Case Based Pediatrics For Medical Students and Residents

Department of Pediatrics, University of Hawaii John A. Burns School of Medicine

Chapter I.4. Immunizations

Dennis A. Conrad, MD
August 2003
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A four year old boy presents to your office for the first time with a chief complaint of
deficient immunizations. His mother, who in prior generations would have been
characterized most accurately as an aging hippie, tells you, "He needs his shots to get
into school, and he doesn't have any." You confirm that he has not received a single
immunization prior to this time. When you ask why he hasn't been immunized, his
mother replies that she "hasn't gotten around to it yet," and furthermore, that she "read
on the Web and saw on TV that vaccines can hurt you." She then inquires of you,
"What shots does a kid actually need, what are vaccines actually made of, and how
safe are those immunizations, anyway?"
You perform a physical examination that reveals a healthy boy who is height and
weight proportionate and developmentally appropriate for age, has no evidence of
concomitant illness, and no abnormal findings upon thorough evaluation.
You then roll your eyes, sigh, and tell your nurse to reschedule your afternoon
appointments. You attempt to address the mother's questions and concerns. Following
your informative and comprehensive discourse, you obtain informed consent from the
mother, then immunize the child using an accelerated schedule to "catch-up" the
deficient immunizations. The child tolerates the vaccines without any significant
adverse event occurring. After having been provided the remaining required
immunizations during subsequent office visits, he begins school the autumn of his 5th
year of life protected from vaccine-preventable diseases and meeting the statutory
requirements for school entry. He does not acquire a vaccine-preventable disease
throughout the remainder of his full and successful life as a professional surfer.

Immunizations children routinely receive currently during childhood are those that
protect against hepatitis B, diphtheria, pertussis, tetanus, polio, Haemophilus
influenzae type b, Streptococcus pneumoniae, measles, mumps, rubella, and varicella
(1). In addition, selected populations receive immunization to protect against hepatitis
A and seasonal influenza viruses. The number and ages of administration for these
vaccines differ, but the goal of the recommended schedule for childhood
immunizations is to provide full protection against vaccine-preventable diseases.
Immunization policy has established the practice of universal childhood immunization
to provide vaccines at a time (childhood) an individual is more likely to have contact
with health care providers (to increase convenience and minimize delivery costs), to
protect children from vaccine-preventable diseases, to establish the foundation for an

immune adult population, and to have a enforcement mechanism in order to ensure

compliance (required for school entry).
Hepatitis B virus (HBV) vaccine is a recombinant subunit vaccine containing purified
Hepatitis B surface antigen, synthesized by insertion of a plasmid encoding for the
Hepatitis B surface antigen protein into baker's yeast (2). Hepatitis B vaccine exists as
monovalent vaccine (RecombivaxHB, Engerix-B), in combination with Haemophilus
influenzae type b vaccine (Comvax), and in combination with Hepatitis A vaccine
(Twinrix).
The monovalent Hepatitis B vaccines are administered as a 3 dose series, with the
first dose given between birth and 2 months of age, the second dose between 2 months
and 4 months of age, and the third dose between 6 months and 18 months of age.
Comvax should not be given before 6 weeks of age due to the Haemophilus
influenzae type b component, and Twinrix is not yet approved in the United States for
use in persons less than 18 years old.
Universal immunization of infants with hepatitis B vaccine is recommended to
provide global protection of that birth cohort against hepatitis B infection, to provide
vaccine at a time health care visits are otherwise being made, and to afford protection
to infants born to mothers who have chronic hepatitis B infection. If hepatitis B
vaccination is not provided in infancy at the recommended ages, then at least a 1
month interval should separate administration of the first and second vaccine doses,
and at least a 5 month interval should separate the second and third vaccine doses.
The most common adverse reactions to hepatitis B immunization are fever and local
reactions at the injection site. Allergic reactions occur infrequently. No causal
association with multiple sclerosis or sudden infant death syndrome has been
demonstrated.
Diphtheria (D; d) vaccine is a toxoid vaccine that provides formalin-inactivated
diphtheria toxin, derived from a potent exotoxin produced by Corynebacterium
diphtheriae (3). A "toxoid" is a denatured (nonpathogenic) toxin which stimulates an
immune response against the toxin but not necessarily the organism as a whole.
Immunization promotes an antibody response that neutralizes the exotoxin, protecting
against the cardiotoxic and neurotoxic effects of the exotoxin which is produced
during infection. Diphtheria toxoid is combined with tetanus toxoid in a pediatric
(DT) and adult (dT) formulation that differs by amount of diphtheria antigen.
Diphtheria and tetanus toxoids are also combined with acellular pertussis vaccine
(DTaP) for use during routine childhood immunization.
DTaP is given by intramuscular injection as a primary 3 dose series at 2 months, 4
months, and 6 months of age, and as a 2 dose booster series at 12-18 months and 4-6
years. A reduced diphtheria-antigen adult formulation booster (dT) is administered at
11-12 years, and subsequent boosters are then administered at 10 year intervals
throughout life.
Tetanus (T) vaccine is a toxoid vaccine that provides formalin-inactivated tetanus
toxin, derived from the neuromuscular toxin tetanospasmin produced by Clostridium
tetani (3). Immunization promotes an antibody response that neutralizes the toxin.

Tetanus vaccine may be monovalent (TT), or combined with either diphtheria toxoid
(DT or dT) or with diphtheria toxoid and acellular pertussis (DTaP).
Persons who sustain injuries more likely to become infected with Clostridium tetani
(crush wounds with devitalized tissue, deep puncture wounds, wounds contaminated
with soil or vegetative matter) should receive a booster dose of tetanus vaccine if at
least 5 years have passed since last receiving a tetanus vaccine booster. The most
common adverse reactions to tetanus immunization are fever and local reactions at the
injection site. Severe allergic reactions, Guillain-Barre syndrome, and brachial
neuritis occur rarely.
Three acellular pertussis (aP) vaccines are currently licensed and available for use in
the United States (Tripedia, Infanrix, Daptacel). These vaccines are called acellular, to
distinguish this formulation from the older whole-cell pertussis vaccine. Whole-cell
pertussis vaccine consisted of inactivated ("killed") but otherwise complete Bordetella
pertussis bacteria. Administration provided protection against disease but was
associated with the potential for adverse effects that occurred frequently and could be
quite severe on rare occasion. In order to provide a vaccine that was better tolerated,
individual bacterial components that contributed to organism virulence and
pathogenicity were identified and purified as individual cell-free (acellular) antigens
that comprise the current acellular pertussis vaccines (3,5).
DTaP is given by intramuscular injection as a primary 3 dose series at 2 months, 4
months, and 6 months of age, and as a 2 dose booster series at 12-18 months and 4-6
years. Whole-cell pertussis vaccine was not provided to persons beyond 7 years old,
due to the increased incidence of adverse reactions associated with immunization.
Currently, acellular pertussis vaccine is not recommended for immunization of
persons older than 7 years of age due to the prior experience of whole-cell pertussis
vaccine in this age group, although research is currently being conducted to see if
adults may safely receive booster doses of the less reactogenic acellular pertussis
vaccine to enhance and extend immunity to pertussis.
The most common adverse reactions to acellular pertussis immunization are fever and
local reactions at the injection site. Allergic reactions occur infrequently. Rare but
potentially serious reactions, including high fevers, prolonged crying, hypotonichyporesponsive episodes, and seizures have occurred, but at significantly lower
frequency than was true for whole cell pertussis vaccine.
Inactivated polio vaccine (IPV) is a trivalent killed virus vaccine (Salk vaccine; IPOL)
that contains formalin-inactivated poliovirus 1, poliovirus 2, and poliovirus 3, which
are the three neurovirulent strains. Improvement in manufacturing techniques has
enhanced the immunogenicity of inactivated polio vaccine (eIPV). Immunization
effectively protects against paralytic poliomyelitis, but may not protect against
subclinical enteric infection due to lack of secretory antibody response to inactivated
polio vaccine (6).
Inactivated polio vaccine is administered as a 4 dose regimen by intramuscular
injection at 2 months, 4 months, between 6 months and 15 months (3 dose primary
series), and between 4 years and 6 years of age (booster dose). The most common
adverse reactions to inactivated polio immunization are fever and local reactions at

the injection site. Allergic reactions occur infrequently. Inactivated polio vaccine
cannot cause vaccine associated paralytic poliomyelitis.
A second formulation of polio vaccine, trivalent oral live attenuated polio vaccine
(tOPV; Sabin vaccine; Orimune), also provides protective immunity against paralytic
poliomyelitis. In addition, oral polio vaccine uniquely protects against enteric
infection by promoting mucosal immunity and offering the benefit of herd immunity
by secondary immunization of susceptible persons exposed to asymptomatic shedding
of vaccine strain virus from vaccine recipients. Unfortunately, as paralytic
poliomyelitis due to wild-type virus was eradicated in the United States by effective
immunization programs, the rare risk of paralytic poliomyelitis due to vaccine strain
virus (3 to 12 cases annually) ultimately has become greater than the risk due to wildtype poliovirus. Therefore, only inactivated polio vaccine is used in the United States
currently, whereas the effective, economically favorable, convenient trivalent oral
polio vaccine continues to be used in wild-virus polio endemic regions in an attempt
to eradicate paralytic poliomyelitis worldwide.
A vaccine containing DTaP, HBV, and IPV (Pediarix) has recently been licensed for
use in the United States to provide the primary series of immunizations (first 3 doses)
for children 6 months to 7 years old. This combination vaccine may be used for all 3
vaccine doses, or used to complete the primary series in infants who have already
received 1 or 2 doses of DTaP, HBV, or IPV. The combination vaccine was developed
to reduce the number of injections infants receive during routine childhood
immunization, and provides the same vaccines that have previously existed
individually (Infanrix, IPV, and Engerix-B).
Haemophilus influenzae type b (Hib) vaccine is a conjugated vaccine containing the
Haemophilus influenzae type b capsular polysaccharide polyribosylribitol phosphate
(PRP), which is the major virulence factor, conjugated with a carrier protein to
enhance immunogenicity (7). Infants less than 6 weeks old should not be exposed to
vaccines containing Haemophilus influenzae type b PRP antigen, as premature
exposure may create immune tolerance, causing suboptimal antibody response upon
subsequent antigen exposure and resulting in failure to develop protective antibody
concentrations.
The four monovalent conjugated Haemophilus influenzae type b vaccines currently
available are differentiated by their respective carrier proteins. Infants receiv