Subject: General Recommendations on Immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP)
From: <Salvato con Microsoft Internet Explorer 5>
Date: Sun, 30 May 2004 19:30:59 +0200

General Recommendations on
Immunization

Recommendations of the Advisory Committee on Immunization
Practices (ACIP) and the American Academy of Family Physicians
(AAFP)

Prepared by
William L. Atkinson, M.D.1
Larry K.
Pickering, M.D.2
Benjamin Schwartz,
M.D.3
Bruce G. Weniger, M.D.3
John K.
Iskander, M.D.3
John C. Watson,
M.D.4
1Immunization Services
Division
2Office of the Director
3Epidemiology
and Surveillance Division
National Immunization
Program
4Division of Parasitic Diseases
National Center
for Infectious Diseases

The material in this report was prepared for publication by the
National Immunization Program, Walter A. Orenstein, M.D., Director; and
the Immunization Services Division, Lance E. Rodewald, M.D.,
Director.

Summary

This report is a revision of General Recommendations on Immunization
and updates the 1994 statement by the Advisory Committee on Immunization
Practices (ACIP) (CDC. General recommendations on immunization:
recommendations of the Advisory Committee on Immunization Practices
[ACIP]. MMWR 1994;43[No. RR-1]:1--38). The principal changes include
expansion of the discussion of vaccination spacing and timing,
recommendations for vaccinations administered by an incorrect route,
information regarding needle-free injection technology, vaccination of
children adopted from countries outside the United States, timing of
live-virus vaccination and tuberculosis screening, expansion of the
discussion and tables of contraindications and precautions regarding
vaccinations, and addition of a directory of immunization resources. These
recommendations are not comprehensive for each vaccine. The most recent
ACIP recommendations for each specific vaccine should be consulted for
additional details. This report, ACIP recommendations for each vaccine,
and other information regarding immunization can be accessed at CDC's
National Immunization Program website at http://www.cdc.gov/nip (accessed October
11, 2001).

Introduction

This report provides technical guidance regarding common immunization
concerns for health-care providers who administer vaccines to children,
adolescents, and adults. Vaccine recommendations are based on
characteristics of the immunobiologic product, scientific knowledge
regarding the principles of active and passive immunization, the
epidemiology and burden of diseases (i.e., morbidity, mortality, costs of
treatment, and loss of productivity), the safety of vaccines, and the cost
analysis of preventive measures as judged by public health officials and
specialists in clinical and preventive medicine.

Benefits and risks are associated with using all immunobiologics. No
vaccine is completely safe or 100% effective. Benefits of vaccination
include partial or complete protection against the consequences of
infection for the vaccinated person, as well as overall benefits to
society as a whole. Benefits include protection from symptomatic illness,
improved quality of life and productivity, and prevention of death.
Societal benefits include creation and maintenance of herd immunity
against communicable diseases, prevention of disease outbreaks, and
reduction in health-care--related costs. Vaccination risks range from
common, minor, and local adverse effects to rare, severe, and
life-threatening conditions. Thus, recommendations for immunization
practices balance scientific evidence of benefits for each person and to
society against the potential costs and risks of vaccination programs.

Standards for child and adolescent immunization practices and standards
for adult immunization practices (1,2)
have been published to assist with implementing vaccination programs and
maximizing their benefits. Any person or institution that provides
vaccination services should adopt these standards to improve immunization
delivery and protect children, adolescents, and adults from
vaccine-preventable diseases.

To maximize the benefits of vaccination, this report provides general
information regarding immunobiologics and provides practical guidelines
concerning vaccine administration and technique. To minimize risk from
vaccine administration, this report delineates situations that warrant
precautions or contraindications to using a vaccine. These recommendations
are intended for use in the United States because vaccine availability and
use, as well as epidemiologic circumstances, differ in other countries.
Individual circumstances might warrant deviations from these
recommendations. The relative balance of benefits and risks can change as
diseases are controlled or eradicated. For example, because wild
poliovirus transmission has been interrupted in the United States since
1979, the only indigenous cases of paralytic poliomyelitis reported since
that time have been caused by live oral poliovirus vaccine (OPV). In 1997,
to reduce the risk for vaccine-associated paralytic polio (VAPP),
increased use of inactivated poliovirus vaccine (IPV) was recommended in
the United States (3).
In 1999, to eliminate the risk for VAPP, exclusive use of IPV was
recommended for routine vaccination in the United States (4),
and OPV subsequently became unavailable for routine use. However, because
of superior ability to induce intestinal immunity and to prevent spread
among close contacts, OPV remains the vaccine of choice for areas where
wild poliovirus is still present. Until worldwide eradication of
poliovirus is accomplished, continued vaccination of the U.S. population
against poliovirus will be necessary.

Timing and Spacing of
Immunobiologics

General Principles for Vaccine Scheduling

Optimal response to a vaccine depends on multiple factors, including
the nature of the vaccine and the age and immune status of the recipient.
Recommendations for the age at which vaccines are administered are
influenced by age-specific risks for disease, age-specific risks for
complications, ability of persons of a certain age to respond to the
vaccine, and potential interference with the immune response by passively
transferred maternal antibody. Vaccines are recommended for members of the
youngest age group at risk for experiencing the disease for whom efficacy
and safety have been demonstrated.

Certain products, including inactivated vaccines, toxoids, recombinant
subunit and polysaccharide conjugate vaccines, require administering
>2 doses for development of an adequate and persisting antibody
response. Tetanus and diphtheria toxoids require periodic reinforcement or
booster doses to maintain protective antibody concentrations. Unconjugated
polysaccharide vaccines do not induce T-cell memory, and booster doses are
not expected to produce substantially increased protection. Conjugation
with a protein carrier improves the effectiveness of polysaccharide
vaccines by inducing T-cell--dependent immunologic function. Vaccines that
stimulate both cell-mediated immunity and neutralizing antibodies (e.g.,
live attenuated virus vaccines) usually can induce prolonged, often
lifelong immunity, even if antibody titers decline as time progresses
(5). Subsequent exposure to infection usually does not lead to
viremia but to a rapid anamnestic antibody response.

Approximately 90%--95% of recipients of a single dose of a parenterally
administered live vaccine at the recommended age (i.e., measles, mumps,
rubella [MMR], varicella, and yellow fever), develop protective antibody
within 2 weeks of the dose. However, because a limited proportion of
recipients (<5%) of MMR vaccine fail to respond to one dose, a
second dose is recommended to provide another opportunity to develop
immunity (6).
The majority of persons who fail to respond to the first dose of MMR
respond to a second dose (7). Similarly, approximately 20% of
persons aged >13 years fail to respond to the first dose of
varicella vaccine; 99% of recipients seroconvert after two doses (8).

The recommended childhood vaccination schedule is revised annually and
is published each January. Recommendations for vaccination of adolescents
and adults are revised less frequently, except for influenza vaccine
recommendations, which are published annually. Physicians and other
health-care providers should always ensure that they are following the
most up-to-date schedules, which are available from CDC's National
Immunization Program website at http://www.cdc.gov/nip (accessed October
11, 2001).

Spacing of Multiple Doses of the Same Antigen

Vaccination providers are encouraged to adhere as closely as possible
to the recommended childhood immunization schedule. Clinical studies have
reported that recommended ages and intervals between doses of multidose
antigens provide optimal protection or have the best evidence of efficacy.
Recommended vaccines and recommended intervals between doses are provided
in this report (Table
1).

In certain circumstances, administering doses of a multidose vaccine at
shorter than the recommended intervals might be necessary. This can occur
when a person is behind schedule and needs to be brought up-to-date as
quickly as possible or when international travel is impending. In these
situations, an accelerated schedule can be used that uses intervals
between doses shorter than those recommended for routine vaccination.
Although the effectiveness of all accelerated schedules has not been
evaluated in clinical trials, the Advisory Committee on Immunization
Practices (ACIP) believes that the immune response when accelerated
intervals are used is acceptable and will lead to adequate protection. The
accelerated, or minimum, intervals and ages that can be used for
scheduling catch-up vaccinations is provided in this report (Table
1). Vaccine doses should not be administered at intervals less than
these minimum intervals or earlier than the minimum age.*

In clinical practice, vaccine doses occasionally are administered at
intervals less than the minimum interval or at ages younger than the
minimum age. Doses administered too close together or at too young an age
can lead to a suboptimal immune response. However, administering a dose a
limited number of days earlier than the minimum interval or age is
unlikely to have a substantially negative effect on the immune response to
that dose. Therefore, ACIP recommends that vaccine doses administered
<4 days before the minimum interval or age be counted as
valid.† However, because of its unique schedule, this
recommendation does not apply to rabies vaccine (9).
Doses administered >5 days 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 the recommended minimum interval as provided in this report (Table
1). For example, if Haemophilus influenzae type b (Hib) doses
one and two were administered only 2 weeks apart, dose two is invalid and
should be repeated. The repeat dose should be administered >4
weeks after the invalid (second) dose. The repeat dose would be counted as
the second valid dose. Doses administered >5 days before the
minimum age should be repeated on or after the child reaches the minimum
age and >4 weeks after the invalid dose. For example, if
varicella vaccine were administered at age 10 months, the repeat dose
would be administered no earlier than the child's first birthday.

Certain vaccines produce increased rates of local or systemic reactions
in certain recipients when administered too frequently (e.g., adult
tetanus-diphtheria toxoid [Td], pediatric diphtheria-tetanus toxoid [DT],
and tetanus toxoid) (10,11). Such reactions are thought to result
from the formation of antigen-antibody complexes. Optimal record keeping,
maintaining patient histories, and adhering to recommended schedules can
decrease the incidence of such reactions without adversely affecting
immunity.

Simultaneous Administration

Experimental evidence and extensive clinical experience have
strengthened the scientific basis for administering vaccines
simultaneously (i.e., during the same office visit, not combined in the
same syringe). Simultaneously administering all vaccines for which a
person is eligible is critical, including for childhood vaccination
programs, because simultaneous administration increases the probability
that a child will be fully immunized at the appropriate age. A study
conducted during a measles outbreak demonstrated that approximately one
third of measles cases among unvaccinated but vaccine-eligible preschool
children could have been prevented if MMR had been administered at the
same visit when another vaccine was administered (12). Simultaneous
administration also is critical when preparing for foreign travel and if
uncertainty exists that a person will return for further doses of vaccine.

Simultaneously administering the most widely used live and inactivated
vaccines have produced seroconversion rates and rates of adverse reactions
similar to those observed when the vaccines are administered separately
(13--16). Routinely administering all vaccines simultaneously is
recommended for children who are the appropriate age to receive them and
for whom no specific contraindications exist at the time of the visit.
Administering combined MMR vaccine yields results similar to administering
individual measles, mumps, and rubella vaccines at different sites.
Therefore, no medical basis exists for administering these vaccines
separately for routine vaccination instead of the preferred MMR combined
vaccine (6).
Administering separate antigens would result in a delay in protection for
the deferred components. Response to MMR and varicella vaccines
administered on the same day is identical to vaccines administered a month
apart (17). No evidence exists that OPV interferes with
parenterally administered live vaccines. OPV can be administered
simultaneously or at any interval before or after parenteral live
vaccines. No data exist regarding the immunogenicity of oral Ty21a typhoid
vaccine when administered concurrently or within 30 days of live virus
vaccines. In the absence of such data, if typhoid vaccination is
warranted, it should not be delayed because of administration of virus
vaccines (18).

Simultaneously administering pneumococcal polysaccharide vaccine and
inactivated influenza vaccine elicits a satisfactory antibody response
without increasing the incidence or severity of adverse reactions
(19). Simultaneously administering pneumococcal polysaccharide
vaccine and inactivated influenza vaccine is strongly recommended for all
persons for whom both vaccines are indicated.

Hepatitis B vaccine administered with yellow fever vaccine is as safe
and immunogenic as when these vaccines are administered separately
(20). Measles and yellow fever vaccines have been administered
safely at the same visit and without reduction of immunogenicity of each
of the components (21,22).

Depending on vaccines administered in the first year of life, children
aged 12--15 months can receive <7 injections during a single
visit (MMR, varicella, Hib, pneumococcal conjugate, diphtheria and tetanus
toxoids and acellular pertussis [DTaP], IPV, and hepatitis B vaccines). To
help reduce the number of injections at the 12--15-month visit, the IPV
primary series can be completed before the child's first birthday. MMR and
varicella vaccines should be administered at the same visit that occurs as
soon as possible on or after the first birthday. The majority of children
aged 1 year who have received two (polyribosylribitol
phosphate-meningococcal outer membrane protein [PRP-OMP]) or three
(PRP-tetanus [PRP-T], diphtheria CRM197 [CRM, cross-reactive
material] protein conjugate [HbOC]) prior doses of Hib vaccine, and three
prior doses of DTaP and pneumococcal conjugate vaccine have developed
protection (23,24).
The third (PRP-OMP) or fourth (PRP-T, HbOC) dose of the Hib series, and
the fourth doses of DTaP and pneumococcal conjugate vaccines are critical
in boosting antibody titer and ensuring continued protection (24--26).
However, the booster dose of the Hib or pneumococcal conjugate series can
be deferred until ages 15--18 months for children who are likely to return
for future visits. The fourth dose of DTaP is recommended to be
administered at ages 15--18 months, but can be administered as early as
age 12 months under certain circumstances (25).
For infants at low risk for infection with hepatitis B virus (i.e., the
mother tested negative for hepatitis B surface antigen [HBsAg] at the time
of delivery and the child is not of Asian or Pacific Islander descent),
the hepatitis B vaccine series can be completed at any time during ages
6--18 months. Recommended spacing of doses should be maintained (Table
1).

Use of combination vaccines can reduce the number of injections
required at an office visit. Licensed combination vaccines can be used
whenever any components of the combination are indicated and its other
components are not contraindicated. Use of licensed combination vaccines
is preferred over separate injection of their equivalent component
vaccines (27).
Only combination vaccines approved by the Food and Drug Administration
(FDA) should be used. Individual vaccines must never be mixed in the same
syringe unless they are specifically approved for mixing by FDA. Only one
vaccine (DTaP and PRP-T Hib vaccine, marketed as TriHIBit®
[manufactured by Aventis Pasteur]) is FDA-approved for mixing in the same
syringe. This vaccine should not be used for primary vaccination in
infants aged 2, 4, and 6 months, but it can be used as a booster after any
Hib vaccine.

Nonsimultaneous Administration

Inactivated vaccines do not interfere with the immune response to other
inactivated vaccines or to live vaccines. An inactivated vaccine can be
administered either simultaneously or at any time before or after a
different inactivated vaccine or live vaccine (Table
2).

The immune response to one live-virus vaccine might be impaired if
administered within 30 days of another live-virus vaccine (28,29).
Data are limited concerning interference between live vaccines. In a study
conducted in two U.S. health maintenance organizations, persons who
received varicella vaccine <30 days after MMR vaccination had an
increased risk for varicella vaccine failure (i.e., varicella disease in a
vaccinated person) of 2.5-fold compared with those who received varicella
vaccine before or >30 days after MMR (30).
In contrast, a 1999 study determined that the response to yellow fever
vaccine is not affected by monovalent measles vaccine administered 1--27
days earlier (21). The effect of nonsimultaneously administering
rubella, mumps, varicella, and yellow fever vaccines is unknown.

To minimize the potential risk for interference, parenterally
administered live vaccines not administered on the same day should be
administered >4 weeks apart whenever possible (Table
2). If parenterally administered live vaccines are separated by <4
weeks, the vaccine administered second should not be counted as a valid
dose and should be repeated. The repeat dose should be administered
>4 weeks after the last, invalid dose. Yellow fever vaccine can
be administered at any time after single-antigen measles vaccine. Ty21a
typhoid vaccine and parenteral live vaccines (i.e., MMR, varicella, yellow
fever) can be administered simultaneously or at any interval before or
after each other, if indicated.

Spacing of Antibody-Containing Products and Vaccines

Live Vaccines

Ty21a typhoid and yellow fever vaccines can be administered at any time
before, concurrent with, or after administering any immune globulin or
hyperimmune globulin (e.g., hepatitis B immune globulin and rabies immune
globulin). Blood (e.g., whole blood, packed red blood cells, and plasma)
and other antibody-containing blood products (e.g., immune globulin,
hyperimmune globulin, and intravenous immune globulin [IGIV]) can inhibit
the immune response to measles and rubella vaccines for >3
months (31,32). The effect of blood and immune globulin
preparations on the response to mumps and varicella vaccines is unknown,
but commercial immune globulin preparations contain antibodies to these
viruses. Blood products available in the United States are unlikely to
contain a substantial amount of antibody to yellow fever vaccine virus.
The length of time that interference with parenteral live vaccination
(except yellow fever vaccine) can persist after the antibody-containing
product is a function of the amount of antigen-specific antibody contained
in the product (31--33). Therefore, after an antibody-containing
product is received, parenteral live vaccines (except yellow fever
vaccine) should be delayed until the passive antibody has degraded (Table
3). Recommended intervals between receipt of various blood products
and measles-containing vaccine and varicella vaccine are listed in this
report (Table
4). If a dose of parenteral live-virus vaccine (except yellow fever
vaccine) is administered after an antibody-containing product but at an
interval shorter than recommended in this report, the vaccine dose should
be repeated unless serologic testing indicates a response to the vaccine.
The repeat dose or serologic testing should be performed after the
interval indicated for the antibody-containing product (Table
4).

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 (34). Because of the importance of
rubella immunity among childbearing-age women (6,35),
the 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 (6).

Interference can occur if administering an antibody-containing product
becomes necessary after administering MMR, its individual components, or
varicella vaccine. Usually, vaccine virus replication and stimulation of
immunity will occur 1--2 weeks after vaccination. Thus, if the interval
between administering any of these vaccines and subsequent administration
of an antibody-containing product is <14 days, vaccination should be
repeated after the recommended interval (Tables
3,4),
unless serologic testing indicates that antibodies were produced.

A humanized mouse monoclonal antibody product (palivizumab) is
available for prevention of respiratory syncytial virus infection among
infants and young children. This product contains only antibody to
respiratory syncytial virus; hence, it will not interfere with immune
response to live or inactivated vaccines.

Inactivated Vaccines

Antibody-containing products interact less with inactivated vaccines,
toxoids, recombinant subunit, and polysaccharide vaccines than with live
vaccines (36). Therefore, administering inactivated vaccines and
toxoids either simultaneously with or at any interval before or after
receipt of an antibody-containing product should not substantially impair
development of a protective antibody response (Table
3). The vaccine or toxoid and antibody preparation should be
administered at different sites by using the standard recommended dose.
Increasing the vaccine dose volume or number of vaccinations is not
indicated or recommended.

Interchangeability of Vaccines from Different Manufacturers

Numerous vaccines are available from different ma00048610.htmnufacturers,
and these vaccines usually are not identical in antigen content or amount
or method of formulation. Manufacturers use different production
processes, and their products might contain different concentrations of
antigen per dose or different stabilizers or preservatives.

Available data indicate that infants who receive sequential doses of
different Hib conjugate, hepatitis B, and hepatitis A vaccines produce a
satisfactory antibody response after a complete primary series
(37--40). All brands of Hib conjugate, hepatitis B,§ and
hepatitis A vaccines are interchangeable within their respective series.
If different brands of Hib conjugate vaccine are administered, a total of
three doses is considered adequate for the primary series among infants.
After completing the primary series, any Hib conjugate vaccine can be used
for the booster dose at ages 12--18 months.

Data are limited regarding the safety, immunogenicity, and efficacy of
using acellular pertussis (as DTaP) vaccines from different manufacturers
for successive doses of the pertussis series. Available data from one
study indicate that, for the first three doses of the DTaP series, one or
two doses of Tripedia® (manufactured by Aventis Pasteur)
followed by Infanrix® (manufactured by GlaxoSmithKline) for the
remaining doses(s) is comparable to three doses of Tripedia with regard to
immunogenicity, as measured by antibodies to diphtheria, tetanus, and
pertussis toxoid, and filamentous hemagglutinin (41). However, in
the absence of a clear serologic correlate of protection for pertussis,
the relevance of these immunogenicity data for protection against
pertussis is unknown. Whenever feasible, the same brand of DTaP vaccine
should be used for all doses of the vaccination series; however,
vaccination providers might not know or have available the type of DTaP
vaccine previously administered to a child. In this situation, any DTaP
vaccine should be used to continue or complete the series. Vaccination
should not be deferred because the brand used for previous doses is not
available or is unknown (25,42).

Lapsed Vaccination Schedule

Vaccination providers are encouraged to administer vaccines as close to
the recommended intervals as possible. However, longer-than-recommended
intervals between doses do not reduce final antibody concentrations,
although protection might not be attained until the recommended number of
doses has been administered. An interruption in the vaccination schedule
does not require restarting the entire series of a vaccine or toxoid or
the addition of extra doses.

Unknown or Uncertain Vaccination Status

Vaccination providers frequently encounter persons who do not have
adequate documentation of vaccinations. Providers should only accept
written, dated records as evidence of vaccination. With the exception of
pneumococcal polysaccharide vaccine (43),
self-reported doses of vaccine without written documentation should not be
accepted. Although vaccinations should not be postponed if records cannot
be found, an attempt to locate missing records should be made by
contacting previous health-care providers and searching for a personally
held record. If records cannot be located, these persons should be
considered susceptible and should be started on the age-appropriate
vaccination schedule. Serologic testing for immunity is an alternative to
vaccination for certain antigens (e.g., measles, mumps, rubella,
varicella, tetanus, diphtheria, hepatitis A, hepatitis B, and poliovirus)
(see Vaccination of Internationally Adopted Children).

Contraindications and
Precautions

Contraindications and precautions to vaccination dictate circumstances
when vaccines will not be administered. The majority of contraindications
and precautions are temporary, and the vaccination can be administered
later. A contraindication is a condition in a recipient that increases the
risk for a serious adverse reaction. A vaccine will not be administered
when a contraindication is present. For example, administering influenza
vaccine to a person with an anaphylactic allergy to egg protein could
cause serious illness in or death of the recipient.

National standards for pediatric immunization practices have been
established and include true contraindications and precautions to
vaccination (Table
5) (1).
The only true contraindication applicable to all vaccines is a history of
a severe allergic reaction after a prior dose of vaccine or to a vaccine
constituent (unless the recipient has been desensitized). Severely
immunocompromised persons should not receive live vaccines. Children who
experience an encephalopathy <7 days after administration of a
previous dose of diphtheria and tetanus toxoids and whole-cell pertussis
vaccine (DTP) or DTaP not attributable to another identifiable cause
should not receive further doses of a vaccine that contains pertussis.
Because of the theoretical risk to the fetus, women known to be pregnant
should not receive live attenuated virus vaccines (see Vaccination During
Pregnancy).

A precaution is a condition in a recipient that might increase the risk
for a serious adverse reaction or that might compromise the ability of the
vaccine to produce immunity (e.g., administering measles vaccine to a
person with passive immunity to measles from a blood transfusion). Injury
could result, or a person might experience a more severe reaction to the
vaccine than would have otherwise been expected; however, the risk for
this happening is less than expected with a contraindication. Under normal
circumstances, vaccinations should be deferred when a precaution is
present. However, a vaccination might be indicated in the presence of a
precaution because the benefit of protection from the vaccine outweighs
the risk for an adverse reaction. For example, caution should be exercised
in vaccinating a child with DTaP who, within 48 hours of receipt of a
prior dose of DTP or DTaP, experienced fever >40.5C (105F); had
persistent, inconsolable crying for >3 hours; collapsed or
experienced a shock-like state; or had a seizure <3 days after
receiving the previous dose of DTP or DTaP. However, administering a
pertussis-containing vaccine should be considered if the risk for
pertussis is increased (e.g., during a pertussis outbreak) (25).
The presence of a moderate or severe acute illness with or without a fever
is a precaution to administration of all vaccines. Other precautions are
listed in this report (Table
5).

Physicians and other health-care providers might inappropriately
consider certain conditions or circumstances to be true contraindications
or precautions to vaccination. This misconception results in missed
opportunities to administer recommended vaccines (44). Likewise,
physicians and other health-care providers might fail to understand what
constitutes a true contraindication or precaution and might administer a
vaccine when it should be withheld. This practice can result in an
increased risk for an adverse reaction to the vaccine. Conditions often
inappropriately regarded as contraindications to vaccination are listed in
this report (Table
5). Among the most common are diarrhea and minor upper-respiratory
tract illnesses (including otitis media) with or without fever, mild to
moderate local reactions to a previous dose of vaccine, current
antimicrobial therapy, and the convalescent phase of an acute illness.

The decision to administer or delay vaccination because of a current or
recent acute illness depends on the severity of symptoms and the etiology
of the disease. All vaccines can be administered to persons with minor
acute illness (e.g., diarrhea or mild upper-respiratory tract infection
with or without fever). Studies indicate that failure to vaccinate
children with minor illnesses can seriously impede vaccination efforts
(45--47). Among persons whose compliance with medical care cannot
be ensured, use of every opportunity to provide appropriate vaccinations
is critical.

The majority of studies support the safety and efficacy of vaccinating
persons who have mild illness (48--50). For example, in the United
States, >97% of children with mild illnesses produced measles antibody
after vaccination (51). Only one limited study has reported a lower
rate of seroconversion (79%) to the measles component of MMR vaccine among
children with minor, afebrile upper-respiratory tract infections
(52). Therefore, vaccination should not be delayed because of the
presence of mild respiratory tract illness or other acute illness with or
without fever.

Persons with moderate or severe acute illness should be vaccinated as
soon as they have recovered from the acute phase of the illness. This
precaution avoids superimposing adverse effects of the vaccine on the
underlying illness or mistakenly attributing a manifestation of the
underlying illness to the vaccine.

Routine physical examinations and measuring temperatures are not
prerequisites for vaccinating infants and children who appear to be
healthy. Asking the parent or guardian if the child is ill and then
postponing vaccination for those with moderate to severe illness, or
proceeding with vaccination if no contraindications exist, are appropriate
procedures in childhood immunization programs.

A family history of seizures or other central nervous system disorders
is not a contraindication to administration of pertussis or other
vaccines. However, delaying pertussis vaccination for infants and children
with a history of previous seizures until the child's neurologic status
has been assessed is prudent. Pertussis vaccine should not be administered
to infants with evolving neurologic conditions until a treatment regimen
has been established and the condition has stabilized (25).

Vaccine Administration

Infection Control and Sterile Technique

Persons administering vaccines should follow necessary precautions to
minimize risk for spreading disease. Hands should be washed with soap and
water or cleansed with an alcohol-based waterless antiseptic hand rub
between each patient contact. Gloves are not required when administering
vaccinations, unless persons administering vaccinations are likely to come
into contact with potentially infectious body fluids or have open lesions
on their hands. Syringes and needles used for injections must be sterile
and disposable to minimize the risk of contamination. A separate needle
and syringe should be used for each injection. Changing needles between
drawing vaccine from a vial and injecting it into a recipient is
unnecessary. Different vaccines should never be mixed in the same syringe
unless specifically licensed for such use.

Disposable needles and syringes should be discarded in labeled,
puncture-proof containers to prevent inadvertent needle-stick injury or
reuse. Safety needles or needle-free injection devices also can reduce the
risk for injury and should be used whenever available (see Occupational
Safety Regulations).

Recommended Routes of Injection and Needle Length

Routes of administration are recommended by the manufacturer for each
immunobiologic. Deviation from the recommended route of administration
might reduce vaccine efficacy (53,54) or increase local adverse
reactions (55--57). Injectable immunobiologics should be
administered where the likelihood of local, neural, vascular, or tissue
injury is limited. Vaccines containing adjuvants should be injected into
the muscle mass; when administered subcutaneously or intradermally, they
can cause local irritation, induration, skin discoloration, inflammation,
and granuloma formation.

Subcutaneous Injections

Subcutaneous injections usually are administered at a 45-degree angle
into the thigh of infants aged <12 months and in the upper-outer
triceps area of persons aged >12 months. Subcutaneous injections
can be administered into the upper-outer triceps area of an infant, if
necessary. A 5/8-inch, 23--25-gauge needle should be inserted into the
subcutaneous tissue.

Intramuscular Injections

Intramuscular injections are administered at a 90-degree angle into the
anterolateral aspect of the thigh or the deltoid muscle of the upper arm.
The buttock should not be used for administration of vaccines or toxoids
because of the potential risk of injury to the sciatic nerve (58).
In addition, injection into the buttock has been associated with decreased
immunogenicity of hepatitis B and rabies vaccines in adults, presumably
because of inadvertent subcutaneous injection or injection into deep fat
tissue (53,59).

For all intramuscular injections, the needle should be long enough to
reach the muscle mass and prevent vaccine from seeping into subcutaneous
tissue, but not so long as to involve underlying nerves and blood vessels
or bone (54,60--62). Vaccinators should be familiar with the
anatomy of the area into which they are injecting vaccine. An individual
decision on needle size and site of injection must be made for each person
on the basis of age, the volume of the material to be administered, the
size of the muscle, and the depth below the muscle surface into which the
material is to be injected.

Although certain vaccination specialists advocate aspiration (i.e., the
syringe plunger pulled back before injection), no data exist to document
the necessity for this procedure. If aspiration results in blood in the
needle hub, the needle should be withdrawn and a new site should be
selected.

Infants (persons aged <12 months). Among the majority
of infants, the anterolateral aspect of the thigh provides the largest
muscle mass and is therefore the recommended site for injection. For the
majority of infants, a 7/8--1-inch, 22--25-gauge needle is sufficient to
penetrate muscle in the infant's thigh.

Toddlers and Older Children (persons aged >12
months--18 years). The deltoid muscle can be used if the muscle
mass is adequate. The needle size can range from 22 to 25 gauge and from
7/8 to 1¼ inches, on the basis of the size of the muscle. For toddlers,
the anterolateral thigh can be used, but the needle should be longer,
usually 1 inch.

Adults (persons aged >18 years). For adults, the
deltoid muscle is recommended for routine intramuscular vaccinations. The
anterolateral thigh can be used. The suggested needle size is 1--1½ inches
and 22--25 gauge.

Intradermal Injections

Intradermal injections are usually administered on the volar surface of
the forearm. With the bevel facing upwards, a 3/8--3/4-inch, 25--27-gauge
needle can be inserted into the epidermis at an angle parallel to the long
axis of the forearm. The needle should be inserted so that the entire
bevel penetrates the skin and the injected solution raises a small bleb.
Because of the small amounts of antigen used in intradermal vaccinations,
care must be taken not to inject the vaccine subcutaneously because it can
result in a suboptimal immunologic response.

Multiple Vaccinations

If >2 vaccine preparations are administered or if vaccine and
an immune globulin preparation are administered simultaneously, each
preparation should be administered at a different anatomic site. If
>2 injections must be administered in a single limb, the thigh
is usually the preferred site because of the greater muscle mass; the
injections should be sufficiently separated (i.e., >1 inch) so
that any local reactions can be differentiated (55,63). For older
children and adults, the deltoid muscle can be used for multiple
intramuscular injections, if necessary. The location of each injection
should documented in the person's medical record.

Jet Injection

Jet injectors (JIs) are needle-free devices that drive liquid
medication through a nozzle orifice, creating a narrow stream under high
pressure that penetrates skin to deliver a drug or vaccine into
intradermal, subcutaneous, or intramuscular tissues (64,65).
Increasing attention to JI technology as an alternative to conventional
needle injection has resulted from recent efforts to reduce the frequency
of needle-stick injuries to health-care workers (66) and to
overcome the improper reuse and other drawbacks of needles and syringes in
economically developing countries (67--69). JIs have been reported
safe and effective in administering different live and inactivated
vaccines for viral and bacterial diseases (69). The immune
responses generated are usually equivalent to, and occasionally greater
than, those induced by needle injection. However, local reactions or
injury (e.g., redness, induration, pain, blood, and ecchymosis at the
injection site) can be more frequent for vaccines delivered by JIs
compared with needle injection (65,69).

Certain JIs were developed for situations in which substantial numbers
of persons must be vaccinated rapidly, but personnel or supplies are
insufficient to do so with conventional needle injection. Such
high-workload devices vaccinate consecutive patients from the same nozzle
orifice, fluid pathway, and dose chamber, which is refilled automatically
from attached vials containing <50 doses each. Since the 1950s,
these devices have been used extensively among military recruits and for
mass vaccination campaigns for disease control and eradication
(64). An outbreak of hepatitis B among patients receiving
injections from a multiple-use--nozzle JI was documented (70,71),
and subsequent laboratory, field, and animal studies demonstrated that
such devices could become contaminated with blood (69,72,73).

No U.S.-licensed, high-workload vaccination devices of unquestioned
safety are available to vaccination programs. Efforts are under way for
the research and development of new high-workload JIs using
disposable-cartridge technology that avoids reuse of any unsterilized
components having contact with the medication fluid pathway or patient's
blood. Until such devices become licensed and available, the use of
existing multiple-use--nozzle JIs should be limited. Use can be considered
when the theoretical risk for bloodborne disease transmission is
outweighed by the benefits of rapid vaccination with limited personnel in
responding to serious disease threats (e.g., pandemic influenza or
bioterrorism event), and by any competing risks of iatrogenic or
occupational infections resulting from conventional needles and syringes.
Before such emergency use of multiple-use--nozzle JIs, health-care workers
should consult with local, state, national, or international health
agencies or organizations that have experience in their use.

In the 1990s, a new generation of low-workload JIs were introduced with
disposable cartridges serving as dose chambers and nozzle (69).
With the provision of a new sterile cartridge for each patient and other
correct use, these devices avoid the safety concerns described previously
for multiple-use--nozzle devices. They can be used in accordance with
their labeling for intradermal, subcutaneous, or intramuscular
administration.

Methods for Alleviating Discomfort and Pain Associated with
Vaccination

Comfort measures and distraction techniques (e.g., playing music or
pretending to blow away the pain) might help children cope with the
discomfort associated with vaccination. Pretreatment (30-60 minutes before
injection) with 5% topical lidocaine-prilocaine emulsion (EMLA®
cream or disk [manufactured by AstraZeneca LP]) can decrease the pain of
vaccination among infants by causing superficial anesthesia
(74,75). Preliminary evidence indicates that this cream does not
interfere with the immune response to MMR (76). Topical
lidocaine-prilocaine emulsion should not be used on infants aged <12
months who are receiving treatment with methemoglobin-inducing agents
because of the possible development of methemoglobinemia (77).
Acetaminophen has been used among children to reduce the discomfort and
fever associated with vaccination (78). However, acetaminophen can
cause formation of methemoglobin and, thus, might interact with
lidocaine-prilocaine cream, if used concurrently (77). Ibuprofen or
other nonaspirin analgesic can be used, if necessary. Use of a topical
refrigerant (vapocoolant) spray can reduce the short-term pain associated
with injections and can be as effective as lidocaine-prilocaine cream
(79). Administering sweet-tasting fluid orally immediately before
injection can result in a calming or analgesic effect among certain
infants.

Nonstandard Vaccination Practices

Recommendations regarding route, site, and dosage of immunobiologics
are derived from data from clinical trials, from practical experience, and
from theoretical considerations. ACIP strongly discourages variations from
the recommended route, site, volume, or number of doses of any vaccine.

Variation from the recommended route and site can result in inadequate
protection. The immunogenicity of hepatitis B vaccine and rabies vaccine
is substantially lower when the gluteal rather than the deltoid site is
used for administration (53,59). Hepatitis B vaccine administered
intradermally can result in a lower seroconversion rate and final titer of
hepatitis B surface antibody than when administered by the deltoid
intramuscular route (80,81). Doses of rabies vaccine administered
in the gluteal site should not be counted as valid doses and should be
repeated. Hepatitis B vaccine administered by any route or site other than
intramuscularly in the anterolateral thigh or deltoid muscle should not be
counted as valid and should be repeated, unless serologic testing
indicates that an adequate response has been achieved.

Live attenuated parenteral vaccines (e.g., MMR, varicella, or yellow
fever) and certain inactivated vaccines (e.g., IPV, pneumococcal
polysaccharide, and anthrax) are recommended by the manufacturers to be
administered by subcutaneous injection. Pneumococcal polysaccharide and
IPV are approved for either intramuscular or subcutaneous administration.
Response to these vaccines probably will not be affected if the vaccines
are administered by the intramuscular rather then subcutaneous route.
Repeating doses of vaccine administered by the intramuscular route rather
than by the subcutaneous route is unnecessary.

Administering volumes smaller than those recommended (e.g., split
doses) can result in inadequate protection. Using larger than the
recommended dose can be hazardous because of excessive local or systemic
concentrations of antigens or other vaccine constituents. Using multiple
reduced doses that together equal a full immunizing dose or using smaller
divided doses is not endorsed or recommended. Any vaccination using less
than the standard dose should not be counted, and the person should be
revaccinated according to age, unless serologic testing indicates that an
adequate response has been achieved.

Preventing Adverse Reactions

Vaccines are intended to produce active immunity to specific antigens.
An adverse reaction is an untoward effect that occurs after a vaccination
that is extraneous to the vaccine's primary purpose of producing immunity.
Adverse reactions also are called vaccine side effects.

All vaccines might cause adverse reactions (82).
Vaccine adverse reactions are classified by three general categories:
local, systemic, and allergic. Local reactions are usually the least
severe and most frequent. Systemic reactions (e.g., fever) occur less
frequently than local reactions. Serious allergic reactions (e.g.,
anaphylaxis) are the most severe and least frequent. Severe adverse
reactions are rare.

The key to preventing the majority of serious adverse reactions is
screening. Every person who administers vaccines should screen patients
for contraindications and precautions to the vaccine before it is
administered (Table
5). Standardized screening questionnaires have been developed and are
available from certain state immunization programs and other sources
(e.g., the Immunization Action Coalition at http://www.immunize.org/ [accessed
October 31, 2001]).

Severe allergic reactions after vaccination are rare. However, all
physicians and other health-care providers who administer vaccines should
have procedures in place for the emergency management of a person who
experiences an anaphylactic reaction. All vaccine providers should be
familiar with the office emergency plan and be certified in
cardiopulmonary resuscitation.

Syncope (vasovagal or vasodepressor reaction) can occur after
vaccination, most commonly among adolescents and young adults. During
1990--August 2001, a total of 2,269 reports to the Vaccine Adverse Event
Reporting system were coded as syncope. Forty percent of these episodes
were reported among persons aged 10--18 years (CDC, unpublished data,
2001). Approximately 12% of reported syncopal episodes resulted in
hospitalization because of injury or medical evaluation. Serious injury,
including skull fractures and cerebral bleeding, have been reported to
result from syncopal episodes after vaccination. A published review of
syncope after vaccination reported that 63% of syncopal episodes occurred
<5 minutes after vaccination, and 89% occurred within 15 minutes
after vaccination (83). Although syncopal episodes are uncommon and
serious allergic reactions are rare, certain vaccination specialists
recommend that persons be observed for 15--20 minutes after being
vaccinated, if possible (84). If syncope develops, patients should
be observed until the symptoms resolve.

Managing Acute Vaccine Reactions

Although rare after vaccination, the immediate onset and
life-threatening nature of an anaphylactic reaction require that personnel
and facilities providing vaccinations be capable of providing initial care
for suspected anaphylaxis. Epinephrine and equipment for maintaining an
airway should be available for immediate use.

Anaphylaxis usually begins within minutes of vaccine administration.
Rapidly recognizing and initiating treatment are required to prevent
possible progression to cardiovascular collapse. If flushing, facial
edema, urticaria, itching, swelling of the mouth or throat, wheezing,
difficulty breathing, or other signs of anaphylaxis occur, the patient
should be placed in a recumbent position with the legs elevated. Aqueous
epinephrine (1:1000) should be administered and can be repeated within
10--20 minutes (84). A dose of diphenhydramine hydrochloride might
shorten the reaction, but it will have little immediate effect.
Maintenance of an airway and oxygen administration might be necessary.
Arrangements should be made for immediate transfer to an emergency
facility for further evaluation and treatment.

Occupational Safety Regulations

Bloodborne diseases (e.g., hepatitis B and C and human immunodeficiency
virus [HIV]) are occupational hazards for health-care workers. In November
2000, to reduce the incidence of needle-stick injuries among health-care
workers and the consequent risk for bloodborne diseases acquired from
patients, the Needlestick Safety and Prevention Act was signed into law.
The act directed the Occupational Safety and Health Administration (OSHA)
to strengthen its existing bloodborne pathogen standards. Those standards
were revised and became effective in April 2001 (66). These federal
regulations require that safer injection devices (e.g., needle-shielding
syringes or needle-free injectors) be used for parenteral vaccination in
all clinical settings when such devices are appropriate, commercially
available, and capable of achieving the intended clinical purpose. The
rules also require that records be kept documenting the incidence of
injuries caused by medical sharps (except in workplaces with <10
employees) and that nonmanagerial employees be involved in the evaluation
and selection of safer devices to be procured.

Needle-shielding or needle-free devices that might satisfy the
occupational safety regulations for administering parenteral injections
are available in the United States and are listed at multiple websites
(69,85--87).¶ Additional information regarding
implementation and enforcement of these regulations is available at the
OSHA website at http://www.osha-slc.gov/needlesticks
(accessed October 31, 2001).

Storage and Handling of
Immunobiologics

Failure to adhere to recommended specifications for storage and
handling of immunobiologics can reduce potency, resulting in an inadequate
immune response in the recipient. Recommendations included in a product's
package insert, including reconstitution of the vaccine, should be
followed carefully. Vaccine quality is the shared responsibility of all
parties from the time the vaccine is manufactured until administration.
All vaccines should be inspected upon delivery and monitored during
storage to ensure that the cold chain has been maintained. Vaccines should
continue to be stored at recommended temperatures immediately upon
receipt. Certain vaccines (e.g., MMR, varicella, and yellow fever) are
sensitive to increased temperature. All other vaccines are sensitive to
freezing. Mishandled vaccine usually is not distinguishable from potent
vaccine. When in doubt regarding the appropriate handling of a vaccine,
vaccination providers should contact the manufacturer. Vaccines that have
been mishandled (e.g., inactivated vaccines and toxoids that have been
exposed to freezing temperatures) or that are beyond their expiration date
should not be administered. If mishandled or expired vaccines are
administered inadvertently, they should not be counted as valid doses and
should be repeated, unless serologic testing indicates a response to the
vaccine.

Live attenuated virus vaccines should be administered promptly after
reconstitution. Varicella vaccine must be administered <30
minutes after reconstitution. Yellow fever vaccine must be used
<1 hour after reconstitution. MMR vaccine must be administered
<8 hours after reconstitution. If not administered within these
prescribed time periods after reconstitution, the vaccine must be
discarded.

The majority of vaccines have a similar appearance after being drawn
into a syringe. Instances in which the wrong vaccine inadvertently was
administered are attributable to the practice of prefilling syringes or
drawing doses of a vaccine into multiple syringes before their immediate
need. ACIP discourages the routine practice of prefilling syringes because
of the potential for such administration errors. To prevent errors,
vaccine doses should not be drawn into a syringe until immediately before
administration. In certain circumstances where a single vaccine type is
being used (e.g., in advance of a community influenza vaccination
campaign), filling multiple syringes before their immediate use can be
considered. Care should be taken to ensure that the cold chain is
maintained until the vaccine is administered. When the syringes are
filled, the type of vaccine, lot number, and date of filling must be
carefully labeled on each syringe, and the doses should be administered as
soon as possible after filling.

Certain vaccines are distributed in multidose vials. When opened, the
remaining doses from partially used multidose vials can be administered
until the expiration date printed on the vial or vaccine packaging,
provided that the vial has been stored correctly and that the vaccine is
not visibly contaminated.

Special Situations

Concurrently Administering Antimicrobial Agents and Vaccines

With limited exceptions, using an antibiotic is not a contraindication
to vaccination. Antimicrobial agents have no effect on the response to
live attenuated vaccines, except live oral Ty21a typhoid vaccine, and have
no effect on inactivated, recombinant subunit, or polysaccharide vaccines
or toxoids. Ty21a typhoid vaccine should not be administered to persons
receiving antimicrobial agents until >24 hours after any
antibiotic dose (18).

Antiviral drugs used for treatment or prophylaxis of influenza virus
infections have no effect on the response to inactivated influenza vaccine
(88).
Antiviral drugs active against herpesviruses (e.g., acyclovir or
valacyclovir) might reduce the efficacy of live attenuated varicella
vaccine. These drugs should be discontinued >24 hours before
administration of varicella vaccine, if possible.

The antimalarial drug mefloquine (Lariam® [manufactured by
Roche Laboratories, Inc.]) could affect the immune response to oral Ty21a
typhoid vaccine if both are taken simultaneously (89,90). To
minimize this effect, administering Ty21a typhoid vaccine >24
hours before or after a dose of mefloquine is prudent.

Tuberculosis Screening and Skin Test Reactivity

Measles illness, severe acute or chronic infections, HIV infection, and
malnutrition can create an anergic state during which the tuberculin skin
test (usually known as purified protein derivative [PPD]
skin test) might give a false negative reaction (91--93). Although
any live attenuated measles vaccine can theoretically suppress PPD
reactivity, the degree of suppression is probably less than that occurring
from acute infection from wild measles virus. Although routine PPD
screening of all children is no longer recommended, PPD screening is
sometimes needed at the same time as administering a measles-containing
vaccine (e.g., for well-child care, school entrance, or for employee
health reasons), and the following options should be considered:

PPD and measles-containing vaccine can be administered at the same
visit (preferred option). Simultaneously administering PPD and
measles-containing vaccine does not interfere with reading the PPD
result at 48--72 hours and ensures that the person has received measles
vaccine.

If the measles-containing vaccine has been administered recently,
PPD screening should be delayed >4 weeks after vaccination. A
delay in performing PPD will remove the concern of any theoretical but
transient suppression of PPD reactivity from the vaccine.

PPD screening can be performed and read before administering the
measles-containing vaccine. This option is the least favored because it
will delay receipt of the measles-containing vaccine.

No data exist for the potential degree of PPD suppression that might be
associated with other parenteral live attenuated virus vaccines (e.g.,
varicella or yellow fever). Nevertheless, in the absence of data,
following guidelines for measles-containing vaccine when scheduling PPD
screening and administering other parenteral live attenuated virus
vaccines is prudent. If a risk exists that the opportunity to vaccinate
might be missed, vaccination should not be delayed only because of these
theoretical considerations.

Mucosally administered live attenuated virus vaccines (e.g., OPV and
intranasally administered influenza vaccine) are unlikely to affect the
response to PPD. No evidence has been reported that inactivated vaccines,
polysaccharide vaccines, recombinant, or subunit vaccines, or toxoids
interfere with response to PPD.

PPD reactivity in the absence of tuberculosis disease is not a
contraindication to administration of any vaccine, including parenteral
live attenuated virus vaccines. Tuberculosis disease is not a
contraindication to vaccination, unless the person is moderately or
severely ill. Although no studies have reported the effect of MMR vaccine
on persons with untreated tuberculosis, a theoretical basis exists for
concern that measles vaccine might exacerbate tuberculosis (6).
Consequently, before administering MMR to persons with untreated active
tuberculosis, initiating antituberculosis therapy is advisable (6).
Ruling out concurrent immunosuppression (e.g., immunosuppression caused by
HIV infection) before administering live attenuated vaccines is also
prudent.

Severe Allergy to Vaccine Components

Vaccine components can cause allergic reactions among certain
recipients. These reactions can be local or systemic and can include mild
to severe anaphylaxis or anaphylactic-like responses (e.g., generalized
urticaria or hives, wheezing, swelling of the mouth and throat, difficulty
breathing, hypotension, and shock). Allergic reactions might be caused by
the vaccine antigen, residual animal protein, antimicrobial agents,
preservatives, stabilizers, or other vaccine components (94). An
extensive listing of vaccine components, their use, and the vaccines that
contain each component has been published (95) and is also
available from CDC's National Immunization Program website at http://www.cdc.gov/nip  (accessed
October 31, 2001).

The most common animal protein allergen is egg protein, which is found
in vaccines prepared by using embryonated chicken eggs (influenza and
yellow fever vaccines). Ordinarily, persons who are able to eat eggs or
egg products safely can receive these vaccines; persons with histories of
anaphylactic or anaphylactic-like allergy to eggs or egg proteins should
not be administered these vaccines. Asking persons if they can eat eggs
without adverse effects is a reasonable way to determine who might be at
risk for allergic reactions from receiving yellow fever and influenza
vaccines. A regimen for administering influenza vaccine to children with
egg hypersensitivity and severe asthma has been developed (96).

Measles and mumps vaccine viruses are grown in chick embryo fibroblast
tissue culture. Persons with a serious egg allergy can receive measles- or
mumps-containing vaccines without skin testing or desensitization to egg
protein (6).
Rubella and varicella vaccines are grown in human diploid cell cultures
and can safely be administered to persons with histories of severe allergy
to eggs or egg proteins. The rare serious allergic reaction after measles
or mumps vaccination or MMR are not believed to be caused by egg antigens,
but to other components of the vaccine (e.g., gelatin) (97--100).
MMR, its component vaccines, and other vaccines contain hydrolyzed gelatin
as a stabilizer. Extreme caution should be exercised when administering
vaccines that contain gelatin to persons who have a history of an
anaphylactic reaction to gelatin or gelatin-containing products. Before
administering gelatin-containing vaccines to such persons, skin testing
for sensitivity to gelatin can be considered. However, no specific
protocols for this approach have been published.

Certain vaccines contain trace amounts of antibiotics or other
preservatives (e.g., neomycin or thimerosal) to which patients might be
severely allergic. The information provided in the vaccine package insert
should be reviewed carefully before deciding if the rare patient with such
allergies should receive the vaccine. No licensed vaccine contains
penicillin or penicillin derivatives.

Certain vaccines contain trace amounts of neomycin. Persons who have
experienced anaphylactic reactions to neomycin should not receive these
vaccines. Most often, neomycin allergy is a contact dermatitis, a
manifestation of a delayed type (cell-mediated) immune response, rather
than anaphylaxis (101,102). A history of delayed type reactions to
neomycin is not a contraindication for administration of these vaccines.

Thimerosal is an organic mercurial compound in use since the 1930s and
added to certain immunobiologic products as a preservative. A joint
statement issued by the U.S. Public Health Service and the American
Academy of Pediatrics (AAP) in 1999 (103)
and agreed to by the American Academy of Family Physicians (AAFP) later in
1999, established the goal of removing thimerosal as soon as possible from
vaccines routinely recommended for infants. Although no evidence exists of
any harm caused by low levels of thimerosal in vaccines and the risk was
only theoretical (104), this goal was established as a
precautionary measure.

The public is concerned about the health effects of mercury exposure of
any type, and the elimination of mercury from vaccines was judged a
feasible means of reducing an infant's total exposure to mercury in a
world where other environmental sources of exposure are more difficult or
impossible to eliminate (e.g., certain foods). Since mid-2001, vaccines
routinely recommended for children have been manufactured without
thimerosal as a preservative and contain either no thimerosal or only
trace amounts. Thimerosal as a preservative is present in certain other
vaccines (e.g., Td, DT, one of two adult hepatitis B vaccines, and
influenza vaccine). A trace thimerosal formulation of one brand of
influenza vaccine was licensed by FDA in September 2001.

Receiving thimerosal-containing vaccines has been believed to lead to
induction of allergy. However, limited scientific basis exists for this
assertion (94). Hypersensitivity to thimerosal usually consists of
local delayed type hypersensitivity reactions (105--107).
Thimerosal elicits positive delayed type hypersensitivity patch tests in
1%--18% of persons tested, but these tests have limited or no clinical
relevance (108,109). The majority of patients do not experience
reactions to thimerosal administered as a component of vaccines even when
patch or intradermal tests for thimerosal indicate hypersensitivity
(109). A localized or delayed type hypersensitivity reaction to
thimerosal is not a contraindication to receipt of a vaccine that contains
thimerosal.

Latex Allergy

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 lesser amounts. Natural rubber latex is used to produce medical
gloves, catheters, and other products. Dry 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 (110). However, injection-procedure--associated latex
allergies among patients with diabetes have been described
(111--113). Allergic reactions (including anaphylaxis) after
vaccination procedures are rare. Only one report of an allergic reaction
after administering hepatitis B vaccine in a patient with known severe
allergy (anaphylaxis) to latex has been published (114).

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 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.

Vaccination of Premature Infants

In the majority of cases, infants born prematurely, regardless of birth
weight, should be vaccinated at the same chronological age and according
to the same schedule and precautions as full-term infants and children.
Birth weight and size are not factors in deciding whether to postpone
routine vaccination of a clinically stable premature infant
(115--117), except for hepatitis B vaccine. The full recommended
dose of each vaccine should be used. Divided or reduced doses are not
recommended (118).

Studies demonstrate that decreased seroconversion rates might occur
among certain premature infants with low birth weights (i.e., <2,000
grams) after administration of hepatitis B vaccine at birth (119).
However, by chronological age 1 month, all premature infants, regardless
of initial birth weight or gestational age are as likely to respond as
adequately as older and larger infants (120--122). A premature
infant born to HBsAg-positive mothers and mothers with unknown HBsAg
status must receive immunoprophylaxis with hepatitis B vaccine and
hepatitis B immunoglobulin (HBIG) <12 hours after birth. If
these infants weigh <2,000 grams at birth, the initial vaccine dose
should not be counted towards completion of the hepatitis B vaccine
series, and three additional doses of hepatitis B vaccine should be
administered, beginning when the infant is age 1 month. The optimal timing
of the first dose of hepatitis B vaccine for premature infants of
HBsAg-negative mothers with a birth weight of <2,000 grams has not been
determined. However, these infants can receive the first dose of the
hepatitis B vaccine series at chronological age 1 month. Premature infants
discharged from the hospital before chronological age 1 month can also be
administered hepatitis B vaccine at discharge, if they are medically
stable and have gained weight consistently.

Breast-Feeding and Vaccination

Neither inactivated nor live vaccines administered to a lactating woman
affect the safety of breast-feeding for mothers or infants. Breast-feeding
does not adversely affect immunization and is not a contraindication for
any vaccine. Limited data indicate that breast-feeding can enhance the
response to certain vaccine antigens (123). Breast-fed infants
should be vaccinated according to routine recommended schedules
(124--126).

Although live vaccines multiply within the mother's body, the majority
have not been demonstrated to be excreted in human milk. Although rubella
vaccine virus might be excreted in human milk, the virus usually does not
infect the infant. If infection does occur, it is well-tolerated because
the viruses are attenuated (127). Inactivated, recombinant,
subunit, polysaccharide, conjugate vaccines and toxoids pose no risk for
mothers who are breast-feeding or for their infants.

Vaccination During Pregnancy

Risk to a developing fetus from vaccination of the mother during
pregnancy is primarily theoretical. No evidence exists of risk from
vaccinating pregnant women with inactivated virus or bacterial vaccines or
toxoids (128,129). Benefits of vaccinating pregnant women usually
outweigh potential risks when the likelihood of disease exposure is high,
when infection would pose a risk to the mother or fetus, and when the
vaccine is unlikely to cause harm.

Td toxoid is indicated routinely for pregnant women. Previously
vaccinated pregnant women who have not received a Td vaccination within
the last 10 years should receive a booster dose. Pregnant women who are
not immunized or only partially immunized against tetanus should complete
the primary series (130).
Depending on when a woman seeks prenatal care and the required interval
between doses, one or two doses of Td can be administered before delivery.
Women for whom the vaccine is indicated, but who have not completed the
recommended three-dose series during pregnancy, should receive follow-up
after delivery to ensure the series is completed.

Women in the second and third trimesters of pregnancy have been
demonstrated to be at increased risk for hospitalization from influenza
(131). Therefore, routine influenza vaccination is recommended for
healthy women who will be beyond the first trimester of pregnancy (i.e.,
>14 weeks of gestation) during influenza season (usually
December--March in the United States) (88).
Women who have medical conditions that increase their risk for
complications of influenza should be vaccinated before the influenza
season, regardless of the stage of pregnancy.

IPV can be administered to pregnant women who are at risk for exposure
to wild-type poliovirus infection (4).
Hepatitis B vaccine is recommended for pregnant women at risk for
hepatitis B virus infection (132).
Hepatitis A, pneumococcal polysaccharide, and meningococcal polysaccharide
vaccines should be considered for women at increased risk for those
infections (43,133,134).

Pregnant women who must travel to areas where the risk for yellow fever
is high should receive yellow fever vaccine, because the limited
theoretical risk from vaccination is substantially outweighed by the risk
for yellow fever infection (22,135).
Pregnancy is a contraindication for measles, mumps, rubella, and varicella
vaccines. Although of theoretical concern, no cases of congenital rubella
or varicella syndrome or abnormalities attributable to fetal infection
have been observed among infants born to susceptible women who received
rubella or varicella vaccines during pregnancy (6,136).
Because of the importance of protecting women of childbearing age against
rubella, reasonable practices in any immunization program include asking
women if they are pregnant or intend to become pregnant in the next 4
weeks, not vaccinating women who state that they are pregnant, explaining
the potential risk for the fetus to women who state that they are not
pregnant, and counseling women who are vaccinated not to become pregnant
during the 4 weeks after MMR vaccination (6,35,137).
Routine pregnancy testing of women of childbearing age before
administering a live-virus vaccine is not recommended (6).
If a pregnant woman is inadvertently vaccinated or if she becomes pregnant
within 4 weeks after MMR or varicella vaccination, she should be counseled
regarding the theoretical basis of concern for the fetus; however, MMR or
varicella vaccination during pregnancy should not ordinarily be a reason
to terminate pregnancy (6,8).

Persons who receive MMR vaccine do not transmit the vaccine viruses to
contacts (6).
Transmission of varicella vaccine virus to contacts is rare (138).
MMR and varicella vaccines should be administered when indicated to the
children and other household contacts of pregnant women (6,8).

All pregnant women should be evaluated for immunity to rubella and be
tested for the presence of HBsAg (6,35,132).
Women susceptible to rubella should be vaccinated immediately after
delivery. A woman known to be HBsAg-positive should be followed carefully
to ensure that the infant receives HBIG and begins the hepatitis B vaccine
series <12 hours after birth and that the infant completes the
recommended hepatitis B vaccine series (132).
No known risk exists for the fetus from passive immunization of pregnant
women with immune globulin preparations.

Vaccination of Internationally Adopted Children

The ability of a clinician to determine that a person is protected on
the basis of their country of origin and their records alone is limited.
Internationally adopted children should receive vaccines according to
recommended schedules for children in the United States. Only written
documentation should be accepted as evidence of prior vaccination. Written
records are more likely to predict protection if the vaccines, dates of
administration, intervals between doses, and the child's age at the time
of immunization are comparable to the current U.S. recommendations.
Although vaccines with inadequate potency have been produced in other
countries (139,140), the majority of vaccines used worldwide are
produced with adequate quality control standards and are potent.

The number of American families adopting children from outside the
United States has increased substantially in recent years (141).
Adopted children's birth countries often have immunization schedules that
differ from the recommended childhood immunization schedule in the United
States. Differences in the U.S. immunization schedule and those used in
other countries include the vaccines administered, the recommended ages of
administration, and the number and timing of doses.

Data are inconclusive regarding the extent to which an internationally
adopted child's immunization record reflects the child's protection. A
child's record might indicate administration of MMR vaccine when only
single-antigen measles vaccine was administered. A study of children
adopted from the People's Republic of China, Russia, and Eastern Europe
determined that only 39% (range: 17%--88% by country) of children with
documentation of >3 doses of DTP before adoption had protective levels
of diphtheria and tetanus antitoxin (142). However, antibody
testing was performed by using a hemagglutination assay, which tends to
underestimate protection and cannot directly be compared with antibody
concentration (143). Another study measured antibody to diphtheria
and tetanus toxins among 51 children who had records of having received
>2 doses of DTP. The majority of the children were from Russia,
Eastern Europe, and Asian countries, and 78% had received all their
vaccine doses in an orphanage. Overall, 94% had evidence of protection
against diphtheria (EIA > 0.1 IU/mL). A total of 84% had protection
against tetanus (enzyme-linked immunosorbent assay [ELISA] > 0.5
IU/mL). Among children without protective tetanus antitoxin concentration,
all except one had records of >3 doses of vaccine, and the
majority of nonprotective concentrations were categorized as indeterminate
(ELISA = 0.05--0.49 IU/mL) (144). Reasons for the discrepant
findings in these two studies probably relate to different laboratory
methodologies; the study using a hemagglutination assay might have
underestimated the number of children who were protected. Additional
studies using standardized methodologies are needed. Data are likely to
remain limited for countries other than the People's Republic of China,
Russia, and Eastern Europe because of the limited number of adoptees from
other countries.

Physicians and other health-care providers can follow one of multiple
approaches if a question exists regarding whether vaccines administered to
an international adoptee were immunogenic. Repeating the vaccinations is
an acceptable option. Doing so is usually safe and avoids the need to
obtain and interpret serologic tests. If avoiding unnecessary injections
is desired, judicious use of serologic testing might be helpful in
determining which immunizations are needed. This report provides guidance
on possible approaches to evaluation and revaccination for each vaccine
recommended universally for children in the United States (see Table
6 and the following sections).

MMR Vaccine

The simplest approach to resolving concerns regarding MMR immunization
among internationally adopted children is to revaccinate with one or two
doses of MMR vaccine, depending on the child's age. Serious adverse events
after MMR vaccinations are rare (6).
No evidence indicates that administering MMR vaccine increases the risk
for adverse reactions among persons who are already immune to measles,
mumps, or rubella as a result of previous vaccination or natural disease.
Doses of measles-containing vaccine administered before the first birthday
should not be counted as part of the series (6).
Alternatively, serologic testing for immunoglobulin G (IgG) antibody to
vaccine viruses indicated on the vaccination record can be considered.
Serologic testing is widely available for measles and rubella IgG
antibody. A child whose record indicates receipt of monovalent measles or
measles-rubella vaccine at age >1 year and who has protective
antibody against measles and rubella should receive a single dose of MMR
as age-appropriate to ensure protection against mumps (and rubella if
measles vaccine alone had been used). If a child whose record indicates
receipt of MMR at age >12 months has a protective concentration
of antibody to measles, no additional vaccination is needed unless
required for school entry.

Hib Vaccine

Serologic correlates of protection for children vaccinated >2 months
previously might be difficult to interpret. Because the number of
vaccinations needed for protection decreases with age and adverse events
are rare (24),
age-appropriate vaccination should be provided. Hib vaccination is not
recommended routinely for children aged >5 years.

Hepatitis B Vaccine

Serologic testing for HBsAg is recommended for international adoptees,
and children determined to be HBsAg-positive should be monitored for the
development of liver disease. Household members of HBsAg-positive children
should be vaccinated. A child whose records indicate receipt of
>3 doses of vaccine can be considered protected, and additional
doses are not needed if >1 doses were administered at age
>6 months. Children who received their last hepatitis B vaccine
dose at age <6 months should receive an additional dose at age
>6 months. Those who have received <3 doses should complete
the series at the recommended intervals and ages (Table
1).

Poliovirus Vaccine

The simplest approach is to revaccinate internationally adopted
children with IPV according to the U.S. schedule. Adverse events after IPV
are rare (4).
Children appropriately vaccinated with three doses of OPV in economically
developing countries might have suboptimal seroconversion, including to
type 3 poliovirus (125). Serologic testing for neutralizing
antibody to poliovirus types 1, 2, and 3 can be obtained commercially and
at certain state health department laboratories. Children with protective
titers against all three types do not need revaccination and should
complete the schedule as age-appropriate. Alternately, because the booster
response after a single dose of IPV is excellent among children who
previously received OPV (3), a
single dose of IPV can be administered initially with serologic testing
performed 1 month later.

DTaP Vaccine

Vaccination providers can revaccinate a child with DTaP vaccine without
regard to recorded doses; however, one concern regarding this approach is
that data indicate increased rates of local adverse reactions after the
fourth and fifth doses of DTP or DTaP (42).
If a revaccination approach is adopted and a severe local reaction occurs,
serologic testing for specific IgG antibody to tetanus and diphtheria
toxins can be measured before administering additional doses. Protective
concentration** indicates that further doses are unnecessary and
subsequent vaccination should occur as age-appropriate. No established
serologic correlates exist for protection against pertussis.

For a child whose record indicates receipt of >3 doses of DTP
or DTaP, serologic testing for specific IgG antibody to both diphtheria
and tetanus toxin before additional doses is a reasonable approach. If a
protective concentration is present, recorded doses can be considered
valid, and the vaccination series should be completed as age-appropriate.
Indeterminate antibody concentration might indicate immunologic memory but
antibody waning; serology can be repeated after a booster dose if the
vaccination provider wishes to avoid revaccination with a complete series.

Alternately, for a child whose records indicate receipt of >3
doses, a single booster dose can be administered, followed by serologic
testing after 1 month for specific IgG antibody to both diphtheria and
tetanus toxins. If a protective concentration is obtained, the recorded
doses can be considered valid and the vaccination series completed as
age-appropriate. Children with indeterminate concentration after a booster
dose should be revaccinated with a complete series.

Varicella Vaccine

Varicella vaccine is not administered in the majority of countries. A
child who lacks a reliable medical history regarding prior varicella
disease should be vaccinated as age-appropriate (8).

Pneumococcal Vaccines

Pneumococcal conjugate and pneumococcal polysaccharide vaccines are not
administered in the majority of countries and should be administered as
age-appropriate or as indicated by the presence of underlying medical
conditions (26,43).

Altered Immunocompetence

ACIP's statement regarding vaccinating immunocompromised persons
summarizes recommendations regarding the efficacy, safety, and use of
specific vaccines and immune globulin preparations for immunocompromised
persons (145).
ACIP statements regarding individual vaccines or immune globulins contain
additional information regarding those concerns.

Severe immunosuppression can be the result of congenital
immunodeficiency, HIV infection, leukemia, lymphoma, generalized
malignancy or therapy with alkylating agents, antimetabolites, radiation,
or a high dose, prolonged course of corticosteroids. The degree to which a
person is immunocompromised should be determined by a physician. Severe
complications have followed vaccination with live-virus vaccines and live
bacterial vaccines among immunocompromised patients (146--153).
These patients should not receive live vaccines except in certain
circumstances that are noted in the following paragraphs. MMR vaccine
viruses are not transmitted to contacts, and transmission of varicella
vaccine virus is rare (6,138).
MMR and varicella vaccines should be administered to susceptible household
and other close contacts of immunocompromised patients when indicated.

Persons with HIV infection are at increased risk for severe
complications if infected with measles. No severe or unusual adverse
events have been reported after measles vaccination among HIV-infected
persons who did not have evidence of severe immunosuppression
(154--157). As a result, MMR vaccination is recommended for all
HIV-infected persons who do not have evidence of severe
immunosuppression†† and for whom measles vaccination would
otherwise be indicated.

Children with HIV infection are at increased risk for complications of
primary varicella and for herpes zoster, compared with immunocompetent
children (138,158).
Limited data among asymptomatic or mildly symptomatic HIV-infected
children (CDC class N1 or A1, age-specific CD4+ lymphocyte
percentages of >25%) indicate that varicella vaccine is
immunogenic, effective, and safe (138,159).
Varicella vaccine should be considered for asymptomatic or mildly
symptomatic HIV-infected children in CDC class N1 or A1 with age-specific
CD4+ T lymphocyte percentages of >25%. Eligible
children should receive two doses of varicella vaccine with a 3-month
interval between doses (138).

HIV-infected persons who are receiving regular doses of IGIV might not
respond to varicella vaccine or MMR or its individual component vaccines
because of the continued presence of passively acquired antibody. However,
because of the potential benefit, measles vaccination should be considered
approximately 2 weeks before the next scheduled dose of IGIV (if not
otherwise contraindicated), although an optimal immune response is
unlikely to occur. Unless serologic testing indicates that specific
antibodies have been produced, vaccination should be repeated (if not
otherwise contraindicated) after the recommended interval (Table
4). An additional dose of IGIV should be considered for persons on
maintenance IGIV therapy who are exposed to measles >3 weeks
after administering a standard dose (100--400 mg/kg body weight) of IGIV.

Persons with cellular immunodeficiency should not receive varicella
vaccine. However, ACIP recommends that persons with impaired humoral
immunity (e.g., hypogammaglobulinemia or dysgammaglobulinemia) should be
vaccinated (138,160).

Inactivated, recombinant, subunit, polysaccharide, and conjugate
vaccines and toxoids can be administered to all immunocompromised
patients, although response to such vaccines might be suboptimal. If
indicated, all inactivated vaccines are recommended for immunocompromised
persons in usual doses and schedules. In addition, pneumococcal,
meningococcal, and Hib vaccines are recommended specifically for certain
groups of immunocompromised patients, including those with functional or
anatomic asplenia (145,161).

Except for influenza vaccine, which should be administered annually
(88),
vaccination during chemotherapy or radiation therapy should be avoided
because antibody response is suboptimal. Patients vaccinated while
receiving immunosuppressive therapy or in the 2 weeks before starting
therapy should be considered unimmunized and should be revaccinated
>3 months after therapy is discontinued. Patients with leukemia
in remission whose chemotherapy has been terminated for >3
months can receive live-virus vaccines.

Corticosteroids

The exact amount of systemically absorbed corticosteroids and the
duration of administration needed to suppress the immune system of an
otherwise immunocompetent person are not well-defined. The majority of
experts agree that corticosteroid therapy usually is not a
contraindication to administering live-virus vaccine when it is short-term
(i.e., <2 weeks); a low to moderate dose; long-term, alternate-day
treatment with short-acting preparations; maintenance physiologic doses
(replacement therapy); or administered topically (skin or eyes) or by
intra-articular, bursal, or tendon injection (145).
Although of theoretical concern, no evidence of increased severity of
reactions to live vaccines has been reported among persons receiving
corticosteroid therapy by aerosol, and such therapy is not a reason to
delay vaccination. The immunosuppressive effects of steroid treatment
vary, but the majority of clinicians consider a dose equivalent to either
>2 mg/kg of body weight or a total of 20 mg/day of prednisone or
equivalent for children who weigh >10 kg, when administered for
>2 weeks as sufficiently immunosuppressive to raise concern
regarding the safety of vaccination with live-virus vaccines (84,145).
Corticosteroids used in greater than physiologic doses also can reduce the
immune response to vaccines. Vaccination providers should wait
>1 month after discontinuation of therapy before administering a
live-virus vaccine to patients who have received high systemically
absorbed doses of corticosteroids for >2 weeks.

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). The source of the
transplanted stem cells can be from either a donor's bone marrow or
peripheral blood or harvested from the umbilical cord of a newborn infant
(162).

Antibody titers to vaccine-preventable diseases (e.g., tetanus,
poliovirus, measles, mumps, rubella, and encapsulated bacteria) decline
during the 1--4 years after allogeneic or autologous HSCT if the recipient
is not revaccinated (163--167). HSCT recipients are at increased
risk for certain vaccine-preventable diseases, including those caused by
encapsulated bacteria (i.e., pneumococcal and Hib infections). As a
result, HSCT recipients should be routinely revaccinated after HSCT,
regardless of the source of the transplanted stem cells. Revaccination
with inactivated, recombinant, subunit, polysaccharide, and Hib vaccines
should begin 12 months after HSCT (162).
An exception to this recommendation is for influenza vaccine, which should
be administered at >6 months after HSCT and annually for the
life of the recipient thereafter. 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 recommended for HSCT recipients because of insufficient
experience using these vaccines among HSCT recipients (162).
The household and other close contacts of HSCT recipients and health-care
workers who care for HSCT recipients, should be appropriately vaccinated,
including against influenza, measles, and varicella. Additional details of
vaccination of HSCT recipients and their contacts can be found in a
specific CDC report on this topic (162).

Vaccinating Persons with Bleeding Disorders and Persons Receiving
Anticoagulant Therapy

Persons with bleeding disorders (e.g., hemophilia) and persons
receiving anticoagulant therapy have an increased risk for acquiring
hepatitis B and at least the same risk as the general population of
acquiring other vaccine-preventable diseases. However, because of the risk
for hematoma formation after injections, intramuscular injections are
often avoided among persons with bleeding disorders by using the
subcutaneous or intradermal routes for vaccines that are administered
normally by the intramuscular route. Hepatitis B vaccine administered
intramuscularly to 153 persons with hemophilia by using a 23-gauge needle,
followed by steady pressure to the site for 1--2 minutes, resulted in a 4%
bruising rate with no patients requiring factor supplementation
(168). Whether antigens that produce more local reactions (e.g.,
pertussis) would produce an equally low rate of bruising is unknown.

When hepatitis B or any other intramuscular vaccine is indicated for a
patient with a bleeding disorder or a person receiving anticoagulant
therapy, the vaccine should be administered intramuscularly if, in the
opinion of a physician familiar with the patient's bleeding risk, the
vaccine can be administered with reasonable safety by this route. If the
patient receives antihemophilia or similar therapy, intramuscular
vaccinations can be scheduled shortly after such therapy is administered.
A fine needle (<23 gauge) should be used for the vaccination and
firm pressure applied to the site, without rubbing, for >2
minutes. The patient or family should be instructed concerning the risk
for hematoma from the injection.

Vaccination Records

Consent to Vaccinate

The National Childhood Vaccine Injury Act of 1986 (42 U.S.C. §
300aa-26) requires that all health-care providers in the United States who
administer any vaccine covered by the act§§ must provide a copy
of the relevant, current edition of the vaccine information materials that
have been produced by CDC before administering each dose of the vaccine.
The vaccine information material must be provided to the parent or legal
representative of any child or to any adult to whom the physician or other
health-care provider intends to administer the vaccine. The Act does not
require that a signature be obtained, but documentation of consent is
recommended or required by certain state or local authorities.

Provider Records

Documentation of patient vaccinations helps ensure that persons in need
of a vaccine receive it and that adequately vaccinated patients are not
overimmunized, possibly increasing the risk for local adverse events
(e.g., tetanus toxoid). Serologic test results for vaccine-preventable
diseases (e.g., those for rubella screening) as well as documented
episodes of adverse events also should be recorded in the permanent
medical record of the vaccine recipient.

Health-care providers who administer vaccines covered by the National
Childhood Vaccine Injury Act are required to ensure that the permanent
medical record of the recipient (or a permanent office log or file)
indicates the date the vaccine was administered, the vaccine manufacturer,
the vaccine lot number, and the name, address, and title of the person
administering the vaccine. Additionally, the provider is required to
record the edition date of the vaccine information materials distributed
and the date those materials were provided. Regarding this Act, the term
health-care provider is defined as any licensed health-care
professional, organization, or institution, whether private or public
(including federal, state, and local departments and agencies), under
whose authority a specified vaccine is administered. ACIP recommends that
this same information be kept for all vaccines, not just for those
required by the National Childhood Vaccine Injury Act.

Patients' Personal Records

Official immunization cards have been adopted by every state,
territory, and the District of Columbia to encourage uniformity of records
and to facilitate assessment of immunization status by schools and child
care centers. The records also are key tools in immunization education
programs aimed at increasing parental and patient awareness of the need
for vaccines. A permanent immunization record card should be established
for each newborn infant and maintained by the parent or guardian. In
certain states, these cards are distributed to new mothers before
discharge from the hospital. Using immunization record cards for
adolescents and adults also is encouraged.

Registries

Immunization registries are confidential, population-based,
computerized information systems that collect vaccination data for as many
children as possible within a geographic area. Registries are a critical
tool that can increase and sustain increased vaccination coverage by
consolidating vaccination records of children from multiple providers,
generating reminder and recall vaccination notices for each child, and
providing official vaccination forms and vaccination coverage assessments
(169).
A fully operational immunization registry also can prevent duplicate
vaccinations, limit missed appointments, reduce vaccine waste, and reduce
staff time required to produce or locate immunization records or
certificates. The National Vaccine Advisory Committee strongly encourages
development of community- or state-based immunization registry systems and
recommends that vaccination providers participate in these registries
whenever possible (170,171).
A 95% participation of children aged <6 years in fully operational
population-based immunization registries is a national health objective
for 2010 (172).

Reporting Adverse Events After
Vaccination

Modern vaccines are safe and effective; however, adverse events have
been reported after administration of all vaccines (82).
These events range from frequent, minor, local reactions to extremely
rare, severe, systemic illness (e.g., encephalopathy). Establishing
evidence for cause-and-effect relationships on the basis of case reports
and case series alone is impossible because temporal association alone
does not necessarily indicate causation. Unless the syndrome that occurs
after vaccination is clinically or pathologically distinctive, more
detailed epidemiologic studies to compare the incidence of the event among
vaccinees with the incidence among unvaccinated persons are often
necessary. Reporting adverse events to public health authorities,
including serious events, is a key stimulus to developing studies to
confirm or refute a causal association with vaccination. More complete
information regarding adverse reactions to a specific vaccine can be found
in the ACIP recommendations for that vaccine and in a specific statement
on vaccine adverse reactions (82).

The National Childhood Vaccine Injury Act requires health-care
providers to report selected events occurring after vaccination to the
Vaccine Adverse Event Reporting System (VAERS). Events for which reporting
is required appear in the Vaccine Injury Table.¶¶ Persons other
than health-care workers also can report adverse events to VAERS. Adverse
events other than those that must be reported or that occur after
administration of vaccines not covered by the act, including events that
are serious or unusual, also should be reported to VAERS, even if the
physician or other health-care provider is uncertain they are related
causally. VAERS forms and instructions are available in the FDA Drug
Bulletin, by calling the 24-hour VAERS Hotline at 800-822-7967, or from
the VAERS website at http://www.vaers.org/ (accessed November
7, 2001).

Vaccine Injury Compensation Program

The National Vaccine Injury Compensation Program, established by the
National Childhood Vaccine Injury Act, is a no-fault system in which
persons thought to have suffered an injury or death as a result of
administration of a covered vaccine can seek compensation. The program,
which became operational on October 1, 1988, is intended as an alternative
to civil litigation under the traditional tort system in that negligence
need not be proven. Claims arising from covered vaccines must first be
adjudicated through the program before civil litigation can be pursued.

The program relies on a Vaccine Injury Table listing the vaccines
covered by the program as well as the injuries, disabilities, illnesses,
and conditions (including death) for which compensation might be awarded.
The table defines the time during which the first symptom or substantial
aggravation of an injury must appear after vaccination. Successful
claimants receive a legal presumption of causation if a condition listed
in the table is proven, thus avoiding the need to prove actual causation
in an individual case. Claimants also can prevail for conditions not
listed in the table if they prove causation. Injuries after administration
of vaccines not listed in the legislation authorizing the program are not
eligible for compensation through the program. Additional information is
available from the following:

National Vaccine Injury Compensation Program
Health Resources and
Services Administration
Parklawn Building, Room 8-46
5600 Fishers
Lane
Rockville, MD 20857
Telephone: 800-338-2382 (24-hour
recording)
Internet: http://www.hrsa.gov/bhpr/vicp
(accessed November 7, 2001)

Persons wishing to file a claim for vaccine injury should call or write
the following:

U.S. Court of Federal Claims
717 Madison Place,
N.W.
Washington, D.C. 20005
Telephone: 202-219-9657

Benefit and Risk Communication

Parents, guardians, legal representatives, and adolescent and adult
patients should be informed regarding the benefits and risks of vaccines
in understandable language. Opportunity for questions should be provided
before each vaccination. Discussion of the benefits and risks of
vaccination is sound medical practice and is required by law.

The National Childhood Vaccine Injury Act requires that vaccine
information materials be developed for each vaccine covered by the Act.
These materials, known as Vaccine Information Statements, must be
provided by all public and private vaccination providers each time a
vaccine is administered. Copies of Vaccine Information Statements are
available from state health authorities responsible for immunization, or
they can be obtained from CDC's National Immunization Program website at
http://www.cdc.gov/nip (accessed
November 7, 2001). Translations of Vaccine Information Statements into
languages other than English are available from certain state immunization
programs and from the Immunization Action Coalition website at http://www.immunize.org/ (accessed
November 7, 2001).

Health-care providers should anticipate that certain parents or
patients will question the need for or safety of vaccination, refuse
certain vaccines, or even reject all vaccinations. A limited number of
persons might have religious or personal objections to vaccinations.
Others wish to enter into a dialogue regarding the risks and benefits of
certain vaccines. Having a basic understanding of how patients view
vaccine risk and developing effective approaches in dealing with vaccine
safety concerns when they arise is imperative for vaccination providers.

Each person understands and reacts to vaccine information on the basis
of different factors, including prior experience, education, personal
values, method of data presentation, perceptions of the risk for disease,
perceived ability to control those risks, and their risk preference.
Increasingly, through the media and nonauthoritative Internet sites,
decisions regarding risk are based on inaccurate information. Only through
direct dialogue with parents and by using available resources, health-care
professionals can prevent acceptance of media reports and information from
nonauthoritative Internet sites as scientific fact.

When a parent or patient initiates discussion regarding a vaccine
controversy, the health-care professional should discuss the specific
concerns and provide factual information, using language that is
appropriate. Effective, empathetic vaccine risk communication is essential
in responding to misinformation and concerns, although recognizing that
for certain persons, risk assessment and decision-making is difficult and
confusing. Certain vaccines might be acceptable to the resistant parent.
Their concerns should then be addressed in the context of this
information, using the Vaccine Information Statements and offering other
resource materials (e.g., information available on the National
Immunization Program website).

Although a limited number of providers might choose to exclude from
their practice those patients who question or refuse vaccination, the more
effective public health strategy is to identify common ground and discuss
measures that need to be followed if the patient's decision is to defer
vaccination. Health-care providers can reinforce key points regarding each
vaccine, including safety, and emphasize risks encountered by unimmunized
children. Parents should be advised of state laws pertaining to school or
child care entry, which might require that unimmunized children stay home
from school during outbreaks. Documentation of these discussions in the
patient's record, including the refusal to receive certain vaccines (i.e.,
informed refusal), might reduce any potential liability if a
vaccine-preventable disease occurs in the unimmunized patient.

Vaccination Programs

The best way to reduce vaccine-preventable diseases is to have a highly
immune population. Universal vaccination is a critical part of quality
health care and should be accomplished through routine and intensive
vaccination programs implemented in physicians' offices and in public
health clinics. Programs should be established and maintained in all
communities to ensure vaccination of all children at the recommended age.
In addition, appropriate vaccinations should be available for all
adolescents and adults.

Physicians and other pediatric vaccination providers should adhere to
the standards for child and adolescent immunization practices (1).
These standards define appropriate vaccination practices for both the
public and private sectors. The standards provide guidance on practices
that will result in eliminating barriers to vaccination. These include
practices aimed at eliminating unnecessary prerequisites for receiving
vaccinations, eliminating missed opportunities to vaccinate, improving
procedures to assess vaccination needs, enhancing knowledge regarding
vaccinations among parents and providers, and improving the management and
reporting of adverse events. Additionally, the standards address the
importance of recall and reminder systems and using assessments to monitor
clinic or office vaccination coverage levels among patients.

Standards of practice also have been published to increase vaccination
coverage among adults (2).
Persons aged >65 years and all adults with medical conditions
that place them at risk for pneumococcal disease should receive
>1 doses of pneumococcal polysaccharide vaccine. All persons
aged >50 years and those with medical conditions that increase
the risk for complications from influenza should receive annual influenza
vaccination. All adults should complete a primary series of tetanus and
diphtheria toxoids and receive a booster dose every 10 years. Adult
vaccination programs also should provide MMR and varicella vaccines
whenever possible to anyone susceptible to measles, mumps, rubella, or
varicella. Persons born after 1956 who are attending college (or other
posthigh school educational institutions), who are employed in
environments that place them at increased risk for measles transmission
(e.g., health-care facilities), or who are traveling to areas with endemic
measles, should have documentation of having received two doses of MMR on
or after their first birthday or other evidence of immunity (6,173).
All other adults born after 1956 should have documentation of >1
doses of MMR vaccine on or after their first birthday or have other
evidence of immunity. No evidence indicates that administering MMR vaccine
increases the risk for adverse reactions among persons who are already
immune to measles, mumps, or rubella as a result of previous vaccination
or disease. Widespread use of hepatitis B vaccine is encouraged for all
persons who might be at increased risk (e.g., adolescents and adults who
are either in a group at high risk or reside in areas with increased rates
of injection-drug use, teenage pregnancy, or sexually transmitted
disease).

Every visit to a physician or other health-care provider can be an
opportunity to update a patient's immunization status with needed
vaccinations. Official health agencies should take necessary steps,
including developing and enforcing school immunization requirements, to
ensure that students at all grade levels (including college) and those in
child care centers are protected against vaccine-preventable diseases.
Agencies also should encourage institutions (e.g., hospitals and long-term
care facilities) to adopt policies regarding the appropriate vaccination
of patients, residents, and employees (173).

Dates of vaccination (day, month, and year) should be recorded on
institutional immunization records (e.g., those kept in schools and child
care centers). This record will facilitate assessments that a primary
vaccination series has been completed according to an appropriate schedule
and that needed booster doses have been administered at the appropriate
time.

The independent, nonfederal Task Force on Community Preventive Services
(the Task Force) gives public health decision-makers recommendations on
population-based interventions to promote health and prevent disease,
injury, disability, and premature death. The recommendations are based on
systematic reviews of the scientific literature regarding effectiveness
and cost-effectiveness of these interventions. In addition, the Task Force
identifies critical information regarding the other effects of these
interventions, as well as the applicability to specific populations and
settings and the potential barriers to implementation. This information is
available through the Internet at http://www.thecommunityguide.org/
(accessed November 7, 2001).

Beginning in 1996, the Task Force systematically reviewed published
evidence on the effectiveness and cost-effectiveness of population-based
interventions to increase coverage of vaccines recommended for routine use
among children, adolescents, and adults. A total of 197 articles were
identified that evaluated a relevant intervention, met inclusion criteria,
and were published during 1980--1997. Reviews of 17 specific interventions
were published in 1999 (174--176). Using the results of their
review, the Task Force made recommendations regarding the use of these
interventions (177). A number of interventions were identified and
recommended on the basis of published evidence. The interventions and the
recommendations are summarized in this report (Table
7).

Vaccine Information
Sources

In addition to these general recommendations, other sources are
available that contain specific and updated vaccine information.

National Immunization Information Hotline

The National Immunization Information Hotline is supported by CDC's
National Immunization Program and provides vaccination information for
health-care providers and the public, 8:00 am--11:00 pm, Monday--Friday:

Telephone (English): 800-232-2522
Telephone (Spanish):
800-232-0233
Telephone (TTY): 800-243-7889
Internet: http://www.ashastd.org/ (accessed
November 7, 2001)

CDC's National Immunization Program

CDC's National Immunization Program website provides direct access to
immunization recommendations of the Advisory Committee on Immunization
Practices (ACIP), vaccination schedules, vaccine safety information,
publications, provider education and training, and links to other
immunization-related websites. It is located at http://www.cdc.gov/nip (accessed
November 7, 2001).

Morbidity and Mortality Weekly Report

ACIP recommendations regarding vaccine use, statements of vaccine
policy as they are developed, and reports of specific disease activity are
published by CDC in the Morbidity and Mortality Weekly Report
(MMWR) series. Electronic subscriptions are free and available at
http://www.cdc.gov/subscribe.html
(accessed November 7, 2001). Printed subscriptions are available at

Superintendent of Documents
U.S. Government Printing
Office
Washington, D.C. 20402-9235

American Academy of Pediatrics (AAP)

Every 3 years, AAP issues the Red Book: Report of the Committee on
Infectious Diseases, which contains a composite summary of AAP
recommendations concerning infectious diseases and immunizations for
infants, children, and adolescents.

Telephone: 888-227-1770
Internet: http://www.aap.org/ (accessed November 7,
2001)

American Academy of Family Physicians (AAFP)

Information from the professional organization of family physicians is
available at http://www.aafp.org/
(accessed November 7, 2001).

Immunization Action Coalition

This source provides extensive free provider and patient information,
including translations of Vaccine Information Statements into multiple
languages. The Internet address is http://www.immunize.org/ (accessed
November 7, 2001).

National Network for Immunization Information

This information source is provided by the Infectious Diseases Society
of America, Pediatric Infectious Diseases Society, AAP, American Nurses
Association, and other professional organizations. It provides objective,
science-based information regarding vaccines for the public and providers.
The Internet site is http://www.immunizationinfo.org/
(accessed November 7, 2001).

Vaccine Education Center

Located at the Children's Hospital of Philadelphia, this source
provides patient and provider information. The Internet address is http://www.vaccine.chop.edu/
(accessed November 7, 2001).

Institute for Vaccine Safety

Located at Johns Hopkins University School of Public Health, this
source provides information regarding vaccine safety concerns and
objective and timely information to health-care providers and parents. It
is available at http://www.vaccinesafety.edu/
(accessed November 7, 2001).

National Partnership for Immunization

This national organization encourages greater acceptance and use of
vaccinations for all ages through partnerships with public and private
organizations. Their Internet address is http://www.partnersforimmunization.org/
(accessed November 7, 2001).

State and Local Health Departments

State and local health departments provide technical advice through
hotlines, electronic mail, and Internet sites, including printed
information regarding vaccines and immunization schedules, posters, and
other educational materials.

Acknowledgments

The members of the Advisory Committee on Immunization Practices are
grateful for the contributions of Margaret Hostetter, M.D., Yale Child
Health Research Center; Mary Staat, M.D., Children's Hospital Medical
Center of Cincinnati; Deborah Wexler, M.D., Immunization Action Coalition;
and John Grabenstein, Ph.D., U.S. Army Medical Command.

References

CDC.
Standards for pediatric immunization practices: recommended by the
National Vaccine Advisory Committee; approved by the U.S. Public Health
Service. MMWR 1993;42(No. RR-5):1--13.***

CDC.
Health objectives for the nation public health burden of
vaccine-preventable diseases among adults: standards for adult
immunization practice. MMWR 1990;39:725--9.***

CDC.
Poliomyelitis prevention in the United States: introduction of a
sequential vaccination schedule of inactivated poliovirus vaccine
followed by oral poliovirus vaccine; recommendations of the Advisory
Committee on Immunization Practices (ACIP). MMWR 1997;46(No.
RR-3):1--25.

CDC.
Poliomyelitis prevention in the United States: updated recommendations
of the Advisory Committee on Immunization Practices (ACIP). MMWR
2000;49(No. RR-5):1--22.

Plotkin SA. Immunologic correlates of protection induced by
vaccination. Pediatr Infect Dis J 2001;20:63--75.

CDC.
Measles, mumps, and rubella---vaccine use and strategies for elimination
of measles, rubella, and congenital rubella syndrome and control of
mumps: recommendations of the Advisory Committee on Immunization
Practices (ACIP). MMWR 1998;47(No. RR-8):1--57.

Watson JC, Pearson JA, Markowitz LE, et al. Evaluation of measles
revaccination among school-entry-aged children. Pediatrics
1996;97:613--8.

CDC.
Prevention of varicella: recommendations of the Advisory Committee on
Immunization Practices (ACIP). MMWR 1996;45(No. RR-11):8.

CDC.
Human rabies prevention---United States, 1999: recommendations of the
Advisory Committee on Immunization Practices (ACIP). MMWR 1999;48(No.
RR-1):1--21.

Levine L, Edsall G. Tetanus toxoid: what determines reaction
proneness [Letter]? J Infect Dis 1981;144:376.

Edsall, G, Elliot MW, Peebles TC, Levine L, Eldred MC. Excessive use
of tetanus toxoid boosters. JAMA 1967;202:17--9.

Hutchins SS, Escolan J, Markowitz LE, et al. Measles outbreak among
unvaccinated preschool-age children: opportunities missed by health care
providers to administer measles vaccine. Pediatrics 1989;83:369--74.

Deforest A, Long SS, Lischner HW, et al. Simultaneous administration
of measles-mumps-rubella vaccine with booster doses of
diphtheria-tetanus-pertussis and poliovirus vaccines. Pediatrics
1988;81:237--46.

King GE, Hadler SC. Simultaneous administration of childhood
vaccines: an important public health policy that is safe and
efficacious. Pediatr Infect Dis J 1994;13:394--407.

Dashefsky B, Wald E, Guerra N, Byers C. Safety, tolerability, and
immunogenicity of concurrent administration of Haemophilus
influenzae type B conjugate vaccine (meningococcal protein
conjugate) with either measles-mumps-rubella vaccine or
diphtheria-tetanus-pertussis and oral poliovirus vaccines in 14- to
23-month-old infants. Pediatrics 1990;85(4 Pt 2):682--9.

Giammanco G, Li Volti S, Mauro L, et al. Immune response to
simultaneous administration of a recombinant DNA hepatitis B vaccine and
multiple compulsory vaccines in infancy. Vaccine 1991;9:747--50.

Shinefield HR, Black SB, Staehle BO, et al. Safety, tolerability and
immunogenicity of concomitant injections in separate locations of
M-M-R®II, VARIVAX® and
TETRAMUNE® in healthy children vs. concomitant injections of
M-M-R®II and TETRAMUNE® followed six
weeks later by VARIVAX®. Pediatr Infect Dis J 1998;17:980--5.

CDC.
Typhoid immunization: recommendations of the Advisory Committee on
Immunization Practices (ACIP). MMWR 1994;43(No. RR-14):1--7.

DeStefano F, Goodman RA, Noble GR, McClary GD, Smith SJ, Broome CV.
Simultaneous administration of influenza and pneumococcal vaccines. JAMA
1982;247:2551--4.

Yvonnet B, Coursaget P, Deubel V, Diop-Mar I, Digoutte JP, Chiron J.
Simultaneous administration of hepatitis B and yellow fever
vaccinations. J Med Virol 1986;19:307--11.

Stefano I, Sato HK, Pannuti CS, et al. Recent immunization against
measles does not interfere with the sero-response to yellow fever
vaccine. Vaccine 1999;17:1042--6.

CDC.
Yellow fever vaccine: recommendations of the Immunization Practices
Advisory Committee (ACIP). MMWR 1990;39(No. RR-6):1--6.

Shinefield HR, Black S, Ray P, et al. Safety and immunogenicity of
heptavalent pneumococcal CRM197 conjugate vaccine in infants
and toddlers. Pediatr Infect Dis J 1999;18:757--63.

CDC.
Haemophilus b conjugate vaccines for prevention of Haemophilus
influenzae type b disease among infants and children two months of
age and older: recommendations of the Immunization Practices Advisory
Committee (ACIP). MMWR 1991;40(No. RR-1):1--7.

CDC.
Pertussis vaccination: use of acellular pertussis vaccines among infants
and young children: recommendations of the Advisory Committee on
Immunization Practices (ACIP). MMWR 1997;46(No. RR-7):1--25.

CDC.
Preventing pneumococcal disease among infants and young children:
recommendations of the Advisory Committee on Immunization Practices
(ACIP). MMWR 2000;49(No. RR-9):1--35.

CDC.
Combination vaccines for childhood immunization: recommendations of the
Advisory Committee on Immunization Practices (ACIP), the American
Academy of Pediatrics (AAP), and the American Academy of Family
Physicians (AAFP). MMWR 1999;48(No. RR-5):5.

Petralli JK, Merigan TC, Wilbur JR. Action of endogenous interferon
against vaccinia infection in children. Lancet 1965;2:401--5.

Petralli, JK, Merigan TC, Wilbur JR. Circulating interferon after
measles vaccination. N Eng J Med 1965;273:198--201.

CDC.
Simultaneous administration of varicella vaccine and other recommended
childhood vaccines---United States, 1995--1999. MMWR
2001;50:1058--61.

Siber GR, Werner BC, Halsey NA, et al. Interference of immune
globulin with measles and rubella immunization. J Pediatr
1993;122:204--11.

Mason W, Takahashi M, Schneider T. Persisting passively acquired
measles antibody following gamma globulin therapy for Kawasaki disease
and response to live virus vaccination [Abstract 311]. Presented at the
32nd meeting of the Interscience Conference on Antimicrobial
Agents and Chemotherapy, Los Angeles, California, October 1992.

Kaplan JE, Nelson DB, Schonberger LB, et al. Effect of immune
globulin on the response to trivalent oral poliovirus and yellow fever
vaccinations. Bull World Health Organ 1984;62:585--90.

Black NA, Parsons A, Kurtz JB, McWhinney N, Lacey A, Mayon-White RT.
Post-partum rubella immunization: a controlled trial of two vaccines.
Lancet 1983;2:990--2.

CDC.
Control and prevention of rubella: evaluation and management of
suspected outbreaks, rubella in pregnant women, and surveillance for
congenital rubella syndrome. MMWR 2001;50(No. RR-12):1--24.

Siber GR, Snydman DR. Use of immune globulin in the prevention and
treatment of infections. In: Remington J, Swartz M, eds. Current
clinical topics in infectious diseases, vol 12. Oxford: Blackwell
Scientific, 1992.

Greenberg DP, Lieberman JM, Marcy SM, et al. Enhanced antibody
responses in infants given different sequences of heterogeneous
Haemophilus influenzae type B conjugate vaccines. J Pediatr
1995;126:206--11.

Anderson EL, Decker MD, Englund JA, et al. Interchangeability of
conjugated Haemophilus influenzae type b vaccines in infants.
JAMA 1995;273:849--53.

Piazza M, Abrescia N, Picciotto L, et al. Demonstration of the
interchangeability of 2 types of recombinant anti-hepatitis-B vaccine.
Boll Soc Ital Biol Sper 1993;69:273--80.

Bryan JP, Henry CH, Hoffman AG, et al. Randomized, cross-over,
controlled comparison of two inactivated hepatitis A vaccines. Vaccine
2000;19:743--50.

Greenberg DP, Pickering LK, Senders SD, et al. Interchangeability of
two diphtheria-tetanus-acellular pertussis vaccines in infancy.
Pediatrics 2002 (in press).

CDC.
Use of diphtheria toxoid-tetanus toxoid-acellular pertussis vaccine as a
five-dose series: supplemental recommendations of the Advisory Committee
on Immunization Practices (ACIP). MMWR 2000;49(No. RR-13):1--8.

CDC.
Prevention pneumococcal disease: recommendations of the Advisory
Committee on Immunization Practices (ACIP). MMWR 1997;46(No.
RR-8):1--24.

Szilagyi PG, Rodewald LE. Missed opportunities for immunizations: a
review of the evidence. Journal of Public Health Management Practice
1996;2:18--25.

Wald ER, Dashefsky B, Byers C, Guerra N, Taylor F. Frequency and
severity of infections in day care. J Pediatr 1988;112:540--6.

Lewis T, Osborn LM, Lewis K, Brockert J, Jacobsen J, Cherry JD.
Influence of parental knowledge and opinions on 12-month diphtheria,
tetanus, and pertussis vaccination rates. Am J Dis Child
1988;142:283--6.

Farizo KM, Stehr-Green PA, Markowitz LE, Patriarca PA. Vaccination
levels and missed opportunities for measles vaccination: a record audit
in a public pediatric clinic. Pediatrics 1992;89:589--92.

Halsey NA, Boulos R, Mode F, et al. Response to measles vaccine in
Haitian infants 6 to 12 months old: influence of maternal antibodies,
malnutrition, and concurrent illnesses. N Engl J Med 1985;313:544--9.

Ndikuyeze A, Munoz A, Stewart S, et al. Immunogenicity and safety of
measles vaccine in ill African children. Int J Epidemiol
1988;17:448--55.

Lindegren ML, Reynolds S, Atkinson W, Davis A, Falter K, Patriarca
P. Adverse events following measles vaccination of ill preschool-aged
children [Abstract 270]. Abstracts of the 31st Interscience
Conference on Antimicrobial Agents and Chemotherapy, September
29--October 2, 1991, Chicago, Illinois:144.

Atkinson W, Markowitz L, Baughman A, et al. Serologic response to
measles vaccination among ill children [Abstract 422]. Abstracts of the
32nd Interscience Conference on Antimicrobial Agents and
Chemotherapy, October 1992, Anaheim, California:181.

Krober MS, Stracener LE, Bass JW. Decreased measles antibody
response after measles-mumps-rubella vaccine in infants with colds. JAMA
1991;265:2095--6.

Shaw FE Jr, Guess HA, Roets JM, et al. Effect of anatomic injection
site, age and smoking on the immune response to hepatitis B vaccination.
Vaccine 1989;7:425--30.

Zuckerman JN. Importance of injecting vaccines into muscle:
different patients need different needle sizes. Brit Med J
2000;321:1237--8.

Ipp MM, Gold R, Goldback M, et al. Adverse reactions to diphtheria,
tetanus, pertussis-polio vaccination at 18 months of age: effect of
injection site and needle length. Pediatrics 1989;83:679--82.

Michaels L, Poole RW. Injection granuloma of the buttock. Can Med
Assoc J 1970;102:626--8.

Haramati N, Lorans R, Lutwin M, Kaleya RN. Injection granulomas:
intramuscle or intrafat? Arch Fam Med 1994;3:146--8.

Giles FH, French JH. Postinjection sciatic nerve palsies in infants
and children. J Pediatr 1961;58:195--204.

Fishbein DB, Sawyer LA, Reid-Sanden FL, Weir EH. Administration of
human diploid-cell rabies vaccine in the gluteal area [Letter]. N Engl J
Med 1988;318:124--5.

Bergeson PS, Singer SA, Kaplan AM. Intramuscular injections in
children. Pediatrics 1982;70:944--8.

Poland GA, Borrund A, Jacobson RM, et al. Determination of deltoid
fat pad thickness: implications for needle length in adult immunization.
JAMA 1997;277:1709--11.

Groswasser J, Kahn A, Bouche B, Hanquinet S, Perlmuter N, Hessel L.
Needle length and injection technique for efficient intramuscular
vaccine delivery in infants and children evaluated through an
ultrasonographic determination of subcutaneous and muscle layer
thickness. Pediatrics 1997;100:400--3.

Scheifele D, Bjornson G, Barreto L, Meekison W, Guasparini R.
Controlled trial of Haemophilus influenzae type b diphtheria
toxoid conjugate combined with diphtheria, tetanus and pertussis
vaccines, in 18-month-old children, including comparison of arm versus
thigh injection. Vaccine 1992;10:455--60.

Hingson RA, Davis HS, Rosen M. Historical development of jet
injection and envisioned uses in mass immunization and mass therapy
based upon two decades' experience. Mil Med 1963;128:516--24.

Reis EC, Jacobson RM, Tarbell S, Weniger BG. Taking the sting out of
shots: control of vaccination-associated pain and adverse reactions.
Pediatric Ann 1998;27:375--85.

Occupational Safety and Health Administration. Occupational exposure
to bloodborne pathogens; needlestick and other sharps injuries; final
rule (29 CFR Part 1910). Federal Register 2001;66:5318--25. Available at
http://www.osha-slc.gov/FedReg_osha_pdf/FED20010118A.pdf.
Accessed November 8, 2001.

Simonsen L, Kane A, Lloyd J, Zaffran M, Kane M. Unsafe injections in
the developing world and transmission of bloodborne pathogens: a review.
Bull World Health Organ 1999;77:789--800.

Kane A, Lloyd J, Zaffran M, Simonsen L, Kane M. Transmission of
hepatitis B, hepatitis C and human immunodeficiency viruses through
unsafe injections in the developing world: model-based regional
estimates. Bull World Health Organ 1999;77:801--7.

CDC. Needle-free injection technology. Atlanta, GA: US Department of
Health and Human Services, CDC, National Immunization Program, 2001.
Available at <www.cdc.gov/nip/dev/jetinject.htm.
Accessed November 8, 2001.

CDC.
Hepatitis B associated with jet gun injection---California
[Epidemiologic notes and reports]. MMWR 1986;35:373--6.

Canter J, Mackey K, Good LS, et al. Outbreak of hepatitis B
associated with jet injections in a weight reduction clinic. Arch Intern
Med 1990;150:1923--7.

Brito GS, Chen RT, Stefano IC, Campos AM, Oselka G. Risk of
transmission of HIV and other blood-born diseases via jet injectors
during immunization mass campaigns in Brazil [Abstract PC0132].
10th International Conference on AIDS, Yokohama, 7--12 August
1994;10:301. Available at http://www.aegis.com/pubs/aidsline/1994/dec/m94c3258.html.
Accessed November 8, 2001.

Hoffman PN, Abuknesha RA, Andrews NJ, Samuel D, Lloyd JS. Model to
assess the infection potential of jet injectors used in mass
immunization. Vaccine 2001;19:4020--7.

Taddio A, Nulman I, Goldbach M, Ipp M, Koren G. Use of
lidocaine-prilocain cream for vaccination pain in infants. J Pediatr
1994;124:643--8.

Uhari M. Eutectic mixture of lidocaine and prolocaine for
alleviating vaccination pain in infants. Pediatrics 1993;92:719--21.

Halperin SA, McGrath P, Smith B, Houston T. Lidocaine-prilocaine
patch decreases the pain associated with subcutaneous administration of
measles-mumps-rubella vaccine but does not adversely affect the antibody
response. J Pediatr 2000;136:789--94.

Frayling IM, Addison GM, Chatterge K, Meakin G. Methaemoglobinaemia
in children treated with prilocaine-lignocaine cream. Br Med J
1990;301:153--4.

Lewis K, Cherry JD, Sachs MH, et al. Effect of prophylactic
acetaminophen administration on reactions to DTP vaccination. Am J Dis
Child 1988;142:62--5.

Reis E, Holubkov R. Vapocoolant spray is equally effective as EMLA
cream in reducing immunization pain in school-aged children. Pediatrics
1997;100:e5. Available at http://www.pediatrics.org/cgi/content/full/100/6/e5.
Accessed November 8, 2001.

Redfield RR, Innis BL, Scott RM, Cannon HG, Bancroft WH. Clinical
evaluation of low-dose intradermally administered hepatitis B vaccine: a
cost reduction strategy. JAMA 1985;254:3203--6.

Coleman PJ, Shaw FE, Serovich J, Hadler SC, Margolis HS. Intradermal
hepatitis B vaccination in a large hospital employee population. Vaccine
1991;9:723--7.

CDC.
Update: vaccine side effects, adverse reactions, contraindications, and
precautions: recommendations of the Advisory Committee on Immunization
Practices (ACIP). MMWR 1996;45(No. RR-12):1--35.

Braun MM, Patriarca PA, Ellenberg SS. Syncope after immunization.
Arch Pediatr Adolesc Med 1997;151:255--9.

American Academy of Pediatrics. Active immunization. In: Pickering
LK, ed. 2000 red book: report of the Committee on Infectious Diseases.
25th ed. Elk Grove Village, IL: American Academy of
Pediatrics, 2000.

International Health Care Worker Safety Center. List of
safety-engineered sharp devices and other products designed to prevent
occupational exposures to bloodborne pathogens. Charlottesville, VA:
University of Virginia, 2001. Available at http://www.med.virginia.edu/medcntr/centers/epinet/safetydevice.html.
Accessed November 8, 2001.

California Department of Health Services. California list of
needleless systems and needles with engineered sharps injury protection.
Sacramento, CA: California Department of Health Services, 2001.
Available at http://www.dhs.cahwnet.gov/ohb/SHARPS/disclaim.htm.
Accessed November 8, 2001.

National Alliance for the Primary Prevention of Sharps Injuries.
NAPPSI: National Alliance for the Primary Prevention of Sharps Injuries.
Carlsbad, CA: NAPPSI, 2001. Available at http://www.nappsi.org/. Accessed
November 13, 2001.

CDC.
Prevention and control of influenza: recommendations of the Advisory
Committee on Immunization Practices (ACIP). MMWR 2001;50(No.
RR-4):1--44.

Ambrosch F, Hirschl A, Kollaritsch H, et al. Immunologic
investigations with oral live typhoid vaccine Ty21a strain. In: Steffen
R, Lobel HO, Bradley DJ, eds. Travel medicine: proceedings of the first
Conference on International Travel Medicine. Berlin, Germany:
Springer-Verlog, 1989:248--53.

Horowitz H, Carbonaro CA. Inhibition of the Salmonella typhi
oral vaccine strain, Ty21a, by mefloquine and chloroquine [Letter]. J
Infect Dis 1992;166:1462--4.

Starr S, Berkovich S. Effects of measles, gamma-globulin-modified
measles and vaccine measles on the tuberculin test. N Engl J Med
1964;270:386--91.

Brickman HF, Beaudry PH, Marks MI. Timing of tuberculin tests in
relation to immunization with live viral vaccines. Pediatrics
1975;55:392--6.

Berkovich S, Starr S. Effects of live type 1 poliovirus vaccine and
other viruses on the tuberculin test. N Engl J Med 1966;274:67--72.

Grabenstein JD. Clinical management of hypersensitivities to vaccine
components. Hospital Pharmacy 1997;32:77--87.

Grabenstein JD. ImmunoFacts: vaccines & immunologic drugs. St.
Louis, MO: Wolters Kluwer Co, Facts and Comparisons, 2001:K1--5.

Murphy KR, Strunk RC. Safe administration of influenza vaccine in
asthmatic children hypersensitive to egg proteins. J Pediatr
1985;106:931--3.

Kelso JM, Jones RT, Yunginger JW. Anaphylaxis to measles, mumps, and
rubella vaccine mediated by IgE to gelatin. J Allergy Clin Immunol
1993;91:867--72.

Sakaguchi M, Ogura H, Inouye S. IgE antibody to gelatin in children
with immediate-type reactions to measles and mumps vaccines. J Allergy
Clin Immunol 1995;96:563--5.

Sakaguchi M, Yamanaka T, Ikeda K, et al. IgE-mediated systemic
reactions to gelatin included in the varicella vaccine. J Allergy Clin
Immunol 1997;99:263--4.

Sakaguchi M, Nakayama T, Inouye S. Food allergy to gelatin in
children with systemic immediate-type reactions, including anaphylaxis,
to vaccines. J Allergy Clin Immunol 1996;98:1058--61.

Reitschel RL, Bernier R. Neomycin sensitivity and the MMR vaccine
[Letter]. JAMA 1981;245:571.

Elliman D, Dhanraj B. Safe MMR vaccination despite neomycin allergy
[Letter]. Lancet 1991;337:365.

CDC.
Thimerosal in vaccines: a joint statement of the American Academy of
Pediatrics and the Public Health Service [Notice to readers]. MMWR
1999;48:563--5.

Ball LK, Ball R, Pratt RD. Assessment of thimerosal use in childhood
vaccines. Pediatrics 2001;107:1147--54.

Aberer W. Vaccination despite thimerosal sensitivity. Contact
Dermatitis 1991;24:6--10.

Kirkland LR. Ocular sensitivity to thimerosal: a problem with
hepatitis B vaccine? South Med J 1990;83:497--9.

Cox NH, Forsyth A. Thiomersal allergy and vaccination reactions.
Contact Dermatitis 1988;18:229--33.

Möller H. All these positive tests to thimerosal. Contact Dermatitis
1994;31:209--13.

Wantke F, Demmer CM, Götz M, Jarisch R. Contact dermatitis from
thimerosal: 2 year's experience with ethylmercuric chloride in patch
testing thimerosal-sensitive patients. Contact Dermatitis
1994;30:115--8.

Slater JE. Latex allergy. J Allergy Clin Immunol 1994;94:139--49.

Towse A, O'Brien M, Twarog FJ, Braimon J, Moses A. Local reaction
secondary to insulin injection: a potential role for latex antigens in
insulin vials and syringes [Short reports]. Diabetes Care
1995;18:1195--7.

Bastyr EJ. Latex allergen allergic reactions [Letter]. Diabetes Care
1996;19:546.

MacCracken J, Stenger P, Jackson T. Latex allergy in diabetic
patients: a call for latex-free insulin tops [Letter]. Diabetes Care
1996;19:184.

Lear JT, English JSC. Anaphylaxis after hepatitis B vaccination
[Letter]. Lancet 1995;345:1249.

Bernbaum JC, Daft A, Anolik R, et al. Response of preterm infants to
diphtheria-tetanus- pertussis immunizations. J Pediatr 1985;107:184--8.

Koblin BA, Townsend TR, Munoz A, Onorato I, Wilson M, Polk BF.
Response of preterm infants to diphtheria-tetanus-pertussis vaccine.
Pediatr Infect Dis J 1988;7:704--11.

Smolen P, Bland R, Heiligenstein E, et al. Antibody response to oral
polio vaccine in premature infants. J Pediatr 1983;103:917--9.

Bernbaum J, Daft A, Samuelson J, Polin RA. Half-dose immunization
for diphtheria, tetanus, pertussis: response of preterm infants.
Pediatrics 1989;83:471--6.

Lau YL, Tam AY, Ng KW, et al. Response of preterm infants to
hepatitis B vaccine. J Pediatr 1992;121:962--5.

Patel DM, Butler J, Feldman S, Graves GR, Rhodes PG. Immunogenicity
of hepatitis B vaccine in healthy very low birth weight infants. J
Pediatr 1997;131:641--3.

Kim SC, Chung EK, Hodinka RL, et al. Immunogenicity of hepatitis B
vaccine in preterm infants. Pediatrics 1997;99:534--6.

Losonsky GA, Wasserman SS, Stephens I, et al. Hepatitis B
vaccination of premature infants: a reassessment of current
recommendations for delayed immunization. Pediatrics 1999;103:E14.

Pickering LK, Granoff DM, Erickson JR, et al. Modulation of the
immune system by human milk and infant formula containing nucleotides.
Pediatrics 1998;101:242--9.

Kim-Farley R, Brink E, Orenstein W, Bart K. Vaccination and breast
feeding [Letter]. JAMA 1982;248:2451--2.

Patriaca PA, Wright PF, John TJ. Factors affecting the
immunogenicity of oral polio vaccine in developing countries: review.
Rev Infect Dis 1991;13:926--39.

Hahn-Zoric M, Fulconis F, Minoli I, et al. Antibody responses to
parenteral and oral vaccines are impaired by conventional and
low-protein formulas as compared to breast feeding. Acta Paediatr Scand
1990;79:1137--42.

Krogh V, Duffy LC, Wong D, Rosenband M, Riddlesberger KR, Ogra PL.
Postpartum immunization with rubella virus vaccine and antibody response
in breast-feeding infants. J Lab Clin Med 1989;113:695--9.

Koren G, Pastuszak A, Ito S. Drugs in pregnancy. N Eng J Med
1998;338:1128--37.

Grabenstein JD. Vaccines and antibodies in relation to pregnancy and
lactation. Hospital Pharmacy 1999;34:949--60.

CDC.
Diphtheria, tetanus, and pertussis: recommendations for vaccine use and
other preventive measures; recommendations of the Immunization Practices
Advisory Committee (ACIP). MMWR 1991;40(No. RR-10):1--28.

Neuzil KM, Reed GW, Mitchel EF, Simonsen L, Griffin MR. Impact of
influenza on acute cardiopulmonary hospitalizations in pregnant women.
Am J Epidemiol 1998;148:1094--102.

CDC.
Hepatitis B virus: a comprehensive strategy for eliminating transmission
in the United States through universal childhood vaccination;
recommendations of the Immunization Practices Advisory Committee (ACIP).
MMWR 1991;40(No. RR-13):1--25.

CDC.
Prevention of hepatitis A through active or passive immunization:
recommendations of the Advisory Committee on Immunization Practices
(ACIP). MMWR 1999;48(No. RR-12):1--37.

CDC.
Prevention and control of meningococcal disease and meningococcal
disease and college students: recommendations of the Advisory Committee
on Immunization Practices (ACIP). MMWR 2000;49(No. RR-7):1--20.

Tsai TF, Paul R, Lynberg MC, Letson GW. Congenital yellow fever
virus infection after immunization in pregnancy. J Infect Dis
1993;168:1520--3.

Shields KE, Galil K, Seward J, Sharrar RG, Cordero JF, Slater E.
Varicella vaccine exposure during pregnancy: data from the first 5 years
of the pregnancy registry. Obstet Gynecol 2001;98:14--9.

CDC.
Revised ACIP recommendation for avoiding pregnancy after receiving a
rubella-containing vaccine [Notice to readers]. MMWR 2001;50:1117.

CDC.
Prevention of varicella: update recommendations of the Advisory
Committee on Immunization Practices (ACIP). MMWR 1999;48(No.
RR-6):1--5.

Hlady WG, Bennett JV, Samadi AR, et al. Neonatal tetanus in rural
Bangladesh: risk factors and toxoid efficacy. Am J Publ Health
1992;82:1365--9.

de Quadros CA, Andrus JK, Olive J-M, de Macedo CG. Polio eradication
from the Western Hemisphere. Ann Rev Publ Health 1992;13:239--52.

U.S. Department of State. International adoptions. Washington, DC:
US Department of State, 2001. Available at http://www.travel.state.gov/adopt.html.
Accessed November 13, 2001.

Hostetter MK, Johnson DE. Immunization status of adoptees from
China, Russia, and Eastern Europe [Abstract 851]. Presented at the 1998
Pediatric Academic Societies Annual Meeting, New Orleans, May 5, 1998.

Kriz B, Burian V, Sladky K, et al. Comparison of titration results
of diphtheric antitoxic antibody obtained by means of Jensen's method
and the method of tissue cultures and haemagglutination. J Hyg Epidemiol
Microbiol Immunol 1978;22:485--93.

Staat MA, Daniels D. Immunization verification in internationally
adopted children [Abstract]. Pediatr Res 2001;49(4):468a.

CDC.
Recommendations of the Advisory Committee on Immunization Practices
(ACIP): use of vaccines and immune globulins in persons with altered
immunocompetence. MMWR 1993;42(No. RR-4):1--18.

Sixbey JW. Routine immunization of the immunocompromised child. Adv
Pediatr Infect Dis 1987;2:79--114.

Wright PF, Hatch MH, Kasselberg AG, Lowry SP, Wadlington WB, Karzon
DT. Vaccine-associated poliomyelitis in a child with sex-linked
agammaglobulinemia. J Pediatr 1977;91:408--12.

Wyatt HV. Poliomyelitis in hypogammaglobulinemics. J Infect Dis
1973;128:802--6.

Davis LE, Bodian D, Price D, Butler IJ, Vickers JH. Chronic
progressive poliomyelitis secondary to vaccination of an immunodeficient
child. N Engl J Med 1977;297:241--5.

CDC.
Disseminated Mycobacterium bovis infection from BCG vaccination
of a patient with acquired immunodeficiency syndrome [Epidemiologic
notes and reports]. MMWR 1985;34:227--8.

Ninane J, Grymonprez A, Burtonboy G, Francois A, Cornu G.
Disseminated BCG in HIV infection. Arch Dis Child 1988;63:1268--9.

Redfield RR, Wright DC, James WD, Jones TS, Brown C, Burke DS.
Disseminated vaccinia in a military recruit with human immunodeficiency
virus (HIV) disease. N Engl J Med 1987;316:673--6.

CDC.
Measles pneumonitis following measles-mumps-rubella vaccination of a
patient with HIV infection, 1993. MMWR 1996;45:603--6.

Sprauer MA, Markowitz LE, Nicholson JKA, et al. Response of human
immunodeficiency virus-infected adults to measles-rubella vaccination. J
Acquir Immune Defic Syndr 1993;6:1013--6.

McLaughlin M, Thomas P, Onorato I, et al. Live virus vaccines in
human immunodeficiency virus-infected children: a retrospective survey.
Pediatrics 1988;82:229--33.

Onorato IM, Markowitz LE, Oxtoby MJ. Childhood immunization,
vaccine-preventable diseases and infection with human immunodeficiency
virus. Pediatr Infect Dis J 1988;6:588--95.

Palumbo P, Hoyt L, Demasio K, Oleske J, Connor E. Population-based
study of measles and measles immunization in human immunodeficiency
virus-infected children. Pediatr Infect Dis J 1992;11:1008--14.

Derryck A, LaRussa P, Steinberg S, Capasso M, Pitt J, Gershon AA.
Varicella and zoster infection in children with human immunodeficiency
virus infection. Pediatr Infect Dis J 1998;17:931--3.

CDC.
1994 revised classification system for human immunodeficiency virus
infection in children less than 13 years of age. MMWR 1994;43(No.
RR-12):1--10.

Levin MJ, Gershon AA, Weinberg A, et al. Immunization of
HIV-infected children with varicella vaccine. J Pediatr
2001;139:305--10.

CDC.
Update on adult immunization recommendations of the Immunization
Practices Advisory Committee (ACIP). MMWR 1991;40(No. RR-12):1--94.

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(No. RR-10):1--128.

Guinan EC, Molrine DC, Antin JH, et al. Polysaccharide conjugate
vaccine responses in bone marrow transplant patients. Transplantation
1994;57:677--84.

Pauksen K, Hammarstrom V, Ljungman P, et al. Immunity to poliovirus
and immunization with inactivated poliovirus vaccine after autologous
bone marrow transplantation. Clin Infect Dis 1994;18:547--52.

Pauksen K, Duraj V, Ljungman P, et al. Immunity to and immunization
against measles, rubella and mumps in patients after autologous bond
marrow transplantation. Bone Marrow Transplant 1992;9:427--32.

Ljungman P, Wiklund-Hammarsten M, Duraj V, et al. Response to
tetanus toxoid immunization after allogeneic bone marrow
transplantation. J Infect Dis 1990;162:496--500.

Ljungman P, Fridell E, Lonnqvist B, et al. Efficacy and safety of
vaccination of marrow transplant recipients with a live attenuated
measles, mumps, and rubella vaccine. J Infect Dis 1989;159:610--5.

Evans DI, Shaw A. Safety of intramuscular injection of hepatitis B
vaccine in haemophiliacs, BMJ 1990;300:1694--5.

CDC.
Progress in development of immunization registries---United States,
2000. MMWR 2001;50:3--7.

National Vaccine Advisory Committee (NVAC). Development of
community- and state-based immunization registries; approved January 12,
1999. Atlanta, GA: US Department of health and Human Services, CDC,
1999. Available at http://www.cdc.gov/nip/registry/nvac.htm.
Accessed November 13, 2001.

CDC.
Development of community- and state-based immunization registries: CDC
response to a report from the National Vaccine Advisory Committee. MMWR
2001;50(No. RR-17):1--17.

U.S. Department of Health and Human Services. Immunization and
infectious diseases [Goal 14-26]. In: Healthy People 2010 (conference
ed, vol 1). Washington, DC: US Government Printing Office, 2000.
Available at http://www.health.gov/healthypeople/Document/HTML/Volume1/14Immunization.htm#_Toc494510242.
Accessed November 13, 2001.

CDC.
Immunization of health-care workers: recommendations of the Advisory
Committee on Immunization Practices (ACIP) and the Hospital Infection
Control Practices Advisory Committee (HICPAC). MMWR 1997;46(No.
RR-18):1--42.

Shefer A, Briss P, Rodewald L, et al. Improving immunization
coverage rates: an evidence-based review of the literature. Epidemiol
Rev 1999;21:96--142.

CDC.
Vaccine-preventable diseases: improving vaccination coverage in
children, adolescents, and adults; a report on recommendations of the
Task Force on Community Preventive Services. MMWR 1999;48(No.
RR-8):1--15.

Briss PA, Rodewald LE, Hinman AR, et al. and the Task Force on
Community Preventive Services. Reviews of evidence regarding
interventions to improve vaccination coverage in children, adolescents,
and adults. Am J Prev Med 2000;18(1 Suppl):97--140.

Task Force on Community Preventive Services. Recommendations
regarding interventions to improve vaccination coverage in children,
adolescents, and adults.. Am J Prev Med 2000;18(1 Suppl):92--6.

* During measles outbreaks, if cases are occurring among infants aged
<12 months, measles vaccination of infants as young as 6 months can be
undertaken as an outbreak control measure. However, doses administered at
ages <12 months should not be counted as part of the series
(Source: CDC. Measles, mumps, and rubella vaccine use and
strategies for elimination of measles, rubella, and congenital rubella
syndrome and control of mumps: recommendations of the Advisory Committee
on Immunization Practices [ACIP]. MMWR 1998;47[No. RR-8]:157).

† In certain situations, local or state requirements might
mandate that doses of selected vaccines be administered on or after
specific ages. For example, a school entry requirement might not accept a
dose of MMR or varicella vaccine administered before the child's first
birthday. ACIP recommends that physicians and other health-care providers
comply with local or state vaccination requirements when scheduling and
administering vaccines.

§ The exception is the two-dose hepatitis B vaccination
series for adolescents aged 1115 years. Only Recombivax HB®
(Merck Vaccine Division) should be used in this schedule.
Engerix-B® is not approved by FDA for this schedule.

¶ Internet sites with device listings are identified for
information purposes only. CDC, the U.S. Public Health Service, and the
Department of Health and Human Services do not endorse any specific device
or imply that the devices listed would all satisfy the needle-stick
prevention regulations.

** Toxin neutralization testing is reliable but not readily available.
Enzyme immunoassay tests are the most readily available, although passive
hemagglutination is available in certain areas. Physicians should contact
the laboratory performing the test for interpretive standards and
limitations. Protective concentrations for diphtheria are defined as
>0.1 IU/mL and for tetanus as >0.10.2 IU/mL.

†† As defined by a low age-specific total CD4+ T
lymphocyte count or a low CD4+ T lymphocyte count as a
percentage of total lymphocytes. ACIP recommendations for using MMR
vaccine contain additional details regarding the criteria for severe
immunosuppression in persons with HIV infection (Source: CDC.
Measles, mumps, and rubella vaccine use and strategies for elimination of
measles, rubella, and congenital rubella syndrome and control of mumps:
recommendations of the Advisory Committee on Immunization Practices
[ACIP]. MMWR 1998;47[No. RR-8]:157).

§§ As of January 2002, vaccines covered by the act include
diphtheria, tetanus, pertussis, measles, mumps, rubella, poliovirus,
hepatitis B, Hib, varicella, and pneumococcal conjugate.

¶¶ The Vaccine Injury Table can be obtained from the Vaccine
Injury Compensation Program Internet site at <http://www.hrsa.dhhs.gov/bhpr/vicp/table.htm>
(accessed November 7, 2001).

*** Standards for pediatric, adolescent, and adult immunization
practices are being revised and will be posted on CDC's National
Immunization Program Interne site (http://www.cdc.gov/nip; accessed
November 7, 2001) as soon as the updates are available.

Abbreviations Used in This
Publication

AAFP

American Academy of Family Physicians

AAP

American Academy of Pediatrics

ACIP

Advisory Committee on Immunization Practices

DT

pediatric diphtheria-tetanus toxoid

DTaP

diphtheria and tetanus toxoids and acellular pertussis vaccine

DTP

diphtheria and tetanus toxoids and whole-cell pertussis vaccine

EIA/ELISA

enzyme immunoassay

FDA

Food and Drug Administration

GBS

Guillain-Barré syndrome

HBIG

hepatitis B immune globulin

HbOC

diphtheria CRM197 (CRM, cross-reactive material) protein
conjugate

HBsAg

hepatitis B surface antigen

Hib

Haemophilus influenzae type b

HIV

human immunodeficiency virus

HSCT

hematopoietic stem cell transplant

IgG

immunoglobulin G

IGIV

intravenous immune globulin

IPV

inactivated poliovirus vaccine

JIs

jet injectors

MMR

measles, mumps, rubella vaccine

OPV

oral poliovirus vaccine

OSHA

Occupational Safety and Health Administration

PCV

pneumococcal conjugate vaccine

PPD

purified protein derivative

PRP-OMP

polyribosylribitol phosphate-meningococcal outer membrane protein

PRP-T

PRP-tetanus

PPV

pneumococcal polysaccharide vaccine

Td

adult tetanus-diphtheria toxoid

VAERS

Vaccine Adverse Event Reporting System

VAPP

vaccine-associated paralytic polio

Definitions Used in This
Report

Adverse event. An untoward event that occurs after a vaccination
that might be caused by the vaccine product or vaccination process. It
includes events that are 1) vaccine-induced: caused by the intrinsic
characteristic of the vaccine preparation and the individual response of
the vaccinee; these events would not have occurred without vaccination
(e.g., vaccine-associated paralytic poliomyelitis); 2)
vaccine-potentiated: would have occurred anyway, but were precipitated by
the vaccination (e.g., first febrile seizure in a predisposed child); 3)
programmatic error: caused by technical errors in vaccine preparation,
handling, or administration; 4) coincidental: associated temporally with
vaccination by chance or caused by underlying illness. Special studies are
needed to determine if an adverse event is a reaction or the result of
another cause (Sources: Chen RT. Special methodological issues in
pharmacoepidemiology studies of vaccine safety. In: Strom BL, ed.
Pharmacoepidemiology. 3rd ed. Sussex, England: John Wiley &
Sons, 2000:707--32; and Fenichel GM, Lane DA, Livengood JR, Horwitz SJ,
Menkes JH, Schwartz JF. Adverse events following immunization: assessing
probability of causation. Pediatr Neurol 1989;5:287--90).

Adverse reaction. An undesirable medical condition that has been
demonstrated to be caused by a vaccine. Evidence for the causal
relationship is usually obtained through randomized clinical trials,
controlled epidemiologic studies, isolation of the vaccine strain from the
pathogenic site, or recurrence of the condition with repeated vaccination
(i.e., rechallenge); synonyms include side effect and adverse effect).

Immunobiologic. Antigenic substances (e.g., vaccines and
toxoids) or antibody-containing preparations (e.g., globulins and
antitoxins) from human or animal donors. These products are used for
active or passive immunization or therapy. The following are examples of
immunobiologics:

Vaccine. A suspension of live (usually attenuated) or
inactivated microorganisms (e.g., bacteria or viruses) or fractions
thereof administered to induce immunity and prevent infectious disease
or its sequelae. Some vaccines contain highly defined antigens (e.g.,
the polysaccharide of Haemophilus influenzae type b or the
surface antigen of hepatitis B); others have antigens that are complex
or incompletely defined (e.g., killed Bordetella pertussis or
live attenuated viruses).

Toxoid. A modified bacterial toxin that has been made
nontoxic, but retains the ability to stimulate the formation of
antibodies to the toxin.

Immune globulin. A sterile solution containing antibodies,
which are usually obtained from human blood. It is obtained by cold
ethanol fractionation of large pools of blood plasma and contains
15%--18% protein. Intended for intramuscular administration, immune
globulin is primarily indicated for routine maintenance of immunity
among certain immunodeficient persons and for passive protection against
measles and hepatitis A.

Intravenous immune globulin. A product derived from blood
plasma from a donor pool similar to the immune globulin pool, but
prepared so that it is suitable for intravenous use. Intravenous immune
globulin is used primarily for replacement therapy in primary
antibody-deficiency disorders, for treatment of Kawasaki disease, immune
thrombocytopenic purpura, hypogammaglobulinemia in chronic lymphocytic
leukemia, and certain cases of human immunodeficiency virus infection
(Table
2).

Hyperimmune globulin (specific). Special preparations obtained
from blood plasma from donor pools preselected for a high antibody
content against a specific antigen (e.g., hepatitis B immune globulin,
varicella-zoster immune globulin, rabies immune globulin, tetanus immune
globulin, vaccinia immune globulin, cytomegalovirus immune globulin,
respiratory syncytial virus immune globulin, botulism immune globulin).

Monoclonal antibody. An antibody product prepared from a
single lymphocyte clone, which contains only antibody against a single
microorganism.

Antitoxin. A solution of antibodies against a toxin. Antitoxin
can be derived from either human (e.g., tetanus antitoxin) or animal
(usually equine) sources (e.g., diphtheria and botulism antitoxin).
Antitoxins are used to confer passive immunity and for treatment.

Vaccination and Immunization. The terms vaccine and
vaccination are derived from vacca, the Latin term for cow.
Vaccine was the term used by Edward Jenner to describe material
used (i.e., cowpox virus) to produce immunity to smallpox. The term
vaccination was used by Louis Pasteur in the 19th
century to include the physical act of administering any vaccine or
toxoid. Immunization is a more inclusive term, denoting the process
of inducing or providing immunity by administering an immunobiologic.
Immunization can be active or passive. Active immunization is the
production of antibody or other immune responses through administration of
a vaccine or toxoid. Passive immunization means the provision of
temporary immunity by the administration of preformed antibodies. Four
types of immunobiologics are administered for passive immunization: 1)
pooled human immune globulin or intravenous immune globulin, 2)
hyperimmune globulin (specific) preparations, 3) monoclonal antibody
preparations, and 4) antitoxins from nonhuman sources. Although persons
often use the terms vaccination and immunization
interchangeably in reference to active immunization, the terms are not
synonymous because the administration of an immunobiologic cannot be
equated automatically with development of adequate immunity.

Table 1

Return to
top.
Table 2

Return to
top.
Table 3

Return to
top.
Table 4

Return to
top.
Table 5

Return to
top.
Table 6

Return to
top.
Table 7

Return to
top.

Advisory Committee on Immunization
Practices
Membership List, June 2001

Chairman: John F. Modlin, M.D., Professor of Pediatrics and
Medicine, Dartmouth Medical School, Lebanon, New Hampshire.

Executive Secretary: Dixie E. Snider, Jr., M.D., Associate
Director for Science, Centers for Disease Control and Prevention, Atlanta,
Georgia.

Members: Dennis A. Brooks, M.D., Johnson Medical Center,
Baltimore, Maryland; Richard D. Clover, M.D., University of Louisville
School of Medicine, Louisville, Kentucky; Jaime Deseda-Tous, M.D., San
Jorge Children's Hospital, San Juan, Puerto Rico; Charles M. Helms, M.D.,
Ph.D., University of Iowa Hospital and Clinics, Iowa City, Iowa ; David R.
Johnson, M.D., Michigan Department of Community Health, Lansing, Michigan
; Myron J. Levin, M.D., University of Colorado School of Medicine, Denver,
Colorado; Paul A. Offit, M.D., Children's Hospital of Philadelphia,
Philadelphia, Pennsylvania; Margaret B. Rennels, M.D., University of
Maryland School of Medicine, Baltimore, Maryland; Natalie J. Smith, M.D.,
California Department of Health Services, Berkeley, California; Lucy S.
Tompkins, M.D., Ph.D., Stanford University Medical Center, Stanford,
California; Bonnie M. Word, M.D., Monmouth Junction, New Jersey.

Ex-Officio Members: James Cheek, M.D., Indian Health Service,
Albuquerque, New Mexico; Carole Heilman, M.D., National Institutes of
Health, Bethesda, Maryland; Karen Midthun, M.D., Food and Drug
Administration, Bethesda, Maryland; Martin G. Myers, M.D., National
Vaccine Program Office, Atlanta, Georgia; Kristin Lee Nichol, M.D., VA
Medical Center, Minneapolis, Minnesota; Col. Benedict M. Didiega, M.D.,
Department of Defense, Falls Church, Virginia; Geoffrey S. Evans, M.D.,
Health Resources and Services Administration, Rockville, Maryland; T.
Randolph Graydon, Health Care Financing Administration, Baltimore,
Maryland.

Liaison Representatives: American Academy of Family Physicians,
Martin Mahoney, M.D., Ph.D., Clarence, New York; Richard Zimmerman, M.D.,
Pittsburgh, Pennsylvania; American Academy of Pediatrics, Jon Abramson,
M.D., Winston-Salem, North Carolina; Gary Overturf, M.D., Albuquerque, New
Mexico; American Association of Health Plans, Eric K. France, M.D.,
Denver, Colorado; American College of Obstetricians and Gynecologists,
Stanley A. Gall, M.D., Louisville, Kentucky; American College of
Physicians, Kathleen M. Neuzil, M.D., Seattle, Washington; American
Hospital Association, William Schaffner, M.D., Nashville, Tennessee;
American Medical Association, H. David Wilson, M.D., Grand Forks, North
Dakota; Association of Teachers of Preventive Medicine, W. Paul McKinney,
M.D. Louisville, Kentucky; Canadian National Advisory Committee on
Immunization, Victor Marchessault, M.D., Cumberland, Ontario, Canada;
Hospital Infection Control Practices Advisory Committee, Jane D. Siegel,
M.D., Dallas, Texas; Infectious Diseases Society of America, Samuel L.
Katz, M.D., Durham, North Carolina; London Department of Health, David M.
Salisbury, M.D., London, United Kingdom; National Immunization Council and
Child Health Program, Mexico, Jose Ignacio Santos, M.D., Mexico City,
Mexico; National Medical Association, Rudolph E. Jackson, M.D., Atlanta,
Georgia; National Vaccine Advisory Committee, Georges Peter, M.D.,
Providence, Rhode Island; Pharmaceutical Research and Manufacturers of
America, Kevin Reilly, Radnor, Pennsylvania.

Members of the General Recommendations on Immunization
Working Group

Advisory Committee on Immunization Practices (ACIP), Lucy Tompkins,
M.D.; Chinh Le, M.D.; Richard Clover, M.D.; Natalie Smith, M.D. ACIP
Liaison and Ex-Officio Members, David H. Trump, M.D., Office of the
Assistant Secretary of Defense (Health Affairs); Pierce Gardner, M.D.,
American College of Physicians; Georges Peter, M.D., National Vaccine
Advisory Committee; Victor Marchessault, M.D., Canadian National Advisory
Committee on Immunization; Goeffrey Evans, M.D., Health Resources and
Services Administration; Richard Zimmerman, M.D., American Academy of
Family Physicians; Larry Pickering, M.D., American Academy of Pediatrics;
CDC staff member, William L. Atkinson, M.D.; other members and
consultants, Margaret Hostetter, M.D., Yale Child Health Research Center;
Mary Staat, M.D., Children's Hospital Medical Center of Cincinnati;
Deborah Wexler, M.D., Immunization Action Coalition; John Grabenstein,
Ph.D., U.S. Army Medical Command; Thomas Vernon, M.D., Merck Vaccine
Division; and Fredrick Ruben, M.D., Aventis-Pasteur.

Use of trade names and commercial sources is for
identification only and does not imply endorsement by the U.S.
Department of Health and Human Services.

References to
non-CDC sites on the Internet are provided as a service to
MMWR readers and do not constitute or imply endorsement of
these organizations or their programs by CDC or the U.S. Department
of Health and Human Services. CDC is not responsible for the content
of pages found at these sites.

Disclaimer
All MMWR HTML versions of articles are electronic
conversions from ASCII text into HTML. This conversion may have resulted
in character translation or format errors in the HTML version. Users
should not rely on this HTML document, but are referred to the electronic
PDF version and/or the original MMWR paper copy for the official
text, figures, and tables. An original paper copy of this issue can be
obtained from the Superintendent of Documents, U.S. Government Printing
Office (GPO), Washington, DC 20402-9371; telephone: (202) 512-1800.
Contact GPO for current prices.
**Questions or messages
regarding errors in formatting should be addressed to [email-masked].

Page converted: 2/6/2002

Print
Help

MMWR Home | MMWR Search |
Help | Contact
Us

CDC Home | Search | Health Topics
A-Z

This page
last reviewed 2/6/2002

Centers for Disease Control and Prevention

Morbidity and Mortality Weekly Report