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{{SI}}
{{Infobox medical condition
| name            = Diphtheria
| image          = [[File:Dirty_white_pseudomembrane_classically_seen_in_diphtheria_2013-07-06_11-07.jpg|alt=Dirty white pseudomembrane classically seen in diphtheria]]
| caption        = Dirty white pseudomembrane classically seen in diphtheria
| field          = [[Infectious disease]]
| symptoms        = [[Sore throat]], [[fever]], [[swollen lymph nodes]], [[weakness]]
| complications  = [[Myocarditis]], [[peripheral neuropathy]], [[kidney problems]]
| onset          = 2–5 days after exposure
| duration        = Variable
| causes          = ''[[Corynebacterium diphtheriae]]''
| risks          = [[Unvaccinated]], [[crowded living conditions]]
| diagnosis      = [[Throat culture]], [[PCR test]]
| prevention      = [[Diphtheria vaccine]]
| treatment      = [[Diphtheria antitoxin]], [[antibiotics]]
| medication      = [[Erythromycin]], [[penicillin]]
| prognosis      = 5–10% mortality rate
| frequency      = Rare in developed countries
| deaths          = 2,100 (2015)
}}
Diphtheria is a bacterial infection that causes a fever, headache, sore throat, and possibly death.
Diphtheria is a bacterial infection that causes a fever, headache, sore throat, and possibly death.
[[File:Corynebacterium diphtheriae Gram stain.jpg|alt=Corynebacterium diphtheriae Gram stain|thumb|'''Corynebacterium diphtheriae Gram stain''']]
[[File:Corynebacterium diphtheriae Gram stain.jpg|alt=Corynebacterium diphtheriae Gram stain|left|thumb|'''Corynebacterium diphtheriae Gram stain''']]
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== Epidemiology==
== Epidemiology==
* Diphtheria is an acute, bacterial disease caused by toxin-producing strains of Corynebacterium diphtheriae.  
* Diphtheria is an acute, bacterial disease caused by toxin-producing strains of Corynebacterium diphtheriae.  
Line 19: Line 30:
* Invasive disease, including bacteremia and endocarditis, has been reported for non-toxin-producing strains of C. diphtheriae.
* Invasive disease, including bacteremia and endocarditis, has been reported for non-toxin-producing strains of C. diphtheriae.
* Vaccination is highly protective against disease caused by toxin-producing strains, but does not prevent carriage of C. diphtheriae, regardless of toxin production status.
* Vaccination is highly protective against disease caused by toxin-producing strains, but does not prevent carriage of C. diphtheriae, regardless of toxin production status.
[[File:Throat of adult and of a child infected with diphtheria (Diphtheria, 1859).jpg|alt=Throat of adult and of a child infected with diphtheria|thumb|Throat of adult and of a child infected with diphtheria]]
[[File:Throat of adult and of a child infected with diphtheria (Diphtheria, 1859).jpg|alt=Throat of adult and of a child infected with diphtheria|left|thumb|Throat of adult and of a child infected with diphtheria]]
==Clinical Resource==
Key questions to consider when assessing suspected respiratory diphtheria cases pdf icon[1 page]
[[File:Diphtheria is Deadly Art.IWMPST14182.jpg|alt=Diphtheria is Deadly Art|left|thumb|Diphtheria is Deadly Art]]
==Corynebacterium diphtheriae==
C. diphtheriae is an aerobic gram-positive bacillus. Toxin production (toxigenicity) occurs only when the bacillus is itself infected (lysogenized) by a specific virus (bacteriophage) carrying the genetic information for the toxin (tox gene).
[[File:Diphtheria bull neck.5325 lores.jpg|left|thumb]]
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==Clinical Resource==
Key questions to consider when assessing suspected respiratory diphtheria cases pdf icon[1 page]
[[File:Diphtheria is Deadly Art.IWMPST14182.jpg|alt=Diphtheria is Deadly Art|thumb|Diphtheria is Deadly Art]]
==Corynebacterium diphtheriae==
C. diphtheriae is an aerobic gram-positive bacillus. Toxin production (toxigenicity) occurs only when the bacillus is itself infected (lysogenized) by a specific virus (bacteriophage) carrying the genetic information for the toxin (tox gene).
[[File:Diphtheria bull neck.5325 lores.jpg|thumb]]
==Transmission==
==Transmission==
Transmission is most often person-to-person spread from the respiratory tract. Rarely, transmission may occur from skin lesions or articles soiled with discharges from lesions of infected persons (fomites).
Transmission is most often person-to-person spread from the respiratory tract. Rarely, transmission may occur from skin lesions or articles soiled with discharges from lesions of infected persons (fomites).
==Clinical Features==
==Clinical Features==
Doctor examining adult male patient
Doctor examining adult male patient
A clinician palpates for lymphadenopathy.
A clinician palpates for lymphadenopathy.
The incubation period of diphtheria is usually 2–5 days (range: 1–10 days). Diphtheria can involve almost any mucous membrane. For clinical purposes, it is convenient to classify diphtheria into type of manifestation, depending on the site of disease:
The incubation period of diphtheria is usually 2–5 days (range: 1–10 days). Diphtheria can involve almost any mucous membrane. For clinical purposes, it is convenient to classify diphtheria into type of manifestation, depending on the site of disease:
* Mild fever
* Mild fever
* Sore throat
* Sore throat
Line 51: Line 58:
* Loss of appetite
* Loss of appetite
* Hoarseness (if the larynx is involved)
* Hoarseness (if the larynx is involved)
==Respiratory symptoms==
==Respiratory symptoms==
The hallmark of respiratory diphtheria is a pseudomembrane that appears within 2–3 days of illness over the mucous lining of the tonsils, pharynx, larynx, or nares and that can extend into the trachea. Fatal airway obstruction can result if the pseudomembrane extends into the larynx or trachea or if a piece of it becomes dislodged.
The hallmark of respiratory diphtheria is a pseudomembrane that appears within 2–3 days of illness over the mucous lining of the tonsils, pharynx, larynx, or nares and that can extend into the trachea. Fatal airway obstruction can result if the pseudomembrane extends into the larynx or trachea or if a piece of it becomes dislodged.
==Cutaneous diphtheria==
==Cutaneous diphtheria==
Cutaneous diphtheria may present as a scaling rash or as ulcers with clearly demarcated edges and membrane, but any chronic skin lesion may harbor C. diphtheriae along with other organisms. The systemic complications from cutaneous diphtheria with toxigenic strains appear to be less than from other sites.
Cutaneous diphtheria may present as a scaling rash or as ulcers with clearly demarcated edges and membrane, but any chronic skin lesion may harbor C. diphtheriae along with other organisms. The systemic complications from cutaneous diphtheria with toxigenic strains appear to be less than from other sites.
==Diagnosis==
==Diagnosis==
* Confirmatory testing ensures appropriate public health action
* Confirmatory testing ensures appropriate public health action
* When C. diphtheriae is identified, it is critical that state and local public health laboratories submit specimens or isolates to CDC for confirmatory testing so that appropriate public health action can be taken.
* When C. diphtheriae is identified, it is critical that state and local public health laboratories submit specimens or isolates to CDC for confirmatory testing so that appropriate public health action can be taken.
[[File:Corynebacterium diphtheriae albert stain.jpg|alt=Corynebacterium diphtheriae albert stain|thumb|Corynebacterium diphtheriae albert stain]]
[[File:Corynebacterium diphtheriae albert stain.jpg|alt=Corynebacterium diphtheriae albert stain|left|thumb|Corynebacterium diphtheriae albert stain]]
* Diagnostic Testing and Differential Diagnoses
* Diagnostic Testing and Differential Diagnoses
* Diagnosis of diphtheria is confirmed by isolating C. diphtheriae and testing the isolate for toxin production by the Elek test, an in vitro immunoprecipitation (immunodiffusion) assay.  
* Diagnosis of diphtheria is confirmed by isolating C. diphtheriae and testing the isolate for toxin production by the Elek test, an in vitro immunoprecipitation (immunodiffusion) assay.  
Other tests, such as polymerase chain reaction (PCR) and matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF), may identify C. diphtheriae.  
Other tests, such as polymerase chain reaction (PCR) and matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF), may identify C. diphtheriae.  
However, when used alone, these tests do not confirm toxin production and are considered supplemental.
However, when used alone, these tests do not confirm toxin production and are considered supplemental.
* Specimens for culture should be obtained from the nares and oropharynx, or any mucosal or cutaneous lesion.  
* Specimens for culture should be obtained from the nares and oropharynx, or any mucosal or cutaneous lesion.  
If possible, material should be obtained from beneath the membrane (if present) or a portion of the membrane itself. Specimens are more likely to be culture-positive if obtained before the patient receives antibiotic treatment.
If possible, material should be obtained from beneath the membrane (if present) or a portion of the membrane itself. Specimens are more likely to be culture-positive if obtained before the patient receives antibiotic treatment.
[[File:Corynebacterium diphtheriae.svg|alt= Corynebacterium diphtheriae|thumb|Corynebacterium diphtheriae]]
[[File:Corynebacterium diphtheriae.svg|alt= Corynebacterium diphtheriae|left|thumb|Corynebacterium diphtheriae]]
* Respiratory diphtheria is uncommon in the United States. Infection with other pathogens could result in a similar clinical presentation as diphtheria; testing for other pathogens should be considered.  
* Respiratory diphtheria is uncommon in the United States. Infection with other pathogens could result in a similar clinical presentation as diphtheria; testing for other pathogens should be considered.  
Pathogens include group A beta-hemolytic Streptococcus, Staphylococcus aureus, Candida albicans, and viruses such as Epstein-Barr, cytomegalovirus, adenovirus, and herpes.
Pathogens include group A beta-hemolytic Streptococcus, Staphylococcus aureus, Candida albicans, and viruses such as Epstein-Barr, cytomegalovirus, adenovirus, and herpes.
[[File:Diphtheria toxin.png|alt=Diphtheria toxin|thumb|Diphtheria toxin]]
[[File:Diphtheria toxin.png|alt=Diphtheria toxin|left|thumb|Diphtheria toxin]]
==Medical Management==
==Medical Management==
* Diagnosis of respiratory diphtheria is usually made on the basis of clinical presentation since it is imperative to begin presumptive therapy quickly. After making the provisional clinical diagnosis, obtain appropriate clinical specimens, and start antitoxin and antibiotic treatment. Respiratory support and airway maintenance may be needed.
* Diagnosis of respiratory diphtheria is usually made on the basis of clinical presentation since it is imperative to begin presumptive therapy quickly. After making the provisional clinical diagnosis, obtain appropriate clinical specimens, and start antitoxin and antibiotic treatment. Respiratory support and airway maintenance may be needed.
Line 78: Line 81:
* Treatment of cutaneous diphtheria with antibiotics is usually sufficient, and antitoxin is typically not needed.
* Treatment of cutaneous diphtheria with antibiotics is usually sufficient, and antitoxin is typically not needed.
* Diphtheria disease might not confer immunity. Persons recovering from diphtheria should begin or complete active immunization with diphtheria toxoid during convalescence if not fully up to date with vaccination.
* Diphtheria disease might not confer immunity. Persons recovering from diphtheria should begin or complete active immunization with diphtheria toxoid during convalescence if not fully up to date with vaccination.
===Antibiotics===
===Antibiotics===
The recommended antibiotics for respiratory or cutaneous diphtheria is either erythromycin or penicillin.
The recommended antibiotics for respiratory or cutaneous diphtheria is either erythromycin or penicillin.
===Complications===
===Complications===
* Most complications of respiratory diphtheria, including death, are attributable to effects of the toxin. The most frequent complications of respiratory diphtheria are myocarditis and neuritis. Other complications include otitis media and respiratory insufficiency due to airway obstruction, especially in infants.
* Most complications of respiratory diphtheria, including death, are attributable to effects of the toxin. The most frequent complications of respiratory diphtheria are myocarditis and neuritis. Other complications include otitis media and respiratory insufficiency due to airway obstruction, especially in infants.
* The overall case-fatality rate for diphtheria is 5%–10%, with higher death rates (up to 20%) among persons younger than 5 and older than 40 years of age.
* The overall case-fatality rate for diphtheria is 5%–10%, with higher death rates (up to 20%) among persons younger than 5 and older than 40 years of age.
* Cutaneous diphtheria infection rarely results in severe disease.
* Cutaneous diphtheria infection rarely results in severe disease.
==Cause==
==Cause==
* Diphtheria is a serious infection caused by strains of bacteria called Corynebacterium diphtheriae that make a toxin (poison). It is the toxin that can cause people to get very sick.
* Diphtheria is a serious infection caused by strains of bacteria called Corynebacterium diphtheriae that make a toxin (poison). It is the toxin that can cause people to get very sick.
* Diphtheria bacteria spread from person to person, usually through respiratory droplets, like from coughing or sneezing.  People can also get sick from touching infected open sores or ulcers.
* Diphtheria bacteria spread from person to person, usually through respiratory droplets, like from coughing or sneezing.  People can also get sick from touching infected open sores or ulcers.
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==Complications==
==Complications==
human heart model
human heart model
Respiratory diphtheria can damage the heart muscle.
Respiratory diphtheria can damage the heart muscle.
Complications from respiratory diphtheria (when the bacteria infect parts of the body involved in breathing) may include:
Complications from respiratory diphtheria (when the bacteria infect parts of the body involved in breathing) may include:
* Airway blockage
* Airway blockage
* Damage to the heart muscle (myocarditis)
* Damage to the heart muscle (myocarditis)
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* Kidney failure
* Kidney failure
* For some people, respiratory diphtheria can lead to death. Even with treatment, about 1 in 10 patients with respiratory diphtheria die. Without treatment, up to half of patients can die from the disease.
* For some people, respiratory diphtheria can lead to death. Even with treatment, about 1 in 10 patients with respiratory diphtheria die. Without treatment, up to half of patients can die from the disease.
==Vaccination==
==Vaccination==
* Keeping up to date with recommended vaccines is the best way to prevent diphtheria.
* Keeping up to date with recommended vaccines is the best way to prevent diphtheria.
* In the United States, there are four vaccines used to prevent diphtheria: DTaP, Tdap, DT, and Td. Each of these vaccines prevents diphtheria and tetanus; DTaP and Tdap also help prevent pertussis (whooping cough).
* In the United States, there are four vaccines used to prevent diphtheria: DTaP, Tdap, DT, and Td. Each of these vaccines prevents diphtheria and tetanus; DTaP and Tdap also help prevent pertussis (whooping cough).
==DAT==
==DAT==
* [[The Food and Drug Administration]] has not licensed diphtheria antitoxin (DAT) for use in the United States.  
* [[The Food and Drug Administration]] has not licensed diphtheria antitoxin (DAT) for use in the United States.  
* However, [[CDC]] is authorized to distribute DAT to treating clinicians as an investigational new drug (IND).
* However, [[CDC]] is authorized to distribute DAT to treating clinicians as an investigational new drug (IND).
==Who Should Receive DAT==
==Who Should Receive DAT==
* Patients who have suspected or confirmed respiratory diphtheria, according to the Council of State and Territorial Epidemiologists case definition, are eligible to receive DAT.  
* Patients who have suspected or confirmed respiratory diphtheria, according to the Council of State and Territorial Epidemiologists case definition, are eligible to receive DAT.  
* DAT may also be used in cases of respiratory diphtheria-like illness caused by laboratory-confirmed toxigenic C. ulcerans.  
* DAT may also be used in cases of respiratory diphtheria-like illness caused by laboratory-confirmed toxigenic C. ulcerans.  
* A patient’s eligibility for treatment will be determined through discussion between the CDC diphtheria duty officer and the treating clinician.
* A patient’s eligibility for treatment will be determined through discussion between the CDC diphtheria duty officer and the treating clinician.
 
== External links ==
== External links ==
* [https://www.cdc.gov/diphtheria/index.html CD page]
* [https://www.cdc.gov/diphtheria/index.html CD page]
{{Gram-positive actinobacteria diseases}}
{{Gram-positive actinobacteria diseases}}
{{Authority control}}
{{Authority control}}

Latest revision as of 18:43, 5 April 2025

Editor-In-Chief: Prab R Tumpati, MD
Obesity, Sleep & Internal medicine
Founder, WikiMD Wellnesspedia &
W8MD medical weight loss NYC and sleep center NYC

Diphtheria
Dirty white pseudomembrane classically seen in diphtheria
Synonyms N/A
Pronounce N/A
Specialty N/A
Symptoms Sore throat, fever, swollen lymph nodes, weakness
Complications Myocarditis, peripheral neuropathy, kidney problems
Onset 2–5 days after exposure
Duration Variable
Types N/A
Causes Corynebacterium diphtheriae
Risks Unvaccinated, crowded living conditions
Diagnosis Throat culture, PCR test
Differential diagnosis N/A
Prevention Diphtheria vaccine
Treatment Diphtheria antitoxin, antibiotics
Medication Erythromycin, penicillin
Prognosis 5–10% mortality rate
Frequency Rare in developed countries
Deaths 2,100 (2015)


Diphtheria is a bacterial infection that causes a fever, headache, sore throat, and possibly death.

Corynebacterium diphtheriae Gram stain
Corynebacterium diphtheriae Gram stain

Epidemiology[edit]

  • Diphtheria is an acute, bacterial disease caused by toxin-producing strains of Corynebacterium diphtheriae.
  • Infection can result in respiratory or cutaneous disease.
  • Two other Corynebacterium species (C. ulcerans and C. pseudotuberculosis) may produce diphtheria toxin; both species are zoonotic.
  • Toxin-producing C. ulcerans may cause classic respiratory diphtheria-like illness in humans, but person-to-person spread has not been documented.
  • Non-toxin-producing strains of C. diphtheriae can also cause disease.
  • It is generally less severe, potentially causing a mild sore throat and, rarely, a membranous pharyngitis.
  • Invasive disease, including bacteremia and endocarditis, has been reported for non-toxin-producing strains of C. diphtheriae.
  • Vaccination is highly protective against disease caused by toxin-producing strains, but does not prevent carriage of C. diphtheriae, regardless of toxin production status.
Throat of adult and of a child infected with diphtheria
Throat of adult and of a child infected with diphtheria

Clinical Resource[edit]

Key questions to consider when assessing suspected respiratory diphtheria cases pdf icon[1 page]

Diphtheria is Deadly Art
Diphtheria is Deadly Art

Corynebacterium diphtheriae[edit]

C. diphtheriae is an aerobic gram-positive bacillus. Toxin production (toxigenicity) occurs only when the bacillus is itself infected (lysogenized) by a specific virus (bacteriophage) carrying the genetic information for the toxin (tox gene).

Transmission[edit]

Transmission is most often person-to-person spread from the respiratory tract. Rarely, transmission may occur from skin lesions or articles soiled with discharges from lesions of infected persons (fomites).

Clinical Features[edit]

Doctor examining adult male patient A clinician palpates for lymphadenopathy. The incubation period of diphtheria is usually 2–5 days (range: 1–10 days). Diphtheria can involve almost any mucous membrane. For clinical purposes, it is convenient to classify diphtheria into type of manifestation, depending on the site of disease:

  • Mild fever
  • Sore throat
  • Difficulty swallowing
  • Malaise
  • Loss of appetite
  • Hoarseness (if the larynx is involved)

Respiratory symptoms[edit]

The hallmark of respiratory diphtheria is a pseudomembrane that appears within 2–3 days of illness over the mucous lining of the tonsils, pharynx, larynx, or nares and that can extend into the trachea. Fatal airway obstruction can result if the pseudomembrane extends into the larynx or trachea or if a piece of it becomes dislodged.

Cutaneous diphtheria[edit]

Cutaneous diphtheria may present as a scaling rash or as ulcers with clearly demarcated edges and membrane, but any chronic skin lesion may harbor C. diphtheriae along with other organisms. The systemic complications from cutaneous diphtheria with toxigenic strains appear to be less than from other sites.

Diagnosis[edit]

  • Confirmatory testing ensures appropriate public health action
  • When C. diphtheriae is identified, it is critical that state and local public health laboratories submit specimens or isolates to CDC for confirmatory testing so that appropriate public health action can be taken.
Corynebacterium diphtheriae albert stain
Corynebacterium diphtheriae albert stain
  • Diagnostic Testing and Differential Diagnoses
  • Diagnosis of diphtheria is confirmed by isolating C. diphtheriae and testing the isolate for toxin production by the Elek test, an in vitro immunoprecipitation (immunodiffusion) assay.

Other tests, such as polymerase chain reaction (PCR) and matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF), may identify C. diphtheriae. However, when used alone, these tests do not confirm toxin production and are considered supplemental.

  • Specimens for culture should be obtained from the nares and oropharynx, or any mucosal or cutaneous lesion.

If possible, material should be obtained from beneath the membrane (if present) or a portion of the membrane itself. Specimens are more likely to be culture-positive if obtained before the patient receives antibiotic treatment.

Corynebacterium diphtheriae
Corynebacterium diphtheriae
  • Respiratory diphtheria is uncommon in the United States. Infection with other pathogens could result in a similar clinical presentation as diphtheria; testing for other pathogens should be considered.

Pathogens include group A beta-hemolytic Streptococcus, Staphylococcus aureus, Candida albicans, and viruses such as Epstein-Barr, cytomegalovirus, adenovirus, and herpes.

Diphtheria toxin
Diphtheria toxin

Medical Management[edit]

  • Diagnosis of respiratory diphtheria is usually made on the basis of clinical presentation since it is imperative to begin presumptive therapy quickly. After making the provisional clinical diagnosis, obtain appropriate clinical specimens, and start antitoxin and antibiotic treatment. Respiratory support and airway maintenance may be needed.
  • Even though disease is usually not contagious 48 hours after antibiotic treatment begins, maintain droplet precautions until the diphtheria patient has completed the antibiotic course and is culture-negative. Document elimination of the organism by obtaining two consecutive negative cultures 24 hours apart, once antibiotic therapy is completed.
  • Treatment of cutaneous diphtheria with antibiotics is usually sufficient, and antitoxin is typically not needed.
  • Diphtheria disease might not confer immunity. Persons recovering from diphtheria should begin or complete active immunization with diphtheria toxoid during convalescence if not fully up to date with vaccination.

Antibiotics[edit]

The recommended antibiotics for respiratory or cutaneous diphtheria is either erythromycin or penicillin.

Complications[edit]

  • Most complications of respiratory diphtheria, including death, are attributable to effects of the toxin. The most frequent complications of respiratory diphtheria are myocarditis and neuritis. Other complications include otitis media and respiratory insufficiency due to airway obstruction, especially in infants.
  • The overall case-fatality rate for diphtheria is 5%–10%, with higher death rates (up to 20%) among persons younger than 5 and older than 40 years of age.
  • Cutaneous diphtheria infection rarely results in severe disease.

Cause[edit]

  • Diphtheria is a serious infection caused by strains of bacteria called Corynebacterium diphtheriae that make a toxin (poison). It is the toxin that can cause people to get very sick.
  • Diphtheria bacteria spread from person to person, usually through respiratory droplets, like from coughing or sneezing. People can also get sick from touching infected open sores or ulcers.

Complications[edit]

human heart model Respiratory diphtheria can damage the heart muscle. Complications from respiratory diphtheria (when the bacteria infect parts of the body involved in breathing) may include:

  • Airway blockage
  • Damage to the heart muscle (myocarditis)
  • Nerve damage (polyneuropathy)
  • Loss of the ability to move (paralysis)
  • Kidney failure
  • For some people, respiratory diphtheria can lead to death. Even with treatment, about 1 in 10 patients with respiratory diphtheria die. Without treatment, up to half of patients can die from the disease.

Vaccination[edit]

  • Keeping up to date with recommended vaccines is the best way to prevent diphtheria.
  • In the United States, there are four vaccines used to prevent diphtheria: DTaP, Tdap, DT, and Td. Each of these vaccines prevents diphtheria and tetanus; DTaP and Tdap also help prevent pertussis (whooping cough).

DAT[edit]

  • The Food and Drug Administration has not licensed diphtheria antitoxin (DAT) for use in the United States.
  • However, CDC is authorized to distribute DAT to treating clinicians as an investigational new drug (IND).

Who Should Receive DAT[edit]

  • Patients who have suspected or confirmed respiratory diphtheria, according to the Council of State and Territorial Epidemiologists case definition, are eligible to receive DAT.
  • DAT may also be used in cases of respiratory diphtheria-like illness caused by laboratory-confirmed toxigenic C. ulcerans.
  • A patient‚Äôs eligibility for treatment will be determined through discussion between the CDC diphtheria duty officer and the treating clinician.

External links[edit]



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