Diphtheria

Organism

C. diphtheriae. Pleomorphic Gram+ bacillus. “CHINESE-LETTER”/cuneiform pattern (snapping division, see Bacterial Morphology topic). Volutin/metachromatic granules (Albert’s/Neisser’s stain, beaded polar-body appearance).

Toxin/Lysogeny

Diphtheria toxin: AB exotoxin, ADP-ribosylates + inactivates EF-2 (elongation factor-2, translation machinery) → blocks protein synthesis in essentially ANY cell type → explains heart/nerve/kidney damage despite infection confined to URT.

KEY: ONLY LYSOGENIZED strains (phage carrying tox gene) produce toxin (see Bacteriophage + Bacterial Genetics topics). Non-lysogenized strain = harmless (mild local infection only). Toxigenicity = PHAGE property, not bacterium’s own — curing prophage cures toxin production.

Pathogenesis

Respiratory droplets or skin contact (cutaneous diphtheria, milder, tropical). Organism stays LOCALLY CONFINED to URT mucosa — NEVER invasive/bacteremic. Disease = LOCAL tissue destruction + DISTANT toxin-mediated effects from single local source.

Local: toxin-induced necrosis + fibrin exudate → PSEUDOMEMBRANE (tough, adherent, grey-white, over tonsils/pharynx). BLEEDS ON FORCIBLE REMOVAL (unlike ordinary exudate) — clinically useful bedside distinguisher.

Clinical Manifestations

Respiratory diphtheria: sore throat, low fever, pseudomembrane → can extend larynx/trachea → MECHANICAL AIRWAY OBSTRUCTION (immediate emergency, separate from toxin effects). Severe: “BULL NECK” (neck swelling + LAD).

Systemic complications (absorbed toxin):

• Myocarditis: LEADING mortality cause, 1-2wk into illness, arrhythmia+HF
• Peripheral/cranial neuropathy: DELAYED, BIPHASIC — early palatal/pharyngeal weakness (swallowing) → weeks later generalized peripheral neuropathy (limb strength) Both from EF-2 toxicity reaching high-turnover/metabolically demanding tissue via blood from pharyngeal source.

Laboratory Diagnosis

Direct smear (beneath pseudomembrane, Albert’s/Neisser’s stain): beaded Chinese-letter bacilli — rapid presumptive. Culture: Löffler’s serum slope (selective/favors growth) or Tellurite agar (selective, black/grey colonies from tellurite reduction).

CRITICAL: isolating organism ≠ confirms diphtheria (non-toxigenic strains exist). TOXIGENICITY TESTING essential:

• Elek immunodiffusion test — precipitin line where toxin meets antitoxin (classic)
• PCR (tox gene) — increasingly used

Treatment

Diphtheria ANTITOXIN (equine): CORNERSTONE, give ASAP on CLINICAL SUSPICION ALONE, don’t wait for lab confirmation (same urgency principle as Botulism) — neutralizes only FREE circulating toxin, not already-bound toxin, delay = irreversible worse outcome.

Antibiotics (penicillin/erythromycin): alongside antitoxin, eliminate organism/halt further toxin production. ANTIBIOTICS ALONE NEVER SUFFICIENT — don’t address already-circulating toxin. Antitoxin = the life-saving intervention.

Prevention

DPT/DTaP vaccine (DIPHTHERIA TOXOID — chemically inactivated toxin, see Vaccines topic). Highly effective, made diphtheria rare with good coverage. Protects against TOXIN effects, NOT colonization/carriage — vaccinated person can still carry/transmit while clinically protected. Close contacts: prophylactic antibiotics + vaccination status review/booster.

The Organism

Corynebacterium diphtheriae is a pleomorphic, Gram-positive bacillus, characteristically arranged at angles to each other in a “Chinese-letter” or “cuneiform” pattern on Gram stain (from a snapping, incomplete-separation cell division pattern) — a distinctive morphological clue covered in more depth under Bacterial Cell Structure and Morphology, along with its volutin (metachromatic) granules, visualized with Albert’s or Neisser’s stain as the classic diagnostic feature giving the organism its beaded, polar-body appearance.

Toxin and the Central Role of Lysogeny

Diphtheria’s entire pathogenic significance rests on a single virulence factor: diphtheria toxin, an AB exotoxin that inhibits host protein synthesis by ADP-ribosylating and inactivating elongation factor-2 (EF-2), a component of the translation machinery essential in virtually every human cell type — this broad cellular target is exactly why diphtheria toxin can damage the heart, nerves, and kidneys as readily as the respiratory tract, despite the infection itself being confined to the upper respiratory mucosa. Genuinely important, and covered in more depth under both Bacteriophage and Bacterial Genetics: only strains lysogenized by a specific bacteriophage carrying the tox gene produce toxin at all — a non-lysogenized C. diphtheriae strain is essentially harmless, causing at most a mild local infection, which means toxigenicity is a property of the phage, not the bacterium itself, and a strain can be experimentally “cured” of toxin production simply by curing it of the prophage.

Pathogenesis

Transmission is by respiratory droplets or direct contact with skin lesions in cutaneous diphtheria (a milder, less toxin-driven variant more common in tropical settings). The organism remains locally confined to the upper respiratory mucosa — it is never invasive or bacteraemic in the way many other respiratory pathogens are — and disease results entirely from the local tissue-destructive and distant toxin-mediated effects of the toxin produced at that single local site. Locally, toxin-induced epithelial necrosis, combined with a fibrin-rich inflammatory exudate, forms the disease’s hallmark pseudomembrane — a tough, adherent, grey-white membrane over the tonsils/pharynx that, genuinely importantly, bleeds when forcibly removed (unlike ordinary exudate, which can be wiped away without bleeding) — a real, clinically useful bedside distinguishing feature from other causes of pharyngeal exudate.

Clinical Manifestations

Respiratory (pharyngeal/tonsillar) diphtheria presents with sore throat, low-grade fever, and the characteristic adherent pseudomembrane, which can extend to involve the larynx and trachea, risking mechanical airway obstruction — a genuine, immediate emergency distinct from anything toxin-related, since a large, sloughing pseudomembrane can physically occlude the airway. Extensive neck swelling with lymphadenopathy can produce the classically described “bull neck” appearance in severe disease. Beyond the local disease, absorbed toxin causes the feared systemic complications: myocarditis (the leading cause of diphtheria mortality, typically emerging 1–2 weeks into illness, with arrhythmia and heart failure) and peripheral/cranial neuropathy (classically a delayed, sometimes biphasic pattern — early palatal/pharyngeal weakness affecting swallowing, followed weeks later by a more generalized peripheral neuropathy affecting limb strength) — both complications reflecting the toxin’s broad EF-2-mediated cellular toxicity reaching susceptible, high-turnover or metabolically demanding tissue (cardiac muscle, myelinated peripheral nerve) via the bloodstream from the local pharyngeal source.

Laboratory Diagnosis

Direct smear from beneath the pseudomembrane, stained with Albert’s or Neisser’s stain, shows the characteristic beaded, Chinese-letter-pattern bacilli — a rapid, presumptive bedside test. Culture on Löffler’s serum slope (a selective, growth-favouring medium for this organism) or tellurite agar (selective, with C. diphtheriae reducing tellurite to produce characteristic black/grey colonies) confirms the organism’s identity. Critically, isolating the organism alone does not confirm diphtheria disease, since — as established above — non-toxigenic strains exist and are not clinically significant; toxigenicity testing is therefore an essential additional step, performed classically by the Elek immunodiffusion test (a gel-diffusion assay demonstrating a precipitin line where secreted toxin meets antitoxin diffusing from an antitoxin-impregnated paper strip) or, increasingly, by PCR detecting the tox gene directly.

Treatment

Diphtheria antitoxin (equine-derived) is the cornerstone of treatment and must be given as early as possible, based on clinical suspicion alone, without waiting for laboratory confirmation — mirroring the same “don’t wait for the lab” urgency principle covered under Botulism, and for the same underlying reason: antitoxin neutralizes only free, circulating toxin, not toxin already bound to and acting within host cells, so delay directly and irreversibly worsens outcome. Antibiotics (penicillin or erythromycin) are given alongside antitoxin to eliminate the organism and halt further toxin production, but antibiotics alone are never sufficient treatment — they address the source but do nothing for toxin already released and circulating, which is exactly why antitoxin, not antibiotics, is the genuinely life-saving intervention here.

Prevention

DPT/DTaP vaccination (using diphtheria toxoid — chemically inactivated toxin retaining immunogenicity but not toxicity, the same toxoid principle covered under Vaccines and Immunoprophylaxis) is highly effective and has made diphtheria rare in populations with good vaccine coverage, though it protects against the toxin’s effects rather than preventing colonization/carriage itself, meaning a vaccinated person can still carry and transmit the organism even while being clinically protected from disease themselves. Close contacts of a case need prophylactic antibiotics and vaccination-status review/booster as indicated.

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