Etiology
Diphtheria is predominantly caused by exotoxin-producing strains of Corynebacterium diphtheriae, which are gram-positive, nonmotile, nonspore-forming, pleomorphic bacilli. Humans are the only host and transmission occurs via exposure to bacilli-laden respiratory droplets or direct contact with infected skin lesions. Although asymptomatic carriers can transmit the disease, they cause 76% fewer cases over the course of infection than symptomatic patients.[22] There are four bacterial biotypes of C diphtheria (mitis, intermedius, gravis, and Belfanti), which are differentiated based on colony morphology, hemolysis reaction, and fermentation reaction.[27]
Rarely, diphtheria may also be caused by other zoonotic corynebacteria that produce diphtheria toxin, such as Corynebacterium ulcerans or Corynebacterium pseudotuberculosis.[1]
Only bacteria infected by a bacteriophage carrying the tox gene are capable of producing diphtheria toxin, which affects mucous membranes, myocardium, renal tubular cells, and peripheral nerve myelin.[28] Nontoxigenic strains usually lack the entire tox gene. However, occasionally bacteria carry genetic variants of the tox operon but cannot express it phenotypically. Nontoxigenic strains typically cause milder disease, though severe illness, including endocarditis, has been reported.[7][28][27]
Pathophysiology
C diphtheriae usually infects the epithelium of the skin and the mucosa of the upper respiratory tract, leading to inflammation of the tonsils, pharynx, nose, and larynx. The average incubation period is 2 to 7 days (range 1 to 10 days). Fever may be present.[28][27]
The exotoxin primarily responsible for the pathogenicity of diphtheria is composed of two chains: chain B facilitates entry into host cells, and chain A inhibits protein synthesis causing cell death.[13]
This results in an accumulation of inflammatory cells, necrotic epithelial cells, and bacterial debris in the upper respiratory tract, which coalesce to form the characteristic adherent gray pseudomembrane. Attempts to remove the pseudomembrane can provoke bleeding and expose an inflamed erythematous mucosa. Local neurologic effects of the exotoxin can cause paralysis of the palate and hypopharynx. This combination of effects can lead to airway obstruction. In addition, systemic spread of the toxin can cause injury to the kidneys, heart, and neural tissue.[13]
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