Marianne Billeter
LEARNING OBJECTIVES
Upon completion of the chapter, the reader will be able to:
1. Define vaccination and immunization.
2. Classify each of the routine vaccines as an inactivated, polysaccharide, conjugate, toxoid, or subunit vaccine.
3. Describe the effect of each routine vaccine on preventing infection.
4. Recommend an immunization schedule for a child, including immunocompromised children.
5. Recommend an immunization schedule for an adult based on comorbid conditions and lifestyle issues.
6. Evaluate an adverse reaction and its probable association with a vaccine.
KEY CONCEPTS
Vaccines provide active immunity against viral and bacterial pathogens.
Polysaccharide vaccines are poorly immunogenic in children younger than 2 years of age.
Combination vaccines decrease the number of injections and increase the likelihood of completing the immunization schedule.
Health care professionals should report vaccine-adverse events.
Live virus vaccines should not be given to an immunocompromised host.
Vaccines are cost effective in preventing disease.
The development and widespread use of vaccines is one of the greatest public health achievements of the 20th century. Other than safe drinking water, no other modality has had a greater impact on reducing mortality from infectious diseases. The first accounts of deliberate inoculation to prevent disease date back as far as the tenth century. However it wasn’t until 1798 that Edward Jenner published his work on inoculation of natural cowpox as a means to prevent infection with smallpox. This was the first scientific attempt to prevent infection by inoculation. Since 1900, vaccines have been developed against more than 20 diseases, with half of these recommended for routine use. The widespread use of vaccines has resulted in the eradication of smallpox worldwide and wild-type poliovirus from the Western hemisphere. There have also been dramatic declines in the incidence of diphtheria, pertussis, tetanus, measles, mumps, rubella, and Haemophilus influenzae type b.
Vaccines have traditionally been preparations of killed or attenuated microorganisms that provide active immunity against a variety of viral and bacterial infections. Most vaccines are designed to prevent acute infections that can be rapidly controlled and cleared by the immune system. Successful immunization involves activation of antigen-presenting cells with processing of the antigen by lysosomal or cytoplasmic pathways. T and B lymphocytes will be activated to replicate and differentiate to form large pools of memory cells for protection against subsequent exposure to the antigen.1
Vaccines against viral infections may be attenuated live viruses or inactivated viral particles. Attenuation may be accomplished by several methods to decrease the viruses’ virulence while retaining their immunogenicity. Bacterial vaccines utilize antigenic particles of the outer membrane to elicit an immune response. Outer membrane polysaccharides are poorly immunogenic in children less than 2 years of age unless conjugated with a carrier protein. Also, bacterial toxins may undergo chemical treatment to render them nontoxic to form toxoids against infectious agents.
COMMON TERMINOLOGY
Often the terms vaccination and immunization are used interchangeably even though they are distinct concepts. Vaccination refers to the act of administering a vaccine, while immunization refers to the development of immunity to a pathogen. The delivery of a vaccine does not imply that the individual mounted an adequate immune response to the vaccine to elicit protection. However, immunization implies that the act of vaccination resulted in the development of protective immunity.
Patient Encounter 1
A 1-year-old child is brought to the pediatrician’s office for a routine 1-year checkup. The child is healthy and meeting all growth and developmental targets. The child has received all vaccinations to date. The pediatrician discusses with the mother the need for more vaccinations during this visit.
Which vaccine should the child receive during this visit?
Is there a way to minimize the number of shots the child receives?
What risks are involved with vaccinating this child?
Herd immunity refers to high levels of immunization in one population resulting in protection of another unvaccin-ated population. For example, concentrated vaccination of children with the 7-valent pneumococcal conjugate vaccine resulted in decreased invasive Streptococcus pneumoniae infection not only in the vaccinated children, but also in elderly persons within the same community.
Cocoon immunization is a strategy used to immunize all persons surrounding another high-risk individual, such as vaccinating parents, siblings, and grandparents of a new infant who is too young to be vaccinated. This strategy is used to protect individuals who are not able to be vaccinated themselves.
THE ROUTINE VACCINES
Diphtheria, Tetanus, and Pertussis Vaccines
Diphtheria Toxoid
Diphtheria is a bacterial respiratory infection characterized by membranous pharyngitis. The membrane may cover the pharynx, tonsillar areas, soft palate, and uvula. Diphtheria may also cause anal, cutaneous, vaginal, and conjunctival infections. The impact of diphtheria is not from the causative bacteria, Corynebacterium diphtheriae, but rather from complications attributed to its exotoxin, such as myocarditis and peripheral neuritis. In the late 1800s, annual death rate from diphtheria ranged from 46 to 196 cases per 100,000. Mortality from diphtheria dropped in the 1900s mostly due to the availability of diphtheria antitoxin, which elicited passive immunity. Diphtheria is rarely reported in the United States since the introduction of vaccination with diphtheria toxoid; however, diphtheria continues to be a major problem in developing countries.
In the early 1900s, a balanced mixture of diphtheria toxin and antitoxin was found to produce active immunity in both animals and humans. This preparation gained widespread acceptance and protected approximately 85% of recipients. Several years later, diphtheria toxoid was developed by treating the toxin with small amounts of formalin. This process caused the toxin to lose its toxic properties while maintaining its immunogenic properties. In the mid-1920s, the addition of an alum precipitate enhanced the immunogenic properties of the toxoid.
In the 1940s, diphtheria toxoid was combined with tetanus toxoid and whole cell pertussis vaccines, and later with the acellular pertussis vaccine. The diphtheria toxoid, tetanus toxoid, and acellular pertussis vaccine are part of the routine childhood immunization schedule. Diphtheria toxoid is also combined with tetanus toxoid and is commonly used as a booster vaccine. The pediatric product (DT) has a higher amount of diphtheria toxoid than does the adult product (Td). Diphtheria toxoid is not available as an individual vaccine.
Recent outbreaks of diphtheria have demonstrated that immunity wanes in adulthood. Approximately 50% of all adults no longer have immunity to diphtheria. Regular boosters with tetanus and diphtheria toxoids every 10 years will provide adequate recall immunity to diphtheria provided the adult was previously immunized.2
Tetanus Toxoid
The tetanus vaccine differs from others in that it does not protect against a contagious disease such as diphtheria, but rather against an environmental pathogen. Clostridium tetani is widely found in the environment, especially in dirt and soils. Additionally, animals and humans may harbor and excrete the organism. C tetani produces two neurotoxins, tetanospasmin and tetanolysin, which are responsible for producing the painful muscular contractions associated with tetanus. Tetanus continues to be a major problem in the developing world, causing approximately 1 million deaths each year.3 Approximately 40% of the cases are neonatal tetanus most likely associated with the use of nonsterile instruments or poultices on the umbilical cord. Tetanus is rarely seen in developed countries.
Immunity to tetanus decreases with increasing age; therefore, a regular booster every 10 years with tetanus toxoid is recommended. The preferred agent to use in adults is tetanus and diphtheria toxoid (Td) in order to give a booster for diphtheria. Tetanus immunization status should be assessed in the management of wounds in individuals seeking medical care. A tetanus booster should be administered if a tetanus-containing vaccine has not been given in the preceding 5 years for moderate and severe wounds or contaminated wounds. If the wound is minor and uncontaminated, then a tetanus booster is needed if the previous tetanus vaccination was more than 10 years ago.
Pertussis
Pertussis is a highly contagious respiratory tract infection caused by the bacteria Bordetella pertussis. Pertussis is characterized by a protracted severe cough with or without posttussive vomiting, whoop, difficulty breathing, difficulty sleeping, and rib fractures. It is often referred to as “whooping cough” or the 100-day cough. In the prevaccine era, pertussis accounted for more than 250,000 cases of severe illness and 10,000 deaths per year in the United States. Pertussis has always been thought of as a pediatric disease since most cases occurred in preschool-aged children with relatively no cases seen in adolescents and adults. The first pertussis vaccine was introduced in the 1940s and within 30 years resulted in a 99% reduction in disease. However, during the past two decades there has been a steady increase in reported cases of pertussis among adolescents and adults, indicating a waning immunity after primary immunization.4
The first pertussis whole cell vaccine was a mixture of killed organisms that was associated with frequent local and systemic reactions. In the late 1980s, an acellular pertussis vaccine was introduced that contains purified pertussis components that are immunogenic but associated with fewer adverse reactions. Acellular pertussis vaccine is available in combination with tetanus and diphtheria toxoids. Pertussis is not available as a separate vaccine component. In the spring of 2005, the FDA-approved tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccines for use in adolescents and adults.
Use of Diphtheria, Tetanus, and Acellular Pertussis Vaccine
Diphtheria and tetanus toxoids and acellular pertussis (Dtap) vaccine should be administered in a five-shot series to all children beginning at 2 months of age (Table 86–1). The shots are given at 2, 4, 6, and 15 to 18 months, and 4 to 6 years. Complete immunity to diphtheria and tetanus is achieved after the third vaccination.
Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) is recommended as a single booster for the following groups in place of a tetanus booster.5
• Adolescents 11 to 18 years of age: An interval of 5 years, with a minimum of 2 years, between the last tetanus-containing vaccine is recommended to minimize local and systemic adverse events; however, shorter intervals may be used.
• Adults 19 to 64 years of age: Tdap should replace the next routine tetanus booster. Intervals as short as 2 years between Tdap and Td may be used.
• Tetanus prophylaxis in wound management: Adolescents and adults 11 to 64 years of age, who have completed a primary series and require a tetanus-containing product should receive Tdap instead of Td if they have not already received Tdap.
• Prevention of pertussis among infants less than 12 months of age: Adults who have close contact with infants less than 12 months of age, especially parents, grandparents less than 65 years of age, and child care providers, should receive a single dose of Tdap. An interval of at least 2 years since the last tetanus-containing vaccine was given is suggested, but shorter intervals may be used. Ideally, Tdap should be given 2 weeks prior to contact with the infant.
• Postpartum women: Women should receive a single dose of Tdap in the immediate postpartum period if Tdap has not been previously received. Ideally this should be administered prior to discharge from the hospital or birthing center.
• Health care workers with direct patient contact Such workers should receive a single dose of Tdap.
Haemophilus influenzae Type b Vaccine
Haemophilus influenzae is a bacterial respiratory pathogen that causes a wide spectrum of disease ranging from colonization of the airways to bacterial meningitis. It causes considerable morbidity and mortality, especially in children less than 5 years of age. H influenzae is either encapsulated or unencapsulated. The encapsulated strains can be further differentiated into six antigenically distinct serotypes, a through f. H influenzae type b was primarily found in cerebrospinal fluid and blood of children with meningitis, while the unencapsulated strains were found in the upper respiratory tract of adults. Before the introduction of the vaccine, H influenzae was responsible for 20,000 to 25,000 cases of invasive disease annually and was the most common cause of bacterial meningitis. Since the introduction of the vaccine, invasive disease due to H influenzae type b has been nearly eliminated.
The H influenzae type b vaccine is a protein conjugate that utilizes a carrier-hapten for antigen presentation. The polysaccharide is conjugated to an immunogenic protein carrier, which is recognized by T cells and macrophages that stimulates T-dependent immunity. The conjugated vaccine elicits an immune response characterized by T-helper cell activation. The T-dependent antigens induce an enhanced immune response in younger children. Within 10 years of its introduction, the H influenzae type b vaccine use has resulted in widespread herd immunity.
H influenzae type b conjugate vaccine is a recommended routine childhood vaccine given at 2, 4, 6, and 12 to 15 months of age. Adolescents and adults with functional or anatomic asplenia should also receive a booster dose of H influenzae type b vaccine. The currently available vaccines are labeled for pediatric use, but can be used in adults when vaccination is indicated. There are several H influenzae type b vaccines on the market that differ in the size of the polysaccharide and type of carrier protein; however, the immune response to H influenzae type b is similar among the different vaccines. The different brands are interchangeable without affecting the primary immune response or booster response.
H influenzae type b and influenza vaccines have the potential for confusion and medication errors because of the similarity of the names. Care should be taken when ordering, dispensing, and administering these vaccines.
Hepatitis A Vaccine
Hepatitis A virus continues to be a frequent cause of illness despite the availability of a highly effective vaccine. Hepatitis A typically has an abrupt onset of symptoms including fever, malaise, nausea, abdominal discomfort, and jaundice. Frequently children less than 6 years of age are asymptomatic while adults typically have symptomatic disease. Symptoms may persist for 2 months or longer. There is wide geographic variation in the incidence of hepatitis A infection, with the number of cases ranging from 50 to more than 700 cases per 100,000 persons annually. The economic burden of hepatitis A is greater than $300 million annually in combined direct and indirect costs. Widespread use of the vaccine offers the opportunity to substantially decrease the disease burden caused by hepatitis A infection.6
Table 86–1 Vaccine Dosing
Hepatitis A vaccine was licensed in the United States in 1995. It is an inactivated whole virus vaccine that is administered in a two-dose series. More than 94% of children, adolescents, and adults will have protective antibodies 1 month after receiving the first dose and 100% following the second dose.6 Recommended use of the hepatitis A vaccine utilizes an incremental implementation schedule beginning with high-risk populations or those at increased risk for serious complications from the disease. Currently hepatitis A vaccine is recommended for all children following the first birthday, with the second dose administered 6 months later. Adults who are at high-risk for hepatitis A should receive two doses at least 6 months apart. High-risk adults include persons with clotting disorders or chronic liver disease, men who have sex with men, illicit drug users, international travelers going to areas with high to intermediate endemicity of hepatitis A, or any other person who wishes to become immune.
Hepatitis B Vaccine
Hepatitis B virus is a blood-borne or sexually transmitted virus. Most acute infections occur in adults, while chronic infections usually occur in individuals infected as infants or children. However, about 10% of adults who contract hepatitis B virus will fail to clear their infection and develop chronic hepatitis B infection. Individuals with chronic hepatitis B infection are at risk for cirrhosis or hepatocellular carcinoma. Vaccination with hepatitis B vaccine is the most effective way to prevent hepatitis B infection.7
Hepatitis B vaccine is manufactured using recombinant DNA technology to express hepatitis B surface antigen (HBsAg) in yeast. This is further purified with biochemical separation techniques to produce the vaccine. The vaccines are formulated to contain 10 to 40 mcg of HBsAg protein/mL. Hepatitis B vaccine is available as a single component or in combination vaccines.
Hepatitis B vaccine is recommended for routine use in children. The first dose should be given within 12 hours of birth. The second and third doses are given at 2 months and 6 months after the first dose if using the single component vaccine, or at 2, 4, and 6 months if using a hepatitis B containing combination vaccine. If the infant weighs less than 2,000 g at birth, the birth dose is not counted in the three-dose series. Infants less than 2,000 g do not produce an adequate immune response to the birth dose of hepatitis B vaccine. Adolescents should receive the three-dose series if not previously vaccinated.7
Adults at high-risk for hepatitis B because of occupation or lifestyle should receive the hepatitis B vaccine series. The typical series has the second and third doses given 1 month and 6 months after the first dose. Accelerated schedules may also be used. Frequently, individuals do not follow through with the complete three-dose series and questions arise about restarting the series. Hepatitis B vaccine produces an amnesic response; therefore the series may be continued at any time in order to complete the three doses.
Following vaccination with hepatitis B vaccine, hepatitis B virus serologic markers will remain negative with the exception of anti-HBs (antibody to hepatitis B surface antigen), which will be positive indicating immunity. Persons with anti-HBs concentration greater than 10 mIU/mL after vaccination will have complete protection against acute and chronic infection.7 It is unclear if a booster dose of hepatitis B vaccine should be administered when anti-HBs concentrations fall below 10 mIU/mL, since a good memory response will occur following exposure to hepatitis B virus.
Human Papillomavirus Vaccine
Human papillomavirus (HPV) is the most common sexually transmitted virus and is associated with a wide range of diseases, including genital warts and cervical cancer. More than 100 HPVs have been sequenced and classified as low-risk, nononcogenic or high-risk oncogenic types based on their ability to cause malignant disease. The predominant low-risk types HPV 6 and 11 are associated with 90% of genital warts. High-risk types HPV 16 and 18 are associated with 70% of cervical cancer cases and cervical intra-epithelial neoplasia.8 HPV is also associated with other gynecologic cancers, such as vaginal and vulvovaginal tumors.
Two HPV L-1 virus-like particle vaccines have been developed. The quadrivalent vaccine contains HPV types 6, 11, 16, and 18, and has been approved for use in the United States for the prevention of cervical cancer, precancerous or dysplastic lesions and genital warts in girls and women 9 through 26 years of age. The bivalent vaccine contains HPV types 16 and 18; this vaccine is under review by the FDA, but not yet approved. Both vaccines have shown greater than 95% efficacy in preventing precancerous lesions of the cervix, vulva, and vagina. Additionally, the quadrivalent vaccine is also effective against genital warts. Both HPV vaccines are safe with no unexpected adverse events.
These vaccines are unique in that preventing infection by HPV will translate into prevention of cancer, making these the first cancer prevention vaccines. Clinical trials are utilizing surrogate markers, prevention of precancerous lesions, to determine efficacy of the vaccines. However, the true impact on preventing cancerous tumors will not be known for years. The HPV vaccine is recommended for use in girls and women 9 through 26 years of age.9 Ideally it should be administered to girls before they become sexually active. However, sexually active girls and women should still receive the vaccine. Additionally, girls and women who have been infected with HPV should still receive the vaccine since the vaccine provides protection against more than one type of HPV. Use of the HPV in boys and men is not recommended at this time.
Influenza Vaccine
Influenza is a contagious viral respiratory infection that usually occurs during the winter months in the Northern Hemisphere and all year round in the Southern Hemisphere. All age groups are affected by influenza; however, children have the highest rate of infection. Serious illness and death due to influenza usually occurs in extremes of age, those over 65 years or under 2 years. Influenza is responsible for approximately 36,000 deaths annually in the United States.10
Influenza A and B viruses are responsible for causing human disease. Influenza A is further categorized into subgroups by its surface antigens, hemagglutinin and neuraminidase (e.g., influenza A H1N1 virus). Influenza B virus is not subtyped. Both influenza A and B undergo frequent antigenic drift, creating new influenza variants. Immunity to the surface antigens decreases the likelihood of infection. Unfortunately, antibody to one influenza subgroup does not give complete protection against other influenza subtypes. Therefore, annual influenza vaccination is recommended during October and November, and continuing until the vaccine supply is exhausted.
The best way to protect against influenza is through vaccination. The influenza vaccine is composed of two influenza A subtypes and one influenza B subtype. The viral subtypes contained in the vaccine usually changes each year. The exact composition is selected by a panel of experts and announced by the Centers for Disease Control and Prevention (CDC) in March or April each year. The vaccine becomes available for use in late August and September. Two types of influenza vaccine are licensed for use in the United States; both vaccines contain the same viral subunits. The influenza viruses for both vaccine preparations are grown in eggs. Therefore, the vaccines are contraindicated in individuals with severe allergy to eggs.
The influenza vaccine should be administered to any person wanting to reduce the risk of infection with the influenza virus. Target groups for annual influenza vaccination are all children age 6 months through 18 years, all adults 50 years and older and younger adults at high-risk of complications from influenza. The trivalent inactivated influenza vaccine can be administered to all age groups and risk populations. The live attenuated influenza vaccine may be administered to healthy individuals between the age of 2 and 49 years. If the child is less than 8 years old and is receiving influenza vaccine for the first time, two doses separated by 4 to 6 weeks should be given.10
Measles, Mumps, and Rubella Vaccine
Measles
Measles, also known as rubeola, is characterized by a rash that is often complicated by diarrhea, middle ear infection, or pneumonia. Encephalitis occurs in 1 of every 1,000 reported cases. Individuals who recover from encephalitis usually have permanent brain damage. Death occurs in 1 to 2 of every 1,000 reported measles cases.11
Prior to measles vaccine availability the number of cases of measles approached the birth rate of approximately 3 to 4 million annually. The first measles vaccine was licensed in 1963. Since that time there has been a 99% reduction in reported measles cases. Currently, there is a goal to eliminate measles transmission in the United States through aggressive immunization programs.
There have been several types of measles vaccines used since its introduction. There have been inactive and live attenuated vaccines using different strains of the virus. The current vaccine uses a live attenuated preparation of the Enders-Edmonston virus strain. Following vaccination with measles containing vaccine, a mild noncommunicable infection develops. Approximately 95% of individuals will develop antibodies following a single dose if administered after 12 months of age. More than 99% of individuals who receive two inoculations will develop long-term, probably lifelong, immunity to measles.11
Mumps
Mumps is usually thought of as a disease of children, but it has also gained notoriety as a prominent illness affecting military units. Mumps produces a typical acute parotitis, but may also cause nonspecific respiratory symptoms. In postpubertal males, mumps may also cause orchitis in 38% of those infected, which may result in infertility.11
Since the introduction of the mumps vaccine in 1967 there has been a 99% reduction in reported cases. The mumps vaccine is a live virus preparation of the Jeryl-Lynn strain. It produces a subclinical, noncommunicable infection following vaccination. Single doses of mumps vaccine will elicit immunity in 75% to 95% of individuals. Vaccine-induced immunity lasts for more than 30 years.
Rubella
German measles, also known as rubella, is a mild exanthematous illness in children and young adults; however, rubella infection in pregnant women can cause a variety of congenital malformations in the infant. Congenital rubella syndrome occurs in approximately 25% of infants whose mother acquires rubella during the first trimester. Congenital rubella syndrome is characterized by congenital cataracts, heart disease, deafness, thrombocytopenia, mental retardation, and numerous other abnormalities.11
The first rubella vaccine was licensed in 1969. Initial vaccination campaigns were targeting young children, as this age group had the highest rate of rubella infection. This strategy significantly decreased rubella cases in children, but did not have the desired effect on infection in adolescents and adults or on congenital rubella syndrome. Adolescents, especially young girls, were then targeted for vaccination. This has resulted in a significant reduction in the number of cases of congenital rubella syndrome.
The live rubella vaccine available in the United States contains the RA 27/3 strain of the virus. Following a single dose of rubella vaccine after the first birthday, more than 90% of individuals will develop long-term immunity. Rarely has congenital rubella syndrome been reported in infants born to mothers with adequate rubella immunization.
Use of Measles, Mumps, and Rubella Vaccine
Measles, mumps, and rubella vaccines are available as single component vaccines or as combinations. Most authorities recommend use of the measles, mumps, and rubella combination vaccine and discourage use of the single- or double-component vaccines. Two doses of the measles, mumps, and rubella vaccine are recommended for all individuals born after 1957. The first dose should be administered soon after the first birthday and the second prior to entering school. For high-risk adolescents and adults who do not have adequate immunity, two doses of the vaccine should be separated by a minimum of 28 days.11
Measles, mumps, and rubella vaccine is a live virus vaccine that should be used with caution in immunosuppressed children, such as those with cancer receiving chemotherapy, solid organ or bone marrow transplantation, or receiving other immunosuppressive drugs, such as steroids in a dose equivalent to prednisone 1 mg/kg/day or higher or 20 mg/day for 2 weeks or longer. If possible, vaccines should be given prior to becoming immunosuppressed. Otherwise, it may be prudent to defer the vaccine until after the immuno-suppression resolves.
Meningococcal Vaccines
Neisseria meningitidis is a significant cause of meningitis and severe sepsis. Meningococcus causes an estimated 2,500 cases of invasive disease each year in the United States. Invasive meningococcal disease is associated with an estimated 15% mortality rate. Morbidity in survivors is substantial, with approximately 20% having loss of limb or neurologic sequelae. The highest rates of meningococcal disease are among young children; however, rates have been increasing in adolescents and young adults. Thirteen meningococcal serogroups have been identified; however, five serogroups, A, B, C, Y, and W-135, are responsible for epidemic and endemic disease worldwide. Despite the availability of highly active antibacterial agents against N meningitidis, there has been little impact on decreasing the morbidity and mortality due to invasive meningococcal disease.12
Patient Encounter 2
An 18-year-old male is having a routine physical before leaving for college. He will be a freshman and is looking forward to dormitory life. The health care provider recommends some vaccinations be given at this visit.
Which vaccines should be administered?
What is the risk of not receiving the vaccines?
A meningococcal polysaccharide vaccine containing serogroups A, C, Y, and W-135 has been available in the United States for a number of years. Meningococcal polysaccharide vaccine is similar to other polysaccharide vaccines, in that it is poorly immunogenic in infants and children less than 2 years of age, and does not produce lasting immunity. Meningococcal polysaccharide vaccine produces a T-cell–independent response and fails to induce a memory response. Repeated vaccination results in hyporesponsiveness to serogroups A and C; the clinical implication of this finding is unknown.
In January 2005, a new meningococcal polysaccharide diphtheria toxoid conjugate vaccine was approved by the FDA. This vaccine also contains meningococcal serogroups A, C, Y, and W-135. Polysaccharide-protein conjugate vaccines are known to produce improved immunogenicity and memory responses. Meningococcal conjugate vaccine has shown similar immunologic response for all four serogroups when compared to meningococcal polysaccharide vaccine. However, this vaccine does not offer protection against diphtheria.
Meningococcal conjugate vaccine is recommended for routine vaccination in individuals 11 to 18 years of age. Ideally, this should be done at the routine preadolescent health care visit. Routine meningococcal vaccination is also recommended for persons aged 19 to 55 years at increased risk for meningococcal disease, such as college freshman living in dormitories, microbiologists who are routinely exposed to isolates of N meningitidis, military recruits, persons who travel to or reside in countries in which N meningitidis is hyperendemic or epidemic, persons who have terminal complement component deficiencies, and persons who have anatomic or functional asplenia.13Additionally, meningococcal conjugate vaccine should be administered to children 2 to 10 years of age who are high-risk of meningococcal disease.14Routine revaccination is not recommended at this time.12 A history of Guillain-Barré syndrome is a relative contraindication to receiving meningococcal conjugate vaccine, and the risk versus benefit should be carefully considered. Individuals may be given the meningococcal polysaccharide vaccine in lieu of the conjugate vaccine.
Pneumococcal Vaccines
Streptococcus pneumoniae is the most common bacterial cause of community-acquired respiratory tract infections. S pneumoniae causes approximately 3,000 cases of meningitis, 50,000 cases of bacteremia, 500,000 cases of pneumonia, and over 1 million cases of otitis media each year. The increasing prevalence of drug-resistant S pneumoniae has highlighted the need to prevent infection through vaccination. Both licensed pneumococcal vaccines are highly effective in preventing disease from the common S pneumoniae sero-types that cause human disease.
The 23-valent pneumococcal polysaccharide vaccine contains 23 serotypes that are responsible for causing more than 80% of invasive S pneumoniae infections in adults. The vaccine includes those serotypes that are associated with drug resistance. Use of the vaccine will not prevent the development of antibiotic-resistant S pneumoniae, but is likely to prevent infection from drug-resistant strains. The 23-valent pneumococcal polysaccharide vaccine has demonstrated good immunogenicity in adults, but an individual will not develop immunity to all 23 serotypes following vaccination.15
The 23-valent pneumococcal polysaccharide vaccine is recommended for use in all adults 65 years of age or older and adults less than 65 years who have medical comorbidities that increase the risk for serious complications from S pneumoniae infection, such as chronic pulmonary disorders, cardiovascular disease, diabetes mellitus, chronic liver disease, chronic renal failure, functional or anatomic asplenia, and immunosuppressive disorders. Alaskan natives and certain Native American populations are also at increased risk. Children over the age of 2 years may be vaccinated with the 23-valent pneumococcal polysaccharide vaccine if they are at increased risk for invasive S pneumoniaeinfections, such as children with sickle cell anemia or those receiving cochlear implants.
Revaccination with the 23-valent pneumococcal polysaccharide vaccine is recommended for adults over the age of 65 years if the first dose was administered when they were less than 65 years of age and at least 5 years have passed. Revaccination results in a blunted immune response and increased local adverse reactions, therefore routine revaccination is not recommended.15 Adults vaccinated at age 65 or greater do not require revaccination.
The 7-valent pneumococcal conjugate vaccine was licensed in February 2000 for use in children. It induces good immunogenicity in children under the age of 2 years. It is now part of the routine childhood immunization schedule beginning at 2 months of age. It is given at 2, 4, 6, and 12 to 18 months of age. The 7-valent pneumococcal conjugate vaccine decreases the carriage rate of S pneumoniae and the incidence of invasive disease in vaccinated populations. Widespread use of the 7-valent pneumococcal conjugate vaccine has resulted in herd immunity and decreased the incidence of invasive S pneumoniaedisease among unvaccinated adults over 20 years of age.15
Poliovirus Vaccine
Poliomyelitis is a highly contagious disease that is often asymptomatic; however, approximately 1 in every 100 to 1,000 cases will develop a rapidly progressive paralytic disease. Polio is caused by poliovirus which has three serotypes; type 1 is most frequently associated with paralytic disease. Poliovirus replicates in the oropharynx and intestinal tract and is excreted in oral secretions and feces, which can infect others. As a result, more than 90% of unvaccinated individuals will become infected with poliovirus following household exposure to wild-type poliovirus. Since the introduction of the first poliovirus vaccine, there has been a significant reduction in the number of polio cases. Today, polio caused by wild-type poliovirus has been eradicated from the Western Hemisphere with the goal of eradicating it from the world.16
The first inactivated poliovirus vaccine was introduced in the 1950s in an injectable formulation, and replaced in the 1960s by a live oral poliovirus vaccine. The oral poliovirus vaccine not only elicits systemic immunogenicity but also a localized immune response in the intestinal tract. Unfortunately, the oral poliovirus vaccine has the risk of vaccine-associated paralytic poliomyelitis occurring in approximately 1 case of every 2.4 million doses distributed. The risk with the first dose of oral poliovirus vaccine is 1 case in 750,000 doses.16
The last reported case of indigenous wild-type poliovirus in the United States was in 1979; subsequent cases were all vaccine-associated. In 1997, a transition period to the inactivated poliovirus vaccine was begun to reduce the risk of vaccine-associated paralytic poliomyelitis. By January 2000, the oral vaccine was no longer recommended for routine use. Currently, the inactivated poliovirus vaccine is recommended for routine use in the United States. The oral poliovirus vaccine is still widely used in some countries where poliovirus eradication has been more difficult.
The enhanced potency inactivated poliovirus vaccine contains all three serotypes. After two doses, more than 90% of those vaccinated will have immunity to the three serotypes and 99% after three doses. Inactivated poliovirus vaccine is recommended to be given at 2, 4, 6 to 18 months, and 4 to 6 years of age.
Rotavirus Vaccine
Rotavirus is the most common cause of diarrhea worldwide. Most children will become infected by the age of 5 years. In the United States, rotavirus is responsible for approximately 50,000 hospitalizations for severe diarrhea and dehydration, and 20 to 40 deaths annually. Most hospitalizations occur in children less than 3 years of age. Rotavirus infections follow a winter–spring seasonal pattern. Rotavirus G1 is the most prevalent strain found in the United States. However, in any given year other strains G2, G3, G4, and G9 may predominate.
The first rotavirus vaccine was a tetravalent rhesus-based rotavirus strain. It was licensed in the United States in 1998 and subsequently withdrawn from the market within the first year due to an association with intussusception. A pentavalent human-bovine reassortant rotavirus vaccine was approved by the FDA in February 2006. This vaccine contains outer capsid proteins for G1, G2, G3, G4 and P1. A monovalent, G1 vaccine has been approved for use in the United States.17 The exact mechanism by which these vaccines produce an immune response is unknown; however, these live virus vaccines replicate in the small intestine and induce immunity.
The rotavirus vaccine is administered in either a two-dose or three-dose series that is orally administered. The first dose is given to infants between 6 and 12 weeks of age.17 One year after the introduction of the rotavirus vaccine the CDC reported a 50% reduction in reported cases of rotavirus in the United States.
Varicella Vaccine
Varicella zoster virus is a herpes virus that infects nearly all humans. Primary infection with Varicella zoster causes chickenpox (varicella), which is one of the most common childhood diseases. Chickenpox has always been thought to be a benign disease causing few serious complications in children. The rate of chickenpox prior to the vaccine becoming available was thought to approximate the birth rate with 3 to 4 million cases annually resulting in 11,000 hospitalizations and 100 deaths. Adults who develop chickenpox have a 25% greater risk for developing serious complications from varicella compared to children. Chickenpox is highly contagious and has a secondary household transmission rate of 87%. Following resolution of the primary infection, varicella becomes latent in cranial nerve, dorsal routs, and autonomic ganglia.
The varicella vaccine is made up of an attenuated Oka strain of varicella zoster virus. This is a live attenuated vaccine. Attenuation was achieved by performing serial passages through human embryonic lung cells, embryonic guinea pig cells, and human diploid cells.
Children less than 12 years of age will have a 97% sero-conversion rate following a single vaccination. Adolescents and adults more than 13 years old will only have 78% seroconversion after a single inoculation, but will have 99% conversion after the second vaccination administered 4 to 8 weeks after the first. Antibody titers appear to persist for at least 20 years following immunization. Despite excellent seroconversion rates, breakthrough chickenpox is reported at a rate of 1 case per 10,000 doses distributed. Most cases occurred within the first year following vaccination, and were due to wild-type varicella zoster virus. The majority of breakthrough cases were mild and of short duration.18
Secondary transmission to household contacts is always a concern with administration of a live vaccine. There are a few cases of possible secondary transmission of varicella following vaccination. Of the cases that varicella typing was done, 62% were wild-type virus, indicating exposure to an unvaccinated person. There are less than 10 confirmed cases of secondary transmission of the Oka vaccine strain following vaccination. A mild rash occurring in less than 5% of persons has been reported following vaccination. The varicella virus may be shed from the rash. Rashes due to the Oka vaccine strain typically occur more than 20 days following vaccination.18
Varicella vaccine should be administered after 12 months of age and a second dose at 4 years of age. Adolescents and adults without evidence of immunity to varicella zoster should receive two doses of varicella vaccine given 4 to 8 weeks apart. Varicella vaccine is available as a single-component vaccine or in combination with measles, mumps, and rubella vaccine.
Zoster Vaccine
Later in life, approximately 15% of the population will develop herpes zoster (shingles). Zoster is the reactivation of latent varicella zoster virus in the sensory ganglia. It produces a classic rash along a single nerve track. Approximately 20% of persons with herpes zoster will develop postherpetic neuralgia, which is a painful debilitating condition that can persist for months after resolution of the herpes zoster rash. Adults get a boost in immunity with repeated exposure to children with the chickenpox. Zoster most frequently occurs in the elderly and immunocompromised individuals who have decreased circulating antibodies to varicella zoster virus.19
Zoster vaccine is a more concentrated form of the varicella vaccine. It is recommended for use in individuals 60 years of age and older. Use of the zoster vaccine has shown a 60% reduction in the incidence of zoster and postherpetic neuralgia. There is decreased effectiveness of the vaccine with increasing age.
The varicella vaccine is relatively new and has only been recommended for use since 1996, therefore its true impact on chickenpox and zoster is not yet known. Continued use of the varicella vaccine will undoubtedly change the epidemiology of both of these diseases. As the prevalence of chickenpox declines, the rate of zoster will likely increase in the elderly making vaccination with the zoster vaccine more prudent.19
COMBINATION VACCINES
The childhood immunization schedule is complex and requires a large number of injections. In small infants the large number of injections can be intolerable to the infant, parent, and health care provider. Limiting the number of injections at each visit can lead to missed vaccinations and increased expense for return visits. Use of combination vaccines decreases the number of injections and increases the likelihood that the immunization schedule would be completed.
Many factors have to be considered when developing combination vaccines. First the selected components need to be given on a similar schedule and all components should already be licensed in the United States. The excipients contained in the individual vaccines may interfere with another component when combined, altering a component’s immunogenicity. Finally, the immunogenicity of the combination must be similar (within 10%) to the immune response when the components are administered separately.20
There are several combination vaccines available in the United States. One of the most popular pediatric combinations is Pediarix, a combination of diphtheria and tetanus toxoids, acellular pertussis, inactivated poliovirus, and hepatitis B vaccines. Pentacel was recently approved and is a combination of diphtheria and tetanus toxoids, acellular pertussis, inactivated poliovirus, and H influenza type b vaccines. ComVax is a combination of H influenzae type b and hepatitis B vaccines. ProQuad contains measles, mumps, rubella, and varicella vaccines. The only combination available for adults is Twinrix, which has hepatitis A and hepatitis B vaccines.
VACCINE ADMINISTRATION SCHEDULES
Most vaccines are administered in two- to four-shot series in order to elicit the best protection. Childhood and adult immunization schedules are revised frequently and published annually by the CDC Advisory Committee on Immunization Practices. Current immunization schedules can be found at www.cdc.gov. The childhood schedule is published in January and the adult schedule in October of each year. Recommendations will be published throughout the year in the Morbidity and Mortality Weekly Report (MMWR) as new vaccines are licensed or new information necessitates a change in previous recommendations.
Table 86–2 Vaccine Reportable Events
VACCINE SAFETY
Vaccination is one of the most powerful tools used to prevent disease. As with all drugs, most vaccines have been reported to cause adverse reactions. The reactions are either acute, such as local reactions, or are related to the risk of developing another disease. Health care professionals are to give vaccine information sheets to individuals or caregivers prior to vaccination; these provide information about the risks and benefits of each vaccine.
Vaccine safety is monitored by the FDA and CDC through a passive reporting system that allows anyone, health professionals or lay public, to report any event. 
Health care professionals are bound by federal regulation to report certain adverse events (Table 86–2). Additionally, any serious, life-threatening or unusual reactions should also be reported. The Vaccine Adverse Event Reporting System (VAERS) can be found at http://vaers.hhs.gov.
The VAERS database is continually monitored to determine if the prevalence of reactions is changing and to identify previously unreported reactions to a particular vaccine. One of the limitations of the VAERS data is that it does not contain denominator data. Therefore it is not possible to calculate a true rate of reaction occurrence: the number of cases of reaction per dose of vaccine administered. Rates are usually calculated using the number of doses distributed from the manufacture as the denominator. This makes the assumption that each dose distributed is administered.
Local Reactions
Pain at the injection site is one of the most commonly reported adverse effects of vaccination. The reaction is usually mild with complaints of pain and tenderness at the injection site that may or may not be accompanied by erythema. Local reactions tend to be more frequent with repeated doses or booster doses of vaccine. The frequency and degree of the reactions appear to be related to the amount of preformed antibodies and rapid immunologic responses reflective of priming from previous doses. More serious Arthus reactions are infrequently reported. Arthus reactions are classified as type III hypersensitivity reactions, and are characterized by a massive local response involving the entire thigh or deltoid. Arthus reactions are also related to preformed antibody complexes that induce an inflammatory lesion.21
Tetanus-containing vaccines are well known for causing localized reactions; however, all vaccines can cause local reactions.
Fever
Fever is the most frequently reported adverse effect in children and adolescents. Fever associated with vaccination is defined as a temperature of greater than or equal to 38°C (100.4°F) measured at any site using a validated device. Fever is caused by a complex reaction induced by the production of cytokines that affect the hypothalamic neurons. This results in raising the hypothalamic set point. Temperature elevations above 40°C (104°F) can result in cellular and multi-organ dysfunction. Excessive temperature elevations rarely result from fever alone, but are usually coupled with other thermoregulatory dysfunction.22
The whole cell pertussis vaccine has been highly associated with temperature elevations; however, the prevalence has significantly decreased since the introduction of the acellular pertussis vaccine. Live virus vaccines are also associated with fever.
Guillain-Barré Syndrome
Guillain-Barré syndrome is a transient neurologic disorder involving inflammatory demyelination of the peripheral nerves. The syndrome is characterized by progressive symmetric weakness of the legs and arms with loss of reflexes. Occasionally sensory abnormalities and paralysis of respiratory muscles will occur.23
The etiology of Guillain-Barré syndrome is unknown, but increasing evidence suggests it is probably a humoral and cellular autoimmune disease induced by infection with a variety of microorganisms. The background rate of Guillain-Barré syndrome is one to two cases per 100,000 persons annually. Guillain-Barré syndrome has been associated with several vaccines. An influenza vaccine used in the mid-1970s (swine flu vaccine) increased the incidence of Guillain-Barré syndrome by a factor of eight.23 Warnings about Guillain-Barré syndrome continue to be given with annual influenza vaccinations. The hepatitis B vaccine derived from pooled plasma was also associated with Guillain-Barré syndrome; however, Guillain-Barré has not been reported with use of the currently available hepatitis B vaccines produced through recombinant DNA technology. Most recently, Guillain-Barré syndrome has been reported to occur with the meningococcal conjugate vaccine.
Other Safety Concerns
A clear cause-and-effect relationship between vaccine administration and chronic diseases, such as diabetes mellitus, multiple sclerosis, and chronic arthritis, has never been scientifically proven.
Thimerosal is a preservative used in vaccines that has been purported to cause autism in children. The assumption is that thimerosal, also known as ethyl mercury, causes similar effects as methyl mercury, which has neurotoxic and nephrotoxic effects at high-doses. Several epidemiologic studies have not shown a higher rate of autism among children receiving thimerosal-containing vaccines when compared to the normal background rate of autism. Additionally, the mercury exposure with vaccination is much lower than through many other environmental exposures. Despite the lack of evidence of thimerosal causing neurologic disorders, vaccine manufacturers are producing vaccines that are thimerosal-free or only contain trace amounts of thimerosal.21
SPECIAL POPULATIONS
Immunocompromised Host
The number of immunocompromised persons is continually increasing as advances are made in medicine. The life expectancy for persons with cancer, HIV infection, and solid organ or bone marrow transplantation is increasing. Vaccination provides one tool to prevent infection in the immunocompromised host; however, the individual’s immunosuppressed state will alter the response to the vaccine. In general all vaccinations should be updated prior to the person becoming immunosuppressed, if possible. Once a person becomes significantly immunosuppressed, live virus vaccines should be avoided.
Patient Encounter 3
A 7-year-old child with acute leukemia is 1-year post bone marrow transplantation. The child’s clinical course has been uneventful since transplantation and everything is going as expected. The physician discusses with the child’s parents the continued need for protection against infections and suggests that the child should receive some vaccinations.
When should the child begin receiving vaccinations?
Which vaccines should be administered and on what schedule?
Should any vaccines be avoided?
Which vaccines should household contacts receive?
Adults with HIV infection should be vaccinated with the 23-valent pneumococcal polysaccharide and hepatitis B vaccines as early in the course of the disease as possible. Inactivated influenza vaccine should be given yearly. Children should continue to receive vaccinations on the standard childhood immunization schedule. The individual may experience a transient elevation in HIV viral load following vaccination.24
Following hematopoietic stem cell transplantation the patient will need virtually all routine vaccines to be administered again; however, the patient will not be able to mount an adequate response for 6 to 12 months posttransplant. Diphtheria, tetanus, acellular pertussis, H influenzae type b, hepatitis B, pneumococcal, and inactivated poliovirus should be given at 12, 14, and 24 months posthematopoietic stem cell transplantation. Inactivated influenza vaccine should be given yearly, starting 6 months after transplant. Measles, mumps, and rubella can be given 2 years after transplant and varicella vaccine is contraindicated.24
Solid organ transplant recipients have a blunted immune response to vaccines because the immunosuppressive regimens used to prevent organ rejection inhibit both T- and B-cell proliferation. Many of these patients will also have secondary hypogammaglobulinemia posttransplantation. Prior to transplant, children should complete primary immunization schedules if possible; accelerated schedules may be used. Adults should have all vaccinations updated prior to transplantation.24
Household contacts of immunocompromised persons should have all routine vaccines as scheduled, including yearly influenza vaccination. Children in the household may receive live virus vaccines without special precautions; however, if a rash develops following varicella vaccination, contact should be avoided with the immunocompromised host until the rash resolves.
Pregnancy
Immunization during pregnancy is done to ensure that the infant has sufficient antibodies during the period the infant is most vulnerable to disease. Maternal antibodies are actively transported to the fetus throughout the pregnancy. However, in the last 4 to 6 weeks of gestation the active transport of immunoglobulins substantially increases. Vaccines administered during pregnancy should produce high antibody concentrations following a single vaccination and are administered in the second and third trimester, but no later than 2 weeks prior to delivery. Maternal vaccination has not shown any harmful effects to the developing fetus. However, live virus vaccines are avoided due to theoretical concerns of the virus being transported across the placenta and infecting the fetus. It is recommended that pregnant women be up to date on tetanus vaccine and receive the influenza vaccine if the second and third trimester will occur during the winter months.25
Health Care Workers
Most health care workers are at risk for exposure to many diseases in the normal course of their work. Additionally, health care workers may transmit vaccine-preventable diseases to their patients. At the time of employment and on a regular basis, health care workers should be screened for immunity to measles, mumps, rubella, and varicella; if found to be nonimmune, the measles, mumps, and rubella, and varicella vaccines should be administered. The hepatitis B series should be given if not already completed. Tetanus should be updated and given every 10 years. Health care personnel in hospitals and ambulatory settings with direct patient contact should receive Tdap if not already received; an interval as short as 2 years from the last tetanus-containing vaccine should be used.
All health care personnel should be strongly encouraged to receive the influenza vaccine yearly in order to prevent transmission of influenza within the health care facility and to decrease employee absenteeism for influenza-related reasons. The vaccine should be made available to employees at the workplace free of charge. Employees should be asked to sign a declination if refusing to receive the influenza vaccine. Additionally, health care facilities should report the number of health care personnel receiving influenza vaccine as a patient safety measure.26
OUTCOME MEASURES
Vaccines are a cost-effective means for disease prevention. For every dollar spent on routine childhood vaccines there will be a savings of $0.90 to $24.00 in direct medical expense. The rates of vaccination for children are well over 90%. This has been attributed to the requirements for proof of vaccination by states for enrollment into day care centers and school. Additionally, children (18 years of age or younger) may receive routine vaccinations free of charge through state health departments or other assistance programs, such as the national Vaccines for Children program. Many states have developed universal immunization databases to document pediatric and adult vaccination status. This eliminates the problems of lost immunization records if a child changes health care providers.
The vaccination rate in adults is much lower than that in children. Only 50% to 60% of adults who meet criteria have received pneumococcal or influenza vaccination. Comprehensive initiatives need to be implemented to increase the adult vaccination rate. Some proven concepts are providing reminders to patients that vaccines are due and implementation of standing orders for vaccines. This latter concept allows nurses and pharmacists to screen patients to see if pneumococcal, influenza, or other vaccines are needed and to vaccinate without a physician’s order.
The Centers for Medicare and Medicaid Services has incorporated pneumococcal and influenza immunization rates into some of their quality standards. Patients admitted to a hospital for community-acquired pneumonia should be screened for, offered, and vaccinated with pneumococcal and influenza vaccines prior to discharge if not previously administered. In physicians’ office practice, all persons over 65 years of age who have been hospitalized in the past year should be screened for, offered, and vaccinated with pneumococcal and influenza vaccines if not previously administered. Both of these standards will affect payment if the standard is not met. The Joint Commission has also incorporated these standards into their accreditation reviews of health care facilities.
Abbreviations Introduced in This Chapter
Self-assessment questions and answers are available at http://www.mhpharmacotherapy.com/pp.html.
REFERENCES
1. MacKay IR, Rosen FS. Vaccines and vaccination. N Engl J Med 2001;345:1042–1053.
2. Mattos-Guaraldi AL, Moreira LO, Damasco PV, Junior RH. Diphtheria remains a threat to health in the developing world—An overview. Mern Inst Oswaldo Cruz 2003;98:987–993.
3. Rhee P, Nunley MK, Demetriades D, Velmahos G, Doucet JJ. Tetanus and trauma: A review and recommendations. J Trauma 2005;58: 1082–1088.
4. Hewlett El, Edwards KM. Pertussis—Not just for kids. N Engl J Med 2005;352:1215–1222.
5. Centers for Disease Control and Prevention. Preventing tetanus, diphtheria, and pertussis among adults: Use of the tetanus toxiod, reduced diphtheria toxiod and acellular pertussis vaccine. MMWR 2006;55 (No. RR-17):1–34.
6. Centers for Disease Control and Prevention. Prevention of hepatitis A through active and passive immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1999; 48(No. RR-12):1–37.
7. Centers for Disease Control and Prevention. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP); Part 1 immunization of infants, children, and adolescents. MMWR 2005; 55(No. RR-16):1–32.
8. Govan VA. A novel vaccine for cervical cancer: Quadrivalent human papillomavirus (types 6, 11, 16 and 18) recombinant vaccine (Gardasil®). Ther Clin Risk Manag 2008;4:65–70.
9. Centers for Disease Control and Prevention: Quadrivalent human papillomavirus vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2007;57 (No. RR-2):1–23.
10. Centers for Disease Control and Prevention. Prevention and control of influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR 2008;57(No. RR-7): 1–59.
11. Centers for Disease Control and Prevention. Measles, mumps, and rubella—Vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1998;47(No. RR-8):1–57.
12. Centers for Disease Control and Prevention. Prevention and control of meningococcal disease recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2005;54(No. RR-7):1–21.
13. Centers for Disease Control and Prevention. Revised recommendations of the Committee on Immunization Practices to vaccinate all persons aged 11–18 years with meningococcal conjugate vaccine. MMWR 2007;56: 794–795.
14. Centers for Disease Control and Prevention. Recommendation from the Committee on Immunization Practices (ACIP) for use of the quadrivalent meningococcal conjugate vaccine (MCV4) in children aged 2–10 years at increased risk for invasive meningococcal disease. MMWR 2007;56:1265–1266.
15. American Society of Health-Systems Pharmacists. ASHP therapeutic position statement on strategies for identifying and preventing pneumococcal resistance. Am J Health-Syst Pharm 2004;61: 2430–2435.
16. Centers for Disease Control and Prevention. Poliomyelitis in the United States: Updated recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2000;49(No. RR-5):1–22.
17. Centers for Disease Control and Prevention. Prevention of rotavirus gastroenteritis among infants and children: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2006; 55 (No. RR-12):1–13.
18. Sharrar RG, LaRussa P, Galea SA, et al. The postmarketing safety profile of varicella vaccine. Vaccine 2001;19:916–923.
19. Quan D, Cohrs RJ, Mahalingam R, Gilden DH. Prevention of shingles: Safety and efficacy of live zoster vaccine. Ther Clin Risk Manag 2007; 3:633–639.
20. Edwards KM, Decker MD. Combination vaccines. Infect Dis Clin N Am 2001;15:209–230.
21. Moylett EH, Hanson IC. Mechanistic actions of the risks and adverse events associated with vaccine administration. J Allerg Clin Immunol 2004;114: 1010–1020.
22. Kohl KS, Marcy SM, Blum M, et al. Fever after immunization: Current concepts and improved future scientific understanding. Clin Infect Dis 2004;39:389–394.
23. Shoenfeld Y, Aron-Maor A. Vaccination and autoimmunity – ‘vaccinosis’: A dangerous liaison? J Autoimmune 2000;14:1–10.
24. Weber DJ, rutala WA. Immunization of immunocompromised persons. Immunol Allergy Clin North Am 2003;23:605–634.
25. Munoz FM, Englund JA. Vaccines in pregnancy. Infect Dis Clin North Am 2001;15:253–271.
26. Centers for Disease Control and Prevention. Influenza vaccination of health-care personnel: Recommendations of the Healthcare Infection Control Practices Advisory Committee (HICPAC) and the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2006:55 (RR-2):1–16.