Makindo Medical Notes

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 diphtheriae and 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.