TETANUS

Pradita Sri Mitasari 08/265250/KU/12686

Tetanus is an acute, often fatal, disease caused by an exotoxin produced by the bacterium Clostridium tetani. It is characterized by generalized rigidity and convulsive spasms of skeletal muscles. The muscle stiffness usually involves the jaw (lockjaw) and neck and then becomes generalized.

 C.

tetani is a slender, gram-positive, anaerobic rod that may develop a terminal spore. The organism is sensitive to heat and cannot survive in the presence of oxygen. The spores, in contrast, are very resistant to heat and the usual antiseptics. They can survive autoclaving at 249.8F (121C) for 1015 minutes. and tetanospasmin. The function of tetanolysin is not known with certainty. Tetanospasmin is a neurotoxin and causes the clinical manifestations of tetanus. On the basis of weight, tetanospasmin is one of the most potent toxins known. The estimated minimum

C. tetani produces two exotoxins, tetanolysin

 Tetanus occurs worldwide and is endemic in

approximately 90 developing countries, although its incidence varies considerably. The most common form, neonatal (or umbilical) tetanus, kills approximately 500,000 infants each year, with about 80% of deaths in just 12 tropical Asian and African countries. It occurs because the mother was not immunized. In addition, an estimated 15,00030,000 unimmunized women worldwide die each year of maternal tetanus that results from postpartum, postabortal, or postsurgical wound infection with C. tetani

 Neonatal tetanus occurs through infection

of the umbilicus when the cord is cut with an unclean instrument or when substances heavily contaminated with tetanus spores are applied to the umbilical stump.

 Most

non-neonatal cases of tetanus are associated with a traumatic injury, often a penetrating wound inflicted by a dirty object such as a nail, splinter, fragment of glass, or unsterile injection. Tetanus occurring after illicit drug injection is becoming more common. The disease also occurs after the use of contaminated suture material and after intramuscular injection of medicines, most notably quinine for chloroquineresistant falciparum malaria. The disease may also occur in association with animal bites, abscesses (including dental abscesses), ear and other body piercing, chronic skin ulceration, burns, compound fractures, frostbite, gangrene, intestinal surgery, ritual

Patogenesis
C. tetani usually enters the body through a

wound. In the presence of anaerobic (low oxygen) conditions, the spores germinate. Toxins are produced and disseminated via blood and lymphatics. Toxins act at several sites within the central nervous system, including peripheral motor end plates, spinal cord, and brain, and in the sympathetic nervous system. The typical clinical manifestations of tetanus are caused when tetanus toxin interferes with release of neurotransmitters, blocking inhibitor impulses. This leads to unopposed muscle contraction and spasm. Seizures may occur, and the autonomic nervous system may also be affected

 Tetanus is an entirely preventable disease. A

serum antibody titer of 0.01 U/mL is considered protective. Active immunization should begin in early infancy with combined diphtheria toxoid-tetanus toxoid-acellular pertussis (DTaP) vaccine at 2, 4, and 6 mo of age, with a booster at 46 yr of age and at 10 yr intervals thereafter throughout adult life (Td or Tdap). Immunization of women with tetanus toxoid prevents neonatal tetanus, and the World Health Organization is engaged currently in a global elimination of neonatal tetanus campaign through maternal immunization with

Protective antibody concentration

The minimum amount of circulating antitoxin that

in most cases ensures immunity to tetanus is assay-specific. With in vivo neutralization tests or modified ELISA assays, concentrations exceeding 0.01 IU/mL are usually considered protective, whereas antitoxin concentrations of at least 0.10.2 IU/mL are defined as positive when standard ELISA techniques are used for this assessment. In children, three primary doses of DTP vaccine induce an antibody level above the minimum protective threshold, with a mean level above 0.2 IU/ml (Anderson et al.1988; Barkin et al. 1984;

IMMUNE RESPONSE TO IMMUNIZATION

The degree and duration of immunity

increases with the number of tetanus toxoid doses given. One dose of tetanus toxoid ensures little, if any, protection. Two to four weeks after the second dose the mean level of tetanus antitoxin usually exceeds the minimum protective level of 0.01 IU/ml, although the percentage of poorlyprotected persons can still be up to 10%. Immunity also declines with time. After one year the percentage of poorly-protected persons may increase to 20% and the mean titre may fall to the threshold level.

 The level of immunity induced by a course of

three injections is high and durable. One month following the third dose the percentage of poor responders is negligible and the protective level lasts for at least five years. After the third dose, each additional dose given with at least a one-year interval increases the tetanus antitoxin level and prolongs the duration of immunity. Immunity will last for 10 years after the fourth dose and for at least 20 years after the fifth dose.

The ratio of antitoxin in maternal serum to antitoxin in cord serum depends on the intervals between doses of tetanus toxoid and the interval between the last dose and delivery. Longer intervals between doses of tetanus toxoid in the initial series increase the height and duration of the immune response (Table 2). Long intervals between doses of toxoid are best for achieving the optimal immunological results.

Immunization of infants with 3 doses of DPT vaccine will provide tetanus immunity for one to three years. Usually, three doses of tetanus toxoid received as an infant are counted as two doses received as an adult. Reinforcing the infant immunization with a fourth dose given somewhere between the 15th and 24th month of life will prolong tetanus immunity for another five years, e.g. until 6 or 7 years of age. A fifth dose of tetanus toxoid (given as Td or

WOUND MANAGEMENT
Tetanus prophylaxis is an essential part of all wound

management, but specific measures depend on the nature of the injury and the immunization status of the patient. Tetanus toxoid should always be given after a dog or other animal bite, even though C. tetani is infrequently found in canine mouth flora. All nonminor wounds require human TIG except those in a fully immunized patient. In any other circumstance (e.g., patients with an unknown or incomplete immunization history; crush, puncture, or projectile wounds; wounds contaminated with saliva, soil, or feces; avulsion injuries; compound fractures; or frostbite), TIG 250 U should be given intramuscularly, with 500 U for highly tetanus-prone wounds (i.e., unable to be debrided, with substantial bacterial contamination, or >24 hr since injury). If TIG is unavailable, then use of human IGIV may be considered. If neither of these products is available, then 3,000-5,000 U of equine- or bovine-derived TAT may be given intramuscularly after testing for hypersensitivity. Even

 Persons with wounds that are neither clean nor

minor, and who have had 02 prior doses of tetanus toxoid or have an uncertain history of prior doses should receive TIG as well as Td or Tdap. This is because early doses of toxoid may not induce immunity, but only prime the immune system. The TIG provides temporary immunity by directly providing antitoxin. This ensures that protective levels of antitoxin are achieved even if an immune response has not yet occurred.

SUMMARY
Firstly,

improvements in coverage with a primary series (at least three doses in the first year of life), must continue. Although it is generally accepted that the primary series in infancy only gives protection for approximately five years, it is vital in providing not only protection in the very young but the initial immunological stimulus that allows an anamnestic response to subsequent booster doses. Secondly, reinforcing doses of tetanus toxoid in children of school age and adolescents are critical in maintaining antibody levels which can persist for decades

References
Borrow, et al. 2007. The Immunological Basis of

Immunization Series Module 3: Tetanus. WHO: Geneva CDC. 2012. The Pink Book: Course Textbook 12th Edition, Epidemiology and Prevention of Vaccine-Preventable Diseases : Tetanus. WHO. 2006. Maternal Immunization Against Tetanus.