Children Out of Step With Immunization Carol F.

Phillips Pediatrics 1975;55;877

The online version of this article, along with updated information and services, is located on the World Wide Web at:
http://pediatrics.aappublications.org/content/55/6/877

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright 1975 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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Children
Carol F. Phillips,

Out of Step With

M.D.
of Pediatrics, University

Immunization

From

the

Department

of Vermont

College

of Medicine,

Burlington

One
medicine

of the
is

most
the

important
ability to

advances
prevent

in modern
disease by

increasing

incidence and that

of local pain) and these

reactions systemic patients

(swelling, (urticarial

appropriate immunization. prophylaxis many formerly as poliomyelitis, diphtheria,

becoming medical rarities.

By means of immunodreaded diseases such and measles are

In fact, in vaccination

redness, itching, and angioneurotic

Studies showed

edema)

reactions

were

seen.

possessed

against
no States. longer

smallpox
Schedules

has
for

been
routine

so successful
the immunizations

that

it is
of

considered

necessary

United

extremely high levels of tetanus It is generally accepted that 0.01 antitoxin units per milliliter protect against tetanus. Gold3
that immunity one shot but of serves tetanus as a toxoid

antibody. a serum level of is sufficient to showed in 1938

produces A second no

infants are published by the American Academy of Pediatrics and are familiar to all who deliver medical care to children. This schedule includes DPT (diphtheria-tetanus and pertussis) and trivalent oral polio vaccine at age 2, 4, and 6
months months diphtheria Measles, and and a booster preschool. boosters mumps, and are rubella of DPT Subsequently given are and every polio tetanus ten at 18 and at

primer.

injection, produce 14 days. produced

tetanus

provided
consisted

given up to two years later, will protective levels of antibody within 5 to Peebles et al.4 studied the antibody level by varying numbers of injections of toxoid and the length of protection by these immunizations. Their study
mainly of patients having a well-docu-

years.

recommended

mented
injections months patients

history

of four

or

more

tetanus
the age later). In antibody

toxoid
of 7 these was

1 year of age. There is no difficulty in following this routine if the child is seen for well-child care at or near the recommended schedule. The dilemma for all doctors is the child who receives sporadic crisis care or no care at all. This is the child who is out of step with immunization. Recent studies have provided valuable information meet on the ways that the present immunization

(usually three before and a booster 12 months they showed that tetanus

extremely long-lasting and that these patients were probably protected for 30 years. With a 99.9% confidence, they would be protected for 12.3 years. His study group included ten children who had received only three tetanus toxoid
immunizations These patients in early had they or ten infancy and antibody no boosters. levels but for show adequate

schedules

can

be

modffied
needs

and
of these

consolidated
children.

to

individual

had TETANUS Tetanus is an organism widespread in the soil. The effectiveness of tetanus toxoid was well proven during World War II where extensive immunization of American soldiers virtually elimmated the disease in our troops. The vaccine became so popular that, during the 1950s and 1960s, summer camps required yearly boosters as one of the requirements for acceptance. Every
laceration room was or injury seen also treated in a hospital emergency with a tetanus booster, Analysis about

the
nine

steepest
shows

rate
were years.

of

fall-off
probably These

of
studies

antibody.

protected

clearly
agent

that
which

(1)
protection;

tetanus
(2) (there

is a good
stable antibody interruption

immunizing
providing of the

produces

long-term immunization resulting

schedule
immunity

does
is no

not
need

affect
to restart

the

occasionally
of tetanus

without
toxoid had

determining
ever been

if a basic
given.

series an

(Received November

August 21; 1 1, 1974.)

revision

accepted

for

publication

ADDRESS
University Vermont

FOR

REPRINTS:
College

Department
of Medicine,

of

Pediatrics,
Burlington,

In patients

who

had

received

frequent

booster

shots,

of Vermont 05401.

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877

immunizations; count all DPT or DT shots when determining the number of tetanus immunizations the child has received); (3) after a basic series of two or three injections plus a booster, diphtheria tetanus booster every ten years is a very safe, conservative recommendation;5 and (4) if the patient has had four doses of toxoid and the immunization history is well documented, there is no need to give a tetanus booster at the time of injury if the last tetanus toxoid was given within five years. DIPHTHERIA
Several outbreaks of diphtheria have occurred

commercially except in combination us. Therefore DT boosters should emergency rooms when tetanus deemed necessary. PERTUSSIS

with tetanbe given in boosters are

Pertussis is a prolonged and debilitating disease at any age but most of the mortality occuis in infants under the age of 1 year. There is good evidence that adequate pertussis immunization can decrease the incidence of disease.#{176} For immunizations to protect the group at highest risk (i.e., infants), they must be started early. The currently recommended immunization
schedule calls for a basic series of three pertussis

in the
miological

United

States
investigation

in the

past

few

years.

Epide-

of one

of these

outbreaks6

showed acquiring culture complete,

immunization.

no statistical difference in diphtheria infection (defined positive for diphtheria) in partial, or no previous
However, the risk

the risk of as a throat those with diphtheria

diph-

immunizations at 2, 4, and 6 months of age and two boosters. The basic series is spaced at twomonth intervals because it is most convenient to give polio vaccine at the same time, and trivalent oral polio vaccine is best given at intervals of
eight weeks or longer. Wilkins et

of clinical

have

theria
dipthena those

was
with

30
partial

times

immunizations

greater and

for those with 11.5 times greater

when compared

no in

immunizations

with those who were fully immunized. Diphtheria immunization prevents clinical disease but has no effect on the carrier state. Therefore, high
percentages of immune citizens in a community

will not prevent

diphtheria

serve to protect epidemics. The

is adequate

the unimmunized only protection

immunization

or to against
of all inch-

viduals. Diphtheria toxoid is a good immunizing agent which produces long-lasting antibody comparable with that produced by tetanus toxoid. Scheibel et al.7 studied 191 children for persistence of dliphthena and tetanus antibody. These children received two immunizations in early infancy and a booster one year later. At 13 to 14 years of age 88% still had protective levels of antibody against diphtheria and 96% against tetanus. Adult and pediatric diphtheria tetanus preparations differ only in the amount of diphtheria toxoid present. Since there is good evidence that the incidence of adverse reactions to diphtheria toxoid increases with age,8 the adult preparation
is carefully units controlled to contain toxoid.9 The no more pediatric than 2 if of diphtheria prepa-

recently shown that if the interval between pertussis shots is 60 days or longer the antibody produced by two immunizations is equal to that produced by three monthly injections and is protective. As previously mentioned, Scheibel et al.7 have shown that two doses of diphtheriatetanus in infancy plus a booster one year later gives adequate long-lasting protection against diphtheria and tetanus. These data suggest that a basic series of two DPT injections spaced at least 60 days apart plus a booster one year later would be as effective as the currently recommended series. Neurologic complications have been reported after pertussis immunization. The incidence of these reactions in Sweden is 1 in 3,600.12 Comparable incidence figures in the United States are difficult to find. There is no evidence that the adverse reactions to pertussis immunization increase with age. However, the mortality of the
disease is mainly in infants. Therefore, the risk of

immunization older children.

immunization

would seem to be unjustified in The exact age at which pertussis

should be discontinued is unclear.

The current immunization

recommendations is not usually

state that given after VIRAL

pertussis age 6.

ration contains a varying amount up to 25 if units. Patients over the age of 5 years should receive adult DT. After the basic series plus a booster, a
DT

COMBINING

DPT WITH

VACCINES

booster

every

ten

years

is

adequate

for

maintenance diphtheria. only tetanus be difficult body since 878

of immunity to both tetanus and if a patient receives a booster dose of toxoid at the time of an injury, it will to maintain adequate diphtheria antidiphtheria toxoid is not available

With the increased number of vaccines recommended for routine use, it is desirable to be able to give several immunizations at the same time. Hardy et al.3 have shown that DPT and oral polio vaccine may be safely given together. In older unimmunized children it would be advantageous to give DT, polio, and measles simultaneously. Two recent studies have shown that DPT does

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not interfere with the immune response to measles vaccine. Marshall4 et al. studied 50 Guatemalan children. One haif of the group was given measles (Schwartz strain) vaccine alone and the other one half received DPT and measles vaccine. The rate of seroconversion for measles was similar in both groups. In a larger field trial done in Nigeria, Landrigan et al.5 studied four groups of 125 children each. One group received
measles (Schwartz) and smallpox vaccines; the

second was given yellow fever vaccine only; the third group received DPT and polio; and group 4 received measles, smallpox, yellow fever, DPT, and polio. Analysis of the data is not yet complete but measles antibody developed in 92% of the children in group 1 and 95% in group 4. Therefore, DPT (or DT), polio, and measles can be given simultaneously with safety and efficacy. POLIO The basic series of Sabin polio immunizations recommended by the American Academy of Pediatrics is three doses of trivalent vaccine given approximately eight weeks apart and a booster one year later for a total of four doses. The US. Public Health Service recommends a total of three doses of vaccine-the first dose at 6 to 12 weeks, a second 8 weeks later, and a booster in 8 to 12 months. Hardy et al.3 compared these two
recommended schedules in a large group of

seventh-graders. They confirmed the immunization history in 82%. When serum of these children were screened at a dilution of 1:8, their findings were in agreement with the Syracuse study. When the sera were tested at a dilution of 1:2, an extremely high percentage of children had neutralizing antibody. The level of antibody needed to protect against infection has never really been determined. However, it is most probable that any detectable level of neutralizing antibody is sufficient to protect the individual from disease. This study also showed no difference in antibody titer between those who received
three, four, significant or five difference doses in of vaccine. There the proportion was no of chil-

dren with low antibody titer when compared by socioeconomic group. The percentage of children demonstrating antibody was similar in the two age groups, demonstrating that polio antibody is long-lasting. Large numbers of children were immunized in the 1950s with inactivated Salk vaccine. A series of three monthly injections plus a booster one
year later was considered adequate immuniza-

tion.

Serum

antibody
tract

was

produced
was

but

no local,
achieved.

gastrointestinal

immunity

infants. After the booster dose, satisfactory levels of immunity were achieved in both groups. Therefore, a child can be adequately immunized with a schedule of two trivalent oral polio immunizations eight weeks apart and a booster one

Many of these children have subsequently received a complete series of oral polio vaccine. McCollough et al.8 studied 200 school-aged children who had received a complete series of Salk vaccine. They showed that a single dose of trivalent vaccine provided an adequate booster response in these children. COMBINATIONS OF LIVE VIRAL VACCINES Until recently, it has been felt that live viral vaccines could not be given together because they would interfere with each other and one could not be sure that the patient would develop
immunity to all-or indeed to any-of the viruses.

year later. The need vaccine at

documented.

for an additional booster dose of polio ages 4 to 6 years has not been well
Occasionally, a child will fail to

develop antibody after vaccine Interference caused by preexisting,

enterovirus infection has been

has

been given. asymptomatic

as a

suggested

possible explanation. The rationale for the preschool booster dose is to immunize children who may have failed to respond to a previous immunization. A recent serum survey6 of Syracuse children
aged 4 to 6 years, most with documented history

of immunization body was not

to type III in

against polio, detected to type

37%. The serum

showed I polio
in this

that antiin 45% and

study was

screened for neutralizing antibody at a dilution of 1:8. The authors concluded that these children were apparently susceptible to polio and probably need to be reimmunized. To further study this problem Linnemann et aL7 studied 296 first-grade children and 319

Oral polio vaccine containing all three types of polio virus is now well accepted. We also know now that we can safely and effectively combine live viral vaccines-either in one shot as with measles-mumps-rubella vaccine or by different routes such as oral polio plus smallpox, measles, and mumps. Stokes et al.9 immunized 715 children aged 7 months to 7 years with a vaccine containing attenuated measles, mumps and rubella virus, combined into a 1-mi injection. These children had no detectable antibody to any of
these three viruses. They found that reactions,

mostly fever, were similar to those seen in children receiving measles immunization alone. Antibody to measles developed in 96% of the children, mumps antibody in 95%, and rubella antibody in 879

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94%. Other studies have confirmed the efficacy and safety of this combination. The individual vaccines which we commonly use can also be administered simultaneously. Karchmer et al.#{176} studied 235 children aged 9
months to doses 3 years. of oral vaccination, These polio children previously. had To received one group

SUMMARY From
be seen.

the

many and
produce is adequate

studies tetanus

cited are

several good plus

points immunizing

can

(1) Diphtheria
agents which

long-term for basic

immunity.

(2) A

two they

series a
of year

of two
later

diphtheria-tetanus

a booster

one
(3)

administered strain only

fever vaccination was similar

a dose
and

of trivalent
separate

oral Lynn

polio, strain
children

immunization.

smallpox

injections other

Schwartz mumps received

subsequent

measles one
in

and
The

Jeryl The
receiving

subcutaneously.

vaccine.
children

incidence
all

of
four

immunizations
measles version

was

similar
alone. whether

to
The

that

seen

with

rate of seroconthe vaccines were

Two injections of pertussis at least 60 days apart produce levels of agglutinin that are equal to the amount produced by three injections. (4) Prolonged time between the injections of the basic series of diphtheria-tetanus does not interfere with the final immunity. There is no need to restart a DPT series. (5) After the basic series and booster a DT every ten years is adequate to
preserve immunity. (6) A series of two trivalent

given singly or in combination. There are no published studies on the efficacy of combining in a single syringe several individual vaccines (i.e., a measles and a mumps vaccine) made by different manufacturers. The advantage to the child of receiving less shots is obvious. However, unexpected problems have resulted from combining vaccines. In the late 1950s a quadruple vaccine containing diphtheria-pertussis-tetanus Tests of the and killed polio of several virus lots was marketed. vaccine potency of this

oral polio doses eight weeks apart and a booster one year later is adequate for basic immunization. (7) Live viral vaccines can be given together, and, if desired, oral polio, smallpox, measles, and mumps can be given simultaneously. For a child over the age of 1 year who has had
no be immunizations, utilized. First the visit: following DPT (or schedule DT), could trivalent (or DT),

were conducted by the Massachusetts Department of Health. These tests showed that the antigenicity of the pertussis component of the vaccine was unexpectedly low if the vaccine was not used very promptly after manufacture. Immunizations against mumps, measles, and
rubella are given only once, antibody titers are

polio, tine test; two months later: DPT trivalent polio, measles; and one year later: trivalent polio. If desired, mumps and rubella
also current be given at the time of the second it is now visit. information available,

DT, can
With

possible

for us as physicians to adequately three visits the child who is out

immunization.

immunize of step

in with

not usually done, and no boosters are given. Therefore, until studies have been done to prove efficacy, combining individual vaccines from
different manufacturers into one shot can not be

REFERENCES
1. American Academy of Pediatrics: Report of the

recommended. TINE Testing important

it

Committee nois: AAP,

on Infectious 1974, p. 3.

Diseases.

Evanston,

Illi-

TESTING

for tuberculin reactivity is considered in routine well-child care. In addition,

that children who are known

is recommended

to be tuberculin reactors should losis therapy prior to receiving Many live viral vaccines interfere
testing,3 several days usually when the weeks to several after

receive tubercumeasles vaccine. with tuberculin

is attempted the vaccine is

testing

given. Berkovich and Starr4 studied the effect of live poiio type I vaccine on routine tuberculin testing. They found that the first decrease in tuberculin sensitivity occurred four to six weeks after ingestion of the vaccine and persisted for as long as two months. This effect was seen in only about one third of the children tested. In the remaining two thirds no change occurred. 880

C., Elliott, M. W., Peebles, T. C., Levine, L., and Eldred, M. C.: Excessive use of tetanus toxoid boosters. JAMA, 202:17, 1967. 3. Gold, H.: Active Immunization againt tetanus by means of tetanus toxoid alum-precipitated refined. J. Lab. Clin. Med., 23:903, 1938. 4. Peebles, T. C., Levine, L., Eldred, M. C., and Edsall, C.: Tetanus toxoid emergency boosters. N. EngI. J. Med., 280:575, 1969. 5. Communicable Disease Center, U.S Public Health Service: Recommendation of the Public Health Service Advisory Committee on Immunization

2.

Edsall,

Practices:
pertussis

Diphtheria
vaccine.
1971.

and

tetanus
and

toxoids

and

Morbidity

Mortality

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20:396,

Older, J. J., Drake, J., and Zimmerman, S.: Diphtheria immunization: Effect upon carriers and the control of outbreaks. A. J. Dis. Child., 123:197, L. W.,
1972.

7.

Scheibel, I., Bentzon, M. W., Christensen, P. E., Biering, A.: Duration of immunity to diphtheria

and and

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tetanus after active immunization. Microbiol. Scand., 67:380, 1966.

8. Pappenheimer, A. M., Edsall, G., Lawrence,

Acta

Pathol.

16. Lamb,

H. S., and 17.

H. J.: A study of reactions following adminof crude and purified diphtheria toxoid in an adult population. Am. J. Hyg., 52:353, 1950. 9. Sisk, C. W., and Lewis, C. E.: Reactions to tetanusBanton, istration
diphtheria toxoid 11:34, 1965. Peck#{235}tt, G.: Symposium

18.

C. A., and Feldman, H. A.: Rubella vaccine responses and other viral antibodies in Syracuse children. Am. J. Dis. Child., 122:117, 1971. Linnemann, C. C., Stefanovic, B. A., Shea, L., May, D. B., and Schiff, C. M.: Polio virus antibody in urban school children. J. Pediatr., 54:404, 1974. McCollough, R. H., Glezen, W. P., Lamb, C. A., and Chin, T. D. Y.: Booster effect of oral poliovaccine. Am. J. Dis. Child., 117:161, 1969.

(adult).

Arch.

Environ.
immunization in her 80th

Health,
in year. 19.

10.

honor
Health

of Dr.
Lab.

Pearl
Sci.,

on pertussis L. Kendrick
8:198, 1971.

Stokes,

J., Weibel, R. E., Villarejos, J. A., Buynak, E. B., and Hilleman, combined measles-mumps-rubella
218:57,

V. M., Arguedas, M. R.: Trivalent vaccine. JAMA,

11. Wilkins,
B.: 12. Strom,

J., Williams,

13.

14.

1971. experience of reactions, especially of a cerebral nature, in conjunction with triple vaccination: A study based on vaccinations in Sweden 1959-65. Br. Med. J., 4:320, 1967. Hardy, C. E., Hopkins, C. C., Linnemann, C. C., Hatch, M. H., Chambers, J. C., and Witte, J. J.: Trivalent oral poliovirus vaccine: A comparison of two infant immunization schedules. Pediatrics, 45:444, 1970. Marshall, R., Habicht, J., Landrigan, P. J., Foege, W. H., and Delgado, H.: Effectiveness of measles vaccine given simultaneously with DPT. J. Trop. Pediatr.,

Agglutinin Pediatr., 79: 197,

F. F., Wehrle, P. F., and Portnoy, response to pertussis vaccine. J.

20. Karchmer,

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15. Landrigan, P., communication, Noonan, June A., and 1974. Smith, E. A.: Oral

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1971. A. W., Friedman, J. P., Casey, H. L., Shope, T. C., Biker, J. B., Kappelman, M. M., and Witte, J. J.: Simultaneous administration of live virus vaccines. Am. J. Dis. Child., 121:382, 1971. Editorial: Quadruple vaccine. N. Engi. J. Med., 264:1214-15, 1961. Meliman, W. J., and Wetton, R.: Depression of the tuberculin reaction by attenuated measles virus vaccine. J. Lab. Clin. Med., 61:453, 1963. Kupers, T. A., Petrich, J. M., Holloway, A. W., and St. Geme, J. W., Jr.: Depression of tuberculin delayed hypersensitivity by live attenuated mumps virus. J. Pediatr., 76:716, 1970. Berkovich, S., and Starr, S.: Effects of live type I poliovirus vaccine and other viruses on the tuberculin test. N. Engl. J. Med., 274:67, 1966.

PEDIATRICS

FOR THE

CLINICIAN

881

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Children Out of Step With Immunization Carol F. Phillips Pediatrics 1975;55;877

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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright 1975 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on March 29, 2013