Diphtheria
Classification and external resources
Diphtheria causes a characteristic swollen neck, sometimes referred to as “bull neck”.
ICD-10	A36
ICD-9	032
DiseasesDB	3122
MedlinePlus	001608
eMedicine	emerg/138 med/459 oph/674 ped/596
MeSH	D004165

Diphtheria (Greek διφθέρα (diphthera) "pair of leather scrolls") is an upper respiratory tract illness caused by Corynebacterium diphtheriae, a facultative anaerobic, Gram-positive bacterium.^[1][2] It is characterized by sore throat, low fever, and an adherent membrane (a pseudomembrane) on the tonsils, pharynx, and/or nasal cavity.^[3] A milder form of diphtheria can be restricted to the skin. Less common consequences include myocarditis (about 20% of cases) ^[4] and peripheral neuropathy (about 10% of cases).^[5]

Diphtheria is a contagious disease spread by direct physical contact or breathing the aerosolized secretions of infected individuals. Historically quite common, diphtheria has largely been eradicated in industrialized nations through widespread vaccination. In the United States, for example, there were 52 reported cases of diphtheria between 1980 and 2000; between 2000 and 2007, there were only three cases^[6] as the diphtheria–pertussis–tetanus (DPT) vaccine is recommended for all school-age children. Boosters of the vaccine are recommended for adults, since the benefits of the vaccine decrease with age without constant re-exposure; they are particularly recommended for those traveling to areas where the disease has not been eradicated.

Signs and symptoms[link]

The symptoms of diphtheria usually begin two to seven days after infection. Symptoms of diphtheria include fever of 38°C (100.4°F) or above, chills, fatigue, bluish skin coloration, sore throat, hoarseness, cough, headache, difficulty swallowing, painful swallowing, difficulty breathing, rapid breathing, foul-smelling bloodstained nasal discharge and lymphadenopathy.^[7][8] Symptoms can also include cardiac arrhythmias, myocarditis, and cranial and peripheral nerve palsies.^{[citation needed]}

Diphtheria toxin mechanism[link]

A diphtheria skin lesion on the leg

Diphtheria toxin is produced by C. diphtheriae only when it is infected with a bacteriophage that integrates the toxin-encoding genetic elements into the bacteria.^[9][10]

Diphtheria toxin is a single, 60,000 molecular weight protein composed of two peptide chains, fragment A and fragment B, held together by a disulfide bond. Fragment B is a recognition subunit that gains the toxin entry into the host cell by binding to the EGF-like domain of heparin-binding EGF-like growth factor (HB-EGF) on the cell surface. This signals the cell to internalize the toxin within an endosome via receptor-mediated endocytosis. Inside the endosome, the toxin is split by a trypsin-like protease into its individual A and B fragments. The acidity of the endosome causes fragment B to create pores in the endosome membrane, thereby catalyzing the release of fragment A into the cell's cytoplasm.

Fragment A inhibits the synthesis of new proteins in the affected cell. It does this by catalyzing ADP-ribosylation of elongation factor EF-2—a protein that is essential to the translation step of protein synthesis. This ADP-ribosylation involves the transfer of an ADP-ribose from NAD+ to a diphthamide (a modified histidine) residue within the EF-2 protein. Since EF-2 is needed for the moving of tRNA from the A-site to the P-site of the ribosome during protein translation, ADP-ribosylation of EF-2 prevents protein synthesis.

ADP-ribosylation of EF-2 is reversed by giving high doses of nicotinamide (a form of vitamin B₃), since this is one of the reaction's end-products, and high amounts will drive the reaction in the opposite direction.^{[citation needed]}

Diagnosis[link]

The current definition of diphtheria used by the Centers for Disease Control and Prevention (CDC) is based on both laboratory and clinical criteria.

Laboratory criteria[link]

• Isolation of Corynebacterium diphtheriae from a gram stain or throat culture from a clinical specimen ^[11], or
• Histopathologic diagnosis of diphtheria

Clinical criteria[link]

• Upper respiratory tract illness with sore throat
• Low-grade fever (>102 °F (39 °C) is rare)
• An adherent pseudomembrane of the tonsil(s), pharynx, and/or nose.

Case classification[link]

• Probable: a clinically compatible case that is not laboratory-confirmed and is not epidemiologically linked to a laboratory-confirmed case
• Confirmed: a clinically compatible case that is either laboratory-confirmed or epidemiologically linked to a laboratory-confirmed case

Empirical treatment should generally be started in a patient in whom suspicion of diphtheria is high.

Treatment[link]

The disease may remain manageable, but in more severe cases, lymph nodes in the neck may swell, and breathing and swallowing will be more difficult. People in this stage should seek immediate medical attention, as obstruction in the throat may require intubation or a tracheotomy. Abnormal cardiac rhythms can occur early in the course of the illness or weeks later, and can lead to heart failure. Diphtheria can also cause paralysis in the eye, neck, throat, or respiratory muscles. Patients with severe cases will be put in a hospital intensive care unit and be given a diphtheria antitoxin. Since antitoxin does not neutralize toxin that is already bound to tissues, delaying its administration is associated with an increase in mortality risk. Therefore, the decision to administer diphtheria antitoxin is based on clinical diagnosis, and should not await laboratory confirmation.^[6]

Antibiotics have not been demonstrated to affect healing of local infection in diphtheria patients treated with antitoxin. Antibiotics are used in patients or carriers to eradicate C. diphtheriae and prevent its transmission to others. The CDC recommends^[12] either:

• Metronidazole
• Erythromycin (orally or by injection) for 14 days (40 mg/kg per day with a maximum of 2 g/d), or
• Procaine penicillin G given intramuscularly for 14 days (300,000 U/d for patients weighing <10 kg and 600,000 U/d for those weighing >10 kg). Patients with allergies to penicillin G or erythromycin can use rifampin or clindamycin.

In cases that progress beyond a throat infection, diphtheria toxin spreads through the blood and can lead to potentially life-threatening complications that affect other organs, such as the heart and kidneys. The toxin can cause damage to the heart that affects its ability to pump blood or the kidneys' ability to clear wastes. It can also cause nerve damage, eventually leading to paralysis. About 40% to 50% of those left untreated can die.

Epidemiology[link]

Disability-adjusted life year for diphtheria per 100,000 inhabitants.

  no data

  ≤ 1

  1-2

  2-3

  3-4

  4-5

  5-6

  6-7

  7-9

  9-10

  10-15

  15-50

  ≥ 50

Diphtheria cases reported to the World Health Organization between 1997 and 2006 (see description for legend)

Diphtheria is a serious disease, with fatality rates between 5% and 10%. In children under five years and adults over 40 years, the fatality rate may be as much as 20%.^[6] Outbreaks, though very rare, still occur worldwide, even in developed nations, such as Germany and Canada. After the breakup of the former Soviet Union in the late 1980s, vaccination rates in its constituent countries fell so low that there was an explosion of diphtheria cases. In 1991, there were 2,000 cases of diphtheria in the USSR. By 1998, according to Red Cross estimates, there were as many as 200,000 cases in the Commonwealth of Independent States, with 5,000 deaths.^[13] This was so great an increase that diphtheria was cited in the Guinness Book of World Records as "most resurgent disease".^{[citation needed]}

History[link]

The disease was named by French doctor Pierre Bretonneau in 1855 (substituted for his earlier term diphthérite).

In 1878, Queen Victoria's daughter Princess Alice and her family became infected with it, causing two deaths, Princess Marie of Hesse and by Rhine and Princess Alice herself.

In the 1920s, there were an estimated 100,000 to 200,000 cases of diphtheria per year in the United States, causing 13,000 to 15,000 deaths per year.^[6] Children represented a large majority of these cases and fatalities. One of the most famous outbreaks of diphtheria was in Nome, Alaska; the "Great Race of Mercy" to deliver diphtheria antitoxin is now celebrated by the Iditarod Trail Sled Dog Race.

One of the first effective treatments for diphtheria was discovered in the 1880s by U.S. physician Joseph O'Dwyer (1841–1898). O'Dwyer developed tubes that were inserted into the throat, and prevented victims from suffocating due to the membrane sheath that grows over and obstructs airways. In 1884, Friedrich Loeffler discovered the causative organism (Corynebacterium diphtheriae). In December 1890, the German physician Emil von Behring developed an antitoxin that did not kill the bacterium, but neutralized the toxic poisons the bacterium releases into the body. Von Behring discovered that animal blood has antitoxins in it, so he took the blood, removed the clotting agents and injected it into human patients. "The paper shook the scientific world. Work on diphtheria at a level of intensity heretofore unknown proceeded in laboratories. Over the Christmas holiday in 1891 in Berlin, the first attempt to cure a person of diphtheria was made. It succeeded. . . . It was the first cure." ^[14] Von Behring was awarded the first Nobel Prize in Medicine for his role in the discovery, and development of a serum therapy for diphtheria. (Americans William H. Park and Anna Wessels Williams, and Pasteur Institute scientists Emile Roux and Auguste Chaillou also independently developed diphtheria antitoxin in the 1890s.) The first successful vaccine for diphtheria was developed in 1913 by Behring. However, antibiotics against diphtheria were not available until the discovery and development of sulfa drugs.

The Schick test, invented between 1910 and 1911, is a test used to determine whether or not a person is susceptible to diphtheria. It was named after its inventor, Béla Schick (1877–1967), a Hungarian-born American pediatrician. A massive five-year campaign was coordinated by Dr. Schick. As a part of the campaign, 85 million pieces of literature were distributed by the Metropolitan Life Insurance Company with an appeal to parents to "Save your child from diphtheria." A vaccine was developed in the next decade, and deaths began declining in earnest in 1924.^[15]

In early May 2010, a case of diphtheria was diagnosed in Port-au-Prince, Haiti after the devastating 2010 Haiti earthquake. The 15-year-old male patient died while workers searched for antitoxin.^[16]

References[link]

Further reading[link]

Wikimedia Commons has media related to: Diphtheria

• Holmes, R .K. (2005). "Diphtheria and other corynebacterial infections". In Kasper; et al.. Harrison's Principles of Internal Medicine (16th ed.). New York: McGraw-Hill. ISBN 0-07-139140-1. 
• "Antitoxin dars 1735 and 1740." The William and Mary Quarterly, 3rd Ser., Vol 6, No 2. p. 338.
• Shulman, S. T. (2004). "The History of Pediatric Infectious Diseases". Pediatric Research 55 (1): 163–176. DOI:10.1203/01.PDR.0000101756.93542.09. PMID 14605240. 

Sean Penn
Penn at the premiere for Milk at the Castro Theatre, San Francisco, October 2008
Ambassador-at-large for Haiti
Incumbent
Assumed office January 31, 2012
President	Michel Martelly
Personal details
Born	Sean Justin Penn (1960-08-17) August 17, 1960 (age 51) Los Angeles County, California, U.S.
Nationality	American
Political party	Democratic
Spouse(s)	Madonna (1985–1989) Robin Wright (1996–2010)
Relations	Aimee Mann (sister-in-law), Leo Penn (father), Eileen Ryan (mother), Chris Penn (brother), Michael Penn (brother)
Children	1 son, 1 daughter
Residence	Los Angeles, California
Alma mater	Santa Monica College
Occupation	Actor, screenwriter, director, producer
Religion	Agnostic
Awards	Academy Award, Golden Globe, Screen Actors Guild Award, Christopher Reeve First Amendment Award

Sean Justin Penn (born August 17, 1960) is an American actor, screenwriter and film director, also known for his left-wing political and social activism (including humanitarian work). He is a two-time Academy Award winner for his roles in Mystic River (2003) and Milk (2008), as well as the recipient of a Golden Globe Award for the former and a Screen Actors Guild Award for the latter.

Penn began his acting career in television with a brief appearance in a 1974 episode of Little House on the Prairie, directed by his father Leo Penn. Following his film debut in 1981's Taps and a diverse range of film roles in the 1980s, Penn emerged as a prominent leading actor with the 1995 drama film Dead Man Walking, for which he earned his first Academy Award nomination and the Best Actor Award at the Berlin Film Festival. Penn received another two Oscar nominations for Sweet and Lowdown (1999) and I Am Sam (2001), before winning his first Academy Award for Best Actor in 2003 for Mystic River and a second one in 2008 for Milk. He has also won a Best Actor Award of the Cannes Film Festival for She's So Lovely (1997), and two Best Actor Awards at the Venice Film Festival for Hurlyburly (1998) and 21 Grams (2003).

Penn made his feature film directorial debut with 1991's The Indian Runner, followed by the drama film The Crossing Guard (1995) and the mystery film The Pledge (2001). In 2002, Penn directed one of the 11 segments of 11'09"01 September 11, a compilation film made in response to the September 11 attacks. His fourth feature film, Into the Wild (2007), garnered critical acclaim and two Academy Award nominations.

In addition to his film work, Penn is known for his political and social activism, most notably his criticism of the George W. Bush administration, his contact with the Presidents of Venezuela and Cuba, and his humanitarian work in the aftermath of Hurricane Katrina and the 2010 Haiti earthquake. Penn also attracted media attention for his previous marriages to pop icon Madonna and actress Robin Wright.

Early life[link]

Penn was born in Los Angeles County, California,^[1] the middle son of actor and director Leo Penn and actress Eileen Ryan (née Annucci). His older brother is musician Michael Penn. His younger brother, actor Chris Penn, died in 2006. His paternal grandparents were Jewish emigrants from Lithuania and Russia,^[2][3][4] while his mother is a Catholic of Italian and Irish descent.^[4][5] Penn was raised in a secular home^[2] and is an agnostic.^[6] He attended Santa Monica High School^[7] and began making short films with some of his childhood friends, including actors Emilio Estevez and Charlie Sheen, who lived near his home.^[8]

Career[link]

Acting[link]

Penn appeared in a 1974 episode of the Little House on the Prairie television series as a then blond-haired extra when his father, Leo, directed some of the episodes.

Penn launched his film career with the 1981 action-drama Taps, where he played a key role, as a military high school cadet, opposite protagonist Timothy Hutton.^[8] Tom Cruise also made one of his first film appearances, as another cadet. A year later, Penn appeared in the hit comedy Fast Times at Ridgemont High, in the role of surfer-stoner Jeff Spicoli, with his character helping popularize the word "dude" in popular culture.^[8] In 1983, Penn appeared as Mick O'Brien, a troubled youth, in the drama Bad Boys.^[8] The role earned Penn favorable reviews and jump-started his career as a serious actor.

In 1985, Penn played Andrew Daulton Lee in the film The Falcon and the Snowman, which closely followed an actual criminal case.^[8] Lee was a former drug dealer by trade, convicted of espionage for the Soviet Union and originally sentenced to life in prison, later being paroled in 1998. Penn later hired Lee as his personal assistant, partly because he wanted to reward Lee for allowing him to play Lee in the film; also, he was a firm believer in rehabilitation and thought Andrew Lee should be successfully reintegrated into society, since he was a free man again.^[9]

At the 1997 Cannes Film Festival.

In 1986, he starred in the drama At Close Range, opposite Christopher Walken.^[8] The film featured his then-wife Madonna's single "Live to Tell". The music video for the song, which featured clips from the film, played heavily on MTV and helped promote the film. Penn stopped acting for a few years in the early 1990s, having been dissatisfied with the industry, and focused on making his directing debut.^[8]

Penn, nominated for the Academy Award for Best Actor five times, has won the award twice. The Academy first recognized his work in nominating him for playing a racist murderer on death row in Tim Robbins' 1995 drama Dead Man Walking. Penn was nominated again for his comedic performance as an egotistical jazz guitarist in Woody Allen's 1999 release Sweet and Lowdown. He received his third nomination after portraying a mentally-handicapped father in 2001's I am Sam. Penn finally won for his role in Clint Eastwood's 2003 Boston crime-drama Mystic River. In 2004, he played a disturbed man bent on killing the president in The Assassination of Richard Nixon. He was invited to join the Academy of Motion Picture Arts and Sciences in 2004.^[10]

In 2006, he portrayed populist governor Willie Stark (based on Huey Long) in an adaptation of the classic American novel All the King's Men, though the film was a critical and commercial failure. In November 2008, Penn earned rave reviews for his portrayal of real-life gay-rights icon and politician Harvey Milk in the biopic Milk and was nominated for best actor for the 2008 Independent Spirit Awards.^[11] The film also earned Penn his fifth nomination and second win for the Academy Award for Best Actor. In 2010 he starred as Joseph Wilson in Fair Game, a film adaptation of Valerie Plame's 2007 memoir. Penn co-starred with Brad Pitt and Jessica Chastain in the drama The Tree of Life which won the Palme d'Or at the 2011 Cannes Film Festival.

Directing[link]

In 1991, Penn made his directorial debut with The Indian Runner, a film based on Bruce Springsteen's song "Highway Patrolman", from the Nebraska album.^[8] He also directed music videos, such as Shania Twain's "Dance with the One That Brought You" and Lyle Lovett's "North Dakota" in 1993, and Peter Gabriel's "The Barry Williams Show" in 2002. He has since directed three more films, all of which^{[citation needed]} were well-received by critics: The Crossing Guard in 1995, The Pledge in 2001, and Into the Wild in 2007.

Personal life[link]

Penn with Robin Wright in 2006

Penn was engaged to actress Elizabeth McGovern, his co-star in 1984's Racing with the Moon. Penn's personal life began to attract media attention when he married pop star Madonna in 1985. The two starred in the panned and much-derided Shanghai Surprise, directed by Jim Goddard, and Madonna dedicated her third studio album True Blue to Penn, referring to him in the liner notes as "the coolest guy in the universe".^[12] The relationship was marred by violent outbursts against the press, including one incident for which he was arrested for assaulting a photographer on a film set; Penn was sentenced to 60 days in jail in mid-1987, of which he served 33 days.^[13] It is also alleged that when Penn discovered the paparazzo in his hotel room, he hung him by his ankles from the ninth-floor balcony.^[14] Later in the marriage, Penn was charged with felony domestic assault, a charge for which he pleaded to a misdemeanor.^[15] Penn and Madonna divorced in 1989.

He soon began a relationship with actress Robin Wright, and their first child – a daughter named Dylan Frances – was born in 1991. Their second child, a son whom they named Hopper Jack, was born in 1993. Penn and Wright married in 1996 and lived in Ross, California. The relationship went through on-and-off periods in the late 2000s (decade).^{[citation needed]} The couple filed for divorce in December 2007, but reconciled several months later, requesting a court dismissal of their divorce case.^[16] In April 2009, Penn filed for legal separation, only to withdraw the case once again when the couple reconciled in May.^[17][18][19] On August 12, 2009, Wright Penn filed for divorce again.^[20][21] The couple's divorce was finalized on July 22, 2010, with the couple reaching a private agreement on child and spousal support, division of assets, and custody over their underage son.^[22]

Political and social causes[link]

Penn has been active in supporting several political and social causes. On June 10, 2005, Penn made a visit to Iran. Acting as a journalist on an assignment for the San Francisco Chronicle, he attended a Friday prayer at Tehran University.^[23]

On January 7, 2006, Penn was a special guest at the Progressive Democrats of America, where he was joined by author and media critic Norman Solomon, Democratic congressional candidate Charles Brown, and activist Cindy Sheehan. The "Out of Iraq Forum", which took place in Sacramento, California, was organized to promote the anti-war movement calling for an end to the War in Iraq.

In August 2008, Penn made an appearance at one of Ralph Nader's "Open the Debates" Super Rallies. He protested the political exclusion of Nader and other third parties.^[24]

In October 2008, Penn traveled to Cuba, where he met with and interviewed President Raúl Castro.^[25]

In March 2010 he called for the arrest of those referring to Hugo Chávez of Venezuela as a dictator ^[26]

In February 2012, he stood beside Hugo Chávez while Venezuela supported the Syrian government during the 2011–2012 Syrian uprising.^[27]

Criticism of President Bush[link]

Penn at an anti-war rally in Washington, D.C., January 27, 2007

On October 18, 2002, Penn placed a US$56,000 advertisement in the Washington Post asking then President George W. Bush to end a cycle of violence. It was written as an open letter and referred to the planned attack on Iraq and the War on Terror.^[28] In the letter, Penn also criticized the Bush administration for its "deconstruction of civil liberties" and its "simplistic and inflammatory view of good and evil."^[29] Penn visited Iraq briefly in December 2002.^[28]

This advertisement was cited as a primary reason for the development of his relationship with Venezuelan president Hugo Chávez. In one of his televised speeches, Chávez used and read aloud an open letter Penn wrote to Bush.^[14] The letter condemned the Iraq War, called for Bush to be impeached, and also called Bush, Vice President Dick Cheney, and Secretary of State Condoleezza Rice "villainously and criminally obscene people.".^[30] In August 2007, Penn met with Chávez in Caracas for two hours, after which Chávez praised him for urging Americans to impeach Bush. Penn also visited a new film studio on the outskirts of Caracas, though he did not speak publicly.^[30]

On April 19, 2007, Penn appeared on The Colbert Report and had a "Meta-Free-Phor-All" versus Stephen Colbert that was judged by Robert Pinsky. This stemmed from some of Penn's criticisms of Bush. His exact quote was "We cower as you point your fingers telling us to support our troops. You and the smarmy pundits in your pocket– those who bathe in the moisture of your soiled and blood-soaked underwear– can take that noise and shove it."^[31][32] He won the contest with 10,000,000 points to Colbert's 1.^[33]

On December 7, 2007, Penn said he supported Ohio Congressman Dennis J. Kucinich for U.S. President in 2008, and criticized Bush's handling of the Iraq war. Penn questioned whether Bush's twin daughters supported the war in Iraq.^[34]

Hurricane Katrina[link]

In September 2005, Penn traveled to New Orleans, Louisiana, to aid Hurricane Katrina victims. He was physically involved in rescuing people,^[35] although there was criticism that his involvement was a PR stunt as he hired a photographer to come along with his entourage.^[36] Penn denied such accusation in an article he wrote for The Huffington Post.^[37]

Director Spike Lee interviewed Penn for his documentary When the Levees Broke: A Requiem in Four Acts, about Hurricane Katrina.

Support for same-sex marriage[link]

Filming Milk, 2008

On February 22, 2009, Penn received the Academy Award for Best Actor for the film Milk. In his acceptance speech, Penn said " ... I think that it is a good time for those who voted for the ban against gay marriage to sit and reflect and anticipate their great shame and the shame in their grandchildren's eyes if they continue that way of support. We've got to have equal rights for everyone!"^[38]

2010 Haiti earthquake: Manager of Relief Organization and Tent Camp[link]

After the 2010 Haiti earthquake, Sean Penn co-founded the J/P Haitian Relief Organization and has been running a 55,000 person tent camp.^[39]

Due to his visibility as an on-the-ground advocate for rescue and aid efforts in the aftermath, Penn was designated by president Michel Martelly as Ambassador-at-Large for Haiti, the first time that a non-Haitian citizen has been designated as such in the country's history. Penn received the designation on January 31, 2012.^[40]

Falkland Islands/Malvinas controversy[link]

In February 2012 Penn met with the President of Argentina, Cristina Fernández de Kirchner in Buenos Aires where he made a statement on the long-running dispute between Argentina and the United Kingdom over the Falkland Islands saying "I know I came in a very sensitive moment in terms of diplomacy between Argentina and the UK over the Malvinas islands. And I hope that diplomats can establish true dialogue in order to solve the conflict as the world today cannot tolerate ridiculous demonstrations of colonialism. The way of dialogue is the only way to achieve a better solution for both nations."^[41][42][43] The comments evoked strong reactions in the British media, with one satirical article in The Daily Telegraph requesting that Penn "return his Malibu estate to the Mexicans."^[44] Penn described the deployment of Prince William to the region as a "provocation" and a message of "pre-emptive intimidation", citing war ships that would accompany him, and stated "My oh my, aren't people sensitive to the word colonialism, particularly those who implement colonialism."^[45][46] In a piece written in The Guardian, Penn wrote that the legalisation of Argentinian immigration to the "Malvinas/Falkland Islands is one that it seems might have been addressed, but for the speculative discovery of booming offshore oil in the surrounding seas this past year."^[46][47] Of the furore, Lauren Collins wrote in The New Yorker "As of today, Sean Penn is the new Karl Lagerfeld—the man upon whom, having disrespected something dear to the United Kingdom, the British papers most gleefully pile contempt".^[48]

Pakistan[link]

Penn gained significant attention in Pakistani media when he visited Karachi and Badin in 2012.

On 23 March 2012, he visited flood-stricken villages of Karim Bux Jamali, Dargah Shah Gurio and Peero Lashari in Badin District. He was accompanied by US Consul General Willian J. Martin and distributed blankets, quilts, kitchen items and other goods amongst flood survivors.^[49][50]

On 24 March 2012, Penn also visited Bilquis Edhi Female Child Home and met Pakistan’s iconic humanitarian worker Abdul Sattar Edhi and his wife, Bilquis Edhi. He also laid floral wreaths and paid respect at the shrine of Abdullah Shah Ghazi.^[51][52]

Filmography and awards[link]

On December 18, 2006, Penn received the Christopher Reeve First Amendment Award from the Creative Coalition.^[53]

Actor[link]

Director[link]

References[link]

External links[link]

Wikimedia Commons has media related to: Sean Penn

Wikiquote has a collection of quotations related to: Sean Penn

• Sean Penn at the Internet Movie Database
• Sean Penn at the Internet Broadway Database
• Guardian Interview, April 8, 2005
• Esquire magazine interview/profile
• Sean Penn's visit to Iran at the San Francisco Chronicle
• Smiles for Smirks by Sean Penn, The Huffington Post, April 21, 2009
• Sean Penn on Managing a Tent Camp of 55,000 Displaced Haitians – video report by Democracy Now!