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Treponema pallidum.jpg
Electron micrograph of Treponema pallidum
Specialty Infectious disease
SymptomsFirm, 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, not having sex [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) but 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]

Sexually transmitted infection Infection transmitted through human sexual behavior

Sexually transmitted infections (STI), also referred to as sexually transmitted diseases (STD), are infections that are commonly spread by sexual activity, especially vaginal intercourse, anal sex and oral sex. Many times STIs initially do not cause symptoms. This results in a greater risk of passing the disease on to others. Symptoms and signs of disease may include vaginal discharge, penile discharge, ulcers on or around the genitals, and pelvic pain. STIs can be transmitted to an infant before or during childbirth and may result in poor outcomes for the baby. Some STIs may cause problems with the ability to get pregnant.

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

Treponema pallidum is a spirochaete bacterium with subspecies that cause the diseases syphilis, bejel, and yaws and is transmitted only amongst humans. It is a helically coiled microorganism usually 6–15 µm long and 0.1–0.2 µm wide. The treponemes have a cytoplasmic and an outer membrane. Using light microscopy, treponemes are visible only by using dark field illumination.

Subspecies taxonomic rank subordinate to species

In biological classification, the term subspecies refers to a unity of populations of a species living in a subdivision of the species' global range and varies from other populations of the same species by morphological characteristics. A subspecies cannot be recognized independently. A species is either recognized as having no subspecies at all or at least two, including any that are extinct. The term is abbreviated subsp. in botany and bacteriology, or ssp. in zoology. The plural is the same as the singular: subspecies.


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 the Treponema bacteria include yaws (subspecies pertenue), pinta (subspecies carateum), and nonvenereal endemic syphilis (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]

Human sexual activity human behaviour which is sexually motivated, including sexual intercourse

Human sexual activity, human sexual practice or human sexual behaviour is the manner in which humans experience and express their sexuality. People engage in a variety of sexual acts, ranging from activities done alone to acts with another person in varying patterns of frequency, for a wide variety of reasons. Sexual activity usually results in sexual arousal and physiological changes in the aroused person, some of which are pronounced while others are more subtle. Sexual activity may also include conduct and activities which are intended to arouse the sexual interest of another or enhance the sex life of another, such as strategies to find or attract partners, or personal interactions between individuals. Sexual activity may follow sexual arousal.

Congenital syphilis syphilis that results in a multisystem infection in the fetus via the placenta

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. Babies exposed in utero can have deformities, delays in development, or seizures along with many other problems such as rash, fever, an enlarged liver and spleen, anemia, and jaundice. 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. Rarely, the symptoms of syphilis go unseen in infants so that they develop the symptoms of latent syphilis, including damage to their bones, teeth, eyes, ears, and brain.

Yaws Human disease: tropical infection of the skin, bones and joints caused by the spirochete bacterium Treponema pallidum pertenue

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 centimeters in diameter. The center may break open and form an ulcer. This initial skin lesion typically heals after three to six 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 five years or more large areas of skin may die, leaving a scar.

The risk of sexual transmission of syphilis can be reduced by using a latex 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]

Benzathine benzylpenicillin chemical compound

Benzathine benzylpenicillin, also known as benzathine penicillin G, is an antibiotic useful for the treatment of a number of bacterial infections. Specifically it is to treat strep throat, diphtheria, syphilis, and yaws. It is also used to prevent rheumatic fever. It is given by injection into a muscle.

Doxycycline chemical compound

Doxycycline is an antibiotic that is used in the treatment of infections caused by bacteria and certain other parasites. It is useful for bacterial pneumonia, acne, chlamydia infections, early Lyme disease, cholera and syphilis. It is also useful for the treatment of malaria when used with quinine and for the prevention of malaria. Doxycycline can be used either by mouth or intravenously.

Tetracycline chemical compound

Tetracycline, sold under the brand name Sumycin among others, is an antibiotic used to treat a number of infections. This includes acne, cholera, brucellosis, plague, malaria, and syphilis. It is taken by mouth.

In 2015, about 45.4 million people were infected with syphilis, [4] with 6 million 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] In 2015, Cuba became the first country to eliminate mother-to-child transmission of syphilis. [14]

HIV human retrovirus, cause of AIDS

The human immunodeficiency viruses (HIV) are two species of Lentivirus that causes HIV infection and over time acquired immunodeficiency syndrome (AIDS). AIDS is a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment, average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype. In most cases, HIV is a sexually transmitted infection and occurs by contact with or transfer of blood, pre-ejaculate, semen, and vaginal fluids. Non-sexual transmission can occur from an infected mother to her infant during pregnancy, during childbirth by exposure to her blood or vaginal fluid, and through breast milk. Within these bodily fluids, HIV is present as both free virus particles and virus within infected immune cells.

Promiscuity is the practice of having sex frequently with different partners or being indiscriminate in the choice of sexual partners. The term can carry a moral judgment if the social ideal for sexual activity is monogamous relationships. A common example of behavior viewed as promiscuous by many cultures is the one-night stand, and its frequency is used by researchers as a marker for promiscuity.

Prostitution practice of engaging in sexual relations in exchange for payment

Prostitution is the business or practice of engaging in sexual activity in exchange for payment. Prostitution is sometimes described as sexual services, commercial sex or, colloquially, hooking. It is sometimes referred to euphemistically as "the world's oldest profession" in the English-speaking world. A person who works in this field is called a prostitute, and is a type of sex worker.

Signs and symptoms

Syphilis can present in one of four different stages: primary, secondary, latent, and tertiary, [2] and may also occur congenitally. [15] It was referred to as "the great imitator" by Sir William Osler due to its varied presentations. [2] [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 3 to 90 days after the initial exposure (average 21 days) a skin lesion, called a chancre, appears at the point of contact. 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. In the classic form, it evolves from a macule to a papule and finally to an erosion or ulcer. [18] Occasionally, multiple lesions may be present (~40%), [2] with multiple lesions being more common when coinfected with HIV. Lesions may be painful or tender (30%), and they may occur in places other than the genitals (2–7%). 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%). [18] Lymph node enlargement frequently (80%) occurs around the area of infection, [2] occurring seven to 10 days after chancre formation. [18] The lesion may persist for three to six weeks if left untreated. [2]

Chancre sore

A chancre is a painless genital ulcer most commonly formed during the primary stage of syphilis. This infectious lesion forms approximately 21 days after the initial exposure to Treponema pallidum, the gram-negative spirochaete bacterium yielding syphilis. Chancres transmit the sexually transmissible disease of syphilis through direct physical contact. These ulcers usually form on or around the anus, mouth, penis and vagina. Chancres may diminish between four and eight weeks without the application of medication.


A papule is a circumscribed, solid elevation of skin with no visible fluid, varying in area from a pinhead to 1 cm. It can be brown, purple, pink or red in color, and can cluster into a papular rash. Papules may open when scratched and become infected and crusty. Larger non-blisterform elevated lesions may be termed nodules.

Ulcer (dermatology) type of cutaneous condition

An ulcer is a sore on the skin or a mucous membrane, accompanied by the disintegration of tissue. Ulcers can result in complete loss of the epidermis and often portions of the dermis and even subcutaneous fat. Ulcers are most common on the skin of the lower extremities and in the gastrointestinal tract. An ulcer that appears on the skin is often visible as an inflamed tissue with an area of reddened skin. A skin ulcer is often visible in the event of exposure to heat or cold, irritation, or a problem with blood circulation. They can also be caused due to a lack of mobility, which causes prolonged pressure on the tissues. This stress in the blood circulation is transformed to a skin ulcer, commonly known as bedsores or decubitus ulcers. Ulcers often become infected, and pus forms.


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. [19] There may be a symmetrical, reddish-pink, non-itchy rash on the trunk and extremities, including the palms and soles. [2] [20] The rash may become maculopapular or pustular. It may form flat, broad, whitish, wart-like lesions on mucous membranes, known as condyloma latum. All of these lesions harbor bacteria and are infectious. 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] [21] The acute symptoms usually resolve after three to six weeks; [21] about 25% of people may present with a recurrence of secondary symptoms. 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. [19]


Latent syphilis is defined as having serologic proof of infection without symptoms of disease. [17] It is further described as either early (less than 1 year after secondary syphilis) or late (more than 1 year after secondary syphilis) in the United States. [21] The United Kingdom uses a cut-off of two years for early and late latent syphilis. [18] Early latent syphilis may have a relapse of symptoms. Late latent syphilis is asymptomatic, and not as contagious as early latent syphilis. [21]


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] [21] Without treatment, a third of infected people develop tertiary disease. [21] 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. This stage is characterized by the formation of chronic gummas, which are soft, tumor-like balls of inflammation which may vary considerably in size. They typically affect the skin, bone, and liver, but can occur anywhere. [2]

Neurosyphilis refers to an infection involving the central nervous system. It may occur early, being either asymptomatic or in the form of syphilitic meningitis, or late as meningovascular syphilis, general paresis, or tabes dorsalis, which is associated with poor balance and lightning pains in the lower extremities. Late neurosyphilis typically occurs 4 to 25 years after the initial infection. Meningovascular syphilis typically presents with apathy and seizures, and general paresis with dementia and tabes dorsalis. [2] Also, there may be Argyll Robertson pupils, which are bilateral small pupils that constrict when the person focuses on near objects (accommodation reflex) but do not constrict when exposed to bright light (pupillary reflex).

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


Congenital syphilis is that which is transmitted during pregnancy or during birth. Two-thirds of syphilitic infants are born without symptoms. 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%). If untreated, late congenital syphilis may occur in 40%, including saddle nose deformation, Higoumenakis sign, saber shin, or Clutton's joints among others. [6] Infection during pregnancy is also associated with miscarriage. [22]



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] [18] 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. [15] It is unable to survive more than a few days without a host. [18] This is due to its small genome (1.14Mbp) failing to encode the metabolic pathways necessary to make most of its macronutrients. [18] It has a slow doubling time of greater than 30 hours. [18]


Syphilis is transmitted primarily by sexual contact or during pregnancy from a mother to her fetus; the spirochete is able to pass through intact mucous membranes or compromised skin. [2] [15] It is thus transmissible by kissing near a lesion, as well as oral, vaginal, and anal sex. [2] [23] Approximately 30% to 60% of those exposed to primary or secondary syphilis will get the disease. [21] Its infectivity is exemplified by the fact that an individual inoculated with only 57 organisms has a 50% chance of being infected. [18] Most (60%) of new cases in the United States occur in men who have sex with men; and in this population 20% of syphilis were due to oral sex alone. [23] [2] 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 limited. [2]

It is not generally possible to contract syphilis through toilet seats, daily activities, hot tubs, or sharing eating utensils or clothing. [24] This is mainly because the bacteria die very quickly outside of the body, making transmission by objects extremely difficult. [25]


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).

Syphilis is difficult to diagnose clinically during early infection. [18] Confirmation is either via blood tests or direct visual inspection using dark field microscopy. 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. [26]

Blood tests

Blood tests are divided into nontreponemal and treponemal tests. [18]

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. [18] 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. Hospitals do not always have equipment or experienced staff members, and testing must be done within 10 minutes of acquiring the sample.Sensitivity has been reported to be nearly 80%; therefore the test can only be used to confirm a diagnosis, not to rule one out. Two other tests can be carried out on a sample from the chancre: direct fluorescent antibody (DFA) and polymerase chain reaction (PCR) tests. DFA uses antibodies tagged with fluorescein, which attach to specific syphilis proteins, while PCR uses techniques to detect the presence of specific syphilis genes. These tests are not as time-sensitive, as they do not require living bacteria to make the diagnosis. [18]



As of 2018, there is no vaccine effective for prevention. [15] Several vaccines based on treponemal proteins reduce lesion development in an animal model but research continues. [27]


Condom use reduces the likelihood of transmission during sex, but does not completely eliminate the risk. [28] 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. 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." [29]

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." [29]

Congenital disease

Portrait of Mr. J. Kay, affected with what is now believed to have been congenital syphilis c. 1820 CE 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 CE

Congenital syphilis in the newborn can be prevented by screening mothers during early pregnancy and treating those who are infected. [31] The United States Preventive Services Task Force (USPSTF) strongly recommends universal screening of all pregnant women, [32] while the World Health Organization (WHO) recommends all women be tested at their first antenatal visit and again in the third trimester. If they are positive, it is recommend their partners also be treated. [33] 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. It still occasionally occurs in the developed world, as those most likely to acquire syphilis are least likely to receive care during pregnancy. [31] Several measures to increase access to testing appear effective at reducing rates of congenital syphilis in low- to middle-income countries. [33] 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. [34]


The CDC recommends that sexually active men who have sex with men be tested at least yearly. [35] The USPSTF also recommends screening among those at high risk. [36]

Syphilis is a notifiable disease in many countries, including Canada [37] the European Union, [38] and the United States. [39] This means health care providers are required to notify public health authorities, which will then ideally provide partner notification to the person's partners. [40] Physicians may also encourage patients to send their partners to seek care. [41] Several strategies have been found to improve follow-up for STI testing, including email and text messaging of reminders for appointments. [42]


Early infections

The first-line treatment for uncomplicated syphilis remains a single dose of intramuscular benzathine benzylpenicillin. [43] 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. [43] Resistance to macrolides, rifampicin, and clindamycin is often present. [15] 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. [24]

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 for a minimum of 10 days. [2] [15] If a person is allergic to penicillin, ceftriaxone may be used or penicillin desensitization attempted. Other late presentations may be treated with once-weekly intramuscular benzathine penicillin for three weeks. Treatment at this stage solely limits further progression of the disease and has a limited effect on damage which has already occurred. [2]

Jarisch-Herxheimer reaction

One of the potential side effects of treatment is the Jarisch-Herxheimer reaction. 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. [44]


Penicillin is an effective treatment for syphilis in pregnancy [45] but there is no agreement on which dose or route of delivery is most effective. [46]


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. [15] 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, rates of syphilis as of 2007 were six times greater in men than in women; they were nearly equal ten years earlier. [48] African Americans accounted for almost half of all cases in 2010. [49] As of 2014, syphilis infections continue to increase in the United States. [50]

Syphilis was very common in Europe during the 18th and 19th centuries. [10] Flaubert found it universal among nineteenth-century Egyptian prostitutes. [51] 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. [15] 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. [52] Increased rates among heterosexuals have occurred in China and Russia since the 1990s. [15] This has been attributed to unsafe sexual practices, such as sexual promiscuity, prostitution, and decreasing use of barrier protection. [15] [52] [53]

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. [19] With early treatment, few complications result. [18] Syphilis increases the risk of HIV transmission by two to five times, and coinfection is common (30–60% in some urban centers). [2] [15] In 2015, Cuba became the first country in the world to eradicate mother to child transmission of syphilis. [14]


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, [55] 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. These are the Columbian and pre-Columbian hypotheses, respectively, with the Columbian hypothesis better supported by the evidence. [26] [56] [57]

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] [26] Since it was claimed to have been spread by French troops, it was initially called the "French disease" by the people of Naples. [58] 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 describing the ravages of the disease in Italy. [59] [60] It was also called the "Great Pox". [61] [62]

In the 16th through 19th centuries, syphilis was one of the largest public health burdens in prevalence, symptoms, and disability, [63] :208–209 [64] although records of its true prevalence were generally not kept because of the fearsome and sordid status of sexually transmitted diseases in those centuries. [63] :208–209 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.

The causative organism, Treponema pallidum, was first identified by Fritz Schaudinn and Erich Hoffmann, in 1905. [65] [10] The first effective treatment for syphilis was Salvarsan, developed in 1910 by Paul Ehrlich. The effectiveness of treatment with penicillin was confirmed in trials in 1943. [10] [61]

Before the discovery and use of antibiotics in the mid-twentieth century, mercury and isolation were commonly used, with treatments often worse than the disease. [61] 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.

Many famous historical figures, including Franz Schubert, Arthur Schopenhauer, Édouard Manet, [10] Charles Baudelaire, [66] and Guy de Maupassant are believed to have had the disease. [67] Friedrich Nietzsche was long believed to have gone mad as a result of tertiary syphilis, but that diagnosis has recently come into question. [68]

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. [69] 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 . [70] [71]

The artist Jan van der Straet painted 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 1580. [72]

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. [73] [74] 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 health care from the United States government. [75]

The Public Health Service started working on this study in 1932 in collaboration with Tuskegee University, a historically black college in Alabama. Investigators enrolled in the study a total of 600 impoverished, African-American sharecroppers from Macon County, Alabama. Of these men, 399 had previously contracted syphilis before the study began, and 201 did not have the disease. [74] The men were given free medical care, meals, and free burial insurance for participating in the study. The men were told that the study was only going to last six months, but it actually lasted 40 years. [74] After funding for treatment was lost, the study was continued without informing the men that they would never be treated. None of the men infected were ever told that they had the disease, and none were treated with penicillin even after the antibiotic was proven to successfully treat syphilis. According to the Centers for Disease Control, the men were told that they were being treated for "bad blood", a colloquialism that described various conditions such as syphilis, anemia, and fatigue. "Bad blood"—specifically the collection of illnesses the term included—was a leading cause of death within the southern African-American community. [74]

The 40-year study was controversial for reasons related to ethical standards. Researchers knowingly failed to treat patients appropriately after the 1940s validation of penicillin was found as an effective cure for the disease that they were studying. The revelation in 1972 of 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, [76] communication of diagnosis, and accurate reporting of test results. [77]

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. [78] Doctors infected soldiers, prostitutes, prisoners and mental patients with syphilis and other sexually transmitted diseases, without the informed consent of the subjects, and treated most subjects with antibiotics. The experiment resulted in at least 83 deaths. [79] [80] In October 2010, the U.S. formally apologized to Guatemala for the ethical violations that took place. [81] The experiments were led by physician John Charles Cutler who also participated in the late stages of the Tuskegee syphilis experiment. [82]

Related Research Articles

Chlamydia infection sexually transmitted infection caused by the bacterium Chlamydia trachomatis.

Chlamydia infection, often simply known as chlamydia, is a sexually transmitted infection caused by the bacterium Chlamydia trachomatis. Most people who are infected have no symptoms. When symptoms do develop this can take a few weeks following infection to occur. Symptoms in women may include vaginal discharge or burning with urination. Symptoms in men may include discharge from the penis, burning with urination, or pain and swelling of one or both testicles. The infection can spread to the upper genital tract in women causing pelvic inflammatory disease which may result in future infertility or ectopic pregnancy. Repeated infections of the eyes that go without treatment can result in trachoma, a common cause of blindness in the developing world.

Trichomoniasis Gagoparasitic protozoa infectious disease that is caused by singled-celled protozoan parasites Trichomonas vaginalis or Trichomonas tenax, which infect the urogenital tract and mouth respectively

Trichomoniasis (trich) is an infectious disease caused by the parasite Trichomonas vaginalis. About 70% of women and men do not have symptoms when infected. When symptoms do occur they typically begin 5 to 28 days after exposure. Symptoms can include itching in the genital area, a bad smelling thin vaginal discharge, burning with urination, and pain with sex. Having trichomoniasis increases the risk of getting HIV/AIDS. It may also cause complications during pregnancy.

Tuskegee syphilis experiment Human Experiment

The Tuskegee Study of Untreated Syphilis in the Negro Male was an infamous and unethical clinical study conducted between 1932 and 1972 by the U.S. Public Health Service. 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 health care from the United States government.

Venereal Disease Research Laboratory test blood test for syphilis that was developed by the eponymous lab

The Venereal Disease Research Laboratory test (VDRL) is a blood test for syphilis 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.

Chancroid primary bacterial infectious disease that is a sexually transmitted infection located_in skin of the genitals, has_material_basis_in Haemophilus ducreyi, which is transmitted_by sexual contact. The infection has_symptom painful and soft ulcers.

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. While uncommon in the western world, it is the most common cause of genital ulceration worldwide.

Nonvenereal endemic syphilis Human disease

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 trepanematoses", 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.


Neurosyphilis refers to infection of the central nervous system in a patient with syphilis and can occur at any stage. 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.

Genital herpes infection by herpes simplex virus (HSV) of the genitals

Genital herpes is an infection by the herpes simplex virus (HSV) of the genitals. Most people either have no or mild symptoms and thus do not know they are infected. When symptoms do occur, they typically include small blisters that break open to form painful ulcers. Flu-like symptoms, such as fever, aching, or swollen lymph nodes, may also occur. Onset is typically around 4 days after exposure with symptoms lasting up to 4 weeks. Once infected further outbreaks may occur but are generally milder.

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.

Gonorrhea sexually transmitted infection

Gonorrhea, colloquially known as the clap, is a sexually transmitted infection (STI) caused by the bacterium Neisseria gonorrhoeae. Many of those infected have no symptoms. Men may have burning with urination, discharge from the penis, or testicular pain. Women may have 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. If untreated, gonorrhea can spread to joints or heart valves.

Herpes simplex viral disease caused by the herpes simplex virus

Herpes simplex is a viral infection caused by the herpes simplex virus. Infections are categorized based on the part of the body infected. Oral herpes involves the face or mouth. It may result in small blisters in groups often called cold sores or fever blisters or may just cause a sore throat. Genital herpes, often simply known as herpes, may have minimal symptoms or form blisters that break open and result in small ulcers. These typically heal over two to four weeks. Tingling or shooting pains may occur before the blisters appear. Herpes cycles between periods of active disease followed by periods without symptoms. The first episode is often more severe and may be associated with fever, muscle pains, swollen lymph nodes and headaches. Over time, episodes of active disease decrease in frequency and severity. Other disorders caused by herpes simplex include: herpetic whitlow when it involves the fingers, herpes of the eye, herpes infection of the brain, and neonatal herpes when it affects a newborn, among others.

<i>Treponema pallidum</i> particle agglutination assay

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.

Epidemiology of syphilis Epidemiology of syphillis

Syphilis is a bacterial infection caused 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 Human disease

Meningeal syphilis is a chronic form of syphilis infection that affects the central nervous system. Treponema pallidum, which is a spirochate bacterium, is the main cause of syphilis, which spreads drastically throughout the body and can infect all the systems of the body if not treated appropriately. The bacterium 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.


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