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| {{DiseaseDisorder infobox |
| | #REDIRECT [[Syphilis]] |
| Name = Syphilis |
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| Image = Treponema pallidum.jpg |
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| Caption = Image of spiral-shaped organisms responsible for causing syphilis |
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| ICD10 = {{ICD10|A|50||a|50}}-{{ICD10|A|53||a|50}} |
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| ICD9 = {{ICD9|090}}-{{ICD9|097}} |
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| ICDO = |
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| OMIM = |
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| DiseasesDB = |
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| MedlinePlus = 001327 |
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| eMedicineSubj = med|
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| eMedicineTopic = 2224|
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| eMedicine_mult = {{eMedicine2|emerg|563}} {{eMedicine2|derm|413}}
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| }}
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| {{SI}}
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| {{CMG}}
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| __NOTOC__
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| ==Overview==
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| '''Syphilis''' is a curable [[sexually transmitted disease]] caused by the ''[[Treponema pallidum]]'' [[spirochete]]. The route of transmission of syphilis is almost always by [[sexual]] contact, although there are examples of [[congenital syphilis]] via transmission from mother to child [[in utero]]. The signs and [[symptoms]] of syphilis are numerous; before the advent of [[serological testing]], precise [[diagnosis]] was very difficult. In fact, the disease was dubbed the "Great Imitator" because it was often confused with other diseases, particularly in its tertiary stage. Syphilis (unless [[antibiotic resistance|antibiotic-resistant]]) can be easily treated with [[antibiotics]] including [[penicillin]]. The oldest and still most effective method is an [[intramuscular injection]] of [[Penicillin#Benzathine benzylpenicillin|benzathine penicillin]]. If not treated, syphilis can cause serious effects such as damage to the [[heart]], [[aorta]], [[brain]], [[eyes]], and [[bones]]. In some cases these effects can be fatal. In 1998, the complete [[genetic sequence]] of ''T. pallidum'' was published which may aid understanding of the [[pathogenesis]] of syphilis.
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| ==Syphilis infection==
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| Different manifestations occur depending on the stage of the disease:
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| ===Primary syphilis===
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| [[Image:Extragenital syphilitic chancre of the left index finger PHIL 4147 lores.jpg|thumb|left|200px|Primary [[chancre]] of syphilis at the site of infection on the hand]]
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| ''Primary syphilis'' is typically acquired via direct sexual contact with the infectious lesions of a person with syphilis.<ref name=RedBookSyphilis>{{citation | editor=Pickering LK | contribution=Syphilis | title= Red Book | publisher=American Academy of Pediatrics | location= Elk Grove Village, IL | date=2006 | pages=631-644 | accessdate=5-19-2007}}</ref> Approximately 10-90 days after the initial exposure (average 21 days), a skin lesion appears at the point of contact, e.g. the [[genitalia]]. This lesion, called a ''[[chancre]]'', is a firm, painless skin ulceration localized at the point of initial exposure to the spirochete, often on the [[penis]], [[vagina]] or [[rectum]]. Rarely, there may be multiple lesions present although typically only one lesion is seen. The [[lesion]] may persist for 4 to 6 weeks and usually heals spontaneously. Local [[lymph node]] swelling can occur. During the initial incubation period, individuals are otherwise [[asymptomatic]]. As a result, many patients do not seek medical care immediately.
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| Syphilis can ''not'' be contracted through toilet seats, daily activities, hot tubs, or sharing eating utensils or clothing.<ref>{{cite web | last = Centers for Disease Control (CDC) | authorlink = Centers for Disease Control and Prevention | title =STD Facts - Syphilis | publisher = [[Centers for Disease Control]] | date = 05-2004 | url = http://www.cdc.gov/std/syphilis/STDFact-Syphilis.htm | accessdate = 2007-05-30 }}</ref>
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| [[Image:Secondary Syphilis on palms CDC 6809 lores.rsh.jpg|left|thumb|200px|Typical presentation of secondary syphilis rash on the palms of the hands and usually also seen on soles of feet]]
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| ===Secondary syphilis===
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| ''Secondary syphilis'' occurs approximately 1-6 months (commonly 6 to 8 weeks) after the primary infection. There are many different manifestations of secondary disease. There may be a symmetrical reddish-pink non-itchy rash on the trunk and extremities..<ref name=2darySyphilis>{{cite journal | author=Dylewski J, Duong M | title=The rash of secondary syphilis | journal=CMAJ. | date= 2007 Jan 2 | volume=176 | issue=1 | pages=33-5 | doi= 10.1503/cmaj.060665}}</ref> The rash can involve the palms of the hands and the soles of the feet. In moist areas of the body, the rash becomes flat broad whitish lesions known as condylomata lata. Mucous patches may also appear on the genitals or in the mouth. All of these lesions are infectious and harbor active treponeme organisms. A patient with syphilis is most contagious when he or she has secondary syphilis. Other symptoms common at this stage include [[fever]], [[sore throat]], [[malaise]], [[weight loss]], [[headache]], [[meningismus]], and enlarged [[lymph node]]s. Rare manifestations include an acute [[meningitis]] that occurs in about 2% of patients, [[hepatitis]], [[kidney|renal]] disease, hypertrophic [[gastritis]], patchy [[proctitis]], [[ulcerative colitis]], [[rectum|rectosigmoid]] mass, [[arthritis]], [[periostitis]], [[optic neuritis]], intersitial keratitis, [[iritis]], and [[uveitis]].
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| ===Latent syphilis===
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| ''Latent syphilis'' is defined as having serologic proof of infection without signs or symptoms of disease.<ref name=RedBookSyphilis/> Latent syphilis is further described as either early or late. Early latent syphilis is defined as having syphilis for two years or less from the time of initial infection without signs or symptoms of disease. Late latent syphilis is infection for greater than two years but without clinical evidence of disease. The distinction is important for both therapy and risk for transmission. In the real-world, the timing of infection is often not known and should be presumed to be late for the purpose of therapy. Early latent syphilis may be treated with a single intramuscular injection of a long-acting penicillin. Late latent syphilis, however, requires three weekly injections. For infectiousness, however, late latent syphilis is not considered as contagious as early latent syphilis.
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| ===Tertiary syphilis===
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| ''Tertiary syphilis'' usually occurs 1-10 years after the initial infection, though in some cases it can take up to 50 years. This stage is characterized by the formation of [[gumma (pathology)|gummas]] which are soft, tumor-like balls of inflammation known as [[granuloma]]s. The granulomas are chronic and represent an inability of the immune system to completely clear the organism. Gummas were once readily seen in the skin and mucous membranes although they tend to occur internally in recent history. They may appear almost anywhere in the body including in the skeleton. The gummas produce a [[chronic inflammatory]] state in the body with mass-effects upon the local anatomy. Other characteristics of untreated tertiary syphilis include [[neuropathic joint disease]], which are a degeneration of joint surfaces resulting from loss of sensation and fine position sense ([[proprioception]]). The more severe manifestations include [[neurosyphilis]] and cardiovascular syphilis. In a study of untreated syphilis, 10% of patients developed cardiovascular syphilis, 16% had gumma formation, and 7% had neurosyphilis.<ref name=Oslo>{{cite journal | author=Clark EG, Danbolt N |title=The Oslo study of the natural course of untreated syphilis: An epidemiologic investigation based on a re-study of the Boeck-Bruusgaard material | journal=Med Clin North Am. | date=1964 | volume=48 | pages=613}}</ref>
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| [[Nervous system|Neurological]] complications at this stage can be diverse. In some patients, manifestations include [[general paresis of the insane|generalized paresis of the insane]] which results in personality changes, changes in emotional affect, hyperactive reflexes, and [[Argyll-Robertson pupil]]. This is a diagnostic sign in which the small and irregular pupils constrict in response to focusing the eyes, but not to light. [[Tabes dorsalis]], also known as [[locomotor ataxia]], a disorder of the [[spinal cord]], often results in a characteristic shuffling gait. See below for more information about neurosyphilis.
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| [[Cardiovascular system|Cardiovascular]] complications include [[syphilitic aortitis]], [[aortic aneurysm]], [[aneurysm of sinus of Valsalva]], and [[aortic regurgitation]]. Syphilis infects the ascending [[aorta]] causing [[dilation]] and [[aortic regurgitation]]. This can be heard with a stethoscope as a [[heart murmur]]. The course can be insidious, and [[heart failure]] may be the presenting sign after years of disease. The infection can also occur in the [[coronary artery|coronary arteries]] and cause narrowing of the vessels. Syphilitic aortitis can cause ''[[de Musset's sign]]'',<ref>{{cite journal | author=Sapira JD | title="Quincke, de Musset, Duroziez, and Hill: some aortic regurgitations" | journal=South Med J. | date=1981 Apr | volume=74 | issue=4 | pages=459-67 }}</ref> a bobbing of the head that de Musset first noted in Parisian prostitutes.
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| ===Neurosyphilis===
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| [[Image:DürerSyphilis1496.jpg|thumb|left|100px|In this medical illustration attributed to [[Albrecht Dürer]] (1496), the disease is believed to have astrological causes.]]
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| ''Neurosyphilis'' refers to a site of infection involving the [[central nervous system]] (CNS). Neurosyphilis may occur at any stage of syphilis. Before the advent of antibiotics, it was typically seen in 25-35% of patients with syphilis. Neurosyphilis is now most common in patients with [[HIV]] infection. Reports of neurosyphilis in HIV-infected persons are similar to cases reported before the HIV [[pandemic]]. The precise extent and significance of neurologic involvement in HIV-infected patients with syphilis, reflected by either laboratory or clinical criteria, have not been well characterized. Furthermore, the alteration of host [[immunosuppression]] by [[antiretroviral drug|antiretroviral therapy]] in recent years has further complicated such characterization.
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| Approximately 35% to 40% of persons with secondary syphilis have [[asymptomatic]] [[central nervous system]] (CNS) involvement, as demonstrated by any of these on [[cerebrospinal fluid]] (CSF) examination:
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| *An abnormal leukocyte cell count, protein level, or glucose level
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| *Demonstrated reactivity to Venereal Disease Research Laboratory ([[VDRL]]) antibody test
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| There are four clinical types of neurosyphilis:
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| * Asymptomatic neurosyphilis
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| * Meningovascular syphilis
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| * [[General paresis]]<ref name=AMN>{{cite journal | author = Richard B. Jamess, MD, PhD | title = [http://www.health.am/sex/syphilis/ Syphilis- Sexually Transmitted Infections], 2006. | journal =Sexually transmitted diseases treatment guidelines | volume = | issue = | pages = | year = 2002}}</ref>
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| * [[Tabes dorsalis]]
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| The late forms of neurosyphilis (tabes dorsalis and general paresis) are seen much less frequently since the advent of antibiotics. The most common manifestations today are asymptomatic or symptomatic meningitis. Acute syphilitic [[meningitis]] usually occurs within the first year of infection; 10% of cases are diagnosed at the time of the secondary rash. Patients present with headache, meningeal irritation, and [[cranial nerve]] abnormalities, especially the [[optic nerve]], [[facial nerve]], and the [[vestibulocochlear nerve]]. Rarely, it affects the spine instead of the brain, causing focal muscle weakness or sensory loss.
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| Meningovascular syphilis occurs a few months to 10 years (average, 7 years) after the primary syphilis infection. Meningovascular syphilis can be associated with [[prodromal]] symptoms lasting weeks to months before focal deficits are identifiable. Prodromal symptoms include unilateral numbness, [[paresthesia]]s, upper or lower extremity weakness, [[headache]], [[vertigo (medical)|vertigo]], [[insomnia]], and psychiatric abnormalities such as personality changes. The focal deficits initially are intermittent or progress slowly over a few days. However, it can also present as an infectious [[arteritis]] and cause an [[ischemia|ischemic]] [[stroke]], an outcome more commonly seen in younger patients. [[Angiography]] may be able to demonstrate areas of narrowing in the blood vessels or total occlusion.
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| General paresis, otherwise known as general paresis of the insane, is a severe manifestation of neurosyphilis. It is a chronic [[dementia]] which ultimately results in death in as little as 2-3 years. Patients generally have progressive personality changes, memory loss, and poor judgment. More rarely, they can have [[psychosis]], [[clinical depression|depression]], or [[mania]]. Imaging of the brain usually shows atrophy.
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| ==Diagnostic tests==
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| ===Early 20th century===
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| In 1906, the first effective test for syphilis, the [[Wassermann test]], was developed. Although it had some false positive results, it was a major advance in the prevention of syphilis. By allowing testing before the acute symptoms of the disease had developed, this test allowed the prevention of transmission of syphilis to others, even though it did not provide a cure for those infected. In the 1930s the '''Hinton test''', developed by [[William Augustus Hinton]], and based on [[flocculation]], was shown to have fewer [[Type I and type II errors|false positive]] reactions than the Wassermann test. Both of these early tests have been superseded by newer analytical methods.
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| ===Modern diagnostic tests===
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| It was only in the 20th century that effective tests and treatments for syphilis were developed. [[Microscopy]] of fluid from the primary or secondary lesion using darkfield illumination can diagnose treponemal disease with high accuracy. As there are other treponemes that may be confused with ''T. pallidum,'' care must be taken in evaluating with microscopy to correlate symptoms with the correct disease.
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| Present-day syphilis screening tests, such as the [[Rapid Plasma Reagin]] (RPR) and [[Venereal Disease Research Laboratory test|Venereal Disease Research Laboratory]] (VDRL) tests are cheap and fast but not completely [[specificity (tests)|specific]], as many other conditions can cause a positive result. These tests are routinely used to screen [[Blood Donation|blood donors]]. Notably, the spirochete that causes syphilis does not survive the conditions used to store blood and the number of transfusion transmitted cases of syphilis is minuscule, but the test is used to identify donors that might have contracted [[HIV]] from high risk sexual activity. The requirement to test for syphilis has been challenged due to the vast improvements in [[HIV testing]]. False positives on the rapdi tests can be seen in viral infections ([[Epstein-Barr]], [[hepatitis]], [[varicella]], [[measles]]), [[lymphoma]], [[tuberculosis]], [[malaria]], [[endocarditis]], [[connective tissue disease]], [[pregnancy]], intravenous drug abuse, or contamination.<ref name=RedBookSyphilis/> As a result, these two screening tests should always be followed up by a more specific treponemal test. Tests based on [[monoclonal antibodies]] and [[immunofluorescence]], including Treponema pallidum hemagglutination assay ([[TPHA]]) and Fluorescent Treponemal Antibody Absorption ([[FTA-ABS]]) are more specific and more expensive. Unfortunately, false positives can still occur in related treponomal infections such as [[yaws]] and [[Pinta (disease)|pinta]]. Tests based on [[enzyme]]-linked [[immunoassay]]s are also used to confirm the results of simpler screening tests for syphilis.
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| Neurosyphilis is diagnosed by finding high numbers of [[leukocytes]] in the [[cerebrospinal fluid|CSF]] or abnormally high protein concentration in the setting of syphilis infection.<ref name=RedBookSyphilis/> In addition, CSF should be tested with the VDRL test although some advocate using the FTA-ABS test to improve sensitivity. There is anecdotal evidence that the incidence of neurosyphilis is higher in HIV patients, and some have recommended that all HIV-positive patients with syphilis should have a [[lumbar puncture]] to look for asymptomatic neurosyphilis.<ref>{{cite journal | author=Walter T, Lebouche B, Miailhes P, ''et al.'' | title=Symptomatic relapse of neurologic syphilis after benzathine penicillin G therapy for primary or secondary syphilis in HIV-infected patients | journal=Clin Infect Dis | year=2006 | volume=43 | issue=6 | pages=787-90 | id=PMID 16912958 }}</ref>
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| ===Diseases caused by other species of Treponema===
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| These diseases are caused by other species or subspecies of ''[[Treponema]]'':
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| *[[Yaws]] is a tropical disease characterized by an infection of the skin, bones and joints; it is caused by a spirochete bacterium, ''Treponema pallidum, sp. pertenue'', also called ''Treponema pertenue''
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| *[[Pinta (disease)|Pinta]] - caused by ''Treponema carateum''
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| *[[Bejel]] - caused by ''Treponema endemicum''
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| ==Treatment==
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| [[Image:Syphilis-poster-wpa-cure.jpg|thumb|200px|Depression-era U.S. poster advocating early syphilis treatment]]
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| ===Prevention===
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| While abstinence from any sexual activity is very effective at helping prevent Syphilis, it should be noted that ''T. pallidum'' readily crosses intact [[mucosa]] and cut skin, including areas not covered by a condom. Proper and consistent use of a [[latex condom]] can reduce, but not eliminate, the spread of syphilis.[http://www.cdc.gov/std/syphilis/STDFact-Syphilis.htm#protect]
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| Individuals sexually exposed to a person with primary, secondary, or early latent syphilis within 90 days preceding the diagnosis should be assumed to be infected and treated for syphilis, even if they are currently [[seronegative]]. If the exposure was more than 90 days before the diagnosis, presumptive treatment is recommended if serologic testing is not immediately available or if follow-up is uncertain. Patients with syphilis of unknown duration and nontreponemal serologic titers ≥1:32 may be considered as having early syphilis for purposes of partner notification and presumptive treatment of sex partners. Long-term sex partners of patients with late syphilis should be evaluated clinically and serologically and treated appropriately. All patients with syphilis should be tested for HIV. Patient education is important as well.
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| ===History===
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| [[Image:400Behandlung der Syphilis.jpg|thumb|Application of mercury.]]
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| There were originally no effective treatments for syphilis. The Spanish priest Francisco Delicado wrote ''El modo de adoperare el legno de India'' (Rome, 1525) about the use of ''[[Guaiacum]]'' in the treatment of syphilis. He himself suffered from syphilis. Another common remedy was [[mercury (element)|mercury]]: the use of which gave rise to the saying "A night in the arms of Venus leads to a lifetime on Mercury".<ref>{{cite web |url=http://www.dailymail.co.uk/pages/live/articles/news/news.html?in_article_id=460406&in_page_id=1770 |title=The magical properties of Mercury, the metal the EU wants to ban | the Daily Mail |accessdate=2007-08-07 |format= |work=}}</ref> It was administered multiple ways including by mouth and by rubbing it on the skin. One of the more curious methods was fumigation, in which the patient was placed in a closed box with his head sticking out. Mercury was placed in the box and a fire was started under the box which caused the mercury to vaporize. It was a grueling process for the patient and the least effective for delivering mercury to the body.
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| As the disease became better understood, more effective treatments were found. The first antibiotic to be used for treating disease was the [[arsenic]]-containing drug [[Arsphenamine|Salvarsan]], developed in 1908 by [[Sahachiro Hata]] while working in the laboratory of [[Nobel prize]] winner [[Paul Ehrlich]]. This was later modified into [[Neosalvarsan]]. Unfortunately, these drugs were not 100% effective, especially in late disease. It had been observed that some who develop high fevers could be cured of syphilis. Thus, for a brief time [[malaria]] was used as treatment for tertiary syphilis because it produced prolonged and high fevers. This was considered an acceptable risk because the malaria could later be treated with [[quinine]] which was available at that time. This discovery was championed by [[Julius Wagner-Jauregg]], who won the 1927 [[Nobel Prize for Medicine]] for his work in this area. Malaria as a treatment for syphilis was usually reserved for late disease, especially neurosyphilis, and then followed by either Salvarsan or Neosalvarsan as adjuvant therapy. These treatments were finally rendered obsolete by the discovery of [[penicillin]], and its widespread manufacture after World War II allowed syphilis to be effectively and reliably cured.<ref name=Brown>{{cite book | author=Brown, Kevin| date=2006 | title=The Pox: The Life and Near Death of a Very Social Disease | location=Stroud | publisher=WSutton | pages=85-111, 185-91}}</ref>
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| ===Current treatment===
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| The first-choice treatment for all manifestations of syphilis remains [[penicillin]] in the form of [[Penicillin#Benzylpenicillin .28penicillin G.29|penicillin G]].<ref name=CDC>{{cite journal | author=Centers for Disease Control | title=Sexually Transmitted Diseases Treatment Guidelines, 2006 | journal=MMWR | volume=55 | date=08-04-2006 | issue=RR-11 | pages=24-32}}</ref> The effect of penicillin on syphilis was widely known before randomized clinical trials were used; as a result, treatment with penicillin is largely based on case series, expert opinion, and years of clinical experience. [[Parenteral]] penicillin G is the only therapy with documented effect during pregnancy. For early syphilis, one dose of penicillin is sufficient.
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| Non-pregnant individuals who have severe allergic reactions to penicillin (e.g., [[anaphylaxis]]) may be effectively treated with oral [[tetracycline]] or [[doxycycline]] although data to support this is limited. [[Ceftriaxone]] may be considered as an alternative therapy, although the optimal dose is not yet defined. However, cross-reactions in penicillin-allergic patients with [[cephalosporin]]s such as ceftriaxone are possible. [[Azithromycin]] was suggested as an alternative. However, there have been reports of treatment failure due to resistance in some areas.<ref name=Azith>{{cite journal | author=Lukehart SA, Godornes C, Molini BJ, et al | title=Macrolide resistance in Treponema pallidum in the United States and Ireland | journal=N Engl J Med. | volume=351 | pages=154-8 | date=2004 | PMID=15247355}}</ref> If compliance and follow-up cannot be ensured, the [[Centers for Disease Control and Prevention|CDC]] recommends [[Desensitization (medicine)|desensitization]] with penicillin followed by penicillin treatment. All pregnant women with syphilis should be desensitized and treated with penicillin. Follow-up includes clinical evaluation at 1 to 2 weeks followed by clinical and serologic evaluation at 3, 6, 9, 12, and 24 months after treatment.
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| ====Late latent and infections of unknown duration====
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| Late latent syphilis is defined as latency for greater than one year. If CSF examination yields no evidence of neurosyphilis, then penicillin G is recommended as weekly doses for 3 weeks. If allergic, then tetracycline or doxycycline may also be used for this stage, but for 28 days instead of the normal 14. As with before, the data to support use of tetracycline and ceftriaxone are limited.
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| ====Neurosyphilis====
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| For patients diagnosed with neurosyphilis including ocular or auditory syphilis with or without positive CSF results, aqueous crystalline penicillin G is the treatment of choice. The recommended regimen is intravenous treatment every 4 hours or continuously for 10-14 days. If intravenous administration is not possible, then [[Penicillin#Procaine benzylpenicillin|procaine penicillin]] is an alternative (administered daily with [[probenecid]] for two weeks). Procaine injections are painful, however, and patient compliance may be difficult to ensure. To approximate the 21-day course of therapy for late latent disease and to address concerns about slowly dividing treponemes, most experts now recommend 3 weekly doses of benzathine penicillin G after the completion of a 14-day course of aqueous crystalline or aqueous procaine penicillin G for neurosyphilis. No oral antibiotic alternatives are recommended for the treatment of neurosyphilis. The only alternative that has been studied and shown to be effective is intramuscular [[ceftriaxone]] daily for 14 days.
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| ====Alternative regimens====
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| Alternative regimens such as tetracyclines are not well studied in HIV infection and a careful follow-up is recommended. Tetra-cyclines are contraindicated in pregnancy.
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| HIV-infected patients with early syphilis may have a higher risk of neurological complications and a higher rate of treatment failure with currently recommended regimens. The magnitude of these risks, however, although not precisely defined, is probably small. Skin testing or desensitization is recommended in latent syphilis and neurosyphilis in other patients with HIV infection.
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| ===Jarisch-Herxheimer reaction===
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| Before administering any treatment, clinicians should warn all patients about the possibility of a [[Jarisch-Herxheimer reaction]], which occurs most often in secondary syphilis and with penicillin therapy, and may be more common in HIV-infected patients.<ref>{{cite journal |author=Rolfs RT, Joesoef MR, Hendershot EF, ''et al'' |title=A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. The Syphilis and HIV Study Group |journal=N. Engl. J. Med. |volume=337 |issue=5 |pages=307-14 |year=1997 |pmid=9235493 |doi=}}</ref> This reaction is characterized by fever, fatigue, and transient worsening of any mucocutaneous symptoms, and usually subsides within 24 hours. These symptoms can be alleviated with [[acetaminophen]] (paracetamol) and should not be mistaken for drug allergy. In addition, clinicians should inform HIV-infected patients that currently recommended regimens may be less effective for them than for patients without HIV infection and that close serologic follow-up is therefore essential.
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| ===Tuskegee syphilis study===
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| {{main|Tuskegee Study of Untreated Syphilis in the Negro Male}}
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| One of the best-documented cases of [[medical ethics|unethical human medical experimentation]] in the twentieth century was the [[Tuskegee syphilis study]]. The study took place in Tuskegee, Alabama and was supported by the Tuskegee Institute and the [[U.S. Public Health Service]] (PHS).<ref>{{cite web |url=http://www.pbs.org/wnet/aaworld/reference/articles/tuskegee_syphilis_study.html |title=A A World . Reference Room . Articles . Tuskegee Syphilis Study | PBS |accessdate=2007-08-07 |format= |work=}}</ref>
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| The study began in 1932 using a group of 600 black sharecroppers. Of these 600, 399 of the men had the disease and 201 were uninfected control patients. The PHS stated at first that treatment was supposed to be a part of the study, but they were unable to produce any useful data. It was then discovered that the PHS had decided to leave the men untreated and follow the course of the disease to these men's eventual deaths. They thought they were receiving experimental treatment for "bad blood" in exchange for free meals and a $50 death benefit. However, the study was designed to measure the progression of untreated syphilis and to determine whether syphilis caused [[cardiovascular]] damage more often than neurological damage, and to determine if the natural course of the disease was different in black men versus white men. By 1947 penicillin had become the standard treatment of syphilis. The men were never advised that they had syphilis, nor were they offered a treatment including [[Salvarsan]] or the other arsenical drugs that were in use at the beginning of the study.
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| The original study was meant to last six to nine months, but continued for 40 years, ending in 1972, long after wives and children had been infected, and many of the men had died of syphilis. It was estimated that more than one hundred men and women died as a result of this study. The study ended because of a story printed in the ''Washington Star''. A class-action lawsuit was then filed against the federal government for the study. This lawsuit was settled out of court and the living subjects and their descendants were awarded a total of ten million dollars. After the settlement was awarded, the government passed the [[National Research Act]], which required the government to review and approve all medical studies involving human subjects.
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| == Alternative names==
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| The name "syphilis" was coined by the Italian physician and poet [[Girolamo Fracastoro]] in his epic noted poem, written in Latin, entitled ''Syphilis sive morbus gallicus'' (Latin for "Syphilis or The French Disease") in 1530. The protagonist of the poem is a shepherd named Syphilus (perhaps a variant spelling of Sipylus, a character in Ovid's ''Metamorphoses''). Syphilus is presented as the first man to contract the disease, sent by the god Apollo as punishment for the defiance that Syphilus and his followers had shown him. From this character Fracastoro derived a new name for the disease, which he also used in his medical text ''De Contagionibus'' ("On Contagious Diseases").
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| Until that time, as Fracastoro notes, syphilis had been called the "French disease" in Italy and Germany, and the "Italian disease" in France. In addition, the Dutch called it the "Spanish disease", the Russians called it the "Polish disease", the Turks called it the "Christian disease" or "Frank disease" (''frengi'') and the Tahitians called it the "British disease". These 'national' names are due to the disease often being present among invading armies or sea crews, due to the high instance of unprotected sexual contact with prostitutes. It's interesting to notice how the invaders named it after the invaded country and vice versa. It was also called "Great pox" in the 16th century to distinguish it from [[smallpox]]. In its early stages, the Great pox produced a rash similar to smallpox (also known as [[variola]]). However, the name is misleading, as smallpox was a far more deadly disease. The terms "[http://www.merriam-webster.com/dictionary/lues Lues]" (or ''Lues venerea'', Latin for "venereal plague") and "Cupid's disease" have also been used to refer to syphilis. In Scotland, Syphilis was referred to as the ''Grandgore''. It was also called [http://www.antiquusmorbus.com/English/EnglishB.htm The Black Lion].
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| == Origins ==
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| There have been three theories on the origin of syphilis which formed an ongoing debate in anthropological and historical fields.
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| The '''pre-Columbian theory''' holds that syphilis symptoms are described by [[Hippocrates]] in Classical Greece in its [[venereal]]/tertiary form. There are other suspected syphilis findings for pre-contact Europe, including at a 13–14th century Augustinian friary in the northeastern English port of Kingston upon Hull. This city's maritime history is thought to have been a key factor in the transmission of syphilis.<ref>
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| {{cite web
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| |url = http://news.independent.co.uk/health/article266422.ece
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| |title = English syphilis epidemic pre-dated European outbreaks by 150 years
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| |author = Keys, David
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| |accessdate = 2007-09-22
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| |publisher = Independent News and Media Limited
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| |date = 2007
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| }}
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| </ref>
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| Carbon dated skeletons of monks who lived in the friary showed bone lesions typical of venereal syphilis. Skeletons in pre-Columbus Pompeii and Metaponto in Italy demonstrating signs of congenital syphilis have also been found<ref>Henneberg M, Henneberg RJ, 1994, Treponematosis in an Ancient Greek colony of Metaponto, Southern Italy 580-250 BCE [in:] O Dutour, G Palfi, J Berato, J-P Brun (eds), The Origin of Syphilis in Europe, Before or After 1493?, Centre Archeologique du Var, Editions Errance Toulon-Paris, pp. 92-98, Henneberg M, Henneberg RJ, 2002 Reconstructing Medical Knowledge in Ancient Pompeii from the Hard Evidence of Bones and Teeth. In: J Renn, G Castagnetti (eds) Homo Faber: Studies on Nature. Technology and Science at the Time of Pompeii, “L’ERMA” di Bretschneider, Rome, pp.169-187.</ref>, although the interpretation of the evidence has been disputed.<ref>[http://www.archaeology.org/9701/newsbriefs/syphilis.html Origins of Syphilis]</ref>
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| The '''Columbian Exchange theory''' holds that syphilis was a New World disease brought back by Columbus and Martin Alonzo Pinzon. Supporters of the Columbian theory find syphilis [[lesion]]s on pre-contact Native Americans and cite documentary evidence linking crewmen of Columbus's voyages to the Naples outbreak of 1494.<ref>Baker, et al.</ref> A recent study of the genes of venereal syphilis and related bacteria have supported this theory, by locating an intermediate disease between yaws and syphilis in Guyana, South America. <ref>http://www.newscientist.com/article/dn13186-columbus-blamed-for-spread-of-syphilis-.html</ref><ref>http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0000148</ref>
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| Historian Alfred Crosby suggests both theories are correct in a '''combination theory.''' Crosby's argument is built on the similarities of the species of [[bacteria]] which cause yaws and syphilis. The bacteria that causes syphilis belongs to the same phylogenetic family as the bacteria which cause [[yaws]] and several other diseases. Despite a tradition of assigning yaws's homeland to sub-Saharan Africa, Crosby notes that there is no unequivocal evidence of any related disease being present in pre-Columbian Europe, Africa, or Asia, while there is indisputable evidence of syphilis' presence in the pre-Columbian Americas. Conceding this point, Crosby writes, "It is not impossible that the organisms causing [[treponema]]tosis arrived from America in the 1490s...and evolved into both venereal and non-venereal syphilis and yaws."<ref>ref:225 Crosby</ref>
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| However, Crosby considers it somewhat more likely that a highly contagious ancestral species of bacteria moved with early human ancestors across the land bridge of the Bering Straits many thousands of years ago without dying out in the original source population. He hypothesizes that "the differing ecological conditions produced different types of [[treponema]]tosis and, in time, closely related but different diseases".<ref>ref:225 Crosby</ref>
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| Thus, a weak, non-syphilitic bacteria survived in the Old World to eventually give rise to yaws or [[bejel]], while a New World version evolved into the milder [[Pinta (disease)|pinta]] and the more aggressive syphilis.
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| Going further than Crosby in arguing for worldwide incidence of syphilis prior to Columbus, Douglas Owsley, the famed physical anthropologist at the Smithsonian Institution, has written that many medieval European cases of leprosy, colloquially called "lepra," were actually cases of syphilis. Although folklore claimed that syphilis was unknown in Europe until the return of the diseased sailors of the Columbian voyages, {{cquote|. . . syphilis probably cannot be "blamed"—as it often is—on any geographical area or specific race. The evidence suggests that the disease existed in both hemispheres from prehistoric times. It is only coincidental with the Columbus expeditions that the syphilis previously thought of as "lepra" flared into virulence at the end of the fifteenth century.<ref name="OWSLEY">[http://www.jstor.org/ ] John Lobdell and Douglas Owsley, [[Journal of Sex Research]], August 1974, Vol. 10:1 pp. 76-79. Accessed via [[JSTOR]] August 5, 2007.</ref>}}Owsley noted that a Chinese medical case recorded in 2637 B.C.E. seems to be describing a case of syphilis, and that a European writer who recorded an outbreak of "lepra" in 1303 C.E. is "clearly describing syphilis".<ref name="OWSLEY"/>
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| == History ==
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| [[Image:Rembrandt Harmensz. van Rijn 095.jpg|thumb|200px|Portrait of [[Gerard de Lairesse]] by [[Rembrandt van Rijn]], ca. 1665-67, oil on canvas. De Lairesse, himself a painter and art theorist, suffered from congenital syphilis that severely deformed his face and eventually blinded him.<ref>''[[Metropolitan Museum of Art|The Metropolitan Museum of Art Bulletin]]'', Summer 2007, pp. 55-56.</ref>]]
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| While working at the Rockefeller Institute in 1913, [[Hideyo Noguchi]], a Japanese scientist, demonstrated the presence of the spirochete ''[[Treponema pallidum]]'' in the brain of a progressive paralysis patient, proving that ''Treponema pallidum'' was the cause of the disease. [http://www.bartleby.net/65/no/NoguchiH.html] Prior to Noguchi's discovery, syphilis had been a burden to humanity in many lands, sometimes misdiagnosed and often misattributed to political enemies.
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|
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| The insanity caused by late-stage syphilis was once one of the more common forms of [[dementia]]; this was known as the [[general paresis of the insane]].
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| ===European outbreak===
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| The first well-recorded European outbreak of what is now known as syphilis occurred in 1494 when it broke out among French troops besieging Naples.<ref name=Scars_of_Venus>{{cite book | author=Oriel, J.D. | title=The Scars of Venus: A History of Venereology | location=London | publisher= Springer-Verlag | date=1994 }}</ref> The French may have caught it via Spanish mercenaries serving King Charles of France in that siege.<ref name="OWSLEY"/> From this centre, the disease swept across Europe. As Jared Diamond describes it, "when syphilis was first definitely recorded in Europe in 1495, its pustules often covered the body from the head to the knees, caused flesh to fall from people's faces, and led to death within a few months." In addition, the disease was more frequently fatal than it is today. Diamond concludes that "by 1546, the disease had evolved into the disease with the symptoms so well known to us today."<ref name=Diamond1>{{cite book | author=Diamond, Jared | date=1997 | title=Guns, Germs and Steel | location=New York | publisher=W.W. Norton | pages=210}}</ref> The [[epidemiology]] of this first syphilis epidemic shows that the disease was either new or a mutated form of an earlier disease.
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| ==See also==
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| *[[Tuberculosis]] ([[TB]])
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| *[[Dyphtheria]]
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| *[[Side-chain theory]]
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| *[[Paul Ehrlich]]
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| ==References==
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| {{Reflist|2}}
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| [http://213.156.0.164/foo.html]
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| ==External links==
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| *[http://www.stdhelp.org/forum/ Syphilis Community]
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| *[http://hivinsite.ucsf.edu/InSite?page=kb-05-01-04 UCSF HIV InSite Knowledge Base Chapter: Syphilis and HIV]
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| *[http://colman.net/eadv/index.html "A New Gold Standard For Syphilis?" Poster Presentation for European Academy of Dermatology and Venereology 2004 Spring Symposium]
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| *[http://medinfo.ufl.edu/other/histmed/clancy/ Kipkeepers, Pox and Gleet Vendors: A Rapid History of Syphilis]
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| *[http://www.poxhistory.com/ POX: Genius, Madness, and the Mysteries of Syphilis]
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| *[http://www.yourstdhelp.com/syphilis.html Syphilis Informational resource ]
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| *[http://www.pbs.org/wnet/secrets/case_syphilis/index.html Secrets of the Dead (PBS): The Syphilis Enigma]
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| *[http://www.cbc.ca/ideas/Aids Syphilis and AIDS: Lessons from history]
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| *[http://www.cdc.gov/std/Syphilis/STDFact-Syphilis.htm "Syphilis fact sheet" from the Center for Disease Control]
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| *[http://www.nobel.se/medicine/laureates/1927/wagner-jauregg-lecture.html The treatment of dementia paralytica by malaria inoculation (A Nobel Prize lecture, December 13, 1927)]
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| *[http://www.niaid.nih.gov/factsheets/stdsyph.htm National Institute of Allergy and Infectious Diseases Factsheet]
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| *[http://uk.reuters.com/article/oddlyEnoughNews/idUKN1443055520080115 New study blames Columbus for syphilis spread] from Reuters Jan 15, 2008
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| {{STD/STI}}
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| {{Spirochetal diseases}}
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| [[ar:زهري]]
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