Chapter 138

Diphtheria is a nasopharyngeal and skin infection caused by Corynebacterium diphtheriae. Toxigenic strains of C. diphtheriae produce a protein toxin that causes systemic toxicity, myocarditis, and polyneuropathy. The toxin is associated with the formation of pseudomembranes in the pharynx during respiratory diphtheria. While toxigenic strains most frequently cause pharyngeal diphtheria, nontoxigenic strains commonly cause cutaneous disease.

In the United States and Europe, diphtheria has been controlled in recent years with effective vaccination, although sporadic outbreaks have occurred. Diphtheria is still common in the Caribbean, Latin America, and the Indian subcontinent, where mass immunization programs are not enforced. Large epidemics have occurred in the independent states formerly encompassed by the Soviet Union. Additional outbreaks have been reported in Algeria, China, and Ecuador.

### Etiology

C. diphtheriae is a gram-positive, unencapsulated, nonmotile, nonsporulating bacillus. C. diphtheriae organisms have a characteristic club-shaped bacillary appearance and typically form clusters of parallel rays (palisades) that are referred to as Chinese characters. In the specific laboratory media recommended for the cultivation of C. diphtheriae, tellurite, colistin, or nalidixic acid allows selective isolation of the organism in the presence of other autochthonous pharyngeal microbes. Human isolates of C. diphtheriae may display nontoxigenic (tox) or toxigenic (tox+) phenotypes. Corynebacteriophage beta carries the structural gene (tox) encoding diphtheria toxin, and a family of closely related corynebacteriophages are responsible for toxigenic conversion of toxC. diphtheriae to the tox+ phenotype. Moreover, lysogenic conversion from a nontoxigenic to a toxigenic phenotype has been shown to occur in situ. Growth of toxigenic strains of C. diphtheriae under iron-limiting conditions leads to the optimal expression of diphtheria toxin, and these conditions are believed to trigger tox expression and subsequent pathogenesis during human infection.

### Epidemiology

C. diphtheriae is transmitted via the aerosol route, primarily during close contact. There are no significant reservoirs other than humans. The incubation period for respiratory diphtheria is 2–5 days; however, disease can develop as long as 10 days after exposure. Before the vaccine era, most individuals over the age of 10 were immune to C. diphtheriae; infants were protected by maternal IgG antibodies but became susceptible after ∼6 months of age. Thus, the disease was seen primarily in children and nonimmune young adults. In temperate regions, respiratory diphtheria occurs year-round but is most common during winter months.

The development of diphtheria antitoxin and diphtheria toxoid vaccine led to the near-elimination of diphtheria in Western countries. The annual peak incidence rate was 191 cases per 100,000 population in the United States in 1921; in contrast, since 1980, the annual figure for the United States as a whole has been <5 cases. Nevertheless, pockets of colonization have persisted in North America, particularly in South Dakota, Ontario, and Washington state. Immunity induced by vaccination during childhood gradually decreases in adulthood. An estimated 30% of men 60–69 years old have antitoxin titers below the protective level. In addition to older age and lack of vaccination, ...

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