Immunity can be achieved
Actively by using antigens (eg, vaccines, toxoids)
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.
The most current recommendations for immunization are available at the Centers for Disease Control and Prevention (CDC) web sites Recommended Child and Adolescent Immunization Schedule 2021 and Recommended Adult Immunization Schedule 2021 and as a free mobile app. A summary of changes to the 2021 adult immunization schedule is available here.
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 Smallpox Smallpox is a highly contagious disease caused by the smallpox virus, an orthopoxvirus. It causes death in up to 30%. Natural infection has been eradicated. The main concern for outbreaks is... read more , polio Poliomyelitis Poliomyelitis is an acute infection caused by a poliovirus (an enterovirus). Manifestations include a nonspecific minor illness (abortive poliomyelitis), sometimes aseptic meningitis without... read more , diphtheria Diphtheria Diphtheria is an acute pharyngeal or cutaneous infection caused mainly by toxigenic strains of the gram-positive bacillusCorynebacterium diphtheriae and rarely by other, less common Corynebacterium... read more ) are now rare or have been eliminated. However, except for smallpox, these infections still occur in parts of the developing world.
On October 6, 2021, the World Health Organization (WHO) recommended widespread use of the RTS,S/AS01 (RTS,S) malaria Malaria Malaria is infection with Plasmodium species. Symptoms and signs include fever (which may be periodic), chills, rigors, sweating, diarrhea, abdominal pain, respiratory distress, confusion... read more vaccine among children in sub-Saharan Africa and in other regions with moderate to high Plasmodium falciparum malaria transmission.
Effective vaccines are not yet available for many important infections, including
Most sexually transmitted infections (eg, HIV infection Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more , herpes Genital Herpes Genital herpes is a sexually transmitted infection caused by human herpesvirus 1 or 2. It causes ulcerative genital lesions. Diagnosis is clinical with laboratory confirmation by culture, polymerase... read more , syphilis Syphilis Syphilis is caused by the spirochete Treponema pallidum and is characterized by 3 sequential clinical, symptomatic stages separated by periods of asymptomatic latent infection. Common... read more , gonorrhea Gonorrhea Gonorrhea is caused by the bacteria Neisseria gonorrhoeae. It typically infects epithelia of the urethra, cervix, rectum, pharynx, or conjunctivae, causing irritation or pain and purulent... read more , chlamydial infections Chlamydial, Mycoplasmal, and Ureaplasmal Mucosal Infections Sexually transmitted urethritis, cervicitis, proctitis, and pharyngitis not due to gonorrhea are caused predominantly by chlamydiae and infrequently by mycoplasmas or Ureaplasma sp. Chlamydiae... read more )
Tick-borne infections (eg, Lyme disease Lyme Disease Lyme disease is a tick-transmitted infection caused by the spirochete Borrelia species. Early symptoms include an erythema migrans rash, which may be followed weeks to months later by... read more , ehrlichiosis and anaplasmosis Ehrlichiosis and Anaplasmosis Ehrlichiosis and anaplasmosis are caused by rickettsial-like bacteria. Ehrlichiosis is caused mainly by Ehrlichia chaffeensis; anaplasmosis is caused by Anaplasma phagocytophilum... read more , babesiosis Babesiosis Babesiosis is infection with Babesia species of protozoa. Infections can be asymptomatic or cause a malaria-like illness with fever and hemolytic anemia. Disease is most severe in asplenic... read more )
Many tropical diseases (eg, Chikungunya disease Chikungunya disease Arbovirus (arthropod-borne virus) applies to any virus that is transmitted to humans and/or other vertebrates by certain species of blood-feeding arthropods, chiefly insects (flies and mosquitoes)... read more , dengue Dengue Dengue is a mosquito-borne disease caused by a flavivirus. Dengue fever usually results in abrupt onset of high fever, headache, myalgias, arthralgias, and generalized lymphadenopathy, followed... read more )
Many emerging diseases (eg, West Nile virus infection, Zika virus infection Zika Virus (ZV) Infections The Zika virus is a mosquito-borne flavivirus that is antigenically and structurally similar to the viruses that cause dengue, yellow fever, and West Nile virus. Zika virus infection is typically... read more )
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 Prevention , bacille Calmette-Guérin Vaccination Tuberculosis (TB) is a chronic, progressive mycobacterial infection, often with a period of latency following initial infection. TB most commonly affects the lungs. Symptoms include productive... read more , typhoid Vaccination Typhoid fever is a systemic disease caused by the gram-negative bacterium Salmonella enterica serotype Typhi (S. Typhi). Symptoms are high fever, prostration, abdominal pain, and... read more , yellow fever Prevention ) are not routinely given but are recommended only for specific people and circumstances (see the CDC's Recommended Adult Immunization Schedule 2021 and under the specific disorder, elsewhere in THE MANUAL; 1 General reference Immunity can be achieved Actively by using antigens (eg, vaccines, toxoids) Passively by using antibodies (eg, immune globulins, antitoxins) A toxoid is a bacterial toxin that has been modified... read more ).
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.
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 intramuscularly 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 General Best Practice Guidelines for Vaccine Administration from the Advisory Committee for Immunization Practices (ACIP) and Administering Vaccines to Adults from the Immunization Action Coalition.
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 ( 1 Vaccine administration reference Immunity can be achieved Actively by using antigens (eg, vaccines, toxoids) Passively by using antibodies (eg, immune globulins, antitoxins) A toxoid is a bacterial toxin that has been modified... read more ).
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.
Pearls & Pitfalls
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 Use of multiple, simultaneous vaccines Despite the rigorous vaccine safety systems in place in the US, some parents remain concerned about the safety of the use and schedule of vaccines in children. These concerns have led some parents... read more is safe, effective, and convenient; it is particularly recommended when children may be unavailable for future vaccination or when adults require multiple vaccines 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 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 reference
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.
For many vaccines, the only contraindication is a serious allergic reaction (eg, anaphylactic reaction Anaphylaxis Anaphylaxis is an acute, potentially life-threatening, IgE-mediated allergic reaction that occurs in previously sensitized people when they are reexposed to the sensitizing antigen. Symptoms... read more ) 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 Influenza Vaccine Based on recommendations by the World Health Organization and the Centers for Disease Control and Prevention (CDC), vaccines for influenza are modified annually to include the most prevalent... read more , 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 (considered generalizable to other egg-derived vaccines) 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:
Only hives after exposure to egg: Patients should be given an age-appropriate influenza vaccine.
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 a medical setting and supervised by a health care practitioner who can recognize and manage 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.
Asplenic patients Asplenia By structure and function, the spleen is essentially 2 organs: The white pulp, consisting of periarterial lymphatic sheaths and germinal centers, acts as an immune organ. The red pulp, consisting... read more 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):
Hib conjugate vaccine Haemophilus influenzae Type b (Hib) Vaccine Haemophilus influenzae type b (Hib) vaccines help prevent Haemophilus infections but not infections caused by other strains of H. influenzae bacteria. H. influenzae causes... read more (HbCV): Patients are given a single dose and no booster.
Meningococcal conjugate vaccine Meningococcal Vaccine The meningococcal serogroups that most often cause meningococcal disease in the US are serogroups B, C, and Y. Serogroups A and W cause disease outside the US. Current vaccines are directed... read more (MenACWY): Patients are given 2 doses at least 8 weeks apart and a booster every 5 years.
Meningococcal B vaccine Dose and Administration The meningococcal serogroups that most often cause meningococcal disease in the US are serogroups B, C, and Y. Serogroups A and W cause disease outside the US. Current vaccines are directed... read more (MenB): Patients are given a 2-dose series of MenB-4C ≥ 1 month apart or a 3-dose series of MenB-FHbp at 0, 1 to 2, and 6 months (if dose 2 was given at least 6 months after dose 1, dose 3 is not needed).
Pneumococcal conjugate (PCV13) and polysaccharide vaccines (PPSV23) Pneumococcal Vaccine Pneumococcal disease (eg, otitis media, pneumonia, sepsis, meningitis) is caused by some of the > 90 serotypes of Streptococcus pneumoniae (pneumococci). Vaccines are directed against... read more : Patients are given PCV13 if they did not receive a full series previously as a routine vaccination, then PPSV23 8 weeks later (≥ 2 weeks before or after splenectomy). At age 65 years or older, 1 booster dose of PPSV23 is given at least 5 years after the most recent PPSV23 dose.
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 Live-microbial vaccines Immunity can be achieved Actively by using antigens (eg, vaccines, toxoids) Passively by using antibodies (eg, immune globulins, antitoxins) A toxoid is a bacterial toxin that has been modified... read more 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.
Patients who developed Guillain-Barré syndrome Guillain-Barré Syndrome (GBS) Guillain-Barré syndrome is an acute, usually rapidly progressive but self-limited inflammatory polyneuropathy characterized by muscular weakness and mild distal sensory loss. Cause is thought... read more (GBS) within 6 weeks after a previous influenza or diphtheria-tetanus-acellular pertussis (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.
Immunocompromised patients should, in general, not receive live-microbial 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). Patients taking immune-suppressing drugs for any of a wide variety of disorders, including dermatologic, gastrointestinal, rheumatologic, and lung disorders, should not receive live-virus vaccines. For patients receiving long-term immunosuppressive therapy, clinicians should discuss risks and benefits of vaccination and/or revaccination with an infectious disease specialist.
Pearls & Pitfalls
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 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. Immunocompromised patients Immunocompromise Immunity can be achieved Actively by using antigens (eg, vaccines, toxoids) Passively by using antibodies (eg, immune globulins, antitoxins) A toxoid is a bacterial toxin that has been modified... read more should, in general, not receive live-virus vaccines.
Live-microbial vaccines include the following:
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 and Other Indications 2021).
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.
In the US, the safety of vaccines is ensured through two surveillance systems: the CDC's and the U.S. Food and Drug Administration's (FDA) Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD).
VAERS is a safety program cosponsored by the FDA and the CDC; VAERS collects reports from individual patients who believe that they had an adverse event after a recent vaccination. Health care practitioners are also required to report certain events after vaccination and may report events even if they are unsure the events are vaccine-related. VAERS reports originate all across the country and provide a rapid assessment of potential safety issues. However, VAERS reports can show only temporal associations between vaccination and the suspected adverse event; they do not prove causation. Thus, VAERS reports must be further evaluated using other methods. One such method uses the VSD, which uses data from 9 large managed care organizations (MCOs) representing more than 9 million people. The data include vaccine administration (noted in the medical record as part of routine care), as well as subsequent medical history, including adverse events. Unlike VAERS, the VSD includes data from patients who have not received a given vaccine as well as those who have. As a result, the VSD can help distinguish actual adverse events from symptoms and disorders that occurred coincidentally after vaccination and thus determine the actual incidence of adverse events.
Nonetheless, many parents remain concerned about the safety of childhood vaccines Effectiveness and Safety of Childhood Vaccination Vaccination has been profoundly effective in preventing serious disease. Given their modest cost (particularly in comparison to drugs that must be taken long-term), vaccines are one of the most... read more 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 Vaccine Hesitancy Vaccine Hesitancy Despite the rigorous vaccine safety systems in place in the US, some parents remain concerned about the safety of the use and schedule of vaccines in children. These concerns have led some parents... read more ). 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 Autism Spectrum Disorders Autism spectrum disorders are neurodevelopmental disorders characterized by impaired social interaction and communication, repetitive and stereotyped patterns of behavior, and uneven intellectual... read more . Reasons cited include
A possible connection between the combination measles-mumps-rubella vaccine and autism (see MMR vaccine and autism Measles-mumps-rubella (MMR) vaccine Despite the rigorous vaccine safety systems in place in the US, some parents remain concerned about the safety of the use and schedule of vaccines in children. These concerns have led some parents... read more )
The possibility that thimerosal might cause autism (thimerosal is a mercury-based preservative used in some vaccines—see Thimerosal and autism Thimerosal and autism Despite the rigorous vaccine safety systems in place in the US, some parents remain concerned about the safety of the use and schedule of vaccines in children. These concerns have led some parents... read more )
Use of multiple, simultaneous vaccines Use of multiple, simultaneous vaccines Despite the rigorous vaccine safety systems in place in the US, some parents remain concerned about the safety of the use and schedule of vaccines in children. These concerns have led some parents... read more , given as recommended
In 1998, Andrew Wakefield and colleagues published a brief report in The Lancet (see MMR vaccine and autism Measles-mumps-rubella (MMR) vaccine Despite the rigorous vaccine safety systems in place in the US, some parents remain concerned about the safety of the use and schedule of vaccines in children. These concerns have led some parents... read more ). 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 Vaccine safety references Immunity can be achieved Actively by using antigens (eg, vaccines, toxoids) Passively by using antibodies (eg, immune globulins, antitoxins) A toxoid is a bacterial toxin that has been modified... read more ). 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 Vaccine safety references Immunity can be achieved Actively by using antigens (eg, vaccines, toxoids) Passively by using antibodies (eg, immune globulins, antitoxins) A toxoid is a bacterial toxin that has been modified... read more ).
At this time, virtually every vaccine given to children in the US 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 the Institute for Vaccine Safety's web site for Thimerosal Content in Some US Licensed Vaccines. Thimerosal is also in many vaccines used in developing countries.
As with any treatment, clinicians should talk to their patients about the relative risks and benefits of recommended vaccines ( 3 Vaccine safety references Immunity can be achieved Actively by using antigens (eg, vaccines, toxoids) Passively by using antibodies (eg, immune globulins, antitoxins) A toxoid is a bacterial toxin that has been modified... read more ). 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
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
2. Institute of Medicine Immunization Safety Review Committee: Immunization safety review: Vaccines and autism. Washington DC, National Academies Press, 2004.
3. Spencer JP, Trondsen Pawlowski RH, Thomas S: Vaccine adverse events: Separating myth from reality. Am Fam Physician 95(12):786–794, 2017.
Immunization for Travelers
Immunizations may be required for travel to areas where infectious diseases are endemic (see table Vaccines for International Travel 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.
The following are some English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
Advisory Committee on Immunization Practices (ACIP): Vaccine-Specific Recommendations
World Health Organization (WHO): WHO recommends groundbreaking malaria vaccine for children at risk
U.S. Food and Drug Administration (FDA): Thimerosal and Vaccines
Institute for Vaccine Safety: Thimerosal Content in Some US Licensed Vaccines
Children's Hospital of Philadelphia: Vaccine Education Center
See the following Centers for Disease Control and Prevention (CDC) sites for comprehensive information about immunization schedules, recommendations for vaccine administration, vaccine resources for travelers, vaccine safety, and vaccine-related patient-friendly resources:
CDC: Travelers' Health
CDC, FDA, and agencies of the U.S. Department of Health and Human Services (HHS): Vaccine Adverse Event Reporting System (VAERS)
CDC and the Food and Drug Administration: Vaccine Safety Datalink
Immunization Action Coalition: Administering Vaccines to Adults: Dose, Route, Site, and Needle Size
Immunization Action Coalition: Administering Vaccines to Children: Dose, Route, Site, and Needle Size