Diphtheria Corynebacterium Diphtheriae Essay Research Paper Diphtheria

Diphtheria (Corynebacterium Diphtheriae) Essay, Research Paper

Diphtheria (Corynebacterium diphtheriae)

Corynebacteria are Gram-positive, aerobic, nonmotile, rod-shaped bacteria

related to the Actinomycetes. They do not form spores or branch as do the

actinomycetes, but they have the characteristic of forming irregular shaped,

club-shaped or V-shaped arrangements in normal growth. They undergo snapping

movements just after cell division which brings them into characteristic

arrangements resembling Chinese letters.

The genus Corynebacterium consists of a diverse group of bacteria including

animal and plant pathogens, as well as saprophytes. Some corynebacteria are part

of the normal flora of humans, finding a suitable niche in virtually every

anatomic site. The best known and most widely studied species is Corynebacterium

diphtheriae, the causal agent of the disease diphtheria.

History and Background

No bacterial disease of humans has been as successfully studied as diphtheria.

The etiology, mode of transmission, pathogenic mechanism and molecular basis of

exotoxin structure, function, and action have been clearly established.

Consequently, highly effective methods of treatment and prevention of diphtheria

have been developed.

The study of Corynebacterium diphtheriae traces closely the development of

medical microbiology, immunology and molecular biology. Many contributions to

these fields, as well as to our understanding of host-bacterial interactions,

have been made studying diphtheria and the diphtheria toxin.

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

“El garatillo” (the strangler”), in Italy and Sicily, “the gullet disease”.

In the 18th century, the disease reached the American colonies and reached

epidemic proportions in 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.

Two years later, von Behring and Kitasato succeeded in immunizing guinea pigs

with a heat-attenuated form of the toxin and demonstrated that the sera of

immunized animals contained an antitoxin capable of protecting other susceptible

animals against the disease. This modified toxin was suitable for immunizing

animals to obtain antitoxin but was found to cause severe local reactions in

humans and could not be used as a vaccine.

In 1909, Theobald Smith, in the U.S., demonstrated that diphtheria toxin

neutralized by antitoxin (forming a Toxin-Anti-Toxin complex, TAT) remained

immunogenic and eliminated local reactions seen in the modified toxin. For some

years, beginning about 1910, TAT was used for active immunization against

diphtheria. TAT had two undesirable characteristics as a vaccine. First, the

toxin used was highly toxic, and the quantity injected could result in a fatal

toxemia unless the toxin was fully neutralized by antitoxin. Second, the

antitoxin mixture was horse serum, the components of which tended to be

allergenic and to sensitize individuals to the serum.

In 1913, Schick designed a skin test as a means of determining susceptibility or

immunity to diphtheria in humans. Diphtheria toxin will cause an inflammatory

reaction when very small amounts are injected intracutaneously. The Schick Test

involves injecting a very small dose of the toxin under the skin of the forearm

and evaluating the injection site after 48 hours. A positive test (inflammatory

reaction) indicates susceptibility (nonimmunity). A negative test (no reaction)

indicates immunity (antibody neutralizes toxin).

In 1929, Ramon demonstrated the conversion of diphtheria toxin to its nontoxic,

but antigenic, equivalent (toxoid) by using formaldehyde. He provided humanity

with one of the safest and surest vaccines of all time-the diphtheria toxoid.

In 1951, Freeman made the remarkable discovery that pathogenic (toxigenic)

strains of C. diphtheriae are lysogenic, (i.e., are infected by a temperate B

phage), while non lysogenized strains are avirulent. Subsequently, it was shown

that the gene for toxin production is located on the DNA of the B phage.

In the early 1960s, Pappenheimer and his group at Harvard conducted experim

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