Corynebacterium diphtheriae

Corynebacterium diphtheriae is a Gram-positive, non-motile, rod-shaped bacterium that is the causative agent of diphtheria, a serious infectious disease affecting the mucous membranes of the respiratory tract, skin, and occasionally other organs. It belongs to the genus Corynebacterium, which includes a wide range of species, some of which are commensals while others are opportunistic pathogens. The pathogenicity of C. diphtheriae is primarily associated with the production of the diphtheria toxin, a potent exotoxin encoded by a lysogenic bacteriophage.

Morphology and Characteristics

• Gram Stain: Gram-positive, but may show irregular staining.
• Shape: Club-shaped bacilli (the name “coryne” derives from the Greek koryne, meaning club). They often appear in palisades or angular arrangements, described as “Chinese letter” formations.
• Motility: Non-motile and non-spore forming.
• Oxygen Requirement: Facultatively anaerobic.
• Culture: Grows well on enriched media such as Loeffler’s serum slope or blood agar. Selective media like Tinsdale agar help differentiate pathogenic strains.
• Biotypes: Four main biotypes are recognised—gravis, mitis, intermedius, and belfanti—differentiated by colony morphology and biochemical reactions.

Pathogenic Mechanism

The virulence of C. diphtheriae depends largely on its ability to produce the diphtheria toxin:

• The toxin gene (tox) is carried by a lysogenic bacteriophage (β-phage).
• The exotoxin inhibits protein synthesis by inactivating elongation factor-2 (EF-2) through ADP-ribosylation.
• This leads to cell death, tissue necrosis, and systemic toxic effects when the toxin spreads via the bloodstream.

Clinical Manifestations

Diphtheria caused by C. diphtheriae can present in different forms:

• Respiratory Diphtheria:
  • Most common and severe form.
  • Symptoms include sore throat, fever, and the characteristic thick grey pseudomembrane over the tonsils, pharynx, and larynx.
  • Complications may include airway obstruction, myocarditis, and neuropathies.
• Cutaneous Diphtheria:
  • Causes non-healing ulcers with a greyish membrane.
  • More common in tropical climates and in areas with poor hygiene.
• Systemic Complications:
  • Toxin absorption can damage the heart (causing myocarditis), nervous system (leading to paralysis), and kidneys.

Diagnosis

• Clinical Suspicion: Presence of pseudomembrane in throat is highly suggestive.
• Microscopy: Gram staining shows characteristic club-shaped bacilli. Albert stain demonstrates metachromatic granules (volutin).
• Culture: Growth on selective media such as Tinsdale agar produces black colonies due to tellurite reduction.
• Toxin Detection:
  • Elek’s immunodiffusion test identifies toxin production.
  • PCR can detect the tox gene.

Treatment

• Antitoxin Therapy: Early administration of diphtheria antitoxin neutralises circulating toxin but cannot reverse damage already caused.
• Antibiotics: Penicillin or erythromycin is used to eradicate the organism and prevent transmission.
• Supportive Care: Airway management, cardiac monitoring, and treatment of complications.

Prevention

• Vaccination: The most effective preventive measure is the diphtheria toxoid vaccine, often administered in combination as part of the DTP/DTaP (diphtheria, tetanus, pertussis) vaccine.
• Booster Doses: Required throughout life to maintain immunity.
• Public Health Measures: Isolation of cases, treatment of carriers, and contact tracing.

Historical and Epidemiological Significance

Before the introduction of widespread vaccination, diphtheria was a major cause of childhood mortality worldwide. The introduction of the diphtheria toxoid vaccine in the 1940s drastically reduced incidence in most countries. However, outbreaks have occurred in regions with low vaccination coverage, notably in the former Soviet Union in the 1990s.