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| '''For patient information click [[{{PAGENAME}} (patient information)|here]]'''
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| {{Infobox_Disease | | {{Infobox_Disease |
| | Name = {{PAGENAME}} | | | Name = {{PAGENAME}} |
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| | Caption = Diphtheria causes a characteristic swollen neck, sometimes referred to as “bull neck”. | | | Caption = Diphtheria causes a characteristic swollen neck, sometimes referred to as “bull neck”. |
| | Width = 150 | | | Width = 150 |
| | DiseasesDB = 3122
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| | ICD10 = {{ICD10|A|30||a|30}}
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| | ICD9 = {{ICD9|032}}
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| | ICDO =
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| | OMIM =
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| | MedlinePlus = 001608
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| | eMedicineSubj = emerg
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| | eMedicineTopic = 138
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| | eMedicine_mult = {{eMedicine2|med|459}} {{eMedicine2|oph|674}} {{eMedicine2|ped|596}}
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| | MeshID = D004165
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| }} | | }} |
| {{SI}} | | {{Diphtheria}} |
| {{CMG}} | | {{About1|Corynebacterium diphtheriae}} |
| | | '''For patient information click [[{{PAGENAME}} (patient information)|here]]''' |
| ==Overview==
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| '''Diphtheria''' ([[Greek language|Greek]] ''διφθερα'' (''diphthera'') — “pair of leather scrolls”), is an upper [[Respiration (physiology)|respiratory]] tract illness characterized by sore throat, low-grade [[fever]], and an adherent membrane (a ''pseudomembrane'') on the [[tonsil]]s, [[pharynx]], and/or nasal cavity.<ref name=Sherris>{{cite book | author = Ryan KJ, Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th ed. | pages =299–302 | publisher = McGraw Hill | year = 2004 | isbn = 0838585299 }}</ref> A milder form of diphtheria can be restricted to the skin. It is caused by ''[[Corynebacterium diphtheriae]]'', a [[Facultative anaerobic organism|facultatively anaerobic]] [[Gram-positive]] [[bacterium]].<ref>Office of Laboratory Security, Public Health Agency of Canada [http://www.phac-aspc.gc.ca/msds-ftss/msds42e.html ''Corynebacterium diphtheriae''] Material Safety Data Sheet. January 2000.</ref>
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| Diphtheria is a highly contagious disease spread by direct physical contact or breathing the [[particulate|aerosolized]] secretions of infected individuals. Once quite common, diphtheria has largely been eradicated in developed nations through wide-spread [[vaccination]]. In the [[United States]] for instance, between 1980 and 2004 there have been 57 reported cases of diphtheria (and only five cases since 2000)<ref name = Pinkbook>{{cite book | author = Atkinson W, Hamborsky J, McIntyre L, Wolfe S, eds. | title = Diphtheria. ''in:'' Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book) | edition = 10th ed. | pages = 59–70 | publisher = Washington DC: Public Health Foundation | year = 2007 | url = http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/dip.pdf }}</ref> as the [[DPT vaccine|DPT]] (''Diphtheria–[[Pertussis]]–[[Tetanus]]'') vaccine is given to all school children. Boosters of the vaccine are recommended for adults since the benefits of the vaccine decrease with age; they are particularly recommended for those traveling to areas where the disease has not been eradicated.
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| ==History==
| | {{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}, {{DN}}, {{AAA}} |
| [[Image:Antitoxin diphtheria.jpg|thumb|left|One of the first bottles of diphtheria antitoxin (1895), produced by the United States Hygienic Laboratory (now the [[National Institutes of Health]]).]]
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| Diphtheria was named in 1826 by French physician [[Pierre Bretonneau]]. The name alludes to the leathery, sheath-like membrane that grows on the [[tonsils]], [[throat]], and in the nose. The pronunciation {{IPA|/ˌdipˈθiɹˌi.ə/}} was originally considered incorrect, but has become the most common way of saying the word<!--(Oxford Dictionary of English)-->, and is accepted as a correct form. While many writers today use the spelling "diptheria" which fits the modern pronunciation, this spelling is rarely found in dictionaries.
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| Diphtheria was once a dreaded disease, with frequent large-scale outbreaks. A diphtheria epidemic in the New England colonies between 1735 and 1740 was said to have killed as many as 80% of the children under 10 years of age in some towns.<ref>Caulfield, Ernest. (1949) "A True History of the Terrible Epidemic Vulgarly Called the Throat Distemper, Which Occurred in His Majesty's New England Colonies between the Years 1735 and 1740." ''The William and Mary Quarterly'', 3rd Ser., Vol 6, No 2. p. 338. See Also: Shulman, Stanford (2004) [http://scholar.google.com/scholar?hl=en&lr=&safe=off&q=cache:FVEy_eca3ToJ:binf.gmu.edu/rkadoi/sysbio/PediatricInfectious.pdf+diphtheria+history+1735+and+1740 ''The History of Pediatric Infectious Diseases'' (Html by Google)] Pediatric Research. Vol. 55, No. 1</ref>
| | ==[[diphtheria overview|Overview]]== |
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| 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.<ref name= Pinkbook/> Children represented a large majority of these cases and fatalities. One of the most famous outbreaks of diphtheria was in Nome, Alaska; the [[1925 serum run to Nome|trip made to get the antitoxin]] is now celebrated by the Iditarod Trail Sled Dog Race.
| | ==[[diphtheria historical perspective|Historical Perspective]]== |
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| Diphtheria was also prevalent in the British royal family during the late 19th century. Famous cases included a daughter and granddaughter of Britain's Queen Victoria. Princess Alice of Hesse (second daughter of Queen Victoria) died of diphtheria after she contracted it from her children in December of 1878 while nursing them. One of Princess Alice's own daughters, Princess May, also died of diphtheria in November of 1878.<ref> Baker, Raegan [http://www.alexanderpalace.org/palace/alicehessebio.html Princess Alice of Hesse and by Rhine] Alexander Palace Time Machine.</ref>
| | ==[[diphtheria classification|Classification]]== |
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| 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 [[intubation|tubes]] that were inserted into the throat, and prevented victims from suffocating due to the membrane sheath that grows over and obstructs airways. In the 1890s, the German physician [[Emil von Behring]] developed an antitoxin that did not kill the bacteria, but neutralized the toxic poisons that the bacteria releases into the body. 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 1923. However, antibiotics against diphtheria were not available until the discovery and development of [[sulfa drugs]] following World War II.
| | ==[[diphtheria pathophysiology|Pathophysiology]]== |
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| ==Mechanism== | | ==[[diphtheria causes|Causes]]== |
| [[Diphtheria toxin]] catalyzes the [[ADP-ribosylation]] of, and inactivates, the [[Eukaryotic elongation factors|elongation factor]] eEF-2. In this way, it acts to inhibit [[Translation (biology)|translation]] during eukaryotic protein synthesis. | |
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| ==Signs and symptoms== | | ==[[diphtheria differential diagnosis|Differentiating Diphtheria from other Diseases]]== |
| The respiratory form has an [[incubation period]] of 2-5 days. The onset of disease is usually gradual. Symptoms include fatigue, fever, a mild sore throat and problems swallowing. Children infected have symptoms that include nausea, vomiting, chills, and a high fever, although some do not show symptoms until the infection has progressed further. In 10% of cases, patients experience neck swelling. These cases are associated with a higher risk of death.
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| In addition to symptoms at the site of infection (sore throat), the patient may experience more '''generalized symptoms''', such as listlessness, pallor, and fast heart rate. These symptoms are caused by the [[toxin]] released by the bacterium. [[Low blood pressure]] may develop in these patients. Longer-term effects of the diphtheria toxin include [[cardiomyopathy]] and [[peripheral neuropathy]] (sensory type).<ref>[http://www.neuro.wustl.edu/neuromuscular/nother/toxic.htm#diphtheria Toxic Neuropathies]. Neuromuscular Disease Center Washington University, St. Louis, MO USA</ref>
| | ==[[diphtheria epidemiology and demographics|Epidemiology and Demographics]]== |
| [[Image:A diphtheria skin lesion on the leg. PHIL 1941 lores.jpg|thumb|left|A diphtheria skin lesion on the leg.]]
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| The cutaneous form of diphtheria is often a [[secondary infection]] of a preexisting skin disease. Signs of cutaneous diphtheria infection develop an average of seven days after the appearance of the primary skin disease.
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| ===Diagnosis=== | | ==[[diphtheria risk factors|Risk Factors]]== |
| The current definition of diphtheria used by the [[Centers for Disease Control and Prevention]] (CDC) is based on both laboratory and clinical criteria.
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| ====Laboratory criteria==== | | ==[[diphtheria screening|Screening]]== |
| * Isolation of ''[[Corynebacterium diphtheriae]]'' from a clinical specimen, or
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| * Histopathologic diagnosis of diphtheria.
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| ====Clinical criteria==== | | ==[[diphtheria natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| * Upper respiratory tract illness with sore throat
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| * Low-grade fever, and
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| * An adherent pseudomembrane of the tonsil(s), pharynx, and/or nose.
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| ====Case classification==== | | ==Diagnosis== |
| * Probable: a clinically compatible case that is not laboratory-confirmed and is not epidemiologically linked to a laboratory-confirmed case
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| * Confirmed: a clinically compatible case that is either laboratory-confirmed or epidemiologically linked to a laboratory-confirmed case
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| Empirical treatment should generally be started in a patient in whom suspicion of diphtheria is high.
| | [[diphtheria history and symptoms|History and Symptoms]] | [[diphtheria physical examination|Physical Examination]] | [[diphtheria laboratory findings|Laboratory Findings]] | [[diphtheria electrocardiogram|Electrocardiogram]] | [[diphtheria echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[diphtheria other imaging findings|Other Imaging Findings]] | [[diphtheria other diagnostic studies|Other Diagnostic Studies]] |
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| ==Treatment== | | ==Treatment== |
| 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]]. In addition, an increase in heart rate may cause cardiac arrest. 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]] (ICU) and be given a diphtheria anti-toxin. 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.
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| 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<ref>''The first version of this article was adapted from the [[Centers for Disease Control and Prevention|CDC]] document "Diphtheria - 1995 Case Definition" at http://www.cdc.gov/epo/dphsi/casedef/diphtheria_current.htm. As a work of an agency of the U.S. Government without any other copyright notice it should be available as a public domain resource''.</ref> either:
| | [[diphtheria medical therapy|Medical Therapy]] | [[diphtheria primary prevention|Primary Prevention]] | [[diphtheria secondary prevention|Secondary Prevention]] | [[diphtheria cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[diphtheria future or investigational therapies|Future or Investigational Therapies]] |
| * [[Erythromycin]] (orally or by injection) for 14 days (40 mg/kg per day with a maximum of 2 g/d), or
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| * [[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]].
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| ==Epidemiology== | | ==Case Studies== |
| [[Image:Diphterie.png|thumb|left|Diphtheria cases reported to the World Health Organization between 1997 and 2006 (see description for legend).]] | | [[diphtheria case study one|Case #1]] |
| *Diphtheria is a serious disease, with fatality rates between 5% and 10%.
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| *In children under 5 years and adults over 40 years, the fatality rate may be as much as 20%.<ref name= Pinkbook/> Outbreaks, though very rare, still occur worldwide, even in developed nations.
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| *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.
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| *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.
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| *This was so great an increase that diphtheria was cited in the Guinness Book of World Records as "most resurgent disease".
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| ==References==
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| <!-- ---------------------------------------------------------------
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| {{Reflist|2}}
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| ===Further reading===
| | {{WikiDoc Help Menu}} |
| * Holmes RK, Diphtheria and other corynebacterial infections. in Harrison's ''Principles of Internal Medicine'', 16th Ed. (2005)
| | {{WikiDoc Sources}} |
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| ==External links==
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| {{commons|Diphtheria}} | |
| {{Bacterial diseases}} | |
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