Pathogenesis C. diphtheriae (korynee - club, refers to the shape of thebacteria; diphtheria = leather, refers to the pharyngealmembrane) infects the nose, throat, larynx and trachea orthe skin. It causes local inflammation, but its major effectsresult from the production of a protein toxin of MW 62000which inhibits ribosomal polypeptide chain production byinhibiting elongation factor 2. The toxin is elaborated onlyby C. diphtheriae strains infected by a bacteriophagecarrying the toxin production gene. Its main effects are onthe myocardium and nervous tissue.
Clinical features After an incubation period of 2-6 days there is a slow onsetof malaise and fever, sometimes with mild sore throat.Immunized subjects develop disease at the site of infectionbut no toxin-mediated effects. In the unimmunized, at anearly stage the predominant findings are profound weakness,restlessness and irritability, with fever, pallor and arapid thready pulse. The pharynx shows the characteristicmembrane which is adherent; attempts to scrape it offresult in bleeding. In laryngeal diphtheria the membraneinvolves the larynx and trachea, causing respiratoryobstruction which may require tracheostomy. The primaryinfection may also involve the nose, larynx or bronchi.ECG abnormalities suggesting myocarditis (flattening orinversion of T waves) or first-degree heart block appearafter the first week and can progress to major dysrhythmiasand circulatory collapse. Neurological complications startlater, with paralysis of the palate, followed by the ocularmuscles, then the pharynx, larynx and respiratory muscles,and lastly the limbs.
Diagnosis C. diphtheriae can be isolated from sites of infection but demonstration of toxin production takes several more days- too long to delay management decisions. Polymerase chain reaction for the tox+ gene has revolutionizedmanagement, as it can demonstrate the presence of thebacteriophage on the same day that a positive cultureis obtained.
Management and outcome Diphtheria antitoxin is administered without waiting for bacteriological confirmation in suspected cases, but it isno longer used for prophylaxis because of the danger ofhypersensitivity reactions. The treatment dose is 10000-30000 units i.m. for mild disease, increasing to as much as100000 units for severe cases of more than 3 days' duration.For doses greater than 30000 units the remainder isgiven intravenously after an interval of 0.5-2 hours. Penicillinor erythromycin will eradicate the organism from theprimary infection site but the patient must be isolated untilthe risk of cross-infection has been removed. Intensivenursing is required to protect the airway, and tracheostomymay be needed. ECG monitoring is used to detect dysrhythmias,and physiotherapy to preserve the range ofmovement in paralysed limbs. Contacts must be traced,treated if infected, and immunized. If the patient survivesthe acute illness, recovery from complications such asparalysis is complete.
