Tetanus - Major Public Health Problem

Tetanus

        Tetanus is a major public health problem in the developing, non-industrialized countries around the world and is still rarely encountered in the developed, industrialized countries. There are around million reported cases of tetanus that occur worldwide each year that cause an estimated 300,000 to 500,000 deaths each year (Mayo Clinic 1).Tetanus did not become a reportable disease in the United States until the late 1940’s. During that time, there were 500–600 cases reported per year (Tetanus: Q & A 1). Once the tetanus vaccine became available, the number of reported cases of tetanus dropped steadily. “During 2001 through 2008, the last years for which data have been compiled, a total of 233 tetanus cases was reported, an average of 29 cases per year. Among the 197 cases with known outcomes the case-fatality rate was 13%” (CDC 291). Tetanus is a rare disease in the United States because children are routinely vaccinated against it. However, the disease is more common in places that do not have rigorous immunization policies. Without treatment, tetanus can be fatal.

        The discovery of tetanus dates back to the 5th century BCE, where it was first described by Hippocrates (CDC 291). He provided countless observations of the disease. However, the etiology of the disease was not discovered until 1884 by Antonio Carle and Giorgio Rattone (National Institutes of Health 13). They were the first to obtain positive results in demonstrating the transmissibility of the disease. They produced tetanus in rabbits by injecting them with pus from a fatal human tetanus case (13). During the same year, a German physician named Arthur Nicolaier discovered the tetanus bacillus. He confirmed that the bacteria generated the tetanus toxin by injecting garden soil containing the bacteria into animals and observing the resultant symptoms of tetanus (13). In 1889, the Japanese bacteriologist Shibasaburo Kitasato isolated the organism from a human victim, showed that it produced disease when injected into animals, and reported that the toxin could be neutralized by specific antibodies (14). In 1897, Nocard demonstrated the protective effect of the passively transferred antitoxin. Passive tetanus immunization was first implemented during World War I (14). After World War I, English scientists developed an improved antitoxin that was put to use after World War II when the establishment of active immunization for all children became a standard practice (14).

        Tetanus is one of the oldest diseases known to afflict human beings. It is a disease that attacks the central nervous system causing lockjaw and other symptoms. Tetanus is caused by infection of a wound by an exotoxin produced by the bacterium Clostridium tetani (CDC 291).  C. tetani is a gram positive, spore-forming, obligate anaerobe, rod shaped, bacillus bacterium (291). It stains gram positive in fresh cultures, but may stain gram negative or gram-variable in older cultures (Todar 1). C.tetani is a bacterial member of the phylum firmicutes, which are also known as the low-GC gram positives because they have a relatively low percentage of the nucleotide pairs, GC, in their DNA and they produce endospores. Their endospores are produced in a swollen sporangium that gives them their shape that resembles a drumstick or a tennis racket (1). C.tetani is sensitive to heat and is strictly anaerobic meaning that it cannot survive in the presence of oxygen (CDC 291). However, the spores it produces are able to withstand oxygenated environments and other harmful environments (291). The spores are also resistant to heat, desiccation, and disinfectants. They can survive autoclaving at 249.8°F (121°C) for 10–15 minutes (291).

Figure 1:  C. tetani endospores in a swollen sporangium that are magnified 3,000 times their actual size

[pic 1]

Clostridium Tetani Endospores. Photograph. Clostridium Tetani. Pathogen Profile Dictionary, 2007. Web. 01 Apr. 2013.

        Tetanus can be spread through a variety of ways. The reservoir for the tetanus spores are widely distributed in the soil, dust, and in the intestines and feces of horses, sheep, cattle, dogs, cats, rats, guinea pigs, and chickens (CDC 291). Also manure treated soils may have a significant number of tetanus spores. Tetanus spores are extremely hardy and can survive in extreme conditions for prolonged periods (291). Spores that gain entry can persist in normal tissue for months to years (291). The transmission of the spores is usually through entry into the body after contamination of an abrasion or minor puncture wound; although, in 20% of cases, no entry site can be found (Taylor 101). Spores also gain entry through skin ulcers, abscesses, gangrene, and burns or after abdominal/pelvic surgery, childbirth and abortion (101). Under the proper anaerobic [low oxygen] conditions, the spores present around the wound will germinate (101).

        When the spores germinate they produce two exotoxins: tetanolysin and tetanospasmin (Hinfey 1). The function of tetanolysin is not known with certainty and has no recognized pathologic activity (1). The toxin tetanospasmin, or commonly referred to as the tetanus toxin, is an extremely potent neurotoxin that is responsible for the clinical manifestations of tetanus (1). This toxin is produced by the growing cells and is only released during cell lysis. The cells lyse naturally during the germination process, as well as during vegetative growth (PCIBT 3). After inoculation of a wound with C. tetani spores, they only need a minimal amount of spore germination and vegetative cell growth until the toxin is produced (3).

        There have been 11 strains of C. tetani identified primarily on the basis of flagellar antigens (PCIBT 3). They all differ in their ability to produce the tetanus toxin (tetanospasmin), but all strains produce a toxin which is identical in its immunological and pharmacological properties (3). The toxin gene is encoded on a plasmid which is present in all strains that produce the toxin. The tetanus toxin is one of the three most potent toxins known, with an estimated minimum human lethal dose of 2.5 ng/kg (Hinfey 1). With the other two toxins being botulism and diphtheria (PCIBT 3).

        Tetanospasmin is synthesized as a 150-kd polypeptide protein chain, called the progenitor toxin, that is cleaved extracellularly by a bacterial protease into a 100 kDa heavy chain (fragment B) and a 50kDa light chain (fragment A), which remain connected by a disulfide bond (PCIBT 3). The heavy chain is responsible for the binding of tetanospasmin to the motor neurons and creates a pore for the entry of the light chain (3). When the light chain enters the motor neurons, it travels by retrograde axonal transport from the contaminated wound site to the spinal cord in 2-14 days (3). Once the toxin reaches the spinal cord, it enters central inhibitory neurons. Then the light chain cleaves the protein synaptobrevin, a vesicle-associated membrane protein which is essential for the release of neurotransmitters (Taylor 1). As a result, the release of glycine and gamma-aminobutyric acid (GABA) are prevented causing a failure to inhibit action on motor and autonomic neurons (PCIBT 3).  This causes increased muscle tone and rigidity, interposed by uncontrolled muscle contraction and spasms (Taylor1).

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