CHAPTER 256 Passive Immunization 3401
C H A P T E R
Passive Immunization
256 E. Richard Stiehm ❂ Margaret A. Keller
GENERAL PRINCIPLES OF
PASSIVE IMMUNITY
DEFINITION
Passive immunization is the administration of antibodies from an
immune subject to provide immediate protection against a micro-
bial agent, toxic substance, or cell. In general, passive immuniza-
tion is used to provide temporary immunity in an unimmunized
subject exposed to an infectious disease when active immuniza-
tion is unavailable (e.g., respiratory syncytial virus infection), is
contraindicated (e.g., varicella in an immunocompromised child),
or has not been given before exposure (e.g., tetanus, rabies).
Passive immunization also is used in the management of
certain disorders associated with toxins (e.g., diphtheria), in
certain bites (e.g., snake and spider), in drug overdose (e.g.,
digoxin), as a specific (e.g., Rh0[D] immune globulin) or nonspe-
cific (e.g., antithymocyte globulin) immunosuppressant, and in
the treatment of certain infectious diseases.
Several types of preparations are used in passive immunization
(Table 256–1):
1. standard human immune serum globulin (HISG) for
general use, which is available in three forms: immune globulin
(IG) for intramuscular use (IGIM), intravenous use (IGIV), and
subcutaneous use (IGSC);
2. special high-titer IGs with a known antibody content for
specific illnesses;
3. animal serums and antitoxins;
4. monoclonal antibodies (Tables 256–1, 256-2).
These preparations are listed in Table 256–1. Most of the
licensed special IGs are for intramuscular use only. Plasma,
serum, and even breast milk also can be used in passive
immunization.
Passive immunization is not always effective; the duration is
short and variable (1-6 weeks), and undesirable reactions may
occur, especially if the antibody is of nonhuman origin. High-
titer special IGs and IGIVs are identical to regular IGs and
IGIVs, except that they are derived from patients hyperimmu-
nized or convalescing from a specific infection or selected from
donors with high titers to a specific antigen; they are useful in
several disorders in which regular IG and IGIV are of little or
no value.
ANIMAL SERUMS AND ANTITOXINS
Animal serums and antitoxins are derived from the serum of
immunized animals, usually horses (equine). Because these sera
are foreign proteins, they carry a significant risk of sensitization.
Thus, they should be administered only when specifically indi-
cated, after sensitivity tests, and by a physician prepared to deal
with a hypersensitivity reaction.
A careful history must be taken before an animal serum is
injected. Inquiry must be made about asthma, hay fever, urticaria,
and previous injections of animal serum. Patients with a history
of asthma, allergic rhinitis, or other allergic symptoms on expo-
sure to horses may be dangerously sensitive to the corresponding
serum and should be given only with the utmost caution.
SENSITIVITY TESTS FOR ANIMAL SERUM
A scratch, prick, or puncture skin test, followed by an intradermal
skin test, always should be performed before any injection of
animal serum, regardless of whether the patient has had the
serum previously. A scratch, prick, or puncture test is performed
by applying a drop of a 1 : 100 dilution of the serum in saline to
the site of a superficial scratch, prick, or puncture on the volar
aspect of the forearm and observing it for 20 minutes. A positive
control (histamine phosphate, 0.1%) and negative control (saline)
also should be applied. A positive reaction consists of erythema
or wheal formation 3 mm greater than the control. (Note: pre-
vious use of antihistamines may render results of these tests
negative.)
If the scratch, prick, or puncture test result is negative, an
intradermal test is performed by injecting 0.02 mL of a 1 : 1000
saline dilution; again, positive (histamine phosphate, 0.1%) and
negative control tests should be performed. The reaction is read
after 10 to 30 minutes and is positive if a wheal appears that is
3 mm greater than the negative control. If the test result is nega-
tive, it should be repeated with 0.02 mL of a 1 : 100 dilution. For
persons with negative histories of animal allergy and no previous
exposure to animal sera, the 1 : 100 dilution may be used initially
if the scratch, prick, or puncture test result is negative.
Although intradermal skin tests have resulted in fatalities,
scratch, prick, or puncture tests have not but can still be associ-
ated with immediate reactions. Therefore, a skin test never
should be performed (nor a serum injected) unless a syringe
containing 1 mL of 1 : 1000 epinephrine is within immediate
reach.
Skin tests can indicate the probability of sensitivity. However,
a negative skin test result is not an absolute guarantee of the
absence of sensitivity. Therefore, either a specific history of
allergy or a positive skin test reaction with horse serum is suffi-
cient reason for special caution. A positive history of sensitivity
to horse dander is an indication of the need for extreme
caution.
ADMINISTRATION OF ANIMAL SERUM
If the history and sensitivity test reactions are negative, the indi-
cated dose of serum may be given intramuscularly, with epineph-
rine at hand. The patient should be watched closely for an hour
for adverse reactions.
Intravenous injection may be indicated if a high concentration
of circulating antibody is required rapidly, as in severe tetanus or
diphtheria. The manufacturer’s instructions should be consulted.
If they are unavailable, a preliminary dose of 0.5 mL of serum
should be diluted in 10 mL of either physiologic saline or 5
percent glucose solution. This preparation should be given intra-
venously during the course of 5 minutes, and the patient should
be watched for 30 minutes for reactions. If no reaction occurs,
the remainder of the serum, diluted 1 : 20, may be given at a rate
not to exceed 1 mL/min.