Diphtheria is caused by Corynebacterium diphtheriae, a Gram-positive, club-shaped bacillus.
Hippocrates provided the first clinical description of diphtheria in the 4th century B.C. There are also references to the disease in ancient Syria and Egypt.
In the 17th century, murderous epidemics of diphtheria swept Europe; in Spain the disease became known as "El garatillo" (the strangler"), in Italy and Sicily as "the gullet disease".
In the 18th century, the disease reached the American colonies where it reached epidemic proportions about 1735. Often, whole families died of the disease in a few weeks.
The bacterium that caused diphtheria was first described by Klebs in 1883, and was cultivated by Loeffler in 1884, who applied Koch's postulates and properly identified Corynebacterium diphtheriae as the agent of the disease.
In 1884, Loeffler concluded that C. diphtheriae produced a soluble toxin, and thereby provided the first description of a bacterial exotoxin.
In 1888, Roux and Yersin demonstrated the presence of the toxin in the cell-free culture fluid of C. diphtheriae which, when injected into suitable lab animals, caused the systemic manifestation of diphtheria.
In the early 1960s, Pappenheimer and his group at Harvard conducted experiments on the mechanism of a action of the diphtheria toxin. They studied the effects of the toxin in HeLa cell cultures and in cell-free systems, and concluded that the toxin inhibited protein synthesis by blocking the transfer of amino acids from tRNA to the growing polypeptide chain on the ribosome. They found that this action of the toxin could be neutralized by prior treatment with diphtheria antitoxin.
Subsequently, the exact mechanism of action of the toxin was shown, and the toxin has become a classic model of a bacterial exotoxin.
At the turn of the century, in the United States, diphtheria was common, occurring primarily in children, and was one of the leading causes of death in infants and children. In the 1920's, when data were first gathered, in the United States there were approximately 150,000 cases and 13,000 deaths reported annually. After diphtheria immunization was introduced, the number of cases gradually fell to about 19,000 in 1945. When diphtheria immunization became widespread in the late 1940's, a more rapid decrease in the number of cases and deaths occurred.
Essentially a childhood disease, diphtheria is usually transmitted through airborne droplets and rarely via fomites. The incubation period is between 2-7 days, the illness being of insidious onset. The fever is low grade unless there is secondary infection with other bacteria resulting in a high spiking fever.
Nasal diphtheria is characterised by a nasal discharge that crusts around the nostrils.
Pharyngeal diphtheria causes significant tonsil and pharyngeal inflammation. The membrane formed is greyish yellow and is firmly adherent to the underlying tissue. This mesh of fibrin, bacteria, epithelial cells, mononuclear cells and polymorphs is called the pseudomembrane.
Laryngeal diphtheria is usually the result of extension of pharyngeal diphtheria. This results in a husky voice, a brassy cough and later dyspnoea (shortness of breath). Cyanosis due to respiratory obstruction may occur.
cutaneous diphtheria is seen in patients with burns and in individuals with poor hygiene. The ulcer is punched out with undermined edges and is covered with a greyish white adherent membrane.
Three strains of C. diphtheria are known - mitis, intermedius and gravis. These are listed in order of increasing severity of the disease caused. Humans are the only known hosts for diphtheria.
The toxin: the exotoxin affects the heart and the peripheral nervous system. It may cause myocarditis, resulting in circulatory failure if severe. Neurologically, it may cause palatal and pharyngeal paralysis, cranial nerve palsies, parasthesiae, polyneuropathy or encephalitis.
diagnosis: diagnosis is on clinical suspicion since treatment is urgent and needs to be started before the results of bacteriological studies are known.
Treatment: antibiotics (usually penicillin) should be given to eliminate the organism and therefore remove the source of toxin production. in addition, antitoxin derived from horse serum antitoxin should be given quickly to neutralize any remaining toxin in the circulation. there is a risk of anaphylaxis from the antitoxin and of serum sickness 2-3 weeks later. the risk of not giving the antitoxin (death) outweighs the risk of anaphylaxis however.
Prevention: diphtheria is preventable through childhood immunization.