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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


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 Problem-
Solving ("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.

Tetanus Immunity
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 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.

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 give 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 finished discussing the pretest, you should read the "Instructions for the Clinical Problem" on
the next page of your booklet.

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 (or anamnestic) 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. 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.

Tetanus Immunity

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 severe 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 previous immunizations. After treating
the wound, what do you do to prevent tetanus? Indicate your therapy on the "Lester Williams" part of the Tetanus
Immunity Clinical Problem Answer Sheet (next page).

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).

Tommy Criton (Third Patient)

? 1. Give tetanus toxin.

? 2. Give tetanus toxoid.

? 3. Give tetanus antitoxin (equine).

? 4. Give tetanus immune globulin (human).

Alice Wipple (Fourth Patient)

? 1. Give tetanus toxin.

? 2. Give tetanus toxoid.

? 3. Give tetanus antitoxin (equine).

? 4. Give tetanus immune globulin (human).

Tetanus Immunity

Correct Answers for Lester 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 lethal 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 antibodies 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 and 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.)

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 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 TIG = tetanus immune globulin (human)

History of Clean, minor Other than minor

tetanus wounds wounds
(doses) Td TIG Td TIG

Uncertain Yes No Yes** Yes**

0-1 Yes No Yes** Yes**
2 Yes No Yes No*
3 or more No† No No¶ 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.

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 Last Dose ? Type of wound Tet Vac boost TIg

3 or more < 5 yrs ALL no no

5-10 yrs Clean,minor No No

All other Yes No

> 10 years All Yes No

<3 or unknown Clean,minor Yes No

All other Yes Yes

So, the only real indication for TIg is the nasty wound with inadequate or unknown immunization