Syphilis

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 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]

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 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]

Syphilis
Treponema pallidum
Electron micrograph of Treponema pallidum
SpecialtyInfectious disease
SymptomsFirm, painless, non-itchy skin ulcer[1]
CausesTreponema pallidum usually spread by sex[1]
Diagnostic methodBlood tests, dark field microscopy of infected fluid[1][2]
Differential diagnosisMany other diseases[1]
PreventionCondoms, not having sex[1]
TreatmentAntibiotics[3]
Frequency45.4 million / 0.6% (2015)[4]
Deaths107,000 (2015)[5]

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

Chancres on the penile shaft due to a primary syphilitic infection caused by Treponema pallidum 6803 lores
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]

Secondary

Secondary Syphilis on palms CDC 6809 lores.rsh
Typical presentation of secondary syphilis with a rash on the palms of the hands
2ndsyphil2
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

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]

Tertiary

Tertiary syphilis head
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

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]

Cause

Bacteriology

Treponema pallidum 01
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]

Transmission

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]

Diagnosis

Syphilis false shame and fear may destroy your future
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]

Prevention

Vaccine

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]

Sex

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, afflicted with a rodent disease. Unknown artist, c. 1820 CE. The Wellcome Collection, London
Portrait of Mr. J. Kay, affected with what is now believed to have been congenital syphilis c. 1820 CE[30]

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]

Screening

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]

Treatment

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]

Pregnancy

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]

Epidemiology

Syphilis world map-Deaths per million persons-WHO2012
Syphilis deaths per million persons in 2012
  0–0
  1–1
  2–3
  4–10
  11–19
  20–28
  29–57
  58–138
Syphilis world map - DALY - WHO2004
Age-standardized disability adjusted life years from syphilis per 100,000 inhabitants in 2004[47]

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]

History

Rembrandt Harmensz. van Rijn 095
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.[54]

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

400Behandlung der Syphilis
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

Stop syphilis LCCN98509573
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]

Names

Historical names have included "button scurvy", sibbens, frenga, and dichuchwa among others.[83]

References

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External links

External resources
Arsphenamine

Arsphenamine, also known as Salvarsan or compound 606, is a drug that was introduced at the beginning of the 1910s as the first effective treatment for syphilis, and was also used to treat trypanosomiasis.

This organoarsenic compound was the first modern chemotherapeutic agent.

Benzathine benzylpenicillin

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.Side effects include allergic reactions including anaphylaxis, and pain at the site of injection. When used to treat syphilis a reaction known as Jarisch-Herxheimer may occur. It is not recommended in those with a history of penicillin allergy or those with syphilis involving the nervous system. Use during pregnancy is generally safe. It is in the penicillin and beta lactam class of medications and works via benzylpenicillin. The benzathine component slowly releases the penicillin making the combination long acting.Benzathine benzylpenicillin was patented in 1950. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is about 0.27 to 1.71 USD for a course of treatment. In the United States the medication costs 50 to 100 USD for a dose as of 2015. In the United Kingdom it costs the NHS about 0.95 to 1.89 pounds a dose as of 2015.

Chancroid

Chancroid ( SHANG-kroyd) (also known as soft chancre and ulcus molle) 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.

Congenital syphilis

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 (i.e. generalized body rash). 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.

Epidemiology of syphilis

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.In the developed world, syphilis infections were in decline until the 1980s and 1990s due to widespread use of antibiotics. Since the year 2000, rates of syphilis have been increasing in the US, UK, Australia, and Europe primarily among men who have sex with men. This is attributed to unsafe sexual practices. A STD Surveillance study done by the Centers for Disease Control and Prevention in 2016 showed that men who have sex with men only account for over half (52%) of the 27,814 cases during that year. Nationally, the highest rates of primary and secondary syphilis in 2016 were observed among men aged 20–34 years, among men in the West, and among Black men. Increased rates among heterosexuals have occurred in China and Russia since the 1990s. Syphilis increases the risk of HIV transmission by two to five times and co-infection is common (30–60% in a number of urban centers).Untreated, it has a mortality rate of 8% to 58%, with a greater death rate in males. The symptoms of syphilis have become less severe over the 19th and 20th century in part due to widespread availability of effective treatment and partly due to decreasing virulence of the spirochete. With early treatment few complications result.

Guatemala syphilis experiment

The syphilis experiments in Guatemala were United States-led human experiments conducted in Guatemala from 1946 to 1948. The experiments were led by physician John Charles Cutler who also participated in the late stages of the Tuskegee syphilis experiment. Doctors infected soldiers, prostitutes, prisoners and mental patients with syphilis and other sexually transmitted diseases, without the informed consent of the subjects. The experiment resulted in at least 83 deaths. Serology studies continued through 1953 involving the same vulnerable populations in addition to children from state-run schools, an orphanage, and rural towns, though the intentional infection of patients ended with the original study. On October 1, 2010, the U.S. President, Secretary of State and Secretary of Health and Human Services formally apologized to Guatemala for the ethical violations that took place. Guatemala condemned the experiment as a crime against humanity, and a lawsuit has since been filed.

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

Neurosyphilis

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.

To diagnose neurosyphilis, patients undergo a lumbar puncture to obtain cerebrospinal fluid (CSF) for analysis. The CSF is tested for antibodies for specific Treponema pallidum antigens. The preferred test is the VDRL test, which is sometimes supplemented by fluorescent treponemal antibody absorption test (FTA-ABS).Historically, the disease was studied under the Tuskegee study, which was one of the most notable examples of scientific misconduct in history. The study was done on approximately 400 African-American men with untreated syphilis were followed from 1932 to 1972 and compared to approximately 200 men without syphilis. The study began without informed consent of the subjects and was continued by the United States Public Health Service until 1972. The researchers failed to notify and withheld treatment for patients despite knowing penicillin was found as an effective cure for neurosphyilis. After four years of follow up, neurosyphilis was identified in 26.1% of patients vs. 2.5% of controls. After 20 years of followup, 14% showed signs of neurosyphilis and 40% had died from other causes. Research practices were changed, in part in response to the Tuskegee study, with the passing of the National Research Act in 1974, the establishment of institutional review boards and informed consent practices, and a presidential apology issued in 1997.

Nonvenereal endemic syphilis

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" (endemic infections caused by spiral-shaped bacteria called treponemes), 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.

Pinta (disease)

Pinta (also known as Azul, Carate, Empeines, Lota, Mal del Pinto and Tina) is a human skin disease endemic to Mexico, Central America, and South America caused by infection with the spirochete, Treponema carateum, which is morphologically and serologically indistinguishable from the bacterium that causes syphilis.

Sex Hygiene

Sex Hygiene is a short 1942 American drama film directed by John Ford and Otto Brower. It belonged to the instructional social guidance film genre, which offered adolescent and adult behavioural advice, medical information, and moral exhortations. The Academy Film Archive preserved Sex Hygiene in 2007.

Sexually transmitted infection

Sexually transmitted infections (STIs), also referred to as sexually transmitted diseases (STDs), 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.More than 30 different bacteria, viruses, and parasites can be transmitted through sexual activity. Bacterial STIs include chlamydia, gonorrhea, and syphilis. Viral STIs include genital herpes, HIV/AIDS, and genital warts. Parasitic STIs include trichomoniasis. While usually spread by sex, some STIs can be spread by non-sexual contact with donor tissue, blood, breastfeeding, or during childbirth. STI diagnostic tests are usually easily available in the developed world, but this is often not the case in the developing world.The most effective way of preventing STIs is by not having sex. Some vaccinations may also decrease the risk of certain infections including hepatitis B and some types of HPV. Safer sex practices such as use of condoms, having a smaller number of sexual partners, and being in a relationship where each person only has sex with the other also decreases the risk. Circumcision in males may be effective to prevent some infections. During school, comprehensive sex education may also be useful. Most STIs are treatable or curable. Of the most common infections, syphilis, gonorrhea, chlamydia, and trichomoniasis are curable, while herpes, hepatitis B, HIV/AIDS, and HPV are treatable but not curable. Resistance to certain antibiotics is developing among some organisms such as gonorrhea.In 2015, about 1.1 billion people had STIs other than HIV/AIDS. About 500 million were infected with either syphilis, gonorrhea, chlamydia or trichomoniasis. At least an additional 530 million people have genital herpes and 290 million women have human papillomavirus. STIs other than HIV resulted in 108,000 deaths in 2015. In the United States there were 19 million new cases of sexually transmitted infections in 2010. Historical documentation of STIs date back to at least the Ebers papyrus around 1550 BC and the Old Testament. There is often shame and stigma associated with these infections. The term sexually transmitted infection is generally preferred over sexually transmitted disease or venereal disease, as it includes those who do not have symptomatic disease.

Tabes dorsalis

Tabes dorsalis, also known as syphilitic myelopathy, is a slow degeneration (specifically, demyelination) of the neural tracts primarily in the dorsal columns (posterior columns) of the spinal cord (the portion closest to the back of the body) and dorsal roots. These nerves normally help maintain a person's sense of position (proprioception), vibration, and discriminative touch.

Treponema pallidum

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.

Tuskegee syphilis experiment

The Tuskegee Study of Untreated Syphilis in the African American 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.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. 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. After funding for treatment was lost, the study was continued without informing the men that they would never be treated. None of the men were 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.The 40-year study was unethical 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, communication of diagnosis, and accurate reporting of test results.By 1947, penicillin had become the standard treatment for syphilis. Choices available to the doctors involved in the study might have included treating all syphilitic subjects and closing the study, or splitting off a control group for testing with penicillin. Instead, the Tuskegee scientists continued the study without treating any participants; they withheld penicillin and information about it from the patients. In addition, scientists prevented participants from accessing syphilis treatment programs available to other residents in the area. The study continued, under numerous US Public Health Service supervisors, until 1972, when a leak to the press resulted in its termination on November 16 of that year. The victims of the study, all African American, included numerous men who died of syphilis, 40 wives who contracted the disease, and 19 children born with congenital syphilis.

The Tuskegee Syphilis Study, cited as "arguably the most infamous biomedical research study in U.S. history", led to the 1979 Belmont Report and to the establishment of the Office for Human Research Protections (OHRP). It also led to federal laws and regulations requiring Institutional Review Boards for the protection of human subjects in studies involving them. The OHRP manages this responsibility within the US Department of Health and Human Services (HHS).On May 16, 1997, President Bill Clinton formally apologized on behalf of the United States to victims of the experiment.

United States Public Health Service

The United States Public Health Service (USPHS) is a division of the Department of Health and Human Services concerned with public health. It contains eight out of the department's eleven operating divisions. The Assistant Secretary for Health (ASH) oversees the PHS. The Public Health Service Commissioned Corps (PHSCC) is the federal uniformed service of the USPHS, and is one of the seven uniformed services of the United States.

Its origins can be traced to the establishment in 1798 of a system of marine hospitals. In 1870 these were consolidated into the Marine Hospital Service, and the position of Surgeon General was established. In 1889, the PHSCC was established. As the system's scope grew, it was renamed the Public Health Service in 1912. The Public Health Service Act of 1944 consolidated and revised previous laws and is the current legal basis for the PHS. It became part of the Federal Security Agency and later the Department of Health, Education and Welfare, which became the Department of Health and Human Services in 1979.

Venereology

Venereology is a branch of medicine that is concerned with the study and treatment of sexually transmitted diseases. The name derives from Roman goddess Venus, associated with love, beauty and fertility. A physician specializing in venereology is called a venereologist. In many areas of the world, the specialty is usually combined with dermatology.

The venereal diseases include bacterial, viral, fungal, and parasitic infections. Some of the important diseases are HIV infection, syphilis, gonorrhea, candidiasis, herpes simplex, human papillomavirus infection, and genital scabies. Other sexually transmitted infections studied in the field include chancroid, lymphogranuloma venereum, granuloma inguinale, hepatitis B, and cytomegalovirus infection.

In India, formal training of venerologists started in 1910, prompting microscopy and serology to come into general use throughout the Empire. Before this, many cases of early syphilis were either diagnosed as chancroid or missed altogether. To come to a diagnosis, doubtful atypical cases were at times left untreated to see whether or not they developed secondary syphilis. Today, an MD in venereology is a 2 to 3-year long postgraduate course in medicine. The minimum eligibility is the successful completion of any of MBBS, DMS, BHMS, and BDS, etc degrees. Major subjects of study that form part of the program are immunology of dermatological diseases, cellular and molecular inflammation, skin genetics, skin structure and development of skin, and basic reactions of skin, repair, and carcinogenesis.

Diseases of the skin and appendages by morphology
Growths
Rashes
Miscellaneous
disorders
Sexually transmitted infection (STI) (primarily A50–A64, 090–099)
Bacterial
Protozoal
Parasitic
Viral
General
inflammation
Spirochaete
Chlamydiaceae
Bacteroidetes
Fusobacteria
Gestational
During birth
Late pregnancy
By breastfeeding

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