• 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

2. Describe the offending organism, its appearance, characteristics and their normal habitat

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.

3. What kinds of hosts are susceptible?

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

4. How do these organisms gain access to humans?

5. What are the pathogenic mechanisms of this organism that facilitate infection? 

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.

6. Where does the toxin gene reside, and how does the organism acquire it?

• 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?

8. What is the end result of this battle between organisms and humans?

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%.

9. How do you diagnose this infection?

• 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

10. What will be your therapeutic strategy?

• 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

11. How can you prevent it from spreading to others? Prevent its occurrence?

• 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 

12. What are the problems created by other species?

Corynebacterium ulcerans:

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