Tetanus: Routine Immunizations Prevent Eleva Essay, Research Paper
AbstractThe mortality rate among untreated tetanus patients remains significantly high despite the availability of vaccinations, and implementation of immunization programs for children. Periodic boosters of the vaccine are also strongly recommended.1,2 Although the incidence of tetanus has decreased, the death rate that still exists due to the disease is alarming. The largest challenge of reducing this statistic lies in convincing healthy persons, patients, and health care providers to consider tetanus immunization.2 Tetanospasmin, or tetanus toxin, is the toxin produced by the gram-positive, spore forming bacilli Clostridium tetani.1,2 Tetanus toxin is responsible for the clinical manifestations of tetanus, which presents itself in various degrees of severity. The disease is diagnosed solely through physical evaluations since microbiological and blood tests do not exist to confirm diagnosis of tetanus.1 Treatment for infected patients includes airway maintenance and stabilization of patient, tetanospasmin absorption inhibition, elimination of the pathogen, and other supportive measures. Infection of tetanus shows an inadequate immunization against the neurotoxin. Tetanus is a prime example of a serious preventable disease that remains a threat even in developed countries, such as the United States.2 Over the last fifty years, the incidence of tetanus has steadily decreased. Despite the widespread availability of a safe and effective vaccine against tetanus, the mortality rate among untreated patients remains significantly high.1 The success in the reduction of tetanus cases in the United States can be contributed to the immunization program for children and the recommendation of routine booster shots for patients every 10 years.1,2 However, the high percentage of tetanus related death, is of concern. This serious disease can be thwarted with preventative measures. The challenge lies in convincing healthy persons, patients, and health care providers to consider tetanus immunization.2 Clostridium tetani (C. tetani), the pathogens responsible for tetanus, or “lock jaw,” are gram positive, spore-forming bacilli that are found primarily in the soil and feces.1,2 Under anaerobic conditions, the spores of C. tetani germinate to produce two toxins: tetanolysin and tetanospasmin. Tetanolysin is a hemolysin that has not been recognized to exhibit pathologic activity. Tetanospasmin, or tetanus toxin, is the toxin responsible for the clinical manifestations of tetanus. C. tetani require a compromise of the host’s skin barrier for inoculation to occur.1 Infection most commonly originates in a minor wound.1,2 The germination and conversion to toxin-producing vegetative form of the bacilli occurs only in wounds favorable to the proliferation of C. tetani, which includes low oxygen tension.1 When the bacteria die and lyse, the neurotoxin, tetanospasmin, is released.3 Tetanospasmin is synthesized by the bacteria as a single 151-kd chain. It is subsequently cleaved to generate toxins with two chains joined by a single disulfide bond. The neurotoxin’s heavy chain is responsible for specific binding to neuronal cells and for transport proteins.2 The light chain of tetanospasmin, a zinc endopeptidase, selectively cleaves the synaptic vesicle membrane protein synaptobrevin. The cleavage prevents exocytosis and release of inhibitory neurotransmitters (gamma-aminobutyric acid and glycine) at synapses within the spinal cord motor nerves.1 Tetanospasmin reaches the central nervous system either by blood-borne delivery to peripheral nerves or by retrograde intraneuronal transport, which takes from two to 14 days.1,2With inhibitory control suppressed, the resting firing rate of motor neurons increases, leading to muscle rigidity and spontaneous muscle contraction.1 The autonomic nervous system is also effected. Sympathetic overactivity is caused by the inhibition of acetylcholine, norepinephrine, and enkephalin release at neuromuscular junctions.Muscle rigidity, generalized spasms, and autonomic instability characterize generalized tetanus, the most common form of the disease.1 Incubation periods range from a few hours to greater than one month, but periods less than 7 days correlate with severe disease and complications. Approximately 75% of the cases begin with stiffness in the masseter muscles, commonly referred to as “lock jaw.” The patient may also have stiffness in the shoulders and back muscles. As this form of the disease progresses over the next one to four days, reflex muscles spasms begin to occur. Complications, such as hypoxia, aspiration, and pneumonia may result in death if treatment is not received promptly and properly. Recovery, if not severe tetanus, usually takes three weeks to two months.A rarer manifestation of tetanus is cephalic tetanus, which is associated with head wounds and chronic otitis media.1 Patients inflicted with this form present with trismus (lockjaw) and cranial nerve damage. Cephalic tetanus may progress to generalized tetanus, which indicates poor prognosis for the patient.Local tetanus, a less severe form of the disease, is associated with muscle spasm and rigidity restricted to the area of the infection site.1 Muscle rigidity may be mild and persist for several months, or it may progress to generalized tetanus or chronic abnormalities in muscle function. Although the prognosis for local tetanus is quite favorable, this presentation of the disease is rare.Neonatal tetanus is more prevalent in underdeveloped countries.1,2 A degree of passive immunity is passed from an immunized mother to fetus. In countries that do not have an immunization program such as that of the United States, children are at risk for developing neonatal tetanus. This generally occurs due to unsterile manipulations of the umbilical cord. Clinical manifestations of neonatal tetanus exhibit irritability, generalized weakness, rigidity, opisthotonos, and an irritability to nurse within 10 days of their birth. Progression to generalized tetanus is very common. Infant mortality, once contracting the disease, is approximately 90 percent.The diagnosis of tetanus is exclusively based upon physical evaluation and patient history.1,2 Laboratory findings are generally used to rule out other possibilities. Microbiological or blood tests do not exist to confirm diagnosis of tetanus. Results from lab tests, including cerebrospinal fluid values, are generally normal. Other conditions must be ruled out, however, including strichnine poisoning, which can mimic the symptoms of tetanus in exclusion of abdominal rigidity and trismus. Patients who receive proper treatment for tetanus have good potential for recovery considering the severity of the disease and its prolonged course.1 The course of the disease could take weeks or even months of treatment depending on the severity and complications of the patient. Treatment of tetanus includes initial stabilization of the patient and airway, prevention of further tetanospasmin absorption, destruction of the organism, and supportive measures.
Control of the muscle spasms that occur in tetanus inflicted patients is the key to initial management of tetanus.2 This allows for the maintenance of ventilation and oxygenation of the patient. The establishment of an airway to prevent potential respiratory complications caused by laryngeal spasms is essential for survival.1 Intubation may be necessary in victims with more severe forms of the disease. Patients are also kept in dark, quiet rooms in order to minimize the chance of hypertensive events that could stimulate muscle spasms.Tetanus infection indicates the inadequate immunization against the tetanus toxin.1 The amount of toxin released in tetanus cases is not enough to induce an immune response that is adequate. For this reason, patients need to be given a booster dose of tetanus toxoid. The toxoid aids in removing free toxin by stimulating antibody production. Since this effect will not occur for days to weeks, infected individuals should also be administered human tetanus immune globulin (HTIG) to directly neutralize the free tetanospasmin. HTIG should be administered as soon as the patient’s airway is protected and muscle spasms have been controlled, but before surgical debridement of the wound since free tetanospasmin may be released into the bloodstream secondary to wound manipulation.Antimicrobial therapy is used in the management of tetanus although it has not been demonstrated to affect morbidity and mortality.1 Penicillins, cephalosporins, macrolides, tetracyclines, imipenem, and metronidazole all display activity against C. tetani. Penicillin G, while it has been widely used in this treatment for many years, is not the drug of choice in elimination of this pathogen.2 Metronidazole, alternatively, has shown superiority in significantly lowering the mortality rate compared to penicillin.1 There is argument that this is not the result of metronidazole’s superior ability to eradicate C. tetani, but rather, that penicillin may adversely affect the treatment outcome. Penicillin is a known antagonist of gamma-aminobutyric acid (GABA), as is tetanus, and it may actually work in synergy with tetanospasmin in producing muscle spasms.Supportive measures, in addition to continuation of respiratory support, include administration of benzodiazepines for sedation, amnesia and muscle relaxation.1 For the treatment of sympathetic overactivity, beta-blockers, magnesium sulfate, and morphine have been used. Hypermetabolism, resulting in increased caloric requirements, is often observed in more severe tetanus patients. Enteral nutrition is the preferred method of nutrition, but central venous nutrition may be necessary if aspiration is a risk. Supportive therapy also includes prevention of decubitus ulcers, and physical therapy. Public health intervention in the prevention of tetanus is most cost-effective in the form of vaccinations.4 The effort to immunize against tetanus in the United States has been largely concentrated on the children. Laws have been adopted in all 50 states requiring the immunization of children prior to enrollment in school. Now, more than 96 percent of school-age children receive at least three vaccinations with diphtheria, tetanus toxoids, and pertussis (DTP) vaccine. An initial dose of DTP is administered a few months after birth, a second dose four to six months later, and a reinforcing dose six to 12 months after the second injection.3 A final booster is given in childhood between the ages of four and six years.In order to enhance protection from tetanus, the United States Immunization Practices Advisory Committee (ACIP) recommends the use of an adult formulation of the vaccine as a booster every 10 years.5 Tetanus toxoid booster doses were given every three to five years at one time.3 This was discontinued due to serious hypersensitivity reactions that have occurred when too many doses of toxoid were administered over a period of years. Boosters are also recommended as part of the treatment of trauma wounds if the victim is at risk of being exposed.5 In the United States, morbidity and mortality due to tetanus is more prevalent in the elderly.2,4 Those 60 years of age and older are found to comprise 59 percent of the cases and 75 percent of the deaths that occur due to tetanus. The estimated risk of tetanus in individuals above the age of 80 is approximately 10 times that of persons aged 20 to 29 years.1 Serologic surveys indicate that a substantial percentage of adults, the majority older than 60 years of age, lack protective levels of circulating tetanus antitoxin.5 Since levels of antibodies decline over time in a person’s body, more emphasis should be placed routine booster shots in older persons.2The United Kingdom has introduced an accelerated schedule for immunization against tetanus, along with their vaccinations for diphtheria and pertussis).6 The more widely spaced schedule of 3, 5 and 9 months has been replaced with injections at 2, 3, and 4 months of age. There is concern that this new immunization schedule may be less protective than the old one. Immunization by the old schedule led to significantly higher antibody concentrations against both tetanus and diphtheria than did the new schedule. The findings also suggest that with an accelerated immunization schedule, maternal antibodies can have an inhibitory effect of the responses to immunization against tetanus and pertussis.Tetanus is a example of a serious but preventable disease that remains a threat even in developed countries, such as the United States.1,2 The elevated rate of mortality associated with the infection is unnecessary in a developed country with widespread availability of vaccine against the disease. The implementation of immunization programs for school-age children has played an crucial role in lowering the incidence of tetanus, but the persistence of the mortality rate to remain high underscores the importance of routine immunization of the population.
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1. Ernst Michael E, Klepser Michael E, Fouts Michelle, Marangos Markos N. Tetanus: Pathophysiology and Management. The Annals of Pharmacotherapy. 1997 December;31:1507-13. 2. Sanford Jay P. Tetanus–Forgotten But Not Gone. The New England Journal of Medicine. 1995 March 23;332(12). 3. Prescott Lansing M, Harley John P, Klein Donald A. Microbiology 3rd Edition. Dubuque, IA: Wm. C. Brown Publishers; 1996, pp. 764-66. 4. Green Peter J, et al. A Population-Based Serologic Survey of Immunity to Tetanus in the United States. The New England Journal of Medicine. 1995 March 23;332(12):761-66. 5. Dal-Re Rafeal, Gil Angel, Gonzalez Antonio, Lasheras Luisa. Does Tetanus Immune Globulin Interfere with the Immune Response to Simultaneous Administration of Tetanus-Diphtheria Vaccine? A Comparative Clinical Trial in Adults. Journal of Clinical Pharmacology. 1995;35:420-425. 6. Booy R, et al. Immunogenicity of combined diphtheria, tetanus, and pertussis vaccine given at 2, 3, and 4 months versus 3, 5, and 9 months of age. Lancet. 1992 Feb 29;339(8792):507-10.