Chapter 10: Immunization

Immunization is widely recognized as one of the greatest public health achievements of modern times. Largely due to immunization, the annual incidences of diphtheria, paralytic poliomyelitis, measles, mumps, rubella, and Haemophilus influenzae type b (Hib) in the United States have fallen by more than 99% compared with the average annual incidences of these diseases in the 20th century. Invasive pneumococcal disease in children younger than 5 years has declined steeply since routine pneumococcal vaccination began in 2000. Similarly, rotavirus vaccination is associated with substantial declines in hospitalizations and emergency department visits for diarrheal illnesses in young children. Childhood immunization has also led, through herd immunity, to significant decreases in several infectious illnesses in adults, including pneumococcal, rotavirus, and varicella disease.

Every year, approximately 4 million children are born in the United States, and successful immunization of each birth cohort requires the concerted effort of parents, health care providers, public health officials, and vaccine manufacturers. Public perceptions about immunization, particularly routine childhood immunization, are generally positive. However, parent concerns about the safety of vaccines have risen in recent years, in part fueled by unfounded speculation about an association between various vaccines or vaccine components and autism. Modern vaccines have a high degree of safety, serious adverse events following vaccination are rare, and vaccination benefits strongly outweigh these rare risks. Nonetheless, health care providers need to be prepared to discuss the benefits and risks of vaccination with uncertain parents, providing factual information in a clear, empathic, and nonjudgmental manner.

This chapter starts with general principles regarding immunization and the recommended pediatric and adolescent vaccination schedules, followed by a discussion of vaccine safety. Each recommended vaccine is then discussed. Vaccines only given in special circumstances are discussed in the final section. Several acronyms commonly used in this and other vaccine-related publications are summarized in Table 10–1.

Because the immunization field is rapidly changing, it is important for health care providers to seek the most up-to-date information available. The recommendations outlined are current but will change as technology evolves and our understanding of the epidemiology of vaccine-preventable diseases changes. Several useful sources for regularly updated information about immunization are:

1. The Centers for Disease Control and Prevention (CDC). It maintains a website with extensive vaccine-related resources, including recommendations of the Advisory Committee on Immunization Practices (ACIP), vaccination schedules, Vaccine Information Statements (VISs), and detailed information for the public and providers. Available at: www.cdc.gov/vaccines.

2. CDC Contact Center. The CDC-INFO contact center provides services to the public and health care professionals regarding a variety of health-related issues, including immunizations. Available at: www.cdc.gov/cdc-info, or by phone at 1-800-232-4636 (English and Spanish).

3. The Red Book: Report of the Committee on Infectious Diseases. Published at 2- to 3-year intervals by the American Academy of Pediatrics (AAP). A newly revised Red Book was published in 2018. Updates are published in the journal Pediatrics and can also be accessed at redbook.solutions.aap.org/.

4. Immunization Action Coalition. This nonprofit organization creates and distributes educational materials for the public and health care providers. All materials are provided free of charge and can be accessed at www.vaccineinformation.org (for the public) or www.immunize.org (for health care providers).

5. The Vaccine Education Center at Children’s Hospital of Philadelphia. Contains extensive vaccine-related materials, including regarding vaccine safety and vaccine ingredients. Available at: www.chop.edu/centers-programs/vaccine-education-center.

In the United States, every infant requires more than 25 doses of vaccine by age 18 months to be protected against 14 or more childhood diseases. In 2017, immunization coverage rates for children aged 19–35 months were more than 90% for poliovirus, measles-mumps-rubella, varicella, and hepatitis B (HepB) vaccines, and have maintained stable rates around 75% for more recently recommended vaccines such as rotavirus and hepatitis A (HepA) vaccines. CDC recommends the following specific proven strategies to increase vaccination coverage rates: (1) assessing and providing feedback on practice/provider immunization rates; (2) keeping accurate immunization records; (3) recommending vaccination to parents, and reinforcing when to return for vaccination; (4) sending reminder messages to parents; (5) sending reminder messages to providers; (6) reducing missed opportunities to vaccinate; and (7) reducing barriers to immunize within the practice.

The National Childhood Vaccine Injury Act of 1986 requires that for each vaccine covered under the Vaccine Injury Compensation Program, parents should be advised about the risks and benefits of vaccination in a standard manner, using VIS forms produced by CDC. Each time a Vaccine Injury Compensation Program–covered vaccine is administered, the current version of the VIS must be provided to the nonminor patient or legal guardian. Required vaccination documentation in the medical record includes the vaccine manufacturer, lot number, administration date, and expiration date. The VIS version and date and site and route of administration should also be recorded.

Needles used for vaccination should be sterile and disposable to minimize contamination. A 70% solution of alcohol is appropriate for disinfecting the stopper of the vaccine container and the skin at the injection site. A 5% topical emulsion of lidocaine-prilocaine applied to the site of vaccination for 30–60 minutes prior to the injection minimizes pain, especially when multiple vaccines are administered. A separate syringe and needle should be used for each vaccine.

Compliance with the manufacturer’s recommendations for route and site of administration of injectable vaccines are critical for safety and efficacy. With few exceptions (Bacillus Calmette-Guérin [BCG] vaccine), all vaccines are given either intramuscularly or subcutaneously. All vaccines containing an adjuvant must be administered intramuscularly to avoid local irritation or granuloma formation. Intramuscular injections are given at a 90-degree angle to the skin, using a needle that is sufficiently long to reach the muscle tissue, but not so long as to injure underlying nerves, blood vessels, or bones. The anterolateral thigh is the preferred site of vaccination in newborns and children up to 2 years of age, and the deltoid muscle is the preferred site for children aged 3–18 years, although the anterolateral thigh is an acceptable site. Needle length and location should be: ⅝ inch in newborn infants (thigh); 1 inch in infants 1- to 12-month-olds (thigh), 1–1¼ inches in 1- to 18-year-olds (thigh), and ⅝–1 inch in 1- to 18-year-olds (deltoid). Subcutaneous injections should be administered at a 45-degree angle into the anterolateral aspect of the thigh (for infants < 12 months) or the upper outer triceps area (for children aged ≥ 12 months) using a 23- or 25-gauge, ⅝-inch needle. Pulling back on the syringe prior to vaccine injection (aspiration) is not recommended.

Many combinations of vaccines can be administered simultaneously without increasing the risk of adverse effects or compromising immune response. Depending on the combination vaccine used, children may receive an “extra” dose of HepB or Hib; these additional doses are not harmful. Inactivated vaccines can be given simultaneously with, or at any time after, a different vaccine. Injectable or intranasal live-virus vaccines (eg, measles-mumps-rubella [MMR], varicella [VAR], or live attenuated influenza [LAIV]), if not administered on the same day, should be given at least 4 weeks apart. If an immunoglobulin (Ig) or blood product has been administered, live-virus vaccination should be delayed 3–11 months to avoid interference with the immune response. The interval depends on the product given (details can be found at: www.cdc.gov/vaccines/hcp/acip-recs/general-recs/timing.html#t-05).

With the large number of vaccine preparations available, interchangeability of vaccines is an issue. All brands of Hib conjugate, HepB, and HepA vaccines are interchangeable. For vaccines containing acellular pertussis antigens, it is recommended that the same brand be used, but when the brand is unknown or the same brand is unavailable, any vaccine with diphtheria and tetanus toxoids and acellular pertussis should be used to continue vaccination. Exceptions to this rule are the serogroup B meningococcal (MenB) vaccines, which are not interchangeable under any circumstance. Extending recommended intervals between vaccinations does not alter final antibody titers, and lapsed schedules do not require restarting the series.

The numerous vaccines and other immunologic products used in routine practice vary in the storage temperatures required. The majority of vaccines should never be subjected to freezing temperatures, except varicella-containing vaccines (MMRV, VAR, and herpes zoster) that should be stored frozen. Product package inserts should be consulted for detailed information on vaccine storage conditions and shelf life.

Vaccines very rarely (about one case per million doses) cause acute anaphylactic-type reactions. All vaccine providers should have the equipment, medications, staff, established protocols, and training to manage emergencies that may occur following vaccination.

Each year, CDC recommends immunization schedules for children and adolescents, which are an important guide for vaccination providers. Vaccines in the schedules are roughly ordered by the age at which the vaccines are first given. Table 10–2 is the 2020 schedule of routine immunizations for normal infants, children, and adolescents from birth through 18 years of age. Table 10–3 is the 2020 schedule for persons aged 4 months through 18 years who start vaccination late or are more than 1 month behind the routine immunization schedule. Annually updated immunization schedules are available at www.cdc.gov/vaccines.

Combination vaccines address the problem of large numbers of injections during a clinic visit. Currently available combination vaccines include MMR, MMRV, and various combinations of Hib, HepB, IPV, and DTaP, including DTaP-HepB-IPV and DTaP-IPV-Hib. There is a newly approved hexavalent (DTaP-IPV-Hib-HepB) vaccine that will likely be available in 2021. Separate vaccines should not be combined into one syringe by the provider unless approved by the Food and Drug Administration (FDA), because this could decrease the efficacy of vaccine components.

VACCINE SAFETY

Vaccine Safety Monitoring

The United States has a sophisticated, multifaceted system to monitor the safety of licensed vaccines. The Vaccine Adverse Event Reporting System (VAERS), the Vaccine Safety Datalink (VSD), the Post-Licensure Rapid Immunization Safety Monitoring (PRISM) system, and the Clinical Immunization Safety Assessment (CISA) system each provide distinct contributions to monitoring vaccine safety. VAERS is a national passive surveillance system administered jointly by the FDA and CDC to accept reports from health care providers and the public about possible vaccine-related adverse events. Reports of adverse events possibly related to vaccination can be made via the Internet (vaers.hhs.gov) or by telephone (1-800-822-7967). As a passive surveillance system, VAERS is subject to limitations, including underreporting, overreporting, the reporting of events that are temporally but not causally related to vaccination, the lack of denominator data, and the lack of a comparison group. The VSD and PRISM, in comparison, are active surveillance systems with continuous safety monitoring of vaccines in defined patient populations. The VSD and PRISM can conduct timely investigations of newly licensed vaccines or emerging vaccine safety concerns. The CISA system is designed to develop protocols for the evaluation, diagnosis, and treatment of adverse events following immunization. Patients with rare and serious adverse events following immunization can be referred to CISA for evaluation.

Vaccine Contraindications & Precautions

All vaccines have certain contraindications and precautions that guide their administration. A contraindication indicates that the potential vaccine recipient is at increased risk of a serious adverse event. A vaccine should not be given when a contraindication to that vaccine is present, whereas a precaution indicates a circumstance that might increase the risk of adverse events or diminish vaccine effectiveness. In the setting of precautions, the risks and benefits of vaccination must be carefully weighed prior to a decision regarding vaccination. Precautions are often temporary, in which case vaccination can resume once the precaution no longer applies. Contraindications and precautions are listed with each vaccine in this chapter. Additional, more detailed, information is available from the CDC (www.cdc.gov/vaccines), in the AAP’s Red Book, and in vaccine package inserts.

VACCINATION IN SPECIAL CIRCUMSTANCES

Minor Acute Illnesses

Minor acute illnesses, with or without low-grade fever, are not contraindications to vaccination, because there is no evidence that vaccination under these conditions increases the rate of adverse effects or decreases efficacy. A moderate to severe febrile illness may be a reason to postpone vaccination. Routine physical examination and temperature assessment are not necessary before vaccinating healthy infants and children.

Children With Chronic Illnesses

Most chronic diseases are not contraindications to vaccination; in fact, children with chronic diseases may be at greater risk of complications from vaccine-preventable diseases, such as influenza and pneumococcal infections. Premature infants are a good example. They should be immunized according to their chronologic, not gestational, age. Vaccine doses should not be reduced for preterm or low-birth-weight infants. One exception is children with progressive central nervous system disorders. Vaccination with DTaP should be deferred until the neurologic condition has been clarified and is stable.

Immunodeficient Children

Congenitally immunodeficient children should not be immunized with live-virus vaccines (oral polio vaccine [OPV, not available in the United States], rotavirus, MMR, VAR, MMRV, yellow fever, or LAIV) or live-bacteria vaccines (BCG or live typhoid fever vaccine). Depending on the nature of the immunodeficiency, other vaccines are safe but may fail to evoke an immune response. Children with cancer and children receiving high-dose corticosteroids or other immunosuppressive agents should not be vaccinated with live-virus or live-bacteria vaccines. This contraindication does not apply if the malignancy is in remission and chemotherapy has not been administered for at least 90 days. Live-virus vaccines may also be administered to previously healthy children receiving low to moderate doses of corticosteroids (defined as up to 2 mg/kg/day of prednisone or prednisone equivalent, with a 20 mg/day maximum) for less than 14 days; children without other immunodeficiency receiving short-acting alternate-day corticosteroids; children being maintained on physiologic corticosteroid therapy; and children receiving only topical, inhaled, or intra-articular corticosteroids.

Contraindication of live-pathogen vaccines also applies to children with HIV infection who are severely immunosuppressed. Those who receive MMR should have at least 15% CD4 cells, a CD4 lymphocyte count equivalent to CDC immunologic class 2, and be asymptomatic from their HIV. MMR for these children is recommended at 12 months of age (after 6 months of age during an epidemic); some experts suggest delaying MMR vaccination in HIV-infected children until they have received antiretroviral therapy for 3 months. For HIV-infected children, a booster MMR dose may be given at least 1 month after the initial dose; in fact, giving this booster dose earlier than at 4–6 years of age is often encouraged. Doses given before 1 year of age should not be considered part of a complete series. VAR vaccination is also recommended for HIV-infected children with CD4 cells preserved or recovered as listed earlier. The ACIP recommends only IPV vaccination for children. Thus, immunodeficient children should no longer be exposed to OPV through household contacts. MMR and VAR are not contraindicated in household contacts of immunocompromised children. HIV-infected children who were vaccinated before their HIV was treated should be reimmunized to ensure adequate protection. The recommended immunization schedule for immunocompromised children is available at https://www.cdc.gov/vaccines/schedules/hcp/imz/child-indications.html.

Allergic or Hypersensitive Children

Severe hypersensitivity reactions are rare following vaccination (1.53 cases per 1 million doses). They are generally attributable to a trace component of the vaccine other than to the antigen; for example, MMR, IPV, and VAR contain microgram quantities of neomycin, and IPV also contains trace amounts of streptomycin and polymyxin B. Children with known anaphylactic responses to these antibiotics should not be given these vaccines. Trace quantities of egg antigens may be present in both inactivated and live influenza and yellow fever vaccines. Guidelines for influenza vaccination in children with egg allergies have recently changed. The trace amounts of egg protein are generally considered below the threshold needed to induce an allergic reaction and there has been no increased risk of anaphylaxis documented in children with severe egg allergies. Therefore, children with severe egg allergy can be vaccinated with influenza vaccine with no special precautions beyond those for any other vaccine. Some vaccines (MMR, MMRV, and VAR) contain gelatin. For any persons with a history of anaphylactic reaction to gelatin or any component contained in a vaccine, the vaccine package insert should be reviewed and additional consultation sought, such as from a pediatric allergist. Some tips and rubber plungers of vaccine syringes contain latex. These vaccines should not be administered to individuals with a history of severe anaphylactic allergy to latex, but may be administered to people with less severe allergies. Thimerosal is an organic mercurial compound used as a preservative in vaccines since the 1930s. While there is no evidence that thimerosal has caused serious allergic reactions or autism, all routinely recommended vaccines for infants have been manufactured without thimerosal since mid-2001. Thimerosal-free formulations of injectable influenza vaccine are available, and LAIV does not contain thimerosal.

Other Special Circumstances

Detailed recommendations for preterm low-birth-weight infants; pediatric transplant recipients; Alaskan Natives/American Indians; children in residential institutions or military communities; or refugees, new immigrants, or travelers are available from the CDC (at http://www.cdc.gov/vaccines) and from the AAP’s Red Book.

COMMUNICATING WITH PARENTS ABOUT VACCINES

Most parents in the United States choose to vaccinate their children. In 2017, 1.1% of young children received no vaccines. However, parental concern about vaccines is on the rise, and an increasing number of parents are choosing to delay or decline vaccination for their children. While there are myriad reasons given for not vaccinating, several themes recur. Some parents do not believe their children are at risk for diseases such as poliomyelitis, measles, and tetanus. Other parents do not believe that certain vaccine-preventable diseases, such as varicella and pertussis, are particularly serious. There are also widespread concerns about the safety of vaccines. Health care providers have a critically important role in discussing the known risks and benefits of vaccination with parents. In this context, it is important that providers recognize that parent decisions are often based on inaccurate information about vaccine risk provided by the media or Internet sources.

AAP, CDC, and others have developed resources to guide providers on how best to communicate with parents about vaccines. A presumptive recommendation (“We have three shots to do today”) is likely more effective than a participatory approach (“Have you thought about the shots he is due for today?”) for the infant series of vaccines. The presumptive approach has also been shown in a randomized trial to be an effective technique for increasing uptake of HPV vaccine. For parents who resist or have questions about vaccines, some will agree to be vaccinated after simply receiving the necessary knowledge. For many, however, simply correcting misinformation is not enough, and may increase resistance to vaccination. For these parents, it is best to avoid arguments or rebuttals. Motivational interviewing has shown promise as an effective communication technique for both childhood and adolescent vaccines. Other promising techniques include pivoting away from discussions of vaccine side effects to emphasize the importance of the vaccine for disease prevention, personal recommendations (“I vaccinate my own children according to the recommended schedule”), promotion of social norms (“Almost all of our patients are fully vaccinated”), or highlighting circumstances which increase risk (“These infectious diseases are just a plane flight away.”).

Parents with questions about vaccine safety may be directed to trusted websites, such as those of the AAP (https://healthychildren.org), CDC (www.cdc.gov/vaccines), and the Immunization Action Coalition (www.immunize.org).

HEPATITIS B VACCINATION

Reported cases of acute hepatitis B has declined dramatically in the United States, largely attributable to vaccination. Based on surveillance data from 2015, acute hepatitis B incidence has declined by at least 87% since 1985. The greatest declines are in children younger than 15 years, in whom rates have decreased by 98%.

Success in reducing hepatitis B in the United States is due, in large part, to a comprehensive hepatitis B prevention strategy initiated in 1991. The four central elements of this approach are: (1) immunization of all infants beginning at birth; (2) routine screening of all pregnant women for hepatitis B infection, and provision of hepatitis B immunoglobulin (HBIg) to all infants born to infected mothers; (3) routine vaccination of previously unvaccinated children and adolescents; and (4) vaccination of adults at increased risk of hepatitis B infection.

While high immunization rates have been achieved in young children (> 90% were fully immunized in 2017), there has been less success in identifying hepatitis B–infected mothers and at immunizing high-risk adults. Of the estimated 23,000 mothers who deliver each year who are hepatitis B surface antigen (HBsAg) positive, only 9000 are identified through prenatal screening. While there is an average of 90 cases of perinatally acquired hepatitis B infection reported to the CDC every year, the actual number of perinatal HBV infections is estimated to be 10–20 times higher than the number currently detected and reported. This circumstance represents a significant missed opportunity for prevention in exposed infants, given that administration of HepB vaccine in conjunction with HBIg is 95% effective at preventing mother-to-infant transmission of the virus. Further, many hospitals do not routinely offer HepB to all newborns, despite AAP and ACIP recommendations for universal newborn HepB vaccination. Similarly, while HepB alone is 90%–95% effective at preventing hepatitis B infection, only 45% of high-risk adults have been vaccinated.

All pregnant women should be routinely screened for HBsAg. Infants born to HBsAg-positive mothers should receive both HepB and HBIg immediately after birth. Infants for whom the maternal HBsAg status is unknown should receive vaccine (but not HBIg) within 12 hours of birth. In such circumstances, the mother’s HBsAg status should be determined as soon as possible during her hospitalization, and the infant given HBIg if the mother is found to be HBsAg positive. For all infants, the hepatitis B immunization series should be started at birth, with the first dose given prior to 24 hours of age without exception. In 2015, 72% of infants nationally received HepB within 3 days after birth, with wide variation by state (49%–88%).

Routine immunization with three doses of HepB is recommended for all infants and all previously unvaccinated children aged 0–18 years. A two-dose schedule is available for adolescents. Screening for markers of past infection before vaccinating is not indicated for children and adolescents, but may be considered for high-risk adults. Because HepB vaccines consist of an inactivated subunit of the virus, they are not infectious and not contraindicated in immunosuppressed individuals or pregnant women.

Vaccines Available

1. HepB vaccine (Recombivax HB, Merck) contains recombinant HepB only.

2. HepB vaccine (Engerix-B, GlaxoSmithKline) contains recombinant HepB only.

3. DTaP-HepB-IPV (Pediarix, GlaxoSmithKline) contains vaccines against diphtheria, tetanus, pertussis, hepatitis B, and poliovirus.

4. HepB vaccine (Heplisav-B, Dynavax Technologies) contains recombinant HepB only, but with a novel adjuvant, and is approved for adults 18 years and older.

5. DTaP-IPV-Hib-HepB (Vaxelis, Merck) contains DTaP, IPV, Hib, and HepB vaccines. Approved for use as a three-dose series at 2, 4, and 6 months of age; not approved for use at 4–6 years of age as the final booster dose of IPV; given intramuscularly (not available until at least 2021).

Only the noncombination vaccines (Recombivax HB and Engerix-B) can be given between birth and 6 weeks of age. Any single or combination vaccine listed above can be used to complete the HepB vaccination series. A combination vaccine against hepatitis A and hepatitis B (Twinrix, GlaxoSmithKline) is available, but is only licensed in the United States for persons 18 years and older.

Dosage Schedule of Administration

HepB is recommended for all infants and children in the United States. Table 10–4 presents the vaccination schedule for newborn infants, dependent on maternal HBsAg status. Infants born to mothers with positive or unknown HBsAg status should receive HepB vaccine within 12 hours of birth. Infants born to HBsAg-negative mothers should receive the vaccine prior to 24 hours of age.

For children younger than 11 years not previously immunized, three intramuscular doses of HepB are needed. Adolescents aged 11–15 years have two options: the standard pediatric three-dose schedule or two doses of adult Recombivax HB (1.0 mL dose), with the second dose administered 4–6 months after the first dose. Certain patients may have reduced immune response to HepB vaccination, including preterm infants weighing less than 2000 g at birth, the elderly, immunosuppressed patients, and those receiving dialysis. Preterm infants whose mothers are HBsAg-positive or with unknown HBsAg status should receive both HepB and HBIg within 12 hours of birth. For preterm infants whose mothers are known to be HBsAg-negative, initiation of the vaccination series should be delayed until 30 days of age if the infant is medically stable, or prior to hospital discharge if the infant is discharged before 30 days of age. Pediatric hemodialysis patients and immunocompromised persons may require larger doses or an increased number of doses, with dose amounts and schedules available in the most recent CDC hepatitis B recommendations (see references).

Contraindications & Precautions

HepB should not be given to persons with a serious allergic reaction to yeast or to any vaccine components. Individuals with a history of serious adverse events, such as anaphylaxis, after receiving HepB should not receive additional doses. Vaccination is not contraindicated in persons with a history of Guillain-Barré syndrome, multiple sclerosis, autoimmune disease, other chronic conditions, or in pregnancy.

Adverse Effects

The overall rate of adverse events following vaccination is low. Those reported are minor, including fever (1%–6%) and pain at the injection site (3%–29%). There is no evidence of an association between vaccination and sudden infant death syndrome, multiple sclerosis, autoimmune disease, or chronic fatigue syndrome.

Postexposure Prophylaxis

Postexposure prophylaxis is indicated for unvaccinated persons with perinatal, sexual, household, percutaneous, or mucosal exposure to hepatitis B virus. When prophylaxis is indicated, unvaccinated individuals should receive HBIg (0.06 mL/kg) and the first dose of HepB at a separate anatomic site. Sexual and household contacts of someone with chronic (as opposed to acute) infection should receive HepB only. All vaccinated persons not previously tested for antibody should be tested for anti-HBs after exposure to hepatitis B. If antibody levels are adequate (≥ 10 mIU/mL), no treatment is necessary. If levels are inadequate (< 10 mIU/mL) and the exposure was to HBsAg-positive blood, HBIg and vaccination are required. For non-vaccinated individuals with percutaneous or mucosal exposure to blood, HepB should be given, and HBIg considered depending on the HBsAg status of the person who was the source of the blood exposure.

Antibody Preparations

HBIg is prepared from HIV-negative and hepatitis C virus-negative donors with high titers of hepatitis B surface antibody. The process used to prepare this product inactivates or eliminates any undetected HIV and hepatitis C virus.

ROTAVIRUS VACCINATION

Rotavirus is the leading cause of hospitalization and death from acute gastroenteritis in young children worldwide. The burden of rotavirus is particularly severe in the developing world, where as many as 215,000 children die each year from rotavirus-associated dehydration and other complications. While deaths from rotavirus were uncommon in the United States (20–60 deaths per year), prior to the introduction of rotavirus vaccine, rotavirus infections caused substantial morbidity annually with an estimated 2.7 million diarrheal illnesses, 410,000 office visits, and 55,000–70,000 hospitalizations.

Rotavirus vaccination has been routinely recommended in the United States since 2006. Two rotavirus vaccines are currently available, a pentavalent rotavirus vaccine (RV5; RotaTeq) and a monovalent rotavirus vaccine (RV1; Rotarix). Hospitalizations and outpatient visits for rotavirus disease have fallen significantly among vaccinated infants in the United States, and disease has also declined among unimmunized older children and adults reflecting herd protection.

Rotavirus vaccination has also reduced morbidity and mortality from rotavirus disease worldwide. While effectiveness of rotavirus vaccines is somewhat lower in developing countries, disease burden is so high that the public health impact of rotavirus vaccination is substantial in developing countries which have introduced these vaccines. Extensive efforts are underway to develop more effective, lower cost, heat-stable (ie, not requiring refrigeration) rotavirus vaccines for use in the developing world.

RV5 and RV1 are known to cause intussusception, although rarely. Intussusception risk has been estimated at 1 excess cases per 20,000 to 100,000 vaccinated infants. At this level of risk, the benefits of vaccination against rotavirus disease continue to greatly outweigh the risks in the United States and globally.

Vaccines Available

1. RV5 (Rotateq, Merck) is a pentavalent, live, oral, human-bovine reassortant rotavirus vaccine. The vaccine is a liquid, does not require any reconstitution, and does not contain any preservatives. The dosing tube is latex-free.

2. RV1 (Rotarix, GlaxoSmithKline) is a monovalent, live, oral, attenuated human rotavirus vaccine. The vaccine needs to be reconstituted with 1 mL of diluent using a prefilled oral applicator. The vaccine does not contain any preservatives. The oral applicator contains latex.

Dosage & Schedule of Administration

Either RV5 or RV1 can be used to prevent rotavirus gastroenteritis. RV5 should be administered orally, as a three-dose series, at 2, 4, and 6 months of age. RV1 should be administered orally, as a two-dose series, at 2 and 4 months of age. For both rotavirus vaccines, the minimum age for dose 1 is 6 weeks, and the maximum age for dose 1 is 14 weeks and 6 days. The vaccination series should not be started at 15 weeks of age or older, because of the lack of safety data around administering dose 1 to older infants. The minimum interval between doses is 4 weeks. All doses should be administered by 8 months and 0 days of age. While the ACIP recommends that the vaccine series be completed with the same product (RV5 or RV1) used for the initial dose, if this is not possible, providers should complete the series with whichever product is available.

Either rotavirus vaccine can be given simultaneously with all other recommended infant vaccines. No restrictions are placed on infant breast or formula feeding before or after receiving rotavirus vaccine. Infants readily swallow the vaccine in most circumstances; however, if an infant spits up or vomits after a dose is administered, the dose should not be readministered; the infant can receive the remaining doses at the normal intervals.

Contraindications & Precautions

Rotavirus vaccine should not be given to infants with a severe hypersensitivity to any components of the vaccine, to infants who had a serious allergic reaction to a previous dose of the vaccine, or to infants with a history of intussusception from any cause. RV1 should not be given to infants with a severe latex allergy. Both vaccines are contraindicated in infants with severe combined immunodeficiency (SCID). RV vaccines should be avoided in infants whose mother received a biologic response modifier (eg, etanercept) during pregnancy. Vaccination should be deferred in infants with acute moderate or severe gastroenteritis. Limited data suggest that rotavirus vaccination is safe and effective in premature infants. Small trials in Africa demonstrated that RV1 and RV5 were well tolerated and immunogenic in HIV-infected children. However, vaccine safety and efficacy in infants with immunocompromising conditions other than SCID, preexisting chronic gastrointestinal conditions (eg, Hirschsprung disease or short-gut syndrome), or a prior episode of intussusception, has not been established. Clinicians should weigh the potential risks and benefits of vaccination in such circumstances. Infants living in households with pregnant women or immunocompromised persons can be vaccinated.

Adverse Effects

In addition to the aforementioned slightly increased risk of intussusception, in prelicensure trials, RV5 was associated with a very small but statistically significant increased risk of vomiting and diarrhea, and RV1 with a similarly small but significant increased risk of cough or runny nose.

DIPHTHERIA-TETANUS-ACELLULAR PERTUSSIS VACCINATION

Diphtheria, tetanus, and pertussis vaccines have been given in a combined vaccine for many decades and have dramatically reduced each of these diseases. The efficacy with antigens in the combined vaccine is similar to that with antigens in single component vaccines. DTP vaccines containing whole-cell pertussis antigens are used widely in the world, but have been entirely replaced in the United States with DTaP vaccines, which contain purified, inactivated components of the pertussis bacterium.

Diphtheria is caused by a gram-positive bacillus, Corynebacterium diphtheriae. It is a toxin-mediated disease, with diphtheria toxin causing local tissue destruction, as in pharyngeal and tonsillar diphtheria, as well as systemic disease, particularly myocarditis and neuritis. The overall case fatality rate is between 5% and 10%, with higher death rates in persons younger than 5 years or older than 40 years. Largely because of successful vaccination programs, only two cases of diphtheria have been reported in the United States since 2004. The majority of the rare cases of diphtheria in the United States have been in unimmunized or inadequately immunized persons. The clinical efficacy of diphtheria vaccine is estimated to be greater than 95%.

The anaerobic gram-positive rod Clostridium tetani causes tetanus, usually through infection of a contaminated wound. When C tetani colonizes devitalized tissue, the exotoxin tetanospasmin is disseminated to inhibitory motor neurons, resulting in generalized rigidity and spasms of skeletal muscles. Tetanus-prone wounds include (1) puncture wounds, including those acquired due to body piercing, tattooing, and intravenous drug abuse; (2) animal bites; (3) lacerations and abrasions; and (4) wounds resulting from nonsterile neonatal delivery and umbilical cord care (neonatal tetanus). In persons who have completed the primary vaccination series and have received a booster dose within the past 10 years, vaccination is virtually 100% protective. In 2014, 29 cases of tetanus and 2 deaths occurred in the United States, almost all in persons who have had inadequate, distant (> 10 years), or no tetanus immunization.

Pertussis is also primarily a toxin-mediated disease caused by Bordetella pertussis, which is called “whooping cough” because of the high-pitched inspiratory whoop that can follow intense paroxysms of cough. Pertussis complications include death, often from associated pneumonia, seizures, and encephalopathy. Pertussis incidence in the United States declined dramatically between the 1940s and 1980s, but beginning in the early 1980s, incidence has been slowly increasing, with adolescents and adults accounting for a greater proportion of reported cases. Reasons for increased incidence include improved detection of cases with better laboratory testing methodology (polymerase chain reaction), increased recognition of cases in adolescents and adults, and waning protection from prior infection or with childhood vaccination with only acellular pertussis vaccines. Infants younger than 6 months have the highest rate of pertussis infection (78 cases per 100,000); greater than 90% of pertussis deaths occur in neonates and infants younger than 3 months.

In 2017, 18,975 cases of pertussis were reported in the United States despite widespread underreporting with many localized outbreaks necessitating enhanced vaccination programs. A single booster dose of a different formulation, Tdap, is now recommended for all adolescents and adults, and pregnant women with each pregnancy. Providing a booster dose of pertussis-containing vaccine may prevent adolescent and adult pertussis cases, and also has the potential to reduce the spread of pertussis to infants, who are most susceptible to pertussis complications.

Vaccines Available

A. Diphtheria, Tetanus, and Acellular Pertussis Combinations

1. DTaP (Daptacel, Sanofi; Infanrix, GlaxoSmithKline) contains tetanus toxoid, diphtheria toxoid, and acellular pertussis vaccine. DTaP is licensed for ages 6 weeks through 6 years and can be used for doses 1–5.

2. Tdap (Boostrix, GlaxoSmithKline) is a tetanus-reduced dose diphtheria-acellular pertussis vaccine formulated for persons 10 years of age and older, including adults and the elderly.

3. Tdap (Adacel, Sanofi) is a tetanus-diphtheria-acellular pertussis vaccine approved for persons 11–64 years of age.

B. DTaP Combined With Other Vaccines

1. DTaP-HepB-IPV (Pediarix, GlaxoSmithKline) contains DTaP combined with poliovirus and HepB vaccines. It is approved for the first three doses of the DTaP and IPV series, given at 2, 4, and 6 months of age. Although it is approved for use through age 6 years, it is not licensed for booster doses. It cannot be used, for example, as the fourth dose of DTaP (typically given at 15–18 months of age).

2. DTaP-IPV-Hib (Pentacel, Sanofi) contains DTaP, IPV, and Hib vaccines. The Hib component is Hib capsular polysaccharide bound to tetanus toxoid. This vaccine is approved for use as doses 1–4 of the DTaP series among children 6 weeks to 4 years of age. It is typically given at 2, 4, 6, and 15–18 months of age, and should not be used as the fifth dose in the DTaP series.

3. DTaP-IPV (Kinrix, GlaxoSmithKline, Quadracel, Sanofi) contains DTaP and IPV vaccines. The vaccine is licensed for children 4–6 years of age, for use as the fifth dose of the DTaP vaccine series and the fourth dose of the IPV series. Using this vaccine would reduce by one the number of injections a 4- to 6-year-old child would receive.

4. DTaP-IPV-Hib-HepB (Vaxelis, Merck) contains DTaP, IPV, Hib, and HepB vaccines. Approved for use as a three-dose series at 2, 4, and 6 months of age; not approved for use at 4–6 years of age as the final booster dose of IPV; given intramuscularly (not available until at least 2021).

C. Diphtheria and Tetanus Combinations

1. DT (generic, Sanofi) contains tetanus toxoid and diphtheria toxoid to be used only in children younger than 7 years with a contraindication to pertussis vaccination.

2. Td (Tenivac, Sanofi; generic, Massachusetts Biological Labs) contains tetanus toxoid and a reduced quantity of diphtheria toxoid, which is typically used for adults requiring tetanus prophylaxis.

D. Tetanus Only

TT (generic, Sanofi) contains tetanus toxoid only and can be used for adults or children. However, the use of this single-antigen vaccine is generally not recommended, because of the need for periodic boosting for both diphtheria and tetanus, and is available only on the international market.

Dosage & Schedule of Administration

Although several different vaccines are available, a few general considerations can guide their use in specific circumstances. DTaP (alone or combined with other vaccines) is used for infants and children between 6 weeks and 6 years of age. Children 7–10 years of age not fully immunized against pertussis (meaning those who have not received five prior doses of DTaP, or four doses of DTaP if the fourth dose was given on or after the fourth birthday), who have no contraindications to pertussis immunization, should receive a single dose of Tdap for pertussis protection. For adolescents and adults, a single dose of Tdap is used, followed by booster doses of Td every 10 years; a detailed description of Tdap use is provided later in this chapter.

The primary series of DTaP vaccination should consist of four doses, given at 2, 4, 6, and 15–18 months of age. The fourth dose may be given as early as 12 months of age if 6 months have elapsed since the third dose. Giving the fourth dose between 12 and 15 months of age is indicated if the provider thinks the child is unlikely to return for a clinic visit between 15 and 18 months of age. Children should receive a fifth dose of DTaP at 4–6 years of age. However, a fifth dose of DTaP is not needed if the fourth dose was given after the child’s fourth birthday. The same brand of DTaP should be used for all doses if feasible.

Contraindications & Precautions

DTaP vaccines should not be used in individuals who have had an anaphylactic-type reaction to a previous vaccine dose or to a vaccine component. DTaP should not be given to children who developed encephalopathy, not attributable to another identified cause, within 7 days of a previous dose of DTaP or DTP. DTaP vaccination should also be deferred in individuals with progressive neurologic disorders, such as infantile spasms, uncontrolled epilepsy, or progressive encephalopathy, until their neurologic status is clarified and stabilized.

Precautions to DTaP vaccination include high fever (≥ 40.5°F), persistent inconsolable crying, or shock-like state within 48 hours of a previous dose of DTP or DTaP; seizures within 3 days of a previous dose of DTP or DTaP; Guillain-Barré syndrome less than 6 weeks after a previous tetanus-containing vaccine; or incident moderate or severe acute illness with or without a fever.

Adverse Effects

Local reactions, fever, and other mild systemic effects occur with acellular pertussis vaccines at one-fourth to two-thirds the frequency noted following whole-cell DTP vaccination. Moderate to severe systemic effects, including fever of 40.5°C, persistent inconsolable crying lasting 3 hours or more, and hypotonic-hyporesponsive episodes, are much less frequent than with whole-cell DTP. These are without sequelae. Severe neurologic effects have not been temporally associated with DTaP vaccines in use in the United States. Data are limited regarding differences in reactogenicity among currently licensed DTaP vaccines. More severe local reactions at injection sites appear to occur with increasing dose number (including swelling of the thigh or entire upper arm) after receipt of the fourth and fifth doses for all currently licensed DTaP vaccines.

Diphtheria Antibody Preparations

Diphtheria antitoxin is manufactured in horses. Sensitivity to diphtheria antitoxin must be tested before it is given. Dosage depends on the size and location of the diphtheritic membrane and an estimate of the patient’s level of intoxication. Consultation on the use of diphtheria antitoxin is available from the CDC’s National Center for Immunization and Respiratory Diseases. Diphtheria antitoxin is not commercially available in the United States and must be obtained from the CDC.

Tetanus Antibody Preparations

Human tetanus immune globulin (TIg) is indicated in the management of tetanus-prone wounds in individuals who have had an uncertain number or fewer than three tetanus immunizations. Persons fully immunized with at least three doses do not require TIg, regardless of the nature of their wounds (Table 10–5). The optimal dose of TIg has not been established, but some experts recommend 500 IU, which appears to be as effective and causing less discomfort, as a single dose of 3000–6000 units with part of the dose infiltrated around the wound.

HAEMOPHILUS INFLUENZAE TYPE B VACCINATION

H influenzae type b (Hib) causes a wide spectrum of serious illnesses, particularly in young children, including meningitis, epiglottitis, pneumonia, septic arthritis, and cellulitis. Before the introduction of effective vaccines, Hib was the leading cause of invasive bacterial disease in children younger than 5 years in the United States.

Hib is surrounded by a polysaccharide capsule (polyribosylribitol phosphate [PRP]) that contributes to virulence. Antibodies to this polysaccharide capsule confer immunity to the disease. When Hib polysaccharide is chemically bonded (conjugated) to certain protein carriers, the conjugate vaccine induces T-cell–dependent immune memory that is highly effective in young children. Importantly, polysaccharide-protein conjugate vaccines also prevent carriage of the bacterium, and therefore limit spread from asymptomatic carriers to others in the community. All Hib vaccines are polysaccharide-protein conjugates.

Bacterial serotyping is required to differentiate infections caused by Hib from those caused by other encapsulated and nonencapsulated H influenzae species. In the early 1980s, roughly 20,000 cases of invasive Hib disease occurred each year in the United States. Because of the introduction of protein conjugate Hib vaccines, only about 40 cases of invasive Hib disease occurred in children younger than 5 years in 2017.

Vaccines Available

Four vaccines against Hib disease are available in the United States; three are Hib-only vaccines, and one is a combination vaccines. Each vaccine contains Hib polysaccharide conjugated to a protein carrier, but different protein carriers are used. The Hib conjugate vaccine that uses a meningococcal outer membrane protein carrier is abbreviated PRP-OMP. PRP-T vaccine uses a tetanus toxoid carrier.

Hib-Only Vaccines

1. Hib (PedvaxHIB, Merck, uses PRP-OMP), for use at 2, 4, and 12–15 months of age.

2. Hib (ActHIB, Sanofi, uses PRP-T), for use at 2, 4, 6, and 12–15 months of age.

3. Hib (Hiberix, GlaxoSmithKline, uses PRP-T), for use at 2, 4, 6, and 12–15 months of age.

Hib Combined With Other Vaccines

1. DTaP-IPV-Hib (Pentacel, Sanofi, uses PRP-T) contains DTaP, IPV, and Hib vaccines. This vaccine is approved for use in children 6 weeks to 4 years of age and administered at 2, 4, 6, and 15–18 months of age.

Dosage & Schedule of Administration

Hib vaccination is recommended for all infants in the United States. The vaccine dose is 0.5 mL given intramuscularly. Vaccines containing PRP-OMP (PedvaxHib) are given at 2, 4, and 12–15 months of age; vaccines containing PRP-T (ActHib, Hiberix, Pentacel) are given at 2, 4, 6, and 12–15 months of age. The recommended interval between doses in the primary series is 8 weeks, but a minimal interval of 4 weeks is permitted. For infants who missed the primary vaccination series, a catch-up schedule is used (see Table 10–3). Hib vaccine is not generally recommended for children 5 years of age or older.

Contraindications & Precautions

Hib vaccine should not be given to anyone who has had a severe allergic reaction to a prior Hib vaccine dose or to any vaccine components. Hib vaccine should not be given to infants before 6 weeks of age.

Adverse Effects

Adverse reactions following Hib vaccination are uncommon. Between 5% and 30% of vaccine recipients experience swelling, redness, or pain at the vaccination site. Systemic reactions such as fever and irritability are rare.

PNEUMOCOCCAL VACCINATION

Before the routine use of pneumococcal conjugate vaccines in infants, Streptococcus pneumoniae (pneumococcus) was the leading cause of invasive bacterial disease in children. Pneumococcus remains a leading cause of febrile bacteremia, bacterial sepsis, meningitis, and pneumonia in children and adults in the United States and worldwide. It is also a common cause of otitis media and sinusitis. Over 90 different serotypes of pneumococcus have been identified, and immunity to the capsular polysaccharide antigen of one serotype does not confer immunity to other serotypes.

A conjugate vaccine against a seven-valent pneumococcal conjugate vaccine (PCV7) was first licensed in the United States in 2000. Routine use of PCV7 led to a dramatic decrease in pneumococcal disease overall, however, disease caused by pneumococcal serotypes not included in PCV7 increased. In 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) was licensed for use in the United States. This vaccine contains the serotypes in PCV7 and an additional six pneumococcal serotypes, with the capsular polysaccharide antigens of each serotype individually conjugated to a nontoxic diphtheria cross-reactive material (CRM) carrier protein.

A 23-valent pneumococcal nonconjugated polysaccharide vaccine (PPSV23) is available in the United States, but its use in children is limited to those with certain chronic medical conditions. PPSV23 protects against 23 serotypes and provides protection against the approximately 25% of pneumococcal infections not prevented by PCV13. However, it does not produce a long-lasting immune response and does not reduce nasopharyngeal carriage. While all children and adults are at risk of pneumococcal disease, certain children are at particularly high risk and need enhanced protection against pneumococcal disease including the use of PPSV23 (Table 10–6).

Since the introduction of PCV13, the incidence of invasive pneumococcal disease has decreased dramatically among children younger than 5 years and decreased by more than 50% among older adults, largely due to indirect effects of vaccination among children.

Vaccines Available

1. PCV13 (Prevnar13, Pfizer), for use in children 6 weeks of age and older and for adults.

2. PPSV23 (Pneumovax23, Merck), for use in children 2 years of age and older and for adults.

Dosage & Schedule of Administration

PCV13 is given as a 0.5-mL intramuscular dose. PPSV23 is given as a 0.5-mL dose by either the intramuscular or subcutaneous route.

PCV13 is routinely recommended for infants at 2, 4, 6, and 12–15 months of age. For healthy children 24–59 months of age, if they are unvaccinated or did not complete the four-dose PCV13 series, they should receive a single dose of PCV13. Children 24–59 months of age and at high risk of pneumococcal disease (see Table 10–6) should receive two doses of PCV13 (if they previously received fewer than three doses) or one dose of PCV13 (if they previously received three doses). Higher-risk children 24–59 months of age should also receive a dose of PPSV23, at least 8 weeks after their final dose of PCV13. If not previously vaccinated against pneumococcus, higher-risk children 6–18 years of age should receive one dose of PCV13, followed at least 8 weeks later by PPSV23, with PPSV23 repeated 5 years later. Updated and detailed schedule information is available at the CDC (at http://www.cdc.gov/vaccines) and the Immunization Action Coalition (at www.immunize.org).

The rationale for using both PCV13 and PPSV23 in some high-risk children is that while PPSV23 is less immunogenic than PCV13, PPSV23 covers additional serotypes that may cause disease. Table 10–6 also includes the indications for revaccination with PPSV23.

Contraindications & Precautions

For both PCV13 and PPSV23, vaccination is contraindicated in individuals who suffered a severe allergic reaction such as anaphylaxis after a previous vaccine dose or to a vaccine component. PCV13 and PPV23 vaccination should be deferred during moderate or severe acute illness, with or without fever.

Adverse Effects

The most common adverse effects associated with PCV13 administration are fever, injection site reactions, irritability, and increased or decreased sleep. Although not definitely proven, PCV13 administered simultaneously with inactivated influenza vaccine may lead to a small increased risk of febrile seizures. With PPSV23, 30%–50% of vaccine recipients develop pain and redness at the injection site. Fewer than 1% develop systemic side effects such as fever and myalgia. Anaphylaxis is rare. PPSV23 appears to be safe and immunogenic during pregnancy, although safety data are lacking regarding vaccination during the first trimester of pregnancy.

POLIOMYELITIS VACCINATION

Polioviruses are highly infectious, spread primarily by fecal-oral and oral-oral routes, and cause acute flaccid paralysis via destruction of motor neurons. There are three polio serotypes; immunity to one serotype does not confer immunity to the others. Poliomyelitis can be prevented by vaccination. Type 2 poliovirus was declared eradicated in 2015, and type 3 poliovirus was last detected in 2012. While the goal of polio eradication has not yet been achieved, the global incidence of polio has decreased from roughly 350,000 cases annually in the prevaccination era, to 33 polio cases detected in 2018. Polio remains endemic in Afghanistan, Nigeria, and Pakistan.

Although extraordinary progress has been made toward the goal of global polio eradication, complex challenges remain. Armed conflict and civil strife continue to impede access to vulnerable populations, and vaccinators have been the target of violence. Also, the attenuated vaccine strains used in trivalent OPV can rarely mutate into pathogenic strains and cause polio disease. To address this issue, while maintaining population immunity to all three poliovirus strains, several steps have been necessary: (1) introduction of IPV into all countries using OPV; (2) switch from trivalent OPV to a more immunogenic bivalent form of OPV; and (3) eventually stopping routine use of OPV altogether. This massive global public health transition occurred during 2015 and 2016 and has largely been successful. However, an IPV vaccine shortage resulted, and strategies are in place to prioritize IPV use and significantly increase vaccine production. Despite setbacks, a polio-free world is achievable. Timely updates on the worldwide polio eradication program can be found at www.polioeradication.org.

IPV, a trivalent inactivated vaccine, is the only vaccine against poliomyelitis available in the United States. IPV cannot cause polio.

Vaccines Available

1. IPV (IPOL, Sanofi) is given intramuscularly or subcutaneously.

2. DTaP-HepB-IPV (Pediarix, GlaxoSmithKline) contains DTaP, HepB, and IPV vaccines. Approved for use at 2, 4, and 6 months of age; not approved for use at 4–6 years of age as the final booster dose of IPV; given intramuscularly.

3. DTaP-IPV-Hib (Pentacel, Sanofi) contains DTaP, IPV, and Hib vaccines. Approved for use at 2, 4, 6, and 15–18 months of age; not approved for use at 4–6 years of age as the final booster dose of IPV; given intramuscularly.

4. DTaP-IPV-Hib-HepB (Vaxelis, Merck) contains DTaP, IPV, Hib, and HepB vaccines. Approved for use as a three-dose series at 2, 4, and 6 months of age; not approved for use at 4–6 years of age as the final booster dose of IPV; given intramuscularly (not available until at least 2021).

5. DTaP-IPV (Kinrix, GlaxoSmithKline) contains DTaP and IPV vaccines. Licensed for children 4–6 years of age, for use as a final booster dose of IPV; given intramuscularly.

Dosage & Schedule of Administration

In the United States, all children without contraindications should receive an IPV-containing vaccine at 2, 4, 6–18 months, and 4–6 years of age. A dose of IPV should be given at 4 years of age or older, regardless of the number of prior doses of IPV. Completely immunized adult visitors to areas of continuing wild-type poliovirus circulation should receive a booster dose of IPV. Unimmunized or incompletely immunized adults and children should receive two (preferably three) doses of IPV prior to travel.

Contraindications & Precautions

IPV vaccination is contraindicated in individuals who suffered a severe allergic reaction such as anaphylaxis after a previous vaccine dose or to a vaccine component. IPV vaccination should be deferred during moderate or severe acute illness with or without fever. Pregnancy is also a precaution to IPV vaccination. Receipt of previous doses of OPV is not a contraindication to IPV.

Adverse Effects

Minor local reactions, such as pain or redness at the injection site, may occur following IPV vaccination. No serious adverse reactions following IPV vaccination have been described.

INFLUENZA VACCINATION

Influenza occurs each winter-early spring period, often associated with significant morbidity and mortality in certain high-risk persons. Since 2010, CDC estimates that between 140,000 and 960,000 hospitalizations and up to 36,000 deaths per year in the United States are attributable to influenza, and global epidemics (pandemics) can occur. The recent pandemic H1N1 strain is now incorporated into the seasonal vaccine. Each year, recommendations are formulated in the spring regarding the constituents of influenza vaccine for the coming season. Influenza vaccines contain either three strains (two influenza A strains and one of two influenza B lineages), or all four strains, including two influenza A and two influenza B lineages. It is difficult to predict which influenza B lineages (or both) will predominate in any given influenza season. Children at high risk of seasonal influenza-related complications include those with hemoglobinopathies or with chronic cardiac, pulmonary (including asthma), metabolic, renal, and immunosuppressive diseases (including immunosuppression caused by medications or by HIV); and those with any condition (eg, cognitive dysfunction, spinal cord injuries, seizure disorders, or other neuromuscular disorders) that can compromise respiratory function or the handling of respiratory secretions, or that can increase the risk of aspiration. Children and adolescents receiving long-term aspirin therapy are also at risk of influenza-related Reye syndrome. Healthy children aged 6–23 months are at substantially increased risk of influenza-related hospitalizations, and children aged 24–59 months (ie, 2–4 years) remain at increased risk of influenza-related clinic and emergency department visits and hospitalizations, but less so than younger children.

Annual influenza vaccination is routinely recommended for all persons older than 6 months. Physicians should identify high-risk children in their practices and encourage parents to seek influenza vaccination for their children and themselves as soon as influenza vaccine is available. Influenza prevention will help prevent lower respiratory tract disease or other secondary complications in high-risk groups, thereby decreasing hospitalizations and deaths.

Vaccines Available

Most inactivated influenza vaccine virus is grown in eggs, formalin inactivated, and may contain trace quantities of thimerosal as a preservative. Only split-virus or purified viral antigens are available in the United States. Fluzone (Sanofi), Afluria (Seqirus), Fluarix (GlaxoSmithKline), and FluLaval (Biomedical Corp of Quebec) are approved for children 6 months and older. A cell-culture–based vaccine Flucelvax (Seqirus) is approved for children 4 years and older. There are a number of additional influenza vaccines licensed for adults but not for children, including a high-dose vaccine for older adults, and a recombinant vaccine. Intranasal live attenuated influenza vaccine (LAIV [FluMist, AstraZeneca) is approved for healthy children and adults aged 2 through 49 years.

Dosage & Schedule of Administration

A. Inactivated Influenza Virus Vaccine (IIV)

Because influenza can circulate from November through early March in the US states, the optimal time to initiate vaccination is as soon as vaccine is available in the early fall. However, providers should continue vaccinating individuals as long as vaccine is available, and there is influenza activity in the community. Children younger than age 6 months should not be immunized. Two doses are recommended for children younger than 9 years who did not receive two vaccine doses in the past. Older children receiving vaccine for the first time require only a single dose. The dose for all children is 0.5 mL given intramuscularly. Pregnancy is not a contraindication to use of inactivated vaccine, which is recommended for all pregnant women and those contemplating pregnancy during the influenza season as complications from influenza infection are greatly increased in the third trimester and up to 2 weeks postpartum. Simultaneous administration with other routine vaccines is acceptable.

B. Live Attenuated Influenza Virus Vaccine (LAIV)

The vaccine is supplied in a prefilled single-use sprayer containing 0.2 mL of the vaccine, approximately half of which is sprayed into each nostril. A dose divider clip is provided to assist in dividing the dose. If the patient sneezes during administration, the dose should not be repeated. It can be administered to children with minor illnesses but should not be given if significant nasal congestion is present. Because it is a live vaccine, it should be administered 48 hours after cessation of therapy in children receiving anti-influenza antiviral drugs, and these should not be given for 2 weeks after vaccination. Two doses are recommended for children younger than 9 years who did not receive two vaccine doses in the past. One dose is recommended for individuals 9–49 years of age.

Contraindications & Precautions

A. Inactivated Influenza Virus Vaccine

Inactivated influenza vaccine is contraindicated in individuals with a severe allergic reaction, such as anaphylaxis, to a previous dose of an inactivated influenza vaccine component. However, guidelines for influenza vaccination in children with egg allergies have recently changed. Children with only urticaria following exposure to egg can be vaccinated. Children with more serious allergic reactions to egg, such as angioedema, respiratory symptoms, or anaphylaxis, may be eligible for inactivated influenza vaccine but should be referred to an allergist for an assessment of vaccination risk and should receive vaccine in an inpatient or outpatient medical setting and by a health care provider who is able to recognize and manage severe allergic conditions.

B. Live Attenuated Influenza Virus Vaccine

LAIV is contraindicated in individuals with a history of severe allergic reaction to any component of the vaccine or to a previous dose of any influenza vaccine, with egg allergy, and in children and adolescents receiving concomitant aspirin or aspirin-containing therapy. LAIV should not be administered to the following persons: (1) children younger than 24 months, because of an increased risk of hospitalization and wheezing that was observed in clinical trials; (2) individuals with asthma or children younger than 5 years with recurrent wheezing unless the potential benefit outweighs the potential risk; (3) pregnant women; (4) and individuals with known or suspected immunodeficiency diseases or immunosuppressed states.

All health care workers, including those with asthma and other underlying health conditions, can administer LAIV. Health care workers who are vaccinated with LAIV can safely provide care to patients within a hospital or clinic, except for severely immunosuppressed patients that require a protected environment (ie, bone marrow transplant patients). In this instance, there should be a 7-day interval between receiving LAIV and care for these patients.

Adverse Effects

A. Inactivated Influenza Virus Vaccine

Injection site reactions are the most common adverse events after inactivated influenza vaccine administration. A small proportion of children will experience some systemic toxicity, consisting of fever, malaise, and myalgias. These symptoms generally begin 6–12 hours after vaccination and may last 24–48 hours. Cases of Guillain-Barré syndrome followed the swine influenza vaccination program in 1976–1977, but careful study by the Institute of Medicine showed no association with that vaccine in children and young adults—nor in any age group that received vaccines in subsequent years.

B. Live Attenuated Influenza Virus Vaccine

The most common adverse reactions include runny nose or nasal congestion in all ages and fever higher than 37.7°C in children 2–6 years of age. These reactions occurred more with the first dose and were self limited.

MEASLES, MUMPS, & RUBELLA VACCINATION

Due to an effective vaccination program beginning in 1963, measles was declared eliminated from the United States in 2000. Until 2008, there were sporadic importations of measles from countries with lower vaccination rates, but since then there have been numerous outbreaks of measles, primarily from viral transmission within the United States after initial exposure to imported cases. In 2018–2019, there were numerous outbreaks of measles across the United States, primarily in insular communities, resulting in over 1000 cases in the first half of 2019, the most cases in the United States in any year since 1992. The largest of these outbreaks occurred in New York State in orthodox Jewish communities. In outbreaks such as these, the majority of people who developed measles were unvaccinated.

In the United States, after adding mumps vaccine to the childhood schedule in 1977, there was a 99% decline in mumps to fewer than 300 cases each year between 2001 and 2003. However, since then, there have been several large outbreaks, particularly in 2016–2017 when there were over 9000 cases. University outbreaks accounted for half of all outbreaks and 40% of total mumps cases. Many of these outbreaks were in populations who had a high proportion of individuals fully vaccinated with two doses of MMR vaccine. As a result of these large outbreaks, in 2017 ACIP recommended a third dose of a mumps-containing vaccine in persons previously vaccinated with two doses of a mumps-containing vaccine who are identified by public health as at increased risk for mumps because of an outbreak.

The rubella vaccine is primarily intended to prevent the serious consequences of rubella infection in pregnant women: miscarriage, fetal demise, and congenital rubella syndrome. In the United States and elsewhere, the approach has been to vaccinate young children. Over time, this approach has led to most women being rubella immune by the time they reach child-bearing age; herd immunity also reduces transmission to susceptible women. With the use of rubella vaccines, rubella and congenital rubella syndrome were declared eliminated in the United States in 2004. There are now fewer than 10 rubella cases per year, and all recent cases were infected while living or traveling outside the country. There were only four cases of congenital rubella syndrome in the United States between 2010 and 2015.

Despite many reports in the lay press and on the Internet of a link between MMR and autism, there is overwhelming scientific evidence that there is no causal association between the two. There is also no evidence that separation of MMR into its individual component vaccines lessens the risk of any vaccine adverse event, and such practice is not recommended.

Vaccines Available

1. Measles-mumps-rubella (MMR II, Merck): MMR II is a lyophilized preparation of measles, mumps, and rubella vaccines. The measles and mumps portions are prepared using chick embryo tissue cultures, and rubella is grown in human diploid cells. There is no adjuvant and no preservative. It contains small amounts of gelatin, sorbitol, and neomycin. The individual components of MMR II are no longer available.

2. MMRV: A combined live attenuated measles, mumps, rubella, and varicella vaccine (ProQuad, Merck) is licensed for use in children 1–12 years of age. The measles, mumps, and rubella components are identical to MMR II. The varicella component has a higher varicella-zoster virus titer than the varicella-only (VAR) vaccine.

Dosage & Schedule of Administration

A. Routine Vaccination

Measles, mumps, and rubella vaccinations should be given as MMR or MMRV at 12–15 months and again at 4–6 years of age. Both MMR and MMRV can cause febrile seizures, although uncommonly. Because febrile seizures following MMRV occur at a rate twice that of MMR at the younger age, the ACIP recommends that after a discussion of the benefits and risks of both vaccination options with the parents or caregivers, either MMR or MMRV may be given at 12–15 months of age. MMRV is the preferred vaccine at 4–6 years of age if available; no excess risk of febrile seizures following MMRV vaccination has been observed at 4–6 years of age. A personal or family history of febrile seizures in an infant is considered a precaution for the use of MMRV, and MMR and VAR given separately are preferred. A dose of 0.5 mL should be given subcutaneously. The second dose of MMR or MMRV is recommended at school entry to help prevent school-based measles and mumps outbreaks. Children not reimmunized at school entry should receive their second dose by age 11–12 years. If an infant receives MMR before 12 months of age (such as for travel), two additional doses are required to complete the series, the first after 12 months of age and the second at least 1 month later. Ig interferes with the immune response to the attenuated vaccine strains of MMR and MMRV. Therefore, MMR and MMRV immunization should be deferred by 3–11 months after Ig administration, depending on the type of Ig product received. Consult the AAP’s Red Book for specific recommendations.

For measles, mumps, and rubella, most persons can be considered immune if they were fully vaccinated at appropriate intervals, or were born before 1957, or if there is laboratory evidence of serologic immunity or disease. However, special considerations apply to health care workers: for those born before 1957, laboratory confirmation of immunity or disease should be performed, and nonimmune health care workers should be vaccinated. A clinical diagnosis of any of these diseases is not acceptable evidence of immunity. For rubella, susceptible pubertal girls and postpubertal women identified by prenatal screening should be immunized after delivery. Whenever rubella vaccination is offered to a woman of childbearing age, pregnancy should be ruled out and the woman advised to prevent conception for 3 months following vaccination. If a pregnant woman is vaccinated or becomes pregnant within 3 weeks of vaccination, she should be counseled regarding the risk to her fetus, although no cases of rubella-vaccine–related fetal anomalies have been reported. The risk of congenital rubella syndrome after wild-type maternal infection in the first trimester of pregnancy is 20%–85%. All susceptible adults in institutional settings (including colleges), day care center personnel, military personnel, and hospital and health care personnel should be immunized.

B. Vaccination of Travelers

People traveling abroad should be immune to measles, mumps, and rubella. Infants 6–11 months of age traveling to high-risk areas should receive one dose of MMR prior to travel followed by either MMR or MMRV at 12–15 months of age (given at least 4 weeks after the initial dose) and either MMR or MMRV at 4–6 years of age to complete the series. Children over 12 months of age who are traveling to high-risk areas should receive two doses separated by at least 4 weeks. Children traveling internationally to lower-risk areas should be immunized as soon as possible after their first birthday and complete the series at 4–6 years of age in the usual fashion.

C. Revaccination Under Other Circumstances

Persons entering college and other institutions for education beyond high school, medical personnel beginning employment, and persons traveling abroad should have documentation of immunity to measles and mumps, defined as receipt of two doses of measles vaccine after their first birthday, birth before 1957, or a laboratory documented measles or mumps history.

D. Outbreak Control of Measles

A community outbreak is defined as a single documented case of measles. Control depends on immediate protection of all susceptible persons (defined as persons who have no documented immunity to measles in the affected community). In the case of unvaccinated individuals, the following recommendations hold: (1) age 6–11 months, give MMR if cases are occurring in children younger than 1 year, followed by a dose of MMR or MMRV at age 12–15 months and again at age 4–6 years; and (2) age 12 months or older, give MMR or MMRV followed by revaccination at age 4–6 years. A child with an unclear or unknown vaccination history should be reimmunized with MMR or MMRV. Anyone with a known exposure who is not certain of having previously received two doses of MMR should receive an additional dose. Unimmunized persons who are not immunized within 72 hours of exposure, which is the acceptable interval for active postexposure prophylaxis, should be excluded from contact with potentially infected persons until at least 2 weeks after the onset of rash of the last case of measles.

E. Outbreak Control of Mumps

Persons previously vaccinated with two doses of a mumps-containing vaccine who are identified by public health as at increased risk for mumps because of an outbreak should receive a third dose of a mumps-containing vaccine to improve protection against mumps disease and related complications.

Contraindications & Precautions

MMR and MMRV vaccines are contraindicated in pregnant women, women intending to become pregnant within the next 28 days, immunocompromised persons, and persons with an anaphylactic reaction to a prior dose or vaccine component. It is also contraindicated in children receiving high-dose corticosteroid therapy (≥ 2 mg/kg/day, or 20 mg/day total, for longer than 14 days) with the exception of those receiving physiologic replacement doses. In these patients, an interval of 1 month between cessation of steroid therapy and vaccination is sufficient. Leukemic patients who have been in remission and off chemotherapy for at least 3 months can receive MMR and MMRV safely. Persons with HIV infection should receive two doses of MMR vaccine according to the recommended schedule if they do not have evidence of current severe immunosuppression (for persons aged ≤ 5 years, they must have CD4 percentages ≥ 15% for ≥ 6 months; and for persons aged > 5 years, they must have CD4 percentages ≥ 15% and CD4 ≥ 200 lymphocytes/mm³ for ≥ 6 months). MMRV is contraindicated in HIV-positive individuals. Children with minor acute illnesses (including febrile illnesses), egg allergy, or a history of tuberculosis should be immunized. MMR and MMRV may be safely administered simultaneously with other routine pediatric immunizations.

Adverse Effects

Between 5% and 15% of individuals receiving MMR become febrile to 39.5°C or higher about 6–12 days following vaccination, lasting approximately 1–2 days, and 5% may develop a transient morbilliform rash. MMR and MMRV vaccines can cause febrile seizures, typically 8–14 days after vaccination; these febrile seizures have not been associated with any long-term complications. Other serious adverse events following vaccination are rare and include anaphylaxis, transient thrombocytopenia (1 per 40,000 vaccine recipients), and arthralgias (more common in adults than children).

Antibody Preparations Against Measles

Ig is effective at preventing measles, if given to a nonimmune person within 6 days of exposure to measles. However, the immunity conferred by Ig should be considered temporary. Infants younger than 12 months who have been exposed to measles should receive 0.5 mL/kg of Ig, given intramuscularly. MMR vaccine should also be used, as appropriate, for infants aged 6–11 months. Pregnant women without evidence of measles immunity and severely immune-compromised persons (regardless of evidence of measles immunity) who are exposed to measles should receive 400 mg/kg of Ig given intravenously. Ig given intramuscularly (0.5 mL/kg, maximum dose, 15 mL) may be given to more immune-competent exposed persons without evidence of immunity, with priority for those with the most intense contact with a case.

VARICELLA VACCINATION

Prior to the availability of vaccine, about 4 million cases of varicella-zoster virus (VZV) infection occurred as chickenpox annually in the United States, mostly in children younger than 10 years. This resulted in 11,000 hospitalizations and 100 deaths per year due to severe complications such as secondary bacterial infections, pneumonia, encephalitis, hepatitis, and Reye syndrome.

A live, attenuated varicella vaccine (VAR) was licensed in the United States in 1995, and routine immunization of children 12 months of age and older was instituted. The vaccine is almost 100% effective at preventing severe disease. The incidence, morbidity, mortality, and medical costs associated with varicella infection have significantly declined since VAR was licensed. Vaccination prevents an estimated 3.5 million cases of varicella, 9000 hospitalizations, and 100 deaths in the United States each year. Once the routine use of VAR was achieved, it became apparent that there is “breakthrough” (usually very mild) varicella occurring in about 15% of immunized patients. Outbreaks of wild-type infectious VZV were reported in schools with high one-dose VAR vaccination coverage (96%–100%). Varicella attack rates among these children varied between 11% and 17%, and thus it was concluded that a single VAR dose could not prevent endemic varicella.

A second dose of VAR in children, when given 3 months or 4–6 years after the initial dose, greatly increased the magnitude of the anti-VZV antibody response, which is a correlate of vaccine efficacy. A combination MMRV vaccine has also been shown to be immunologically noninferior to the MMR and VAR components administered separately. MMRV is effective as primary immunization or as a booster administered to children age 4–6 years. The two-dose regimen is almost 100% effective against severe varicella, and the risk of breakthrough varicella is threefold less than the risk with a one-dose regimen. Therefore, ACIP and the AAP recommend two doses of VAR for children older than 12 month and for adolescents and adults without evidence of immunity.

The vaccine is also effective in preventing or modifying VZV severity in susceptible individuals exposed to VZV if used within 3 days (and possibly up to 5 days) of exposure, with an efficacy of 95% for preventing any postexposure disease and 100% for preventing moderate or severe disease. There is no evidence that postexposure prophylaxis increases the risk of vaccine-related adverse events or interferes with development of immunity.

Vaccines Available

1. A cell-free preparation of Oka strain VZV is produced and marketed in the United States as Varivax (Merck). Each dose of VAR contains not less than 1350 plaque-forming units of VZV and trace amounts of neomycin, fetal bovine serum, and gelatin. There is no preservative.

2. MMRV (measles-mumps-rubella-varicella, ProQuad, Merck) is licensed for use in children 1–12 years of age. MMRV is well tolerated and provides adequate immune response to all of the antigens it contains. In MMRV, the varicella component is present in higher titer than in VAR. Concomitant administration of MMRV with DTaP, Hib, and HepB vaccines is acceptable.

Dosage & Schedule of Administration

Two doses (0.5 mL) of VAR are recommended for immunization of healthy children aged 12 months and older, and for adolescents and adults without evidence of immunity. For children aged 12 months to 12 years, the immunization interval is at least 3 months, and for persons 13 years or older, it is 4 weeks. MMRV is approved only for healthy children aged 12 months to 12 years. A second dose of catch-up vaccination is required for children, adolescents, and adults who previously received one dose of VAR vaccine. All children should have received two doses of VAR before prekindergarten or school. HIV-infected children (≥ 15% CD4⁺ cells) should receive two doses of the single-antigen vaccine (with a least a 3-month interval between doses).

VAR may be given simultaneously with MMR at separate sites. If not given simultaneously, the interval between administration of VAR and MMR must be greater than 28 days. Simultaneous VAR administration does not appear to affect the immune response to other childhood vaccines. VAR should be delayed 5 months after receiving intravenous immune globulin, blood, or plasma. In addition, persons who received VAR should not be administered an antibody-containing product for at least 2 weeks or an antiviral medication active against varicella for at least 3 weeks. If this occurs, the individual may need to be tested for immunity or revaccinated. After a discussion of the benefits and risks of both vaccination options with the parents or caregivers (see section “Adverse Effects”), either MMR or MMRV may be given at 12–15 months. MMRV is the preferred vaccine if available at 4–6 years of age.

Contraindications & Precautions

Contraindications to VAR vaccination include a severe allergic reaction after a previous vaccine dose or to a vaccine component. Because VAR and MMRV are live-virus vaccines, they are also contraindicated in children who have acquired treatment-related cellular immunodeficiencies or congenital T-cell abnormalities. The exception to this rule is the recommendation that VAR be administered to HIV-infected children who are not severely immunosuppressed. Household contacts of immunodeficient patients should be immunized. VAR should not be given to pregnant women; however, the presence of a pregnant mother in the household is not a contraindication to immunization of a child within that household. A personal or family history of febrile seizures in an infant is considered a precaution for the use of MMRV; administration of MMR and VAR separately is preferred for the first dose.

Adverse Events

The most commonly recognized adverse reactions, occurring in approximately 20% of vaccines, are minor injection site reactions. Additionally, 3%–5% of patients will develop a rash at the injection site, and an additional 3%–5% will develop a sparse varicelliform rash outside of the injection site. These rashes typically consist of two to five lesions and may appear 5–26 days after immunization. The two-dose vaccine regimen is generally well tolerated with a safety profile comparable to that of the one-dose regimen. The incidence of fever and varicelliform rash is lower after the second dose than the first. Although VAR is contraindicated in pregnancy, there have been hundreds of inadvertent administrations of vaccine to pregnant women tracked by the “Pregnancy Registry for Varivax” with no known cases of congenital varicella syndrome or increases in fetal abnormalities.

Studies comparing MMRV to MMR and VAR administered concomitantly showed more systemic adverse events following MMRV (fever 21.5% vs 14.9% and measles-like rash 3% vs 2.1%, respectively). The risk of febrile seizures in children 12–23 months old with the MMRV preparation is twice that of MMR and VAR given separately, resulting in one additional febrile seizure per 2300–2600 children vaccinated with MMRV.

Transmission of vaccine virus from healthy vaccines to other healthy persons is very rare; has never been documented in the absence of a rash in the index case; and has only resulted in mild disease. Herpes zoster infection occurs in recipients of VAR in immunocompetent and immunocompromised persons within 25–722 days after immunization. Many of these cases were found to be caused by unappreciated latent wild-type virus. Vaccine-strain varicella does cause herpes zoster in children, but the age-specific risk of herpes zoster infection is much lower in children following VAR immunization than after natural infection, and it also tends to be milder.

Antibody Preparations

In the event of an exposure to varicella, there are currently two antibody preparations potentially available in the United States for postexposure prophylaxis, VariZIG (Cangene Corporation) and intravenous Ig. Exposure is defined as a household contact or playmate contact (> 1 h/day), hospital contact (in the same or contiguous room or ward) or intimate contact with a person with herpes zoster deemed contagious. Susceptibility is defined as the absence of a reliable history of varicella or varicella vaccination. Uncertainty in this designation can be resolved with an appropriate test for anti-VZV antibody. Passive postexposure prophylaxis is indicated for neonates, pregnant women, and immunocompromised patients, including those with cancer or taking immunosuppressive therapies.

VariZIG should be administered as soon as possible after exposure, ideally within 96 hours, but may be given within 10 days postexposure. If VariZIG is not available, it is recommended that intravenous Ig be used in its place. The dose is 400 mg/kg administered once. A subsequent exposure does not require additional prophylaxis if this occurs within 3 weeks of intravenous Ig administration.

HEPATITIS A VACCINATION

The incidence of hepatitis A in the United States had decreased dramatically from an average of 28,000 cases annually in the years prior to availability of a HepA vaccine to 1390 cases reported in 2015. However, more recently hepatitis A incidence has increased to over 11,000 cases reported in 2018 in part related to outbreaks among persons who report drug use or homelessness.

Initial vaccination recommendations for hepatitis A targeted high-risk individuals, primarily adults. However, children, who are more likely than adults to be asymptomatic while infected, usually contribute to the spread of hepatitis A through households and communities. Therefore, since 2006 HepA vaccination has been routinely recommended for children 12–23 months of age. As a consequence of vaccination, the epidemiology of hepatitis A infection has changed such that most cases now occur in adults, often related to travel or contaminated food.

In addition to routine immunization of all children 12–23 months of age, HepA vaccination is indicated for the following groups: (1) travelers to countries with moderate to high rates of hepatitis A, (2) children with chronic liver disease, (3) children with clotting factor disorders, (4) adolescent and adult males who have sex with men, (5) persons with an occupational exposure to hepatitis A, (6) persons reporting drug use, and (7) all previously unvaccinated persons who anticipate close personal contact with an international adoptee from countries with moderate to high rates of hepatitis A. Vaccination should also be considered in previously unimmunized children 2–18 years old, even if none of the above risk factors are present.

HepA vaccines are all inactivated and included two single-antigen vaccines and one combination vaccine.

Vaccines Available

1. HepA (Havrix, GlaxoSmithKline), for use in children 12 months of age and older, and adults.

2. HepA (Vaqta, Merck), for use in children 12 months of age and older, and adults.

3. HepA-HepB (Twinrix, GlaxoSmithKline) contains HepA and HepB vaccines. Approved for use in adults 18 years of age and older.

Dosage & Schedule of Administration

The two HepA vaccines given in childhood (Havrix and Vaqta) are given as a two-dose series. The first dose is recommended at 12–23 months of age; the second dose is recommended 6–18 months later. For individuals 12 months through 18 years of age, these vaccines are administered intramuscularly in a dose of 0.5 mL. Adults 19 years of age and older can receive Havrix (two doses of 1.0 mL each, separated by at least 6 months), Vaqta (two doses of 1.0 mL each, separated by at least 6 months), or Twinrix (for adults 18 years and older, 1.0 mL per dose, in a three-dose series). If needed, such as for imminent travel, Twinrix can be given on an accelerated four-dose schedule, with doses on days 1, 7, and 21–30, with a booster dose given 12 months after the first dose.

Contraindications & Precautions

HepA vaccine should not be given to anyone with a prior severe allergic reaction, such as anaphylaxis, after a previous vaccine dose or to a vaccine component. Precautions to vaccination include pregnancy and moderate or severe acute illness.

Adverse Effects

Adverse reactions, which are uncommon and mild, consist of pain, swelling, and induration at the injection site, headache, and loss of appetite. There have been no reports of serious adverse events attributed definitively to HepA vaccine.

Postexposure Prophylaxis

Postexposure prophylaxis is recommended for household or sexual contacts of persons with serologically confirmed hepatitis A, and for day care staff and attendees in outbreak situations. Postexposure prophylaxis may also be recommended in food-borne outbreaks, depending on the extent and timing of exposure. Postexposure prophylaxis of unimmunized persons should consist of either a single dose of HepA vaccine or Ig (0.1 mL/kg), given as soon as possible after exposure. The efficacy of Ig when given more than 2 weeks after exposure has not been established. For healthy people 12 months through 40 years of age who have not previously completed the two-dose vaccine series, HepA vaccine should be given. For those older than 40 years, Ig may be given in addition to HepA vaccine if there was a high-risk exposure or high risk of complications related to HepA infection. Ig should also be used for children younger than 12 months, immunocompromised persons, those with chronic liver disease, and anyone for whom vaccination is contraindicated. If HepA vaccine and Ig are given at the same time, the vaccine and Ig should be administered at different injection sites.

Preexposure Prophylaxis

Children aged 6–11 months should receive HepA vaccine for preexposure prophylaxis prior to travel and then receive two additional doses on the age-appropriate schedule. Ig is indicated as preexposure prophylaxis in children younger than 6 months at increased risk of hepatitis A infection (eg, those traveling to endemic areas or those with clotting factor disorders) and for travelers > 6 months of age for whom vaccination is contraindicated. Recommended IgIM dosages are 0.1 mL/kg in a single intramuscular dose if the duration of exposure is up to 1 month, 0.2 mL/kg for exposure up to 2 months, and 0.2 mL/kg repeated every 2 months for exposure > 2 months.

MENINGOCOCCAL VACCINATION

Infections with Neisseria meningitidis cause significant morbidity and mortality, with approximately 350 cases occurring in the United States annually. Even with appropriate treatment, meningococcal disease has an estimated case-fatality rate of 10%–14%, and up to 19% of survivors are left with serious disabilities, including neurologic deficits, hearing loss, and loss of limbs. Six serogroups of meningococcus (A, B, C, W, X, and Y) cause nearly all serious disease worldwide; serogroups B, C, and Y predominate in the United States, while serogroups A and C cause most disease in developing countries. Serogroup B is responsible for more than 50% of cases in children younger than 1 year in the United States; it is also responsible for several recent outbreaks on college campuses.

Five different meningococcal vaccines are available in the United States. Vaccination recommendations are somewhat complex, because disease rates vary substantially by age and depending on whether a chronic condition increasing meningococcal disease risk is present. Updated vaccination recommendations are available at www.cdc.gov/vaccines/vpd/mening/.

Two quadrivalent meningococcal polysaccharide-protein conjugate vaccines are available (MCV4; tradenames Menactra and Menveo), providing protection against serogroups A, C, W, and Y. Menactra is licensed for persons 9 months through 55 years of age; Menveo is licensed for 2 months through 55 years of age. Two doses of either Menactra or Menveo are recommended for all adolescents in the United States, with a first dose at 11–12 years of age and a second dose at 16 years of age.

Two vaccines are available that protect against serogroup B disease (MenB), Bexsero and Trumenba, licensed for use at 10–25 years of age. For healthy young adults who do not have a chronic health condition predisposing to meningococcal disease, Bexsero and Trumenba are not recommended. However, these vaccines may be used with clinical discretion to reduce the risk of serogroup B meningococcal disease. These two vaccines are not interchangeable; the same vaccine product must be used for all doses in the series.

Meningococcal disease risk is significantly higher among children with certain chronic conditions, including anatomic or functional asplenia (including children: with sickle cell disease), with HIV infection, children with complement component deficiencies, being treated with complement inhibitors (eculizumab and possibly ravulizumab). In these circumstances, Menveo may be given as a four-dose series beginning at 2 months of age. Additionally, MenHibrix is a vaccine protecting against Hib as well as meningococcal serogroups C and Y, and can be given as a four-dose series beginning at 6 weeks of age. Alternatively, Menactra may be given to children with anatomic or functional asplenia, or HIV infection, beginning at 2 years of age, or to children with complement deficiencies beginning at 9 months of age.

Children with anatomic or functional asplenia are also at increased risk of meningococcal serogroup B disease and should receive Bexsero or Trumenba starting at 10 years of age. Additionally, individuals traveling abroad to areas with endemic serogroups A, C, and W meningococcal disease should be vaccinated with Menactra or Menveo. Finally, meningococcal disease outbreaks occasionally occur in the United States, and vaccination may be recommended against the serogroups causing the outbreak.

Vaccines Available

1. MCV4 (Menactra, Sanofi): A single 0.5-mL dose contains capsular polysaccharide from serogroups A, C, Y, and W conjugated to diphtheria toxoid.

2. MCV4 (Menveo, Novartis): A single 0.5-mL dose contains serogroups A, C, Y, and W capsular polysaccharide, all of which are conjugated to CRM₁₉₇, a nontoxic mutant of diphtheria toxoid.

3. Hib-MenCY-TT (MenHibrix, GlaxoSmithKline): A single 0.5-mL dose contains serogroups C and Y capsular polysaccharide conjugated to tetanus toxoid, and Hib capsular polysaccharide conjugated to tetanus toxoid.

4. MenB (Trumenba, Pfizer): A single 0.5-mL dose contains 120 mcg of recombinant lipidated factor H binding protein (fHBP) variants from N meningitidis serogroup B, 0.018 mg of polysorbate 80, and 0.25 mg of aluminum phosphate as an adjuvant.

5. MenB (Bexsero, Novartis): A single 0.5-mL dose contains 50 mcg each of recombinant N meningitidis serogroup B proteins: Neisserial adhesin A (NadA), neisserial heparin-binding antigen (NHBA), factor H–binding protein (fHbp), and 25 mcg of outer membrane vesicles (OMV).

Dosage & Schedule of Administration

MCV4 is given as an intramuscular dose of 0.5 mL. If a dose is inadvertently administered subcutaneously, it does not need to be repeated. Hib-MenCY-TT is given as an intramuscular dose of 0.5 mL; MenB as an intramuscular dose of 0.5 mL in a prefilled syringe. These vaccines can be given at the same time as other vaccines, at a different anatomic site. If a four-dose schedule of Hib-MenCY-TT is given, no additional Hib doses are needed. Protective antibody levels are typically achieved within 10 days of vaccination. The schedule of administration of MCV4 and Hib-MenCY-TT is described previously. Trumenba may be given as a three-dose series (at 0, 1–2, and 6 months) or a two-dose series (at 0 and 6 months). Bexsero is a two-dose series given at least 1 month apart. MenB should be given to persons age 10 years or older at increased risk of meningococcal disease (complement deficiencies, taking complement inhibitors, asplenia, microbiologists, or serogroup B outbreaks). MenB may also be given to healthy adolescents and young adults, but use is discretionary.

Contraindications & Precautions

MCV4 is contraindicated in anyone with a known severe allergic reaction to any component of the vaccine, including diphtheria toxoid (for MCV4) and rubber latex. Although MCV4 vaccination is not contraindicated in someone with a prior history of Guillain-Barré syndrome; providers should discuss the possible risks and benefits of vaccination in anyone with this history. MCV4 can be given to individuals who are immunosuppressed. MCV4 can be given during pregnancy if clinically indicated.

Adverse Effects

MCV4 is generally well tolerated in adolescent patients. Local vaccination reactions (redness, swelling, or induration) occur in 11%–16% of persons 11–18 years old receiving MCV4. The most common solicited complaints among children aged 2–10 years were injection site pain and irritability. More severe systemic reactions (presence of any of the following: fever of ≥ 39.5°C; headache, fatigue, malaise, chills, or arthralgias requiring bed rest; anorexia; multiple episodes of vomiting or diarrhea; rash; or seizures) occur in 4.3% of MCV4 recipients. Although cases of Guillain-Barré syndrome have been reported after MCV4, the current observed rate is above that expected in the absence of vaccination.

TETANUS-REDUCED DIPHTHERIA-ACELLULAR PERTUSSIS VACCINATION (ADOLESCENTS & ADULTS)

Pertussis causes disease in all age groups. Although the burden of disease is highest in infants younger than 12 months, pertussis incidence has been rising in children and adolescents, due in part to waning immunity after administration of acellular pertussis vaccines. Routine vaccination with tetanus-reduced dose diphtheria-acellular pertussis (Tdap) has been recommended since 2006. Adolescent, adult, and elderly immunization not only has the capacity to protect vaccine recipients from pertussis but also should limit spread of pertussis from adults to infants and decrease overall pertussis endemicity.

Vaccines Available

1. Tdap (Boostrix, GlaxoSmithKline) contains tetanus toxoid, diphtheria toxoid, and three acellular pertussis antigens (detoxified pertussis toxin [PT], filamentous hemagglutinin [FHA], and pertactin) and is licensed for use in persons aged 10 years and older; this vaccine can be used in adults and the elderly.

2. Tdap (Adacel, Sanofi) contains tetanus toxoid, diphtheria toxoid, and five acellular pertussis antigens (PT, FHA, pertactin, and fimbriae types 2 and 3) and is licensed for use in persons aged 11–64 years.

Dosage & Schedule of Administration

Adolescents 11–18 years of age should receive a 0.5-mL dose of Tdap intramuscularly in the deltoid; the preferred age for Tdap immunization is 11–12 years. Adults 19–64 years of age should receive a single dose of Tdap. Adults 65 years of age and older should receive a single dose of Tdap if they have not previously received Tdap and if they anticipate close contact with an infant younger than 12 months. Women who are pregnant should receive a Tdap booster with each pregnancy, ideally early between 27 and 36 weeks of gestation. Tdap can be administered regardless of the interval since the last tetanus- or diphtheria-toxoid–containing vaccine. Tdap and MCV4 should be administered during the same visit if both vaccines are indicated.

Contraindications & Precautions

Contraindications to Tdap include severe allergic reaction to any vaccine component and encephalopathy (eg, coma, prolonged seizures) not attributable to an identifiable cause within 7 days of administration of a vaccine with pertussis components. Precautions for Tdap administration include Guillain-Barré syndrome occurring within 6 weeks of a previous dose of a tetanus toxoid-containing vaccine, history of Arthus reaction following a previous dose of tetanus or diphtheria toxoid-containing vaccine, a progressive neurologic disorder, uncontrolled epilepsy, or progressive encephalopathy until the condition has stabilized.

Adverse Effects

Pain at the injection site was the most frequently reported local adverse event among adolescents. Headache and fatigue were the most frequently reported systemic adverse events.

HUMAN PAPILLOMAVIRUS VACCINATION

Genital human papillomavirus (HPV) is the most common sexually transmitted infection in the United States and worldwide. Most of the estimated 14 million persons newly infected every year in the United States have no symptoms. Up to 75% of new infections occur among persons 15–24 years of age. HPV infection is associated with cancers in females (cervical, vulvar, vaginal, oral, and anal) and in males (penile, anal, oral). Other HPV serotypes, distinct from those that cause cancer, cause genital warts in females and males.

A nine-valent HPV vaccine (9vHPV; tradename Gardasil 9) is currently available for use in the United States and is approved for females and males. The vaccine protects against seven cancer-causing HPV types (types 16, 18, 31, 33, 45, 52, and 58), and two genital wart-associated HPV types (types 6 and 11). Two other HPV vaccines licensed in the United States, including a bivalent vaccine (tradename Cervarix) and a quadrivalent vaccine (Gardasil), are no longer distributed in the United States.

Routine HPV vaccination is recommended by ACIP for females and males aged 11–12 years and may be given as early as age 9 years. Because there is some evidence of increased uptake when introduced at a younger age, the AAP recommends starting the series between the ages of 9 and 12, at an age that the provider deems optimal for acceptance and completion of the vaccination series. Catch-up vaccination is recommended for females and males aged 13–26 years who were not previously vaccinated or have not completed the full vaccine series. While not universally recommended, vaccination of adults 27–45 years of age not previously vaccinated can be considered. Females who test positive for a high-risk HPV type, have an abnormal Pap test, or may have been exposed to HPV are still likely to benefit from HPV vaccination through prevention of other HPV types.

More than 10 years has passed since HPV vaccines were licensed. In that time, substantial population-level positive health impacts have been observed, with large reductions in HPV infections, anogenital wart diagnoses, and cervical intraepithelial neoplasia. For example, the prevalence of types 16 and 18, the HPV types most commonly associated with cervical cancer, has fallen by more than 80% in the 5–8 years after vaccination.

Vaccines Available

1. Quadrivalent HPV vaccine (Gardasil, Merck), a nonlive vaccine; a 0.5-mL dose contains HPV-6, 11, 16, and 18 L1 proteins. This vaccine is no longer distributed in the United States.

2. Nine-valent HPV vaccine (Gardasil 9, Merck), a nonlive vaccine; a 0.5-mL dose contains HPV-6, 11, 16, 18, 31, 33, 45, 52, and 58 L1 proteins.

3. Bivalent HPV vaccine (Cervarix, GlaxoSmithKline), a nonlive vaccine is a 0.5-mL dose that contains HPV-16 and HPV-18 L1 protein and the adjuvant AS04. Licensed for use in females only. This vaccine is no longer distributed in the United States.

Dosage & Schedule of Administration

HPV vaccine is administered intramuscularly as two or three separate 0.5-mL doses depending on age at initial vaccination. For healthy adolescents initiating the series prior to their 15th birthday, two doses separated by 6–12 months are recommended (minimum interval 5 months). Three doses are recommended for those initiating vaccination on or after the 15th birthday and for persons with immunocompromising conditions. The second dose should be administered 1–2 months after the first dose and the third dose 6 months after the first dose. The minimum interval between the first and second doses is 4 weeks; the minimum recommended interval between the second and third doses of vaccine is 12 weeks. HPV vaccine may be administered with other vaccines. If the vaccine schedule is interrupted, the series need not be restarted. There is currently no recommendation for repeat vaccination with 9vHPV for persons who have completed a vaccination series with bivalent or quadrivalent HPV vaccine. Additional information on HPV vaccination recommendations can be found at: www.cdc.gov/vaccines/vpd/hpv/hcp/recommendations.html.

Contraindications & Precautions

HPV vaccine is contraindicated in persons with a history of anaphylaxis to any vaccine component. HPV vaccine is not recommended for use in pregnancy. The vaccine can be administered to persons with minor acute illnesses and to immunocompromised persons.

Adverse Effects

Injection site pain (83.9%) and mild to moderate swelling and erythema were the most common adverse events reported by vaccine recipients. Fever (10.3%), nausea (4.2%), and dizziness (2.8%) were reported as systemic adverse events. As with any vaccination, syncope can occur following HPV vaccination; adolescents should be seated or lying down during and for 15 minutes after vaccination, to prevent injuries from falls should syncope occur.

RABIES VACCINATION

After symptoms of infection develop, rabies is almost invariably fatal in humans. While sylvan animal and bat rabies in the United States is common, the incidence of human rabies is very low, with fewer than three cases per year. Although dogs represent the most important vector for human rabies worldwide, in the United States because of widespread vaccination of dogs and cats, the most common rabies virus variants responsible for human rabies are bat-related. Rabies is also common in skunks, raccoons, and foxes; it is uncommon in rodents.

Human rabies is preventable with appropriate and timely postexposure prophylaxis. Postexposure care consists of local wound care and both passive and active immunization. Immediately after an animal bite, wounds should be flushed and aggressively cleaned with soap and water. If possible, the wound should not be sutured. Passive immunization after high-risk exposure consists of the injection of human rabies immune globulin (RIg) near the wound. Active immunization is accomplished by completing a schedule of immunization with one of the two available rabies vaccines licensed in the United States. Because bites from bats are often unrecognized, prophylaxis should be considered if a bat is found indoors even if there is no history of contact, especially if found in the same room with a sleeping or unattended child or with an intoxicated or otherwise incapacitated individual.

Local public health officials should be consulted before postexposure rabies prophylaxis is started to avoid unnecessary vaccination and to assist in the proper handling of the animal (if confinement or testing of the animal is appropriate). To facilitate consultation, the health care provider should know the species of animal, its availability for testing or confinement, the nature of the attack (provoked or unprovoked), and the nature of the exposure (bite, scratch, lick, or aerosol of saliva). Rabies immunization should also be considered for some children traveling to countries where rabies is endemic.

Vaccines Available

Rabies vaccines stimulate immunity after 7–10 days, and immunity persists for 2 years or more.

1. HDCV (human diploid cell vaccine; Imovax, Sanofi)

2. PCECV (purified chick embryo cell vaccine; RabAvert, Novartis)

Dosage & Schedule of Administration

These two inactivated rabies vaccines are equally safe and effective for both preexposure and postexposure prophylaxis. For each vaccine, 1 mL is given intramuscularly in the deltoid (for adults and older children) or anterolateral thigh (for infants and young children). The volume of the dose is not reduced for children. Vaccine should not be given in the gluteal region.

Preexposure Vaccination

Preexposure rabies immunization should be considered for individuals at high risk of exposure to rabies (eg, veterinarians, animal handlers, spelunkers, and people moving to or extensively traveling in areas with endemic rabies). Three intramuscular injections of any vaccine are given on days 0, 7, and 21 or 28. Previously vaccinated individuals with potential continued exposure to rabies should have a serum sample tested for rabies antibody every 2 years to assess whether repeat vaccination is indicated.

Postexposure Prophylaxis

After an individual has possibly been exposed to rabies, decisions about whether to initiate postexposure prophylaxis need to be made urgently, in consultation with local public health officials.

1. In previously unvaccinated individuals

After prompt and thorough wound cleansing, an individual exposed to rabies should receive rabies vaccination and RIg. Vaccination is given on the day of exposure (day 0) and on days 3, 7, and 14 following exposure. Immune suppressed individuals should receive an additional dose on day 28. RIg should also be given as soon as possible after exposure, ideally on the day of exposure, in a recommended dose of 20 IU/kg. If anatomically possible, the entire dose of RIg should be infiltrated into and around the wound. Any remaining RIg should be administered intramuscularly at an anatomic site distant from the location used for rabies vaccination. If RIg was not administered when vaccination was begun, it can be administered up to 7 days after the first dose of vaccine. Postexposure failures have occurred only when some deviation from the approved protocol occurred (eg, no cleansing of the wound, less than usual amount of RIg, no RIg at the wound site, or vaccination in the gluteal area).

2. In previously vaccinated individuals

RIg should not be administered, and only two doses of vaccine on days 0 and 3 after exposure are needed.

Adverse Effects

The rabies vaccines are relatively free of serious reactions. Local reactions at the injection site such as pain, swelling, induration, or erythema range in frequency from 11% to 89% of vaccine recipients. Mild systemic reactions, such as headache, nausea, muscle aches, and dizziness, occur in 6%–55% of vaccine recipients. An immune complex-like reaction occurs in about 6% of adults 2–21 days after receiving booster doses of rabies vaccine; symptoms may include generalized urticaria, arthralgias, arthritis, and angioedema.

Travelers to countries where rabies is endemic may need immediate postexposure prophylaxis and may have to use locally available vaccines and RIg. In many developing countries, the only vaccines readily available may be nerve tissue vaccines derived from the brains of adult animals or suckling mice, and the RIg may be of equine origin. Although adverse reactions to RIg are uncommon and typically mild, the nervous tissue vaccines may induce neuroparalytic reactions in 1:200–1:8000 vaccines; this is a significant risk and is another justification for preexposure vaccination prior to travel in areas where exposure to potentially rabid animals is likely.

Antibody Preparations

In the United States, RIg is prepared from the plasma of human volunteers hyperimmunized with rabies vaccine. The recommended dose is 20 IU/kg body weight. The rabies-neutralizing antibody content is 150 IU/mL, supplied in 2- or 10-mL vials.

TYPHOID FEVER VACCINATION

Typhoid fever causes an estimated 11–21 million illnesses and over 128,000 deaths each year worldwide; in the United States an estimated 5700 cases occur (about 350 cases are reported) each year, predominantly related to international travel.

Two vaccines against Salmonella enterica typhi, the bacterium that causes typhoid fever, are available in the United States: a live attenuated vaccine given orally (Ty21a) and an inactivated vaccine composed of purified capsular polysaccharide (ViCPS) given parenterally. Both vaccines protect 50%–80% of vaccine recipients. The oral vaccine is most commonly used because of its ease of administration. However, noncompliance with the oral vaccine dosing schedule occurs frequently, and correct usage should be stressed or the parenteral ViCPS vaccine used.

Routine typhoid vaccination is recommended only for children who are traveling to typhoid-endemic areas or who reside in households with a documented typhoid carrier. Although typhoid fever occurs throughout the world, areas of highest incidence include southern Asia and sub-Saharan Africa. Travelers should be advised that because the typhoid vaccines are not fully protective, and because of the potential for other food- and waterborne illnesses, careful selection of food and drink and appropriate hygiene remain necessary when traveling internationally.

Vaccines Available

1. Parenteral inactivated ViCPS (Typhim Vi, Sanofi) is for intramuscular use in people 2 years or older.

2. Oral live attenuated Ty21a vaccine (Vivotif Berna Vaccine, Swiss Serum and Vaccine Institute) is supplied as enteric-coated capsules for use in people 6 years or older.

Dosage & Schedule of Administration

ViCPS is administered as a single intramuscular dose (0.5 mL) in the deltoid muscle, with boosters needed every 2 years if exposure continues.

The dose of the oral vaccine (Ty21a) is one capsule every other day for a total of four capsules, taken 1 hour before meals. The capsules should be kept refrigerated and taken with cool liquids. A repeat full course of four capsules is recommended every 5 years if exposure continues. Mefloquine and chloroquine may be given at the same time as the oral vaccine; however, if mefloquine is administered, immunization with Ty21a should be delayed for 24 hours. Proguanil should be administered only if 10 days have lapsed since the last dose of oral vaccine. Oral typhoid vaccine should be given more than 3 days after completing other systemic antibiotics.

Contraindications & Precautions

As with all live attenuated vaccines, Ty21a should not be given to immunocompromised patients.

Adverse Reactions

Both the oral and parenteral vaccines are well tolerated, and adverse reactions are uncommon and usually self-limited. The oral vaccine can cause gastroenteritis-like illness, fatigue, and myalgia, whereas the parenteral vaccine can cause injection site pain, abdominal pain, dizziness, and pruritus.

CHOLERA VACCINATION

Cholera is caused by toxigenic Vibrio cholera bacteria of serogroup O1 (> 99% of global cases) or O139. The illness manifests as watery diarrhea that can be severe and rapidly fatal without prompt fluid rehydration. Annually in the United States fewer than 25 cases are reported and most occur among travelers to countries where cholera is endemic or epidemic.

A single-dose, live-attenuated monovalent oral vaccine, CVD103-HgR (Vaxchora) is approved by the FDA and available in the United States for use for travelers, age 18–64 years, who are traveling to areas of the world with active cholera transmission. The vaccine has 90% efficacy against severe diarrhea at 10 days after vaccination and 80% efficacy 3 months post-vaccination. CVD103-HgR should not be given to patients who have received antibiotics within the preceding 14 days. CVD103-HgR is an oral live attenuated vaccine that can be shed in the stool and potentially transmitted to close contacts. Additional cholera vaccines are available in countries outside the United States. Vaccinated travelers should continue to utilize careful selection of food and drink and use appropriate hygiene when traveling internationally.

Vaccine Available

1. CVD 103-HgR (Vaxchora, PaxVax, Redwood City, California) is a live-attenuated monovalent oral vaccine that is FDA approved and available in the United States.

JAPANESE ENCEPHALITIS VACCINATION

Japanese encephalitis (JE) virus is a mosquito-borne flavivirus. Although most infections are asymptomatic, the disease carries high morbidity and mortality for those with neurologic involvement. It is endemic in parts of Asia, although the risk to most travelers to Asia is low. Travel to rural areas and extended travel in endemic areas may increase the risk. One safe and effective vaccine is available in the United States. Travelers to JE-endemic countries should be advised of risks of JE and the importance of measures to reduce mosquito bites. Vaccination is not recommended for short-term travelers whose visit will be restricted to urban areas or outside of a well-defined JE transmission season, but vaccination is recommended for travelers who plan to spend more than 1 month in endemic areas during the JE transmission season. Vaccination should be considered for short-term travelers to endemic areas during the JE transmission season if they will travel outside of an urban area and their activities will increase the risk of JE exposure (time outdoors in rural/agricultural areas, outdoor recreation activities, sleeping in places without mosquito protection) and should also be considered for travelers to an area with an ongoing JE outbreak.

Vaccines Available & Schedule of Administration

JE-VC (Ixiaro, Novartis) is an inactivated Vero cell–derived JE vaccine licensed for use in people ≥2 months of age. It is given intramuscularly in a two-dose series at 0 and 28 days (or 0 and 7–28 days for adults 18–65 years). A booster dose should be given 1 year or more after the primary series if ongoing or repeat exposure to JE virus is expected. For adults and children 3 years or older, each dose is 0.5 mL. For children aged 2–35 months, each dose is 0.25 mL. Adverse reactions include pain at the injection site, headache, myalgias, and fever. JE vaccination is contraindicated for anyone who has had a severe allergic reaction to a previous vaccine dose or component.

TUBERCULOSIS VACCINATION

Approximately one-fourth of the world’s population is infected with Mycobacterium tuberculosis, which is a leading cause of death in low- and middle-income nations, killing approximately 1.3 million people annually. It is relatively uncommon in the United States, and most cases occur in persons born abroad or their close contacts. BCG vaccine consists of live attenuated Mycobacterium bovis. BCG is the most widely used vaccine in the world, having been administered to over 3 billion people, with a low incidence of adverse events following immunization. BCG vaccine is inexpensive, can be given any time after birth, sensitizes the vaccinated individual for 5–50 years, and stimulates both B-cell and T-cell immune responses. BCG reduces the risk of tuberculous meningitis and disseminated TB in pediatric populations by 50%–100% when administered in the first month of life. Efficacy against pulmonary tuberculosis has been variable (0%–80%) depending on the study setting and other factors.

BCG vaccination should be considered only in children with a negative TB skin test who are not infected with HIV and who are continually exposed to TB without the possibility of being separated from the infected adult. This is essential if the adult is untreated and the child cannot be given preventive treatment. BCG is not recommended for travel.

There is one licensed BCG vaccine in the United States produced by Organon Teknika Corporation (Tice BCG). It is administered intradermally. Adverse effects occur in 1%–10% of healthy individuals, including local ulceration, regional lymph node enlargement, and very rarely lupus vulgaris. The vaccine is contraindicated in pregnant women and in immunocompromised individuals, including those with HIV infection, because it has caused extensive local adenitis and disseminated or fatal infection.

BCG almost invariably causes its recipients to be tuberculin skin test-positive (5–7 mm), but the reaction often becomes negative after 3–5 years. An interferon-γ release assay (IGRA) TB test should be negative. Thus, a positive TST test in a child with a history of BCG vaccination who is being investigated for TB as a case contact should be interpreted as indicating infection with M tuberculosis. This is discussed in Chapter 42.

YELLOW FEVER VACCINATION

Yellow fever virus is a mosquito-borne flavivirus that is endemic in sub-Saharan Africa and South America. A live, attenuated vaccine against yellow fever is available in the United States but is available only at official yellow fever vaccination locations (typically public health departments) and should only be given after consultation with travel medicine specialists or public health officials. Immunization against yellow fever is indicated for children 9 months or older traveling to endemic areas. Proof of vaccination against yellow fever may be required for travel to certain countries.

Vaccines Available & Schedule of Administration

YF vaccine (YF-VAX, Sanofi) is made from the 17D yellow fever attenuated virus strain grown in chick embryos. When yellow fever vaccine is indicated, a subcutaneous injection of 0.5 mL is administered. Immunity following vaccination is long lasting, and booster doses are no longer recommended for most travelers.

Yellow fever vaccine is contraindicated in infants younger than 6 months (due to an increased risk of vaccine-associated encephalitis), in persons with anaphylactic egg allergy, and in immunocompromised individuals or individuals with a history of thymus disease. In children 6–8 months of age, children with well-controlled HIV, and pregnant women, the vaccine risks and benefits should be weighed on an individual basis. There is no contraindication to giving other live-virus vaccines simultaneously with yellow fever vaccine.

Adverse reactions are generally mild, consisting of low-grade fever, mild headache, and myalgia 5–10 days after vaccination, occurring in fewer than 25% of vaccines. Although very uncommon, several types of severe adverse reactions can occur following vaccination. Serious allergic reactions occur in roughly 1 case per every 55,000 vaccine recipients. The risk of vaccine-associated neurotropic disease within 30 days following vaccination has been estimated to be 1 case per every 125,000 vaccine recipients. The risk of severe multiple organ system failure following vaccination (vaccine-associated viscerotropic disease) has been estimated at 1 case per every 250,000 vaccine recipients. Health care providers should administer yellow fever vaccine only to persons truly at risk of exposure to yellow fever.

PASSIVE PROPHYLAXIS

1. Intramuscular & Specific Intravenous Immune Globulin

Ig may prevent or modify infection with hepatitis A virus if administered in a dose of 0.02 mL/kg within 14 days after exposure. Measles infection may be prevented or modified in a susceptible person if Ig is given in a dose of 0.5 mL/kg within 6 days after exposure. Pathogen-specific preparations of Ig include TIg, HBIg, RIg, CMV Ig (IV), botulism Ig (IV), and varicella-zoster Ig (VariZIG). These are obtained from donors known to have high titers of antibody against the organism in question. Ig must be given only by the route (IV or IM) for which it is recommended. The dose varies depending on the clinical indication. Adverse reactions include pain at the injection site, headache, chills, dyspnea, nausea, and anaphylaxis, although all but the first are rare.

Palivizumab (Synagis, MedImmune) is a humanized monoclonal antibody against RSV that is used to prevent RSV infection in high-risk populations with monthly doses during RSV season (Table 10–7). Palivizumab is administered in a dose of 15 mg/kg once a month beginning with the onset of the RSV season and continuing until the end of the season. Prophylaxis should be discontinued in any child who experiences a breakthrough hospitalization.

The maximum number of doses recommended in any one season is five. Palivizumab is packaged in 50- and 100-mg vials. Palivizumab does not interfere with response to routine childhood vaccinations.

2. Intravenous Immune Globulin

The primary indications for IVIg are for replacement therapy in antibody-deficient individuals; for the treatment of Kawasaki disease, immune thrombocytopenic purpura or hemolytic anemia, Guillain-Barré syndrome and other autoimmune diseases; and replacement therapy in chronic B-cell lymphocytic leukemia. IVIg may be beneficial in some children with toxic shock syndrome and for anemia caused by parvovirus B19. It can also be used as postexposure prophylaxis for varicella in at-risk persons when VariZIG is not available.