រោគ​ស្វាយ

រោគ​ស្វាយ ឬ ជំងឺ​ស្វាយ (Syphilis) គឺ​ជា​ជំងឺ​ឆ្លង​តាម​ការ​រួម​ភេទ (ឆ្លង​តាម​ផ្លូវ​ភេទ) ឬ​ជំងឺ​កាម​រោគ ឬ​រោគ​សង្គម (sexually transmitted infection) អាច​ហៅ​កាត់​ថា STI ឬ STD ប៉ុន្តែ​ពាក្យ​កាត់ STD លែង​មាន​ការ​ពេញ​និយម​ហើយ​ព្រោះ​​ពាក្យ STI មាន​ន័យ​ទូលំទូលាយ​ជាង​ពាក្យ STD ដែល​បង្កប់​អត្ថន័យ​ថា ជំងឺ ។ រោគ​ស្វាយ​ឆ្លង​ដោយ​បាក់តេរី​​​ដែល​មាន​សណ្ឋាន​ដូច​រឺស័រ (spirochete bacterium) ម្យ៉ាង​ឈ្មោះ​ថា ត្រេផឺនីម៉ា ផាល់​លីដឹម (Treponema pallidum) ប្រភេទ palludum ។ ផ្លូវ​ចម្លង​សំខាន់​ជាង​គេ​គឺ​ការ​ប៉ះពាល់​ខាង​ផ្លូវ​ភេទ (sexual contact) ។ ប៉ុន្តែ​រោគស្វាយ​ក៏​អាច​ឆ្លង​ពី​ម្តាយ​ទៅ​ទារក​ក្នុង​ពេល​មាន​គភ៌ ឬ នៅ​ពេល​ឆ្លង​ទន្លេ បង្ក​ទៅ​ជា​រោគស្វាយ​ពីកំណើត (congenital syphilis) ។ ជំងឺ​ផ្សេង​ទៀត​របស់​មនុស្ស​ ដែល​បង្ក​ឡើង​ដោយ​ប្រភេទ​ផ្សេង​ទៀត​នៃ​ពួក​បាក់តេរី Treponema pallidum ដូច​ជា​ជំងឺ yaws ដែល​បង្ក​ឡើង​ដោយ​បាក់តេរី​ប្រភេទ pertenue, ជំងឺ pinta ដែល​បង្ក​ឡើង​ដោយ​បាក់តេរី​ប្រភេទ carateum និង ជំងឺ​ bejel ដែល​បង្ក​ឡើង​ដោយ​បាក់តេរី​ប្រភេទ endemicum ។

រោគសញ្ញា (signs) និង សញ្ញា​តំអូញ (symptoms) នៃ​រោគស្វាយ​ប្រែប្រួល​ទៅតាម​ដំណាក់កាល​នីមួយៗ​នៃ​ដំណាក់កាល​ទាំង​ ៤ ដែល​​រោគស្វាយ (ពោល​គឺ​តំណាក់កាល​ទី ១, ទី ២, ពួន​សង្ងំ និង តំណាក់កាល​ទី ៣) ។ ដំណាក់កាល​ទី ១ រោគសញ្ញា​កើត​មាន​ជាទូទៅ​គឺ​​ដំបៅរលួយ​តែ​មួយ​កន្លែង (chancre) ដែល​ជា​ដំបៅ​ស្បែក​រលួយ​ (ulceration) មាន​លក្ខណៈ​ហាប់ មិន​ឈឺ មិន​រមាស់ ។ តំណាក់កាល​ទី ២ នៃ​រោគស្វាយ​ឃើញ​មាន​ចេញ​រោគសញ្ញា​នៃ​ការកើត​កន្ទួល​រមាស់ (diffuse rash) សព្វ​បាទដៃ​ (palm) និង​ បាត​ជើង (sole of the feet) ។ ដំណាក់កាល​ពួន​សម្ងំ​នៃ​រោគស្វាយ​មាន​បង្ហាញ​រោគសញ្ញា​បន្តិចបន្តួច​ឬ​គ្មាន​រោគសញ្ញា​សោះ​ក៏​មាន ។ ដំណាក់កាល​ទី​ ៣ នៃ​រោគ​ស្វាយ​ឃើញ​មាន​ចេញ​ដុំពកទន់ៗ (gumma) លេច​ឡើង​នៅ​តាម​ទីតាំង​ផ្សេងៗ​ដូច​ជា​​នៅ​ក្នុង​ថ្លើម (liver) (gumma hepatis), នៅ​​ក្នុង​ខួក្បាល (brain), នៅ​ក្នុង​បេះដូង (heart), នៅ​លើ​ស្បែក (skin) ឧទាហរណ៍​ស្បែក​មុខ​ ស្បែក​កន្សោម​ពង​ស្វាស, នៅ​ក្នុង​ឆ្អឹង (bone), នៅ​ក្នុង​ពង​ស្វាស (testis), និង​នៅ​ក្នុង​ជាលិកា​ដទៃ​ទៀត (other tissues), ដែល​បង្ក​ឲ្យ​កើត​ជា​បញ្ហា​ច្រើន​យ៉ាង​ទៀត​រួម​ទាំង​​បញ្ហា​សរសៃ​ប្រសាទ (neurological disorders) ឬ​បញ្ហា​សន្ទះ​​បេះ​ដូង (heart valve disease) ។ រោគស្វាយ​នៅ​ដំណាក់កាល​ទី ៣ នេះ​ត្រូវ​បាន​គេ​ហៅ​ថា​ជា​រោគ​ពូកែ​ត្រាប់ជំងឺ​ផ្សេងៗ (the great imitator) ព្រោះ​វា​បង្ហាញ​រោគសញ្ញា​ច្រើនយ៉ាង​ដែល​មិន​មែន​ជា​រោគសញ្ញា​នៃ​រោគស្វាយ ។ ដើម្បី​វិនិច្ឆ័យ​ថា​អ្នក​ជំងឺ​ម្នាក់​កើត​រោគស្វាយ វេជ្ជបណ្ឌិត​នឹង​បូមឈាម​យក​ទៅ​ធ្វើ​តេស្ត​​ដើម្បី​រក​មើល​វត្តមាន​បាក់តេរី (blood tests) ទោះ​ជា​យ៉ាង​ណា​ក៏ដោយ វេជ្ជបណ្ឌិត​ក៏​អាច​ប្រើវិធីផ្សេង​ទៀត​ដើម្បី​រក​មើល​វត្តមាន​បាក់តេរី​ ពោល​គឺ​ការ​ប្រើ dark field microscopy ។ វេជ្ជបណ្ឌិត​អាច​ព្យាបាល​រោគស្វាយ​ឲ្យ​ជា​ស្រឡះ​ដោយ​ការប្រើ​ថ្នាំ​ពេទ្យ​ប្រភេទ​អង់ទីប៊ីយ៉ូទិច (antibiotics) ជាពិសេស​​​​វេជ្ជបណ្ឌិត​ចូលចិត្ត​ប្រើ​ថ្នាំ​​នៅ​ក្នុង​ក្រុម​ penicillin G សម្រាប់​ចាក់​ក្នុង​សាច់ដុំ (intramuscular) ប៉ុន្តែ​សម្រាប់​ការ​ព្យាបាល​រោគស្វាយ​ដែល​ចេញ​សញ្ញា​នៅ​ក្នុង​ប្រព័ន្ធ​សរសៃប្រសាទ (neurosyphilis) វេជ្ជបណ្ឌិត​នឹង​ប្រើ​ penicillin G ដើម្បី​ចាក់​បញ្ចូល​តាម​សរសៃ​ឈាម​ខ្មៅ (intravenously) ​ហើយ​សម្រាប់​ក្រុម​អ្នក​ជំងឺ​ដែល​មាន​ប្រតិកម្មទាស់​ជាមួយ​នឹង penicillin វេជ្ជបណ្ឌិត​នឹង​ឲ្យ​អ្នក​ជំងឺ​លេប​ថ្នាំ​ ceftriaxone ឬ doxycycline ឬ​ azithromycin ។

កាល​ពី​ឆ្នាំ ១៩៩៩ មាន​របាយការណ៍​បញ្ជាក់​ថា មនុស្ស​ចំនួន ១២ លាន​នាក់​​បន្ថែម​ទៀត​នៅ​​លើ​ពិភពលោក​ បាន​កើត​រោគ​ស្វាយ ដែល​ក្នុង​នោះ​​លើស​ពី​ ៩០% នៃ​អ្នក​ជំងឺ​ដែល​កើត​រោគស្វាយ​ រស់​នៅ​ក្នុង​ប្រទេស​កំពុង​អភិវឌ្ឍន៍ (developing world) ។ ដោយសារ​ការ​ប្រើ​ថ្នាំ​ penicillin ជាទូទៅ​សម្រាប់​ព្យាបាល​អ្នក​ជំងឺ​ស្វាយ​នៅ​ទសវត្សរ៍​ឆ្នាំ ១៩៤០ ចំនួន​អ្នក​កើត​រោគស្វាយ​បាន​ថយ​ចុះ​គួរ​ឲ្យ​កត់​សម្គាល់ ក៏​ប៉ុន្តែ​ចំនួន​អ្នក​កើត​រោគស្វាយ​​នៅ​ក្នុង​ប្រទេស​ជា​ច្រើន​ចាប់​ផ្តើម​កើន​ឡើង​យ៉ាង​រហ័ស​នៅ​ក្នុង​សហវត្ស​ថ្មី ជា​ពិសេស​ដោយសារ​អ្នក​កើត​រោគស្វាយ​​​ក៏​​​មាន​ប្រព័ន្ធភាពស៊ាំ​ថយចុះ​ដោយ​សារ​ពួក​គេ​​មាន​មេរោគ​អេដស៍ (human immunodeficiency virus) ឬ HIV​ នៅ​ក្នុង​ចរន្ត​ឈាម​ផង​ដែរ ។​ បញ្ហា​នេះ​ត្រូវ​បាន​រក​ឃើញ​ថា​ កត្តា​ចូលរួម​មួយ​ក្នុង​ចំណោម​កត្តា​ចូលរួម​ជាច្រើន​ គឺ​ ការ​រួម​ភេទ​គ្មាន​សុវត្ថភាព ដូច​ជា​មនុស្ស​ប្រុស​រួម​ភេទ​ជា​មួយ​មនុស្ស​ប្រុស​, ការ​រួម​ភេទ​ជា​មួយ​ដៃគូ​ច្រើន, ពេស្យាចារ និង ការ​ថយ​ចុះ​នៃ​ចំនួន​អ្នក​ប្រើ​ស្រោម​អនាម័យ (condoms) ។ [1][2][3]

## រោគសញ្ញា និង សញ្ញា​តំអូញ
Syphilis can present in one of four different stages: primary, secondary, latent, and tertiary,[4] and may also occur congenitally.[5] It was referred to as "the great imitator" by Sir William Osler due to its varied presentations.[4][6]

### ដំណាក់កាល​ទី ១
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.[7] Approximately 3 to 90 days after the initial exposure (average 21 days) a skin lesion, called a chancre, appears at the point of contact.[4] This is classically (40% of the time) a single, firm, painless, non-itchy skin ulceration with a clean base and sharp borders between 0.3 and 3.0 cm in size.[4] The lesion, however, may take on almost any form.[8] In the classic form, it evolves from a macule to a papule and finally to an erosion or ulcer.[8] Occasionally, multiple lesions may be present (~40%),[4] with multiple lesions more common when coinfected with HIV. Lesions may be painful or tender (30%), and they may occur outside of the genitals (2–7%). The most common location in women is the cervix (44%), the penis in heterosexual men (99%), and anally and rectally relatively commonly in men who have sex with men (34%).[8] Lymph node enlargement frequently (80%) occurs around the area of infection,[4] occurring seven to 10 days after chancre formation.[8] The lesion may persist for three to six weeks without treatment.[4]

### Secondary
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
Secondary syphilis occurs approximately four to ten weeks after the primary infection.[4] While secondary disease is known for the many different ways it can manifest, symptoms most commonly involve the skin, mucous membranes, and lymph nodes.[9] There may be a symmetrical, reddish-pink, non-itchy rash on the trunk and extremities, including the palms and soles.[4][10] The rash may become maculopapular or pustular. It may form flat, broad, whitish, wart-like lesions known as condyloma latum on mucous membranes. All of these lesions harbor bacteria and are infectious. Other symptoms may include fever, sore throat, malaise, weight loss, hair loss, and headache.[4] Rare manifestations include hepatitis, kidney disease, arthritis, periostitis, optic neuritis, uveitis, and interstitial keratitis.[4][11] The acute symptoms usually resolve after three to six weeks;[11] however, 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 classic chancre of primary syphilis.[9]

### Latent
Latent syphilis is defined as having serologic proof of infection without symptoms of disease.[7] 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.[11] The United Kingdom uses a cut-off of two years for early and late latent syphilis.[8] Early latent syphilis may have a relapse of symptoms. Late latent syphilis is asymptomatic, and not as contagious as early latent syphilis.[11]

### Tertiary
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%).[4][11] Without treatment, a third of infected people develop tertiary disease.[11] People with tertiary syphilis are not infectious.[4]

Patient with tertiary (gummatous) syphilis. Bust in Musée de l'Homme, Paris.
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.[4]
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 seizure, and general paresis with dementia and tabes dorsalis.[4] Also, there may be Argyll Robertson pupils, which are bilateral small pupils that constrict when the person focuses on near objects, but do not constrict when exposed to bright light.
Cardiovascular syphilis usually occurs 10–30 years after the initial infection. The most common complication is syphilitic aortitis, which may result in aneurysm formation.[4]

### Congenital
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 years of life include: hepatosplenomegaly (70%), rash (70%), fever (40%), neurosyphilis (20%), and pneumonitis (20%). If untreated, late congenital syphilis may occur in 40%, including: saddle nose deformation, Higoumenakis sign, saber shin, or Clutton's joints among others.[12]

## Cause
### Bacteriology
Histopathology of Treponema pallidum spirochetes using a modified Steiner silver stain
Main article: Treponema pallidum
Treponema pallidum subspecies pallidum is a spiral-shaped, Gram-negative, highly mobile bacterium.[8][13] Three other human diseases are caused by related Treponema pallidum, including yaws (subspecies pertenue), pinta (subspecies carateum) and bejel (subspecies endemicum).[4] Unlike subtype pallidum, they do not cause neurological disease.[12] Humans are the only known natural reservoir for subspecies pallidum.[5] It is unable to survive without a host for more than a few days. This is due to its small genome (1.14 MDa) failing to encode the metabolic pathways necessary to make most of its macronutrients. It has a slow doubling time of greater than 30 hours.[8]

### Transmission
Syphilis is transmitted primarily by sexual contact or during pregnancy from a mother to her fetus; the spirochaete is able to pass through intact mucous membranes or compromised skin.[4][5] It is thus transmissible by kissing near a lesion, as well as oral, vaginal, and anal sex.[4] Approximately 30 to 60% of those exposed to primary or secondary syphilis will get the disease.[11] Its infectivity is exemplified by the fact that an individual inoculated with only 57 organisms has a 50% chance of being infected.[8] Most (60%) of new cases in the United States occur in men who have sex with men. It can be transmitted via blood products. However, it is tested for in many countries and thus the risk is low. The risk of transmission from sharing needles appears limited.[4] Syphilis cannot be contracted through toilet seats, daily activities, hot tubs, or sharing eating utensils or clothing.[14]

## Diagnosis
Poster for testing of syphilis, showing a man and a woman bowing their heads in shame

This posters 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 early in its presentation.[8] Confirmation is either via blood tests or direct visual inspection using microscopy. Blood tests are more commonly used, as they are easier to perform.[4] Diagnostic tests are, however, unable to distinguish between the stages of the disease.[15]

### Blood tests
Blood tests are divided into nontreponemal and treponemal tests.[8] Nontreponemal tests are used initially, and include venereal disease research laboratory (VDRL) and rapid plasma reagin tests. However, as these tests are occasionally false positives, confirmation is required with a treponemal test, such as treponemal pallidum particle agglutination (TPHA) or fluorescent treponemal antibody absorption test (FTA-Abs).[4] False positives on the nontreponemal tests can occur with some viral infections such as varicella and measles, as well as with lymphoma, tuberculosis, malaria, endocarditis, connective tissue disease, and pregnancy.[7] Treponemal antibody tests usually become positive two to five weeks after the initial infection.[8] 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.[4][7]

### Direct testing
Dark ground microscopy of serous fluid from a chancre may be used to make an immediate diagnosis. However, hospitals do not always have equipment or experienced staff members, whereas testing must be done within 10 minutes of acquiring the sample. Sensitivity has been reported to be nearly 80%, thus can only be used to confirm a diagnosis but not rule one out. Two other tests can be carried out on a sample from the chancre: direct fluorescent antibody testing and nucleic acid amplification tests. Direct fluorescent testing uses antibodies tagged with fluorescein, which attach to specific syphilis proteins, while nucleic acid amplification uses techniques, such as the polymerase chain reaction, 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.[8]

## Prevention
As of 2010, there is no vaccine effective for prevention.[5] Abstinence from intimate physical contact with an infected person is effective at reducing the transmission of syphilis, as is the proper use of a latex condom. Condom use, however, does not completely eliminate the risk.[14][16] Thus, the Centers for Disease Control and Prevention recommends a long-term, mutually monogamous relationship with an uninfected partner and the avoidance of substances such as alcohol and other drugs that increase risky sexual behavior.[14]

Congenital syphilis in the newborn can be prevented by screening mothers during early pregnancy and treating those who are infected.[17] The United States Preventive Services Task Force (USPSTF) strongly recommends universal screening of all pregnant women,[18] while the World Health Organization recommends all women be tested at their first antenatal visit and again in the third trimester.[19] If they are positive, they recommend their partners also be treated.[19] Congenital syphilis is, however, still common in the developing world, as many women do not receive antenatal care at all, and the antenatal care others do receive does not include screening,[17] and it still occasionally occurs in the developed world, as those most likely to acquire syphilis (through drug use, etc.) are least likely to receive care during pregnancy.[17] A number of measures to increase access to testing appear effective at reducing rates of congenital syphilis in low- to middle-income countries.[19]

Syphilis is a notifiable disease in many countries, including Canada[20] the European Union,[21] and the United States.[22] This means health care providers are required to notify public health authorities, which will then ideally provide partner notification to the person's partners.[23] Physicians may also encourage patients to send their partners to seek care.[24] The CDC recommends sexually active men who have sex with men are tested at least yearly.[25]

## Treatment
### Early infections
The first-choice treatment for uncomplicated syphilis remains a single dose of intramuscular penicillin G or a single dose of oral azithromycin.[26] Doxycycline and tetracycline are alternative choices; however, due to the risk of birth defects these are not recommended for pregnant women. Antibiotic resistance has developed to a number of agents, including macrolides, clindamycin, and rifampin.[5] Ceftriaxone, a third-generation cephalosporin antibiotic, may be as effective as penicillin-based treatment.[4]

### Late infections
For neurosyphilis, due to the poor penetration of penicillin G into the central nervous system, those affected are recommended to be given large doses of intravenous penicillin for a minimum of 10 days.[4][5] If a person is allergic, ceftriaxone may be used or penicillin desensitization attempted. Other late presentations may be treated with once-weekly intramuscular penicillin G for three weeks. If allergic, as in the case of early disease, doxycycline or tetracycline may be used, albeit for a longer duration. Treatment at this stage limits further progression, but has only slight effect on damage which has already occurred.[4]

### 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, muscles pains, headache, and tachycardia.[4] It is caused by cytokines released by the immune system in response to lipoproteins released from rupturing syphilis bacteria.[27]

## Epidemiology
Main article: Epidemiology of syphilis

Age-standardized death from syphilis per 100,000 inhabitants in 2004[28]

  no data

  500

Syphilis is believed to have infected 12 million additional people in 1999, with greater than 90% of cases in the developing world.[5] It affects between 700,000 and 1.6 million pregnancies a year, resulting in spontaneous abortions, stillbirths, and congenital syphilis.[12] During 2010 it caused about 113,000 deaths down from 202,000 in 1990.[29] In sub-Saharan Africa, syphilis contributes to approximately 20% of perinatal deaths.[12] Rates are proportionally higher among intravenous drug users, those who are infected with HIV, and men who have sex with men.[1][2][3] In the United States, rates of syphilis as of 2007 were six times greater in men than women, while they were nearly equal in 1997.[30] African Americans accounted for almost half of all cases in 2010.[31]
Syphilis was very common in Europe during the 18th and 19th centuries. In the developed world during the early 20th century, infections declined rapidly with the widespread use of antibiotics, until the 1980s and 1990s.[13] Since the year 2000, rates of syphilis have been increasing in the USA, Canada, the UK, Australia and Europe, primarily among men who have sex with men.[5] Rates of syphilis among American women have, however, remained stable during this time, and rates among UK women have increased, but at a rate less than that of men.[32] Increased rates among heterosexuals have occurred in China and Russia since the 1990s.[5] This has been attributed to unsafe sexual practices, such as sexual promiscuity, prostitution, and decreasing use of barrier protection.[5][32][33]

Untreated, it has a mortality of 8% to 58%, with a greater death rate in males.[4] 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 decreasing virulence of the spirochaete.[9] With early treatment, few complications result.[8] Syphilis increases the risk of HIV transmission by two to five times, and coinfection is common (30–60% in a number of urban centers).[4][5]

## History
Main article: History of syphilis

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.[34]

The exact origin of syphilis is disputed.[4] Syphilis was indisputably present in the Americas before European contact. The dispute is over whether or not syphilis was also present elsewhere in the world at that time. One of the two primary hypotheses proposes that syphilis was carried from the Americas to Europe by the returning crewmen from Christopher Columbus's voyage to the Americas. The other hypothesis says that syphilis existed in Europe previously, but went unrecognized until shortly after Columbus' return. These are referred to as the Columbian and pre-Columbian hypotheses, respectively.[15] The Columbian hypothesis is best supported by the available evidence.[35][36] 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).[13][15] Due to its being spread by returning French troops, it was initially known as the "French disease."[citation needed] In 1530, the name "syphilis" 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.[37] It was also known historically as the "Great Pox".[38][39]

The causative organism, Treponema pallidum, was first identified by Fritz Schaudinn and Erich Hoffmann in 1905.[13] The first effective treatment (Salvarsan) was developed in 1910 by Paul Ehrlich, which was followed by trials of penicillin and confirmation of its effectiveness in 1943.[13][38] Before the advent of effective treatment, mercury and isolation were commonly used, with treatments often worse than the disease.[38]
Many famous historical figures, including Franz Schubert, Arthur Schopenhauer, and Édouard Manet,[13] are believed to have had the disease.

## Society and culture
### Arts and literature
See also: Notable cases of syphilis

The earliest known 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.[40] 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.[41][42]

The artist Jan van der Straet painted a scene of a wealthy man receiving treatment for syphilis with the tropical wood guaiacum sometime around 1580.[43] The title of the work is "Preparation and Use of Guayaco for Treating Syphilis". That the artist chose to include this image in a series of works celebrating the New World indicates how important a treatment, however ineffective, for syphilis was to the European elite at that time. The richly colored and detailed work depicts four servants preparing the concoction while a physician looks on, hiding something behind his back while the hapless patient drinks.[44]

### Tuskegee and Guatemala studies
See also: Tuskegee syphilis experiment and Syphilis experiments in Guatemala
One of the most infamous United States cases of questionable medical ethics in the 20th century was the Tuskegee syphilis study.[45] The study took place in Tuskegee, Alabama, and was supported by the U.S. Public Health Service (PHS) in partnership with the Tuskegee Institute.[46] The study began in 1932, when syphilis was a widespread problem and there was no safe and effective treatment.[6] The study was designed to measure the progression of untreated syphilis. By 1947, penicillin had been validated as an effective cure for syphilis and was becoming widely used to treat the disease. Study directors, however, continued the study and did not offer the participants treatment with penicillin.[46] This is debated, and some have found that penicillin was given to many of the subjects.[6] The study did not end until 1972.[46]

Syphilis experiments were also carried out in Guatemala from 1946 to 1948. They were United States-sponsored human experiments, conducted during the government of Juan José Arévalo with the cooperation of some Guatemalan health ministries and officials. Doctors infected soldiers, prisoners, and mental patients with syphilis and other sexually transmitted diseases, without the informed consent of the subjects, and then treated them with antibiotics. In October 2010, the U.S. formally apologized to Guatemala for conducting these experiments.[47]

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## Further reading
# Parascandola, John. Sex, Sin, and Science: A History of Syphilis in America (Praeger, 2008) 195 pp. ISBN 978-0-275-99430-3 excerpt and text search
# Shmaefsky, Brian, Hilary Babcock and David L. Heymann. Syphilis (Deadly Diseases & Epidemics) (2009)
# Stein, Claudia. Negotiating the French Pox in Early Modern Germany (2009)

## External links
"Syphilis - CDC Fact Sheet" Centers for Disease Control and Prevention (CDC)

UCSF HIV InSite Knowledge Base Chapter: Syphilis and HIV