Syphilis (/ˈsɪfəlɪs,ˈsɪfɪlɪs/) is asexually transmitted infection caused by thebacteriumTreponema pallidumsubspeciespallidum.[1] The signs and symptoms depend on the stage it presents: primary, secondary,latent or tertiary.[1][2] The primary stage classically presents with a singlechancre (a firm, painless, non-itchyskin ulceration usually between 1 cm and 2 cm in diameter), though there may be multiple sores.[2] In secondary syphilis, a diffuserash occurs, which frequently involves the palms of the hands and soles of the feet.[2] There may also be sores in the mouth or vagina.[2] Latent syphilis has no symptoms and can last years.[2] In tertiary syphilis, there aregummas (soft, non-cancerous growths), neurological problems, or heart symptoms.[3] Syphilis has been known as "the great imitator", because it may cause symptoms similar to many other diseases.[2][3]
In 2015, about 45.4 million people had syphilis infections,[5] of which six million were new cases.[9] During 2015, it caused about 107,000 deaths, down from 202,000 in 1990.[6][10] After decreasing dramatically with the availability of penicillin in the 1940s, rates of infection have increased since the turn of the millennium in many countries, often in combination withhuman immunodeficiency virus (HIV).[3][11] This is believed to be partly due to unsafe drug use, increasedprostitution, and decreased use ofcondoms.[12][13][14]
Signs and symptoms
Primary syphilis on a tongue
Syphilis canpresent in one of four different stages: primary, secondary, latent, and tertiary, and may also occurcongenitally.[15] There may beno symptoms.[16] It was referred to as "the great imitator" bySir William Osler due to its varied presentations.[3][17][18]
Primary
Chancre on a penis due to primary syphilis, 1978
Primary syphilis is typically acquired by direct sexual contact with the infectious lesions of another person.[19] Approximately 2–6 weeks after contact (with a range of 10–90 days) a skin lesion, called achancre, appears at the site and this contains infectious bacteria.[20][21] This is classically (40% of the time) a single, firm, painless, non-itchyskin ulceration with a clean base and sharp borders approximately 0.3–3.0 cm in size.[3] The lesion may take on almost any form.[22] In the classic form, it evolves from amacule to apapule and finally to anerosion orulcer.[22] Occasionally, multiple lesions may be present (~40%),[3] with multiple lesions being more common when coinfected with HIV.[22] Lesions may be painful or tender (30%), and they may occur in places other than the genitals (2–7%).[22] The most common location in women is thecervix (44%), thepenis in heterosexual men (99%), andanally andrectally inmen who have sex with men (34%).[22]Lymph node enlargement frequently (80%) occurs around the area of infection,[3] occurring seven to 10 days after chancre formation.[22] Thelesion may persist for three to six weeks if left untreated.[3]
Secondary
Typical presentation of secondary syphilis with a rash on the palms of the hands, 1967Reddishpapules andnodules over much of the body due to secondary syphilis
Secondary syphilis occurs approximately four to ten weeks after the primary infection.[3] While secondary disease is known for the many different ways it can manifest, symptoms most commonly involve theskin,mucous membranes, andlymph nodes.[23] There may be a symmetrical, reddish-pink, non-itchyrash on the trunk and extremities, including the palms and soles.[3][24] The rash may becomemaculopapular orpustular.[3] It may form flat, broad, whitish, wart-like lesions on mucous membranes, known ascondyloma latum.[3] All of these lesions harbor bacteria and are infectious.[3] Other symptoms may includefever,sore throat,malaise,weight loss,hair loss, andheadache.[3] Rare manifestations includeliver inflammation,kidney disease,joint inflammation,periostitis,inflammation of the optic nerve,uveitis, andinterstitial keratitis.[3][25] The acute symptoms usually resolve after three to six weeks;[25] about 25% of people may present with a recurrence of secondary symptoms.[23][26] Many people who present with secondary syphilis (40–85% of women, 20–65% of men) do not report previously having had the classical chancre of primary syphilis.[23]
Latent
Latent syphilis is defined as havingserologic proof of infection without symptoms of disease.[19] It develops after secondary syphilis and is divided into early latent and late latent stages.[27] Early latent syphilis is defined by theWorld Health Organization as less than 2 years after original infection.[27] Early latent syphilis is infectious as up to 25% of people can develop a recurrent secondary infection (during which bacteria are actively replicating and are infectious).[27] Two years after the original infection the person will enter late latent syphilis and is not as infectious as in the early phase.[25][28] The latent phase of syphilis can last many years after which, without treatment, approximately 15–40% of people can develop tertiary syphilis.[29]
Tertiary
Model of a head of a person with tertiary (gummatous) syphilis,Musée de l'Homme, Paris
Tertiary syphilis may occur approximately 3 to 15 years after the initial infection and may be divided into three different forms: gummatous syphilis (15%), lateneurosyphilis (6.5%), and cardiovascular syphilis (10%).[3][25] Without treatment, a third of infected people develop tertiary disease.[25] People with tertiary syphilis are not infectious.[3]
Gummatous syphilis or latebenign syphilis usually occurs 1 to 46 years after the initial infection, with an average of 15 years.[3] This stage is characterized by the formation of chronicgummas, which are soft, tumor-like balls of inflammation which may vary considerably in size.[3] They typically affect the skin, bone, and liver, but can occur anywhere.[3]
Cardiovascular syphilis usually occurs 10–30 years after the initial infection.[3] The most common complication issyphilitic aortitis, which may result inaortic aneurysm formation.[3]
Neurosyphilis refers to an infection involving thecentral nervous system. Involvement of the central nervous system in syphilis (either asymptomatic or symptomatic) can occur at any stage of the infection.[21] It may occur early, being either asymptomatic or in the form ofsyphilitic meningitis; or late as meningovascular syphilis, manifesting asgeneral paresis ortabes dorsalis.[3]
Meningovascular syphilis involves inflammation of the small and medium arteries of the central nervous system. It can present between 1–10 years after the initial infection. Meningovascular syphilis is characterized by stroke, cranial nerve palsies andspinal cord inflammation.[30] Late symptomatic neurosyphilis can develop decades after the original infection and includes 2 types; general paresis and tabes dorsalis. General paresis presents with dementia, personality changes, delusions, seizures, psychosis and depression.[30] Tabes dorsalis is characterized by gait instability, sharp pains in the trunk and limbs, impaired positional sensation of the limbs as well as having a positiveRomberg's sign.[30] Both tabes dorsalis and general paresis may present withArgyll Robertson pupil which are pupils that constrict when the person focuses on near objects (accommodation reflex) but do not constrict when exposed to bright light (pupillary reflex).
Congenital syphilis is that which is transmitted during pregnancy or during birth.[7] Two-thirds of syphilitic infants are born without symptoms.[7] Common symptoms that develop over the first couple of years of life includeenlargement of the liver and spleen (70%), rash (70%), fever (40%), neurosyphilis (20%), andlung inflammation (20%).[7] If untreated,late congenital syphilis may occur in 40%, includingsaddle nose deformation,Higouménakis' sign,saber shin, orClutton's joints among others.[7] Infection during pregnancy is also associated withmiscarriage.[31] The main dental defects seen in congenital syphilis are the peg-shaped, notched incisors known asHutchinson's teeth and so-calledmulberry molars (also known as Moon or Fournier molars), defective permanent molars with rounded, deformed crowns resembling amulberry.[32]
Treponema pallidum subspeciespallidum is a spiral-shaped,Gram-negative, highly mobile bacterium.[11][22] Two other human diseases are caused by relatedTreponema pallidum subspecies,yaws (subspeciespertenue) andbejel (subspeciesendemicum), and one further caused by the very closely relatedTreponema carateum,pinta.[3][33] Unlike subspeciespallidum, they do not cause neurological disease.[7] Humans are the only knownnatural reservoir for subspeciespallidum.[34] It is unable to survive more than a few days without ahost.[22] This is due to its small genome (1.14 Mbp) failing to encode the metabolic pathways necessary to make most of its macronutrients.[22] It has a slowdoubling time of greater than 30 hours.[22] The bacterium is known for its ability to evade the immune system and its invasiveness.[35]
Transmission
Syphilis is transmitted primarily by sexual contact or duringpregnancy from a mother to her baby; the bacterium is able to pass through intact mucous membranes or compromised skin.[3][34] It is thus transmissible bykissing near a lesion, as well asmanual,oral,vaginal, andanal sex.[3][36][37] Approximately 30% to 60% of those exposed to primary or secondary syphilis will get the disease.[25] Itsinfectivity is exemplified by the fact that an individualinoculated with only 57 organisms has a 50% chance of being infected.[22] Most new cases in the United States (60%) occur in men who have sex with men; and in this population 20% of syphilis cases were due to oral sex alone.[3][36] Syphilis can be transmitted byblood products, but the risk is low due to screening ofdonated blood in many countries.[3] The risk of transmission fromsharing needles appears to be limited.[3]
It is not generally possible to contract syphilis through toilet seats, daily activities, hot tubs, or sharing eating utensils or clothing.[38] This is mainly because the bacteria die very quickly outside of the body, making transmission byobjects extremely difficult.[39]
Syphilis is difficult to diagnose clinically during early infection.[22] Confirmation is either viablood tests or direct visual inspection usingdark field microscopy.[3][41] Blood tests are more commonly used, as they are easier to perform.[3] Diagnostic tests are unable to distinguish between the stages of the disease.[42]
Dark field microscopy ofserous fluid from a chancre may be used to make an immediate diagnosis.[22] Hospitals do not always have equipment or experienced staff members, and testing must be done within 10 minutes of acquiring the sample.[22] Two other tests can be carried out on a sample from the chancre:direct fluorescent antibody (DFA) andpolymerase chain reaction (PCR) tests.[22] DFA usesantibodies tagged withfluorescein, which attach to specific syphilis proteins, while PCR uses techniques to detect the presence of specific syphilisgenes.[22] These tests are not as time-sensitive, as they do not require living bacteria to make the diagnosis.[22]
Prevention
Vaccine
As of 2018[update], there is novaccine effective for prevention.[34] Several vaccines based on treponemal proteins reduce lesion development in ananimal model but research continues.[44][45]
Sex
Condom use reduces the likelihood of transmission during sex, but does not eliminate the risk.[46] TheCenters for Disease Control and Prevention (CDC) states, "Correct and consistent use of latex condoms can reduce the risk of syphilis only when the infected area or site of potential exposure is protected. However, a syphilis sore outside of the area covered by a latex condom can still allow transmission, so caution should be exercised even when using a condom."[47]
Abstinence from intimate physical contact with an infected person is effective at reducing the transmission of syphilis. The CDC states, "The surest way to avoid transmission of sexually transmitted diseases, including syphilis, is to abstain from sexual contact or to be in a long-term mutuallymonogamous relationship with a partner who has been tested and is known to be uninfected."[47]
Congenital disease
Portrait of a man affected with what is now believed to have been congenital syphilis,c. 1820[48]
Congenital syphilis in the newborn can be prevented by screening mothers during early pregnancy and treating those who are infected.[49] TheUnited States Preventive Services Task Force (USPSTF) strongly recommends universal screening of all pregnant women,[50] while theWorld Health Organization (WHO) recommends all women be tested at their first antenatal visit and again in thethird trimester.[51][52] If they are positive, it is recommended their partners also be treated.[51] Congenital syphilis is still common in the developing world, as many women do not receiveantenatal care at all, and the antenatal care others receive does not include screening.[49][53] It still occasionally occurs in the developed world, as those most likely to acquire syphilis are least likely to receive care during pregnancy.[49] Several measures to increase access to testing appear effective at reducing rates of congenital syphilis in low- to middle-income countries.[51]Point-of-care testing to detect syphilis appeared to be reliable, although more research is needed to assess its effectiveness and into improving outcomes in mothers and babies.[54]
Screening
The CDC recommends that sexually active men who have sex with men be tested at least yearly.[55] The USPSTF also recommends screening among those at high risk.[56]
Syphilis is anotifiable disease in many countries, including Canada,[57] theEuropean Union,[58] and the United States.[59] This means health care providers are required to notifypublic health authorities, which will then ideally providepartner notification to the person's partners.[60] Physicians may also encourage patients to send their partners to seek care.[61] Several strategies have been found to improve follow-up for STI testing, including email and text messaging of reminders for appointments.[62]
Treatment
Historic use of mercury
The Martyrdom of Mercury (1709), showing 18th-century hospital patients undergoing syphilis treatment.
As a form ofchemotherapy, elemental mercury had been used to treat skin diseases in Europe as early as 1363.[63] As syphilis spread, preparations of mercury were among the first medicines used to combat it. Mercury is in fact highly anti-microbial: by the 16th century it was sometimes found to be sufficient to halt development of the disease when applied to ulcers as aninunction or when inhaled as asuffumigation. It was also treated by ingestion of mercury compounds.[64] Once the disease had gained a strong foothold, however, the amounts and forms of mercury necessary to control its development exceeded the human body's ability to tolerate it, and the treatment became worse and more lethal than the disease. Nevertheless, medically directedmercury poisoning became widespread through the 17th, 18th, and 19th centuries in Europe, North America, and India.[65] Mercury salts such asmercury (II) chloride were still in prominent medical use as late as 1916, and considered effective and worthwhile treatments.[66]
Early infections
The first-line treatment for uncomplicated syphilis (primary or secondary stages) remains a single dose ofintramuscularbenzathine benzylpenicillin.[67] The bacterium is highly vulnerable to penicillin when treated early, and a treated individual is typically rendered non-infective in about 24 hours.[68]Doxycycline andtetracycline are alternative choices for those allergic to penicillin; due to the risk ofbirth defects, these are not recommended for pregnant women.[67]Resistance tomacrolides,rifampicin, andclindamycin is often present.[34]Ceftriaxone, a third-generationcephalosporinantibiotic, may be as effective as penicillin-based treatment.[3] It is recommended that a treated person avoid sex until the sores are healed.[38] In comparison to azithromycin for treatment in early infection, there is lack of strong evidence for superiority of azithromycin to benzathine penicillin G.[69]
Late infections
For neurosyphilis, due to the poor penetration of benzathine penicillin into thecentral nervous system, those affected are given large doses ofintravenouspenicillin G for a minimum of 10 days.[3][34] If a person is allergic to penicillin, ceftriaxone may be used or penicillindesensitization attempted.[3] Other late presentations may be treated with once-weekly intramuscular benzathine penicillin for three weeks.[3] Treatment at this stage solely limits further progression of the disease and has a limited effect on damage which has already occurred.[3] Serologic cure can be measured when the non-treponemal titers decline by a factor of 4 or more in 6–12 months in early syphilis or 12–24 months in late syphilis.[21]
Jarisch–Herxheimer reaction
Jarisch–Herxheimer reaction in a person with syphilis and human immunodeficiency virus[70]
One of the potential side effects of treatment is theJarisch–Herxheimer reaction.[3] It frequently starts within one hour and lasts for 24 hours, with symptoms of fever, muscle pains, headache, and afast heart rate.[3] It results from the release of pro-inflammatory cytokines by the immune system in response tolipoproteins released from rupturing syphilis bacteria.[71]
Pregnancy
Penicillin is an effective treatment for syphilis in pregnancy[72] but there is no agreement on which dose or route of delivery is most effective.[73]
In 2012, about 0.5% of adults were infected with syphilis, with 6 million new cases.[9] In 1999, it is believed to have infected 12 million additional people, with greater than 90% of cases in thedeveloping world.[34] It affects between 700,000 and 1.6 million pregnancies a year, resulting inmiscarriages,stillbirths, and congenital syphilis.[7] During 2015, it caused about 107,000 deaths, down from 202,000 in 1990.[6][10] Insub-Saharan Africa, syphilis contributes to approximately 20% ofperinatal deaths.[7] Rates are proportionally higher amongintravenous drug users, those who are infected withHIV, and men who have sex with men.[12][13][14] In the United States about 55,400 people are newly infected each year as of 2014[update].[75]African Americans accounted for almost half of all cases in 2010.[76] As of 2014, syphilis infections continue to increase in the United States.[77][78] In the United States as of 2020, rates of syphilis have increased by more than threefold; in 2018 approximately 86% of all cases of syphilis in the United States were in men.[21] In 2021, preliminary CDC data illustrated that 2,677 cases of congenital syphilis were found in the population of 332 million in the United States.[79]
Syphilis was very common in Europe during the 18th and 19th centuries.[11]Flaubert found it universal among 19th-century Egyptian prostitutes.[80] In the developed world during the early 20th century, infections declined rapidly with the widespread use ofantibiotics, until the 1980s and 1990s.[11] Since 2000, rates of syphilis have been increasing in the US, Canada, the UK, Australia and Europe, primarily among men who have sex with men.[34] Rates of syphilis among US women have remained stable during this time, while rates among UK women have increased, but at a rate less than that of men.[81] Increased rates among heterosexuals have occurred in China and Russia since the 1990s.[34] This has been attributed to unsafe sexual practices, such as sexual promiscuity, prostitution, and decreasing use of barrier protection.[34][81][82]
Left untreated, it has a mortality rate of 8% to 58%, with a greater death rate among males.[3] The symptoms of syphilis have become less severe over the 19th and 20th centuries, in part due to widespread availability of effective treatment, and partly due tovirulence of the bacteria.[23] With early treatment, few complications result.[22] Syphilis increases the risk of HIV transmission by two to five times, and coinfection is common (30–60% in some urban centers).[3][34] In 2015,Cuba became the first country to eliminate mother-to-child transmission of syphilis.[83]
Portrait ofGerard de Lairesse byRembrandt van Rijn, circa 1665–67, oil on canvas. De Lairesse, himself a painter and art theorist, had congenital syphilis that deformed his face and eventually blinded him[84]
Paleopathologists have known for decades that syphilis was present in the Americas before European contact.[85][86] The situation inAfro-Eurasia has been murkier and caused considerable debate.[87] According to the Columbian theory, syphilis was brought to Spain by the men who sailed withChristopher Columbus in 1492 and spread from there, with a serious epidemic inNaples beginning as early as 1495. Contemporaries believed the disease sprang from American roots, and in the 16th century physicians wrote extensively about the new disease inflicted on them by the returning explorers.[88]
Most evidence supports the Columbian origin hypothesis.[89] However, beginning in the 1960s, examples of probabletreponematosis—the parent disease of syphilis,bejel, andyaws—in skeletal remains shifted the opinion of some towards a "pre-Columbian" origin.[90][91] A 2024 study published inNature supported syphilis having first emerged among humans in the Americas in the mid-Holocene.[92]
When living conditions changed with urbanization, elite social groups began to practice basic hygiene and started to separate themselves from other social tiers. Consequently, treponematosis was driven out of the age group in which it had become endemic. It then began to appear in adults as syphilis. Because they had never been exposed as children, they were not able to fend off serious illness. Spreading the disease via sexual contact also led to victims being infected with a massive bacterial load from open sores on the genitalia. Adults in higher socioeconomic groups then became very sick with painful and debilitating symptoms lasting for decades. Often, they died of the disease, as did their children who were infected with congenital syphilis. The difference between rural and urban populations was first noted by Ellis Herndon Hudson, a clinician who published extensively about the prevalence of treponematosis, including syphilis, in times past.[93] The importance of bacterial load was first noted by the physician Ernest Grin in 1952 in his study of syphilis in Bosnia.[94]
The most compelling evidence for the validity of the pre-Columbian hypothesis is the presence of syphilitic-like damage to bones and teeth in medieval skeletal remains. While the absolute number of cases is not large, new ones are continually discovered, most recently in 2015.[95] 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. In several of the twenty-one cases the evidence may also indicate syphilis.[96]
In 2020, a group of leading paleopathologists concluded that enough evidence had been collected to prove that treponemal disease, almost certainly including syphilis, had existed in Europe prior to the voyages of Columbus.[97] There is an outstanding issue, however. Damaged teeth and bones may seem to hold proof of pre-Columbian syphilis, but there is a possibility that they point to an endemic form of treponemal disease instead. As syphilis, bejel, and yaws vary considerably in mortality rates and the level of human disease 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. (The fourth of the treponemal diseases ispinta, a skin disease and therefore unrecoverable through paleopathology.) AncientDNA (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 differentiatespirochetes that are 99.8 percent identical with absolute accuracy.[98] Progress on uncovering the historical extent of syndromes through aDNA remains slow, however, because the bacterium responsible for treponematosis is rare in skeletal remains and fragile, making it notoriously difficult to recover and analyse. Precise dating to the medieval period is not yet possible but work by Kettu Majander et al. uncovering 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.[99]
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 medieval period. Evidence from art is therefore helpful in settling the issue. Research by Marylynn Salmon has demonstrated that deformities in medieval subjects can be identified by comparing them to those of modern victims of syphilis in medical drawings and photographs.[100] One of the most typical deformities, for example, is a collapsed nasal bridge calledsaddle nose. Salmon discovered that it appeared often inmedieval illuminations, especially among the men tormenting Christ in scenes of the crucifixion. The association of saddle nose with evil is an indication that the artists were thinking of syphilis, which is typically transmitted through sexual intercourse with promiscuous partners, a mortal sin in medieval times.
It remains mysterious why the authors of medieval medical treatises so uniformly refrained from describing syphilis or commenting on its existence in the population. Many may have confused it with other diseases such as leprosy (Hansen's disease) orelephantiasis. The great variety of symptoms of treponematosis, the different ages at which the various diseases appear, 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. In addition, evidence indicates that some writers on disease feared the political implications of discussing a condition more fatal to elites than to commoners. Historian Jon Arrizabalaga has investigated this question forCastile with startling results revealing an effort to hide its association with elites.[101]
The first written records of an outbreak of syphilis in Europe occurred in 1495 inNaples, Italy, during a French invasion (Italian War of 1494–1495).[11][42] Since it was claimed to have been spread by French troops, it was initially called the "French disease" by the people of Naples.[102] The disease reachedLondon in 1497 and was recorded at St Bartholomew's Hospital as infecting 10 out of the 20 patients.[103][full citation needed] In 1530, the pastoral name "syphilis" (the name of a character) was first used by the Italian physician and poetGirolamo Fracastoro as the title of hisLatin poem indactylic hexameter,Syphilis sive morbus gallicus (Syphilis or The French Disease), describing the ravages of the disease in Italy.[104][105] In Great Britain it was also called the "Great Pox".[106][107]
In the 16th through 19th centuries, syphilis was one of the largest public health burdens inprevalence, symptoms, and disability,[108]: 208–209 [109] although records of its true prevalence were generally not kept because of the fearsome and sordid status ofsexually transmitted infections in those centuries.[108]: 208–209 According to a 2020 study, more than 20% of individuals in the age range 15–34 years in late 18th-century London were treated for syphilis.[110] At the time thecausative agent was unknown but it was well known that it was spread sexually and also often from mother to child. Its association with sex, especiallysexual promiscuity andprostitution, made it an object of fear and revulsion and a taboo. The magnitude of its morbidity and mortality in those centuries reflected that, unlike today, there was no adequate understanding of itspathogenesis and no truly effective treatments. Its damage was caused not so much by great sickness or death early in the course of the disease but rather by its gruesome effects decades after infection as it progressed toneurosyphilis withtabes dorsalis.Mercury compounds and isolation were commonly used, with treatments often worse than the disease.[106]
During the 20th century, as bothmicrobiology andpharmacology advanced greatly, syphilis, like many other infectious diseases, became more of a manageable burden than a scary and disfiguring mystery, at least indeveloped countries among those people who could afford to pay for timely diagnosis and treatment. Penicillin was discovered in 1928, and effectiveness of treatment withpenicillin was confirmed in trials in 1943,[106] at which time it became the main treatment.[113]
The Flemish artistStradanus designed a print calledPreparation and Use ofGuayaco for Treating Syphilis, a scene of a wealthy man receiving treatment for syphilis with the tropical woodguaiacum sometime around 1590.[120]
The "Tuskegee Study of Untreated Syphilis in the Negro Male" was an infamous, unethical and racistclinical study conducted between 1932 and 1972 by theU.S. Public Health Service.[121][122] Whereas the purpose of this study was to observe thenatural history of untreated syphilis, the African-American men in the study were told they were receiving free treatment for "bad blood" from the United States government.[123]
The Public Health Service started working on this study in 1932 in collaboration withTuskegee University, ahistorically black college in Alabama. Researchers enrolled 600 poor, African Americansharecroppers fromMacon County,Alabama in the study. Of these men, 399 had contracted syphilis before the study began, and 201 did not have the disease.[122] Medical care, hot meals and free burial insurance were given to those who participated. The men were told that the study would last six months, but in the end, it continued for 40 years.[122] After funding for treatment was lost, the study was continued without informing the men that they were only being studied and would not be treated. Facing insufficient participation, the Macon County Health Department nevertheless wrote to subjects to offer them a "last chance" to get a special "treatment", which was not a treatment at all, but a spinal tap administered exclusively for diagnostic purposes.[121] None of the men infected were ever told that they had the disease, and none were treated withpenicillin even after the antibiotic had been proven to successfully treat syphilis. According to theCenters for Disease Control, the men were told they were being treated for "bad blood"—a colloquialism describing various conditions such as fatigue,anemia and syphilis—which was a leading cause of death among southern African American men.[122]
Preparation and Use of Guayaco for Treating Syphilis, afterStradanus, 1590
The 40-year study became a textbook example of criminally negligentmedical ethics because researchers had knowingly withheld treatment withpenicillin and because the subjects had been misled concerning the purposes of the study. The revelation in 1972 of these study failures by awhistleblower,Peter Buxtun, led to major changes in U.S. law and regulation on the protection of participants in clinical studies. Now studies requireinformed consent,[124] communication ofdiagnosis, and accurate reporting of test results.[125]
Similar experiments were carried out inGuatemala from 1946 to 1948. It was done during the administration of American PresidentHarry S. Truman and Guatemalan PresidentJuan José Arévalo with the cooperation of some Guatemalan health ministries and officials.[126] Doctors infected soldiers, prostitutes, prisoners andmental patients with syphilis and othersexually transmitted infections, without theinformed consent of the subjects and treated most subjects withantibiotics. The experiment resulted in at least 83 deaths.[127][128] In October 2010, the U.S. formally apologized to Guatemala for the ethical violations that took place. Secretary of StateHillary Clinton and Health and Human Services SecretaryKathleen Sebelius stated "Although these events occurred more than 64 years ago, we are outraged that such reprehensible research could have occurred under the guise of public health. We deeply regret that it happened, and we apologize to all the individuals who were affected by such abhorrent research practices."[129] The experiments were led by physicianJohn Charles Cutler who also participated in the late stages of the Tuskegee syphilis experiment.[130]
Names
Syphilis was first calledgrande verole or the "great pox" by the French. Other historical names have included "button scurvy", sibbens, frenga, and dichuchwa, among others.[131][132] Since it was a disgraceful disease, the disease was known in several countries by the name of their neighbouring, often hostile country.[113] The English, the Germans, and the Italians called it "the French disease", while the French referred to it as the "Neapolitan disease". The Dutch called it the "Spanish/Castilian disease".[113] To the Turks it was known as the "Christian disease", whilst in India, the Hindus and Muslims named the disease after each other.[113]
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^Viñals-Iglesias H, Chimenos-Küstner, E (1 September 2009). "The reappearance of a forgotten disease in the oral cavity: syphilis".Medicina Oral, Patologia Oral y Cirugia Bucal.14 (9): e416–20.PMID19415060.
^abCenter for Disease Control and Prevention (CDC)."Syphilis-CDC fact sheet".CDC.Archived from the original on 25 February 2015. Retrieved1 March 2015.
^Francis Steegmuller (1979).Flaubert in Egypt, A Sensibility on Tour. Chicago Review Press, Incorporated.ISBN978-0-89733-018-3.
^abKent ME, Romanelli, F (February 2008). "Reexamining syphilis: an update on epidemiology, clinical manifestations, and management".Annals of Pharmacotherapy.42 (2):226–36.doi:10.1345/aph.1K086.PMID18212261.S2CID23899851.
^Baker, B. J. and Armelagos, G. J., (1988) "The origin and antiquity of syphilis: Paleopathological diagnosis and interpretation".Current Anthropology, 29, 703–738.https://doi.org/10.1086/203691. Powell, M. L. & Cook, D. C. (2005)The Myth of Syphilis: The natural history of treponematosis in North America. Gainesville, FL: University Press of Florida. Williams, H. (1932) "The origin and antiquity of syphilis: The evidence from diseased bones, a review, with some new material from America".Archives of Pathology, 13: 779–814, 931–983.1932).
^Dutour, O., et al. (Eds.). (1994). L'origine de la syphilis in Europe: avant ou après 1493? Paris, France: Éditions Errance. Baker, B. J. et al. (2020) "Advancing the Understanding of Treponemal Disease in the Past and Present".Yearbook of Physical Anthropology 171: 5–41.doi: 10.1002/ajpa.23988. 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.https://doi.org/10.1002/ajpa.21613.
^For an introduction to this literature see Quétel, C. (1990).History of Syphilis. Baltimore, MD: The Johns Hopkins University Press.
^Early work includes Henneberg, M., & Henneberg, R. J. (1994), "Treponematosis in an ancient Greek colony of Metaponto, southern Italy, 580-250 BCE" and Roberts, C. A. (1994), "Treponematosis in Gloucester, England: A theoretical and practical approach to the Pre-Columbian theory". Both in O. Dutour, et al. (Eds.),L'origine de la syphilis in Europe: avant ou après 1493? (pp. 92-98; 101–108). Paris, France: Éditions Errance.
^Hudson, E. H. (1946). "A unitarian view of treponematosis".American Journal of Tropical Medicine and Hygiene, 26 (1946), 135–139.https://doi.org/10.4269/ajtmh.1946.s1-26.135; "The treponematoses—or treponematosis?"The British Journal of Venereal Diseases, 34 (1958), 22–23; "Historical approach to the terminology of syphilis".Archives of Dermatology, 84 (1961), 545–562; "Treponematosis and man's social evolution".American Anthropologist, 67(4), 885–901.doi:10.1001/archderm.1961.01580160009002. On status see also Marylynn Salmon,Medieval Syphilis and Treponemal Disease (Leeds: Arc Humanities Press), 8, 30-33.
^Grin, E. I. (1952) "Endemic Treponematosis in Bosnia: Clinical and epidemiological observations on a successful mass-treatment campaign".Bulletin of the World Health Organization, 7: 11-25.
^Walker, D., Powers, N., Connell, B., & Redfern, R. (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".American Journal of Physical Anthropology, 156, 90–101.https://doi.org/10.1002/ajpa.22630 and Gaul, J.S., Grossschmidt, K., Budenbauer, C., & Kanz, Fabian (2015). "A probable case of congenital syphilis from pre-Columbian Austria".Anthropologischer Anzeiger, 72, 451–472.DOI: 10.1127/anthranz/2015/0504.
^They include Henneberg, M., & Henneberg, R. J. (1994). "Treponematosis in an ancient Greek colony of Metaponto, southern Italy, 580-250 BCE". In O. Dutour, et al. (Eds.),L'origine de la syphilis in Europe: Avant ou après 1493? (pp. 92–98). Paris, France: Éditions Errance. Stirland, Ann. "Evidence for Pre-Columbian Treponematosis in Europe". In Dutour, O., Pálfi, G., Bérato, J., & Brun, J. -P. (Eds.). (1994).L'origine de la syphilis in Europe: avant ou après 1493? Paris, France: Éditions Errance, andCriminals and Paupers: The Graveyard of St. Margaret Fyebriggate in combusto, Norwich. With Contributions from Brian Ayers and Jayne Brown. East Anglian Archaeology 129. Dereham: Historic Environment, Norfolk Museums and Archaeology Service, 2009. Erdal, Y. S. (2006). "A pre-Columbian case of congenital syphilis from Anatolia (Nicaea, 13th century AD)".International Journal of Osteoarchaeology, 16, 16–33.https://doi.org/10.1002/oa.802. Cole G. and T. Waldron, "Apple Down 152: a putative case of syphilis from sixth century AD Anglo-Saxon England".American Journal of Physical Anthropology 2011 Jan;144(1):72-9.doi: 10.1002/ajpa.21371. Epub 2010 Aug 18. PMID 20721939. Roberts, C. A. (1994). "Treponematosis in Gloucester, England: A theoretical and practical approach to the Pre-Columbian theory". In O. Dutour, et al. (Eds.),L'origine de la syphilis in Europe: avant ou après 1493? (pp. 101–108). Paris, France: Éditions Errance.
^Baker, B.J. et al. (2020) "Advancing the Understanding of Treponemal Disease in the Past and Present".Yearbook of Physical Anthropology 171: 5–41.doi: 10.1002/ajpa.23988.
^Fraser, C. M., Norris, S. J., Weinstock, G. M., White, O., Sutton, G. G., Dodson, R., ... Venter, J. C. (1998). "Complete genome sequence ofTreponema pallidum, the syphilis spirochete".Science, 281(5375), 375–388.https://doi.org/10.1371/journal.pntd.0001832. Čejková, D., Zobaníková, M., Chen, L., Pospíšilová, P., Strouhal, M., Qin, X., ... Šmajs, D. (2012). "Whole genome sequences of threeTreponema pallidum ssp.pertenue strains: yaws and syphilis treponemes differ in less than 0.2% of the genome sequence".PLoS Neglected Tropical Diseases, 6(1), e1471.doi: 10.1371/journal.pone.0015713. Mikalová, L., Strouhal, M., Čejková, D.,Zobaníková, M., Pospíšilová, P., Norris, S. J., ... Šmajs, D. (2010). "Genome analysis ofTreponema pallidum subsp.pallidum and subsp.pertenue strains: Most of the genetic differences are localized in six regions".PLoS ONE, 5, e15713. doi.org/10.1371/journal.pone.0015713. Štaudová, B., Strouhal, M., Zobaníková, M., Čejková, D., Fulton, L. L., Chen, L., ... Šmajs, D. (2014). "Whole genome sequence of theTreponema pallidum subsp.endemicum strain Bosnia A: The genome is related to yaws treponemes but contains few loci similar to syphilis treponemes".PLoS Neglected Tropical Diseases, 8(11), e3261.https://doi.org/10.1371/journal.pntd.0003261.
^Majander, K., Pfrengle S., Kocher, A., ..., Kühnert, J. K., Schuenemann, V. J. (2020), "Ancient Bacterial Genomes Reveal a High Diversity ofTreponema pallidum Strains in Early Modern Europe".Current Biology 30, 3788–3803. Elsevier Inc.doi: 10.1016/j.cub.2020.07.058.
^See her Medieval Syphilis and Treponemal Disease (Leeds: Arc Humanities Press, 2022), 61-79.
^Arrizabalaga, Jon. "The Changing Identity of the French Pox in Early Renaissance Castile". InBetween Text and Patient: The Medical Enterprise in Medieval and Early Modern Europe, edited by Florence Eliza Glaze and Brian K. Nance, 397–417. Florence: SISMEL, 2011.
^Grafton A (March 1995). "Drugs and Diseases: New World Biology and Old World Learning".New Worlds, Ancient Texts The Power of Tradition and the Shock of Discovery. Harvard University Press. pp. 159–194.ISBN978-0-674-61876-3.
^Rayment M, Sullivan AK (April 2011)."'He who knows syphilis knows medicine'—the return of an old friend". Editorials.British Journal of Cardiology.18:56–58.Archived from the original on 7 August 2020. Retrieved7 April 2018.'He who knows syphilis knows medicine' said Father of Modern Medicine, Sir William Osler, at the turn of the 20th Century. So common was syphilis in days gone by, all physicians were attuned to its myriad clinical presentations. Indeed, the 19th century saw the development of an entire medical subspecialty – syphilology – devoted to the study of the great imitator,Treponema pallidum.
^Halioua B (30 June 2003)."Comment la syphilis emporta Maupassant" [How syphilis took Maupassant].La Revue du Praticien (in French).Archived from the original on 2 June 2016. Retrieved29 November 2016.
^Reverby SM (2009).Examining Tuskegee: the infamous syphilis study and its legacy. Chapel Hill: University of North Carolina Press.ISBN978-0-8078-3310-0.OCLC496114416.
^Tagarelli A, Lagonia P, Tagarelli G, Quattrone A, Piro A (April 2011). "The relation between the names and designations of syphilis in the 16th century and its clinical gravity".Sexually Transmitted Infections.87 (3): 247.doi:10.1136/sti.2010.048405.PMID21325442.S2CID19185641.
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