Harrison's Practice: Immunization

Harrison's Practice

Immunization

Definition

Immunization is the process of inducing or providing immunity by any means.
- Active immunization: administration of antigens to induce immune defenses
- Passive immunization: provision of temporary protection by the administration of exogenously produced immune substances
Immunizing agents
- Vaccine
  - A preparation of attenuated live or killed microorganisms or antigenic portions of those agents used to induce immunity and prevent disease
  - Vaccination
    - Administration of a vaccine
    - Does not guarantee immunization
  - Toxoid
    - A modified bacterial toxin that has been rendered nontoxic but retains the capacity to stimulate the formation of antitoxin
- Immune globulin
  - An antibody-containing protein fraction derived from human plasma
  - Used for maintaining immunity in immunodeficient persons
  - Used for passive immunization when active immunization is not possible
- Antitoxin
  - An antibody derived from the serum of animals after stimulation with specific antigens
  - Used to provide passive immunity to the toxin protein to which it is directed

Goals

Reduction of morbidity and mortality
- One of the few cost-saving interventions to prevent infectious disease
- Many vaccine-preventable diseases remain prevalent in the developing world.
  - 20–35% of all deaths of children < 5 years old are associated with vaccine-preventable diseases.
- Vaccines represent the best hope for:
  - Stopping the pandemic of HIV infection
  - Efficiently controlling malaria and tuberculosis
Maintenance of individual and herd immunity
- Each subsequent generation must be immunized as long as the threat persists for reintroduction of a disease from anywhere in the world.

Mechanism of Action

Active immunization

Live infectious agents
- Vaccines consist of selected or genetically altered organisms that are avirulent or dramatically attenuated, yet remain immunogenic.
- Agents are expected to cause a subclinical illness and an immunologic response mimicking the results of natural infection (except for the lack of clinically significant disease).
- Advantages include:
  - Long-lasting immunity
  - Replication in vivo, which increases the antigenic load presented to the host’s immune system
  - Presentation of all expressed antigens, overcoming immunogenetic restrictions in some hosts
  - Penetration to local sites most relevant to induction of protective immunity
  - Production of important protective antigens in vivo that are not efficiently expressed in vitro
- Despite advantages, live vaccines are not always preferable.
Inactivated agents
- Currently available nonviable vaccines consist of:
  - Inactivated whole organisms
  - Detoxified protein exotoxins
  - Recombinant protein antigens
  - Carbohydrate antigens, either present as soluble purified capsular material or conjugated to a protein carrier
- Typically (but not always), multiple doses and periodic boosters are required for the maintenance of immunity.
For many diseases, both of the active approaches have been used.

Passive immunization

Generally used to provide temporary immunity when active immunization either is unavailable or has not been implemented before exposure
Used in:
- Treatment of various disorders associated with toxins
- Certain bites (e.g., snakes, spiders)
- Specific or nonspecific immunosuppression
Three types of preparations are used.
- Standard human immune serum globulin for general use, administered IM or IV
- Special immune serum globulins with a known content of antibody to specific agents
- Animal sera and antitoxins

Adjuvant potentiation

Adjuvants are nonspecific boosters of immune responses that are used with inactivated toxoids and vaccines.
The mechanism underlying adjuvant potentiation is not well defined but relates in part to:
- Rendering of soluble antigens into a particulate form
- Mobilization of phagocytes to the site of antigen deposition
- Slowing down of the release of antigens, which prolongs stimulation of the immune response

Immune response

Primary
- A latent period of several days precedes the detection of humoral and cell-mediated immunity.
- The primary response is characterized by early-appearing IgM antibodies, which generally exhibit only low affinity for the antigen.
- Although the immune response begins with recognition of the antigen by the immune system, measurable circulating antibodies do not appear for 7–10 days.
Secondary
- Heightened humoral or cell-mediated responses are elicited by a second exposure to the same antigen and occur rapidly, usually within 4–5 days.
- The secondary response:
  - Is characterized by marked proliferation of IgG antibody–producing B lymphocytes and/or effector T cells
  - Depends on immunologic memory after the first exposure
- Conjugation to proteins converts polysaccharides to T cell–dependent antigens that induce immunologic memory and secondary responses to revaccination.

Mucosal immunity

Some pathogens are confined to and replicate only at mucosal surfaces, whereas others can penetrate the mucosa and replicate.
- At the mucosal site, these organisms induce secretory IgA.
- The induction of secretory IgA by vaccines may be an efficient way to block the essential first steps in pathogenesis, whether the organism is restricted to mucosal surfaces or invades the host across mucosal surfaces.

Herd immunity

At a definable prevalence of immunity in the population, an infectious organism can no longer circulate freely among susceptibles.
- This indirect protection of unvaccinated (nonimmune) persons is called the herd immunity effect.
The level of vaccination coverage needed to elicit herd immunity depends on the mixing patterns of the population and the biology of the specific infectious agents.
Herd immunity may wane if immunization programs are interrupted or if a sufficient percentage of individuals refuse to be immunized.
- Loss of herd immunity has led to renewed circulation of specific organisms and subsequent large outbreaks.

Indications

Vaccines for routine use

Immunization schedule

Children and adolescents: see Figure 1
Adults: see Figure 2

Diphtheria, tetanus, and pertussis vaccines

DtaP (diphtheria/tetanus/acellular pertussis)
- Indicated for all children
- Administered IM
- Adverse events
  - Reduced local reactions compared with those to whole-cell pertussis vaccines
  - No serious reactions reported
DT (diphtheria and tetanus toxoids, adsorbed), Td (tetanus and diphtheria toxoids, adsorbed; adult formulation)
- Administered IM
- Adverse events
  - Local reactions
  - Hypersensitivity to tetanus toxoid

Haemophilus influenzae type b (Hib) vaccine

Bacterial polysaccharide–protein conjugate
Indicated for all children
Administered IM
Adverse events
- Few local reactions
- No serious systemic reactions reported

Hepatitis B (HepB) vaccine

Recombinant antigen
Now routinely recommended for all children
Adults
- Hemodialysis patients
- Patients receiving clotting factor concentrates
- Health care workers and public safety workers exposed to blood
- Students in the health professions
- Injection drug users
- Persons with multiple sex partners within 6 months
- Patients with recent sexually transmitted disease (STD)
- Clients of STD clinics
- Men who have sex with men
- Household contacts and sex partners of persons with chronic hepatitis B virus infection
- Clients and staff of institutions for the mentally disabled
- Inmates of correctional institutions
- International travelers to countries with high prevalence
Administered IM
Adverse events: few (? Guillain-Barré syndrome)

Influenza vaccine

Inactivated virus or viral components
Administered IM
Children 6–24 months of age
- Annually for children ≥6 months old who have certain risk factors
  - Asthma, cardiac disease, sickle cell disease, HIV infection, diabetes mellitus
  - Household members of persons in groups at high risk
- All others wishing to obtain immunity
  - If feasible, influenza vaccination of healthy children 6–23 months old is encouraged because of a substantially increased risk for influenza-related hospitalizations in this group.
Adults
- Age > 50 years
- Chronic cardiovascular or pulmonary disease
- Asthma
- Diabetes
- Renal disease
- Hemoglobinopathy
- Immunosuppression (due to medications or HIV infection)
- Pregnancy (second or third trimester during influenza season)
- Health care employment
- Residence in a nursing home or another long-term-care facility
- High likelihood of transmitting influenza to those at high risk
- Household contact with persons to whom indications apply
Adverse events
- ? Guillain-Barré syndrome with swine influenza vaccine
- In children < 13 years old, only "split-virus" preparations should be used since whole-virus vaccines are associated with higher rates of adverse reactions in this age group.

Measles/mumps/rubella (MMR) vaccine

Live viruses
Indicated for all children
Adults
- Adults born before 1957 are considered immune to measles.
- Adults born after 1957 should have at least 1 dose of MMR vaccine, barring a medical contraindication or documentation of prior immunization.
- A second dose is recommended for adults who:
  - Have recently been exposed to measles in an outbreak setting
  - Have previously received killed measles vaccine
  - Received an unknown measles vaccine between 1963 and 1967
  - Are students at a college or university
  - Work in health care facilities
  - Plan to travel internationally
- All nonpregnant women of childbearing age should be vaccinated unless there is documented proof of immunity.
Administered SC
Adverse events
- Acute encephalopathy (measles)
- Rare parotitis or orchitis (mumps)
- Arthralgia and rare arthropathy (rubella)

Pneumococcal polysaccharide vaccine

Capsular polysaccharide (23 types)
One dose for adults in the following groups:
- ≥65 years of age
- Chronic cardiovascular or pulmonary disease (except asthma)
- Diabetes
- Chronic liver disease
- Chronic renal failure or nephrotic syndrome
- Asplenia
- Immunosuppression
- Certain cancer chemotherapy
- Long-term systemic glucocorticoid therapy
- Alaskan natives
- Certain Native American populations
- Residents of nursing homes and other long-term-care facilities
Revaccination with pneumococcal polysaccharide vaccine
- One-time revaccination after 5 years is indicated in:
  - Chronic renal failure or nephrotic syndrome
  - Asplenia
  - Immunosuppression
  - Certain cancer chemotherapy
  - Long-term systemic glucocorticoid therapy
- Persons > 65 years old should undergo one-time revaccination if their prior vaccination was given at least 5 years before and before age 65.
Administered IM or SC
Adverse events
- Local reactions
- Rare anaphylaxis

Pneumococcal conjugate vaccine

Polysaccharide-protein conjugates (7–11 types)
Indicated for all children 2–23 months old
Administered IM

Inactivated poliovirus vaccine (IPV)

Inactivated virus of 3 types
Indicated for all children
Administered SC

Varicella vaccine

Live virus
Indicated for all children 12–18 months old
Adults
- All persons without a reliable clinical history of varicella or serologic evidence of immunity
- Health care workers
- Family contacts of immunosuppressed persons
- Persons who live or work in high-risk settings (teachers of young children, day-care workers, residents and staff members in institutional settings)
- Adolescents and adults living in households with children
- Women who are not pregnant but intend to become pregnant in the future
Administered SC
Adverse events
- Local reaction
- Varicella-like rash

Hepatitis A vaccine (HepA)

Children and adolescents
- HepA vaccination is recommended for children and adolescents in selected states and regions and for certain high-risk groups.
- Can begin at any age
Adults
- Persons with increased risk of exposure to infection because of residence in communities with elevated rates of HepA
- Persons with clotting factor disorders
- Individuals with chronic liver disease
- Men who have sex with men
- Users of illegal drugs (injection and noninjection)
- Persons working with HepA virus–infected primates or with HepA virus in a laboratory
- Persons traveling to or working in countries with high prevalence

Use of vaccines in special circumstances

High-risk exposure groups
- Groups include:
  - Health care and other institutional workers
  - Prisoners
  - Students
  - Military personnel
  - Injection drug users
  - Men who have sex with men
- Special considerations for health care workers
  - MMR vaccine
    - Rubella is transmitted to and from health care workers at medical facilities, particularly in pediatric practice.
    - Health care workers who might transmit rubella to pregnant patients should be screened for antibodies to rubella virus.
    - Susceptible individuals must be immunized.
    - A second dose should be given to persons who are likely to come into contact with measles- and varicella-infected patients.
  - Influenza vaccine
    - Administer annually to persons employed in caring for patients with chronic diseases.
  - HepB vaccine
    - Mandated by OSHA for immunization of health care workers
- Meningococcal polysaccharide vaccine (covering serogroups A, C, Y, and W-135) should be given to college students, particularly freshmen living at close quarters.
- Special-use vaccines related to travel and occupational exposures should be given per CDC guidelines.
Persons at high risk for severe outcomes of infection (see Figure 3)
- Includes:
  - Elderly persons
  - Persons with chronic medical conditions, including diabetes, alcoholism, immunodeficiency, and renal, hepatic, respiratory, or cardiac disease
- Influenza vaccine and polyvalent pneumococcal polysaccharide vaccine
  - Individuals with chronic illness at any age
- HepA vaccine
  - Persons with clotting disorders or chronic liver disease
- HepB vaccine
  - Patients undergoing hemodialysis and routine recipients of clotting factors
Household contacts of persons at high risk for severe outcomes of infection
- HepB vaccine
  - Household contacts of known carriers of hepatitis B surface antigen (HBsAg)
- Influenza vaccine
  - Persons living in the same household as chronically ill individuals
Pregnancy
- Routine immunization of pregnant women is best avoided.
- If hygienic conditions during delivery cannot be guaranteed, it is essential to prevent neonatal tetanus.
  - Pregnant women can safely receive tetanus toxoid as well as diphtheria toxoid.
- If the risk of exposure is great, polio vaccine and yellow fever vaccine may be safely administered.
- If indicated, some inactivated vaccines (e.g., HepB vaccine, influenza vaccine, and pneumococcal vaccine) may be given during the second and third trimesters of pregnancy.
- Rubella vaccine should be administered to susceptible women as early as possible in the postpartum period.
Breast-feeding
- Neither killed nor live vaccine affects the safety of breast-feeding for either mother or infant.
- Breast-fed infants can be immunized on a normal schedule.
HIV infection and other immunocompromised states
- Limited studies in HIV-infected individuals have found no increase in the risk of adverse events from live or inactivated vaccines.
- Persons known to be infected with HIV should be immunized with recommended vaccines in the same manner as individuals with a normal immune system.
- Vaccinate as early in the course of disease as possible, before immune function becomes significantly impaired.
- Immune responses may not be as vigorous in immunocompromised as in immunocompetent individuals.
- Live attenuated MMR vaccine can be administered.
- When indicated, polio vaccine (IPV) should be administered to immunocompromised HIV-infected individuals and to their household contacts.
Influenza pandemic preparedness
- Per National Preparedness Plan

Vaccines for travel and special use

See Advice to the Traveler for further information on immunizations for travel.
Anthrax vaccine
- Inactivated avirulent bacteria
- Administered SC (6-dose primary series; annual booster)
- For high risk of exposure
  - Persons in contact with or involved in manufacture of animal hides, furs, bone meal, wool, goat hair
  - Military personnel at risk of biowarfare exposure
Tuberculosis (bacille Calmette-Guérin, BCG) vaccine
- Living bacteria (attenuated Mycobacterium bovis)
- PPD-negative individuals in prolonged contact with patients with active tuberculosis
- Adverse events
  - Regional adenitis
  - Disseminated BCG in immunocompromised hosts
HepA vaccine
- Killed virus antigen
- Travelers to or persons living in high-risk areas
- Adverse events: mild local reactions
Cholera vaccine
- Inactivated whole bacteria
- Administered SC or IM
- Not recommended for public health use because of limited efficacy
  - Two new vaccines licensed in Europe
- Adverse events: frequent fever and local reactions, pain, swelling
Meningococcal polysaccharide vaccine
- Bacterial polysaccharides from 4 serotypes (A, C, Y, W-135), not type B
- Adults
  - Military personnel
  - Travelers to endemic areas
  - College students in dormitories
Plague vaccine
- Inactivated bacteria
- Laboratory workers; foresters in endemic areas; travelers
- Adverse events
  - Local reactions (10%)
  - Sterile abscesses and hypersensitivity (rare)
Rabies (human diploid) vaccine
- Inactivated virus grown in cell culture
- Administered IM or ID
- Travelers planning to spend extended periods in areas with high prevalence of rabies among domesticated animals
- Laboratory workers
- Veterinarians
- Exposed persons (postexposure administration)
- Adverse events
  - Local reactions (25%)
  - Arthropathy, arthritis, angioedema (6%)
Yellow fever vaccine
- Live attenuated virus
- Administered SC
- Laboratory workers
- Travelers to endemic areas
  - Contraindicated in patients with immunosuppression
  - HIV-infected patients may receive vaccine if CD4+ cell count is >200 cells/µL.
- Adverse events
  - Encephalitis
  - Encephalopathy
  - Death
Japanese B encephalitis vaccine
- Inactivated virus
- Administered SC
- Travelers to endemic areas
- Adverse events
  - Anaphylactic/severe delayed allergic reactions (common)
    - Recipient should be observed for 10 days.
Typhoid vaccine
- Purified Vi polysaccharide
- Administered IM
- Travelers to endemic areas
- Contacts of carriers
- Adverse events: mild local reactions
Lyme disease vaccine
- No longer available due to poor sales
- Recombinant outer-membrane protein
- Administered IM
- Persons at high risk of exposure to infected ticks
- Adverse events: local reactions

Postexposure immunization

Measles
- Standard human immune globulin is recommended for:
  - Exposed infants and adults with normal immunocompetence (but with a contraindication to measles vaccination)
  - Immunocompromised patients exposed to measles (regardless of immunization status)
- Patients should be actively immunized 3–6 months after immunoglobulin administration.
- Recommended dose: 0.25–0.50 mL/kg (40–80 mg of IgG/kg) IM; 80 mg of IgG/kg for immunocompromised contact; maximum, 15 mL
Rubella
- Efficacy is unreliable.
- Standard human immune globulin is recommended for administration only to antibody-negative pregnant women in the first trimester who have a documented rubella exposure and will not consider terminating the pregnancy.
- Recommended dose: 0.55 mL/kg (90 mg of IgG/kg) IM
Tetanus
- Human tetanus immune globulin (TIG) has replaced equine tetanus antitoxin because of the risk of serum sickness with equine serum.
- Indicated for:
  - Any wound and tetanus vaccine status unknown or < 3 doses of Td
  - Any wound and history of 3 doses of Td, but last dose > 10 years previously
  - Dirty wound and history of 3 doses of Td, but last dose > 5 years previously
  - Treatment of Clostridium tetani infection
- Recommended dose for postexposure prophylaxis: 250–500 units of TIG (10–20 mg of IgG/kg) IM
- Recommended dose for treatment of tetanus: 3000–6000 units of TIG IM
- Survivors with no history of tetanus immunization should receive a primary series of toxoid since disease does not elicit protective levels of antitoxin.
Rabies
- Human rabies immune globulin (RIG) is preferred over equine rabies antiserum because of the risk of serum sickness with equine serum.
- RIG or antiserum is recommended for:
  - Unimmunized individuals sustaining bites from animals in which rabies cannot be ruled out
  - Exposures to known rabid animals
- Recommended dose of RIG: 20 IU/kg (22 mg of IgG/kg)
- Recommended dose of antiserum: 40 IU/kg
- Rabies vaccine is also given at 0, 3, 7, 14, and 28 days.
Hepatitis A
- Persons who have not been actively immunized within 2 weeks of exposure
- Standard immune serum globulin is given:
  - In a single dose of 0.02–0.04 mL/kg or
  - For continuous exposure, up to 0.06 mL/kg every 5 months
- Postexposure treatment with hepatitis A immune globulin has not been studied.
Hepatitis B
- Hepatitis B immunoglobulin (HBIG) is recommended after exposure of an unvaccinated person or a vaccinated person with an anti-HBs titer of < 10 MIU/mL to body fluid from:
  - An HBsAg-positive source
  - A person whose HBsAg status is unknown but who is at high risk of being a hepatitis B source
- Initiate a hepatitis B vaccine series.
- HBIG dose: 0.06 mL/kg

Contraindications

Standards for immunization practice
- The CDC maintains national standards of immunization for adult practice.
  - These standards highlight the need to distinguish between valid contraindications and conditions that are often considered to be but are not in fact contraindications.
Contraindications applicable to all vaccines
- See http://www.cdc.gov/nip/recs/contraindications.pdf for details.
- History of anaphylaxis or other serious allergic reactions to a vaccine or vaccine component
- Moderate or severe illness, with or without fever
Infants who develop encephalopathy within 72 h of a dose of DTP or DTaP should not receive further doses.
- Those who develop a syndrome considered a "precaution" should not normally receive further doses.
Pregnant women should not receive MMR or varicella vaccine.
- Such live-virus vaccines are contraindicated in pregnancy.
Immunosuppressed individuals, including children and their adult contacts, individuals with congenital immunodeficiency syndromes, and those receiving immunosuppressive therapy, should not receive:
- Live oral poliovirus vaccine (OPV)
- Live-virus vaccines, such as MMR, varicella, and yellow fever vaccines
  - MMR and yellow fever vaccines may be given to HIV-infected patients except those with severe immunosuppression (< 200 CD4+ T cells/µL).
Invalid contraindications
- The following are not valid contraindications to routine immunization:
  - Diarrhea
  - Minor respiratory illness (with or without fever)
  - Mild or moderate local reactions to a previous dose of vaccine
  - Concurrent or recent use of antimicrobial agents
  - Mild or moderate malnutrition
  - Convalescent phase of an acute illness
- Failure to vaccinate children because of these conditions is increasingly viewed as a missed opportunity for immunization.

Technique

Precautions and handling
- Health care workers administering vaccines must take precautions to minimize the risk of disease spread—e.g., hand washing between immunizations.
- Different vaccines should not be mixed in the same syringe unless such a practice is specifically endorsed by licensure.
- Disposable needles and syringes must be safely discarded to prevent inadvertent needlestick injury or, in resource-poor settings, the reuse of these items.
- Vaccines must be handled and stored with care.
  - Vaccines should be kept at 2°–8°C and should not be frozen.
    - Exception: Varicella vaccine should be kept frozen at -15°C.
  - Measles vaccine must be protected from light.
Route of administration
- The route used determines the speed and nature of immune responses to vaccines.
- Vaccines can be administered orally, intranasally, intradermally, subcutaneously, or intramuscularly.
- Parenterally administered vaccine may not induce mucosal secretory IgA, and mucosal immunization may not induce good systemic responses.
- Vaccines must be administered by the licensed route to ensure immunogenicity and safety.
Impact of recipient’s age
- Age influences the response to vaccines.
  - Schedules for immunization are based on age-dependent responses determined empirically in clinical trials.
- A high level of maternal antibody and/or the immaturity of the immune system in the early months of life impairs initial immune responses to some vaccines (e.g., measles or Hib polysaccharide) but not to others (e.g., HepB).
- In the elderly, vaccine responses may be diminished because of natural waning of the immune system.
  - Larger amounts of an antigen may be required to produce the desired response (e.g., in vaccination against influenza).
Simultaneous administration of multiple vaccines
- There are no contraindications to the simultaneous administration of several vaccines.
- Combination DTaP/Hib vaccines should not be used for primary immunization of infants because the result is a blunted, suboptimal response to Hib.
  - This combination may be used for booster immunizations.
- When live-virus vaccines are not given together on the same day, an interval of at least 30 days should be allowed.
- Because high doses of immune globulin may inhibit the efficacy of measles and rubella vaccines, an interval of at least 3 months is recommended between the administration of immune globulin and that of MMR vaccine or its components.
- Postpartum vaccination of rubella-susceptible women should not be delayed because of the administration of anti-Rho(D) immune globulin or any other blood product during the last trimester or at delivery.
  - Should administration of an immune globulin preparation become necessary after vaccination, it should be postponed, if possible, for at least 14 days to allow for vaccine-virus replication and development of immunity.
- In general, there is little interaction of immune globulin with inactivated vaccines.

Efficacy

Immune response

Measurement of the immune response
- The response is often gauged by the concentration of specific antibody in serum.
- Seroconversion is a dependable indicator of an immune response but measures only one immunologic parameter and does not necessarily indicate protection.
- The development of circulating antibodies after immunization often correlates directly with clinical protection.
- A minimal circulating level of antibody is known to be required for protection from some diseases (e.g., 0.01 IU/mL for tetanus antitoxin).
Primary vaccine failure
- Some individuals do not respond, even when presented repeatedly with a vaccine antigen.
  - Often the reason is that the vaccine recipient lacks the major histocompatibility complex determinants required to recognize the antigen.
Secondary vaccine failure
- Levels of vaccine-induced antibodies may decline over time.

Reduction in morbidity due to vaccine-preventable diseases

U.S., 1900–2002
- Smallpox
  - Reporting period: 1900–1904
  - Annual morbidity prior to vaccine: 48,164
  - 2002 morbidity: 0
  - Decrease: 100%
- Diphtheria
  - Reporting period: 1920–1922
  - Annual morbidity prior to vaccine: 175,885
  - 2002 morbidity: 1
  - Decrease: 100%
- Pertussis
  - Reporting period: 1922–1925
  - Annual morbidity prior to vaccine: 147,271
  - 2002 morbidity: 8,296
  - Decrease: 94.6%
- Tetanus
  - Reporting period: 1922–1926
  - Annual morbidity prior to vaccine: 1,314
  - 2002 morbidity: 23
  - Decrease: 98.1%
- Neonatal tetanus
  - Reporting period: 1972–1985
  - Annual morbidity prior to vaccine: 785
  - 2002 morbidity: 1
  - Decrease: 98.1%
- Poliomyelitis (paralytic)
  - Reporting period: 1951–1954
- Measles
  - Reporting period: 1958–1962
  - Annual morbidity prior to vaccine: 503,282
  - 2002 morbidity: 37
  - Decrease: 99.9%
- Mumps
  - Reporting period: 1968
  - Annual morbidity prior to vaccine: 152,209
  - 2002 morbidity: 238
  - Decrease: 99.8%
- Rubella
  - Reporting period: 1966–1968
  - Annual morbidity prior to vaccine: 47,745
  - 2002 morbidity: 14
  - Decrease: 99.9%
- Congenital rubella syndrome
  - Reporting period: 1969
  - Annual morbidity prior to vaccine: 834
  - 2002 morbidity: 3
  - Decrease: 99.6%
- Haemophilus influenzae type b
  - Reporting period: before 1985
  - Annual morbidity prior to vaccine: 20,000
  - 2002 morbidity: 27
  - Decrease: 99.9%

Efficacy of individual vaccines

DT, Td (adult)
- Diphtheria: 95%
- Tetanus toxoid: 95%
aP (acellular pertussis): 80–90%
DTaP (diphtheria/tetanus/acellular pertussis): 80–90%
Hib (Haemophilus influenzae type b): 90%
HepB (hepatitis B virus): 80–95%
Influenza: 40–60%
MMR (measles/mumps/rubella)
- Measles: 95%
- Mumps: 90%
- Rubella: 95%
Pneumococcal polysaccharide: 60–80%
Pneumococcal conjugate: 73–94%
IPV (inactivated poliovirus vaccine): 95%
Varicella: 86–100%

Complications

Adverse events
- A reported event may be either a true vaccine reaction or a coincidental event.
- Modern vaccines are associated with adverse events that range from infrequent and mild to rare and life-threatening.
- No link has been found between measles vaccine and autism.
  - The possibility of such a link has been the subject of intense international controversy.
- The Institute of Medicine has issued four recent reports relevant to this issue.
  - Findings fail to support the hypothesis that vaccines are associated with multiple sclerosis, neurodevelopmental disorders, or immune dysfunction.
  - There is no evidence for a temporal association of these conditions with vaccination.
  - There is no biologically plausible basis for the purported relationships.
- Health care providers are required to report certain suspected adverse events following the administration of a mandated vaccine to the FDA’s Vaccine Adverse Events Reporting System (http://www.vaers.hhs.gov/).
Allergic reactions
- May be caused in some recipients by vaccine components, including:
  - Protective antigens
  - Animal proteins introduced during vaccine production
  - Antibiotics or other preservatives or stabilizers
- Reactions may be local or systemic and include urticaria and serious anaphylaxis.
- The most common extraneous allergen is egg protein used in preparation of vaccines such as:
  - Measles
  - Mumps
  - Influenza
  - Yellow fever
- Gelatin, which is used as a heat stabilizer, has been implicated in rare but severe allergic reactions.
Local or systemic reactions
- Can result from too-frequent administration of vaccines such as Td or rabies vaccine.
- Live-virus vaccines can interfere with tuberculin test responses.
  - Necessary tuberculin testing should be done either on the day of immunization or at least 6 weeks later.
Hypersensitivity reactions
- Independent of antibody production, stimulation of the immune system by vaccination may elicit unanticipated responses, especially hypersensitivity reactions.
For adverse events relating to specific vaccines, see Indications.

ICD-9-CM

99.3_ Prophylactic vaccination and inoculation against certain bacterial diseases, (specific disease specified by fourth digit)
99.4_ Prophylactic vaccination and inoculation against certain viral diseases, (specific disease specified by fourth digit)
99.5_ Other vaccination and inoculation