body, it alone can differentiate spirochetes that are 99.8 percent identical with absolute accuracy. [24] [25] [26] Progress on uncovering the historical extent of the various treponemal diseases through their aDNA remains slow, however, because the spirochete responsible for treponematosis, Treponema pallidum, is rare in skeletal remains and fragile, making it notoriously difficult to recover and analyze.[ citation needed ]

The genetic sequence of Treponema pallidum was deciphered by Claire M. Fraser and colleagues in 1998, and success in analyzing a 200-year-old example extracted from bones by Connie J. Kolman et al. came the next year. [27] [28] In 2012, Rafael Montiel and his co-authors were successful in amplifying two Treponema pallidum DNA sequences dated to the sixteenth and seventeenth centuries in southwestern Spain. [29] In 2018 Verena J. Schuenemann and colleagues successfully recovered and reconstructed Treponema pallidum genomes from the skeletons of two infants and a neonate in Mexico City, from the late 17th to the mid-19th centuries. Two are believed to have had congenital syphilis and one congenital yaws. [30] A breakthrough example (2020) from early modern Europe can be found in the work of Karen Giffin and her co-authors, who sequenced a genome of Treponema pallidum subspecies pertenue, the causal agent of yaws, from a Lithuanian tooth radiocarbon-dated to 1447–1616 (95 percent probability). The ability to sequence the entire genome is especially important for distinguishing among syndromes of treponematosis because of their close similarity. In this case, whole genome sequencing has resulted in two startling discoveries: that the subtropical syndrome yaws existed in northern Europe at the turn of the sixteenth century, and that yaws in its modern form is a relatively young disease that emerged only in the 12th to 14th centuries. [31] Finally, in October 2020 Kerttu Majander and colleagues published research revealing that as early as the fifteenth to eighteenth centuries Treponema pallidum existed as syphilis and yaws in Finland, syphilis in Estonia, and a previously unknown basal strain in the Netherlands. [32] Although precise dating to the medieval period is not yet possible, the presence of several different kinds of treponematosis at the beginning of the early modern period argues against its recent introduction from elsewhere. Therefore, they argue, treponematosis— possibly including syphilis—almost certainly existed in medieval Europe.[ citation needed ]

A healthy man and a diseased man torture Christ before his crucifixion. Books of Hours, c. 1375-1435 (detail). France. (Getty Museum Open Content Program). Medieval illumination of Christ being tortured.jpg
A healthy man and a diseased man torture Christ before his crucifixion. Books of Hours, c. 1375-1435 (detail). France. (Getty Museum Open Content Program).

Evidence from art

A man with a diseased penis torments Christ. Diptych with the Passion of Christ c. 1400 (detail). Austria, Styria. (Cleveland Museum of Art Open Access Program) Four men torture Christ before his crucifixion.jpg
A man with a diseased penis torments Christ. Diptych with the Passion of Christ c. 1400 (detail). Austria, Styria. (Cleveland Museum of Art Open Access Program)

Despite significant progress in tracing the presence of syphilis in past historic periods, definitive findings from paleopathology and aDNA studies are still lacking for the period before Columbus. This makes newly available evidence from art helpful for settling the issue. Research by Marylynn Salmon has provided examples of deformities in medieval subjects that can be usefully compared to those of modern victims of the disease in medical drawings and photographs. [33] [34] [35] One of the most typical deformities of treponematosis is a collapsed nasal bridge called saddle nose, usually accompanied by baldness. Salmon demonstrates that it appears often in medieval illuminations, especially among the men tormenting Christ in scenes of the crucifixion. The association of saddle nose with men perceived to be so evil they would kill the son of God indicates the artists were thinking of syphilis, which is typically transmitted through sexual intercourse with promiscuous partners. Such behavior was considered a mortal sin by Christians in medieval times. One illuminator goes so far as to show a flagellant with an exposed penis, red at the tip as though infected with a syphilitic sore. Others show the deformed teeth associated with congenital syphilis—Hutchinson's incisors—or the eye deformity ptosis that often appears in victims of the disease.[ citation needed ]

A historical mystery

It remains mysterious why the authors of medieval medical treatises so uniformly refrained from describing syphilis or commenting on its existence in the population. Probably many confused it with other diseases. The great variety of symptoms of treponematosis, the different ages at which the various diseases appears, and its widely divergent outcomes depending on climate and culture, would have added greatly to the confusion of medical practitioners, as indeed they did right down to the middle of the 20th century.[ citation needed ]

Another factor also seems to have been important, obfuscation in the medical literature. In an age that associated illness with sin, the implications of revealing a disease more often fatal to elites than commoners could be incendiary. [36] Significantly, bejel and yaws were endemic in rural, underdeveloped communities such as those of peasants in medieval Europe. Children became ill by sharing drinking vessels and bedding holding only small bacterial loads, and as a result their cases were not usually serious. Syphilis, in contrast, generally was transmitted by venereal sores holding a massive inoculation of Treponema pallidum. Previously uninfected adults, often elites who had been protected by their more hygienic lifestyles, therefore became much sicker upon infection, and died more often. The importance of bacterial load was first noted by the physician Ernest Grin in 1952 in his study of syphilis in Bosnia. [37]

Such a difference would have been politically dangerous to elites, especially if it became known that they were responsible for spreading syphilis. Historian Jon Arrizabalaga has investigated this question for Castile with startling results revealing an effort to hide its association with the nobility. [38] Still, there are hints of the truth in the historical record. The Spanish physician Gaspare Torrella (1452–1520), who treated several members of the papal court, including Cesare Borgia, wrote that in southern Spain the disease he called "pudendagra" was already known as morbus curialis because of its association with the court. Similarly, in Eastern Europe it was called "the malady of palaces". In France, the association of syphilis with court life was responsible for the term mal de cour, which usage lasted into modern times. The Rouen physician Jacques de Béthencourt (1477–ca. 1527) similarly observed that syphilis was known there as "the disease of the magnates". [39] [40] [41] [42] The fact that following the epidemic of 1495 countries blamed its rapid transmission on each other (in Naples it was called the French Pox and in France the Neapolitan disease) indicates that syphilis was immediately perceived negatively. Conveniently for the European nobility, documentation is abundant that in Europe people believed syphilis had originated not at court, but in the New World.[ citation needed ]

Combination theory

Historian Alfred Crosby suggested in 2003 that both theories are partly correct in a "combination theory". Crosby says that the bacterium that causes syphilis belongs to the same phylogenetic family as the bacteria that cause yaws and several other diseases. Despite the tradition of assigning the homeland of yaws to sub-Saharan Africa, Crosby notes that there is no unequivocal evidence of any related disease having been present in pre-Columbian Europe, Africa, or Asia. Crosby writes, "It is not impossible that the organisms causing treponematosis arrived from America in the 1490s ... and evolved into both venereal and non-venereal syphilis and yaws." [43] However, Crosby considers it more likely that a highly contagious ancestral species of the bacteria moved with early human ancestors across the land bridge of the Bering Straits many thousands of years ago without dying out in the original source population. He hypothesizes that "the differing ecological conditions produced different types of treponematosis and, in time, closely related but different diseases." [43] A more recent, modified version of the Columbian theory that better fits skeletal evidence from the New World, and also "absolved the New World of being the birthplace of syphilis", proposes that a nonvenereal form of treponemal disease, without the lesions common to congenital syphilis, was brought back to Europe by Columbus and his crew. Upon arrival in the Old World, the bacterium, which was similar to modern day yaws, responded to new selective pressures with the eventual birth of the subspecies of sexually transmitted syphilis. [44] This theory is supported by genetic studies of venereal syphilis and related bacteria, which found a disease intermediate between yaws and syphilis in Guyana, South America. [45] [46] However, the study has been criticized in part because some of its conclusions were based on a tiny number of sequence differences between the Guyana strains and other treponemes whose sequences were examined. [44] [47]

European outbreak

A medical illustration attributed to Albrecht Durer (1496) depicting a person with syphilis. Here, the disease is believed to have astrological causes. DurerSyphilis1496.jpg
A medical illustration attributed to Albrecht Dürer (1496) depicting a person with syphilis. Here, the disease is believed to have astrological causes.

The first well-recorded European outbreak of what is now known as syphilis occurred in 1495 among French troops invading Italy. [1] [48] It may have been transmitted to the French via Spanish mercenaries serving Charles VIII of France in that campaign; also of note, is that Charles and his court had intercourse with almost 100 women during his Italian invasions and may have felt the disease upon return from his futile endeavors. [49] From this centre, the disease swept across Europe. As Jared Diamond describes it, "[W]hen syphilis was first definitely recorded in Europe in 1495, its pustules often covered the body from the head to the knees, caused flesh to fall from people's faces, and led to death within a few months." The disease then was much more lethal than it is today. [50] The epidemiology of this first syphilis epidemic shows that the disease was either new or a mutated form of an earlier disease.[ citation needed ]

Some researchers argue that syphilis was carried from the New World to Europe after Columbus' voyages, while others argue the disease has a much longer history in Europe. Many of the crew members who served on this voyage later joined the army of King Charles VIII in his invasion of Italy in 1495, which some argue may have resulted in the spreading of the disease across Europe and as many as five million deaths. [46] Some findings suggest Europeans could have carried the nonvenereal tropical bacteria home, where the organisms may have mutated into a more deadly form in the different conditions and low immunity of the population of Europe. [51] Syphilis was a major killer in Europe during the Renaissance. [52] In his Serpentine Malady (Seville, 1539) Ruy Díaz de Isla estimated that over a million people were infected in Europe. He also postulated that the disease was previously unknown, and came from the island of Hispaniola (modern Dominican Republic and Haiti). [53]

According to a 2020 study, more than 20% of individuals in the range of 15–34 years old in late 18th century London were treated for syphilis. [54]

Historical terms

The name "syphilis" was coined by the Italian physician and poet Girolamo Fracastoro in his pastoral noted poem, written in Latin, titled Syphilis sive morbus gallicus (Latin for "Syphilis or The French Disease") in 1530. [2] [55] The protagonist of the poem is a shepherd named Syphilus (perhaps a variant spelling of Sipylus, a character in Ovid's Metamorphoses ). Syphilus is presented as the first man to contract the disease, sent by the god Apollo as punishment for the defiance that Syphilus and his followers had shown him. [2] From this character Fracastoro derived a new name for the disease, which he also used in his medical text De Contagione et Contagiosis Morbis (1546) ("On Contagion and Contagious Diseases"). [56]

Until that time, as Fracastoro notes, syphilis had been called the "French disease" (Italian : mal francese) in Italy, Malta, [57] Poland and Germany, and the "Italian disease" in France. In addition, the Dutch called it the "Spanish disease", the Russians called it the "Polish disease", and the Turks called it the "Christian disease" or "Frank (Western European) disease" (frengi). These "national" names were generally reflective of contemporary political spite between nations and frequently served as a sort of propaganda; the Protestant Dutch, for example, fought and eventually won a war of independence against their Spanish Habsburg rulers who were Catholic, so referring to Syphilis as the "Spanish" disease reinforced a politically useful perception that the Spanish were immoral or unworthy. However, the attributions are also suggestive of possible routes of the spread of the infection, at least as perceived by "recipient" populations. The inherent xenophobia of the terms also stemmed from the disease's particular epidemiology, often being spread by foreign sailors and soldiers during their frequent sexual contact with local prostitutes. [58]

During the 16th century, it was called "great pox" in order to distinguish it from smallpox. In its early stages, the great pox produced a rash similar to smallpox (also known as variola).[ citation needed ] However, the name is misleading, as smallpox was a far more deadly disease. The terms "lues" [59] (or Lues venerea, Latin for "venereal plague") and "Cupid's disease" [60] have also been used to refer to syphilis. In Scotland, syphilis was referred to as the Grandgore or Spanyie Pockis. [61] The ulcers suffered by British soldiers in Portugal were termed "The Black Lion". [62]

Historical treatments

An artificial nose from the 17th-18th century. Such cosmetic replacements were sometimes used due to effects of the disease. Artificial nose, 17th-18th century. (9663809400).jpg
An artificial nose from the 17th–18th century. Such cosmetic replacements were sometimes used due to effects of the disease.

There were originally no effective treatments for syphilis, although a number of remedies were tried. In the infant stages of this disease in Europe, many ineffective and dangerous treatments were used. The aim of treatment was to expel the foreign, disease-causing substance from the body, so methods included blood-letting, laxative use, and baths in wine and herbs or olive oil. [63]

Mercury was a common, long-standing treatment for syphilis. [64] The Canon of Medicine (1025) by the Persian physician Ibn Sina suggested treating early stages of leprosy with mercury; during an early European outbreak of the disease, Francisco Lopez de Villalobos compared this to syphilis, though he noted major differences between the diseases. [65] Paracelsus likewise noted mercury's positive effects in the Arabic treatment of leprosy, which was thought to be related to syphilis, and used the substance for treating the disease. [58] Giorgio Sommariva of Verona is recorded to have used mercury to treat syphilis in 1496, and is often recognized as the first physician to have done so, although he may not have been a physician. [66] During the sixteenth century, mercury was administered to syphilitic patients in various ways, including by rubbing it on the skin, by applying a plaster, and by mouth. [67] A "Fumigation" method of administering mercury was also used, in which mercury was vaporized over a fire and the patients were exposed to the resulting steam, either by being placed in a bottomless seat over the hot coals, or by having their entire bodies except for the head enclosed in a box (called a "tabernacle") that received the steam. [67] The goal of mercury treatment was to cause the patient to salivate, which was thought to expel the disease. Unpleasant side effects of mercury treatment included gum ulcers and loose teeth. [67] Mercury continued to be used in syphilis treatment for centuries; an 1869 article by Thomas James Walker, M. D., discussed administering mercury by injection for this purpose. [68]

The discovery of guaiacum as cure for syphilis, after Stradanus, 1590 De ontdekking van Guaiacum als middel tegen syfilis, anoniem, Museum Plantin-Moretus, PK OPB 0186 007.jpg
The discovery of guaiacum as cure for syphilis, after Stradanus, 1590

Guaiacum was a popular treatment in the 16th century and was strongly advocated by Ulrich von Hutten and others. [67] Because guaiacum came from Hispaniola where Columbus had landed, proponents of the Columbian theory contended that God had provided a cure in the same location from which the disease originated. [67] In 1525, the Spanish priest Francisco Delicado, who himself suffered from syphilis, wrote El modo de adoperare el legno de India occidentale (How to Use the Wood from the West Indies [69] ) discussing the use of guaiacum for treatment of syphilis. [70] Although it did not have the unpleasant side effects of mercury, guaiacum was not particularly effective, [67] at least not beyond the short term, [70] and mercury was thought to be more effective. [67] Some physicians continued to use both mercury and guaiacum on patients. After 1522, the Blatterhaus—an Augsburg municipal hospital for the syphilitic poor [71] —would administer guaiacum (as a hot drink, followed by a sweating cure) as the first treatment, and use mercury as the treatment of last resort. [67]

Another 16th-century treatment advocated by the Italian physician Antonio Musa Brassavola was the oral administration of Root of China, [67] a form of sarsaparilla (Smilax). [72] In the seventeenth century, English physician and herbalist Nicholas Culpeper recommended the use of heartsease (wild pansy). [73]

Before effective treatments were available, syphilis could sometimes be disfiguring in the long term, leading to defects of the face and nose ("nasal collapse"). Syphilis was a stigmatized disease due to its sexually transmissible nature. Such defects marked the person as a social pariah, and a symbol of sexual deviancy. Artificial noses were sometimes used to improve this appearance. The pioneering work of the facial surgeon Gasparo Tagliacozzi in the 16th century marked one of the earliest attempts to surgically reconstruct nose defects. Before the invention of the free flap, only local tissue adjacent to the defect could be harvested for use, as the blood supply was a vital determining factor in the survival of the flap. Tagliacozzi's technique was to harvest tissue from the arm without removing its pedicle from the blood supply on the arm. The patient would have to stay with their arm strapped to their face until new blood vessels grew at the recipient site, and the flap could finally be separated from the arm during a second procedure. [74]

An early technique for grafting tissue to surgically correct a nose defect. De curtorum chirurgia 8.jpg
An early technique for grafting tissue to surgically correct a nose defect.

As the disease became better understood, more effective treatments were found. An antimicrobial used for treating disease was the organo-arsenical drug Salvarsan, whose anti-syphility properties were discovered in 1908 by Sahachiro Hata in the laboratory of Nobel prize winner Paul Ehrlich. The same group of researchers later discovered the related organo-arsenical, Neosalvarsan. The side-effect profile of Neosalvarsan is gentler and its storage and preparation were more convenient than those of Salvarsan, which must be stored under nitrogen. [75]

It was observed that sometimes patients who developed high fevers were cured of syphilis[ by whom? ]. Thus, for a brief time malaria was used as treatment for tertiary syphilis because it produced prolonged and high fevers (a form of pyrotherapy). This was considered an acceptable risk because the malaria could later be treated with quinine, which was available at that time. Malaria as a treatment for syphilis was usually reserved for late disease, especially neurosyphilis, and then followed by either Salvarsan or Neosalvarsan as adjuvant therapy. This discovery was championed by Julius Wagner-Jauregg, [76] who won the 1927 Nobel Prize for Medicine for his discovery of the therapeutic value of malaria inoculation in the treatment of neurosyphilis. Later, hyperthermal cabinets (sweat-boxes) were used for the same purpose. [77] These treatments were finally rendered obsolete by the discovery of penicillin, and its widespread manufacture after World War II allowed syphilis to be effectively and reliably cured. [78]

History of diagnosis

In 1905, Fritz Schaudinn and Erich Hoffmann discovered Treponema pallidum in tissue of patients with syphilis. [2] One year later, the first effective test for syphilis, the Wassermann test, was developed. Although it had some false positive results, it was a major advance in the detection and prevention of syphilis.[ citation needed ] By allowing testing before the acute symptoms of the disease had developed, this test allowed the prevention of transmission of syphilis to others, even though it did not provide a cure for those infected. In the 1930s the Hinton test, developed by William Augustus Hinton, and based on flocculation, was shown to have fewer false positive reactions than the Wassermann test. [79] Both of these early tests have been superseded by newer analytical methods.

While working at the Rockefeller University (then called the Rockefeller Institute for Medical Research) in 1913, Hideyo Noguchi, a Japanese scientist, demonstrated the presence of the spirochete Treponema pallidum in the brain of a progressive paralysis patient, associating Treponema pallidum with neurosyphilis. [80] Prior to Noguchi's discovery, syphilis had been a burden to humanity in many lands. Without its cause being understood, it was sometimes misdiagnosed and often misattributed to damage by political enemies. It is called "the great pretender" for its variety of symptoms. Felix Milgrom developed a test for syphilis. The Hideyo Noguchi Africa Prize was named to honor the man who identified the agent in association with the late form of the infectious disease. [81]

Prevalence

An excavation of a seventeenth-century cemetery at St Thomas's Hospital in London, England found that 13 per cent of skeletons showed evidence of treponemal lesions. These lesions are only present in a small minority of syphilitic cases, implying that the hospital was treating large numbers of syphilitics. In 1770s London, approximately 1 in 5 people over the age of 35 were infected with syphilis. In 1770s Chester, the figure was about 8.06 per cent. By 1911, the figure for London was 11.4 per cent, about half that of the 1770s. [82] [83]

A 2014 study estimated the prevalence of syphilis in the United Kingdom in 1911–1912 as 7.771%. The location with the highest prevalence was London, at 11.373%, and the social class with the highest prevalence was unskilled working-class, at 11.781%. [84]

The control of syphilis in the United Kingdom began with the 1916 report of a Royal Commission on Venereal Diseases. Clinics were established offering testing and education. This caused a fall in the prevalence of syphilis, leading to almost a halving of tabes dorsalis between 1914 and 1936. With the mass production of penicillin from 1943, syphilis could be cured. Syphilis screening was introduced for every pregnancy. Contact tracing was also introduced. [85] By 1956, congenital syphilis had been almost eliminated, and female cases of acquired syphilis had been reduced to a hundredth of their level just 10 years previously. [86]

In 1978 in England and Wales, homosexual men accounted for 58% of syphilis cases in (and 76% of cases in London), but by 1994–1996 this figure was 25%, possibly driven by safe-sex practices to avoid HIV. In 1995, only 130 total cases were reported. A substantial proportion of infections are linked to foreign travel. Antenatal testing continues. [85]

In the United States in 1917, 6% of World War I servicemen were found to have syphilis. In 1936, a public health campaign began to prescribe arsphenamine to treat syphilis. Between 1945 and 1955 penicillin was used to treat over two million Americans for syphilis, and contact tracing was introduced. Syphilis prevalence dropped to an all time low by 1955. A total of 6993 cases of primary and secondary syphilis were recorded in 1998, the lowest number since 1941. [85] In 2000 and 2001 in the United States, the national rate of reported primary and secondary syphilis cases was 2.1 cases per 100,000 population (6103 cases reported). This was the lowest rate since 1941. As of 2014, the incidence increased to 6.3 cases per 100,000 population (19,999 cases reported). The majority of these new cases were in men who have sex with men. Syphilis in newborns in the United States increased from 8.4 cases per 100,000 live births (334 cases) between 2008 and 2012 to 11.6 cases per 100,000 live births (448 cases) between 2012 and 2014. [87]

Arts and literature

Portrait of Gerard de Lairesse by Rembrandt van Rijn, ca. 1665-67, oil on canvas. De Lairesse, himself a painter and art theorist, suffered from congenital syphilis that severely deformed his face and eventually blinded him. Rembrandt Harmensz. van Rijn 095.jpg
Portrait of Gerard de Lairesse by Rembrandt van Rijn, ca. 1665–67, oil on canvas. De Lairesse, himself a painter and art theorist, suffered from congenital syphilis that severely deformed his face and eventually blinded him.

The earliest known depiction of an individual with syphilis is Albrecht Dürer's Syphilitic Man (1496), a woodcut believed to represent a Landsknecht, a Northern European mercenary. [89] The myth of the femme fatale or "poison women" of the 19th century is believed to be partly derived from the devastation of syphilis, with classic examples in literature including John Keats' La Belle Dame sans Merci . [90] [91] Poet Sebastian Brant in 1496 wrote a poem titled De pestilentiali Scorra sive mala de Franzos which explains the spread of the disease across the European continent. [92] Brant also created artistic creations showing religious and political views of syphilis, especially with a work showing Saint Mary and Jesus throwing lightning to punish or cure those afflicted by syphilis, and he also added Holy Roman Emperor Maximilian I in the work, being rewarded by Mary and Jesus for his work against the immoral disease, to show the strong relationship between church and state during the 16th and 17th centuries. [58]

The Flemish artist Stradanus designed a print of a wealthy man receiving treatment for syphilis with the tropical wood guaiacum sometime around 1580. [93] The title of the work is "Preparation and Use of Guayaco for Treating Syphilis". That the artist chose to include this image in a series of works celebrating the New World indicates how important a treatment, however ineffective, for syphilis was to the European elite at that time. The richly colored and detailed work depicts four servants preparing the concoction while a physician looks on, hiding something behind his back while the hapless patient drinks. [94] Another artistic depiction of syphilis treatment is credited to Jacques Laniet in the seventeenth century as he illustrated a man using the fumigation stove, another popular method of syphilis treatment, with a nearby barrel etched with the saying "For a pleasure, a thousand pains." [58] Remedies to cure syphilis were frequently illustrated to deter those from acts which could lead to the contraction of syphilis because the treatment methods were normally painful and ineffective.[ citation needed ]

Tuskegee and Guatemala studies

A Work Projects Administration poster about syphilis ca. 1940. Stop syphilis LCCN98509573.jpg
A Work Projects Administration poster about syphilis ca. 1940.

One of the most infamous United States cases of questionable medical ethics in the 20th century was the Tuskegee syphilis study. [95] The study took place in Tuskegee, Alabama, and was supported by the U.S. Public Health Service (PHS) in partnership with the Tuskegee Institute. [96] The study began in 1932, when syphilis was a widespread problem and there was no safe and effective treatment. [97] The study was designed to measure the progression of untreated syphilis. By 1947, penicillin had been shown to be an effective cure for early syphilis and was becoming widely used to treat the disease. [96] Its use in later syphilis, however, was still unclear. [97] Study directors continued the study and did not offer the participants treatment with penicillin. [96] This is debated, and some have found that penicillin was given to many of the subjects. [97]

In the 1960s, Peter Buxtun sent a letter to the CDC, who controlled the study, expressing concern about the ethics of letting hundreds of black men die of a disease that could be cured. The CDC asserted that it needed to continue the study until all of the men had died. In 1972, Buxtun went to the mainstream press, causing a public outcry. As a result, the program was terminated, a lawsuit brought those affected nine million dollars, and Congress created a commission empowered to write regulations to deter such abuses from occurring in the future. [96]

On 16 May 1997, thanks to the efforts of the Tuskegee Syphilis Study Legacy Committee formed in 1994, survivors of the study were invited to the White House to be present when President Bill Clinton apologized on behalf of the United States government for the study. [98]

Syphilis experiments were also carried out in Guatemala from 1946 to 1948. They were United States-sponsored human experiments, conducted during the government of Juan José Arévalo with the cooperation of some Guatemalan health ministries and officials. Doctors infected soldiers, prisoners, and mental patients with syphilis and other sexually transmitted diseases, without the informed consent of the subjects, and then treated them with antibiotics. In October 2010, the U.S. formally apologized to Guatemala for conducting these experiments. [99]

List of cases

Elimination

In 2015, Cuba became the first country in the world to receive validation from WHO for eliminating mother to child transmission of syphilis. [100]

See also

Related Research Articles

<span class="mw-page-title-main">Syphilis</span> Sexually transmitted infection

Syphilis is a sexually transmitted infection caused by the bacterium Treponema pallidum subspecies pallidum. The signs and symptoms depend on the stage it presents: primary, secondary, latent or tertiary. The primary stage classically presents with a single chancre though there may be multiple sores. In secondary syphilis, a diffuse rash occurs, which frequently involves the palms of the hands and soles of the feet. There may also be sores in the mouth or vagina. Latent syphilis has no symptoms and can last years. In tertiary syphilis, there are gummas, neurological problems, or heart symptoms. Syphilis has been known as "the great imitator" because it may cause symptoms similar to many other diseases.

<span class="mw-page-title-main">Gumma (pathology)</span> Soft, non-cancerous growth resulting from the tertiary stage of syphilis

A gumma is a soft, non-cancerous growth resulting from the tertiary stage of syphilis.

<i>Treponema pallidum</i> Species of bacterium

Treponema pallidum, formerly known as Spirochaeta pallida, is a microaerophilic, gram-negative, spirochaete bacterium with subspecies that cause the diseases syphilis, bejel, and yaws. It is known to be transmitted only among humans and baboons. It is a helically coiled microorganism usually 6–15 μm long and 0.1–0.2 μm wide. T. pallidum's lack of both a tricarboxylic acid cycle and processes for oxidative phosphorylation results in minimal metabolic activity. The treponemes have cytoplasmic and outer membranes. Using light microscopy, treponemes are visible only by using dark-field illumination. T. pallidum consists of three subspecies, T. p. pallidum, T. p. endemicum, and T. p. pertenue, each of which has a distinct associated disease. The ability of T. pallidum to avoid host immune defenses has allowed for stealth pathogenicity. The unique outer membrane structure and minimal expression of surface proteins of T. pallidum has made vaccine development difficult. Treponema pallidum can be treated with antibiotics such as penicillin.

<span class="mw-page-title-main">Yaws</span> Medical condition

Yaws is a tropical infection of the skin, bones, and joints caused by the spirochete bacterium Treponema pallidum pertenue. The disease begins with a round, hard swelling of the skin, 2 to 5 cm in diameter. The center may break open and form an ulcer. This initial skin lesion typically heals after 3–6 months. After weeks to years, joints and bones may become painful, fatigue may develop, and new skin lesions may appear. The skin of the palms of the hands and the soles of the feet may become thick and break open. The bones may become misshapen. After 5 years or more, large areas of skin may die, leaving scars.

<span class="mw-page-title-main">Rapid plasma reagin</span> Test for syphilis

The rapid plasma reagin test is a type of rapid diagnostic test that looks for non-specific antibodies in the blood of the patient that may indicate an infection by syphilis or related non-venereal treponematoses. It is one of several nontreponemal tests for syphilis. The term reagin means that this test does not look for antibodies against the bacterium itself, Treponema pallidum, but rather for antibodies against substances released by cells when they are damaged by T. pallidum. Traditionally, syphilis serologic testing has been performed using a nontreponemal test (NTT) such as the RPR or VDRL test, with positive results then confirmed using a specific treponemal test (TT) such as TPPA or FTA-ABS. This method is endorsed by the U.S. Centers for Disease Control and Prevention (CDC) and is the standard in many parts of the world. After screening for syphilis, a titer can be used to track the progress of the disease over time and its response to therapy.

<span class="mw-page-title-main">Venereal Disease Research Laboratory test</span> Blood test for syphilis

The Venereal Disease Research Laboratory test (VDRL) is a blood test for syphilis and related non-venereal treponematoses that was developed by the eponymous US laboratory. The VDRL test is used to screen for syphilis, whereas other, more specific tests are used to diagnose the disease.

<span class="mw-page-title-main">Chancroid</span> Sexually transmitted bacterial infection in humans

Chancroid is a bacterial sexually transmitted infection characterized by painful sores on the genitalia. Chancroid is known to spread from one individual to another solely through sexual contact. However, there have been reports of accidental infection through the hand.

<span class="mw-page-title-main">Congenital syphilis</span> Presence of syphilis in a baby due to its mother being infected

Congenital syphilis is syphilis that occurs when a mother with untreated syphilis passes the infection to her baby during pregnancy or at birth. It may present in the fetus, infant, or later. Clinical features vary and differ between early onset, that is presentation before 2-years of age, and late onset, presentation after age 2-years. Infection in the unborn baby may present as poor growth, non-immune hydrops leading to premature birth or loss of the baby, or no signs. Affected newborns mostly initially have no clinical signs. They may be small and irritable. Characteristic features include a rash, fever, large liver and spleen, a runny and congested nose, and inflammation around bone or cartilage. There may be jaundice, large glands, pneumonia, meningitis, warty bumps on genitals, deafness or blindness. Untreated babies that survive the early phase may develop skeletal deformities including deformity of the nose, lower legs, forehead, collar bone, jaw, and cheek bone. There may be a perforated or high arched palate, and recurrent joint disease. Other late signs include linear perioral tears, intellectual disability, hydrocephalus, and juvenile general paresis. Seizures and cranial nerve palsies may first occur in both early and late phases. Eighth nerve palsy, interstitial keratitis and small notched teeth may appear individually or together; known as Hutchinson's triad.

Pinta is a human skin disease caused by infection with the spirochete Treponema carateum, which is morphologically and serologically indistinguishable from the bacterium that causes syphilis and bejel. The disease was previously known to be endemic to Mexico, Central America, and South America; it may have been eradicated since, with the latest case occurring in Brazil in 2020.

<span class="mw-page-title-main">Nonvenereal endemic syphilis</span> Medical condition

Bejel, or endemic syphilis, is a chronic skin and tissue disease caused by infection by the endemicum subspecies of the spirochete Treponema pallidum. Bejel is one of the "endemic treponematoses", a group that also includes yaws and pinta. Typically, endemic trepanematoses begin with localized lesions on the skin or mucous membranes. Pinta is limited to affecting the skin, whereas bejel and yaws are considered to be invasive because they can also cause disease in bone and other internal tissues.

<span class="mw-page-title-main">Parrot's sign</span> Medical condition

Parrot's sign, refers to at least two medical signs; one relating to a large skull and another to a pupil reaction.

<span class="mw-page-title-main">Neurosyphilis</span> Infection of the central nervous system in a patient with syphilis

Neurosyphilis is the infection of the central nervous system in a patient with syphilis. In the era of modern antibiotics, the majority of neurosyphilis cases have been reported in HIV-infected patients. Meningitis is the most common neurological presentation in early syphilis. Tertiary syphilis symptoms are exclusively neurosyphilis, though neurosyphilis may occur at any stage of infection.

The fluorescent treponemal antibody absorption (FTA-ABS) test is a diagnostic test for syphilis. Using antibodies specific for the Treponema pallidum species, such tests would be assumed to be more specific than non-treponemal testing such as VDRL but have been shown repeatedly to be sensitive but not specific for the diagnosis of neurosyphilis in cerebrospinal fluid (CSF). In addition, FTA-ABS turns positive earlier and remains positive longer than VDRL. Other treponemes, such as T. pertenue, may also produce a positive FTA-ABS. The ABS suffix refers particularly to a processing step used to remove nonspecific antispirochetal antibodies present in normal serum.

<span class="mw-page-title-main">Syphilitic aortitis</span> Inflammation of the aorta

Syphilitic aortitis is inflammation of the aorta associated with the tertiary stage of syphilis infection. SA begins as inflammation of the outermost layer of the blood vessel, including the blood vessels that supply the aorta itself with blood, the vasa vasorum. As SA worsens, the vasa vasorum undergo hyperplastic thickening of their walls thereby restricting blood flow and causing ischemia of the outer two-thirds of the aortic wall. Starved for oxygen and nutrients, elastic fibers become patchy and smooth muscle cells die. If the disease progresses, syphilitic aortitis leads to an aortic aneurysm. Overall, tertiary syphilis is a rare cause of aortic aneurysms. Syphilitic aortitis has become rare in the developed world with the advent of penicillin treatments after World War II.

Treponematosis is a term used to individually describe any of the diseases caused by four members of the bacterial genus Treponema. The four diseases are collectively referred to as treponematoses:

A nontreponemal test (NTT) is a blood test for diagnosis of infection with syphilis. Nontreponemal tests are an indirect method in that they detect biomarkers that are released during cellular damage that occurs from the syphilis spirochete. In contrast, treponemal tests look for antibodies that are a direct result of the infection thus, anti-treponeme IgG, IgM and to a lesser degree IgA. Nontreponemal tests are screening tests, very rapid and relatively simple, but need to be confirmed by treponemal tests. Centers for Disease Control and Prevention (CDC)-approved standard tests include the VDRL test, the rapid plasma reagin (RPR) test, the unheated serum reagin (USR) test, and the toluidine red unheated serum test (TRUST). These have mostly replaced the first nontreponemal test, the Wassermann test.

<span class="mw-page-title-main">Pyrotherapy</span> Raising body temperature for medical purposes

Pyrotherapy is a method of treatment by raising the body temperature or sustaining an elevated body temperature using a fever. In general, the body temperature was maintained at 41 °C (105 °F). Many diseases were treated by this method in the first half of the 20th century. In general, it was done by exposing the patient to hot baths, warm air, or (electric) blankets. The technique reached its peak of sophistication in the early 20th century with malariotherapy, in which Plasmodium vivax, a causative agent of malaria, was allowed to infect already ill patients in order to produce intense fever for therapeutic ends. The sophistication of this approach lay in using effective anti-malarial drugs to control the P. vivax infection, while maintaining the fever it causes to the detriment of other, ongoing, and then-incurable infections present in the patient, such as late-stage syphilis. This type of pyrotherapy was most famously used by psychiatrist Julius Wagner-Jauregg, who won the Nobel Prize for Medicine in 1927 for his elaboration of the procedure in treating neurosyphilitics.

<i>Treponema pallidum</i> particle agglutination assay Assay used for detection and titration of antibodies against the causative agent of syphilis

The Treponema pallidum particle agglutination assay is an indirect agglutination assay used for detection and titration of antibodies against the causative agent of syphilis, Treponema pallidum subspecies pallidum. It also detects other treponematoses.

<span class="mw-page-title-main">Epidemiology of syphilis</span> Eradication efforts and prevalence of syphilis

Syphilis is a bacterial infection transmitted by sexual contact and is believed to have infected 12 million people in 1999 with greater than 90% of cases in the developing world. It affects between 700,000 and 1.6 million pregnancies a year, resulting in spontaneous abortions, stillbirths, and congenital syphilis. In Sub-Saharan Africa syphilis contributes to approximately 20% of perinatal deaths.

<span class="mw-page-title-main">Meningeal syphilis</span> Medical condition

Meningeal syphilis is a chronic form of syphilis infection that affects the central nervous system. Treponema pallidum, a spirochate bacterium, is the main cause of syphilis, which spreads drastically throughout the body and can infect all its systems if not treated appropriately. Treponema pallidum is the main cause of the onset of meningeal syphilis and other treponemal diseases, and it consists of a cytoplasmic and outer membrane that can cause a diverse array of diseases in the central nervous system and brain.

References

  1. 1 2 3 Farhi, D; Dupin, N (Sep–Oct 2010). "Origins of syphilis and management in the immunocompetent patient: facts and controversies". Clinics in Dermatology. 28 (5): 533–38. doi:10.1016/j.clindermatol.2010.03.011. PMID   20797514.
  2. 1 2 3 4 5 6 7 8 Franzen, C (December 2008). "Syphilis in composers and musicians – Mozart, Beethoven, Paganini, Schubert, Schumann, Smetana". European Journal of Clinical Microbiology & Infectious Diseases . 27 (12): 1151–57. doi:10.1007/s10096-008-0571-x. PMID   18592279. S2CID   947291.
  3. ↑ Kent ME, Romanelli F (February 2008). "Reexamining syphilis: an update on epidemiology, clinical manifestations, and management". Ann Pharmacother. 42 (2): 226–36. doi:10.1345/aph.1K086. PMID   18212261. S2CID   23899851.
  4. ↑ Rothschild, B. M. (2005-05-15). "History of Syphilis". Clinical Infectious Diseases. 40 (10): 1454–63. doi:10.1086/429626. ISSN   1058-4838. PMID   15844068.
  5. 1 2 3 4 Baker, B.J.; Armelagos, G.J. (1988). "The origin and antiquity of syphilis: Paleopathological diagnosis and interpretation". Current Anthropology. 29 (5): 703–38. doi:10.1086/203691. PMID   11613900. S2CID   3065488.
  6. ↑ Geggel, Laura (5 February 2020). "9,900-year-old skeleton of horribly disfigured woman found in Mexican cave". Live Science. livescience.com. Retrieved February 6, 2020.
  7. ↑ Stinnesbeck, W.; Rennie, S. R.; Avilés Olguín, J.; Stinnesbeck, S. R.; Gonzalez, S.; Frank, N.; Warken, S.; Schorndorf, N.; Krengel, T.; Velázquez Morlet, A.; González González, A. (2020). "New evidence for an early settlement of the Yucatán Peninsula, Mexico: The Chan Hol 3 woman and her meaning for the Peopling of the Americas". PLOS ONE. 15 (2). NIH: e0227984. Bibcode:2020PLoSO..1527984S. doi: 10.1371/journal.pone.0227984 . PMC   7001910 . PMID   32023279.
  8. ↑ Giancani, L.; Lukehart, S. A. (2014). "The Endemic Treponematoses". Clinical Microbiology Reviews. 27 (1): 89–115. doi:10.1128/CMR.00070-13. PMC   3910905 . PMID   24396138.
  9. 1 2 Hudson EH (October 1961). "Historical approach to the terminology of syphilis". Arch Dermatol. 84 (4): 545–62. doi:10.1001/archderm.1961.01580160009002. PMID   14036423.
  10. ↑ Holcomb, R.C. (1935). "The Antiquity of Syphilis". Medical Life. 42: 275–325.
  11. ↑ Osler, W. (1910) Aequanimitas: With Other Addresses to Medical Students, Nurses, and Practitioners of Medicine, 2nd ed. (Philadelphia: Blakiston's), 140.
  12. ↑ Powell, M.L.; Cook, D.C., eds. (2005). The myth of syphilis: The natural history of treponematosis in North America. University Press of Florida. pp. 9–63. ISBN   978-0-8130-2794-4. OCLC   680623126.
  13. ↑ Quétel, C. (1990). History of Syphilis. Baltimore, MD: The Johns Hopkins University Press. pp. 33–49. ISBN   0-8018-4089-9. OCLC   1409014054.
  14. 1 2 Harper, K.N.; Zuckerman, M.K.; Harper, M.L.; Kingston, J.D.; Armelagos, G.J. (2011). "The origin and antiquity of syphilis revisited: An appraisal of Old World Pre-Columbian evidence of treponemal infections". Yearbook of Physical Anthropology. 54: 99–133. doi: 10.1002/ajpa.21613 . PMID   22101689.
  15. ↑ Hudson EH (January 1946). "A unitarian view of treponematosis". Am J Trop Med Hyg. 26: 135–9. doi:10.4269/ajtmh.1946.s1-26.135. PMID   21018590.
  16. ↑ Hudson EH (March 1958). "The treponematoses; or trepanematosis". Br J Vener Dis. 34 (1): 22–3. PMC   1047155 . PMID   13523193.
  17. ↑ Hudson, E. H. (1965). "Treponematosis and man's social evolution". American Anthropologist. 67 (4): 885–901. doi:10.1525/aa.1965.67.4.02a00020.
  18. ↑ Baker, B. J.; Crane-Kramer, G.; Dee, M. W.; Gregoricka, L. A.; Henneberg, M.; Lee, C.; Lukehart, S. A.; Mabey, D. C.; Roberts, C. A.; Stodder, A. L. W.; Stone, A. C.; Winingear, S. (2020). "Advancing the Understanding of Treponemal Disease in the Past and Present" (PDF). Yearbook of Physical Anthropology. 171: 5–41. doi:10.1002/ajpa.23988. PMID   31956996. S2CID   210831211.
  19. ↑ Henneberg, M.; Henneberg, R.J. "Treponematosis in an ancient Greek colony of Metaponto, southern Italy, 580–250 BC." In Dutour 1994 , pp. 92–98
  20. ↑ Cole G, Waldron T (January 2011). "Apple Down 152: a putative case of syphilis from sixth century AD Anglo-Saxon England". Am J Phys Anthropol. 144 (1): 72–9. doi:10.1002/ajpa.21371. PMID   20721939.
  21. ↑ Erdal, Y.S. (2006). "A pre-Columbian case of congenital syphilis from Anatolia (Nicaea, 13th century AD)". International Journal of Osteoarchaeology. 16: 16–33. doi:10.1002/oa.802.
  22. ↑ Roberts, C.A. "Treponematosis in Gloucester, England: A theoretical and practical approach to the Pre-Columbian theory." In Dutour 1994 , pp. 101–8
  23. ↑ Walker D, Powers N, Connell B, Redfern R (January 2015). "Evidence of skeletal treponematosis from the medieval burial ground of St. Mary Spital, London, and implications for the origins of the disease in Europe". Am J Phys Anthropol. 156 (1): 90–101. doi:10.1002/ajpa.22630. PMID   25284594.
  24. ↑ Pětrošová H, Zobaníková M, Čejková D, Mikalová L, Pospíšilová P, Strouhal M, Chen L, Qin X, Muzny DM, Weinstock GM, Šmajs D (2012). "Whole genome sequence of Treponema pallidum ssp. pallidum, strain Mexico A, suggests recombination between yaws and syphilis strains". PLOS Negl Trop Dis. 6 (9): e1832. doi: 10.1371/journal.pntd.0001832 . PMC   3447947 . PMID   23029591.
  25. ↑ Mikalová L, Strouhal M, Čejková D, Zobaníková M, Pospíšilová P, Norris SJ, Sodergren E, Weinstock GM, Šmajs D (December 2010). "Genome analysis of Treponema pallidum subsp. pallidum and subsp. pertenue strains: most of the genetic differences are localized in six regions". PLOS ONE. 5 (12): e15713. Bibcode:2010PLoSO...515713M. doi: 10.1371/journal.pone.0015713 . PMC   3012094 . PMID   21209953.
  26. ↑ Staudová B, Strouhal M, Zobaníková M, Cejková D, Fulton LL, Chen L, Giacani L, Centurion-Lara A, Bruisten SM, Sodergren E, Weinstock GM, Smajs D (2014). "Whole genome sequence of the Treponema pallidum subsp. endemicum strain Bosnia A: the genome is related to yaws treponemes but contains few loci similar to syphilis treponemes". PLOS Negl Trop Dis. 8 (11): e3261. doi: 10.1371/journal.pntd.0003261 . PMC   4222731 . PMID   25375929.
  27. ↑ Fraser CM, Norris SJ, Weinstock GM, White O, Sutton GG, Dodson R, Gwinn M, Hickey EK, Clayton R, Ketchum KA, Sodergren E, Hardham JM, McLeod MP, Salzberg S, Peterson J, Khalak H, Richardson D, Howell JK, Chidambaram M, Utterback T, McDonald L, Artiach P, Bowman C, Cotton MD, Fujii C, Garland S, Hatch B, Horst K, Roberts K, Sandusky M, Weidman J, Smith HO, Venter JC (July 1998). "Complete genome sequence of Treponema pallidum, the syphilis spirochete". Science. 281 (5375): 375–88. Bibcode:1998Sci...281..375F. doi:10.1126/science.281.5375.375. PMID   9665876.
  28. ↑ Kolman CJ, Centurion-Lara A, Lukehart SA, Owsley DW, Tuross N (December 1999). "Identification of Treponema pallidum subspecies pallidum in a 200-year-old skeletal specimen". J Infect Dis. 180 (6): 2060–3. doi:10.1086/315151. PMID   10558971.
  29. ↑ Montiel R, Solórzano E, Díaz N, Álvarez-Sandoval BA, González-Ruiz M, Cañadas MP, Simões N, Isidro A, Malgosa A (2012). "Neonate human remains: a window of opportunity to the molecular study of ancient syphilis". PLOS ONE. 7 (5): e36371. Bibcode:2012PLoSO...736371M. doi: 10.1371/journal.pone.0036371 . PMC   3342265 . PMID   22567153.
  30. ↑ Schuenemann VJ, Kumar Lankapalli A, Barquera R, Nelson EA, Iraíz Hernández D, Acuña Alonzo V, Bos KI, Márquez Morfín L, Herbig A, Krause J (June 2018). "Historic Treponema pallidum genomes from Colonial Mexico retrieved from archaeological remains". PLOS Negl Trop Dis. 12 (6): e0006447. doi: 10.1371/journal.pntd.0006447 . PMC   6013024 . PMID   29927932.
  31. ↑ Gaul JS, Grossschmidt K, Gusenbauer C, Kanz F (2015). "A probable case of congenital syphilis from pre-Columbian Austria". Anthropol Anz. 72 (4): 451–72. doi:10.1127/anthranz/2015/0504. PMID   26482430.
  32. ↑ Majander K, Pfrengle S, Kocher A, Neukamm J, du Plessis L, Pla-Díaz M, Arora N, Akgül G, Salo K, Schats R, Inskip S, Oinonen M, Valk H, Malve M, Kriiska A, Onkamo P, González-Candelas F, Kühnert D, Krause J, Schuenemann VJ (October 2020). "Ancient Bacterial Genomes Reveal a High Diversity of Treponema pallidum Strains in Early Modern Europe". Curr Biol. 30 (19): 3788–3803.e10. Bibcode:2020CBio...30E3788M. doi: 10.1016/j.cub.2020.07.058 . hdl: 21.11116/0000-0006-E0D8-9 . PMID   32795443.
  33. ↑ Salmon, M. (2022). Medieval Syphilis and Treponemal Disease. Arc Humanities Press. pp. 61–79. ISBN   978-1-80270-089-3. OCLC   1345580711.
  34. ↑ Salmon, M. (2022). "Manuscripts and art support archaeological evidence that syphilis was in Europe long before explorers could have brought it home from the Americas". The Conversion.
  35. ↑ Grzegorczyk W, Grzegorczyk J, Grzegorczyk K (2016). "Alleged cases of syphilis immortalized in the Krakow Altarpiece by Veit Stoss in the light of new research on the origins of the disease in Europe". Medical Review. 14 (3): 340–357. doi:10.15584/medrev.2016.3.9. S2CID   57726453.
  36. ↑ Salmon 2022 , pp. 27–35
  37. ↑ Grin EI (1952). "Endemic syphilis in Bosnia; clinical and epidemiological observations on a successful mass-treatment campaign". Bull World Health Organ. 7 (1): 1–74. PMC   2554130 . PMID   13019544.
  38. ↑ Arrizabalaga, Jon (2011). "The Changing Identity of the French Pox in Early Renaissance Castile". In Glaze, F.E.; Nance, B.K. (eds.). Between Text and Patient: The Medical Enterprise in Medieval and Early Modern Europe. SISMEL, Edizioni del Galluzzo. pp. 397–417. hdl:10261/80919. ISBN   978-88-8450-401-2. OCLC   1103411766.
  39. ↑ Arrizabalaga, Jon (2011). "The Changing Identity of the French Pox in Early Renaissance Castile". In Glaze, F.E.; Nance, B.K. (eds.). Between Text and Patient: The Medical Enterprise in Medieval and Early Modern Europe. SISMEL, Edizioni del Galluzzo. pp. 397–417. hdl:10261/80919. ISBN   978-88-8450-401-2. OCLC   1103411766.
  40. ↑ Jankauskas, Rimantas "Syphilis in Eastern Europe: Historical and Paleopathological Evidence." In Dutour 1994 , p. 238
  41. ↑ Arrizabalaga, J.; Henderson, J.; French, R.K. (1997). The Great Pox: The French Disease in Renaissance Europe. Yale University Press. pp.  117. ISBN   0-300-06934-0.
  42. ↑ Major, R.H. (1978) [1945]. Classic descriptions of disease : with biographical sketches of the authors (3rd ed.). C. C. Thomas. pp. 35–36. ISBN   0-398-01202-4. OCLC   4069361. citing Béthencourt's New Litany of Penitence (1527).
  43. 1 2 Crosby, Alfred W. (2003). The Columbian exchange: biological and cultural consequences of 1492. New York: Praeger. p. 146. ISBN   0-275-98092-8. OCLC   51726873.
  44. 1 2 Armelagos, George J.; Zuckerman, Molly K.; Harper, Kristin N. (March 2012). "The Science Behind Pre-Columbian Evidence of Syphilis in Europe: Research by Documentary". Evolutionary Anthropology. 21 (2): 50–57. doi:10.1002/evan.20340. PMC   3413456 . PMID   22499439.
  45. ↑ Debora MacKenzie (15 January 2008). "Columbus blamed for spread of syphilis". New Scientist .
  46. 1 2 Harper, KN; Ocampo, PS; Steiner, BM; George, RW; Silverman, MS; Bolotin, S; Pillay, A; Saunders, NJ; Armelagos, GJ (15 January 2008). "On the Origin of the Treponematoses: A Phylogenetic Approach". PLOS Neglected Tropical Diseases. 2 (1): e148. doi: 10.1371/journal.pntd.0000148 . PMC   2217670 . PMID   18235852 – via New Scientist. Some researchers have argued that the syphilis-causing bacterium, or its progenitor, was brought from the New World to Europe by Christopher Columbus and his men, while others maintain that the treponematoses, including syphilis, have a much longer history on the European continent.
  47. ↑ Mulligan CJ, Norris SJ, Lukehart SA (2008). "Molecular studies in Treponema pallidum evolution: toward clarity?". PLOS Neglected Tropical Diseases. 2 (1): e184. doi: 10.1371/journal.pntd.0000184 . PMC   2270795 . PMID   18357339.
  48. ↑ Rumbaut, Ruben D. (1997). "The Great Pox: The French Disease in Renaissance Europe". JAMA. 278 (5): 440. doi:10.1001/jama.1997.03550050104045. ISSN   0098-7484.
  49. ↑ Lobdell J, Owsley D (August 1974). "The origin of syphilis". Journal of Sex Research. 10 (1): 76–79. doi:10.1080/00224497409550828. S2CID   143393896.
  50. ↑ Diamond, Jared (1997). Guns, Germs and Steel. W.W. Norton. p. 210. ISBN   84-8306-667-X.
  51. ↑ John Noble Wilford (15 January 2008). "Genetic Study Bolsters Columbus Link to Syphilis". The New York Times .
  52. ↑ "Columbus May Have Brought Syphilis to Europe", LiveScience
  53. ↑ "Pox and Paranoia in Renaissance Europe". History Today. [ dead link ]
  54. ↑ Szreter, Simon; Siena, Kevin (2020). "The pox in Boswell's London: an estimate of the extent of syphilis infection in the metropolis in the 1770s†". The Economic History Review. 74 (2): 372–399. doi: 10.1111/ehr.13000 . ISSN   1468-0289.
  55. ↑ Fracastor, Hieronymus (1911). Syphilis. The Philmar Company.
  56. ↑ "Syphilis". Online Etymology Dictionary. 2001.
  57. ↑ Cassar, Charles (2002). "Concepts of Health and Illness in Early Modern Malta". Quaderns de l'Institut Català d'Antropologia (17–18). University of Malta: 55. ISSN   2385-4472. Archived from the original on 25 July 2017.
  58. 1 2 3 4 Tampa, Mircea; et al. (2014). "Brief History of Syphilis". Journal of Medicine and Life. 7 (1): 4–10. PMC   3956094 . PMID   24653750.
  59. ↑ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN   978-1-4160-2999-1.
  60. ↑ Semple, David; Smythe, Robert (2009). Oxford handbook of psychiatry. Oxford: Oxford University Press. p. 160. ISBN   978-0-19-923946-7.
  61. ↑ Tasioulas, Jacqueline (2010). The Makars. Edinburgh: Canongate. p. 302. ISBN   978-1-84767-501-9. OCLC   1255234161.
  62. ↑ Rudy's List of Archaic Medical Terms (2007-04-27). "B". Antiquus Morbus. Archived from the original on 2018-08-25. Retrieved 2008-04-28.
    Referencing: Robley Dunglison (1874). Dunglison's Medical Dictionary – A Dictionary of Medical Science. Philadelphia: Collins.
  63. ↑ Parascandola, John (2009). "From Mercury to Miracle Drugs: Syphilis Therapy over the Centuries". Pharmacy in History. 51 (1).
  64. ↑ Ozuah, Philip O. (March 2000). "Mercury poisoning". Current Problems in Pediatrics. 30 (3): 91–99 [91]. doi:10.1067/mps.2000.104054. PMID   10742922..
  65. ↑ Sir Henry Morris (1926). Summary of the Debate by the President (Speech). The Royal Society of Medicine.
  66. ↑ Grimes, Jill; Fagerberg, Krystyn; Smith, Lori, eds. (2014). Sexually Transmitted Disease: An Encyclopedia of Diseases, Prevention, Treatment, and Issues. Santa Barbara, California: Greenwood. p. 583. ISBN   978-1-4408-0134-1.
  67. 1 2 3 4 5 6 7 8 9 "Infectious Diseases at the Edward Worth Library: Treatment of Syphilis in Early Modern Europe". infectiousdiseases.edwardworthlibrary.ie. Edward Worth Library. 2015. Archived from the original on 2015-05-05. Retrieved 2015-12-19.
  68. ↑ Walker, TJ (December 1869). "The Treatment of Syphilis by the Hypodermic Injection of the Salts of Mercury". British Medical Journal. 2 (466): 605–08. doi:10.1136/bmj.2.466.605. PMC   2261112 . PMID   20745696.
  69. ↑ Membrives, Eva Parra; Peinado, Miguel Ángel García (2012). Aspects of Literary Translation: Building Linguistic and Cultural Bridge in Past and Present. BoD – Books on Demand. p. 55. ISBN   978-3823367086.
  70. 1 2 Dangler, Jean (2001). Mediating Fictions: Literature, Women Healers, and the Go-Between in Medieval and Early Modern Iberia. Lewisburg, Pennsylvania: Bucknell University Press. pp. 128–29. ISBN   0-8387-5452-X.
  71. ↑ Stein, Claudia (2009). Negotiating the French Pox in Early Modern Germany (English ed.). Farnham (Surrey, United Kingdom): Ashgate Publishing. p. 84. ISBN   978-0-7546-6008-8.
  72. ↑ Lach, Donald F. (1994). Asia in the Making of Europe, Volume II. University of Chicago Press. p. 11. ISBN   978-0226467306 . Retrieved 19 January 2017.
  73. ↑ Culpeper, Nicholas (1653). Culpeper's Complete Herbal (1816 ed.). London: Richard Evans. p. 84. A strong decoction of the herbs and flowers...is an excellent cure for the French pox[.]
  74. ↑ Ménard, Sophie (January 2019). "An Unknown Renaissance Portrait of Tagliacozzi (1545–1599), the Founder of Plastic Surgery". Plastic and Reconstructive Surgery - Global Open. 7 (1): e2006. doi:10.1097/GOX.0000000000002006. ISSN   2169-7574. PMC   6382240 . PMID   30859024.
  75. ↑ Bynum, W.F. (1994). Science and the Practice of Medicine in the Nineteenth Century. Cambridge University Press. p. 168. ISBN   978-0-521-25109-9.
  76. ↑ Raju T (2006). "Hot brains: manipulating body heat to save the brain" (PDF). Pediatrics. 117 (2): e320–21. doi: 10.1542/peds.2005-1934 . PMID   16452338. S2CID   21411790.
  77. ↑ Spink, W. W. "Infectious diseases: prevention and treatment in the nineteenth and twentieth centuries" U of Minnesota Press, 1978, p. 316.
  78. ↑ Brown, Kevin (2006). The Pox: The Life and Near Death of a Very Social Disease. Stroud: Sutton. pp. 85–111, 185–91. ISBN   978-0-7509-4041-2. OCLC   70882484.
  79. ↑ Grimes, Fagerberg & Smith 2014 , p.  317
  80. ↑ "Noguchi, Hideyo". The Columbia Encyclopedia (6th ed.). Archived from the original on September 29, 2007.
  81. ↑ Cabinet Office, Japan: Noguchi Prize
  82. ↑ Szreter, Simon; Siena, Kevin (2021). "The pox in Boswell's London: an estimate of the extent of syphilis infection in the metropolis in the 1770s†". The Economic History Review. 74 (2): 372–399. doi: 10.1111/ehr.13000 . ISSN   1468-0289. S2CID   225618214.
  83. ↑ "One in five Londoners had syphilis by age 35 in the late 18th century, historians estimate". MinnPost. 8 July 2020.
  84. ↑ Szreter, S. (25 February 2014). "The Prevalence of Syphilis in England and Wales on the Eve of the Great War: Re-visiting the Estimates of the Royal Commission on Venereal Diseases 1913–1916". Social History of Medicine. 27 (3): 508–529. doi:10.1093/shm/hkt123. PMC   4109696 . PMID   25067890.
  85. 1 2 3 Green, T.; Talbot, M. D.; Morton, R. S. (1 June 2001). "The control of syphilis, a contemporary problem: a historical perspective". Sexually Transmitted Infections. 77 (3): 214–7. doi:10.1136/sti.77.3.214. ISSN   1368-4973. PMC   1744312 . PMID   11402234. S2CID   11160963 . Retrieved 14 December 2021.
  86. ↑ Laird, S. M. (1 March 1959). "Elimination of Congenital Syphilis". Sexually Transmitted Infections. 35 (1): 15–19. doi:10.1136/sti.35.1.15. ISSN   1368-4973. PMC   1047229 . PMID   13651659. S2CID   30231405 . Retrieved 14 December 2021.
  87. ↑ Willeford, Wesley G.; Bachmann, Laura H. (26 September 2016). "Syphilis ascendant: a brief history and modern trends". Tropical Diseases, Travel Medicine and Vaccines. 2: 20. doi: 10.1186/s40794-016-0039-4 . ISSN   2055-0936. PMC   5530970 . PMID   28883964.
  88. ↑ The Metropolitan Museum of Art Bulletin , Summer 2007, pp. 55–56.
  89. ↑ Eisler, CT (Winter 2009). "Who is Dürer's "Syphilitic Man"?". Perspectives in Biology and Medicine. 52 (1): 48–60. doi:10.1353/pbm.0.0065. PMID   19168944. S2CID   207268142.
  90. ↑ Hughes, Robert (2007). Things I didn't know : a memoir (1st Vintage Book ed.). New York: Vintage. p. 346. ISBN   978-0-307-38598-7.
  91. ↑ Entwistle, Joanne; Wilson, Elizabeth, eds. (2005). Body dressing ([Online-Ausg.] ed.). Oxford: Berg Publishers. p.  205. ISBN   978-1-85973-444-5.
  92. ↑ Frith, John (2012). "Syphilis – Its Early History and Treatment until Penicillin and the Debate on its Origin". Journal of Military and Veterans' Health. 20 (4).
  93. ↑ Reid, Basil A. (2009). Myths and realities of Caribbean history ([Online-Ausg.] ed.). Tuscaloosa: University of Alabama Press. p. 113. ISBN   978-0-8173-5534-0.
  94. ↑ "Preparation and Use of Guayaco for Treating Syphilis". Jan van der Straet. Retrieved 6 August 2007.
  95. ↑ Katz RV, Kegeles SS, Kressin NR, et al. (November 2006). "The Tuskegee Legacy Project: Willingness of Minorities to Participate in Biomedical Research". J Health Care Poor Underserved. 17 (4): 698–715. doi:10.1353/hpu.2006.0126. PMC   1780164 . PMID   17242525.
  96. 1 2 3 4 "U.S. Public Health Service Syphilis Study at Tuskegee". Centers for Disease Control and Prevention. 15 June 2011. Retrieved 7 July 2010.
  97. 1 2 3 White, RM (13 March 2000). "Unraveling the Tuskegee Study of Untreated Syphilis". Archives of Internal Medicine. 160 (5): 585–98. doi:10.1001/archinte.160.5.585. PMID   10724044.
  98. ↑ "Bad Blood: The Tuskegee Syphilis Study: President Bill Clinton's Apology". University of Virginia Health Sciences Library. Archived from the original on 30 December 2014. Retrieved 2 December 2014.
  99. ↑ "U.S. apologizes for newly revealed syphilis experiments done in Guatemala". The Washington Post . 1 October 2010. Retrieved 1 October 2010. The United States revealed on Friday that the government conducted medical experiments in the 1940s in which doctors infected soldiers, prisoners and mental patients in Guatemala with syphilis and other sexually transmitted diseases.
  100. ↑ "WHO validates elimination of mother-to-child transmission of HIV and syphilis in Cuba". WHO. 30 June 2015. Archived from the original on July 2, 2015. Retrieved 30 August 2015.

Bibliography

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.