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diphtheria

Tuesday 17 March 2009

Diphtheria is caused by a slender Gram-positive rod with clubbed ends, Corynebacterium diphtheriae, which is passed from person to person through aerosols or skin shedding.

C. diphtheriae causes a range of illnesses: asymptomatic carriage; skin lesions in neglected wounds of combat troops in the tropics; and a life-threatening syndrome that includes formation of a tough pharyngeal membrane and toxin-mediated damage to the heart, nerves, and other organs.

C. diphtheriae has only one toxin, which is a phage-encoded A-B toxin that blocks host cell protein synthesis.

In the cytosol of the cell, the A fragment catalyzes the covalent transfer of adenosine diphosphate (ADP)-ribose to elongation factor-2 (EF-2) which is involved in protein synthesis. A single molecule of diphtheria toxin can kill a cell by ADP-ribosylating, and thus inactivating, more than a million EF-2 molecules.

Immunization with diphtheria toxoid (formalin-fixed toxin) does not prevent colonization with C. diphtheriae but protects immunized people from the lethal effects of the toxin.

Recent large outbreaks of diphtheria in the former Soviet Union resulted from decreased vaccination rates, socioeconomic instability, and a deteriorating health infrastructure.

Morphology

Inhaled C. diphtheriae proliferate at the site of attachment on the mucosa of the nasopharynx, oropharynx, larynx, or trachea but also form satellite lesions in the esophagus or lower airways.

Release of exotoxin causes necrosis of the epithe-lium, accompanied by an outpouring of a dense fibrinosuppurative exudate. The coagulation of this exudate on the ulcerated necrotic surface creates a tough, dirty gray to black, superficial membrane.

Neutrophilic infiltration in the underlying tissues is intense and is accompanied by marked vascular congestion, interstitial edema, and fibrin exudation.

When the membrane sloughs off its inflamed and vascularized bed, bleeding and asphyxiation may occur. With control of the infection, the membrane is coughed up or removed by enzymatic digestion, and the inflammatory reaction subsides.

Although the bacterial invasion remains localized, generalized hyperplasia of the spleen and lymph nodes ensues owing to the absorption of soluble exotoxin into the blood.

The exotoxin may cause fatty myocardial change with isolated myofiber necrosis, polyneuritis with degeneration of the myelin sheaths and axis cylinders, and (less commonly) fatty change and focal necroses of parenchymal cells in the liver, kidneys, and adrenals.