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Delia B. Benthell

and Tran Tinh Hien



Epidemiology updated.

Additions to Further reading.

Updated on 31 May 2012. The previous version of this content can be found here.
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date: 23 April 2017

Diphtheria is a potentially lethal infection caused by toxin-producing strains of Corynebacterium diphtheria, a Gram-positive bacillus. Humans are the only known reservoir, with spread via respiratory droplets or direct contact with skin lesions. Although now rare in developed countries, this vaccine-preventable disease remains an important problem in countries with poor or failing health systems, and is estimated to cause about 5000 deaths per year worldwide, most in children under 5 years of age.

Pathogenesis—diphtheria develops when toxigenic bacteria lodge in the upper airway or on the skin of a susceptible individual. An intense inflammatory reaction develops, leading to a characteristic greyish-coloured pseudomembrane that is adherent to underlying tissues. Systemic effects are caused by release of diphtheria toxin, carried by a lysogenic corynebacteriophage, a single molecule of factor A of which can kill a eukaryotic cell.

Clinical features—after an incubation period of 2 to 6 days the disease presents acutely in a number of ways, classified by the location of the pseudomembrane: (1) anterior nasal—usually relatively mild; (2) tonsillar (faucial)—the commonest form, with malaise, fever, sore throat, painful dysphagia and tender cervical lymphadenopathy; (3) tracheolaryngeal—with particular risk of airway obstruction; (4) malignant—with rapid onset, circulatory shock, cyanosis, gross cervical lymphadenopathy (‘bull neck’), and very poor prognosis; (5) cutaneous—usually mild but chronic; morphological features can be extremely variable. Later complications include (1) myocarditis—seen in 10% of cases; and (2) segmental demyelinative neuropathy—most often palatal paralysis, and more sinister paralyses of pharyngeal, laryngeal, respiratory and limb muscles.

Diagnosis—infection may be confirmed by bacterial culture, with detection of toxin production by one of several laboratory techniques, or of the toxin-producing gene by PCR.

Treatment and prognosis—aside from supportive care, this involves (1) antitoxin—20 000 to 100 000 units, depending on disease severity; preferably given within 48 h of the onset of symptoms; (2) antibiotics—benzylpenicillin (or penicillin V), or erythromycin in those allergic to penicillin; (3) maintaining the airway—life-saving procedures such as tracheostomy may be required. Recovery is usually complete if the patient survives.

Prevention—diphtheria is completely preventable by vaccination, but immunity is not life-long and may wane in adult life if booster doses are not given regularly. Similarly, infection does not necessarily confer complete protection and the disease may recur in previously infected individuals.

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