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DISEASE
20TH CENTURY
ANNUAL CASES
PRECEDING
VACCINE
DEVELOPMENT
2005 PERCENT
CASES DECREASE
Smallpox
48,164
100
Diphtheria
175,885
100
Measles
503,282
66
>99
Mumps
152,209
314
>99
Pertussis
147,271
25,616 83
Polio
(paralytic)
16,316
>99
[]
[]
HEALTHY PEOPLE
2010 COVERAGE
GOAL FOR 1935
MO OLD
COVERAGE
CHILDREN
JULY 2005
4 doses, 90%
86%
1 dose 90%
92%
1 dose, 90%
92%
4 doses, 90%
86%
3 doses, 90%
92%
Rubella
47,745
11
>99
1 dose, 90%
92%
Congenital
rubella
syndrome
823
>99
1 dose, 90%
92%
Tetanus
1314
27
98
4 doses, 90%
86%
226
99
3 doses, 90%
94%
H. influenzae 20,000
type b and
unknown (<5
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yr)
Adapted from Centers for Disease Control and Prevention: Achievements in public health, 1900
1999 impact of vaccines universally recommended for childrenUnited States, 19901998.MMWR
1999;48:243248; and Centers for Disease Control and Prevention: Final 2005 reports of notifiable
diseases.MMWR 2005;54:770780 and MMWR 2006;55:988993.
Record lows.
PASSIVE IMMUNITY.
Postexposure prophylaxis
Prevention of perinatal infection in infants born to HBsAg+
mothers
Postexposure prophylaxis
Wound prophylaxis
Treatment of tetanus
Varicella-Zoster immune globulin Postexposure prophylaxis of susceptible persons at high risk for
(VZIG) or IVIG
complications from varicella
Cytomegalovirus IGIV
Palivizumab (monoclonal
antibody)
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food and wound botulism
Prophylaxis
for infants
born at 29
32 wk
gestation
without CLD
up to 6 mo of
age at time
of respiratory
syncytial
virus (RSV)
season
Prophylaxis
for infants
born at <28
wk gestation
up to 12 mo
of age at the
start of RSV
season
Prophylaxis of
infants born at
3235 wk
gestation who
are <6 mo of
age at start of
RSV season
and with at
least 2 risk
factors
Treat
ment
of
seriou
s
adver
se
event
s
followi
ng
smallp
ox
vaccin
ation
due to
vaccin
ia
replic
ation
Treatment of
infant botulism
Treatment of
diphtheria
Treatment of
1*
Immune Globulin.
for prophylaxis of
after repeat doses. These
hepatitis A for
reactions can include fever,
persons traveling
chills, and a shocklike
internationally to
syndrome. Because these
hepatitis A
reactions are rare, testing for
endemic areas
selective IgA deficiencies is
(0.06 mL/kg), for
not recommended.
children too young
for vaccination (<1 Immune Globulin Intravenous.
yr of age), or in
IGIV is prepared from adult
conjunction with
hepatitis A vaccine plasma donors using alcohol
fractionation and is modified to
when departure to
allow for intravenous use. IGIV
the area must be
undertaken <1 mo is predominantly IgG and is
tested to assure minimum
after receipt of
hepatitis A vaccine. antibody titers to diphtheria,
HepB, measles, and polio.
Liquid and powder preparations
The most
common adverse are available. The major
recommended indications for
reaction to IG is
IGIV are replacement therapy
pain and
for immunodeficiency
discomfort at the
disorders; treatment of
injection site.
Kawasaki disease to prevent
More serious
reactions are rare coronary artery abnormalities
and have included and shorten the clinical course;
prevention of serious bacterial
chest pain,
infections in children with HIV;
dyspnea,
prevention of serious bacterial
anaphylaxis, and
systemic collapse. infections in persons with
hypogammaglobulinemia in
Patients with
chronic B-cell leukemia;
selective IgA
immune-mediated
deficiency can
thrombocytopenia; and
produce
antibodies against prophylaxis of infection
the trace amounts following bone marrow
transplantation. In addition,
of IgA in IG
IGIV may be helpful for patients
preparations and
develop reactions with severe toxic shock
syndrome, Guillain-Barr
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0.25
mL/kg
for
immun
ocomp
etent
children
, 0.5
mL/kg
for
immun
ocompr
omised
children
;
maximu
m dose
15 mL)
and to
prevent
or
modify
hepatiti
s A if
adminis
tered to
children
within
14 days
of
exposu
re
(usual
dose
0.02
mL/kg).
IG also
may be
adminis
tered
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syndrome, and anemia caused by parvovirus B19. IGIV is used for many other conditions
based on clinical experience.
Reactions to IGIV range from 1 to 15%. Some of these reactions appear to be related to the
rate of infusion and can be mitigated by decreasing the rate. Such reactions include fever,
headache, myalgia, chills, nausea, and vomiting. More serious reactions rarely have been
reported, including anaphylactoid events, thromboembolic disorders, aseptic meningitis, and
renal insufficiency.
Specific Immune Globulin Preparations.
Hyperimmune globulins are specific IG preparations that are derived from donors with
high titers of antibodies to specific agents and designed to provide protection against those
agents (see Table 170-2 ).
Hyperimmune Animal Antisera Preparations.
Animal antisera preparations are derived from horses. The IG fraction is concentrated using
ammonium sulfate, and some products are further treated with enzymes to decrease reactions
to foreign proteins. As of 2006, there are 2 horse antisera preparations available for humans:
diphtheria antitoxin, which is used to treat diphtheria, and botulinum antitoxin, which is used to
treat botulism. Great care must be exercised prior to administration of such antisera because of
the potential for severe allergic reactions. This includes testing for sensitivity prior to
administration, desensitization, if necessary, and treatment of potential reactions, including
febrile events, serum sickness, and anaphylaxis.
Monoclonal Antibodies.
Monoclonal antibodies are antibody preparations produced against a single antigen. They are
mass-produced from a hybridoma, created by fusing an antibody-producing B cell with a fastgrowing immortal cell such as a cancer cell. The major monoclonal antibody used in infectious
diseases is palivizumab, which can prevent severe disease from respiratory syncytial virus
(RSV) among children 24 mo of age with chronic lung disease (CLD, also called
bronchopulmonary dysplasia) or with a history of premature birth (<35 wk). The American
Academy of Pediatrics (AAP) has developed specific recommendations for use of palivizumab
(see Chapter 257 ). Monoclonal antibodies also are used for prevention of transplant rejection
and treatment of some types of cancer and autoimmune diseases. Monoclonal antibodies
against interleukin 2 (IL-2) and tumor necrosis factor- (TNF-) are being used as part of the
therapeutic approach to patients with a variety of malignant and autoimmune diseases.
Serious adverse reactions to palivizumab primarily are rare cases of anaphylaxis and
hypersensitivity reactions. Adverse reactions to monoclonal antibodies directed at modifying
the immune response such as antibodies against IL-2 or TNF can be more serious, such as
cytokine release syndrome, fever, chills, tremors, chest pain, immunosuppression, and
infection with various organisms, including mycobacterium.
ACTIVE IMMUNIZATION.
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TYPE
Bacillus Calmette-Gurin (BCG) Live attenuated mycobacterial strain used for prevention of
vaccine
tuberculosis in very limited circumstances
Diphtheria and tetanus toxoids
and acellular pertussis (DTaP)
vaccine
DTaP with Haemophilus
influenzae type b (Hib)
Influenza virus vaccine inactivated Trivalent (A/H3N2, A/H1N1, and B) split and purified
inactivated (TIV) vaccine containing the hemagglutinin (H) and neuraminidase (N)
of each type and other components
Influenza virus vaccine live, Live attenuated, temperature-sensitive, cold-adapted trivalent
intranasal (LAIV)
vaccine containing the H and N genes from the wild strains
reassorted to have the 6 other genes from the cold-adapted
parent
Japanese encephalitis vaccine
Polysaccharide
from each
serogroup conjugated to
diphtheria toxoid
Meningococcal polysaccharide
Polysaccharides from each of the serogroups
vaccine against serogroups A, C,
W135, and Y (MPS4)
Papillomavirus
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Rotavirus vaccine
Smallpox vaccine
Vaccinia virus, an attenuated pox virus that provides crossprotection against smallpox
Varicella vaccine
Single vaccines for measles, rubella, and tetanus not included in table.
Immunizing agents may contain a variety of other constituents besides the immunizing antigen.
Suspending fluids may be sterile water or saline but could be a complex fluid containing small
amounts of proteins or other constituents derived from the biologic system used to grow the
immunobiologic. Preservatives, stabilizers, and antimicrobial agents are used to inhibit
bacterial growth and to prevent degradation of the antigen. Such components may include
gelatin, 2-phenoxyethanol, and specific antimicrobial agents. Preservatives are added to
multidose vials of vaccines, primarily to prevent bacterial contamination on repeated entry of
the vial. In the past, many vaccines for children contained thimerosal, a preservative containing
ethyl mercury. Beginning in 1999, removal of thimerosal as a preservative from vaccines for
children was begun as a precautionary measure in the absence of any data on harm from the
preservative. This was accomplished by switching to single-dose packaging. The only vaccines
in the recommended schedule for young children that contain thimerosal as a preservative are
some preparations of influenza vaccine. Adjuvants are used in some vaccines to enhance the
immune response. In the United States, the only adjuvants currently licensed by the Food and
Drug Administration (FDA) to be part of vaccines are aluminum salts. Vaccines with adjuvants
should be injected deep into muscle masses to avoid local irritation, granuloma formation, and
necrosis associated with subcutaneous or intracutaneous administration.
Vaccines can induce immunity through stimulation of antibody formation, cellular immunity, or
both. Protection induced by most vaccines is thought to be mediated primarily by B
lymphocytes, which produce antibody. Such antibodies can inactivate toxins, neutralize
viruses, and prevent their attachment to cellular receptors, facilitate phagocytosis and killing of
bacteria, interact with complement to lyse bacteria, and prevent adhesion to mucosal surfaces
by interacting with the bacterial cell surface.
Most B-lymphocyte responses require the assistance of T-lymphocyte, CD4 helper cells. These Tlymphocyte or T celldependent responses tend to induce high levels of functional antibody with
high avidity, mature over time from primarily an IgM response to long-term persistent IgG, and
induce immunologic memory that leads to enhanced responses upon boosting. T lymphocyte
dependent vaccines, which include protein moieties, induce good immune responses even in
young infants. In contrast, polysaccharide antigens induce B-lymphocyte responses in the
absence of T-lymphocyte help. These T lymphocyteindependent vaccines
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are associated with poor immune responses in children <2 yr of age, short-term immunity, and
absence of an enhanced or booster response on repeat exposure to the antigen. To overcome
problems of plain polysaccharide vaccines, polysaccharides have been conjugated, or
covalently linked, to protein carriers, converting the vaccine to a T lymphocytedependent
vaccine. In contrast to plain polysaccharide vaccines, conjugate vaccines induce higher avidity
antibody, immunologic memory leading to booster responses on repeat exposure to the
antigen, long-term immunity, and herd immunity by decreasing carriage of the organism. As of
2006 in the United States, there were licensed conjugate vaccines to prevent Hib,
pneumococcal, and meningococcal diseases.
Serum antibodies may be detected as soon as 710 days after injection of antigen. Early
antibodies are usually of the IgM class that can fix complement. IgM antibodies tend to decline
as IgG antibodies increase. The IgG antibodies tend to peak approximately 1 month after
vaccination and with most vaccines persist for some time after a primary vaccine course.
Secondary or booster responses occur more rapidly and result from rapid proliferation of
memory B and T lymphocytes.
Assessment of the immune response to most vaccines is performed through measurement of
serum antibodies. While detection of serum antibody at levels considered protective after
vaccination may indicate immunity, loss of detectable antibody over time does not necessarily
mean susceptibility to disease. Some vaccines may induce immunologic memory leading to a
booster or anamnestic response on exposure to the microorganism leading to protection from
disease. In some instances, cellular immune response is used to evaluate immune status.
Live attenuated vaccines routinely recommended for children and adolescents include
measles, mumps, and rubella (MMR), rotavirus, and varicella. In addition, a cold-adapted live
attenuated influenza vaccine (LAIV) is available as an alternative to the trivalent inactivated
influenza vaccine (TIV) for children 5 yr of age who do not have conditions that place them at
high risk for complications from influenza. Live attenuated vaccines tend to induce long-term
immune responses. They replicate, often similarly to natural infections, until an immune
response shuts down reproduction. Most live vaccines are administered as single-dose
schedules. The purpose of repeat doses, such as a second dose of the MMR vaccine, is to
induce an initial immune response in persons who failed to respond to the first dose.
The remaining vaccines in the routine schedule for children and adolescents are inactivated
vaccines. Inactivated vaccines tend to require multiple doses to induce an adequate immune
response and are more likely to need boosters to maintain that immunity than live
attenuated vaccines. However, some inactivated vaccines appear to induce long-term
immunity, perhaps life-long immunity, after a primary series, including HepB vaccine and
inactivated polio vaccine (IPV).
THE VACCINATION SYSTEM IN THE U.S.
Vaccine Development.
Basic scientific knowledge about an organism, its pathogenesis, and the immune responses
thought to be associated with protection are financed primarily through government
sponsorship of academic research, although private industry plays a major role ( Fig. 170-1 ).
Private industry usually assumes the lead role for guiding potential vaccine candidates through
preclinical testing in humans into human clinical trials. There are three phases of prelicensure
clinical trials: phase I, involving generally <100 participants to gauge safety and dosing; phase
II, involving several hundred or more participants to refine safety and dosing; and phase III or
pivotal trials that can involve thousands or tens of thousands of participants. Phase III trials are
the major basis for licensure. Following successful clinical development, the sponsor applies to
the FDA for approval. Estimates for the cost of development for each vaccine range to $800
million or more. Following licensure by the FDA, postlicensure monitoring is performed on
hundreds of thousands to millions of people to monitor safety and effectiveness.
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Figure 170-1 Vaccine development and testing. (Modified from Pickering LK, Orenstein WE: Development of pediatric
vaccine recommendations and policies. Semin Pediatr Infect Dis 2002;13[3]:148154.)
Vaccine Production.
There are 2 major committees that make vaccine policy for children: the Committee on Infectious
Diseases (COID) of the AAP (the Red Book Committee) and the Advisory Committee on
Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC). At least
annually, the AAP, the ACIP, and the American Academy of Family Physicians (AAFP) issue a
harmonized childhood and adolescent immunization schedule (www.cdc.gov/nip/acip
). The
COID consists primarily of academic pediatric infectious disease specialists with liaisons from
practicing pediatricians, professional organizations, and government agencies including the FDA,
CDC, and National Institutes of Health (NIH). Recommendations of the COID must be approved by
the AAP Board of Directors. The ACIP consists of 15 members who are academic infectious
disease experts (for both children and adults), family physicians, state and local public health
officials, and consumers. The ACIP also has extensive liaison representation from major medical
societies, government agencies, managed care, and others. The AAP recommendations are
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published in the Red Book and in issues of Pediatrics. The ACIP recommendations, available at
www.cdc.gov/nip/acip
, are official only after approval by the CDC director. which leads to
publication in Morbidity and Mortality Weekly Report (MMWR).
Vaccine Financing.
Between 55 and 60% of vaccines routinely administered to children and adolescents <19 yr of
age are purchased thorough a contract negotiated by the federal government with licensed
vaccine manufacturers. There are three major sources of funds that can purchase vaccines
through this contract. The greatest proportion comes from the Vaccines for Children (VFC)
program, a federal entitlement program. The VFC program covers children on Medicaid,
children without any insurance (uninsured), and American Indians and Alaska Natives. In
addition, children who have insurance but whose insurance does not cover immunization
(underinsured) can be covered through VFC but only if they go to a federally qualified health
center (FQHC) [www.cms.hhs.gov/providers/fghc
]. In contrast to other public funding
sources that require approval of discretionary funding by legislative bodies, VFC funds are
immediately available for new recommendations provided the ACIP votes the vaccine and the
recommendation for its use into the VFC, the federal government negotiates a contract, and
the Office of Management and Budget (OMB) apportions funds. The VFC program can
provide free vaccines to participating private providers. The second major federal funding
source is the 317 Discretionary Federal Grant Program to states and selected localities. These
funds must be appropriated annually by Congress, but in contrast to VFC, have not had
eligibility requirements for use. The third major public source of funds is state appropriations.
Vaccine Safety Monitoring.
Monitoring vaccine safety is the responsibility of the FDA, CDC, and vaccine manufacturers.
A critical part of that monitoring depends on reports to the Vaccine Adverse Event Reporting
System (VAERS). Adverse events following immunization can be reported by calling 1-800822-7967 or completing a VAERS form that can be obtained from www.vaers.hhs.gov
.
Individual VAERS case reports may be helpful in generating hypotheses about whether
vaccines are causing certain clinical syndromes but in general are not helpful in evaluating
the causal role of vaccines in the adverse event. This is because most clinical syndromes that
follow vaccination are similar to syndromes that occur in the absence of vaccination. For
causality assessment, epidemiologic studies are often necessary comparing the incidence
rate of the adverse event after vaccination with the rate in the unvaccinated. A higher rate in
the vaccinated would be consistent with causation.
The Vaccine Safety Datalink (VSD) consists of inpatient and outpatient records of some of the
largest managed care organizations in the U.S. and facilitates causality evaluation. In addition, a
clinical immunization safety assessment network (CISA) has been established to advise primary
care physicians on evaluation and management of adverse events
(www.partnersforimmunization.org/cisa/pdf
). The Institute of Medicine (IOM) has reviewed
independently a variety of vaccine safety concerns (available at www.iom.edu/project.asp?
id=4705
and Table 170-4 ). In no instance did the IOM find that evidence favored acceptance
of a causal link between the postulated adverse event and vaccines.
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The National Vaccine Injury Compensation Program (NVICP), established in 1988, is designed to
compensate persons injured by vaccines in the childhood and adolescent immunization schedule.
The program is funded through an excise tax of $0.75 per disease prevented per dose. As of 2006,
all of the routinely recommended vaccines are covered, with the exception of the meningococcal
conjugate vaccine. The NVICP was established to provide a no-fault system. There is a table of
related injuries and time frames. All persons alleging injury from covered vaccines must first file with
the program. If the injury meets the requirements of the table, compensation is automatic. If not, the
claimant has the responsibility to prove causality. If compensation is accepted, the claimant cannot
sue the manufacturer or physician administering the vaccine. If the claimant rejects the judgment of
the compensation system, he or she can enter the tort system, but this has only occurred rarely.
Information on the NVICP is available at 1-800-338-2382 and www.hrsa.gov/osp/vicp
. All
physicians administering a vaccine covered by the program are required by law to give the
approved Vaccine Information Statement (VIS) to the child's parent or guardian at each visit prior to
administration of vaccines. Information on the VIS can be obtained from
www.cdc.gov/nip/publications/VIS/default.htm
Vaccine Delivery.
To ensure potency, vaccines should be stored at recommended temperatures before and after
reconstitution (www.cdc.gov/nip/menus/vaccines.htm#storage
). Expiration dates should be
noted, and expired vaccine should be discarded. Lyophilized vaccines often have long shelf
lives. However, the shelf life of reconstituted vaccines generally is short, ranging from 30 min
for the varicella vaccine and some forms of the Hib vaccine to 8 hr for the MMR vaccine and 24
hr for other forms of the Hib vaccine.
All vaccines have a preferred route of administration, which is specified in package inserts and
in AAP and ACIP recommendations. Most inactivated vaccines, including DTaP, hepatitis A,
HepB, Hib, TIV, PCV7, MCV4, and Tdap, are administered intramuscularly (IM). In contrast,
the commonly used live attenuated vaccines, MMR and varicella, should be dispensed
subcutaneously (SC). IPV and PPS23 (pneumococcal polysaccharide vaccine) can be given
IM or SC. For IM injections, the anterolateral thigh muscle is the preferred site for infants and
young children. The recommended needle length will vary depending on age and size, ranging
from inch for newborn infants, 1 inch for infants from 2 to 12 mo of age, and 1 to 1 inches
for older children. For adolescents and adults, the deltoid muscle of the arm is the preferred
site for IM administration with needle lengths of 11 inches depending on the size of the
patient. Most IM injections can be made with 2325 gauge needles. For SC injections, needle
lengths generally range from to inches with 2325 gauge needles.
RECOMMENDED IMMUNIZATION SCHEDULE.
All children in the U.S. should be vaccinated against 15 diseases (Figs. 170-2 and 170-3 [2] [3])
(updated schedule available at www.cdc.gov/nip/acip
). Girls 1112 yr old should also recieve
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February since influenza seasons typically peak in
January or later. IPV should be given at 2, 4, 618
mo, and 46 yr of age. PCV7 is recommended at
2, 4, 6, and 1215 mo of age. MMR should be
HPV. HepB vaccine is recommended in a 3 dose
schedule starting at birth. The birth dose is critical for administered at 1215 mo of age followed by a
children born to mothers who are hepatitis B surface 2nd dose at 4 6 yr of age. Varicella vaccine
antigen positive (HBsAg) or whose immune status is should be given at 1218 mo of age and at 46
unknown. The DTaP series consists of 5 doses. The yrs. The quadrivalent measles, mumps, rubella,
4th dose of DTaP may be administered as early as 12 and varicella (MMRV) vaccine may be used in
mo of age, provided 6 mo have elapsed since the 3rd place of separate MMR and varicella vaccines both
dose and the child is unlikely to return at 1518 mo of vaccines are indicated. Hepatitis A vaccine,
age. A booster, consisting of an adult preparation of licensed for administration to children 12 mo of
age, is now recommended for universal
Tdap is recommended at 1112 yr of age.
Adolescents 1318 yr of age who missed the 1112 administration to all children at 1223 mo of age
year old Td or Tdap booster dose or in whom it has and for certain high-risk groups. The 2 doses in the
series should be separated by at least 6 mo. A
been 5 yr since the Td booster dose also should
receive a single dose of Tdap if they have completed single dose of MCV4 is recommended for all
adolescents under one of the following
the diphtheria, tetanus, and pertussis (DTP)/DTaP
circumstances: (1) at 1112 yr of age; (2) at high
series. There are 3 licensed preparations of Hib
vaccine. The 2 vaccines conjugated to either tetanus school entry or 15 yr of age, whichever comes first;
(3) for unvaccinated persons entering college,
toxoid (PRP-T) or CRM197, a nontoxic variant of
diphtheria toxin, are given in a 4 dose series, while particularly for freshman who will live in
the Hib vaccine conjugated to meningococcal outer dormitories; and (4) for high-risk groups. All girls,
membrane protein (PRP-OMP) is recommended in a 1112 yr old, should receive a 3 dose schedule of
3 dose series. TIV is recommended for all 659 mo HPV. The second dose should be given 2 mo after
the first; the third is given 4 mo after the second.
old children. Children being vaccinated for the 1st
time require 2 doses at least 4 wk apart. TIV usually Three doses of the rotavirus vaccine are
is given in October or November, although there may recommended; dose one at 612 wk of age; the
series is completed by 32 wk of age.
be benefits even when administered as late as
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Figure 1702
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Figure 170-3
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http://aapredbook.aappublications.org/news/vaccstatus.shtml
www.fda.gov/cber/vaccine/licvacc.htm
.
and
For children who are at least 1 mo behind in their immunizations, catch-up immunization
schedules are available for children 4 mo to 6 yr of age and for children 718 yr of age ( Fig.
170-4 ; also available at www.cdc.gov/nip/recs/child-catchup-508.htm
).
Figure 170-4
Several vaccines are recommended for children at increased risk for complications from vaccinepreventable diseases or children who have an increased risk for exposure to these diseases. In
addition to annual vaccination of all children 659 mo of age with TIV, annual vaccination also is
recommended for all children 60 mo of age with underlying illnesses that increase their risks from
influenza. This includes children with chronic pulmonary disease (including asthma);
hemodynamically significant heart disease; immunocompromise, including HIV and AIDS, sickle
cell disease, and other hemoglobinopathies; chronic renal dysfunction; chronic metabolic diseases,
including diabetes mellitus; and children on long-term salicylate therapy. In addition, TIV is
recommended for all household contacts of children with the above conditions and all
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Immunizations
Review and complete age-appropriate
childhood and adolescent schedule (see text
for details)
[*]
Long-term
Brief, Intermediate, 2 Residential, >3
<2 wk wk to 3 mo
mo
+
+
+
1 DTaP, poliovirus, pneumococcal, and 2
Haemophilus influenzae type b
vaccines may be given at 4 wk
intervals if necessary to complete the
recommended schedule before
departure
Measles: 2
additional
doses given
if younger
than 12 mo
of age at first
dose
3 Rota virus
4 Hepatitis A
5 Varicella
7 Hepatitis B []
8 Tdap
9 Mcv4
6 HPV
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Yellow fever []
Hepatitis A []
+
+
+
+
+
+
Typhoid fever []
Meningococcal disease []
Rabies [#]
+
From the American Academy of Pediatrics: In Pickering LK, Baker CJ, Long SS, McMillan JA
(eds): Red Book 2006: Report of the Committee on Infectious Diseases, 27th ed. Elk Grove
Village, IL, American Academy of Pediatrics, 2006, p 99.
DTaP indicates diphtheria and tetanus toxoids and acellular pertussis;+, recommended;
, consider.
1* See disease-specific chapters in Section 3 for details. For further sources of information, see text.
1 If insufficient time to complete 6 mo primary series, accelerated series can be given (see text for details).
1 For regions with endemic infection (see Health Information for International Travel).
1 Indicated for travelers to areas with intermediate or high endemic rates of hepatitis A virus infection.
1 Indicated for travelers who will consume food and liquids in areas of poor sanitation.
1 Recommended for regions of Africa with endemic infection and during local epidemics, and required for travel to Saudi Arabia for
the Hajj.
1# Indicated for people with high risk for animal exposure (especially to dogs) and for travelers to countries with endemic infection.
1* For regions with endemic infection (see Health Information for International Travel). For high-risk activities in areas experiencing
outbreaks, vaccine is recommended, even for brief travel.
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safe, but
selective subclass IgG
caution is urged
may be
attenuate
d.
Partial defects
Complement
Phagocytic
function
Effectiveness depends on
degree of
immunosuppression.
Inactivated vaccines
recommended.
Deficiency of early
components (C1, C4,
C2, C3)
None
Deficiency of late
components (C5C9),
properdin, factor B
None
Chronic granulomatous
disease
Live-bacteria vaccines []
Leukocyte adhesion
defects
Myeloperoxidase
deficiency
SECONDARY
varicella inchildren
severely
MM ella, and all
may be
immunocompromise
R, inactivated vaccines, effective.
d
varic including influenza, []
and
on
sive [] , []
Effective dep ree of
ssi
Malignant
bacteria,
immune
or
radiation
therapy
ness
of
end
immun
on.
dep
neoplasm,
immuno
stat
transplantat
endi
any
s on e
Live virus
ion,
ng suppres us
vaccine deg suppre
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at 01/11/2015
HIV/AIDS
OPV,
[*] vaccinia, BCG,
LAIV [] ;
withhold
MMR and
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From the American Academy of Pediatrics. In Pickering LK, Baker CJ, Long SS, McMillan JA
(eds): Red Book 2006: Report of the Committee on Infectious Diseases, 27th ed. Elk Grove
Village, IL, American Academy of Pediatrics, 2006.
OPV, oral poliovirus; LAIV, live attenuated influenza vaccine; IGIV, immune globulin intravenous; Ig,
immunoglobulin; BCG, bacille Calmette-Gurin; MMR, measles-mumps-rubella.
1*
Live virus vaccines: LAIV, MMR, OPV, varicella, vaccinia (smallpox). Smallpox vaccine is not recommended for children.
HIV-infected children should receive immune globulin after exposure to measles (see Chapter 243 ) and may receive
varicella vaccine if the CD4+ lymphocyte count is 25% of expected for age (see Chapter 250 ).
Preterm infants generally can be vaccinated at the same chronologic age as full-term infants
according to the recommended childhood immunization schedule. An exception is the birth dose of
HepB vaccine. Infants weighing 2 kg and who are stable may receive a birth dose. However,
HepB vaccination should be deferred in infants weighing <2 kg at birth until 30 days of age, if born
to an HBsAg-negative mother. All preterm, low birth weight infants born to HBsAg-positive mothers
should receive HepB IG and HepB vaccine within 12 hr of birth. However, such infants should
receive an additional 3 doses of vaccine starting at 30 days of age.
Some children will present with situations that are not addressed directly in current
immunization schedules. There are general rules that physicians can use to guide
immunization decisions in some of these instances. In general, vaccines can be given
simultaneously on the same day, whether inactivated or live. Different inactivated vaccines can
be administered at any interval between doses. However, because of theoretical concerns
about viral interference, different live attenuated vaccines (MMR, varicella, LAIV) if not
administered on the same day, should be given at least 1 mo apart. An inactivated and a live
vaccine can be spaced at any interval from each other.
IG does not interfere with killed vaccines. However, IG can interfere with the immune response
to measles vaccine and by inference to varicella vaccine. In general, IG, if needed, should be
administered at least 2 wk after measles vaccine. Depending on the dose of IG received, MMR
should be deferred for as long as 311 mo. IG is not expected to interfere with the immune
response to LAIV. Rotavirus vaccine should be deferred for 6 wk following receipt of an
antibody-containing product; it should not be deferred before 13 wk of age.
Many agents have been considered for potential use as weapons of bioterrorism. For most of
these agents, licensed vaccines are not available in the U.S., although vaccines are being
developed for some organisms, including botulinum toxoid, ebola virus, plague, and others.
Anthrax vaccine and smallpox (vaccinia) vaccine are available, but they are not recommended
for children. Both are indicated in a pre-exposure setting only for selected adults with potential
occupational risks of exposure (www.bt.cdc.gov/
provides details on which groups are
recommended for vaccination).
PRECAUTIONS AND CONTRAINDICATIONS.
Observation of valid precautions and contraindications is critical to assure that vaccines are used in
the safest manner possible and to obtain optimal immunogenicity. When a child presents for
immunization with a clinical condition considered a precaution, the physician must weigh benefits
and risks to that individual child. If benefits are judged to outweigh risks, then the vaccine or
vaccines in question may be administered. A contraindication means the vaccine should not be
administered under any circumstances. A generic contraindication for all vaccines is anaphylaxis to
a prior dose. Anaphylactic hypersensitivity to vaccine constituents is also a contraindication.
However, if a vaccine is essential, there are desensitizing protocols for some vaccines. The major
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constituents of concern are egg proteins for vaccines grown in eggs; gelatin, a stabilizer in many
vaccines; and antimicrobial agents. The measles and mumps components of MMR are grown in
chick embryo fibroblast tissue culture. However, the amount of egg proteins in MMR is so small as
not to require any special procedures prior to administering vaccine to someone with a history of
anaphylaxis following egg ingestion. Vaccines usually should be deferred in children with moderate
to severe acute illnesses, regardless of the presence of fever, until the child recovers. However,
children with mild illnesses may be vaccinated. Studies of undervaccinated children have
documented opportunities that were missed because mild illness was used as an invalid
contraindication. Complete tables of contraindications and contraindication misperceptions can be
found at www.cdc.gov/nip/recs./contraindications.htm
Standards for child and adolescent immunization practices have been developed to support
achievement of high levels of immunization coverage while providing vaccines in a safe and
effective manner, and educating parents about risks and benefits of vaccines ( Table 170-7 ).
1.
2.
Vaccinations are coordinated with other health care services and provided in a
medical home when possible.
3.
4.
5.
Health care professionals review the vaccination and health status of patients at
every encounter to determine which vaccines are indicated.
6.
Health care professionals assess for and follow only medically accepted contraindications.
7.
Parents/guardians and patients are educated about the benefits and risks of vaccination
in a culturally appropriate manner and in easy-to-understand language.
8.
Health care professionals follow appropriate procedures for vaccine storage and handling.
9.
Up-to-date, written vaccination protocols are accessible at all locations where vaccines
are administered.
10. Persons who administer vaccines and staff who manage or support vaccine
administration are knowledgeable and receive ongoing education.
11. Health care professionals simultaneously administer as many indicated vaccine doses
as possible.
12. Vaccination records for patients are accurate, complete, and easily accessible.
13. Health care professionals report adverse events following vaccination promptly and
accurately to the Vaccine Adverse Event Reporting System (VAERS) and are aware of
a separate program, the National Vaccine Injury Compensation Program (VICP).
14. All personnel who have contact with patients are appropriately vaccinated.
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15. Systems are used to remind parents/guardians, patients, and health care
professionals when vaccinations are due and to recall those who are overdue.
16. Office- or clinic-based patient record reviews and vaccination coverage assessments
are performed annually.
Some parents may refuse immunization for their child. Pediatricians should try to open a
dialogue with such parents to understand the reasons for refusal and try to work with them to
overcome their concerns over time during the course of visits. Discussion should be based on
the reason for refusal and the knowledge of the parent. Pediatricians should refer patients to
reputable sources for vaccine information ( Table 170-8 ) and discuss risks and benefits of
vaccines. Physician concerns about liability should be addressed by appropriate documentation
of discussions in the chart. The Committee on Bioethics of the AAP has published guidelines for
dealing with parenteral refusal of immunization. Physicians also may wish to consider having
parents sign a refusal waiver. A sample of a refusal to vaccinate waiver can be found at
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www.cispimmunize.org/pro/pdf/refusaltovaccinate_2pageform.pdf .
TABLE 170-8 -- Vaccine Websites and Resources
HEALTH PROFESSIONAL ASSOCIATIONS
American Academy of Family Physicians (AAFP): www.familydoctor.org
American Academy of Pediatrics (AAP): www.aap.org
Support Program): www.cispimmunize.org
(image library)
www.cdc.gov/travel/vaccinat.htm
National Center for Infectious Diseases (NCID): www.cdc.gov/ncidod
National Immunization Program (NIP)
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www.cdc.gov/nip
www.cdc.gov/nip/publications
National Vaccine Program Office (NVPO): www.hhs.gov/nvpo
National Institute of Allergy and Infectious Diseases (NIAID):
www.niaid.nih.gov/dmid/vaccines
World Health Organization: www.who.int/vaccines
170.1 International Immunization Practices
Vaccines are used to prevent infectious diseases around the world. However, the types of
vaccines in use, the indications and contraindications, and immunization schedules vary
substantially. Most developing countries follow a schedule promulgated by the World Health
Organization's Expanded Programme on Immunization (EPI) [www.who.int/vaccinesdocuments/docspdf02/www557.pdf
]. According to this schedule, all children should be
vaccinated at birth against tuberculosis with bacille Calmette-Gurin (BCG) vaccine. Many
children also receive a dose of the live attenuated oral polio vaccine (OPV) at this time.
Immunization visits are scheduled for 6, 10, and 14 wk of age when DTP vaccine and OPV are
administered. Measles vaccine is given at 9 mo of age. Many developing countries have
implemented HepB vaccination. Two schedules may be used depending on whether
transmission is primarily perinatally from mother to infant or horizontal from postnatal family or
community contacts. To prevent perinatal transmission, doses should be administered at birth
and at 6 and 14 wk of age. For prevention of horizontal transmission, doses are recommended
at 6, 10, and 14 wk of age. Yellow fever vaccine is recommended for children living in endemic
areas at 9 mo of age. Increasing efforts are being made to incorporate Hib and pneumococcal
conjugate vaccines into developing country immunization programs. In 1988, the World Health
Assembly endorsed the goal of eradicating polio from the world by the end of 2000. While that
goal has not been reached, endemic polio transmission has been curtailed to three countries in
south AsiaIndia, Pakistan, and Afghanistan, and one country in Africa. Other countries have
had outbreaks from imported cases. The principal strategy has been use of OPV both for
routine immunization as well as in mass campaigns, at least twice per year, during which all
children <5 yr of age are targeted for immunization, regardless of prior immunization status.
The eventual goal, once termination of wild polio virus transmission is achieved, is to stop use
of OPV, which can rarely cause vaccine-associated polio and which is capable of mutating and
taking on the phenotypic characteristics of the wild viruses.
In Latin America, efforts to eliminate indigenous circulation of measles appear to have been
successful. The strategy called for routine immunization at 9 mo of age, a 1-time mass
campaign targeting all persons 9 mo through 14 yr of age regardless of prior immunization
status, and follow-up campaigns of children born since the prior campaign, generally every 35
yr. Latin American countries are attempting to eliminate indigenous rubella with strategies
consisting of both routine immunization and mass campaigns.
Immunization schedules in the industrialized world are substantially more variable than in the
developing world. Immunization recommendations for Canada are developed by the Canadian
National Advisory Committee on Immunization (NACI) but are implemented somewhat differently
by each province. The Canadian schedule is similar to the U.S. immunization schedule (www.phacaspc.gc.ca/naci-ccni/is-si/index.html
). Conjugate meningococcal serogroup C
vaccine (MCV-C) is recommended in a 3 dose series at 2, 4, and 6 mo of age. A single dose is
recommended after 12 mo of age if the child has never been immunized or received <3 doses
in infancy. The province of Ontario, Canada, has a recommendation for annual vaccination of
all children and adults with TIV.
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that in the U.S. The Japanese do not use MMR
and rely on individual vaccines for measles and
rubella. Japanese children also are vaccinated
www.who.int/vaccines/globalsummary/immunizatio routinely against polio with OPV; against
diphtheria, tetanus, and pertussis with DTaP; and
n/ScheduleSelect.cfm
. As an example, the
against Japanese encephalitis and tuberculosis
U.K. developed an immunization schedule during
with BCG
the late 1980s that includes visits at 2, 3, and 4 mo
(http://idsc.nih.go.jp/vaccine/dschedule/immEN050
of age where a combination DTaP-Hib-IPV is
729rev.gif
). The Japanese
administered along with MCV-C. MMR is
schedule
also
does not include any vaccines
recommended in a 2 dose schedule at 13 mo and
between 3 yr to 5 yr of age. During the 2nd MMR against encapsulated bacteria.
visit, a booster of DTaP and IPV is provided. A
Td/IPV booster is recommended between 13 and Some children will come to the U.S. having
started or completed international
18 yr of age. PCV7 is recommended at 2, 4, 13
immunization schedules with vaccines
mo of age. The U.K. was the first country to use
produced outside of the U.S. In general, doses
MCV-C vaccine during a massive catch-up
administered in other countries should be
campaign for children, adolescents, and young
adults. The effectiveness of the vaccine in the 1st considered valid if administered at the same
year was 88% or greater and herd immunity was ages as recommended in the U.S. For missing
doses, age-inappropriate doses, lost
induced with reduction in the incidence among
immunization records, or other concerns,
unvaccinated children of about . MCV-C is
pediatricians have 2 options: (1) administer or
administered at 3, 4, and 12 mo. As of October
repeat missing or inappropriate doses or (2)
2006, the U.K. schedule did not include HepB
vaccine, varicella vaccine, or influenza vaccine for perform serologic tests, and if negative,
administer vaccines.
universal childhood immunization (see
www.immunisation.nhs.uk
).
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