Syphilis
Classification and external resources
Electron micrograph of Treponema pallidum
ICD-10	A50-A53
ICD-9	090-097
DiseasesDB	29054
MedlinePlus	001327
eMedicine	med/2224 emerg/563 derm/413
MeSH	D013587

Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis. Other human diseases caused by related Treponema pallidum include yaws (subspecies pertenue), pinta (subspecies carateum) and bejel (subspecies endemicum).

The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, and tertiary). The primary stage classically presents with a single chancre (a firm, painless, non-itchy skin ulceration), secondary syphilis with a diffuse rash which frequently involves the palms of the hands and soles of the feet, latent syphilis with little to no symptoms, and tertiary syphilis with gummas, neurological, or cardiac symptoms. It has, however, been known as "the great imitator" due to its frequent atypical presentations. Diagnosis is usually via blood tests; however, the bacteria can also be visualized under a microscope. Syphilis can be effectively treated with antibiotics, specifically the preferred intramuscular penicillin G (given intravenously for neurosyphilis), or else ceftriaxone, and in those who have a severe pencillin allergy, oral doxycycline or azithromycin.

Syphilis is believed to have infected 12 million people worldwide in 1999, with greater than 90% of cases in the developing world. After decreasing dramatically since the widespread availability of penicillin in 1940s, rates of infection have increased since the turn of the millennium in many countries, often in combination with human immunodeficiency virus (HIV). This has been attributed partly to unsafe sexual practices among men who have sex with men, increased promiscuity, prostitution and decreasing use of barrier protection.^[1][2][3]

Signs and symptoms[link]

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

Primary[link]

Primary chancre of syphilis on the hand

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

Secondary[link]

Typical presentation of secondary syphilis with a rash on the palms of the hands

Reddish papules and nodules over much of the body due to secondary syphilis

Secondary syphilis occurs approximately four to ten weeks after the primary infection.^[4] While secondary disease is known for the many different ways it can manifest, symptoms most commonly involve the skin, mucous membranes, and lymph nodes.^[9] There may be a symmetrical, reddish-pink, non-itchy rash on the trunk and extremities, including the palms and soles.^[4][10] The rash may become maculopapular or pustular. It may form flat, broad, whitish, wart-like lesions known as condyloma latum on mucous membranes. All of these lesions harbor bacteria and are infectious. Other symptoms may include fever, sore throat, malaise, weight loss, hair loss, and headache.^[4] Rare manifestations include hepatitis, kidney disease, arthritis, periostitis, optic neuritis, uveitis, and interstitial keratitis.^[4][11] The acute symptoms usually resolve after three to six weeks;^[11] however, about 25% of people may present with a recurrence of secondary symptoms. Many people who present with secondary syphilis (40–85% of women, 20–65% of men) do not report previously having had the classic chancre of primary syphilis.^[9]

Latent[link]

Latent syphilis is defined as having serologic proof of infection without symptoms of disease.^[7] It is further described as either early (less than 1 year after secondary syphilis) or late (more than 1 year after secondary syphilis) in the United States.^[11] The United Kingdom uses a cut-off of two years for early and late latent syphilis.^[8] Early latent syphilis may have a relapse of symptoms. Late latent syphilis is asymptomatic, and not as contagious as early latent syphilis.^[11]

Tertiary[link]

Patient with tertiary (gummatous) syphilis. Bust in Musée de l'Homme, Paris.

Tertiary syphilis may occur approximately three to 15 years after the initial infection, and may be divided into three different forms: gummatous syphilis (15%), late neurosyphilis (6.5%), and cardiovascular syphilis (10%).^[4][11] Without treatment, a third of infected people develop tertiary disease.^[11] People with tertiary syphilis are not infectious.^[4]

Gummatous syphilis or late benign syphilis usually occurs one to 46 years after the initial infection, with an average of 15 years. This stage is characterized by the formation of chronic gummas, which are soft, tumor-like balls of inflammation which may vary considerably in size. They typically affect the skin, bone, and liver, but can occur anywhere.^[4]

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

Cardiovascular syphilis usually occurs 10–30 years after the initial infection. The most common complication is syphilitic aortitis, which may result in aneurysm formation.^[4]

Congenital[link]

Congenital syphilis may occur during pregnancy or during birth. Two-thirds of syphilitic infants are born without symptoms. Common symptoms that then develop over the first couple years of life include: hepatosplenomegaly (70%), rash (70%), fever (40%), neurosyphilis (20%), and pneumonitis (20%). If untreated, late congenital syphilis may occur in 40%, including: saddle nose deformation, Higoumenakis sign, saber shin, or Clutton's joints among others.^[12]

Cause[link]

Bacteriology[link]

Histopathology of Treponema pallidum spirochetes using a modified Steiner silver stain

Treponema pallidum subspecies pallidum is a spiral-shaped, Gram-negative, highly mobile bacterium.^[8][13] Three other human diseases are caused by related Treponema pallidum, including yaws (subspecies pertenue), pinta (subspecies carateum) and bejel (subspecies endemicum).^[4] Unlike subtype pallidum, they do not cause neurological disease.^[12] Humans are the only known natural reservoir for subspecies pallidum.^[5] It is unable to survive without a host for more than a few days. This is due to its small genome (1.14 MDa) and thus its inability to make most of its macronutrients. It has a slow doubling time of greater than 30 hours.^[8]

Transmission[link]

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

Diagnosis[link]

Poster for testing of syphilis, showing a man and a woman bowing their heads in shame (circa 1936)

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

Blood tests[link]

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

Direct testing[link]

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

Prevention[link]

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

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

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

Treatment[link]

Early infections[link]

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

Late infections[link]

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

Jarisch-Herxheimer reaction[link]

One of the potential side effects of treatment is the Jarisch-Herxheimer reaction. It frequently starts within one hour and lasts for 24 hours, with symptoms of fever, muscles pains, headache, and tachycardia.^[4] It is caused by cytokines released by the immune system in response to lipoproteins released from rupturing syphilis bacteria.^[27]

Epidemiology[link]

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

no data   <35   35-70   70-105   105-140   140-175   175-210

210-245   245-280   280-315   315-350   350-500   >500

Syphilis is believed to have infected 12 million people in 1999, with greater than 90% of cases in the developing world.^[5] It affects between 700,000 and 1.6 million pregnancies a year, resulting in spontaneous abortions, stillbirths, and congenital syphilis. In sub-Saharan Africa, syphilis contributes to approximately 20% of perinatal deaths.^[12] Rates are proportionally higher among intravenous drug users, those who are infected with HIV, and men who have sex with men.^[1][2][3] In the United States, rates of syphilis as of 2007 were six times greater in men than women, while they were nearly equal in 1997.^[29] African Americans accounted for almost half of all cases in 2010.^[30]

Syphilis was very common is Europe during the 18th and 19th centuries. In the developed world during the early 20th century, infections declined rapidly with the widespread use of antibiotics, until the 1980s and 1990s.^[13] Since the year 2000, rates of syphilis have been increasing in the USA, Canada, the UK, Australia and Europe, primarily among men who have sex with men.^[5] Rates of syphilis among American women have, however, remained stable during this time, and rates among UK women have increased, but at a rate less than that of men.^[31] Increased rates among heterosexuals have occurred in China and Russia since the 1990s.^[5] This has been attributed to unsafe sexual practices, such as sexual promiscuity, prostitution, and decreasing use of barrier protection.^[5][32][31]

Untreated, it has a mortality of 8% to 58%, with a greater death rate in males.^[4] The symptoms of syphilis have become less severe over the 19th and 20th centuries, in part due to widespread availability of effective treatment and partly due to decreasing virulence of the spirochaete.^[9] With early treatment, few complications result.^[8] Syphilis increases the risk of HIV transmission by two to five times, and coinfection is common (30–60% in a number of urban centers).^[4][5]

History[link]

Portrait of Gerard de Lairesse by Rembrandt van Rijn, circa 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.^[33]

The exact origin of syphilis is unknown.^[4] Of two primary hypotheses, one proposes syphilis was carried to Europe by the returning crewmen from Christopher Columbus's voyage to the Americas, the other proposes syphilis existed in Europe previously, but went unrecognized. These are referred to as the "Columbian" and "pre-Columbian" hypotheses, respectively.^[15] The Columbian hypothesis is best supported by the available evidence.^[34] The first written records of an outbreak of syphilis in Europe occurred in 1494/1495 in Naples, Italy, during a French invasion.^[13][15] Due to it being spread by returning French troops, it was initially known as the "French disease", as it is still traditionally referred. In 1530, the name "syphilis" was first used by the Italian physician and poet Girolamo Fracastoro as the title of his Latin poem in dactylic hexameter describing the ravages of the disease in Italy.^[35] It was also known historically as the "Great Pox".^[36][37]

The causative organism, Treponema pallidum, was first identified by Fritz Schaudinn and Erich Hoffmann in 1905.^[13] The first effective treatment (Salvarsan) was developed in 1910 by Paul Ehrlich, which was followed by trials of penicillin and confirmation of its effectiveness in 1943.^[13][36] Before the advent of effective treatment, mercury and isolation were commonly used, with treatments often worse than the disease.^[36] Many famous historical figures, including Franz Schubert, Arthur Schopenhauer, Édouard Manet^[13] and Adolf Hitler,^[38] are believed to have had the disease.

Society and culture[link]

Arts and literature[link]

Moll dies of syphillis, Hogarth's A Harlot's Progress

The earliest Europe work of art to depict syphilis is Albrecht Dürer's Syphilitic Man, a wood cutting believed to represent a Landsknecht, a Northern European mercenary.^[39] 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.^[40][41]

The artist Jan van der Straet painted a scene of a wealthy man receiving treatment for syphilis with the tropical wood guaiacum sometime around 1580.^[42] The title of the work is "Preparation and Use of Guayaco for Treating Syphilis". That the artist chose to include this image in a series of works celebrating the New World indicates how important a treatment, however ineffective, for syphilis was to the European elite at that time. The richly colored and detailed work depicts four servants preparing the concoction while a physician looks on, hiding something behind his back while the hapless patient drinks.^[43]

Tuskegee and Guatemala studies[link]

One of the most infamous United States cases of questionable medical ethics in the 20th century was the Tuskegee syphilis study.^[44] The study took place in Tuskegee, Alabama, and was supported by the U.S. Public Health Service (PHS) in partnership with the Tuskegee Institute.^[45] The study began in 1932, when syphilis was a widespread problem and there was no safe and effective treatment.^[6] The study was designed to measure the progression of untreated syphilis. By 1947, penicillin had been validated as an effective cure for syphilis and was becoming widely used to treat the disease. Study directors, however, continued the study and did not offer the participants treatment with penicillin.^[45] This is debated, and some have found that penicillin was given to many of the subjects.^[6] The study did not end until 1972.^[45]

Syphilis experiments were also carried out in Guatemala from 1946 to 1948. They were United States-sponsored human experiments, conducted during the government of Juan José Arévalo with the cooperation of some Guatemalan health ministries and officials. Doctors infected soldiers, prisoners, and mental patients with syphilis and other sexually transmitted diseases, without the informed consent of the subjects, and then treated them with antibiotics. In October 2010, the U.S. formally apologized to Guatemala for conducting these experiments.^[46]

References[link]

Further reading[link]

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

External links[link]

Find more about Syphilis on Wikipedia's sister projects:
	Definitions and translations from Wiktionary
	Images and media from Commons
	Learning resources from Wikiversity
	News stories from Wikinews
	Quotations from Wikiquote
	Source texts from Wikisource
	Textbooks from Wikibooks

• "Syphilis - CDC Fact Sheet" Centers for Disease Control and Prevention (CDC)
• UCSF HIV InSite Knowledge Base Chapter: Syphilis and HIV

Demetri Martin
Demetri Martin at Northeastern University on April 11, 2007
Born	(1973-05-25) May 25, 1973 (age 39) New York City, New York, United States
Nationality	American
Years active	Since 2002
Genres	Observational comedy, surreal humor, musical comedy, wit/wordplay, sketch comedy
Subject(s)	Everyday Life, American Culture, Random Subjects
Influences	Steven Wright, Eddie Izzard, Emo Philips, Mitch Hedberg, Socrates
Notable works and roles	· Demetri Martin. Person.  · Correspondent on The Daily Show  · Himself/Various on Important Things with Demetri Martin  · Elliot Tiber in Taking Woodstock (2009)
Website	www.demetrimartin.com

Demetri Martin (born May 25, 1973) is an American comedian, actor, artist, musician, writer and humorist. Martin is best known for his work as a stand-up comedian, contributor on The Daily Show and for his Comedy Central show Important Things with Demetri Martin.

Early life[link]

Demetri Martin was born to a Greek American family^[1] in New York City, New York, and grew up in Toms River, New Jersey. He is the son of Lillian, a nutritionist, and Dean C. Martin, now deceased, a Greek Orthodox priest.^[2] Martin graduated from Yale University in 1995. Although he was accepted into Harvard Law School, he went to New York University School of Law after he received a full scholarship.^[3]

Career[link]

In 2001, Martin caught his first big break in stand-up comedy when he appeared on Comedy Central's stand-up showcase Premium Blend. At the 2003 Edinburgh Festival Fringe he won the Perrier award with his show If I....^[4] The show was turned into a British television special in 2004. From 2003 to 2004, Martin wrote for Late Night with Conan O'Brien.^[5] In 2004, Martin had his own Comedy Central Presents stand-up special. His special was divided into three parts. In the first, he performed in traditional stand-up comedy fashion. In the second segment, he used humorous drawings as visual aids, which would serve either as the punchline or a background. During the third segment, he played a guitar and put on a pseudo-play where he would strum his guitar while alternating between playing harmonica and talking; some of his comedian friends dressed as fairies and dragons acted according to the story he was telling, detailing the magical land where his jokes came from. Martin's mother and grandmother also appeared.

Since late 2005, he has been credited as a contributor on The Daily Show, on which he has appeared as the named "Senior Youth Correspondent" and on which he hosts a segment called "Trendspotting". He has used this segment to talk about so-called hip trends among youth such as hookahs, wine, guerilla marketing and Xbox 360. A piece about social networking featured his profile on MySpace.^[6] On March 22, 2007, Demetri made another appearance on The Daily Show, talking about the Viacom lawsuit against Google and YouTube.

He has recorded a comedy CD/DVD titled These Are Jokes, which was released on September 26, 2006. This album also features Saturday Night Live member Will Forte and stand-up comedian Leo Allen.

Martin returned to The Daily Show on March 22, 2006, as the new Youth Correspondent, calling his segment "Professional Important News with Demetri Martin". In 2007, he starred in a Fountains of Wayne music video for "Someone to Love" as Seth Shapiro, a character in the song. He also starred in the video for the Travis single "Selfish Jean", in which he wears multiple t-shirts with lyrics written on them.

On September 2, 2007, Martin appeared on the season finale of the HBO series Flight of the Conchords. He appeared as a keytar player named Demetri.^[7]

He also had a part in the movie The Rocker (2008) starring Rainn Wilson. Martin played the part of the videographer when the band in the movie was making their first music video.

In 2009, he hosted and starred in his own television show called Important Things With Demetri Martin on Comedy Central. Later in June, it was announced his show had been renewed for a second season.^[8] The second season premiered, again on Comedy Central, on February 4, 2010. Martin has stated that Important Things will not return for a third season.

Prior to completing work on his second season, Martin starred in the comedy-drama film Taking Woodstock (2009), directed by Ang Lee, which premiered at the 2009 Cannes Film Festival. In the film Martin plays Elliot Tiber, a closeted gay artist who has given up his ambitions in the city to move upstate and help his old-world Jewish family run their Catskill Mountains motel. The film is based on the book written by Tiber.

On April 25, 2011, Martin released his first book, titled This Is a Book by Demetri Martin.

Martin was slated to portray Paul DePodesta as Oakland Athletics assistant GM to Billy Beane in the 2011 movie Moneyball, however was dropped and Jonah Hill took his place in the movie.

Plans[link]

Martin sold his movie concept Will to DreamWorks; he is expected to play a key supporting role.^[9] He will play the lead in the film Moon People, a pitch that he sold to Columbia Pictures.

Martin also signed a blind script deal with CBS in October 2010 to produce, write, and star in his own television series.^[10]

After CBS was shown the pilot for the series, they decided not to air it.^[11]

On August 11, 2011, Fox ordered a presentation of a new animated show they might air.^{[citation needed]}

[edit] If I

If I is a Perrier Comedy Award-winning comedy one-man show written and performed by Demetri Martin at the 2003 Edinburgh Festival Fringe.^[12] It was also aired on British television as a special. The show is an autobiographical examination of Martin's life, as seen through various definitions of the word "if."

The title of the special comes from a lengthy palindromic poem that Martin wrote; the words "if I" are at the center of the poem.^[13]

Comedic style[link]

Martin is known for being an unconventional stand-up comic. He uses one-liners and drawings on a "large pad", as well as accompanying his jokes with music on either guitar, harmonica, piano, keyboard, glockenspiel, toy bells, ukulele, or tambourine, sometimes all at once.^[14] He has cited comedian Steven Wright as an important influence (both use deadpan one-liners in their acts) and he is also a fan of Bill Cosby.^[15]

Personal life[link]

According to a July 2011 interview on the WTF with Marc Maron podcast, Demetri had a short-lived marriage to a girl he knew from high school. They began dating after high school and got married when he was in NYU Law School and she was attending NYU Medical School. He was aged 25 and in the end of his marriage when his stand-up career began.^[3]

He is extremely allergic to nuts and peanuts.^[16]

Martin moved to Santa Monica, California in 2009.^[17]

Filmography[link]

• Invite Them Up (2005)
• These Are Jokes (2006)
• Demetri Martin. Person. (2007)
• Important Things with Demetri Martin (2009–2010)

Filmography and television work[link]

Written works[link]

• This Is a Book, April 2011, ISBN 978-0446539708.

Awards and nominations[link]

References[link]

External links[link]

This article's use of external links may not follow Wikipedia's policies or guidelines. Please improve this article by removing excessive or inappropriate external links, and converting useful links where appropriate into footnote references. (May 2012)

• Official website
• Demetri Martin on Myspace
• Demetri Martin at the Internet Movie Database
• Interview from November, 2006, in Onion AV Club
• Interview from October 2006, in The DePaulia
• Article, in The Scotsman
• Article, in Gelf Magazine
• Interview by Brian M. Palmer
• MP3 Audio Interview on The Sound of Young America public radio show and podcast
• Interview Believer Mag
• New Jersey Monthly Magazine
• Fresh Air, NPR.org

This article may require cleanup to meet Wikipedia's quality standards. The specific problem is: The article lacks structure and needs more background information (as well as sources).. Please help improve this article if you can; the talk page may contain suggestions. (December 2011)

This article may require copy editing for grammar, style, cohesion, tone, or spelling. You can assist by editing it. (December 2011)

This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (December 2011)

There are many people in history who are commonly appended with the phrase "the Great", or who were called that or an equivalent phrase in their own language. Other languages have their own suffixes such as e Bozorg and e azam in Persian and Urdu respectively.

In Persia, the title "the Great" at first seems to be a colloquial version of the Old Persian title "Great King". This title was first used by the conqueror Cyrus II of Persia.^[1]

The Persian title was inherited by Alexander III of Macedon (336–323 BC) when he conquered the Persian Empire, and the epithet "Great" eventually became personally associated with him. The first reference (in a comedy by Plautus)^[2] assumes that everyone knew who "Alexander the Great" was; however, there is no earlier evidence that Alexander III of Macedon was called "the Great".

The early Seleucid kings, who succeeded Alexander in Persia, used "Great King" in local documents, but the title was most notably used for Antiochus the Great (223–187 BC).

Later rulers and commanders began to use the epithet "the Great" as a personal name, like the Roman general Pompey. Others received the surname retrospectively, like the Carthaginian Hanno and the Indian emperor Ashoka the Great. Once the surname gained currency, it was also used as an honorific surname for people without political careers, like the philosopher Albert the Great.

As there are no objective criteria for "greatness", the persistence of later generations in using the designation greatly varies. For example, Louis XIV of France was often referred to as "The Great" in his lifetime but is rarely called such nowadays, while Frederick II of Prussia is still called "The Great". A later Hohenzollern - Wilhelm I - was often called "The Great" in the time of his grandson Wilhelm II, but rarely later.

Rulers[link]

• Abbas I of Persia (1571–1629), Shah of Iran
• Akbar (1542–1605), ruler of the Mughal Empire of South Asia, mainly India
• Alain I of Albret (1440–1522), French aristocrat
• Alexander the Great (356-323 BC), King of Macedonia, Persia, Greece, Egypt, and all of Mesopotamia
• Alexander I of Georgia (1386–1446), King of Georgia
• Alfonso III of León (c. 848-910), King of León, Galicia and Asturias
• Alfred the Great (848/849-899), King of Wessex
• Antiochus III the Great (c. 241–187 BC), ruler of the Seleucid Empire
• Ashoka the Great (c. 304–232 BC), Indian emperor of the Maurya dynasty
• Ashot I of Iberia “the Great”(died 826/830), presiding prince of Iberia (modern Georgia),
• Askia Mohammad I (c. 1442–1538), ruler of the Songhai Empire
• Bhumibol Adulyadej (born 1927), King of Thailand
• Bolesław I Chrobry (967-1025), sometimes called "the Great", first King of Poland
• Bruno the Great (925–965), Archbishop of Cologne and Duke of Lotharingia (also listed in the following section)
• Buddha Yodfa Chulaloke (1736–1809), founder and ruler of the Rattanakosin Kingdom (in what is now Thailand)
• Cnut the Great (c. 985 or 995-1035), King of Denmark, England, Norway and parts of Sweden
• Casimir III the Great (1310–1370), King of Poland
• Catherine the Great (1729–1796), Empress of Russia
• Chandragupta II (reigned 375-413/415), also known as Vikramaditya, ruler of the Gupta empire in India
• Charlemagne (died 814), King of the Franks and Emperor of the Romans
• Chulalongkorn (1853–1910), King of Siam (now Thailand)
• Chlothar II (584-629), King of Neustria and King of the Franks
• Conrad, Margrave of Meissen (c. 1097-1157), Margrave of Meissen
• Constantine I (c. 272-337), Roman emperor
• Cyaxares the Great (c. 625-585 BC), third king of Media
• Cyrus the Great (c. 600 BC or 576 BC–530 BC), founder and ruler of the Persian or Achaemenid Empire
• Darius the Great (550 – 486 BC), third ruler of the Persian Empire
• Devapala (died 850), ruler of the Pala Empire in the Indian subcontinent
• Dionysius I, Greek tyrant of Syracuse^[3]
• Ferdinand I of León and Castile (c. 1015–1065), King of León and Count of Castile
• Frederick the Great (1712–1786), King of Prussia
• Genghis Khan (1162?-1227), founder and Great Khan of the Mongol Empire
• Gero (c. 900–965), ruler of Marca Geronis, a very large march in Europe
• Gustavus Adolphus of Sweden (1594–1632), King of Sweden, founder of the Swedish Empire, and noted military leader
• Gwanggaeto the Great, King of Goguryeo, one of the Three Kingdoms of Korea^[4][5]
• Hanno the Great, the name of three leaders of Carthage, in the 4th, 3rd, and 2nd centuries BC
• Henry I, Duke of Burgundy (946–1002)
• Henry IV of France (1553–1610), King of France and King of Navarre
• Herod the Great (73/74 BC-4 BC), King of Judea
• Hugh the Great (898-956), Duke of the Franks and Count of Paris
• Hugh Magnus of France (1007–1025), co-King of France
• Hugh I, Count of Vermandois (1057–1101)
• Humphrey I de Bohun (died c. 1123), Anglo-Norman aristocrat
• Ivan III of Russia (1440–1505), Tsar of Russia
• John I of Portugal (1358–1433), King of Portugal and the Algarve
• John II of Aragon (1398–1479), King of Aragon and, through his wife, King of Navarre
• Justinian I (483-565), Byzantine Emperor
• Kamehameha I (c. 1758-1819), first King of Hawai'i
• Kanishka (died c. 127), ruler of the Kushan Empire in Central Asia and parts of India
• Kvirike III of Kakheti (1010–1029), King of Kakheti in eastern Georgia
• Kublai Khan (1215–1294), Mongol ruler in the 13th century and Emperor of China; founder of the Yuan Dynasty
• Llywelyn the Great (c. 1172–1240), Prince of Gwynedd and de facto ruler of most of Wales
• Louis I of Hungary (1326–1382), King of Hungary, Croatia and Poland
• Mangrai the Great (1238–1317), Lanna, northern Thailand
• Emperor Meiji (1852–1912), Emperor of Japan
• Mircea I of Wallachia (1355–1418)
• Mithridates II of Parthia (died 88 BC), ruler of the Parthian Empire (in present day Iran)
• Mithridates VI of Pontus (134 BC–63 BC), ruler of Pontus and the Bosporan Kingdom
• Mstislav I of Kiev (1076–1132), Grand Prince of Kievan Rus
• Naresuan (1555–1605), King of Ayutthaya
• Narai (1633–1688), King of Ayutthaya (in what is now modern Thailand)
• Odo the Great (died c. 735), Duke of Aquitaine
• Otto I, Holy Roman Emperor (912-973)
• K'inich Janaab' Pakal (603-683), ruler of the Mayan city-state of Palenque
• Parakramabahu I of Polonnaruwa (1123–1186), King of Sri Lanka
• Peter Krešimir IV of Croatia (died 1075), King of Croatia
• Peter the Great (1672–1725), Tsar of Russia
• Peter III of Aragon (1239–1285), King of Aragon and King of Sicily
• Pompey (106 BC-48 BC), military and political leader of the late Roman Republic, rival of Julius Caesar
• Radama I (1793–1828), first king of greater Madagascar
• Raja Raja Chola I (c. 947-1014), Indian emperor of the Cholas.^[6][7][8]
• Rajendra Chola I (reigned 1014–1044), Tamil King of India
• Ramesses II (reigned 1279 BC – 1213 BC), considered the greatest pharaoh of Ancient Egypt
• Ram Khamhaeng (around 1237 to 1247-1298), King of Sukhothai (in present day Thailand)
• Ramon Berenguer III, Count of Barcelona (1082–1131), also Count of Provence and various other counties
• Rhodri the Great (c. 820–878), King of Gwynedd (in present day Wales)
• Roman the Great (after 1160-1205), Grand Prince of Kiev
• Saladin (c. 1138-1193), Kurdish Sultan of Egypt and Syria, founder of the Ayyubid dynasty, and victor over the Crusaders
• Samudragupta (c. 335–375), ruler of the Gupta empire in the Indian subcontinent
• Sancho III of Navarre (c. 992-1035), King of Kingdom of Navarre
• Sargon of Akkad (died c. 2215 BC), ruler of the Akkadian Empire
• Sejong the Great (1397–1450), Korean king^[9]
• Shapur II (309-379), king of the Sassanid Empire, Persia
• Simeon I of Bulgaria (864/865-927), ruler of the First Bulgarian Empire
• Stephen III of Moldavia (1433–1504), Prince of Moldavia (Romania)
• Stephen Uroš IV Dušan of Serbia (c. 1308-1355), King of Serbia and Emperor of the Serbs and Greeks
• Taksin (1734–1782), King of the Thonburi Kingdom (Thailand)
• Tamar (1160-1123), Queen of the Georgian Empire
• Timur (1336–1405), better known as Tamerlane, founder of the Timurid Dynasty
• Theobald II, Count of Champagne (1090–1151), Count of Blois and of Chartres as Theobald IV, Count of Champagne and of Brie
• Theodoric the Great (454-526), King of the Ostrogoths, regent of the Visigoths and a viceroy of the Byzantine Empire
• Theodosius I (347-395), Roman emperor
• Tigranes the Great (140-55 BC), Emperor of Armenia
• Tiridates III of Armenia (285-339), King of Armenia
• Umar (c. 586 to 590–644), second caliph of the Muslim Empire
• Valdemar I of Denmark (1131–1182), King of Denmark
• Valentinian I (364-375), Roman Emperor
• Vladimir I of Kiev (c. 958-1015), ruler of Kievan Rus
• Vytautas (c. 1350-1430), archduke of the Lithuanian Grand Duchy
• William I, Count of Burgundy (1020–1087), Count of Burgandy and Mâcon
• William V, Duke of Aquitaine (969-1030), also Count of Poitou
• Xerxes I (519-465 BC), King of Kings of the Achaemenid Empire (Persia)
• Yu the Great (c. 2200-2100 BC), legendary ruler in ancient China

Religious figures[link]

• Abraham the Great of Kashkar (ca. 492-586), monk and saint of the Assyrian Church of the East
• Abraham Kidunaia (died c. 366, hermit, priest, and Christian saint of Mesopotamia
• Albertus Magnus (1193/1206–1280), medieval German philosopher and theologian
• Anthony the Great (c. 251–356), early Christian saint of Egypt
• Babai the Great (c. 551–628), Assyrian church leader
• Basil of Caesarea (330-379), Greek bishop and theologian
• Bruno the Great (925–965), Archbishop of Cologne and Duke of Lotharingia (also listed in the previous section)
• Euthymius the Great (377-473), abbot and Roman Catholic and Eastern Orthodox saint
• Gertrude the Great (1256-c. 1302), German Benedictine, mystic, theologian and Roman Catholic saint
• Pope Gregory I (c. 540-604)
• Hiyya the Great, 3rd-century rabbi, Palestine
• Pope John Paul II (1920–2005)
• Pope Leo I (c. 391 or 400-461)
• Macarius of Egypt (c. 300-391), Egyptian hermit
• Pope Nicholas I (c. 800-867)
• Photius I of Constantinople (c. 810–c. 893), Eastern Orthodox saint and Patriarch of Constantinople
• William of Maleval (died 1157), founder of the Catholic congregation of Williamites

Other[link]

• Beli Mawr, a figure in medieval Welsh literature and genealogies
• Emmy the Great, folk singer
• Matteo Rosso the Great, Roman politician and father of Pope Nicholas III
• Prokop the Great, Hussite general in Bohemia

See also[link]

• Epithet
• List of monarchs by nickname
• List of nicknames of European Royalty and Nobility: G-I
• James, son of Zebedee, also known as James the Greater, one of the twelve apostles of Jesus
• Ajax (mythology), called Ajax the Greater
• Mohandas Karamchand Gandhi, whose common honorific "Mahatma" means "Great Soul"

Notes[link]