Editing Diphtheria

{{Short description|Bacterial disease}}
{{Redirect|Diphthera|the genus of moth|Diphthera (moth){{!}}''Diphthera'' (moth)}}
{{Use dmy dates|date=November 2019}}
{{Infobox medical condition (new)
| name            = Diphtheria
| image           = Dirty white pseudomembrane classically seen in diphtheria 2013-07-06 11-07.jpg
| caption         = An adherent, dense, grey pseudomembrane covering the [[tonsil]]s is classically seen in diphtheria.
| field           = [[Infectious disease (medical specialty)|Infectious disease]]
| symptoms        = Sore throat, fever, barking cough<ref name=WHO2006/>
| onset           = 2–5 days post-exposure<ref name=CDC2012Pink/>
| complications   = [[Myocarditis]], [[Peripheral neuropathy]], [[Proteinuria]]
| duration        =
| causes          = ''[[Corynebacterium diphtheriae]]'' (spread by direct contact and [[airborne disease|through the air]])<ref name=CDC2012Pink/>
| risks           =
| diagnosis       = Examination of throat, [[microbiological culture|culture]]<ref name=WHO2006/>
| differential    =
| prevention      = [[Diphtheria vaccine]]<ref name=CDC2012Pink/>
| treatment       = [[Antibiotics]], [[tracheostomy]]<ref name=CDC2012Pink/>
| prognosis       = 5–10% risk of death
| medication      =
| frequency       = 4,500 (reported 2015)<ref name=WHO2015/>
| deaths          = 2,100 (2015)<ref name=GBD2015De/>
}}

'''Diphtheria''' is an [[infection]] caused by the [[bacteria|bacterium]] ''[[Corynebacterium diphtheriae]]''.<ref name=CDC2012Pink/> Most infections are asymptomatic or have a mild [[Course (medicine)|clinical course]], but in some outbreaks, the mortality rate approaches 10%.<ref name=WHO2006/>  Signs and symptoms may vary from mild to severe,<ref name=WHO2006/> and usually start two to five days after exposure.<ref name=CDC2012Pink/> Symptoms often develop gradually, beginning with a sore throat and [[fever]].<ref name=WHO2006/> In severe cases, a grey or white patch develops in the throat,<ref name=CDC2012Pink/><ref name=WHO2006/> which can block the airway, and create a barking cough similar to what is observed in [[croup]].<ref name=WHO2006/> The neck may also swell, in part due to the enlargement of the [[facial lymph nodes]].<ref name=CDC2012Pink/> Diphtheria can also involve the skin, eyes, or genitals, and can cause<ref name=CDC2012Pink/><ref name=WHO2006/> complications, including [[myocarditis]] (which in itself can result in an [[cardiac arrhythmia|abnormal heart rate]]), [[peripheral neuropathy|inflammation of nerves]] (which can result in [[paralysis]]), [[proteinuria|kidney problems]], and bleeding problems due to [[thrombocytopenia|low levels of platelets]].<ref name=CDC2012Pink/>

Diphtheria is usually spread between people by direct contact, [[airborne disease|through the air]], or through contact with [[Fomite|contaminated objects]].<ref name=CDC2012Pink/><ref>{{cite book|last1=Kowalski|first1=Wladyslaw|title=Hospital airborne infection control|date=2012|publisher=CRC Press|location=Boca Raton, Florida|isbn=9781439821961|page=54|url=https://books.google.com/books?id=rGS7fCcloBQC&pg=PA54|url-status=live|archive-url=https://web.archive.org/web/20161221095743/https://books.google.com/books?id=rGS7fCcloBQC&pg=PA54|archive-date=21 December 2016}}</ref> Asymptomatic transmission and chronic infection are also possible.<ref name=CDC2012Pink/> Different strains of ''C.&nbsp;diphtheriae'' are the main cause in the variability of lethality,<ref name=CDC2012Pink/> as the lethality and symptoms themselves are caused by the [[exotoxin]] produced by the bacteria.<ref name=WHO2006/> Diagnosis can often be made based on the appearance of the throat with confirmation by [[microbiological culture]].<ref name=WHO2006/> Previous infection may not protect against reinfection.<ref name=WHO2006>{{cite journal|title=Diphtheria vaccine|journal=Wkly Epidemiol Rec|date=20 January 2006|volume=81|issue=3|pages=24–32|pmid=16671240|url=https://www.who.int/wer/2006/wer8103.pdf|url-status=live|archive-url=https://web.archive.org/web/20150606054559/http://www.who.int/wer/2006/wer8103.pdf|archive-date=6 June 2015}}</ref>

A [[diphtheria vaccine]] is effective for prevention, and is available in a number of formulations.<ref name=CDC2012Pink/> Three or four doses, given along with [[tetanus vaccine]] and [[pertussis vaccine]], are recommended during childhood.<ref name=CDC2012Pink/> Further doses of the diphtheria–tetanus vaccine are recommended every ten years.<ref name=CDC2012Pink/> Protection can be verified by measuring the antitoxin level in the blood.<ref name=CDC2012Pink/> Diphtheria can be prevented in those exposed, as well as treated with the [[antibiotics]] [[erythromycin]] or [[benzylpenicillin]].<ref name=CDC2012Pink/> In severe cases a [[tracheotomy]] may be needed to open the airway.<ref name=WHO2006/>

In 2015, 4,500 cases were officially reported worldwide, down from nearly 100,000 in 1980.<ref name=WHO2015>{{cite web|title=Diphtheria|url=https://www.who.int/immunization/monitoring_surveillance/burden/diphtheria/en/|website=who.int|access-date=27 March 2015|date=3 September 2014|url-status=dead|archive-url=https://web.archive.org/web/20150402121723/http://www.who.int/immunization/monitoring_surveillance/burden/diphtheria/en/|archive-date=2 April 2015}}</ref> About a million cases a year are believed to have occurred before the 1980s.<ref name=WHO2006/> Diphtheria currently occurs most often in [[sub-Saharan Africa]], [[South Asia]], and [[Health in Indonesia|Indonesia]].<ref name=WHO2006/><ref>{{cite book|title=Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases|date=2014|publisher=Elsevier Health Sciences|isbn=9780323263733|page=2372|edition=8|url=https://books.google.com/books?id=73pYBAAAQBAJ&pg=PA2372|url-status=live|archive-url=https://web.archive.org/web/20161221092112/https://books.google.com/books?id=73pYBAAAQBAJ&pg=PA2372|archive-date=21 December 2016}}</ref> In 2015, it resulted in 2,100 deaths, down from 8,000 deaths in 1990.<ref name=GBD2015De>{{cite journal| vauthors = ((GBD 2015 Mortality and Causes of Death Collaborators))| title=Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015.| journal=Lancet| date=8 October 2016| volume=388| issue=10053| pages=1459–1544| pmid=27733281| doi=10.1016/s0140-6736(16)31012-1| pmc=5388903}}</ref><ref name=GDB2013>{{cite journal|vauthors = ((GBD 2013 Mortality and Causes of Death Collaborators))|title=Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013.|journal=Lancet|date=17 December 2014|pmid=25530442|doi=10.1016/S0140-6736(14)61682-2|pmc=4340604|volume=385|issue=9963|pages=117–71}}</ref> In areas where it is still common, children are most affected.<ref name=WHO2006/> It is rare in the [[developed world]] due to widespread [[vaccination]], but can re-emerge if vaccination rates decrease.<ref name=WHO2006/><ref>{{Cite journal|last=Al|first=A. E. Paniz-Mondolfi et|title=Resurgence of Vaccine-Preventable Diseases in Venezuela as a Regional Public Health Threat in the Americas – Volume 25, Number 4 – April 2019 – Emerging Infectious Diseases journal – CDC|journal=Emerging Infectious Diseases|volume=25|issue=4|pages=625–632|language=en-us|doi=10.3201/eid2504.181305|pmid=30698523|pmc=6433037|year=2019}}</ref> In the United States, 57 cases were reported between 1980 and 2004.<ref name=CDC2012Pink/> Death occurs in 5–10% of those diagnosed.<ref name=CDC2012Pink/> The disease was first described in the 5th century BC by [[Hippocrates]].<ref name=CDC2012Pink/> The bacterium was identified in 1882 by [[Edwin Klebs]].<ref name=CDC2012Pink>{{cite book|last1=Atkinson|first1=William|title=Diphtheria Epidemiology and Prevention of Vaccine-Preventable Diseases|date=May 2012|publisher=Public Health Foundation|isbn=9780983263135|pages=215–230|edition=12|url=https://www.cdc.gov/vaccines/pubs/pinkbook/dip.html|url-status=live|archive-url=https://web.archive.org/web/20160915204257/http://www.cdc.gov/vaccines/pubs/pinkbook/dip.html|archive-date=15 September 2016}}</ref>

==Signs and symptoms==
[[File:Diphtheria bull neck.5325 lores.jpg|upright=1.3|thumb|Diphtheria can cause a swollen neck, sometimes referred to as a ''bull neck''.<ref name=CDC2012Pink/>]]
[[File:A diphtheria skin lesion on the leg. PHIL 1941 lores.jpg|upright=1.3|thumb|A diphtheria skin lesion on the leg]]

The symptoms of diphtheria usually begin two to seven days after infection. They include fever of 38&nbsp;°C (100.4&nbsp;°F) or above; chills; [[Fatigue (medical)|fatigue]]; bluish skin coloration ([[cyanosis]]); sore throat; [[Dysphonia|hoarseness]]; [[cough]]; headache; difficulty swallowing; painful swallowing; [[Shortness of breath|difficulty breathing]]; rapid breathing; foul-smelling and bloodstained nasal discharge; and [[lymphadenopathy]].<ref>{{cite web|url=http://www.nhs.uk/Conditions/Diphtheria/Pages/Symptoms.aspx|title=Diphtheria—Symptoms—NHS Choices|access-date=28 June 2015|url-status=live|archive-url=https://web.archive.org/web/20150628170154/http://www.nhs.uk/Conditions/Diphtheria/Pages/Symptoms.aspx|archive-date=28 June 2015}}</ref><ref name="MedlinePlusEncyclopedia Diphtheria">{{MedlinePlusEncyclopedia|001608|Diphtheria}}</ref> Within two to three days, diphtheria may destroy healthy tissues in the respiratory system. The dead tissue forms a thick, gray coating that can build up in the throat or nose. This thick gray coating is called a "pseudomembrane." It can cover tissues in the nose, tonsils, voice box, and throat, making it very hard to breathe and swallow.<ref>{{cite web|title=Diphtheria Symptoms|url=https://www.cdc.gov/diphtheria/symptoms/|website=www.cdc.gov|access-date=11 January 2025|language=en-us|date=12 February 2024}}</ref> Symptoms can also include [[cardiac arrhythmia]]s, [[myocarditis]], and [[cranial nerve palsy|cranial]] and [[peripheral nerve palsy|peripheral nerve palsies]].<ref>{{cite web |url=https://www.lecturio.com/concepts/diphtheria/| title=Diphtheria|website=The Lecturio Medical Concept Library | date=4 August 2020|access-date= 12 July 2021}}</ref>

=== {{anchor|diphtheritic croup|Diphtheritic croup|Croup|croup|Diphthery croup|diphthery croup}} Diphtheritic croup ===
Laryngeal diphtheria can lead to a characteristic swollen neck and throat, or "bull neck." The swollen throat is often accompanied by a serious respiratory condition, characterized by a brassy or "barking" cough, [[stridor]], hoarseness, and difficulty breathing; and historically referred to variously as "diphtheritic croup,"<ref name=loving>{{cite journal|last=Loving|first=Starling|title=Something concerning the diagnosis and treatment of false croup|journal=[[JAMA (journal)|JAMA: The Journal of the American Medical Association]]|date=5 October 1895|volume=XXV|issue=14|pages=567–573|url=https://books.google.com/books?id=-FQcAQAAMAAJ&pg=PA567|access-date=16 April 2014|doi=10.1001/jama.1895.02430400011001d|url-status=live|archive-url=https://web.archive.org/web/20140704192208/http://books.google.com/books?id=-FQcAQAAMAAJ&pg=PA567|archive-date=4 July 2014}}</ref> "true croup,"<ref name=cormack>{{cite journal|last=Cormack|first=John Rose|title=Meaning of the Terms Diphtheria, Croup, and Faux Croup|journal=[[British Medical Journal]]|date=8 May 1875|volume=1|issue=749|page=606|doi=10.1136/bmj.1.749.606|pmc=2297755|pmid=20747853 }}</ref><ref name=bennett>{{cite journal|last=Bennett|first=James Risdon|title=True and False Croup|journal=[[British Medical Journal]]|date=8 May 1875 |volume=1 |issue=749 |pages=606–607 |doi=10.1136/bmj.1.749.606-a|pmc=2297754|pmid=20747854 }}</ref> or sometimes simply as "croup."<ref name=beard>{{cite book|last=Beard|first=George Miller|title=Our Home Physician: A New and Popular Guide to the Art of Preserving Health and Treating Disease|year=1875|publisher=E. B. Treat|location=New York|pages=[https://archive.org/details/ourhomephysicia00beargoog/page/n567 560]–564|url=https://archive.org/details/ourhomephysicia00beargoog|access-date=15 April 2014}}</ref> Diphtheritic croup is extremely rare in countries where [[diphtheria vaccination]] is customary. As a result, the term "[[croup]]" nowadays most often refers to an unrelated viral illness that produces similar but milder respiratory symptoms.<ref name=vanderpool>{{cite journal|last=Vanderpool |first=Patricia |title=Recognizing croup and stridor in children |journal=American Nurse Today |date=December 2012 |volume=7 |number=12 |url=http://www.americannursetoday.com/article.aspx?id=9752&fid=9722 |access-date=15 April 2014 |url-status=dead |archive-url=https://web.archive.org/web/20140416174601/http://www.americannursetoday.com/article.aspx?id=9752&fid=9722 |archive-date=16 April 2014  }}</ref>

== Transmission ==
Human-to-human transmission of diphtheria typically occurs through the air when an infected individual coughs or sneezes. Breathing in particles released from the infected individual leads to infection.<ref>[https://www.cdc.gov/diphtheria/about/causes-transmission.html Diphtheria Causes and Transmission] {{webarchive|url=https://web.archive.org/web/20140413123404/http://www.cdc.gov/diphtheria/about/causes-transmission.html |date=13 April 2014 }}. U.S. Center for Disease Control and Prevention (2016).</ref> Contact with any lesions on the skin can also lead to transmission of diphtheria, but this is uncommon.<ref>{{cite journal|author1=Youwang Y. |author2=Jianming D. |author3=Yong X. |author4=Pong Z. |title=Epidemiological features of an outbreak of diphtheria and its control with diphtheria toxoid immunization|journal=International Journal of Epidemiology|volume=21|issue=4|pages=807–11|pmid=1521987|year=1992 |doi=10.1093/ije/21.4.807}}</ref> Indirect infections can occur, as well. If an infected individual touches a surface or object, the bacteria can be left behind and remain viable. Also, some evidence indicates diphtheria has the potential to be [[Zoonosis|zoonotic]], but this has yet to be confirmed. ''Corynebacterium ulcerans'' has been found in some animals, which would suggest zoonotic potential.<ref>{{cite journal|author1=Hogg R. A. |author2=Wessels J. |author3=Hart A. |author4=Efstratiou A. |author5=De Zoysa G. |author6=Mann T. |author7=Pritchard G. C. |title=Possible zoonotic transmission of toxigenic ''Corynebacterium ulcerans'' from companion animals in a human case of fatal diphtheria|journal=The Veterinary Record|volume=165|issue=23|pages=691–2|pmid=19966333|year=2009 |doi=10.1136/vr.165.23.691|s2cid=8726176 }}</ref>

==Mechanism==
[[Diphtheria toxin]] (DT) is produced only by ''C.&nbsp;diphtheriae'' infected with a certain type of [[bacteriophage]].<ref>{{cite journal | author = Freeman, Victor J | title = Studies on the Virulence of Bacteriophage-Infected Strains of Corynebacterium Diphtheriae | journal = Journal of Bacteriology | year = 1951 | pages = 675–688 | pmid = 14850426 | volume = 61 | issue = 6 | pmc=386063| doi = 10.1128/JB.61.6.675-688.1951 }}</ref><ref>{{cite journal | author = Freeman VJ, Morse IU | title = Further Observations on the Change to Virulence of Bacteriophage-Infected Avirulent Strains of Corynebacterium Diphtheriae | journal = Journal of Bacteriology | year = 1953 | pages = 407–414 | pmid = 14927573 | volume = 63 | issue = 3 | pmc=169283| last2 = Morse | doi = 10.1128/JB.63.3.407-414.1952 }}</ref>  [[Toxin|Toxinogenicity]] is determined by phage conversion (also called [[Lysogenic cycle|lysogenic conversion]]); i.e., the ability of the bacterium to make DT changes as a consequence of infection by a particular phage. DT is encoded by the ''tox'' gene. Strains of corynephage are either ''tox''<sup>+</sup> (e.g., corynephage β) or ''tox''<sup>−</sup> (e.g., corynephage γ). The ''tox'' gene becomes integrated into the bacterial genome.<ref name="Holmes">{{cite journal |last1=Holmes |first1=R. K. |title=Biology and molecular epidemiology of diphtheria toxin and the tox gene. |journal=The Journal of Infectious Diseases |date=2000 |volume=181 |issue=Supplement 1 |pages=S156–S167 |doi=10.1086/315554 |pmid=10657208|doi-access=free }}</ref> The chromosome of ''C.&nbsp;diphtheriae'' has two different but functionally equivalent bacterial attachment sites (attB) for integration of β prophage into the chromosome.

The diphtheria toxin precursor is a [[protein]] of [[molecular mass|molecular weight]] 60&nbsp;[[Dalton (unit)|kDa]]. Certain proteases, such as trypsin, selectively cleave DT to generate two [[peptide]] chains, amino-terminal fragment A (DT-A) and carboxyl-terminal fragment B (DT-B), which are held together by a [[disulfide bond]].<ref name="Holmes" /> DT-B is a recognition subunit that gains entry of DT 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, DT is split by a trypsin-like [[protease]] into DT-A and DT-B. The acidity of the endosome causes DT-B to create pores in the endosome membrane, thereby catalysing the release of DT-A into the [[cytoplasm]].<ref name="Holmes" />

Fragment A inhibits the synthesis of new proteins in the affected cell 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.<ref name="entrez">{{cite web | title = Entrez Gene: EEF2 eukaryotic translation elongation factor 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1938}}</ref>

ADP-ribosylation of EF-2 is reversed by giving high doses of [[nicotinamide]] (a form of vitamin B<sub>3</sub>), since this is one of the reaction's end products, and high amounts drive the reaction in the opposite direction.<ref>{{cite journal | author = Collier JR | title = Diphtheria toxin: mode of action and structure. | journal = Bacteriological Reviews | year = 1975 | pages = 54–85 | pmid = 164179 | volume = 39 | issue = 1 | pmc=413884| doi = 10.1128/MMBR.39.1.54-85.1975 }}</ref>

==Diagnosis==
The current [[clinical case definition]] of diphtheria used by the [[United States]]' [[Centers for Disease Control and Prevention]] <!-- (CDC) --> is based on both laboratory and clinical criteria.

===Laboratory criteria===
* Isolation of ''C.&nbsp;diphtheriae'' from a Gram stain or throat culture from a clinical specimen.<ref name="MedlinePlusEncyclopedia Diphtheria"/>
* Histopathologic diagnosis of diphtheria by Albert's stain.

===Toxin demonstration===
* In vivo tests (guinea pig inoculation): Subcutaneous and intracutaneous tests.{{citation needed|date=March 2023}}
* In vitro test: Elek's gel precipitation test, detection of tox gene by PCR, ELISA, ICA.

===Clinical criteria===
* Upper respiratory tract illness with sore throat.
* Low-grade fever (above {{convert|39|C|F}} is rare).
* An adherent, dense, grey pseudomembrane covering the posterior aspect of the pharynx; in severe cases, it can extend to cover the entire tracheobronchial tree.

===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.

==Prevention==
{{Main|Diphtheria vaccine}}
[[File:Diphtheria is Deadly Art.IWMPST14182.jpg|thumb|Diphtheria prevention poster from the UK (around 1939-1945).]]

Vaccination against diphtheria is commonly done in infants, and delivered as a combination vaccine, such as a [[DPT vaccine]] (diphtheria, [[pertussis]], [[tetanus]]). [[Pentavalent vaccine]]s, which vaccinate against diphtheria and four other childhood diseases simultaneously, are frequently used in disease prevention programs in [[developing countries]] by organizations such as [[UNICEF]].<ref>{{cite web |url=http://www.unicef.org/republicadominicana/english/survival_development_12792.htm |title=Immunisation and Pentavalent Vaccine |work=[[UNICEF]] |url-status=live |archive-url=https://web.archive.org/web/20140729161800/http://www.unicef.org/republicadominicana/english/survival_development_12792.htm |archive-date=29 July 2014  }}</ref>

==Treatment==
The disease may remain manageable, but in more severe cases, [[lymph nodes]] in the neck may swell, and breathing and swallowing are 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 are put in a hospital [[intensive care unit]], and given diphtheria [[antitoxin]] (consisting of [[antibodies]] isolated from the [[Serum (blood)|serum]] of horses that have been challenged with diphtheria toxin).<ref name=":1" /> Since antitoxin does not neutralize toxin that is already bound to tissues, delaying its administration increases risk of death. Therefore, the decision to administer diphtheria antitoxin is based on clinical diagnosis, and should not await laboratory confirmation.<ref name="Pinkbook">{{Cite book | vauthors = Atkinson W, Hamborsky J, McIntyre L, ((Wolfe S, eds.)) | chapter = Diphtheria | title = Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book) | edition = 10 | pages = 59–70 | location = Washington, D.C. | publisher = Public Health Foundation | year = 2007 | chapter-url = https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/dip.pdf | url-status = live | archive-url = https://web.archive.org/web/20070927000637/http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/dip.pdf | archive-date = 27 September 2007 | df = dmy-all }}</ref>

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.&nbsp;diphtheriae,'' and prevent its transmission to others. The Centers for Disease Control and Prevention (CDC) recommends<ref>The first version of this article was adapted from the Centers for Disease Control and Prevention document [https://wwwn.cdc.gov/nndss/conditions/diphtheria/case-definition/1995/ "Diphtheria (''Corynebacterium diphtheriae'') 1995 Case Definition"] {{webarchive|url=https://web.archive.org/web/20161220041755/https://wwwn.cdc.gov/nndss/conditions/diphtheria/case-definition/1995/ |date=20 December 2016 }}. 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:
* [[Metronidazole]]
* [[Erythromycin]] is given (orally or by injection) for 14 days (40&nbsp;mg/kg per day with a maximum of 2''&nbsp;''g/d), or
* [[Procaine penicillin G]] is given intramuscularly for 14 days (300,000 U/d for patients weighing <10&nbsp;kg, and 600,000 U/d for those weighing >10&nbsp;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. Damage to the heart caused by the toxin affects the heart's ability to pump blood, or the kidneys' ability to clear wastes. It can also cause nerve damage, eventually leading to paralysis. About 40–50% of those left untreated can die.{{citation needed|date=June 2021}}<ref>{{Cite web |date=September 9, 2022 |title=Diagnosis, Treatment, and Complications |url=https://www.cdc.gov/diphtheria/about/diagnosis-treatment.html |access-date=March 7, 2023 |website=Centers for Disease Control and Prevention}}</ref>

== Epidemiology ==
[[File:Diphtheria world map - DALY - WHO2004.svg|upright=1.3|thumb|[[Disability-adjusted life year]] for diphtheria per 100,000&nbsp;inhabitants in 2004:{{Div col|small=yes|colwidth=10em}}
{{legend|#b3b3b3|no data}}
{{legend|#ffff65|≤ 1}}
{{legend|#fff200|1–2}}
{{legend|#ffdc00|2–3}}
{{legend|#ffc600|3–4}}
{{legend|#ffb000|4–5}}
{{legend|#ff9a00|5–6}}
{{legend|#ff8400|6–7}}
{{legend|#ff6e00|7–9}}
{{legend|#ff5800|9–10}}
{{legend|#ff4200|10–15}}
{{legend|#ff2c00|15–50}}
{{legend|#cb0000|≥ 50}}
{{div col end}}]]
[[File:Diphtheria_Cases_-_1997_-_2006.svg|upright=1.3|thumb|Diphtheria cases reported to the [[World Health Organization]] between 1997 and 2006:
{{legend|#C0C0C0|no data}}
{{legend|#E0E080|1–49 reported cases}}
{{legend|#E08040|Between 50–99 reported cases}}
{{legend|#FF0000|Over 100 reported cases}}]]

Diphtheria is fatal in 5–10% of cases. In children under five years and adults over 40 years, the fatality rate may be as much as 20%.<ref name="Pinkbook" /> In 2013, it resulted in 3,300 deaths, down from 8,000 deaths in 1990.<ref name="GDB2013" /> Better standards of living, mass immunization, improved diagnosis, prompt treatment, and more effective health care have led to a decrease in cases worldwide.<ref name=":0" />

==History==
In 1613, [[Health in Spain|Spain]] experienced an epidemic of diphtheria, referred to as {{lang|es|El Año de los Garrotillos}} (The Year of Strangulations).<ref name=":0">{{cite journal|last=Laval|first=Enrique|title=El garotillo (Difteria) en España (Siglos XVI y XVII)|journal=Revista Chilena de Infectología|date=March 2006|volume=23|issue=1|pages=78–80|doi=10.4067/S0716-10182006000100012|pmid=16462970|doi-access=free}}</ref>

In 1705, the [[Mariana Islands]] experienced an epidemic of diphtheria and [[typhus]] simultaneously, reducing the population to about 5,000 people.<ref>{{cite book |last1=Rogers |first1=Robert F. |title=Destiny's Landfall: A History of Guam |date=June 30, 2011 |publisher=University of Hawai'i Press |location=Honolulu, Hawai'i |isbn=978-0-8248-3334-3 |page=72}}</ref>

In 1735, a diphtheria epidemic swept through [[New England]].<ref>{{cite journal|journal=[[Pediatrics (journal)|Pediatrics]]|year=1975|volume=55|pages=43|issue=1|title=On the Treatment of Diphtheria in 1735|url=http://pediatrics.aappublications.org/content/55/1/43|url-access=subscription|publisher= [[American Academy of Pediatrics]]|doi=10.1542/peds.55.1.43|s2cid=245183270}}</ref>

Before 1826, diphtheria was known by different names across the world. In [[England]], it was known as "Boulogne sore throat," as the illness had spread from [[France]]. In 1826, [[Pierre Bretonneau]] gave the disease the name ''diphthérite'' (from Greek διφθέρα, ''diphthera'' 'leather'), describing the appearance of pseudomembrane in the throat.<ref>Bretonneau, Pierre (1826) ''Des inflammations spéciales du tissu muqueux, et en particulier de la diphtérite, ou inflammation pelliculaire, connue sous le nom de croup, d'angine maligne, d'angine gangréneuse, etc.'' [Special inflammations of mucous tissue, and in particular diphtheria or skin inflammation, known by the name of croup, malignant throat infection, gangrenous throat infection, etc.] Paris, France:  Crevot.<br>
A condensed version of this work is available in:  P. Bretonneau (1826) [http://babel.hathitrust.org/cgi/pt?id=mdp.39015062233708;view=1up;seq=217 "Extrait du traité de la diphthérite, angine maligne, ou croup épidémique"] (Extract from the treatise on diphtheria, malignant throat infection, or epidemic croup), ''Archives générales de médecine'', series 1, 11 :  219–254.  From p. 230:  " … M. Bretonneau a cru convenable de l'appeler diphthérite, dérivé de ΔΙΦθΕΡΑ, … " ( … Mr. Bretonneau thought it appropriate to call it diphtheria, derived from ΔΙΦθΕΡΑ [diphthera], … )</ref><ref>{{cite web|title=Diphtheria|url=http://www.etymonline.com/index.php?term=diphtheria|work=Online Etymology Dictionary|access-date=29 November 2012|url-status=live|archive-url=https://web.archive.org/web/20130113162016/http://www.etymonline.com/index.php?term=diphtheria|archive-date=13 January 2013}}</ref>

In 1856, [[Victor Fourgeaud]] described an epidemic of diphtheria in [[Health in California|California]].<ref>{{cite book |last1=Fourgeaud |first1=Victor John |title=Diphtheritis: A Concise Historical and Critical Essay on the Late Epidemic Pseudo-membranous Sore Throat of California (1856-7) with a Few Remarks Illustrating the Diagnosis, Pathology and Treatment of the Disease |date=1858 |publisher=J. Anthony |oclc=11760038 |url=http://resource.nlm.nih.gov/101179231 }}{{pn|date=February 2024}}</ref>

In 1878, [[Princess Alice of the United Kingdom|Princess Alice]] ([[Queen Victoria]]'s second daughter) and her family became infected with diphtheria; Princess Alice and her four-year-old daughter, [[Princess Marie of Hesse and by Rhine (1874–1878)|Princess Marie]], both died.<ref>{{cite web|title=Diaries and Letters – Princess Alice of Hesse and by Rhine|url=http://www.alexanderpalace.org/palace/alicehessebio.html}}</ref>{{Self-published inline|date=November 2021|certain=y}}

In 1883, [[Edwin Klebs]] identified the bacterium causing diphtheria,<ref>Klebs, E. (1883) [https://books.google.com/books?id=bs0vAAAAIAAJ&pg=RA1-PA139 "III. Sitzung:  Ueber Diphtherie" (Third session:  On diphtheria), ''Verhandlungen des Congresses für innere Medicin. Zweiter Congress gehalten zu Wiesbaden, 18.-23. April 1883''] {{webarchive|url=https://web.archive.org/web/20160522005528/https://books.google.com/books?id=bs0vAAAAIAAJ&pg=RA1-PA139 |date=22 May 2016 }} (Proceedings of the Congress on Internal Medicine.  Second congress held at Wiesbaden, 18–23 April 1883), 2 : 139–154.</ref> and named it [[Corynebacterium diphtheriae|Klebs–Loeffler bacterium]]. The club shape of this bacterium helped Edwin to differentiate it from other bacteria. Over time, it has been called ''Microsporon diphtheriticum'', ''Bacillus diphtheriae'', and ''Mycobacterium diphtheriae''. Current nomenclature is ''Corynebacterium diphtheriae''.<ref>{{Cite web |title=Corynebacterium diphtheriae |url=https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=info&id=1717 |website=NCBI Taxonomy browser }}</ref>

In 1884, German [[bacteriologist]] [[Friedrich Loeffler]] became the first person to cultivate ''C.&nbsp;diphtheriae''.<ref>Loeffler, F. (1884) "Untersuchungen über die Bedeutung der Mikroorganismen für die Entstehung der Diphtherie, beim Menschen, bei der Taube und beim Kalbe" (Investigations into the significance of microorganisms in the development of diphtheria among humans, pigeons, and calves), ''Mitteilungen aus der Kaiserlichen Gesundheitsamte'' (Communications from the Imperial Office of Health), 2 :  421–499.</ref> He used [[Koch's postulates]] to prove association between ''C.&nbsp;diphtheriae'' and diphtheria. He also showed that the bacillus produces an exotoxin.{{citation needed|date=November 2017}}[[File:Diphtheria Immunisation Scheme, London, England, 1941 D3184.jpg|upright=1.3|thumb|left|A diphtheria immunisation scheme in London (1941)]]

In 1885, [[Joseph O'Dwyer|Joseph P. O'Dwyer]] introduced the O'Dwyer tube for laryngeal intubation in patients with an obstructed larynx. It soon replaced [[Tracheotomy|tracheostomy]] as the emergency diphtheric intubation method.<ref>{{cite journal|last=Gifford|first=Robert R.|s2cid=37108037|title=The O'Dwyer tube; development and use in laryngeal diphtheria|journal=Clin Pediatr (Phila)|date=March 1970|volume=9|issue=3|pages=179–185|doi=10.1177/000992287000900313|pmid=4905866}}</ref>

In 1888, [[Emile Roux]] and [[Alexandre Yersin]] showed that a substance produced by ''C.&nbsp;diphtheriae'' caused symptoms of diphtheria in animals.<ref>Roux, E. and Yersin, A. (December 1888)  [https://archive.org/stream/annalesdelinstit02inst#page/n686/mode/1up "Contribution à l'étude de la diphthérte"] {{webarchive|url=https://web.archive.org/web/20160315082939/https://archive.org/stream/annalesdelinstit02inst |date=15 March 2016 }} (Contribution to the study of diphtheria), ''Annales de l'Institute Pasteur'', 2 :  629–661.</ref><ref>{{cite book|last=Parish|first=Henry|title=A history of immunization|year=1965|publisher=E. & S. Livingstone|page=120}}</ref>

In 1890, [[Kitasato Shibasaburō|Shibasaburō Kitasato]] and [[Emil von Behring]] immunized guinea pigs with heat-treated diphtheria toxin.<ref>Behring, E. and Kitasato, S. (1890) [https://archiv.ub.uni-marburg.de/eb/2013/0164/ "Ueber das Zustandekommen der Diphtherie-Immunitat und der Tetanus-Immunitat bei Thieren"] {{webarchive|url=https://web.archive.org/web/20161220042358/https://archiv.ub.uni-marburg.de/eb/2013/0164/ |date=20 December 2016 }} (On the realization of diphtheria immunity and tetanus immunity among animals), ''Deutsche medizinsche Wochenschrift'', ''16'' : 1113–1114.</ref> They also immunized goats and horses in the same way, and showed that an "[[antitoxin]]" made from [[Serum (blood)|serum]] of immunized animals could cure the disease in non-immunized animals. Behring used this antitoxin (now known to consist of [[Antibody|antibodies]] that neutralize the toxin produced by ''C.&nbsp;diphtheriae'') for human trials in 1891, but they were unsuccessful. Successful treatment of human patients with horse-derived antitoxin began in 1894, after production and quantification of antitoxin had been optimized.<ref>{{Cite journal|last=Kaufmann|first=Stefan H. E.|date=8 March 2017|title=Remembering Emil von Behring: from Tetanus Treatment to Antibody Cooperation with Phagocytes|journal=mBio|language=en|volume=8|issue=1|pages=e00117–17|pmid=28246359|pmc=5347343|doi=10.1128/mBio.00117-17}}</ref><ref name=":1">{{Cite news|url=https://journals.lww.com/academicmedicine/Fulltext/2000/04000/Horses_and_the_Diphtheria_Antitoxin.22.aspx|title=Horses and the Diphtheria Antitoxin|date=April 2000|work=Academic Medicine|language=en-US}}</ref> In 1901, Von Behring won the first [[Nobel Prize in Physiology or Medicine|Nobel Prize in medicine]] for his work on diphtheria.<ref>Emil von Behring [https://www.nobelprize.org/nobel_prizes/medicine/laureates/1901/behring-lecture.html Serum Therapy in Therapeutics and Medical Science]. Nobel Lecture, 12 December 1901. nobelprize.org</ref>

In 1895, [[H. K. Mulford Company]] of [[Philadelphia]] started production and testing of diphtheria antitoxin in the United States.<ref>{{cite book|author=H. K. Mulford Company|title=Diphtheria Antitoxin|year=1903|publisher=The Company|url=https://books.google.com/books?id=hV_StgAACAAJ}}</ref> [[William Hallock Park|Park]] and [[Hermann Biggs|Biggs]] described the method for producing serum from horses for use in diphtheria treatment.{{citation needed|date=November 2017}}

In 1897, [[Paul Ehrlich]] developed a standardized unit of measure for diphtheria antitoxin. This was the first ever standardization of a biological product, and played an important role in future developmental work on sera and vaccines.<ref>{{Cite web |title=Difference Between Serums & Vaccines {{!}} What is - YTread |url=https://youtuberead.com/difference-between-serums-vaccines |access-date=2023-04-02 |website=youtuberead.com |language=en}}</ref>

In 1901, 10 of 11 inoculated [[St. Louis]] children died from contaminated diphtheria antitoxin. The horse from which the antitoxin was derived died of [[tetanus]]. This incident, coupled with a tetanus outbreak in [[Camden, New Jersey]],<ref>{{cite journal|title=The Tetanus Cases in Camden, N.J|journal=JAMA|date=7 December 1901|volume=XXXVII|issue=23|pages=1539–1540|doi=10.1001/jama.1901.02470490037010}}</ref> played an important part in initiating federal regulation of biologic products.<ref>{{cite journal|last=Lilienfeld|first=David E.|s2cid=30767303|title=The first pharmacoepidemiologic investigations: national drug safety policy in the United States, 1901–1902|journal=Perspect Biol Med|date=Spring 2008|volume=51|issue=2|pages=188–198|doi=10.1353/pbm.0.0010|pmid=18453724}}</ref>

On 7 January 1904, [[Ruth Cleveland]] died of diphtheria at the age of 12 years in [[Princeton, New Jersey]]. Ruth was the eldest daughter of former [[President of the United States|President]] [[Grover Cleveland]] and the former [[First Lady of the United States|First Lady]], [[Frances Folsom]].{{citation needed|date=June 2022}}

In 1905, Franklin Royer, from Philadelphia's Municipal Hospital, published a paper urging timely treatment for diphtheria and adequate doses of antitoxin.<ref>{{cite journal|last=Royer|first=Franklin|title=The Antitoxin Treatment of Diphtheria, with a Plea for Rational Dosage in Treatment and in Immunizing|journal = The Therapeutic Gazette|year=1905}}</ref> In 1906, [[Clemens Pirquet]] and [[Béla Schick]] described [[serum sickness]] in children receiving large quantities of horse-derived antitoxin.<ref name="pmid11231202">{{cite journal |author=Jackson R |s2cid=7001068 |title=Serum sickness |journal=J Cutan Med Surg |volume=4 |issue=4 |pages=223–5 |date=October 2000 |pmid=11231202 |doi= 10.1177/120347540000400411}}</ref>

Between 1910 and 1911, Béla Schick developed the [[Schick test]] to detect pre-existing immunity to diphtheria in an exposed person. Only those who had not been exposed to diphtheria were vaccinated. 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 significantly 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 |access-date=30 June 2008 |publisher=HealthSentinel.com |archive-url = https://web.archive.org/web/20080514014018/http://www.healthsentinel.com/graphs.php |archive-date = 14 May 2008}}</ref>

In 1919, in [[Dallas|Dallas, Texas]], 10 children were killed and 60 others made seriously ill by toxic antitoxin which had passed the tests of the [[New York State Department of Health|New York State Health Department]]. The manufacturer of the antitoxin, the [[Merck Sharp & Dohme|Mulford Company of Philadelphia]], paid damages in every case.<ref>{{cite book|last=Wilson|first=Graham|title=The Hazards of Immunization|year=2002|publisher=Continuum International Publishing Group, Limited, 2002|isbn=9780485263190|pages=20}}</ref>

During the 1920s, an annual estimate of 100,000 to 200,000 diphtheria cases and 13,000 to 15,000 deaths occurred in the United States.<ref name="Pinkbook"/> Children represented a large majority of these cases and fatalities. One of the most infamous outbreaks of diphtheria occurred in 1925, in [[Nome, Alaska]]; the [[1925 serum run to Nome|"Great Race of Mercy"]] to deliver diphtheria antitoxin is now celebrated by the [[Iditarod Trail Sled Dog Race]].<ref>{{Cite web|url=https://www.cdc.gov/about/24-7/savinglives/diphtheria/index.html|title=Iditarod: Celebrating the "Great Race of Mercy" to Stop Diphtheria Outbreak in Alaska {{!}} About {{!}} CDC|date=11 July 2018|website=www.cdc.gov|language=en-us|access-date=5 March 2019}}</ref>

In 1926, Alexander Thomas Glenny increased the effectiveness of diphtheria [[toxoid]] (a modified version of the toxin used for vaccination) by treating it with aluminum salts.<ref>{{cite web|url=http://www.historyofvaccines.org/content/timelines/diseases-and-vaccines |title=Timeline |at=1926 — Glenny Develops Adjuvant |work=History of Vaccines |access-date=28 October 2013 |url-status=live |archive-url=https://web.archive.org/web/20140701081956/http://www.historyofvaccines.org/content/timelines/diseases-and-vaccines |archive-date=1 July 2014}}</ref> Vaccination with toxoid was not widely used until the early 1930s.<ref>[https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/dip.pdf Immunology and Vaccine-Preventable Diseases – Pink Book – Diphtheria], CDC</ref> In 1939, Dr. [[Nora Wattie]], who was the [[Principal Medical Officer]] (Maternity and Child Welfare) of Glasgow between 1934– 1964,<ref>{{Cite web |date=March 2021 |title=Nora Isabel Wattie |url=https://mathshistory.st-andrews.ac.uk/Extras/Wattie_Nora/ |url-status=live |archive-url=https://archive.today/20230903042427/https://mathshistory.st-andrews.ac.uk/Extras/Wattie_Nora/ |archive-date=3 September 2023 |access-date=2 September 2023 |website=MacTutor |publication-place=[[University of St Andrews]]}}</ref> introduced immunisation clinics across [[Glasgow]], and promoted mother and child health education, resulting in virtual eradication of the infection in the city.<ref>{{Cite journal|last1=Mackie|first1=Elizabeth M|last2=Scott Wilson|first2=T.|date=12 November 1994|title=Obituary N.I.Wattie|journal=British Medical Journal|volume=309|pages=1297}}</ref>

Widespread vaccination pushed cases in the United States down from 4.4 per 100,000 inhabitants in 1932 to 2.0 in 1937. In [[Nazi Germany]], where authorities preferred treatment and isolation over vaccination (until about 1939–1941), cases rose over the same period from 6.1 to 9.6 per 100,000 inhabitants.<ref>{{Cite journal|last1=Baten|first1=Joerg|last2=Wagner|date=2003|title=Autarky, Market Disintegration, and Health: The Mortality and Nutritional Crisis in Nazi Germany 1933–37|journal=Economics and Human Biology |volume=1-1 |issue=1 |pages=1–28 |doi=10.1016/S1570-677X(02)00002-3 |pmid=15463961 |s2cid=36431705 |url=https://www.cesifo.org/DocDL/cesifo_wp800.pdf}}</ref>

Between June 1942 and February 1943, 714 cases of diphtheria were recorded at [[Sham Shui Po Barracks]], resulting in 112 deaths because the [[Imperial Japanese Army]] did not release supplies of anti-diphtheria serum.<ref>{{cite book |last=Felton|first=Mark|author-link=Mark Felton|date=2009|title=The Real Tenko: Extraordinary True Stories of Women Prisoners of the Japanese|url= |location=Great Britain|publisher=Pen & Sword Military|page=41 |isbn=9781848845503}}</ref>

In 1943, diphtheria outbreaks accompanied war and disruption in [[Europe in World War II|Europe]]. The 1 million cases in Europe resulted in 50,000 deaths.{{citation needed|date=March 2017}}

During 1948 in [[Kyoto]], 68 of 606 children died after diphtheria immunization due to improper manufacture of aluminum phosphate toxoid.<ref>{{cite book |editor1-first=Kathleen R. |editor1-last=Stratton |editor2-first=Cynthia J. |editor2-last=Howe |editor3-first=Richard B. |editor3-last=Johnston |chapter=Diphtheria and Tetanus Toxoids |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK236292/ |title=Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality |date=1994 |publisher=National Academies Press |isbn=978-0-309-04895-8 }}</ref>

In 1974, the [[World Health Organization]] included [[DPT vaccine]] in their [[Expanded Programme on Immunization]] for [[Developing country|developing countries]].<ref>{{cite web | title = Immunization, Vaccines and Biologicals | publisher = World Health Organization | url = https://www.who.int/immunization/programmes_systems/en/ | archive-url = https://web.archive.org/web/20131208072315/http://www.who.int/immunization/programmes_systems/en/ | url-status = dead | archive-date = 8 December 2013 | access-date = 10 May 2020}}</ref><ref>{{cite journal |last1=Keja |first1=Ko |last2=Chan |first2=Carole |last3=Hayden |first3=Gregory |last4=Henderson |first4=Ralph H. |title=Expanded Programme on Immunization |journal=World Health Statistics Quarterly |date=1988 |volume=41 |issue=2 |pages=59–63 |pmid=3176515 |hdl=10665/49253 }}</ref>

In 1975, an outbreak of cutaneous diphtheria in [[Seattle|Seattle, Washington]], was reported.<ref>{{cite journal|last=Harnisch|first=JP|author2=Tronca E |author3=Nolan CM |author4=Turck M |author5=Holmes KK |title=Diphtheria among alcoholic urban adults. A decade of experience in Seattle|journal=Annals of Internal Medicine|date=1 July 1989|volume=111|issue=1|pages=71–82|pmid=2472081|doi=10.7326/0003-4819-111-1-71}}</ref>

After the breakup of the former [[Soviet Union]] in 1991, vaccination rates in its constituent countries fell so low that an explosion of diphtheria cases occurred. In 1991, 2,000 cases of diphtheria occurred in the USSR. Between 1991 and 1998, as many as 200,000 cases were reported in the [[Commonwealth of Independent States]], and resulted in 5,000 deaths.<ref name=":0" /> In 1994, the [[Russia|Russian Federation]] had 39,703 diphtheria cases. By contrast, in 1990, only 1,211 cases were reported.<ref>{{cite journal|doi=10.1086/315567|pmid=10657219|title=Contraindications to Vaccination in the Russian Federation|journal=The Journal of Infectious Diseases|volume=181|pages=S228–31|year=2000|last1=Tatochenko|first1=Vladimir|last2=Mitjushin|first2=I. L.|doi-access=free}}
</ref>

In early May 2010, a case of diphtheria was diagnosed in [[Port-au-Prince]], [[Health in Haiti|Haiti]], after the devastating [[2010 Haiti earthquake]]. The 15-year-old male patient died while workers searched for antitoxin.<ref>{{Cite web | url=http://ac360.blogs.cnn.com/2010/05/10/video-diphtheria-epidemic-threatens-haiti/ | title=CNN's Anderson Cooper talks with Sean Penn and Dr. Sanjay Gupta about the threat of diphtheria in Haiti | date=10 May 2010 | work=CNN. | url-status=dead | archive-url=https://web.archive.org/web/20161220045251/http://ac360.blogs.cnn.com/2010/05/10/video-diphtheria-epidemic-threatens-haiti/ | archive-date=20 December 2016 | df=dmy-all }}</ref>

In 2013, three children died of diphtheria in [[Hyderabad, India]].<ref>{{Cite news | url=http://www.thehindu.com/news/cities/Hyderabad/three-kids-die-of-diphtheria/article5065637.ece?homepage=true | title=Three kids die of diphtheria | date=28 August 2013 | work=The Hindu | url-status=live | archive-url=https://web.archive.org/web/20161220221203/http://www.thehindu.com/news/cities/Hyderabad/three-kids-die-of-diphtheria/article5065637.ece?homepage=true | archive-date=20 December 2016 | df=dmy-all }}</ref>

In early June 2015, a case of diphtheria was diagnosed at [[Vall d'Hebron University Hospital]] in [[Barcelona]], [[Spain]]. The six-year-old child who died of the illness had not been previously vaccinated due to parental [[vaccine controversies|opposition to vaccination]].<ref>{{Cite web|title = Parents of diphtheria-stricken boy feel "tricked" by anti-vaccination groups|url = http://elpais.com/elpais/2015/06/05/inenglish/1433512717_575817.html|work = El Pais|date = 5 June 2015|url-status = live|archive-url = https://web.archive.org/web/20150607000140/http://elpais.com/elpais/2015/06/05/inenglish/1433512717_575817.html|archive-date = 7 June 2015|df = dmy-all}}</ref> It was the first case of diphtheria in the country since 1986, as reported by the Spanish daily newspaper ''[[El Mundo (Spain)|El Mundo]],''<ref>{{Cite web|title = Primer caso de difteria en España en casi 30 años|url = http://www.elmundo.es/salud/2015/06/02/556dbc3d268e3e16598b4589.html|work = El Mundo|date = 2 June 2015|url-status = live|archive-url = https://web.archive.org/web/20150602181425/http://www.elmundo.es/salud/2015/06/02/556dbc3d268e3e16598b4589.html|archive-date = 2 June 2015|df = dmy-all}}</ref> or from 1998, as reported by the WHO.<ref>{{Cite web|title = WHO – Diphtheria reported cases|url = http://apps.who.int/immunization_monitoring/globalsummary/timeseries/tsincidencediphtheria.html|access-date = 11 June 2015|url-status = live|archive-url = https://web.archive.org/web/20150612235540/http://apps.who.int/immunization_monitoring/globalsummary/timeseries/tsincidencediphtheria.html|archive-date = 12 June 2015|df = dmy-all}}</ref>

In March 2016, a three-year-old girl died of diphtheria in the University Hospital of [[Antwerp]], [[Health in Belgium|Belgium]].<ref>{{Cite web|url=http://www.standaard.be/cnt/dmf20160317_02188083|title=Meisje (3) overlijdt aan difterie in ziekenhuis|website=De Standaard|date=17 March 2016|url-status=live|archive-url=https://web.archive.org/web/20160319045227/http://www.standaard.be/cnt/dmf20160317_02188083|archive-date=19 March 2016}}</ref>

In June 2016, a three-year-old, five-year-old, and seven-year-old girl died of diphtheria in [[Kedah]], [[Malacca]], and [[Sabah]], [[Health in Malaysia|Malaysia]].<ref>{{Cite web|url=http://www.thestar.com.my/news/nation/2016/06/21/story/|title=Malacca Health Dept works to contain diptheria after seven-year-old dies|date=21 June 2016|author=Murali, R.S.N.|work=thestar.com.my|url-status=live|archive-url=https://web.archive.org/web/20160624034554/http://www.thestar.com.my/news/nation/2016/06/21/story/|archive-date=24 June 2016}}</ref>

In January 2017, more than 300 cases were recorded in [[Health in Venezuela|Venezuela]].<ref>{{Cite news|url=https://www.reuters.com/article/us-venezuela-health-idUSKBN185260|title=Infant mortality and malaria soar in Venezuela, according to government data|date=9 May 2017|work=Reuters|access-date=3 June 2017|url-status=live|archive-url=https://web.archive.org/web/20170524223813/http://www.reuters.com/article/us-venezuela-health-idUSKBN185260|archive-date=24 May 2017}}</ref><ref>{{Cite web|url=http://www.healthmap.org/site/diseasedaily/article/diphtheria-reemerges-venezuela-remains-brink-economic-collapse-22117|title=Diphtheria Reemerges as Venezuela Remains on the Brink of Economic Collapse {{!}} HealthMap|website=www.healthmap.org|access-date=3 June 2017|url-status=live|archive-url=https://web.archive.org/web/20170712034357/http://www.healthmap.org/site/diseasedaily/article/diphtheria-reemerges-venezuela-remains-brink-economic-collapse-22117|archive-date=12 July 2017}}</ref>

In 2017, outbreaks occurred in a [[Rohingya refugees in Bangladesh|Rohingya refugee camp in Bangladesh]], and amongst children unvaccinated due to the [[Yemeni Civil War (2014–present)|Yemeni Civil War]].<ref>[https://www.npr.org/sections/goatsandsoda/2017/12/08/569462246/diphtheria-why-is-it-back-and-what-exactly-is-it Diphtheria: What Exactly Is It ... And Why Is It Back?]</ref>

In November and December 2017, an outbreak of diphtheria occurred in [[Indonesia]], with more than 600 cases found and 38 fatalities.<ref>{{Cite news|url=https://news.detik.com/berita/d-3774591/idi-38-anak-meninggal-karena-difteri|title=IDI: 38 Anak Meninggal karena Difteri|last=Nugraha|first=Indra Komara|work=detiknews|access-date=18 December 2017}}</ref>

In November 2019, two cases of diphtheria occurred in the [[Lothian]] area of [[Health in Scotland|Scotland]].<ref>{{Cite news|url=https://www.bbc.co.uk/news/uk-scotland-edinburgh-east-fife-50358872|title=Two cases of deadly diphtheria detected in Lothian area|date=9 November 2019|author=BBC|work=BBC News}}</ref> Additionally, in November 2019, an unvaccinated 8-year-old boy died of diphtheria in [[Athens]], [[Health in Greece|Greece]].<ref>{{Cite web|url=https://www.amea-care.gr/%ce%bf%ce%ba%cf%84%ce%ac%cf%87%cf%81%ce%bf%ce%bd%ce%bf%cf%82-%cf%80%ce%ad%ce%b8%ce%b1%ce%bd%ce%b5-%ce%b1%cf%80%cf%8c-%ce%b4%ce%b9%cf%86%ce%b8%ce%b5%cf%81%ce%af%cf%84%ce%b9%ce%b4%ce%b1-%cf%83%cf%84/|title=Οκτάχρονος πέθανε από διφθερίτιδα στην Αθήνα - Δεν είχε εμβολιαστεί|date=2019-11-28|website=ΑμεΑ Care|language=el|access-date=2019-11-28}}</ref>

In July 2022, two cases of diphtheria occurred in northern [[New South Wales]], [[Health in Australia|Australia]].<ref>{{Cite news|url=https://www.theguardian.com/australia-news/2022/jul/03/toddler-diagnosed-with-first-case-of-diphtheria-of-the-throat-in-nsw-in-a-century|title=Two children diagnosed with first cases of diphtheria of the throat in NSW this century|access-date=21 July 2022}}</ref>

In October 2022, there was an outbreak of diphtheria at the former [[RAF Manston|Manston airfield]], a former [[Ministry of Defence (United Kingdom)|Ministry of Defence]] (MoD) site in [[Kent]], [[Health in England|England]], which had been converted to an [[Asylum seekers in the United Kingdom|asylum seeker processing centre]]. The capacity of the processing centre was 1,000 people, although about 3,000 were living at the site, with some accommodated in tents. The [[Home Office]], the government department responsible for asylum seekers, refused to confirm the number of cases.<ref>{{Cite web |last=Taylor |first=Diane |date=20 October 2022 |title=Diphtheria outbreak confirmed at asylum seeker centre in Kent |url=https://www.theguardian.com/science/2022/oct/20/diphtheria-outbreak-confirmed-at-asylum-seeker-centre-in-kent |archive-url=https://web.archive.org/web/20221020114017/https://www.theguardian.com/science/2022/oct/20/diphtheria-outbreak-confirmed-at-asylum-seeker-centre-in-kent |archive-date=20 October 2022 |access-date=21 October 2022 |website=The Guardian |language=en}}</ref>

In December 2023 there was an outbreak at a school in [[Luton]], in the [[United Kingdom]]. [[UK Health Security Agency]] (UKHSA) issued a statement saying specialists have been providing public health support following confirmation of the diphtheria case at a primary school in Luton. The agency said it is working closely with local and national partners "to ensure all necessary public health measures are implemented" following the discovery of the new case. The statement added: "We have conducted a risk assessment and close contacts of the case have been identified and where appropriate, vaccination and advice will be given to prevent the spread of the infection."<ref>{{cite web |url=https://www.manchestereveningnews.co.uk/news/health/ukhsa-issues-statement-case-rare-28285751 |title=UKHSA issues statement as case of rare infectious disease confirmed at UK primary school |website=The Manchester Evening News |language=en |date=13 December 2023 |access-date=14 December 2023}}</ref>

==References==
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==Further reading==
* Hammonds, Evelynn Maxine.  ''Childhood's Deadly Scourge: The Campaign to Control Diphtheria in New York City, 1880-1930'' (1999)
** Hammonds, Evelynn Maxine.   "The search for perfect control: A social history of diphtheria, 1880-1930" (PhD dissertation, Harvard University; ProQuest Dissertations & Theses,  1993. 9318671).

* {{cite book |last=Holmes |first=R .K. |chapter=Diphtheria and other corynebacterial infections |editor1-last=Kasper |title=Harrison's Principles of Internal Medicine |edition=16th |location=New York |publisher=McGraw-Hill |isbn=978-0-07-139140-5 |year=2005 |display-editors=etal}}
* "Antitoxin dars 1735 and 1740." ''The William and Mary Quarterly'', 3rd Ser., Vol 6, No 2. p.&nbsp;338.
* {{cite journal |last=Shulman |first=S. T. |title=The History of Pediatric Infectious Diseases |journal=Pediatric Research |volume=55 |issue=1 |year=2004 |pages=163–176 |pmid=14605240 |doi=10.1203/01.PDR.0000101756.93542.09 |pmc=7086672 }}

==External links==
{{Commons}}
* {{cite web | url = https://medlineplus.gov/diphtheria.html | publisher = U.S. National Library of Medicine | work = MedlinePlus | title = Diphtheria }}
* [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)30226-0/fulltext Mapping diphtheria-pertussis-tetanus vaccine coverage in Africa, 2000–2016: a spatial and temporal modelling study]

{{Medical condition classification and resources
| DiseasesDB     = 3122
| ICD11          = {{ICD11|1C17}}
| ICD10          = {{ICD10|A|36||a|36}}
| ICD9           = {{ICD9|032}}
| ICDO           =
| OMIM           =
| MedlinePlus    = 001608
| eMedicineSubj  = emerg
| eMedicineTopic = 138
| eMedicine_mult = {{eMedicine2|med|459}} {{eMedicine2|oph|674}} {{eMedicine2|ped|596}}
| MeshID         = D004165
}}
{{Gram-positive actinobacteria diseases}}
{{Authority control}}

[[Category:Diphtheria| ]]
[[Category:Bacterial diseases]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Wikipedia emergency medicine articles ready to translate]]
[[Category:Vaccine-preventable diseases]]
[[Category:Rare infectious diseases]]