Tetanus Immunity Developed by Parker A. Small, Jr, MD J. Edwin Blalock, PhD Department of Immunology and Medical Microbiology College of Medicine University of Florida Gainesville, Florida Susan M. Johnson, PhD College of Pharmacy University of Florida Gainesville, Florida
BOOK B
Note to Students The fundamental purpose of all activities in the health-care professions is to help other people. Like all behavior, helping behavior becomes more effective and natural with practice. This workbook enables you to practice by helping your fellow students to Ilearn basic science. Your skill at helping your fellow students should relate to your ability to help your patients in the future. This is a Patient-Oriented ProblemSolving ("POPS") workbook designed for four students. Before beginning this session, you should have (a) studied the objectives designed to prepare you for it, (b) taken the pretest, and (c) reviewed the topics listed at the end of the pretest. Now, each of you should take one of the four color-coded booklets and follow the directions in it. If your group has only three students, one of you should take two booklets. Leave the remainder of the workbook intact until you are given further instructions.
B-1
Tetanus Immuni ty Pretest Correct Answers You have the answers to the ten pretest questions. First, study the answers in your booklet and then EXPLAIN them to your g roup . Please don't j ust read them to your class mates, and don't l et your classmates read their answers to you. In explaining something to another person, most people gain a better understanding of it and often transmit a better understanding. The pretest discussion and patient-oriented problem-solving parts of this activity are "open book" Be sure to refer to textbooks, notes, and other written resources whenever questions arise. 2. This patient will need passive immunization to provide immediate but short-lived protection and active immunization to provide antibody for a longer period. Active immunization also provides sensitized lymphocytes (memory cells) that can be quickly "turned on" at any future time by booster immunization. D is the correct answer. The Public Health Service recommends that tetanus toxoid and tetanus immune globulin (human) be given concurrently at separate sites (e.g., - arm and buttocks or left arm and right arm). Ask your group mates why it is important to give the antigen and the antibody in different sites. (Answer: This allows the toxoid [antigen] to get to the lymph nodes before the passive antibody can combine with it. This procedure leads to both active and passive immunity). The patient should return later for two booster immunizations with tetanus toxoid. Passive immunization with a heterologous antitoxin (e.g., tetanus antitoxin [equine] should be avoided if possible because of the risk of serious anaphylactic or serum sickness reactions. One of 20 patients given heterologous serum requires hospitalization for the treatment of serum sickness. B is incorrect since the patient will again be susceptible to tetanus when the passive antibody is eliminated. She needs active immunization with tetanus toxoid as well as passive immunization with tetanus immune globulin (human). Answer A is incorrect since Ab:Ag complexes would be formed in vitro before injection of the mixture, possibly leading to tolerance and certainly decreasing the effectiveness of the passive antibody. C is incorrect because the primary active immune response is not fast enough to g ive protection before the toxin level becomes lethal. 5. Previous passive immunization with heterologous (horse) antiserum (e.g., tetanus antitoxin [equine]) can stimulate the production of antibody to horse serum proteins. This can cause anaphylaxis immediately following another injection of horse serum. B is therefore correct. A is incorrect since blood cells are not being transferred, only serum. Also, this serum does not have a significant amount of antibody directed to human red blood cells. C is incorrect since active immunization with antigens such as tetanus toxoid does not produce sensitivity to horse serum proteins. E is incorrect since injections would have to be repeated every three to four weeks to maintain protection, which would be impossible with heterologous serum. Even more obvious is the idea that snakebite is so rare that prophylactic treatment is inappropriate.
When your group has finish ed discussing the pretest, you shou ld read the "Instructions for th e Clinical Problem" on the next page of your booklet.
B-4
Tetanus Immuni ty Instructions for the Clinical Problem The purpose of this exercise is to allow you to apply your knowledge of active vs. passive immunization and primary vs. secondary (or anamnestic) immune response to a common medical problem. Each of the four group members has a different case history First, deal with your o wn patient. After reading your patient's case history, decide the therapy you would use, the reasons for the choice, and the consequences of alternative therapy. Next, fill out your answer sheet concerning your patient. After everybody has finished his/her problem, the group member with the first patient should present that case history to the other three group members and allow them time to individually decide therapy, the reasons for their choice, and the consequences of a lternative therapy. They should then fill out their answer sheets for that patient (i.e., commit themselves to therapy before the group discussion). The group member who has the first patient should then present his/her choice of therapy to the group and defend it. Members who disagree with this choice, the reasons for it, or consequences of it should present their ideas and defend them. After discussion of the first patient is completed, compare your answers with those on the correct answer sheet for each patient. This process will then be repeated for the other three cases. Patients should be presented in numerical order. At first glance, the patients' cases seem repetitious, but there are subtle and important differences! Remember, this is an "open-book" activity, and you should consult your textbooks about any point you don't understand.
B-5
Tetanus Immuni ty Second Patient: Lester Williams A 23-year-old mountaineer, who arrived in town only last week, has just come to your office with a fractured right upper central incisor and a s evere laceration in the roof of his mouth. The wound does not penetrate his hard palate. He fell on a stick in the woods. The wound has some dirt in it. He has had no pre vious immunizations. After treating the wound, what do you do to prevent tetanus? Indicate your therapy on the "Lester W illiams" part of the Tetanus Immunity Clinical Problem Answer Sheet (next page ).
B-6
Tetanus Immunity Clinical Problem Ans wer Sheet Check the box(es) that indicate(s) the preferred therapy for each patient. Then briefly write the reasons for your choice in the space provided. Finally, describe the consequences of each of the other therapies in the space provided under each therapy. Commit yourself in writing before the discussion begins. The answer sheet will not be collected. Joe Alsop (First Patient) ? 1. Give tetanus toxin. ? 2. Give tetanus toxoid. ? 3. Give tetanus antitoxin (equine). ? 4. Give tetanus immune globulin (human). Lester Williams (Second Patient) ? 1. Give tetanus toxin. ? 2. Give tetanus toxoid. ? 3. Give tetanus antitoxin (equine). ? 4. Give tetanus immune globulin (human). Tommy Criton (Third Patient) ? 1. Give tetanus toxin. ? 2. Give tetanus toxoid. ? 3. Give tetanus antitoxin (equine). ? 4. Give tetanus immune globulin (human). Ali ce Wipp le (Four th Patien t) ? 1. Give tetanus toxin. ? 2. Give tetanus toxoid. ? 3. Give tetanus antitoxin (equine). ? 4. Give tetanus immune globulin (human).
B-7
Tetanus Immuni ty Correct Answ ers for L ester Williams (Patient #2) Tetanus Toxin The patient dies! Tetanus Toxoid If the wound was infected by Clostridium tetani, the patient would die from tetanus within one to two weeks after the injury if this was the only treatment. The patient had never had an immunization, and the primary immune response is not rapid enough to provide antibody before le thal amounts of toxin are produced. Active immunization with tetanus toxoid is not appropriate in this case as the only treatment, but it should be given at the same time as tetanus immune globulin (human) in a separate location. Tetanus Antitoxin (Equine) Passive immunization may have saved this patient's life since an tibodies were provided "instantaneously" to neutralize the toxin produced by Clostridium tetani. However, you should also be aware of the potential problems you have caused Lester by using heterologous antiserum. The most immediate problem is the potential of an anaphylactic response to the horse antiserum at the time it is given. This reaction could be fatal. The second problem is that the antibodies administered are foreign proteins that may induce serum sickness in the patient in one to two weeks. Ask your group mates to briefly describe the pathophysiology of serum sickness. (Answer: See answer to pretest question 9.) A longer range problem is that, due to the immune elimination of the foreign antibody the patient will have no protection from tetanus two or three weeks from now an d probably will be hypersensitive to horse serum, so you could not use tetanus antitoxin (equine) again. In order to give your patient prolonged protection, you will actively immunize him by giving him a series of toxoid injections. Ask your colleagues when the toxoid series should be started. (Answer: Before he leaves your office, since you may not see him again.) Tetanus Immune Globulin (Human) This is half of the optimal treatment for this patient. Passive immunization is the fastest and only foolproof way of producing toxin-neutralizing antibody in time to prevent tetanus. By choosing human antibody, you virtually eliminated the potential adverse effects such as anaphylaxis and serum sickness. However, the passively administered antibody will be eliminated with a half-life of about three weeks. Therefore, you should administer tetanus toxoid at the same time in a separate location followed by a series of active immunizations with tetanus toxoid. Ask your colleagues, "What fraction of the passive antibody will be present in nine weeks?" (Answer: one eighth.)
B-8
Tetanus Immuni ty Summary of Major Concepts of Tetanus Immunity and Boosters Primary Immunization should be given to everybody to prevent tetanus. The precise ages at which diphtheria, pertussis, and tetanus (DPT) shots are given are listed in any pediatrics textbook and are best learned when you are studying pediatrics. In general, however, children receive three doses in the first six months of life and boosters at ages 1 and 5. These injections stimulate lymphocytes to produce antibody. These IgG antibody molecules have a half-life of three weeks, just like passively administered human IgG, but the "antibody factories" continue to turn out more antibody so it persists in high enough concentrations to provide protection for five to ten years (see Table 1). The injections also produce memory lymphocytes that, unlike the antibody, persist throughout life and are ready to rapidly produce antibody the next time the antigen, tetanus toxoid, is administered. Booster immunization with tetanus toxoid can lead to the production of adequate amounts of protective antibody within three to five days (even when there is little or no circulating antibody) if there are memory lymphocytes primed by a previous tetanus toxoid injection. Remember: Previous disease will not stimulate the immune system in patients with tetanus, but it does in patients with most other infectious diseases. Passive, immunization with tetanus immune globulin (human) will provide instantaneous immunity, but antibodies disappear with a half-life of three weeks and memory lymphocytes are not produced to help the next time. It should never be the sole therapy in normal patients. Consult Table 1 for the appropriate treatment. Tetanus antitoxin (equine) should be used only when human antiserum is not available and passive immunization is imperative. When tetanus immune globulin (human) or tetanus antitoxin (equine) and tetanus toxoid are given at the same time, each should always be injected at different sites. TABLE 1. Guide to tetanus prophylaxis in wound management (Modified from Morbidity and Mortality Weekly Report 30:392-396, 401-407, 1981.) Td = tetanus toxoid History of tetanus immunization (doses) Uncertain 0-1 2 3 or more
TIG = tetanus immune globulin (human) Other than mino r wounds
Clean, minor wounds Td
TIG
Td
Yes Yes Yes No†
No No No No
Yes** Yes** Yes No¶
* Unless wound more than 24 hours old † Unless more than 10 years since last dose ¶ Unless more than 5 years since last dose **Administer Td and TIG at separate sites.
B-9
TIG Yes** Yes** No* No
5/21/2012 Update Information from Raymond Smith, MD
Management of tetanus-prone wounds The new Immunization Schedule recommends that 10-yearly tetanus boosters are no longer required up until the age of 50, provided that the primary series of 3 vaccinations plus 2 boosters have been given. The recommendations for the management of tetanus-prone wounds remain the same. Types of wounds likely to favour the growth of tetanus organisms include: compound fractures deep penetrating wounds wounds containing foreign bodies (especially wood splinters) wounds complicated by pyogenic infections wounds with extensive tissue damage (eg. contusions or burns) any wound obviously contaminated with soil, dust or horse manure (especially if topical disinfection is delayed more than 4 hours). Re-implantation of an avulsed tooth is also a tetanus-prone event, as minimal washing and cleaning of the tooth is conducted to increase the likelihood of successful re-implantation. • • • • • •
•
Wounds must be cleaned, disinfected and treated surgically if appropriate. History 3 or more
Last Dose ? < 5 yrs
Type of wound ALL
5-10 yrs
Clean,minor
No
No
All other
Yes
No
All
Yes
No
Clean,minor
Yes
No
All other
Yes
Yes
> 10 years <3 or unknown
Tet Vac boost no
TIg no
So, the only real indication for TIg is the nasty wound with inadequate or unknown immunization history.
