A 7-year-old unvaccinated boy from rural Maharashtra presents with a 3-day history of sore throat, low-grade fever, and progressive difficulty swallowing. On examination, he has a thick, adherent, greyish-white pseudomembrane covering the soft palate and pharyngeal wall that bleeds on attempted removal. Cervical lymph nodes are enlarged and tender. A throat swab is sent for culture. Which of the following is the most likely causative organism and the mechanism by which it causes systemic toxicity?

Explanation

## Diagnosis: Diphtheria **Key Point:** Corynebacterium diphtheriae causes diphtheria, a toxin-mediated disease characterized by a pathognomonic adherent pseudomembrane and systemic complications. ### Clinical Features Pointing to C. diphtheriae | Feature | Significance | |---------|-------------| | Adherent greyish-white pseudomembrane | Hallmark of diphtheria; composed of fibrin, RBCs, WBCs, bacteria | | Bleeds on removal | Indicates deep tissue involvement and inflammation | | Cervical lymphadenopathy ("bull neck") | Classic presentation; lymph node enlargement with soft tissue edema | | Unvaccinated status | Diphtheria is vaccine-preventable (DPT/pentavalent); endemic in under-immunized populations | | Sore throat + systemic symptoms | Begins as acute pharyngitis; progresses to pseudomembrane formation | ### Pathogenesis: Diphtheria Toxin **High-Yield:** C. diphtheriae produces diphtheria toxin ONLY when lysogenized by a β-phage carrying the *tox* gene. Non-lysogenic strains are non-toxigenic. 1. **Lysogenic integration:** The *tox* gene is located on a β-phage genome 2. **Toxin production:** Only lysogenized (toxigenic) strains synthesize diphtheria toxin 3. **Mechanism of toxin:** A-B toxin that catalyzes ADP-ribosylation of elongation factor-2 (EF-2) 4. **Result:** Inhibition of protein synthesis → cell death, especially in heart (myocarditis) and nervous system (neuropathy) **Clinical Pearl:** The pseudomembrane itself is NOT the toxin — it is a local manifestation of tissue necrosis and inflammation. Systemic toxicity (cardiac arrhythmias, cranial nerve palsies, respiratory paralysis) is caused by circulating toxin absorbed from the local site. ### Diagnosis & Confirmation - **Culture:** Löffler's serum medium or tellurite agar (produces black colonies) - **Gram stain:** Gram-positive bacilli with metachromatic granules ("Chinese letter" or "cuneiform" arrangement) - **Toxin confirmation:** Elek immunodiffusion test or PCR for *tox* gene **Mnemonic:** **DIPHTHERIA = Diphtheria toxin + Lysogenic phage** — the toxin gene must be integrated into the bacterial chromosome by a phage for virulence. ### Management 1. **Antitoxin** (equine antitoxin) — neutralizes circulating toxin; must be given early (before complications) 2. **Antibiotics** (penicillin G or erythromycin) — eliminates bacteria and stops toxin production 3. **Supportive care** — airway management, cardiac monitoring (myocarditis, arrhythmias) 4. **Vaccination** — post-recovery, as infection does not guarantee immunity [cite:Textbook of Microbiology by Ananthanarayan & Paniker, Ch 20]