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Treponema pallidum.jpg
Electron micrograph of Treponema pallidum
Specialty Infectious disease
Symptoms Firm, painless, non-itchy skin ulcer [1]
CausesTreponema pallidum usually spread by sex [1]
Diagnostic method Blood tests, dark field microscopy of infected fluid [1] [2]
Differential diagnosis Many other diseases [1]
Prevention Condoms, Long-term monogamous relationships [1]
Treatment Antibiotics [3]
Frequency45.4 million / 0.6% (2015) [4]
Deaths107,000 (2015) [5]

Syphilis is a sexually transmitted infection caused by the bacterium Treponema pallidum subspecies pallidum. [3] The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, and tertiary). [1] The primary stage classically presents with a single chancre (a firm, painless, non-itchy skin ulceration usually between 1 cm and 2 cm in diameter) though there may be multiple sores. [1] In secondary syphilis, a diffuse rash occurs, which frequently involves the palms of the hands and soles of the feet. [1] There may also be sores in the mouth or vagina. [1] In latent syphilis, which can last for years, there are few or no symptoms. [1] In tertiary syphilis, there are gummas (soft, non-cancerous growths), neurological problems, or heart symptoms. [2] Syphilis has been known as "the great imitator" as it may cause symptoms similar to many other diseases. [1] [2]


Syphilis is most commonly spread through sexual activity. [1] It may also be transmitted from mother to baby during pregnancy or at birth, resulting in congenital syphilis. [1] [6] Other diseases caused by Treponema bacteria include yaws ( T. pallidum subspecies pertenue), pinta ( T. carateum ), and nonvenereal endemic syphilis (T. pallidum subspecies endemicum). [2] These three diseases are not typically sexually transmitted. [7] Diagnosis is usually made by using blood tests; the bacteria can also be detected using dark field microscopy. [1] The Centers for Disease Control and Prevention (U.S.) recommend all pregnant women be tested. [1]

The risk of sexual transmission of syphilis can be reduced by using a latex or polyurethane condom. [1] Syphilis can be effectively treated with antibiotics. [3] The preferred antibiotic for most cases is benzathine benzylpenicillin injected into a muscle. [3] In those who have a severe penicillin allergy, doxycycline or tetracycline may be used. [3] In those with neurosyphilis, intravenous benzylpenicillin or ceftriaxone is recommended. [3] During treatment people may develop fever, headache, and muscle pains, a reaction known as Jarisch–Herxheimer. [3]

In 2015, about 45.4 million people had syphilis infections, [4] of which six million were new cases. [8] During 2015, it caused about 107,000 deaths, down from 202,000 in 1990. [5] [9] 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 with human immunodeficiency virus (HIV). [2] [10] This is believed to be partly due to increased promiscuity, prostitution, decreasing use of condoms and unsafe sexual practices among men who have sex with men. [11] [12] [13]

Signs and symptoms

Syphilis can present in one of four different stages: primary, secondary, latent, and tertiary, [2] and may also occur congenitally. [14] It was referred to as "the great imitator" by Sir William Osler due to its varied presentations. [2] [15] [16]


Primary chancre of syphilis at the site of infection on the penis Chancres on the penile shaft due to a primary syphilitic infection caused by Treponema pallidum 6803 lores.jpg
Primary chancre of syphilis at the site of infection on the penis

Primary syphilis is typically acquired by direct sexual contact with the infectious lesions of another person. [17] Approximately 2–6 weeks after contact (with a range of 10–90 days) a skin lesion, called a chancre, appears at the site and this contains infectious spirochetes. [18] [19] This is classically (40% of the time) a single, firm, painless, non-itchy skin ulceration with a clean base and sharp borders approximately 0.3–3.0 cm in size. [2] The lesion may take on almost any form. [20] In the classic form, it evolves from a macule to a papule and finally to an erosion or ulcer. [20] Occasionally, multiple lesions may be present (~40%), [2] with multiple lesions being more common when coinfected with HIV. [20] Lesions may be painful or tender (30%), and they may occur in places other than the genitals (2–7%). [20] The most common location in women is the cervix (44%), the penis in heterosexual men (99%), and anally and rectally in men who have sex with men (34%). [20] Lymph node enlargement frequently (80%) occurs around the area of infection, [2] occurring seven to 10 days after chancre formation. [20] The lesion may persist for three to six weeks if left untreated. [2]


Typical presentation of secondary syphilis with a rash on the palms of the hands Secondary Syphilis on palms CDC 6809 lores.rsh.jpg
Typical presentation of secondary syphilis with a rash on the palms of the hands
Reddish papules and nodules over much of the body due to secondary syphilis 2ndsyphil2.jpg
Reddish papules and nodules over much of the body due to secondary syphilis

Secondary syphilis occurs approximately four to ten weeks after the primary infection. [2] While secondary disease is known for the many different ways it can manifest, symptoms most commonly involve the skin, mucous membranes, and lymph nodes. [21] There may be a symmetrical, reddish-pink, non-itchy rash on the trunk and extremities, including the palms and soles. [2] [22] The rash may become maculopapular or pustular. [2] It may form flat, broad, whitish, wart-like lesions on mucous membranes, known as condyloma latum. [2] All of these lesions harbor bacteria and are infectious. [2] Other symptoms may include fever, sore throat, malaise, weight loss, hair loss, and headache. [2] Rare manifestations include liver inflammation, kidney disease, joint inflammation, periostitis, inflammation of the optic nerve, uveitis, and interstitial keratitis. [2] [23] The acute symptoms usually resolve after three to six weeks; [23] about 25% of people may present with a recurrence of secondary symptoms. [21] [24] 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. [21]


Latent syphilis is defined as having serologic proof of infection without symptoms of disease. [17] It develops after secondary syphilis and is divided into early latent and late latent stages. [25] Early latent syphilis is defined by the World Health Organization as less than 2 years after original infection. [25] Early latent syphilis is infectious as up to 25% of people can develop a recurrent secondary infection (during which spirochetes are actively replicating and are infectious). [25] Two years after the original infection the person will enter late latent syphilis and is not as infectious as the early phase. [23] [26] The latent phase of syphilis can last many years after which, without treatment, approximately 15-40% of people can develop tertiary syphilis. [27]


Model of a head of a person with tertiary (gummatous) syphilis, Musee de l'Homme, Paris Tertiary syphilis head.JPG
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%), late neurosyphilis (6.5%), and cardiovascular syphilis (10%). [2] [23] Without treatment, a third of infected people develop tertiary disease. [23] People with tertiary syphilis are not infectious. [2]

Gummatous syphilis or late benign syphilis usually occurs 1 to 46 years after the initial infection, with an average of 15 years. [2] This stage is characterized by the formation of chronic gummas, which are soft, tumor-like balls of inflammation which may vary considerably in size. [2] They typically affect the skin, bone, and liver, but can occur anywhere. [2]

Cardiovascular syphilis usually occurs 10–30 years after the initial infection. [2] The most common complication is syphilitic aortitis, which may result in aortic aneurysm formation. [2]

Neurosyphilis refers to an infection involving the central nervous system. Involvement of the central nervous system in syphilis (either asymptomatic or symptomatic) can occur at any stage of the infection. [19] It may occur early, being either asymptomatic or in the form of syphilitic meningitis, or late as meningovascular syphilis, general paresis, or tabes dorsalis. [2]

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 and spinal cord inflammation. [28] 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. [28] 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 positive Romberg's sign. [28] Both tabes dorsalis and general paresis may present with Argyll 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. [6] Two-thirds of syphilitic infants are born without symptoms. [6] Common symptoms that develop over the first couple of years of life include enlargement of the liver and spleen (70%), rash (70%), fever (40%), neurosyphilis (20%), and lung inflammation (20%). [6] If untreated, late congenital syphilis may occur in 40%, including saddle nose deformation, Higouménakis' sign, saber shin, or Clutton's joints among others. [6] Infection during pregnancy is also associated with miscarriage. [29] The three main dental defects in congenital syphilis are Hutchinson's incisors (screwdriver shaped incisors), Moon's molars or bud molars, and Fournier's molars or mulberry molars (molars with abnormal occlusal anatomy resembling a mulberry). [30]



Histopathology of Treponema pallidum spirochetes using a modified Steiner silver stain Treponema pallidum 01.png
Histopathology of Treponema pallidum spirochetes using a modified Steiner silver stain

Treponema pallidum subspecies pallidum is a spiral-shaped, Gram-negative, highly mobile bacterium. [10] [20] Three other human diseases are caused by related Treponema pallidum subspecies, including yaws (subspecies pertenue), pinta (subspecies carateum) and bejel (subspecies endemicum). [2] Unlike subspecies pallidum, they do not cause neurological disease. [6] Humans are the only known natural reservoir for subspecies pallidum. [14] It is unable to survive more than a few days without a host. [20] This is due to its small genome (1.14Mbp) failing to encode the metabolic pathways necessary to make most of its macronutrients. [20] It has a slow doubling time of greater than 30 hours. [20] The bacterium is known for its ability to evade the immune system and its invasiveness. [31]


Syphilis is transmitted primarily by sexual contact or during pregnancy from a mother to her baby; the spirochete is able to pass through intact mucous membranes or compromised skin. [2] [14] It is thus transmissible by kissing near a lesion, as well as oral, vaginal, and anal sex. [2] [32] Approximately 30% to 60% of those exposed to primary or secondary syphilis will get the disease. [23] Its infectivity is exemplified by the fact that an individual inoculated with only 57 organisms has a 50% chance of being infected. [20] 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. [2] [32] Syphilis can be transmitted by blood products, but the risk is low due to screening of donated blood in many countries. [2] The risk of transmission from sharing needles appears to be limited. [2]

It is not generally possible to contract syphilis through toilet seats, daily activities, hot tubs, or sharing eating utensils or clothing. [33] This is mainly because the bacteria die very quickly outside of the body, making transmission by objects extremely difficult. [34]


This poster acknowledges the social stigma of syphilis, while urging those who possibly have the disease to be tested (circa 1936). Syphilis false shame and fear may destroy your future.png
This poster acknowledges the social stigma of syphilis, while urging those who possibly have the disease to be tested (circa 1936).
Micrograph of secondary syphilis skin lesions. (A/B) H&E stain of SS lesions. (C/D) IHC staining reveals abundant spirochetes embedded within a mixed cellular inflammatory infiltrate (shown in the red box) in the papillary dermis. The blue arrow points to a tissue histiocyte and the read arrows to two dermal lymphocytes. Micrograph of secondary syphilis.jpg
Micrograph of secondary syphilis skin lesions. (A/B) H&E stain of SS lesions. (C/D) IHC staining reveals abundant spirochetes embedded within a mixed cellular inflammatory infiltrate (shown in the red box) in the papillary dermis. The blue arrow points to a tissue histiocyte and the read arrows to two dermal lymphocytes.

Syphilis is difficult to diagnose clinically during early infection. [20] Confirmation is either via blood tests or direct visual inspection using dark field microscopy. [2] [36] Blood tests are more commonly used, as they are easier to perform. [2] Diagnostic tests are unable to distinguish between the stages of the disease. [37]

Blood tests

Blood tests are divided into nontreponemal and treponemal tests. [20]

Nontreponemal tests are used initially, and include venereal disease research laboratory (VDRL) and rapid plasma reagin (RPR) tests. False positives on the nontreponemal tests can occur with some viral infections, such as varicella (chickenpox) and measles. False positives can also occur with lymphoma, tuberculosis, malaria, endocarditis, connective tissue disease, and pregnancy. [17]

Because of the possibility of false positives with nontreponemal tests, confirmation is required with a treponemal test, such as treponemal pallidum particle agglutination (TPHA) or fluorescent treponemal antibody absorption test (FTA-Abs). [2] Treponemal antibody tests usually become positive two to five weeks after the initial infection. [20] Neurosyphilis is diagnosed by finding high numbers of leukocytes (predominately lymphocytes) and high protein levels in the cerebrospinal fluid in the setting of a known syphilis infection. [2] [17]

Direct testing

Dark field microscopy of serous fluid from a chancre may be used to make an immediate diagnosis. [20] Hospitals do not always have equipment or experienced staff members, and testing must be done within 10 minutes of acquiring the sample. [20] Two other tests can be carried out on a sample from the chancre: direct fluorescent antibody (DFA) and polymerase chain reaction (PCR) tests. [20] DFA uses antibodies tagged with fluorescein, which attach to specific syphilis proteins, while PCR uses techniques to detect the presence of specific syphilis genes. [20] These tests are not as time-sensitive, as they do not require living bacteria to make the diagnosis. [20]



As of 2018, there is no vaccine effective for prevention. [14] Several vaccines based on treponemal proteins reduce lesion development in an animal model but research continues. [38] [39]


Condom use reduces the likelihood of transmission during sex, but does not eliminate the risk. [40] The Centers 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. [41] 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." [42]

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 mutually monogamous relationship with a partner who has been tested and is known to be uninfected." [42]

Congenital disease

Portrait of Mr. J. Kay, affected with what is now believed to have been congenital syphilis c. 1820 Portrait of Mr. J. Kay, afflicted with a rodent disease. Unknown artist, c. 1820 CE. The Wellcome Collection, London.jpg
Portrait of Mr. J. Kay, affected with what is now believed to have been congenital syphilis c. 1820

Congenital syphilis in the newborn can be prevented by screening mothers during early pregnancy and treating those who are infected. [44] The United States Preventive Services Task Force (USPSTF) strongly recommends universal screening of all pregnant women, [45] while the World Health Organization (WHO) recommends all women be tested at their first antenatal visit and again in the third trimester. [46] [47] If they are positive, it is recommended their partners also be treated. [46] Congenital syphilis is still common in the developing world, as many women do not receive antenatal care at all, and the antenatal care others receive does not include screening. [44] [48] It still occasionally occurs in the developed world, as those most likely to acquire syphilis are least likely to receive care during pregnancy. [44] Several measures to increase access to testing appear effective at reducing rates of congenital syphilis in low- to middle-income countries. [46] 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. [49]


The CDC recommends that sexually active men who have sex with men be tested at least yearly. [50] The USPSTF also recommends screening among those at high risk. [51]

Syphilis is a notifiable disease in many countries, including Canada, [52] the European Union, [53] and the United States. [54] This means health care providers are required to notify public health authorities, which will then ideally provide partner notification to the person's partners. [55] Physicians may also encourage patients to send their partners to seek care. [56] Several strategies have been found to improve follow-up for STI testing, including email and text messaging of reminders for appointments. [57]


As a form of chemotherapy, elemental mercury was frequently used to treat syphilis in Europe very early on in the epidemic, and in this respect was rather effective. Mercury is highly anti-microbial, and in the early stages of infection was sometimes sufficient in halting development of the disease when applied to cankers or other wounds. Once the bacterium gained a strong foothold, however, the amounts and forms of mercury necessary to control its development exceeded the human ability to endure this extremely toxic metal, and the treatment became worse and more lethal than the disease. Medically directed mercury poisoning also became widespread, and thousands died in desperate attempts to rid themselves of the excruciating, disfiguring, and humiliating illness. [58]

Early infections

The first-line treatment for uncomplicated syphilis (primary or secondary stages) remains a single dose of intramuscular benzathine benzylpenicillin. [59] Doxycycline and tetracycline are alternative choices for those allergic to penicillin; due to the risk of birth defects, these are not recommended for pregnant women. [59] Resistance to macrolides, rifampicin, and clindamycin is often present. [14] Ceftriaxone, a third-generation cephalosporin antibiotic, may be as effective as penicillin-based treatment. [2] It is recommended that a treated person avoid sex until the sores are healed. [33]

Late infections

For neurosyphilis, due to the poor penetration of benzathine penicillin into the central nervous system, those affected are given large doses of intravenous penicillin G for a minimum of 10 days. [2] [14] If a person is allergic to penicillin, ceftriaxone may be used or penicillin desensitization attempted. [2] Other late presentations may be treated with once-weekly intramuscular benzathine penicillin for three weeks. [2] Treatment at this stage solely limits further progression of the disease and has a limited effect on damage which has already occurred. [2] 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. [19]

Jarisch–Herxheimer reaction

Jarisch-Herxheimer reaction in a person with syphilis and human immunodeficiency virus Jarisch-Herxheimer reaction in patient (cropped).jpg
Jarisch–Herxheimer reaction in a person with syphilis and human immunodeficiency virus

One of the potential side effects of treatment is the Jarisch–Herxheimer reaction. [2] It frequently starts within one hour and lasts for 24 hours, with symptoms of fever, muscle pains, headache, and a fast heart rate. [2] It is caused by cytokines released by the immune system in response to lipoproteins released from rupturing syphilis bacteria. [61]


Penicillin is an effective treatment for syphilis in pregnancy [62] but there is no agreement on which dose or route of delivery is most effective. [63]


Syphilis deaths per million persons in 2012
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58-138 Syphilis world map-Deaths per million persons-WHO2012.svg
Syphilis deaths per million persons in 2012
Age-standardized disability adjusted life years from syphilis per 100,000 inhabitants in 2004
no data
>500 Syphilis world map - DALY - WHO2004.svg
Age-standardized disability adjusted life years from syphilis per 100,000 inhabitants in 2004

In 2012, about 0.5% of adults were infected with syphilis, with 6 million new cases. [8] In 1999, it is believed to have infected 12 million additional people, with greater than 90% of cases in the developing world. [14] It affects between 700,000 and 1.6 million pregnancies a year, resulting in spontaneous abortions, stillbirths, and congenital syphilis. [6] During 2015, it caused about 107,000 deaths, down from 202,000 in 1990. [5] [9] In sub-Saharan Africa, syphilis contributes to approximately 20% of perinatal deaths. [6] Rates are proportionally higher among intravenous drug users, those who are infected with HIV, and men who have sex with men. [11] [12] [13] In the United States about 55,400 people are newly infected each year. [65] 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. [19] African Americans accounted for almost half of all cases in 2010. [66] As of 2014, syphilis infections continue to increase in the United States. [67] [68]

Syphilis was very common in Europe during the 18th and 19th centuries. [10] Flaubert found it universal among nineteenth-century Egyptian prostitutes. [69] In the developed world during the early 20th century, infections declined rapidly with the widespread use of antibiotics, until the 1980s and 1990s. [10] 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. [14] 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. [70] Increased rates among heterosexuals have occurred in China and Russia since the 1990s. [14] This has been attributed to unsafe sexual practices, such as sexual promiscuity, prostitution, and decreasing use of barrier protection. [14] [70] [71]

Left untreated, it has a mortality rate of 8% to 58%, with a greater death rate among males. [2] 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 to virulence of the bacteria. [21] With early treatment, few complications result. [20] Syphilis increases the risk of HIV transmission by two to five times, and coinfection is common (30–60% in some urban centers). [2] [14] In 2015, Cuba became the first country to eliminate mother-to-child transmission of syphilis. [72]


Portrait of Gerard de Lairesse by Rembrandt 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. Rembrandt Harmensz. van Rijn 095.jpg
Portrait of Gerard de Lairesse by Rembrandt 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.

The origin of syphilis is disputed. [2] Syphilis was present in the Americas before European contact, [74] and it may have been carried from the Americas to Europe by the returning crewmen from Christopher Columbus's voyage to the Americas, or it may have existed in Europe previously but gone unrecognized until shortly after Columbus's return. [37] [75] These are the Columbian and pre-Columbian hypotheses, respectively. The Columbian hypothesis is better supported by the evidence [37] [76] [77] and findings from phylogenetic science suggest that it is, in fact, a New World disease. [78]

The timing of the arrival of syphilis in Europe certainly supports the above theory, Columbus having journeyed in 1492. The first written records of an outbreak of syphilis in Europe occurred in 1494 or 1495 in Naples, Italy, during a French invasion (Italian War of 1494–98). [10] [37] Since it was claimed to have been spread by French troops, it was initially called the "French disease" by the people of Naples. [79] The disease reached London in 1497 and was recorded at St Batholomew's Hospital as infected 10 out of the 20 patients. [80] In 1530, the pastoral name "syphilis" (the name of a character) was first used by the Italian physician and poet Girolamo Fracastoro as the title of his Latin poem in dactylic hexameter Syphilis sive morbus gallicus (Syphilis or The French Disease) describing the ravages of the disease in Italy. [81] [82] In Great Britain it was also called the "Great Pox". [83] [84]

In the 16th through 19th centuries, syphilis was one of the largest public health burdens in prevalence, symptoms, and disability, [85] :208–209 [86] although records of its true prevalence were generally not kept because of the fearsome and sordid status of sexually transmitted infections in those centuries. [85] :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. [87] At the time the causative agent was unknown but it was well known that it was spread sexually and also often from mother to child. Its association with sex, especially sexual promiscuity and prostitution, 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 its pathogenesis 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 to neurosyphilis with tabes dorsalis. Mercury compounds and isolation were commonly used, with treatments often worse than the disease. [83]

There is some evidence to suggest that syphilis was a common childhood skin disease in the Old World, and did not originate in the New World. According to this hypothesis, syphilis was a mostly benign infection like chicken pox which for thousands of years had been common among the young who transmitted the disease among themselves—and as adults, they gained immunity and could not be reinfected. Once living conditions in Europe began to change and certain social classes began to practice greater hygiene, syphilis was driven out of the age group in which it was harmless. It then began to appear in adults who were unable to fend off the infection because they had never been exposed as children, and they readily spread it via sexual contact to other adults who also had limited or no resistance, causing deformity and death where before it had been only been a temporary childhood ailment. This transition is reported to have coincided temporally with the return of the Columbus expedition from the New World. The most compelling evidence for its validity is the presence of syphilitic-like damage to bones in a number of adult skeletons found in the British city of Hull who were buried over a century before Columbus made his journey to the Americas. [88]

More recent analysis of that research, however, concluded in 2012 that syphilis almost certainly had a New World origin. [89]

The causative organism, Treponema pallidum, was first identified by Fritz Schaudinn and Erich Hoffmann, in 1905. [90] The first effective treatment for syphilis was arsphenamine, discovered by Sahachiro Hata in 1909, during a survey of hundreds of newly synthesized organic arsenical compounds led by Paul Ehrlich. It was manufactured and marketed from 1910 under the trade name Salvarsan by Hoechst AG. [91] This organoarsenic compound was the first modern chemotherapeutic agent.

During the 20th century, as both microbiology and pharmacology advanced greatly, syphilis, like many other infectious diseases, became more of a manageable burden than a scary and disfiguring mystery, at least in developed countries among those people who could afford to pay for timely diagnosis and treatment. Penicillin was discovered in 1928, and effectiveness of treatment with penicillin was confirmed in trials in 1943, [83] at which time it became the main treatment. [92]

Many famous historical figures, including Franz Schubert, Arthur Schopenhauer, Édouard Manet, [10] Charles Baudelaire, [93] and Guy de Maupassant are believed to have had the disease. [94] Friedrich Nietzsche was long believed to have gone mad as a result of tertiary syphilis, but that diagnosis has recently come into question. [95]

Arts and literature

An early medical illustration of people with syphilis, Vienna, 1498 400Behandlung der Syphilis.jpg
An early medical illustration of people with syphilis, Vienna, 1498

The earliest known depiction of an individual with syphilis is Albrecht Dürer's Syphilitic Man, a woodcut believed to represent a Landsknecht, a Northern European mercenary. [96] 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". [97] [98]

The Flemish artist Stradanus designed a print called Preparation and Use of Guayaco for Treating Syphilis, a scene of a wealthy man receiving treatment for syphilis with the tropical wood guaiacum sometime around 1590. [99]

Tuskegee and Guatemala studies

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

The "Tuskegee Study of Untreated Syphilis in the Negro Male" was an infamous, unethical and racist clinical study conducted between 1932 and 1972 by the U.S. Public Health Service. [100] [101] Whereas the purpose of this study was to observe the natural 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. [102]

The Public Health Service started working on this study in 1932 in collaboration with Tuskegee University, a historically black college in Alabama. Researchers enrolled 600 poor, African-American sharecroppers from Macon County, Alabama in the study. Of these men, 399 had contracted syphilis before the study began, and 201 did not have the disease. [101] 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. [101] 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. [100] None of the men infected were ever told that they had the disease, and none were treated with penicillin even after the antibiotic had been proven to successfully treat syphilis. According to the Centers 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. [101]

The 40-year study became a textbook example of poor medical ethics because researchers had knowingly withheld treatment with penicillin and because the subjects had been misled concerning the purposes of the study. The revelation in 1972 of these study failures by a whistleblower, Peter Buxtun, led to major changes in U.S. law and regulation on the protection of participants in clinical studies. Now studies require informed consent, [103] communication of diagnosis, and accurate reporting of test results. [104]

Preparation and Use of Guayaco for Treating Syphilis, after Stradanus, 1590 De ontdekking van Guaiacum als middel tegen syfilis, anoniem, Museum Plantin-Moretus, PK OPB 0186 007.jpg
Preparation and Use of Guayaco for Treating Syphilis, after Stradanus, 1590

Similar experiments were carried out in Guatemala from 1946 to 1948. It was done during the administration of American President Harry S. Truman and Guatemalan President Juan José Arévalo with the cooperation of some Guatemalan health ministries and officials. [105] Doctors infected soldiers, prostitutes, prisoners and mental patients with syphilis and other sexually transmitted infections, without the informed consent of the subjects, and treated most subjects with antibiotics. The experiment resulted in at least 83 deaths. [106] [107] In October 2010, the U.S. formally apologized to Guatemala for the ethical violations that took place. Secretary of State Hillary Clinton and Health and Human Services Secretary Kathleen 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." [108] The experiments were led by physician John Charles Cutler who also participated in the late stages of the Tuskegee syphilis experiment. [109]


It was first called grande verole or the "great pox" by the French. Other historical names have included "button scurvy", sibbens, frenga and dichuchwa, among others. [110] [111] Since it was a disgraceful disease, the disease was known in several countries by the name of their neighbouring country. The English, German and Italians called it "the French disease", while the French referred to it as the "Neapolitan disease". The Dutch called it the "Spanish pocks" during the Dutch Revolt. To the Turks it was known as the "Christian disease", whilst in India, the Hindus and Muslims named the disease after each other. [92]

Related Research Articles

Bacterial vaginosis Excessive growth of bacteria in the vagina

Bacterial vaginosis (BV) is a disease of the vagina caused by excessive growth of bacteria. Common symptoms include increased vaginal discharge that often smells like fish. The discharge is usually white or gray in color. Burning with urination may occur. Itching is uncommon. Occasionally, there may be no symptoms. Having BV approximately doubles the risk of infection by a number of sexually transmitted infections, including HIV/AIDS. It also increases the risk of early delivery among pregnant women.

Pelvic inflammatory disease Infection of uterus, fallopian tubes, ovaries or the inner surface of pelvis

Pelvic inflammatory disease, also known as pelvic inflammatory disorder (PID), is an infection of the upper part of the female reproductive system, namely the uterus, fallopian tubes, and ovaries, and inside of the pelvis. Often, there may be no symptoms. Signs and symptoms, when present, may include lower abdominal pain, vaginal discharge, fever, burning with urination, pain with sex, bleeding after sex, or irregular menstruation. Untreated PID can result in long-term complications including infertility, ectopic pregnancy, chronic pelvic pain, and cancer.

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

Treponema pallidum is a spirochaete bacterium with various subspecies that cause the diseases syphilis, bejel, and yaws. It is chiefly transmitted amongst humans, but it can also cause a condition found in cattle, bovine digital dermatitis. It is a helically coiled microorganism usually 6–15 μm long and 0.1–0.2 μm wide. T. pallidum's lack of either a tricarboxylic acid cycle or oxidative phosphorylation results in minimal metabolic activity. The treponemes have a cytoplasmic and an outer membrane. Using light microscopy, treponemes are visible only by using dark field illumination. Treponema pallidum consists of three subspecies, T. p. pallidum, T. p. endemicum, and T. p. pertenue, each of which has a distinct associated disease.

Yaws 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.

Rapid plasma reagin 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 algorithm is currently endorsed by the U.S. Centers for Disease Control and Prevention (CDC). In addition to screening for syphilis, a titer can be used to track the progress of the disease over time and its response to therapy. The traditional algorithm using an NTT followed by a TT remains the standard in many parts of the world.

Venereal Disease Research Laboratory test

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

Congenital syphilis Medical condition

Congenital syphilis is syphilis present in utero and at birth, and occurs when a child is born to a mother with syphilis. Untreated early syphilis infections results in a high risk of poor pregnancy outcomes, including saddle nose, lower extremity abnormalities, miscarriages, premature births, stillbirths, or death in newborns. Some infants with congenital syphilis have symptoms at birth, but many develop symptoms later. Symptoms may include rash, fever, an enlarged liver and spleen, and skeletal abnormalities. Newborns will typically not develop a primary syphilitic chancre but may present with signs of secondary syphilis. Often these babies will develop syphilitic rhinitis ("snuffles"), the mucus from which is laden with the T. pallidum bacterium, and therefore highly infectious. If a baby with congenital syphilis is not treated early, damage to the bones, teeth, eyes, ears, and brain can occur.

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. The disease is endemic to Mexico, Central America, and South America.

Nonvenereal endemic syphilis 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.

Vertically transmitted infection Infection caused by pathogens that use mother-to-child transmission

A vertically transmitted infection is an infection caused by pathogens that use mother-to-child transmission, that is, transmission directly from the mother to an embryo, fetus, or baby during pregnancy or childbirth. It can occur when the mother has a pre-existing disease or becomes infected during pregnancy. Nutritional deficiencies may exacerbate the risks of perinatal infections.

Neurosyphilis Infection of the central nervous system in a patient with syphilis

Neurosyphilis refers to 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 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.

A genital ulcer is an open sore located on the genital area, which includes the vulva, penis, perianal region, or anus. Genital ulcers are most commonly caused by infectious agents. However, this is not always the case, as a genital ulcer may have noninfectious causes as well.

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.

Gonorrhea Sexually transmitted infection

Gonorrhea, colloquially known as the clap, is a sexually transmitted infection (STI) caused by the bacterium Neisseria gonorrhoeae. Infection may involve the genitals, mouth, or rectum. Infected men may experience pain or burning with urination, discharge from the penis, or testicular pain. Infected women may experience burning with urination, vaginal discharge, vaginal bleeding between periods, or pelvic pain. Complications in women include pelvic inflammatory disease and in men include inflammation of the epididymis. Many of those infected, however, have no symptoms. If untreated, gonorrhea can spread to joints or heart valves.

Sexually transmitted infection Infection transmitted through human sexual behavior

Sexually transmitted infections (STIs), also referred to as sexually transmitted diseases (STDs) and the older term venereal disease, are infections that are spread by sexual activity, especially vaginal intercourse, anal sex and oral sex. STIs often do not initially cause symptoms, which results in a risk of passing the infection on to others. Symptoms and signs of STIs may include vaginal discharge, penile discharge, ulcers on or around the genitals, and pelvic pain. Some STIs can cause infertility.

Epidemiology of syphilis 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.

History of syphilis

The first recorded outbreak of syphilis in Europe occurred in 1494/1495 in Naples, Italy, during a French invasion. Because it was spread by returning French troops, 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. The causative organism, Treponema pallidum, was first identified by Fritz Schaudinn and Erich Hoffmann in 1905. The first effective treatment, Salvarsan, was developed in 1910 by Sahachirō Hata in the laboratory of Paul Ehrlich. It was followed by the introduction of penicillin in 1943.

Meningeal syphilis 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.

The exact role of Mycoplasma hominis in regards to a number of conditions related to pregnant women and their (unborn) offspring is controversial. This is mainly because many healthy adults have genitourinary colonization with Mycoplasma, published studies on pathogenicity have important design limitations and the organisms are very difficult to detect. The likelihood of colonization with M. hominis appears directly linked to the number of lifetime sexual partners Neonatal colonization does occur, but only through normal vaginal delivery. Caesarean section appears protective against colonization and is much less common. Neonatal colonization is transient.


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