Question
Discuss the pathogenesis and laboratory diagnosis of diphtheria
Answer
Diphtheria (caused by Corynebacterium diphtheriae)
Pathogenesis: C. diphtheriae colonizes the pharyngeal mucosa (a non-invasive organism), and if lysogenized by a bacteriophage carrying the tox gene, produces diphtheria exotoxin. Locally, the toxin causes epithelial necrosis and an intense inflammatory exudate of fibrin, dead cells, and bacteria, forming the characteristic tough, greyish-white pseudomembrane (which bleeds if forcibly removed and can extend to obstruct the airway). The toxin is absorbed systemically and, via ADP-ribosylation of elongation factor-2 (EF-2), inhibits host cell protein synthesis in distant organs, causing toxic myocarditis and peripheral/cranial neuropathy — the major life-threatening complications.
Laboratory diagnosis:
- Direct microscopy — Gram stain and Albert’s/Neisser’s stain of a throat/pseudomembrane swab, showing club-shaped, Gram-positive bacilli arranged in characteristic Chinese-letter/V, L patterns, with metachromatic (volutin) granules on Albert’s stain.
- Culture — on Loeffler’s serum slope (rapid growth, characteristic morphology) and Tellurite blood agar (selective medium, producing characteristic black/grey colonies).
- Toxigenicity testing — Elek’s gel precipitation test (in-vitro toxin-antitoxin precipitation reaction), or PCR detection of the tox gene, to confirm the isolate is toxin-producing (essential, since only toxigenic strains cause the systemic disease).