Tetanus Immunity

Developed by Parker A Small, Jr., M.D.J. Edwin Blalock, Ph.D.Department of Immunology and Medical MicrobiologyCollege of MedicineUniversity of FloridaGainesville, Florida

Susan M. Johnson, Ph.D.College of PharmacyUniversity of FloridaGainesville, Florida

Note to Students

The fundamental aspect of all health professional activities is helping others. Like all behavior, this helping behavior becomes more effective and natural with practice. This workbook enables you to practice by helping your fellow students learn 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 Problem-Solving workbook designed for four students. You should have previously completed reading assignments on tetanus immunity, studied the objectives designed to help prepare you for this session, and taken the pretest. Now, each of you should take one of the four color-coded booklets and follow the directions. 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.

Your answers and your part of the case history should NOT be read to the other group members, but should be paraphrased and taught to them.

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Tetanus Immunity

Introduction

Clostridium tetani is a gram positive, spore forming, anaerobic organism. Spores are commonly found in agricultural and garden environments, and thus can be introduced into wounds. In an area of devitalized tissue, the tetanus spores can germinate and the vegetative cells grow and produce tetanus toxin. Remember that C. tetani is not an invasive microorganism, and that it is the spread of this extremely potent toxin that is responsible for all disease symptoms.

Pretest Correct Answers

You have the answers to some of the ten pretest questions, and other members of your group have the remainder. This arrangement is designed to encourage all members of your group to actively exchange ideas and concepts. First, study the answers in your booklet and then EXPLAIN them to your group. Please don’t just read them to your classmates, and don’t let 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.

You will probably want to make notes on your pretest to help you review questions that you missed. Avoid “collecting pages” for “later study and understanding.” Learn the concepts now so that later you will only need to review them.

6. The correct answer is D. The differences between primary and secondary (memory) immune responses are displayed graphically in question 1. For further information, consult your textbook relative to primary and secondary immune responses.

7. Immunity means insusceptibility to a disease. Immunity can be innate or acquired, as shown in the diagram below. Innate immunity is present from birth and is independent of the life experiences of the person, whereas acquired immunity arises only after an infection or immunization and hence is acquired during life. Acquired immunity is specific for the infecting organism or immunizing antigen. Thus, a chickenpox infection protects specifically against reinfection by chickenpox virus but does not protect against measles virus infection. Innate immunity is usually nonspecific. For example, stomach acid destroys many different bacteria and viruses ingested in food and thereby protects us from infection nonspecifically. Lysozyme in tears digests the cell wall of many bacteria and in so doing nonspecifically prevents conjunctivitis.

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Tetanus Immunity

Specific acquired immunity is further subdivided into “antibody-mediated’ or “cell-mediated,” depending on whether antibody alone provides the protection or whether T-lymphocytes alone provide the protection. Do not be confused by the fact that antibody is synthesized in cells (B-lymphocytes): the origin of the molecules is not relevant to how protection is provided.

Antibody-mediated immunity is active when the person synthesizes his own antibody; it is passive when another person or animal synthesizes the antibody and it is subsequently injected into the person receiving the passive immunization. Cell-mediated immunity is active when the person’s own T-cells are stimulated or adoptive when the source of stimulated T-cells is another person. Adoptive immunization is rarely used with humans because the recipient will reject the cells unless they are histocompatible (e.g., from an identical twin).

Since people are susceptible to tetanus until they are immunized, the immunity is acquired, not innate. Tetanus immunization protects against tetanus but no other disease, so the immunity is specific, not nonspecific. Since passive immunization with antiserum provides protection, that protection is antibody-mediated, not cell-mediated. Thus B is the correct answer.

Go online for complete “Summary of Major Concepts of Tetanus Immunity and Boosters”.

Table 1. Summarized recommendations for the use of tetanus prophylaxis in routinewound management – Advisory Committee on Immunization Practices (ACIP)

History of adsorbed Clean, minor wounds All other wounds* tetanus toxoid Td † TIG§ Td TIG

Unknown or <3 doses Yes No Yes Yes

3 doses¶ No** No No†† No

*Such as, but not limited to, wounds contaminated with dirt, feces, soil, or saliva; puncture wounds; avulsions (disruption of soft tissue with its bony attachment); and wounds resulting from missiles, crushing, burns, or frostbite.†For children aged >7 years the diphtheria and tetanus toxoids and acellular pertussis vaccines (DTaP) or the diphtheria and tetanus toxoids and whole-cell pertussis vaccines (DTP) – or pediatric diphtheria and tetanus toxoids (DT), if pertussis vaccine is contraindicated – is preferred to tetanus toxoid (TT) alone. For persons aged 7 years, the tetanus and diphtheria toxoids (Td) for adults is preferred to TT alone.§TIG=tetanus immune globulin.¶If only three doses of fluid toxoid have been received, a fourth dose of toxoid – preferably an adsorbed toxoid – should be administered.**Yes, if >10 years have elapsed since the last dose.††Yes, if >5 years have elapsed since the last dose. More frequent boosters are not needed and can accentuate side effects

When your group has finished discussing the pretest, move to “Instructions for the Clinical Problem” on the next page of your booklet.

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Tetanus Immunity

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 immune response to a common medical problem.

Each of the four group members has a different case history. First, deal with your own 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 alternative 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.

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.

Third Patient: Tommy Criton

A 5-day-old baby has just been brought to your office by his mother, a Peace Corps nurse. Mother and baby have just flown in from Africa, where the baby was born. The mother is concerned because the baby was cared for by a native friend. She discovered that the umbilicus of the baby was coated with cow manure, a primitive local custom, and she is concerned about neonatal tetanus. What do you plan to do? Indicate your therapy below.

1. Give tetanus toxin.

2. Give tetanus toxoid.

3. Give tetanus antitoxin (equine).

4. Give tetanus immune globulin (human).

YOU CAN FIND THE CORRECT ANSWER ON LINE IN THE POPS SECTION OF TODAY’S SESSION.

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Tetanus Immunity

REST Not copied.

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Tetanus Immunity

Clinical Problem Answer 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).

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Tetanus Immunity

Alice Wipple (Fourth Patient)

1. Give tetanus toxin.

2. Give tetanus toxoid.

3. Give tetanus antitoxin (equine).

4. Give tetanus immune globulin (human).

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Tetanus Immunity

Correct Answers for Tommy Criton (Patient #3)

Tetanus Toxin

The patient dies!

Tetanus Toxoid

Toxoid would not be adequate therapy since a primary response would take seven to ten days to yield significant antibody levels. In addition, an infant’s immune system often lacks the ability to make adult-type immune responses, and the passive antibody that the baby received transplacentally from his mother may further inhibit antibody formation. This situation differs from Lester Williams’ in that the antibody will already be dispersed throughout the extracellular fluid space before the antigen is given. It will therefore combine with the antigen before it gets to the lymph nodes. Thus, at this age there is no benefit to giving a tetanus toxoid “baby shot” along with the correct treatment of tetanus immune globulin (human). Remember that the baby did receive passive antibody from his mother transplacentally. Ask your colleagues what class of antibody the baby received transplacentally (Answer: IgG) and what class via colostrum if he nursed (Answer: IgA).

Tetanus Antitoxin (Equine)

This patient already has passive antibody from his previously immunized mother (all Peace Corps volunteers get tetanus immunization), but he may not have enough and therefore should be given more passive antibody. If tetanus antitoxin (equine) was all you had available, this was good treatment, but in this country it is unnecessarily dangerous.

Tetanus Immune Globulin (Human)

As with Mr. Williams, this is the optimal treatment, Tommy is really a “peculiar mixture” of Mr. Williams and Mr. Alsop. Like Mr. Williams, Tommy has no active immunity, but he is at least partially immune as was Mr. Alsop. Unlike the latter, however, Tommy’s immunity is passive; hence, he cannot give a memory response. To be safe, he needs more passive antibody now and active immunization as part of his regular “baby shots” starting at about three months of age.

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Tetanus Immunity

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 many 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.

The role of antimicrobial therapy in tetanus remains debated. However, antibiotics may be administered to eradicate vegetative cells (source of toxin). Remember that proper immunization is the most important treatment.

Table 1. Summarized recommendations for the use of tetanus prophylaxis in routinewound management – Advisory Committee on Immunization Practices (ACIP)

History of adsorbed Clean, minor wounds All other wounds* tetanus toxoid Td † TIG§ Td TIG

Unknown or <3 doses Yes No Yes Yes

3 doses¶ No** No No†† No

*Such as, but not limited to, wounds contaminated with dirt, feces, soil, or saliva; puncture wounds; avulsions (disruption of soft tissue with its bony attachment); and wounds resulting from missiles, crushing, burns, or frostbite.†For children aged >7 years the diphtheria and tetanus toxoids and acellular pertussis vaccines (DTaP) or the diphtheria and tetanus toxoids and whole-cell pertussis vaccines (DTP) – or pediatric diphtheria and tetanus toxoids (DT), if pertussis vaccine is contraindicated – is preferred to tetanus toxoid (TT) alone. For persons aged 7 years, the tetanus and diphtheria toxoids (Td) for adults is preferred to TT alone.§TIG=tetanus immune globulin.¶If only three does of fluid toxoid have been received, a fourth dose of toxoid – preferably an adsorbed toxoid – should be administered.**Yes, if >10 years have elapsed since the last dose.††Yes, if >5 years have elapsed since the last dose. More frequent boosters are not needed and can accentuate side effects

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