Immunisation targets the diphtheria toxin rather than the bacterium itself. The toxin is produced by a bacteriophage infecting the bacterium, rather than encoded in bacterial DNA.
About
- Caused by Corynebacterium diphtheriaeand occasionally C. ulcerans.
- Fatality rate ranges between 5% and 10%.
- The bacterium releases an exotoxin that blocks protein synthesis.
- The toxin gene is encoded by a bacteriophage (virus) infecting the bacterium.
- Mild cases may go undiagnosed.
Microbiology
- Gram-positive, club-shaped, non-motile rods.
- Organisms grow at angles, forming characteristic "Chinese letter" shapes (V, L, W shapes).
- Optimal growth occurs in oxygen at 37°C.
- Only bacteria infected with the relevant phage produce the exotoxin.
- The exotoxin has two components, A and B:
- A component: An RNA translation inhibitor, blocking protein synthesis.
- B component: Directs the toxin to target oropharynx, heart, and nerve cells.
- Exotoxin structure: 535 residues, 58 kDa, consisting of two polypeptide chains linked by a disulphide bond.
- Effects include local tissue necrosis, toxaemia, demyelinating peripheral neuritis, and myocarditis, potentially leading to cardiac failure.
Virulence
- The corynephage beta-infected bacteria produce an A-B toxin:
- A component: Acts as an ADP-ribosyl transferase, binding to eukaryotic elongation factor 2 and inhibiting protein synthesis.
- B component: Directs the toxin specifically to cells in the oropharynx, heart, and nerves.
Transmission
- Spread by direct contact.
- Inhalation of aerosolized secretions from an infected individual.
Clinical Presentation (Incubation Period: 2-4 days)
- Pharyngitis: A greyish "dirty" pseudomembrane (fibrin and dead cells) forms, often with lymphadenopathy, creating a "bull neck" appearance.
- Nasal, laryngeal, and pharyngeal mucosa are affected.
- Potential airway obstruction and stridor.
- Symptoms: sore throat, fever, malaise.
- Complications:
- Heart failure, heart block, and arrhythmias.
- Cranial nerve palsies (e.g., diplopia, dysarthria, dysphagia).
- Myocarditis leading to cardiac dysfunction, bradycardia, and chest pain.
- Laryngeal nerve palsy causing hoarseness.
Investigations
- Culture: Grows on Hoyle’s medium (blood tellurite) producing black colonies by reducing tellurite to tellurium; Tinsdale's medium with horse serum is an alternative.
- Strain Identification: Three types—gravis (most severe), intermedius, and mitis (least severe), identifiable by hemolysis patterns and colony appearance.
- Biochemical Tests: Catalase, urease, nitrate reduction, pyranzinamidase, and cystinase testing.
- Toxin Detection: Elek test with antitoxin.
- Additional Testing: Serotyping and bacteriophage typing.
- Sample Collection: Culture of laryngeal and pharyngeal swabs.
- Cardiac Monitoring: ECG for heart block and arrhythmias; echocardiogram for left ventricular function.
Diphtheria was largely eradicated in developed countries through mass vaccination programs initiated in the mid-20th century.
Management
- Supportive Care: ABCs (airway, breathing, circulation), bed rest, telemetry, and isolation.
- Diphtheria Antitoxin: Derived from hyperimmune horse serum, it neutralizes unbound toxin but may cause anaphylaxis.
- Antibiotics: Amoxicillin or erythromycin for two weeks, with prophylactic treatment for contacts.
- Airway Management: Removal of pseudomembrane via laryngoscopy or bronchoscopy if obstruction risk is high.
- Immunization of Contacts: Vaccinate or provide booster doses to close contacts; boosters are recommended every 10 years to maintain immunity.