Topic Resources
Immunity can be achieved
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Actively by using antigens (eg, vaccines, toxoids)
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Passively by using antibodies (eg, immune globulins, antitoxins)
A toxoid is a bacterial toxin that has been modified to be nontoxic but that can still stimulate antibody formation.
A vaccine is a suspension of whole (live or inactivated)
or fractionated bacteria or viruses rendered nonpathogenic. For vaccines
available in the US, see Table: Vaccines Available in the US.
The most current recommendations for immunization are available at the Centers for Disease Control and Prevention (CDC) web site and as a free mobile app. Also see Table: Vaccine Administration Guidelines for Adults, see Table: Recommended Immunization Schedule for Ages 7–18 Years (see also the CDC's Child and Adolescent Immunization Schedule), and see Table: Vaccine Administration Guidelines for Adults (see also the CDC's Recommended Adult Immunization Schedule).
For the contents of each vaccine (including additives), see that vaccine's package insert.
Vaccination has been extremely effective in preventing serious
disease and in improving health worldwide. Because of vaccines,
infections that were once very common and/or fatal (eg, smallpox, polio, diphtheria)
are now rare or have been eliminated. However, except for smallpox,
these infections still occur in parts of the developing world.
Effective vaccines are not yet available for many important infections, including
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Most sexually transmitted diseases (eg, HIV infection, herpes, syphilis, gonorrhea, chlamydial infections)
Certain vaccines are recommended routinely for all adults at
certain ages who have not previously been vaccinated or have no evidence
of previous infection. Other vaccines (eg, rabies, bacille Calmette-Guérin, typhoid, yellow fever) are not routinely given but are recommended only for specific people and circumstances (see the CDC's Recommended Adult Immunization Schedule and under the specific disorder, elsewhere in THE MANUAL; 1).
Some adults do not get the vaccines recommended for them. For
example, only 55.1% of those > 65 were given a tetanus vaccine within
a 10-year period. Also, vaccination rates tend to be lower in blacks,
Asians, and Hispanics than in whites.
Vaccine Administration
Vaccines should be given exactly as recommended on the package
insert; however, for most vaccines, the interval between a series of
doses may be lengthened without losing efficacy.
Injection vaccines are usually given IM into the midlateral thigh
(in infants and toddlers) or into the deltoid muscle (in school-aged
children and adults). Some vaccines are given subcutaneously. For
details on vaccine administration, see the CDC's General Best Practice Guidelines for Vaccine Administration and Administering Vaccines to Adults.
Shoulder injury related to vaccine administration (SIRVA) may be
caused by the unintentional injection of a vaccine into tissues and
structures under the deltoid muscle of the shoulder (2).
Clinicians should have a process in place to ensure that patient
vaccination status is reviewed at each visit so that vaccines are given
as per recommendations. Patients (or caregivers) should be encouraged to
keep a history (written or electronic) of their vaccinations and share
this information with new health care practitioners and institutions to
make sure that vaccinations are up to date.
If a vaccine series (eg, for hepatitis B or human papillomavirus)
is interrupted, practitioners should give the next recommended dose the
next time the patient presents, provided that the recommended interval
between doses has passed. They should not restart the series (ie, with
dose 1).
Simultaneous administration of different vaccines
With rare exceptions, simultaneous administration of vaccines
is safe, effective, and convenient; it is particularly recommended when
children may be unavailable for future vaccination or when adults
require multiple simultaneous vaccines (eg, before international
travel). An exception is simultaneous administration of pneumococcal
conjugate vaccine (PCV13) and the meningococcal conjugate vaccine
MenACWY-D (Menactra®) to children with functional or anatomic
asplenia; these vaccinations should not be given during the same visit
but should be separated by ≥ 4 weeks.
Simultaneous administration may involve combination vaccines (see Table: Vaccines Available in the US) or use of ≥ 1 single-antigen vaccines. More than one vaccine may be given at the same time using different injection sites and syringes.
If live-virus vaccines (varicella and MMR) are not given at the same time, they should be given ≥ 4 weeks apart.
Vaccine administration references
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1. Kim DK, Hunter P, on behalf of the Advisory Committee on Immunization Practices: Recommended adult immunization schedule, United States, 2019. Ann Int Med 170:182–192, 2019. doi: 10.7326/M18-3600. Clarification and additional information. Ann Int Med 170(7):512, 2019.
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2. Barnes MG, Ledford C, Hogan K: A "needling" problem: Shoulder injury related to vaccine administration. J Am Board Fam Med 25(6):919–922, 2012. doi: 10.3122/jabfm.2012.06.110334.
Restrictions, Precautions, and High-Risk Groups
Restrictions and precautions are conditions that
increase the risk of an adverse reaction to a vaccine or that compromise
the ability of a vaccine to produce immunity. These conditions are
usually temporary, meaning the vaccine can be given later. Sometimes
vaccination is indicated when a precaution exists because the protective
effects of the vaccine outweigh the risk of an adverse reaction to the
vaccine.
Contraindications are conditions that increases the risk
of a serious adverse reaction. A vaccine should not be given when a
contraindication is present.
Allergy
For many vaccines, the only contraindication is a serious allergic reaction (eg, anaphylactic reaction) to the vaccine or to one of its components.
Egg allergy is common in the US. Some vaccines produced in cell culture systems, including most influenza vaccines,
contain trace amounts of egg antigens; thus, there is concern about
using such vaccines in patients who are allergic to eggs. CDC guidelines
for the influenza vaccine state that although mild reactions may occur,
serious allergic reactions (ie, anaphylaxis) are unlikely, and
vaccination with inactivated influenza vaccine is contraindicated only
in patients who have had anaphylaxis after a previous dose of any
influenza vaccine or to a vaccine component, including egg protein.
Other recommendations for patients with a history of egg allergy include the following:
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Only hives after exposure to egg: Patients should be given an age-appropriate influenza vaccine.
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Other reactions to eggs (eg, angioedema, respiratory distress, light-headedness, recurrent emesis and reactions that required epinephrine or other emergency treatment): Patients may be given an age-appropriate influenza vaccine. However, the vaccine should be given in an inpatient or outpatient medical setting and supervised by a clinician who has experience recognizing and managing severe allergic reactions.
NOTE: A previous severe allergic reaction to influenza vaccine,
regardless of the component suspected of being responsible for the
reaction, is a contraindication to future receipt of the vaccine.
Asplenia
Asplenic patients are predisposed to overwhelming bacteremic infection, primarily due to encapsulated organisms such as Streptococcus pneumoniae, Neisseria meningitidis, or Haemophilus influenzae type b (Hib). Asplenic adults should be given the following vaccines (before splenectomy if possible):
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Meningococcal B vaccine (MenB): 2-dose series of MenB-4C ≥ 1 month apart or 3-dose series of MenB-FHbp at 0, 1–2, and 6 months
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Pneumococcal conjugate (PCV13) and polysaccharide vaccines (PPSV23): PCV13 if patients did not receive a full series previously as a routine vaccination, then PPSV23 8 weeks later (≥ 2 weeks before or after splenectomy) with a single PPSV23 booster after 5 years and a routine booster dose at age 65
Additional doses may be given based on clinical judgment.
Blood product use
Live-microbial vaccines should not be given simultaneously with blood or plasma transfusions or immune globulin;
these products can interfere with development of desired antibodies.
Ideally, live-microbial vaccines should be given 2 weeks before or 6 to
12 weeks after the immune globulins.
Fever or other acute illness
A significant fever (temperature of > 39°
C) or severe illness without fever requires delaying vaccination, but
minor infections, such as the common cold (even with low-grade fever),
do not. This precaution prevents confusion between manifestations of the
underlying illness and possible adverse effects of the vaccine and
prevents superimposition of adverse effects of the vaccine on the
underlying illness. Vaccination is postponed until the illness resolves,
if possible.
Guillain-Barré syndrome
Patients who developed Guillain-Barré syndrome
(GBS) within 6 weeks after a previous influenza or DTaP vaccination may
be given the vaccine if the benefits of vaccination are thought to
outweigh the risks. For example, for patients who developed the syndrome
after a dose of DTaP, clinicians may consider giving them a dose of the
vaccine if a pertussis outbreak occurs; however, such decisions should
be made in consultation with an infectious disease specialist.
The Advisory Committee on Immunization Practices no longer
considers a history of GBS to be a precaution for use of the
meningococcal conjugate vaccine, although it remains listed as a
precaution in the package insert.
Immunocompromise
Immunocompromised patients should, in general, not receive
live-virus vaccines, which could provoke severe or fatal infections. If
immunocompromise is caused by immunosuppressive therapy (eg, high-dose
corticosteroids [≥ 20 mg prednisone
or equivalent for ≥ 2 weeks], antimetabolites, immune modulators,
alkylating compounds, radiation), live-virus vaccines should be withheld
until the immune system recovers after treatment (the interval of time
varies depending on the therapy used). For patients receiving long-term
immunosuppressive therapy, clinicians should discuss risks and benefits
of vaccination and/or revaccination with an infectious disease
specialist.
Patients with HIV infection should generally receive
inactivated vaccines (eg, diphtheria-tetanus-acellular pertussis [Tdap],
polio [IPV], Hib) according to routine recommendations. Despite the
general caution against giving a live-virus vaccine, patients who have
CD4 counts ≥ 200/mcL (ie, are not severely immunocompromised) can be
given certain live-virus vaccines, including measles-mumps-rubella
(MMR). Patients with HIV infection should receive both pneumococcal
conjugate and polysaccharide vaccines (and be revaccinated after 5
years).
Live-microbial vaccines
Live-microbial vaccines should not be given simultaneously with blood, plasma, or immune globulin,
which can interfere with development of desired antibodies; ideally,
such vaccines should be given 2 weeks before or 6 to 12 weeks after the
immune globulins.
Live-microbial vaccines include the following:
Pregnancy
Pregnancy is a contraindication to vaccination with MMR,
intranasal (live) influenza vaccine, varicella, and other live-virus
vaccines.
The Advisory Committee on Immunization Practices recommends
delaying vaccination with HPV vaccine and recombinant zoster vaccine
until after pregnancy. (See Recommended Adult Immunization Schedule by Medical Condition or Other Indications).
Transplantation
Before solid organ transplantation, patients should receive all
appropriate vaccines. Patients who have had allogeneic or autogeneic
hematopoietic stem cell transplantation should be considered unimmunized
and should receive repeat doses of all appropriate vaccines. Care of
these patients is complex, and vaccination decisions for these patients
should involve consultation with the patient's hematologist-oncologist
and an infectious disease specialist.
Vaccine Safety
In the US, the safety of vaccines is ensured through several
surveillance systems; selected events that occur after routine
vaccination must be reported electronically to the CDC's and the Food
and Drug Administration's (FDA) Vaccine Adverse Event Reporting System (VAERS). For additional information about the safety of individual vaccines, see the Vaccine Safety Datalink (VSD) at the CDC web site.
Nonetheless, many parents remain concerned about the safety of childhood vaccines
and their possible adverse effects (particularly autism). These
concerns, perpetuated on the Internet, have led some parents to not
allow their children to be given some or all of the recommended vaccines
(see Anti-Vaccination Movement).
As a result, outbreaks of diseases made uncommon by vaccination (eg,
measles, pertussis) are becoming more common among unvaccinated children
in North America and Europe.
One of the main parental concerns is that vaccines may increase the risk of autism. Reasons cited include
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A possible connection between the combination measles-mumps-rubella vaccine and autism (see MMR vaccine and autism)
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The possibility that thimerosal might cause autism (thimerosal is a mercury-based preservative used in some vaccines—see Thimerosal and autism)
In 1998, Andrew Wakefield and colleagues published a brief report in The Lancet (see Anti-Vaccination Movement : Measles-mumps-rubella (MMR) vaccine and autism).
In it, Wakefield postulated a link between the measles virus in the MMR vaccine and autism. This report received significant media attention worldwide, and many parents began to doubt the safety of the MMR vaccine. However, since then, The Lancet has retracted the report because it contained serious scientific flaws; many subsequent, large studies have failed to show any link between the vaccine and autism.
In it, Wakefield postulated a link between the measles virus in the MMR vaccine and autism. This report received significant media attention worldwide, and many parents began to doubt the safety of the MMR vaccine. However, since then, The Lancet has retracted the report because it contained serious scientific flaws; many subsequent, large studies have failed to show any link between the vaccine and autism.
Gerber and Offit reviewed epidemiologic and biologic studies
concerning this issue and found no evidence to support an association
between use of vaccines and risk of autism (1).
The US Institute of Medicine Immunization Safety Review Committee
reviewed epidemiologic studies (published and unpublished) to determine
whether the measles-mumps-rubella vaccine and vaccines containing
thimerosal cause autism and to identify possible biologic mechanisms for
such an effect; based on the evidence, this group rejected a causal
relationship between these vaccines and autism (2).
At this time, virtually every vaccine given to children is
thimerosal-free. Small amounts of thimerosal continue to be used in
multidose vials of influenza vaccine and in several other vaccines
intended for use in adults. For information about vaccines that contain
low levels of thimerosal, see the Food and Drug Administration's web
site (Thimerosal and Vaccines) and Thimerosal Content in Some US Licensed Vaccines. Thimerosal is also used in many vaccines produced in developing countries.
As with any treatment, clinicians should talk to their patients
about the relative risks and benefits of recommended vaccines. In
particular, clinicians must make sure that the parents of their patients
are aware of the possible serious effects (including death) of
vaccine-preventable childhood diseases such as measles, Hib infection,
and pertussis, and clinicians should discuss any concerns parents may
have about vaccinating their children. Resources for these discussions
include the CDC's Talking with Parents about Vaccines for Infants and Parents' Guide to Childhood Immunizations.
Vaccine safety references
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1. Gerber JS, Offit PA: Vaccines and autism: A tale of shifting hypotheses. Clin Infect Dis 48 (4):456-461, 2009. doi: 10.1086/596476.
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2. Institute of Medicine Immunization Safety Review Committee: Immunization safety review: Vaccines and autism. Washington DC, National Academies Press, 2004.
Immunization for Travelers
Immunizations may be required for travel to areas where infectious diseases are endemic (see Table: Vaccines for International Travel*, † , ‡ , §). The CDC can provide this information; a telephone service (1-800-232-4636 [CDC-INFO]) and web site (Travelers' Health) are available 24 hours/day.
More Information
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Food and Drug Administration: Thimerosal and Vaccines and Thimerosal Content in Some US Licensed Vaccines
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