General Recommendations on Immunization

General Recommendations
on Immunization

This chapter discusses issues that are commonly encountered

in vaccination practices. A more thorough discussion of
issues common to more than one vaccine can be found in
the General Recommendations on Immunization:
Recommendations of the Advisory Committee on
Immunization Practices and the American Academy of
Family Physicians. These recommendations are revised
every 35 years as needed; the most current edition was
published in February 2002 (MMWR 2002;51(RR2):136).
A revised document is expected to be published in 2006.
All providers who administer vaccine should have a copy of
this report and be familiar with its contents. It can be
downloaded from the MMWR website or ordered in print
version from the Centers for Disease Control and Prevention.

Timing and Spacing of Vaccines

The timing and spacing of vaccine doses are two of the
most important issues in the appropriate use of vaccines.
Specific circumstances that are commonly encountered in
immunization practice are the timing of antibody-containing
blood products and live vaccines (particularly measles
vaccine), simultaneous and nonsimultaneous administration
of different vaccines, and the interval between subsequent
doses of the same vaccine.

General Rule
Inactivated vaccines generally are not affected by circulating
antibody to the antigen.
Live attenuated vaccines may be affected by circulating
antibody to the antigen.

AntibodyVaccine Interactions

The presence of circulating antibody to a vaccine antigen

may reduce or completely eliminate the immune response to
the vaccine. The amount of interference produced by
circulating antibody generally depends on the type of
vaccine administered and the amount of antibody.
Inactivated antigens are generally not substantially affected by
circulating antibody, so they can be administered before, after,
or at the same time as the antibody. Simultaneous
administration of antibody (in the form of immune globulin)
and vaccine is recommended for postexposure prophylaxis of
certain diseases, such as hepatitis B, rabies, and tetanus.

General Recommendations on Immunization

2

Live vaccines must replicate in order to cause an immune

response. Antibody against parenteral (injected) live vaccine
antigen may interfere with replication. If a live parenteral
vaccine (measles-mumps-rubella [MMR] or varicella) must
be given around the time that antibody is given, the two
must be separated by enough time so that the antibody does
not interfere with viral replication. If the live vaccine is
given first, it is necessary to wait at least 2 weeks (i.e., an
incubation period) before giving the antibody. If the interval
between the vaccine and antibody is less than 2 weeks, the
recipient should be tested for immunity or the vaccine dose
should be repeated.
If the antibody is given before a dose of MMR or varicella
vaccine, it is necessary to wait until the antibody has waned
(degraded) before giving the vaccine to reduce the chance
of interference by the antibody. The necessary interval
between an antibody-containing product and MMR or varicella
vaccine depends on the concentration of antibody in the
product. A table listing the recommended intervals between
administration of antibody products and live vaccines
(MMR and varicella) is included in Appendix A and in the
General Recommendations on Immunization. The interval
between administration of an antibody product and MMR
or varicella vaccination can be as long as 11 months.
Although passively acquired antibodies can interfere with
the response to rubella vaccine, the low dose of anti-Rho(D)
globulin administered to postpartum women has not been
demonstrated to reduce the response to the RA27/3 strain
rubella vaccine. Because of the importance of rubella
immunity among childbearing age women, postpartum
vaccination of rubella-susceptible women with rubella or
MMR vaccine should not be delayed because of receipt of
anti-Rho(D) globulin or any other blood product during the
last trimester of pregnancy or at delivery. These women
should be vaccinated immediately after delivery and, if
possible, tested 3 months later to ensure immunity to rubella
and, if necessary, to measles.
Oral typhoid, and yellow fever vaccines are not affected by
the administration of immune globulin or blood products.
They may be given simultaneously with blood products, or
separated by any interval. These vaccines are not affected
because few North Americans are immune to yellow fever or
typhoid. Consequently, donated blood products in the
United States do not contain a significant amount of
antibody to these organisms. The effect of circulating
antibody on live attenuated influenza vaccine is not known.
Two antibody products are available for the prevention of
respiratory syncytial virus (RSV) infection in infants and
young children. RSV-IG (RespiGam) is an intravenous

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General Recommendations on Immunization

human immune globulin product. RSV-IG contains other
human antibodies in addition to antibody to RSV, and
may interfere with live parenteral vaccines for as long as
9 months. Palivizumab (Synagis) contains only monoclonal
antibody to respiratory syncytial virus (RSV). It does not
interfere with the response to live virus vaccines.

General Rule
There is no contraindication to the simultaneous
administration of any vaccines.
Simultaneous and Nonsimultaneous
Administration

Simultaneous administration of the most widely used live

and inactivated vaccines does not result in decreased
antibody responses or increased rates of adverse reactions.
Simultaneous administration of all vaccines for which a child
is eligible can be very important in childhood vaccination
programs because it increases the probability that a child
will be fully immunized at the appropriate age. A study
during a measles outbreak in the early 1990s showed that
about one-third of measles cases in unvaccinated but
vaccine-eligible preschool children could have been
prevented if MMR had been administered at the same visit
when another vaccine was given.
Individual vaccines should not be mixed in the same syringe
unless they are licensed for mixing by the Food and Drug
Administration. Only the sanofi-pasteur Hib/DTaP (TriHIBit)
vaccine is licensed for mixing in the same syringe.
Nonsimultaneous Administration
of Different Vaccines

In some situations, vaccines that could be given simultaneously

are not (e.g., if the child is receiving vaccines from two
different providers). Live parenteral (injected) vaccines
(MMR, varicella, and yellow fever) and live attenuated
influenza vaccine (LAIV) that are not administered
simultaneously should be separated by at least 4 weeks.
This precaution is intended to reduce or eliminate interference
from the vaccine given first on the vaccine given later. If
two live parenteral vaccines or LAIV are not administered
simultaneously but are separated by less than 4 weeks, the
vaccine given second should be repeated in 4 weeks or
confirmed to be effective by serologic testing of the recipient
(serologic testing is not recommended for LAIV). An
exception to this recommendation is yellow fever vaccine

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General Recommendations on Immunization

administered less than 4 weeks after single-antigen measles
vaccine. A 1999 study demonstrated that yellow fever vaccine
is not affected by measles vaccine given 127 days earlier.
The effect of nonsimultaneously administered rubella,
mumps, varicella, and yellow fever vaccines is not known.

Live vaccines administered by the oral route (oral polio

vaccine [OPV], oral typhoid) are not believed to interfere
with each other if not given simultaneously. These vaccines
may be given at any time before or after each other. Oral
typhoid is not licensed for children younger than 6 years of
age, and OPV is no longer available in the United States, so
these vaccines are not likely to be given to the same child.
Parenteral live vaccines (MMR, varicella, and yellow fever)
and LAIV are not believed to have an effect on live vaccines
given by the oral route (OPV, oral typhoid). Live oral
vaccines may be given at any time before or after live
parenteral vaccines or LAIV.
All other combinations of two inactivated vaccines, or live
and inactivated vaccines, may be given at any time before
or after each other.

General Rule
Increasing the interval between doses of a multidose
vaccine does not diminish the effectiveness of the vaccine.
Decreasing the interval between doses of a multidose
vaccine may interfere with antibody response and protection.

Interval Between Doses

of the Same Vaccine

Immunizations are recommended for members of the

youngest age group at risk for a disease for whom efficacy,
immunogenicity, and safety of a vaccine have been
demonstrated. Most vaccines in the childhood immunization
schedule require two or more doses for stimulation of an
adequate and persisting antibody response. Studies have
demonstrated that recommended ages and intervals between
doses of the same antigen(s) provide optimal protection or
have the best evidence of efficacy. Table 1 of the General
Recommendations on Immunization (included in Appendix A)
shows the recommended minimal ages and minimal intervals between immunizations for vaccines in the
recommended childhood immunization schedule.

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General Recommendations on Immunization

Administering doses of a multidose vaccine at shorter than
the recommended intervals might be necessary when an
infant or child is behind schedule and needs to be brought
up-to-date quickly or when international travel is pending.
In these cases, an accelerated schedule using the minimum
age or minimum interval criteria can be used. Accelerated
schedules should not be used routinely.

Vaccine doses should not be administered at intervals less

than the recommended minimal intervals or earlier than
the minimal ages. Two exceptions to this may occur. The
first is for measles vaccine during a measles outbreak, when
the vaccine may be administered at an age younger than
12 months (this dose would not be counted, and would be
repeated at 12 months of age or older). The second consideration involves administering a dose a few days earlier than
the minimum interval or age, which is unlikely to have a
substantially negative effect on the immune response to that
dose. Although vaccinations should not be scheduled at an
interval or age less than the recommended minimums, a
child may have erroneously been brought to the office early,
or may have come for an appointment not specifically for
vaccination (for example, for an ear recheck). In these
situations, the clinician can consider administering the
vaccine earlier than the minimum interval or age. If the
parent/child is known to the clinician and is reliable, it is
preferable to reschedule the child for vaccination closer to
the recommended interval. If the parent/child is not known
to the clinician or is not reliable (e.g., habitually misses
appointments), it may be preferable to administer the
vaccine at that visit than to reschedule a later appointment
that may not be kept.
Vaccine doses administered up to 4 days before the minimum
interval or age can be counted as valid. This 4-day
recommendation does not apply to rabies vaccine because
of the unique schedule for this vaccine. Doses administered
5 days or earlier than the minimum interval or age should
not be counted as valid doses and should be repeated as age
appropriate. The repeat dose should be spaced after the
invalid dose by a time greater than the recommended
minimum interval shown in Table 1 of the General
Recommendations. In certain situations, local or state
requirements might mandate that doses of selected vaccines
be administered on or after specific ages, superseding these
4-day recommendations.
In some cases, a scheduled dose of vaccine may not be given
on time. If this occurs, the dose should be given at the next
visit. Not all permutations of all schedules for all vaccines
have been studied. However, available data indicate that
intervals between doses longer than those routinely recom-

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General Recommendations on Immunization

mended do not affect seroconversion rate or titer when the
schedule was completed. Consequently, it is not necessary
to restart the series or add doses of any vaccine because of
an extended interval between doses. The only exception to
this rule is oral typhoid vaccine in some circumstances. In
the case of oral typhoid, some experts recommend repeating
the series if the four-dose series is extended to more than
3 weeks.

General Rule
Live attenuated vaccines generally produce
long-lasting immunity with a single dose.
Inactivated vaccines require multiple doses and
may require periodic boosting to maintain immunity.
Number of Doses

For live injected vaccines, the first dose administered at the

recommended age usually provides protection. An additional
dose is given to ensure seroconversion. For instance, 95%
to 98% of recipients will respond to a single dose of measles
vaccine. The second dose is given to ensure that nearly 100%
of persons are immune (i.e., the second dose is
insurance). Immunity following live vaccines is
long-lasting, and booster doses are not necessary.
For inactivated vaccines, the first dose administered at the
recommended age usually does not provide protection
(hepatitis A vaccine is an exception). A protective immune
response may not develop until the second or third dose.
For inactivated vaccines, antibody titers may decrease
(wane) below protective levels after a few years. This
phenomenon is most notable for tetanus and diphtheria.
For these vaccines, periodic boosting is required.
An additional dose is given to raise antibody back to
protective levels.
Not all inactivated vaccines require boosting throughout life.
For example, Haemophilus influenzae type b (Hib) vaccine does
not require boosting because Hib disease is very rare in
children older than 5 years of age. Hepatitis B vaccine does
not require boosting because of immunologic memory to the
vaccine and the long incubation period of hepatitis B
(which can produce an autoboost).

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General Recommendations on Immunization

Adverse Reactions Following
Vaccination
Vaccines are intended to produce active immunity to specific
antigens. An adverse reaction is an untoward effect caused
by a vaccine that is extraneous to the vaccines primary
purpose of production of immunity. Adverse reactions are
also called vaccine side effect. A vaccine adverse event
refers to any adverse event that occurs following vaccination.
An adverse event could be a true vaccine reaction or just a
coincidental event, with further research needed to
distinguish between them.

Vaccine adverse reactions fall into three general categories:

local, systemic, and allergic. Local reactions are generally
the least severe and most frequent. Allergic reactions are
the most severe and least frequent.
The most common type of adverse reactions are local
reactions, such as pain, swelling, and redness at the site of
injection. Local reactions may occur with up to 50% of
vaccine doses, depending on the type of vaccine. Local
reactions are most common with inactivated vaccines,
particularly those, such as DTaP, that contain adjuvants.
Local adverse reactions generally occur within a few hours
of the injection and are usually mild and self-limited. On
rare occasions, local reactions may be very exaggerated or
severe. These are often referred to as hypersensitivity reactions,
although they are not allergic, as the term implies. These
reactions are also known as Arthus reactions, and are most
commonly seen with tetanus and diphtheria toxoids. Arthus
reactions are believed to be due to very high titers of
antibody, usually because of too many doses of toxoid.
Systemic adverse reactions are more generalized events and
include fever, malaise, myalgias (muscle pain), headache,
loss of appetite, and others. These symptoms are common
and nonspecific; they may occur in a vaccinated persons
because of the vaccine or may be caused by something
unrelated to the vaccine, like a concomitant viral infection.
Systemic adverse reactions were relatively frequent with
DTP vaccine, which contained a whole-cell pertussis component. However, comparison of the frequency of systemic
adverse events among vaccine and placebo recipients shows
they are not common with inactivated vaccines currently in
use, including acellular pertussis vaccine.
Systemic adverse reactions may occur following receipt of
live attenuated vaccines. Live attenuated vaccines must
replicate in order to produce immunity. The adverse
reactions that follow live attenuated vaccines, such as fever
or rash, represent symptoms produced from that replication
and are similar to a mild form of the natural disease.

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2

Systemic adverse reactions following live vaccines are usually

mild, and occur a week or two after the vaccine was given
(i.e., after an incubation period of the vaccine virus). LAIV
replicates in the mucous membranes of the nose and throat,
not in the lung. As a result, LAIV may cause upper respiratory
symptoms (like a cold) but not influenza-like symptoms.
A third type of vaccine adverse reaction is a severe
(anaphylactic) allergic reaction. The allergic reaction may
be caused by the vaccine antigen itself or some other
component of the vaccine, such as cell culture material,
stabilizer, preservatives, or antibiotic used to inhibit bacterial
growth. Severe allergic reactions to vaccines may be lifethreatening. Fortunately, they are very rare, occurring at a
rate of less than one in half a million doses. The risk of an
allergic reaction can be minimized by good screening prior
to vaccination. All providers who administer vaccines must
have an emergency protocol and supplies to treat anaphylaxis.
Reporting Vaccine Adverse Events

From 1978 to 1990, CDC conducted the Monitoring System

for Adverse Events Following Immunization (MSAEFI) in
the public sector. In 1990, MSAEFI was replaced by the
Vaccine Adverse Events Reporting System (VAERS), which
includes reporting from both public and private sectors.
Providers should report any clinically significant adverse
event that occurs after the administration of any vaccine
licensed in the United States.
Providers should report a clinically significant adverse event
even if they are unsure whether a vaccine caused the event.
The telephone number to call for answers to questions and
to obtain VAERS forms is 8008227967, or visit the
VAERS website at http://vaers.hhs.gov. VAERS now accepts
reports of adverse events through their online system.
(See Chapter 4, Vaccine Safety.)

Contraindications and Precautions

to Vaccination
Contraindications and precautions to vaccination generally
dictate circumstances when vaccines will not be given. Most
contraindications and precautions are temporary, and the
vaccine can be given at a later time.
A contraindication is a condition in a recipient that
increases the chance of a serious adverse reaction. It is a
condition in the recipient of the vaccine, not with the vaccine
per se. If the vaccine were given in the presence of that
condition, the resulting adverse reaction could seriously

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General Recommendations on Immunization

harm the recipient. For instance, administering influenza
vaccine to a person with a true anaphylactic allergy to egg
could cause serious illness or death in the recipient. In general,
vaccines should not be administered when a contraindication
condition is present.

A precaution is similar to a contraindication. A precaution

is a condition in a recipient that might increase the chance
or severity of a serious adverse reaction, or compromise the
ability of the vaccine to produce immunity (such as
administering measles vaccine to a person with passive
immunity to measles from a blood transfusion). Injury could
result, but the chance of this happening is less than with a
contraindication. In general, vaccines are deferred when a
precaution condition is present. However, situations may
arise when the benefit of protection from the vaccine
outweighs the risk of an adverse reaction, and a provider
may decide to give the vaccine. For example, prolonged
crying or a high fever after a dose of whole-cell or acellular
pertussis vaccine is considered a precaution to subsequent
doses of pediatric pertussis vaccine. But if the child were at
high risk of pertussis exposure (e.g., during a pertussis
outbreak in the community), a provider may choose to
vaccinate the child and treat the adverse reaction if it
occurs. In this example, the benefit of protection from the
vaccine outweighs the harm potentially caused by the vaccine.
There are very few true contraindication and precaution
conditions. Only two of these conditions are generally
considered to be permanent: severe (anaphylactic) allergic
reaction to a vaccine component or following a prior dose
of a vaccine, and encephalopathy not due to another
identifiable cause occurring within 7 days of vaccination.
Four conditions are considered permanent precautions to
further doses of pediatric pertussis-containing vaccine:
o
temperature greater than 105 F, collapse or shock-like state
(hypotonic hyporesponsive episode), persistent inconsolable
crying lasting 3 or more hours occurring within 48 hours of
a dose, or a seizure, with or without fever, occurring within
3 days of a dose. The occurrence of one of these events
following DTaP vaccine is not a precaution to pertussis
vaccination of an adolescent or adult.
Two conditions are temporary contraindications to vaccination
with live vaccines: pregnancy and immunosuppression.
Two conditions are temporary precautions to vaccination:
moderate or severe acute illness (all vaccines), and recent
receipt of an antibody-containing blood product (MMR
and varicella only).

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General Recommendations on Immunization

Allergy

A severe (anaphylactic) allergic reaction following a dose of

vaccine will almost always contraindicate a subsequent dose
of that vaccine. Severe allergies are those that are mediated
by IgE, occur within minutes or hours of receiving the
vaccine, and require medical attention. Examples of severe
allergic reactions are generalized urticaria (hives), swelling
of the mouth and throat, difficulty breathing, wheezing,
hypotension, or shock. With appropriate screening these
reactions are very rare following vaccination.
A table listing vaccine contents is included in Appendix B.
Persons may be allergic to the vaccine antigen, animal
protein, antibiotics, preservatives, or stabilizers. The most
common animal protein allergen is egg protein found in
vaccines prepared using embryonated chicken eggs (e.g.,
yellow fever and influenza vaccines). Ordinarily, persons
who are able to eat eggs or egg products can receive
vaccines that contain egg; persons with histories of
anaphylactic or anaphylactic-like allergy to eggs or egg
proteins should not. Asking persons whether they can eat
eggs without adverse effects is a reasonable way to screen
for those who might be at risk from receiving yellow fever
and influenza vaccines.
Several studies have shown that children who have a
history of severe allergy to eggs rarely have reactions to
MMR vaccine. This is probably because measles and mumps
vaccine viruses are both grown in chick embryo fibroblasts,
not actually in eggs. It appears that gelatin, not egg, might
be the cause of allergic reactions to MMR. As a result, in
1998, the Advisory Committee on Immunization Practices
removed severe egg allergy as a contraindication to measles
and mumps vaccines. Egg-allergic children may be vaccinated
with MMR without prior skin testing.
Certain vaccines contain trace amounts of neomycin.
Persons who have experienced anaphylactic reactions to
neomycin should not receive these vaccines. Most often,
a neomycin allergy reaction is a contact dermatitis, a
manifestation of a delayed-type (cell-mediated) immune
response, rather than anaphylaxis. A history of delayed-type
reactions to neomycin is not a contraindication for
administration of these vaccines.
Latex is liquid sap from the commercial rubber tree. Latex
contains naturally occurring impurities (e.g., plant proteins
and peptides), which are believed to be responsible for allergic
reactions. Latex is processed to form natural rubber latex
and dry natural rubber. Dry natural rubber and natural
rubber latex might contain the same plant impurities as
latex but in a lesser amounts. Natural rubber latex is used to
produce medical gloves, catheters, and other products. Dry

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natural rubber is used in syringe plungers, vial stoppers, and
injection ports on intravascular tubing. Synthetic rubber
and synthetic latex also are used in medical gloves, syringe
plungers, and vial stoppers. Synthetic rubber and synthetic
latex do not contain natural rubber or natural latex, and
therefore, do not contain the impurities linked to allergic
reactions.

The most common type of latex sensitivity is contact-type

(type 4) allergy, usually as a result of prolonged contact with
latex-containing gloves. However, injection-procedureassociated
latex allergies among diabetic patients have been described.
Allergic reactions (including anaphylaxis) after vaccination
procedures are rare. Only one report of an allergic reaction
after administration of hepatitis B vaccine in a patient with
known severe allergy (anaphylaxis) to latex has been published.
If a person reports a severe (anaphylactic) allergy to latex,
vaccines supplied in vials or syringes that contain natural
rubber should not be administered unless the benefit of
vaccination clearly outweighs the risk of an allergic reaction
to the vaccine. For latex allergies other than anaphylactic
allergies (e.g., a history of contact allergy to latex gloves),
vaccines supplied in vials or syringes that contain dry
natural rubber or natural rubber latex can be administered.
Pregnancy

The concern about vaccinating pregnant women is with

infection of the fetus and is theoretical. Only smallpox
(vaccinia) vaccine has been shown to cause fetal injury.
However, since the theoretical possibility exists, live vaccines
should not be given to women known to be pregnant.
Since inactivated vaccines cannot replicate, they cannot
cause fetal infection. Inactivated vaccines should be
administered to pregnant women for whom they are
indicated. Susceptible household contacts of pregnant
women should receive MMR and varicella vaccines and
may receive LAIV, if eligible.
Immunosuppression

Live vaccines can cause severe or fatal reactions in

immunosuppressed persons due to uncontrolled replication
of the vaccine virus, particularly vaccinia and oral polio
vaccine virus (and rarely measles and varicella vaccine
virus). Severely immunosuppressed persons should not be
given live vaccines for this reason. Persons with isolated
B-cell deficiency may receive varicella vaccine. Inactivated
vaccines cannot replicate, so they are safe to use in
immunosuppressed persons. However, response to the
vaccine may be decreased.

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2

Both diseases and drugs can cause significant immunosuppression. Persons with congenital immunodeficiency,
leukemia, lymphoma, or generalized malignancy should not
receive live vaccines. OPV should not be given if an
immunosuppressed person is in the household. However,
MMR, varicella vaccines, and LAIV may be given when an
immunosuppressed person lives in the same house.
Certain drugs may cause immunosuppression. For instance,
persons receiving cancer treatment with alkylating agents or
antimetabolites, or radiation therapy should not be given
live vaccines. Live vaccines can be given after chemotherapy
has been discontinued for at least 3 months. Persons receiving
large doses of corticosteroids should not receive live vaccines.
For example, this would include persons receiving
20 milligrams or more of prednisone daily or 2 or more
milligrams of prednisone per kilogram of body weight per
day for 14 days or longer.
Aerosolized steroids, such as inhalers for asthma, are not
contraindications to vaccination, nor are alternate-day,
rapidly tapering, and short (less than 14 days) high-dose
schedules, topical formulations, and physiologic replacement
schedules.
The safety and efficacy of live attenuated vaccines
administered concurrently with recombinant human
immune mediators and immune modulators is not known.
There is evidence that use of therapeutic monoclonal
antibodies, especially the anti-tumor necrosis factor agents
adalimumab, infliximab, and etanercept, may lead to
reactivation of latent tuberculosis infection and tuberculosis
disease and predispose to other opportunistic infections.
Because the safety of live attenuated vaccines for persons
receiving these drugs is not known, it is prudent to avoid
administration of live attenuated vaccines for at least a
month following treatment with these drugs.
Inactivated vaccines are not contraindicated for immunosuppressed persons. However, response to the vaccine may
be poor. Because a relatively functional immune system is
required to develop an immune response to a vaccine, an
immunosuppressed person may not be protected even if the
vaccine has been given. Additional recommendations for
vaccination of immunosuppressed persons are detailed in
the General Recommendations on Immunization.
HIV Infection

Persons infected with human immunodeficiency virus

(HIV) may have no symptoms, or may be severely immunosuppressed. In general, the same vaccination recommendations
apply as with other types of immunosuppression. Live-virus
vaccines are usually contraindicated, but inactivated vaccines
are not contraindicated.

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General Recommendations on Immunization

Measles and varicella can be very severe illnesses in persons
with HIV infection and are often associated with complications.
Therefore, measles vaccine (as combination MMR vaccine)
and varicella vaccine are recommended for persons with
HIV infection who are asymptomatic or mildly immunosuppressed. However, persons with severe immunosuppression
due to HIV infection should not receive measles vaccine,
MMR, or varicella vaccine. Susceptible household contacts
of persons with HIV infection should receive MMR and
varicella vaccines. Persons with HIV infection should not
receive LAIV; they should receive inactivated influenza vaccine.

Vaccination of Hematopoietic Stem Cell

Transplant Recipients

Hematopoietic stem cell transplant (HSCT) is the infusion

of hematopoietic stem cells from a donor into a patient who
has received chemotherapy and often radiation, both of
which are usually bone marrow ablative. HSCT is used to
treat a variety of neoplastic diseases, hematologic disorders,
immunodeficiency syndromes, congenital enzyme deficiencies,
and autoimmune disorders. HSCT recipients can receive
either their own cells (i.e., autologous HSCT) or cells from
a donor other than the transplant recipient (i.e., allogeneic
HSCT).
Antibody titers to vaccine-preventable diseases (e.g.,
tetanus, poliovirus, measles, mumps, rubella, and encapsulated
bacteria [i.e., Streptococcus pneumoniae and Haemophilus
influenzae type b]) decline during the 14 years after allogeneic
or autologous HSCT if the recipient is not revaccinated.
HSCT recipients are at increased risk for certain vaccinepreventable diseases. As a result, HSCT recipients should be
routinely revaccinated after HSCT, regardless of the source
of the transplanted stem cells. Revaccination with inactivated
vaccines should begin 12 months after HSCT. An exception
to this recommendation is for influenza vaccine, which
should be administered 6 months after HSCT and annually
thereafter for the life of the recipient. MMR vaccine should
be administered 24 months after transplantation if the
HSCT recipient is presumed to be immunocompetent.
Varicella, meningococcal, and pneumococcal conjugate
vaccines are not currently recommended for HSCT recipients
because of insufficient experience using these vaccines
among HSCT recipients.
Household and other close contacts of HSCT recipients and
healthcare workers who care for HSCT recipients should be
appropriately vaccinated, particularly against influenza,
measles, and varicella. Additional details of vaccination of
HSCT recipients and their contacts can be found in a CDC
report on this topic available at
http://www.cdc.gov/nip/publications/hsct-recs.pdf.

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Moderate or Severe Acute Illness

There is no evidence that a concurrent acute illness reduces

vaccine efficacy or increases vaccine adverse events. The
concern is that an adverse reaction (particularly fever)
following vaccination could complicate the management of
a severely ill person. If a person has a moderate or severe
acute illness, vaccination with both live and inactivated
vaccines should be delayed until the illness has improved.
Minor, common illnesses (such as otitis media, upper
respiratory infections, colds, and diarrhea) are NOT
contraindications to vaccination.

Invalid Contraindications
to Vaccination
Some healthcare providers inappropriately consider certain
conditions or circumstances to be true contraindications or
precautions to vaccinations. Such conditions or circumstances
are known as invalid contraindications; they result in missed
opportunities to administer needed vaccines. Some of the
most common invalid contraindications are minor illnesses,
conditions related to pregnancy and breastfeeding, allergies
that are not anaphylactic in nature, and certain aspects of
the patients family history.
Minor Illness

Children with mild acute illnesses, such as low-grade fever,

upper respiratory infection (URI), colds, otitis media, and
mild diarrhea, can and should be vaccinated.
Several large studies have shown that young children with
URI, otitis media, diarrhea, and/or fever respond to measles
vaccine as well as those without these conditions. These
large studies refute the results of an earlier small study
(Krober, JAMA 1991) which suggested that minor infections
such as URIs might impair the response to measles vaccine.
Further, there is no evidence that mild diarrhea reduces the
success of immunization of infants in this country.
Low-grade fever is not a contraindication to immunization.
Temperature measurement is not necessary before
immunization if the infant or child does not appear ill and
the parent does not say the child is currently ill.
Antimicrobial Therapy

Antimicrobial agents do not have an effect on the immune

response to a vaccine. No commonly used antibiotic or
antiviral agent will inactivate a live-virus vaccine.

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General Recommendations on Immunization

Disease Exposure or Convalescence

If a child is not moderately or severely ill, he or she should

be vaccinated. There is no evidence that either disease
exposure or convalescence will affect the response to a
vaccine or increase the likelihood of an adverse event.

Pregnancy or Immunosuppression in the

Household or Breastfeeding

It is critical that healthy household contacts of pregnant

women and immunosuppressed persons be vaccinated.
Vaccination of healthy contacts reduces the chance of
exposure of pregnant women and immunosuppressed persons.
Most vaccines, including live vaccines (MMR, varicella,
and yellow fever), can be given to infants or children who
are household contacts of pregnant or immunosuppressed
persons, as well as to breastfeeding infants. Vaccinia (smallpox)
vaccine is not recommended for household contacts of a
pregnant or immunosuppressed person in nonemergency
situations. Live attenuated influenza vaccine should not be
administered to persons who have contact with severely
immunosuppressed persons who are hospitalized and require
care in a protected environment (i.e., who are in isolation
because of immunosuppression). LAIV may be administered
to contacts of persons with lesser degrees of immunosuppression.
Measles and mumps vaccine viruses produce a noncommunicable infection and are not transmitted to household
contacts. Rubella vaccine virus has been shown to be shed
in human milk, but transmission to an infant has rarely
been documented. Transmission of varicella vaccine virus is
not common, and most women and older immunosuppressed
persons are immune from having had chickenpox. LAIV
may be administered to a woman who is breastfeeding if she
is otherwise eligible. The risk of transmission of vaccine
virus is not known but is probably low. Breastfeeding does
not decrease the response to routine childhood vaccines.
Breastfeeding also does not extend or improve the passive
immunity to vaccine-preventable disease that is provided by
maternal antibody.
Premature Birth

Vaccines should be started on schedule based on the childs

chronological age. Premature infants have been shown to
respond adequately to vaccines used in infancy.
Studies demonstrate that decreased seroconversion rates
might occur among certain premature infants with low
birth weights (less than 2,000 grams) after administration
of hepatitis B vaccine at birth. However, by 1 month
chronological age, all premature infants, regardless of
initial birthweight or gestational age are as likely to
respond as adequately as older and larger infants.

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General Recommendations on Immunization

2

All premature infants born to hepatitis B surface antigen

(HBsAg)positive mothers and mothers with unknown
HBsAg status must receive immunoprophylaxis with hepatitis B vaccine and hepatitis B immunoglobulin (HBIG) within 12 hours after birth. If these infants weigh less than 2,000
grams at birth, the initial vaccine dose should not be counted toward completion of the hepatitis B vaccine series, and
three additional doses of hepatitis B vaccine should be
administered beginning when the infant is 1 month of age.
The optimal timing of the first dose of hepatitis B vaccine
for premature infants of HBsAg-negative mothers with a
birth weight of less than 2,000 grams has not been determined.
These infants can begin the first dose of the hepatitis B vaccine
series at 1 month of chronological age. Premature infants
discharged from the hospital prior to 1 month chronological
age may also be given hepatitis B vaccine at discharge if
they are medically stable and showing consistent weight gain.
NonVaccine-Related Allergies

Infants and children with nonspecific allergies, duck or

feather allergy, or allergy to penicillin, children who have
relatives with allergies, and children taking allergy shots can
and should be immunized. No vaccine available in the
United States contains duck antigen or penicillin.
Nonanaphylactic Allergy to
Vaccine Component

Anaphylactic allergy to a vaccine component (such as egg

or neomycin) is a true contraindication to vaccination.
Nonanaphylactic allergy to a vaccine constituent is not a
contraindication to that vaccine.
Family History of Adverse Events

The only family history that is relevant in the decision to

vaccinate a child is immunosuppression. A family history of
adverse reactions unrelated to immunosupression or family
history of seizures or sudden infant death syndrome is not a
contraindication to vaccination. Varicella virus vaccine
should not be administered to persons who have a family
history of congenital or hereditary immunodeficiency in
first-degree relatives (e.g., parents and siblings) unless the
immune competence of the potential vaccine recipient has
been clinically substantiated or verified by a laboratory.
Tuberculosis Skin Test (PPD)

Infants and children who need TB skin tests can and should
be immunized. All vaccines, including MMR, can be given
on the same day as a TB skin test, or any time after a TB
skin test is applied. For most vaccines, there are no TB skin
test timing restrictions at all.

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General Recommendations on Immunization

MMR vaccine may decrease the response to a TB skin test,
causing a false-negative response in someone who actually
has an infection with tuberculosis. MMR can be given the
same day as a TB skin test, but if MMR has been given and
1 or more days have elapsed, in most situations a wait of 46
weeks is recommended before giving a routine TB skin test.
No information on the effect of varicella vaccine or LAIV
on a TB skin test is available. Until such information is
available, it is prudent to apply rules for spacing measles
vaccine and TB skin testing to varicella vaccine and LAIV.

Screening for Contraindications and

Precautions to Vaccination
The key to preventing serious adverse reactions is screening.
Every person who administers vaccines should screen
every patient for contraindications and precautions before
giving the vaccine dose. Effective screening is not difficult
or complicated and can be accomplished with just a few
questions.

How is your child (or how are you) today?

This question screens for concurrent moderate or acute illness.
If the child has been examined, this question may not be
necessary or may have already been asked.

Does your child have any allergies

to any food or medication?
A severe allergic reaction to a vaccine component is a
contraindication to vaccination, so this question must
always be asked. It may be more time-efficient to inquire
about allergies in a generic way (i.e., any food or medication)
rather than to inquire about specific vaccine components.
Most parents will not be familiar with minor components of
vaccine, but they should know if the child has had an allergic
reaction to a food or medication that was severe enough to
require medical attention.

Did the child have any problems after

his or her last shots?
This open-ended question explores for allergic reactions to
previous doses and for conditions following pertussis vaccine
that may be precautions to additional doses, such as high
fever or a hypotonic episode.

Does the child have any problems with

his or her immune system?
This question will help identify children with immunodeficiency who generally should not receive live attenuated
vaccines, particularly oral polio vaccine.
continues

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General Recommendations on Immunization

2

Does anyone in your household have a problem

with their immune system?
Oral polio vaccine should not be given to a healthy person
who has household contact with someone who is immunodeficient. LAIV should not be given to household contacts of
severely immunosuppressed persons.

Has the child received any blood products in the last year,
like a transfusion, or immune globulin?
This question helps identify precautions for live attenuated
MMR and varicella vaccines, which should not be given to
persons who have received passive antibody in the last few
months. The question may also expose unreported illnesses
that might not have been revealed in earlier questions.

Are you pregnant, or trying to become pregnant?

This question should be asked of all adolescent and adult
women. MMR, varicella, smallpox (vaccinia), and LAIV
vaccines should not be given to women known to be pregnant
or for 4 weeks prior to pregnancy. Persons with a pregnant
household contact should not receive smallpox (vaccinia)
vaccine in nonemergency situations. ACIP does not
recommend pregnancy testing prior to administration of
any vaccine.
Every person should be screened for contraindications and
precautions before vaccination. Standardized screening
forms for both children and adults, developed by the
Immunization Action Coalition, are included in Appendix A.
Selected References

American Academy of Pediatrics. Active and passive

immunization. In: Pickering LK, ed. Red Book: 2003 Report
of the Committee on Infectious Diseases. Elk Grove Village, IL:
American Academy of Pediatrics;2003:198
Atkinson W, Pickering LK, Watson JC, Peter G. General
immunization practices. In: Plotkin SA, OrentseinWA, eds.
Vaccines. 4th ed., Philadelphia, PA: Saunders;2003:91122.
CDC. General recommendations on immunization: recommendations of the Advisory Committee on Immunization
Practices and the American Academy of Family Physicians.
MMWR 2002;51(RR-2):136.
CDC. Recommendations of the Advisory Committee on
Immunization Practices: use of vaccines and immune globulins
in persons with altered immunocompetence. MMWR
1993;42(RR-4):118.

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General Recommendations on Immunization

CDC. Guidelines for preventing opportunistic infections
among hematopoietic stem cell transplant recipients:
recommendations of CDC, the Infectious Disease Society of
America, and the American Society of Blood and Marrow
Transplantation. MMWR 2000;49(RR-10):1128.

Dietz VJ, Stevenson J, Zell ER, et al. Potential impact on

vaccination coverage levels by administering vaccines
simultaneously and reducing dropout rates. Arch Pediatr
Adolesc Med 1994;148:9439.
James JM, Burks AW, Roberson RK, Sampson HA. Safe
administration of the measles vaccine to children allergic
to eggs. N Engl J Med 1995;332:12629.
King GE, Hadler SC. Simultaneous administration of
childhood vaccines: an important public health policy that
is safe and efficacious. Pediatr Infect Dis J 1994;13:394407.
Plotkin SA. Vaccines, vaccination and vaccinology. J. Infect
Dis 2003;187:134959.

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