• Is an acute contagious illness
• Diphtheria is the result of local and systemic effects of diphtheria toxin. 
• Characterized by membrane formation in throat.
• Infection may produce disease or a carrier state
• Diphtheria used to be an illness of children

Corynebacterium diphtheriae

• Humans are the only reservoir of infection
• Aerobic, club shaped, gram-positive, nonmotile, unencapsulated, pleomorphic bacillus with terminal swellings
• When stained it is often found in clusters that form sharp angles with each other and resemble Chinese letters.

• Children not vaccinated for C. diphtheria.
• Immunocompromised 
• Poorly immunized adults

Pathogenic mechanisms 

Disease is caused by exotoxin which inhibits protein synthesis of eukaryotic cells

• The toxin contains a toxic A subunit (active toxin) and the receptor binding B subunit. 

• The B subunit (fragment) facilitates translocation of the A subunit from the phagosome to the cytosol, followed by separation, allowing full activity of the A subunit on its target protein elongation factor-2. EF-2 transfers polypeptidyl-transfer RNA from acceptor to donor sites on the ribosome of the host cell. 

• The A subunit catalyzes transfer of adenine ribose phosphate from NAD to EF-2 (ADP ribosylation), inactivating EF-2, and turning off protein synthesis, C. diphtheria toxin is able to inhibit protein synthesis of all eukaryotic cells. 

• Fragment A has the enzymatic activity

• Fragment B attaches to cellular receptors and grants fragment A entrance into the cell, where it inhibits protein synthesis.

• The exotoxin is absorbed into the blood stream and distributed, resulting in systemic complications including demyelinating neuritis and myocarditis.

• The diphtheria toxin also causes local destruction at the site of membrane formation.

Toxin gene

• Gene for the diphtheria toxin is carried in genome of a bacteriophage. 

• C. diphtheria strains must contain a bacteriophage (beta-phage), acquired by transduction from other C. diphtheria strains, in order to express the toxin.

• The phage must be Iysogenized following transduction. 

• The toxin expression (fox gene) is regulated by a chromosomally encoded repressor protein (DtxR) when iron is limited.

• We don't seem to have any protection against the toxin. Protection is ensured only by vaccination.
• Organisms are tackled by?

Incubation period is 2-5 days

Diphtheria is the result of local and systemic effects of diphtheria toxin. 

• A "membrane" forms in throat. It is a coagulum of fibrin, leukocytes, cellular debris due to local cytotoxicity by the toxin. 
  • The membrane can extend from the oropharynx to larynx and into the trachea. Sore throat, hoarseness and dysphagia follows. 
  • Respiratory diphtheria may progress rapidly. Respiratory arrest may occur from airway obstruction with tracheobronchial membrane. Cough, stridor wheezing are the result.

• Diphtheria toxin can circulate in blood and affect heart and CNS systems.

  • Myocarditis, with cardiac enlargement, circulatory collapse, heart failure, AV blocks and dysrhythmias.
  • Nervous system can also be involved including paralysis of soft palate, oculomotor dysfunction. They resolve with resolution of infection.
• Fever and chills, malaise,  cervical adenopathy, nausea and vomiting.

Mortality in untreated cases is 10-50%.

• Initial diagnosis is clinical 

• No rapid lab test

• Gram stain of throat not helpful

• Organism can be cultured to confirm diagnosis. Missed on routine cultures. Notify the lab of possible diagnosis.

• Toxin production of cultured strains can be performed by immunodiffusion.

• Serum for antibodies to diphtheria toxin

Other useful evaluations

• EKG and Cardiac enzymes to detect myocarditis

• CXR: Hyperinflation, subglottic narrowing

• Strict isolation

• C. diphtheriae antitoxin is given promptly to neutralize free toxin.  

  • Contact CDC for antitoxin and instructions on use. 

  • Do not wait for culture confirmation. 

  • Antibodies produced against the toxin in natural infection. 

  • Treat with toxin to neutralize free toxin before it binds to cells.

• The organism itself can be treated with penicillin, cephalosporins, and erythromycin.

• Notify the health department

• Clinical diphtheria does not confer immunity, hence active immunization with diphtheria toxoid should be provided during convalescence.

• Bronchodilators if needed.

• Watch for respiratory obstruction and take necessary steps.

• Watch for myocarditis and mange appropriately

• Timely vaccination 
  • Diphtheria: Immunization with toxoid elicits an antibody response that prevents diphtheria infection.
  • Vaccination with toxoid=formalin treated toxin
• Booster dose of Tetanus-Diphtheria every 10 years through adulthood
• Surveillance in communities where Diphtheria was endemic
• Close contacts 
  • Should be identified and treated with oral erythromycin for 7-10 days
  • Provide active immunization 

Other species

Corynebacterium ulcerans:

• Cutaneous Diphtheria
  • Generally caused by tox-strains.
  • Produces natural immunity
  • Can cause epidemics in poorly immunized populations.