Diphtheria 58937 225578447 2008-07-14T11:53:01Z Rjwilmsi 203434 no 'of' between a month and a year per [[Wikipedia:Manual_of_Style_%28dates_and_numbers%29#Longer_periods|MOS]] using [[Project:AutoWikiBrowser|AWB]] {{Infobox_Disease | Name = Diphtheria | Image = Diphtheria bull neck.5325 lores.jpg | Caption = Diphtheria causes a characteristic swollen neck, sometimes referred to as “bull neck”. | Width = 150 | DiseasesDB = 3122 | ICD10 = {{ICD10|A|30||a|30}} | ICD9 = {{ICD9|032}} | ICDO = | OMIM = | MedlinePlus = 001608 | eMedicineSubj = emerg | eMedicineTopic = 138 | eMedicine_mult = {{eMedicine2|med|459}} {{eMedicine2|oph|674}} {{eMedicine2|ped|596}} | MeshID = D004165 }} '''Diphtheria''' ([[Greek language|Greek]] ''διφθερα'' (''diphthera'') &mdash; “pair of leather scrolls") is an upper [[Respiration (physiology)|respiratory]] tract illness characterized by sore throat, low [[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]]'', an [[aerobic]] [[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> Diphtheria causes the progressive deterioration of myelin sheaths in the central and peripheral nervous system leading to degenerating motor control and loss of sensation. Diphtheria is a 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 widespread [[vaccination]]. In the [[United States]] for instance, there were 52 reported cases of diphtheria between 1980 and 2000; since 2000 there have only been five cases<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 = 10 | 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 [[DTP vaccine|DPT]] (''Diphtheria&ndash;[[Pertussis]]&ndash;[[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 without constant re-exposure; they are particularly recommended for those traveling to areas where the disease has not been eradicated. ==History== 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]] to deliver diphtheria antitoxin is now celebrated by the "Great Race of Mercy". Diphtheria was also prevalent in the [[British royal family]] during the late 19th century. One famous case includes [[Victoria of the United Kingdom|Queen Victoria]]'s second daughter, [[Princess Alice of the United Kingdom|Princess Alice of Hesse]] and her family. Princess Alice died of diphtheria after she contracted it from her children in December 1878 while nursing them. One of Princess Alice's own daughters, [[Princess Marie of Hesse and by Rhine|Princess May]], also died of diphtheria in November 1878.<ref> Baker, Raegan [http://www.alexanderpalace.org/palace/alicehessebio.html Princess Alice of Hesse and by Rhine] Alexander Palace Time Machine.</ref> 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 discovered that animal blood has antitoxins in and so he took the blood, removed the clotting agents and injected it into human patients. 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]] following [[World War II]]. 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 [[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]].<ref>{{cite web | url=http://www.healthsentinel.com/graphs.php?id=14&event=graphs_print_list_item | title=United States mortality rate from measles, scarlet fever, typhoid, whooping cough, and diphtheria from 1900-1965 |accessdate=2008-06-30 |work= |publisher=HealthSentinel.com |date= }}</ref> ==Mechanism== Diphtheria toxin catalyzes the ADP-ribosylation of, and inactivates, the [[elongation factor]] eEF-2.<ref>{{cite journal | author=Jørgensen R, Merrill AR. and Andersen GR. | title=The life and death of translation elongation factor 2 | journal= Biochem. Soc. Trans. | year=2006 | volume=34 | issue=1 | pages=1-6 | pmid =16246167}}</ref> In this way, it acts to inhibit [[translation (biology)|translation]] during eukaryotic protein synthesis. The toxin enters the host cell and is hydrolysed by a trypsin-like protease to give a fragment with enzymatic activity. The toxin then transfers an ADP-ribose from [[nicotinamide adenine dinucleotide|NAD<sup>+</sup>]] to a [[diphthamide]] residue, a modified [[histidine]] (amino acid), which is found within the EF-2 protein. EF-2 is needed for translocation of tRNA from the A-site to the P-site of the ribosome during traslation. The ADP-ribosylation is reversible by administering high concentrations of [[nicotinamide]], one of the reaction products. ==Signs and symptoms== 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. 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> [[Image:A diphtheria skin lesion on the leg. PHIL 1941 lores.jpg|thumb|A diphtheria skin lesion on the leg.]] 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. ===Diagnosis=== 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==== * Isolation of ''[[Corynebacterium diphtheriae]]'' from a clinical specimen, or * Histopathologic diagnosis of diphtheria. ====Clinical criteria==== * Upper respiratory tract illness with sore throat * Low-grade fever, and * An adherent pseudomembrane of the tonsil(s), pharynx, and/or nose. ====Case classification==== * 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== 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, the hyper sensitivity of the larynx may cause [[cardiac arrest]] around the intubation. 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. 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: * [[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]]. ==Epidemiology== [[Image:Diphterie.png|thumb|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 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. 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. This was so great an increase that diphtheria was cited in the [[Guinness Book of World Records]] as "most resurgent disease". The disease remains dangerous wherever vaccination rates are low, with a child in [[London]], [[England]] dying of the disease in May 2008<ref>{{cite web |url=http://www.hpa.org.uk/webw/HPAweb&HPAwebStandard/HPAweb_C/1210231700148?p=1204186170287 |publisher=Health Protection Agency |title=Death of a child infected with diphtheria in London |format= |work= |accessdate=2008-07-03 |date=2008-05-08}}</ref>. <br clear="all" /> ==References== <!-- --------------------------------------------------------------- See http://en.wikipedia.org/wiki/Wikipedia:Footnotes for a discussion of different citation methods and how to generate footnotes using the <ref> & </ref> tags and the {{Reflist}} template -------------------------------------------------------------------- --> {{Reflist|2}} ===Further reading=== * Holmes RK, Diphtheria and other corynebacterial infections. in Harrison's ''Principles of Internal Medicine'', 16th Ed. (2005) * Antitoxin dars 1735 and 1740." ''The William and Mary Quarterly'', 3rd Ser., Vol 6, No 2. p. 338. *Shulman ST, [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] Pediatric Research. Vol. 55, No. 1 (2004) ==External links== {{commons|Diphtheria}} {{Bacterial diseases}} [[Category:Bacterial diseases]] [[ar:دفتيريا]] [[bn:ডিপথেরিয়া]] [[bg:Дифтерия]] [[ca:Diftèria]] [[cs:Záškrt]] [[da:Difteri]] [[de:Diphtherie]] [[et:Difteeria]] [[es:Difteria]] [[eo:Difterio]] [[eu:Difteria]] [[fa:دیفتری]] [[fr:Diphtérie]] [[id:Difteri]] [[it:Difterite]] [[he:דיפתריה]] [[ku:Wendaq]] [[la:Diphtheria]] [[lt:Difterija]] [[hu:Diftéria]] [[ms:Difteria]] [[nl:Difterie]] [[ja:ジフテリア]] [[no:Difteri]] [[pl:Błonica]] [[pt:Difteria]] [[ro:Difterie]] [[ru:Дифтерия]] [[sr:Дифтерија]] [[sh:Difterija]] [[fi:Kurkkumätä]] [[sv:Difteri]] [[vi:Bệnh bạch hầu]] [[tr:Difteri]] [[uk:Дифтерія]] [[zh:白喉]]