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 2017 schedule of routine immunizations for normal infants, children, and adolescents from birth through 18 years of age. Table 10–3 is the 2017 schedule for persons aged 4 months through 18 years who start vaccination late or are more than 1 month behind the routine immunization schedule. Updated immunization schedules are available at www.cdc.gov/vaccines.
Table 10–2.Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger, United States, 2017. ||Download (.pdf) Table 10–2.Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger, United States, 2017.
|(FOR THOSE WHO FALL BEHIND OR START LATE, SEE THE CATCH-UP SCHEDULE Table 10–3. |
|These recommendations must be read with the footnotes that follow. For those who fall behind or start late, provide catch-up vaccination at the earliest opportunity as indicated by the green bars in Table 10–2. To determine minimum intervals between doses, see the catch-up schedule (Table 10–3). School entry and adolescent vaccine age groups are shaded in gray. |
Table 10–3.Catch-up immunization schedule for persons aged 4 months through 18 years who start late or who are more than 1 month behind—United States, 2017. ||Download (.pdf) Table 10–3.Catch-up immunization schedule for persons aged 4 months through 18 years who start late or who are more than 1 month behind—United States, 2017.
|The figure below provides catch-up schedules and minimum intervals between doses for children whose vaccinations have been delayed. A vaccine series does not need to be restarted, regardless of the time that has elapsed between doses. Use the section appropriate for the child’s age. Always use this table in conjunction with Table 10–2 and the footnotes that follow. |
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. Through a unique collaboration between competing manufacturers, an application has been submitted to the FDA for a hexavalent vaccine that includes DTaP-IPV-Hib-HepB. 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 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), and the Clinical Immunization Safety Assessment (CISA) system each provide distinct contributions to monitoring of 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 the effectiveness of the vaccine. 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. Additional, more detailed, information is available from the CDC (www.cdc.gov/vaccines), in the AAP’s Red Book, and in vaccine package inserts.
et al: The Vaccine Safety Datalink: a model for monitoring immunization safety. Pediatrics 2011;127(Suppl 1):S45
et al: Parental vaccine safety concerns in 2009. Pediatrics 2010;125:654
et al: A population-based cohort study of undervaccination in 8 managed care organizations across the United States. JAMA Pediatr 2013;167:274
et al: The Food and Drug Administration’s Post-Licensure Rapid Immunization Safety Monitoring program: strengthening the federal vaccine safety enterprise. Pharmacoepidemiol Drug Saf 2012;21(Suppl 1):291
VACCINATION IN SPECIAL CIRCUMSTANCES
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.
Congenitally immunodeficient children should not be immunized with live-virus vaccines (oral polio vaccine [OPV, available only in developing countries], 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 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 http://www.cdc.gov/vaccines/pubs/pinkbook/index.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. Children with only urticaria following exposure to egg can be vaccinated, as long as injectable influenza vaccine is used as opposed to LAIV; vaccination is by a health care provider experienced in recognizing allergic reactions; and the child is observed for 30 minutes following vaccination. Children with more serious allergic reactions to egg, such as angioedema, respiratory symptoms, or anaphylaxis, may be eligible for injectable influenza vaccine, but should be referred to an allergist for an assessment of vaccination risk. 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.
CDC: General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2011;60(RR-02):1
JM: Administering influenza vaccine to egg-allergic persons. Expert Rev Vaccines 2014;13:1049
Communicating With Parents About Vaccines
Most parents in the United States choose to vaccinate their children. In 2013, less than 1% of young children had received no vaccines. However, parental concern about vaccines are 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 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, and some have suggested the use of motivational interviewing or other conversational techniques in these situations. 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 (www.aap.org), CDC (www.cdc.gov/vaccines), and the Immunization Action Coalition (www.immunize.org).
et al: American Academy of Pediatrics: Committee on Infectious Diseases; Committee on Practice and Ambulatory Medicine. Countering vaccine hesitancy. Pediatrics 2016;138
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 (more than 92% were fully immunized in 2015), 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 hepatitis B vaccine (HepB) 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 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. The ACIP has recommended that any decision to defer the birth dose require an explanation in the medical record, accompanied by a copy of the mother’s negative HBsAg test during the current pregnancy. 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.
Hepatitis B vaccine (Recombivax HB, Merck) contains recombinant HepB only.
Hepatitis B vaccine (Engerix-B, GlaxoSmithKline) contains recombinant HepB only.
DTaP-HepB-IPV (Pediarix, GlaxoSmithKline) contains vaccines against diphtheria, tetanus, pertussis, hepatitis B, and poliovirus.
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 hepatitis B 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.
Table 10–4.Hepatitis B vaccine schedules for newborn infants, by maternal hepatitis B surface antigen (HBsAg) status.a ||Download (.pdf) Table 10–4.Hepatitis B vaccine schedules for newborn infants, by maternal hepatitis B surface antigen (HBsAg) status.a
| ||Single Antigen Vaccine ||Single Antigen Followed by Combination Vaccine |
|Maternal HBsAg Status ||Dose ||Age ||Dose ||Age |
|Positiveb ||1c ||Birth (≤ 12 h) ||1c ||Birth (≤ 12 h) |
| ||HBIgd ||Birth (≤ 12 h) ||HBIg ||Birth (≤ 12 h) |
| ||2 ||1–2 mo ||2 ||2 mo |
| || || ||3 ||4 mo |
| ||3e ||6 mo ||4e ||6 mo (Pediarix) or 12–15 mo (Comvax) |
|Unknownf ||1c ||Birth (≤ 12 h) ||1c ||Birth (≤ 12 h) |
| ||2 ||1–2 mo ||2 ||2 mo |
| || || ||3 ||4 mo |
| ||3e ||6 mo ||4e ||6 mo (Pediarix) or 12–15 mo (Comvax) |
|Negative ||1c,g ||Birth (< 24 h) ||1c,g ||Birth (< 24 h) |
| ||2 ||1–2 mo ||2 ||2 mo |
| || || ||3 ||4 mo |
| ||3e ||6–18 mo ||4e ||6 mo (Pediarix) or 12–15 mo (Comvax) |
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.
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 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 permucosal 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.
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.
et al: Advisory Committee on Immunization Practices: A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep 2005;54(RR-16):1
et al: The prevalence of hepatitis B virus infection in the United States in the era of vaccination. J Infect Dis 2010;202:192
et al: Gaps in hospital policies and practices to prevent perinatal transmission of hepatitis B virus. Pediatrics 2010;125:704
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 500,000 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.
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 1.5 excess cases per 100,000 recipients after the first dose for RV5, and 5.3 excess cases per 100,000 recipients after 2 doses of RV1. At this level of risk, the benefits of vaccination against rotavirus disease continue to greatly outweigh the risks in the United States and globally.
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.
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). 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.
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.
UD: CDC: Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2009;58(RR-2):1
et al: The rotavirus vaccine development pipeline. Vaccine 2017; Epub ahead of print
et al: Rotavirus immunization: global coverage and local barriers for implementation. Vaccine 2017;35:1637
et al: Intussusception rates before and after the introduction of rotavirus vaccine. Pediatrics 2016;138:e20161082
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 six cases of diphtheria have been reported in the United States since 2000. 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, 25 cases of tetanus 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 childhood vaccination or prior infection. Infants less than 6 months old have the highest rate of pertussis infection (143 cases per 100,000); greater than 90% of pertussis deaths occur in neonates and infants less than 3 months.
In 2015, 20,762 cases of pertussis were reported in the United States 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.
Diphtheria, Tetanus, and Acellular Pertussis Combinations
DTaP (Daptacel, sanofi pasteur; Infanrix, GlaxoSmith-Kline) 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 through 5.
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.
Tdap (Adacel, sanofi pasteur) is a tetanus-diphtheria-acellular pertussis vaccine approved for persons 11 through 64 years of age.
DTaP Combined With Other Vaccines
DTaP-IPV-Hepatitis B (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).
DTaP-IPV-Hib (Pentacel, sanofi pasteur) 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 through 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.
DTaP-IPV (Kinrix, GlaxoSmithKline) 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.
Diphtheria and Tetanus Combinations
DT (generic, sanofi pasteur) contains tetanus toxoid and diphtheria toxoid to be used only in children younger than age 7 years with a contraindication to pertussis vaccination.
Td (Decavac, sanofi pasteur; generic, Massachusetts Biological Labs) contains tetanus toxoid and a reduced quantity of diphtheria toxoid, which is typically used for adults requiring tetanus prophylaxis.
TT (generic, sanofi pasteur) 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.
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.
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 sources recommend 3000–6000 units as a single dose, with part of the dose infiltrated around the wound.
Table 10–5.Guide to tetanus prophylaxis in routine wound management. ||Download (.pdf) Table 10–5.Guide to tetanus prophylaxis in routine wound management.
|History of Adsorbed Tetanus Toxoid (Doses) ||Clean, Minor Wounds ||All Other Woundsa |
|DTaP, Tdap, or Tdb ||TIGc ||DTaP, Tdap, or Tdb ||TIGc |
|Fewer than 3 or unknown ||Yes ||No ||Yes ||Yes |
|3 or more ||No if < 10 y since last tetanus-containing vaccine dose ||No ||Nod if < 5 y since last tetanus-containing vaccine dose ||No |
| ||Yes if ≥ 10 y since last tetanus-containing vaccine dose ||No ||Yes if ≥ 5 y since last tetanus-containing vaccine dose ||No |
|Tdap indicates booster tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine; DTaP, diphtheria and tetanus toxoids and acellular pertussis vaccine; Td, adult-type diphtheria and tetanus toxoids vaccine; tig, tetanus immune globulin (human). |
HAEMOPHILUS INFLUENZAE TYPE B VACCINATION
H influenzae type b (Hib) causes a wide spectrum of serious bacterial 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 with two-thirds of cases occurring in children younger than 18 months.
Hib is surrounded by a polysaccharide capsule (polyribosylribitol phosphate [PRP]) that contributes to virulence. Antibodies to this polysaccharide confer immunity to the disease. When Hib polysaccharide is chemically bonded (conjugated) to certain protein carriers, the conjugate vaccine induces long-term 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 Hib caused infections 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 40 cases of invasive Hib disease occurred in children younger than age 5 years in 2014. An additional 432 cases were caused by H influenzae species, which were not serotype b or the serotype was not reported.
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; and PRP-T vaccine uses a tetanus toxoid carrier.
Hib (PedvaxHIB, Merck, uses PRP-OMP), for use at 2, 4, and 12–15 months of age.
Hib (ActHIB, sanofi pasteur, uses PRP-T), for use at 2, 4, 6, and 12–15 months of age.
Hib (Hiberix, GlaxoSmithKline, uses PRP-T), for use as the booster (final) dose in the Hib vaccine series for children 15 months of age and older; it is not licensed for the primary series.
Hib Combined With Other Vaccines
DTaP-IPV-Hib (Pentacel, sanofi pasteur, uses PRP-T) contains DTaP, IPV, and Hib vaccines. This vaccine is approved for use in children 6 weeks to 4 years 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, 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 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.
N: Division of Bacterial Diseases; National Center for Immunization and Respiratory Diseases; CDC: Prevention and control of Haemophilus influenzae
type b disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2014;63(RR-01):1
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. At least 90 different serotypes of pneumococcus have been identified, and immunity to one serotype does not confer immunity to other serotypes.
A conjugate vaccine against seven pneumococcal serotypes (PCV7) was first licensed in the United States in 2000. The routine use of PCV7 led to a dramatic decrease in pneumococcal disease. However, as disease from PCV7 serotypes declined, 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 the 13 serotypes individually conjugated to a diphtheria 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 of invasive pneumococcal disease (Table 10–6). These children need enhanced protection against pneumococcal disease, which includes the use of PPSV23.
Table 10–6.Medical conditions or other indications for administration of PCV13a, and indications for PPSV23b administration and revaccination for children aged 6–18 years.c ||Download (.pdf) Table 10–6.Medical conditions or other indications for administration of PCV13a, and indications for PPSV23b administration and revaccination for children aged 6–18 years.c
|Risk Group ||Underlying Medical Condition ||PCV13 Recommended ||PPSV23 Recommended ||PPSV23 Revaccination 5 Years After First Dose |
|Immunocompetent persons ||Chronic heart diseased || ||√ || |
| ||Chronic lung diseasee || ||√ || |
| ||Diabetes mellitus || ||√ || |
| ||Cerebrospinal fluid leaks ||√ ||√ || |
| ||Cochlear implants ||√ ||√ || |
| ||Alcoholism || ||√ || |
| ||Chronic liver disease || ||√ || |
| ||Cigarette smoking || ||√ || |
|Persons with functional or anatomic asplenia ||Sickle cell disease/other hemoglobinopathies ||√ ||√ ||√ |
| ||Congenital or acquired asplenia ||√ ||√ ||√ |
|Immunocompromised persons ||Congenital or acquired immunodeficienciesf ||√ ||√ ||√ |
| ||Human immunodeficiency virus infection ||√ ||√ ||√ |
| ||Chronic renal failure ||√ ||√ ||√ |
| ||Nephrotic syndrome ||√ ||√ ||√ |
| ||Leukemia ||√ ||√ ||√ |
| ||Lymphoma ||√ ||√ ||√ |
| ||Hodgkin disease ||√ ||√ ||√ |
| ||Generalized malignancy ||√ ||√ ||√ |
| ||Iatrogenic immunosuppressiong ||√ ||√ ||√ |
| ||Solid organ transplant ||√ ||√ ||√ |
| ||Multiple myeloma ||√ ||√ ||√ |
PCV13 (Prevnar13, Wyeth). The vaccine contains an aluminum phosphate adjuvant, and does not contain thimerosal preservative. It is licensed for use in children 6 weeks of age and older and for adults.
PPSV23 (Pneumovax23, Merck). The vaccine contains the capsular polysaccharide antigens of 23 pneumococcal serotypes. It contains phenol as a preservative. It is licensed for 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 through 18 years of age should receive one dose of PCV13, followed at least 8 weeks later by PPSV23. Updated and detailed schedule information is available from 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 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.
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, 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.
CDC: Prevention of pneumococcal disease among infants and children—use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine—recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2010;59:1
CDC: Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among children aged 6-18 years with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2013;62:521
et al: Pneumococcal conjugate vaccine failure in children: a systematic review of the literature. Vaccine 2016;34:6126
SI: Pneumococcal disease in the era of pneumococcal conjugate vaccine. Infect Dis Clin North Am 2015;29:679
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, and type 2 poliovirus has been eradicated from the globe. 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 37 polio cases detected in 2016. 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 has resulted, and strategies are in place to prioritize IPV use and significantly increase vaccine production. Despite set-backs, 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.
IPV (IPOL, sanofi pasteur) is given intramuscularly or subcutaneously.
DTaP-HepB-IPV (Pediarix, GlaxoSmithKline) contains diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B, and inactivated poliovirus vaccines. Approved for use at 2, 4, and 6 months of age; not approved for use as the fourth dose of IPV or the fourth or fifth doses of DTaP; given intramuscularly.
DTaP-IPV-Hib (Pentacel, sanofi pasteur) 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.
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 have received at least 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.
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.
et al: Humoral and intestinal immunity induced by new schedules of bivalent oral poliovirus vaccine and one or two doses of inactivated poliovirus vaccine in Latin American infants: an open-label randomised controlled trial. Lancet 2016;388:158
WA: The challenge of global poliomyelitis eradication. Infect Dis Clin North Am 2015;29:651–665
et al: Cessation of trivalent oral poliovirus vaccine and introduction of inactivated poliovirus vaccine-worldwide, 2016. MMWR 2016;65:934
Influenza occurs each winter-early spring period, often associated with significant morbidity and mortality in certain high-risk persons. 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 of age. In a number of prior influenza seasons, LAIV was more effective than inactivated influenza vaccine in children. However, in the 2014–2015 influenza season, this was not the case, and the ACIP made an interim recommendation that LAIV should not be used. 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.
The 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 pasteur) is approved for children 6 months and older; Fluvirin (Novartis) is approved only for children 4 years and older, Fluarix (GlaxoSmithKline) is approved for children 3 years and older, and Afluria (CSL Biotherapies) is recommended for children 9 years and older. There are a number of additional influenza vaccines licensed for adults but not for children, including a high-dose vaccine, a cell culture-based vaccine, and a recombinant vaccine. Intranasal live attenuated influenza vaccine (LAIV [FluMist, MedImmune) is still licensed in the United States, although it is not currently recommended for use.
Dosage & Schedule of Administration
Inactivated Influenza Virus Vaccine
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 age 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 children aged 6–35 months is 0.25 mL given intramuscularly; for older children the dose is 0.5 mL. Pregnancy is not a contraindication to use of inactivated vaccine, and vaccine is recommended for all pregnant women and those contemplating pregnancy during the influenza season. Simultaneous administration with other routine vaccines is acceptable.
Live Attenuated Influenza Virus Vaccine
LAIV is not currently recommended in the United States. However, LAIV continues to be used in Canada, Europe, and elsewhere in the world.
Contraindications & Precautions
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.
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.
AAP; Committee on Infectious Diseases: Recommendations for prevention and control of influenza in children, 2016–2017. Pediatrics 2016;138:e20162527
CDC: Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices, United States, 2016–2017 Influenza Season. MMWR 2015;65:5
MEASLES, MUMPS, & RUBELLA VACCINATION
Due to an effective vaccination program beginning in 1963, measles was declared eliminated from the US 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 2016, there were 70 confirmed measles cases in the United States. In 2015, there was a large multistate outbreak of measles, linked to a theme park in California. In outbreaks such as this, 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, the largest of which occurred in 2009–2010, in which about 3000 people, mostly high school students from an insular religious community in New York City, were diagnosed with mumps. In 2016, there were more than 5000 reported cases of mumps. Risk factors for outbreaks include lack of immunization; close contact, such as in a school setting; two doses of MMR vaccine is only 88% effective in preventing mumps; and waning immunity, which may occur in young adults who had their last dose of a mumps-containing vaccine a decade or more in the past.
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.
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.
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
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, 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 is 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 healthcare 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.
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.
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.
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 age 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.
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.
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 to 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), arthralgias (more common in adults than children), and measles inclusion body encephalitis (which is very rare, and occurs only among persons with specific immunodeficiencies).
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 less than 12 months of age 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.
et al: Mumps outbreak at a university and recommendation for a third dose of measles-mumps-rubella vaccine—Illinois, 2015-2016. MMWR Morb Mortal Wkly Rep 2016;65:731
CDC: Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2013;62:1
et al: Measles outbreak—California, December 2014-February 2015. MMWR Morb Mortal Wkly Rep 2015;64:153
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 old. 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 from varicella 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 have been 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 months of age, 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.
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.
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 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 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.
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 has occurred 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 seems much lower in children following VAR immunization than after natural infection, and it also tends to be milder.
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), intimate contact with a person with herpes zoster deemed contagious, or a newborn contact. 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.
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.
AAP Committee on Infectious Diseases: Prevention of varicella: recommendations for use of quadrivalent and monovalent varicella vaccines in children. Pediatrics 2011;128:630
CDC: Updated recommendations for use of VariZIG—United States, 2013. MMWR Morb Mortal Wkly Rep 2013;62:574
R: Impact of the maturing varicella vaccination program on varicella and related outcomes in the United States, 1994-2012. J Pediatric Infect Dis Soc 2016;5:395
The incidence of hepatitis A in the United States has decreased dramatically from an average of 28,000 cases reported annually in the years prior to availability of a hepatitis A vaccine to 1390 cases reported in 2015.
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 hepatitis A 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 substantially. In a recent investigation, more than 40% of reported cases were associated with international travel, often in foreign-born persons returning to their countries of origin.
In addition to routine immunization of all children 12–23 months of age, hepatitis A vaccination is indicated for the following groups: (1) travelers to countries with moderate to high rates of hepatitis A, (2) children with chronic hepatitis B or hepatitis C infections or other 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) illegal drug users, 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 (Havrix, GlaxoSmithKline): An inactivated vaccine against hepatitis A. Approved for use in children 12 months of age and older, and adults.
HepA (Vaqta, Merck): An inactivated vaccine against hepatitis A. Approved for use in children 12 months of age and older, and adults.
HepA-HepB (Twinrix, GlaxoSmithKline): A combined inactivated vaccine against hepatitis A and hepatitis B. 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
Hepatitis A 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 reactions, which are uncommon and mild, consist of pain, swelling, and induration at the injection site (10%–15%), headache, and loss of appetite. There have been no reports of serious adverse events attributed definitively to hepatitis A vaccine.
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 who are exposed to hepatitis A should consist of either a single dose of hepatitis A vaccine or Ig (0.02 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, hepatitis A vaccine is preferred to Ig for postexposure prophylaxis because of the advantages of vaccination, including long-term protection and ease of administration. For those older than 40 years of age, Ig is preferred, although the vaccine should be used if Ig is not available. Ig should also be used for children less than 12 months of age, immunocompromised persons, those with chronic liver disease, and anyone for whom vaccination is contraindicated. People who are given Ig, and for whom hepatitis A vaccine is recommended for other reasons, should receive a dose of vaccine simultaneously with Ig. If given at the same time, the vaccine and Ig should be administered at different injection sites.
Ig can be used as preexposure as well as postexposure prophylaxis. Ig is indicated as preexposure prophylaxis in children younger than age 12 months at increased risk of hepatitis A infection (eg, those traveling to endemic areas, or those with clotting factor disorders). For preexposure prophylaxis, recommended dosages are 0.02 mL/kg in a single intramuscular dose if the duration of exposure is likely to be less than 3 months and 0.06 mL/kg if exposure is likely to be more than 3 months. For long-term prophylaxis of persons not eligible for vaccination, prophylactic doses can be repeated every 5 months.
CDC: Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2006;55(RR-7):1
Infections with Neisseria meningitidis cause significant morbidity and mortality, with an estimated 800–1200 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. Five serogroups of meningococcus (A, B, C, W, 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 of age in the United States; it is also responsible for several recent outbreaks on college campuses.
Six 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 or not a chronic condition increasing meningococcal disease risk is present. Updated, detailed vaccination recommendations are available at https://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.
Also licensed in the United States is a quadrivalent polysaccharide vaccine against serogroups A, C, W, and Y (MPSV4, tradename Menomune). However, the vaccine is less immunogenic than either Menactra or Menveo, and so is used infrequently. It is used for persons older than 55 years of age needing meningococcal vaccination, and can be used for individuals 2 through 55 years of age if Menactra or Menveo are not available.
Two vaccines are available that protect against serogroup B disease (MenB), Bexsero and Trumenba, licensed for use at 10 years of age and older. For healthy young adults who do not have a chronic health condition predisposing to meningococcal disease, Bexsero and Trumenba are not recommended for universal use. However, these vaccines may be used with clinical discretion to reduce the risk of serogroup B meningococcal disease. These two vaccines are not interchangeable, so 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), children with HIV infection, and children with complement component deficiencies. 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 (including those with sickle cell disease) or children with complement deficiencies 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 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.
MCV4 (Menactra, sanofi pasteur): A single 0.5-mL dose contains capsular polysaccharide from serogroups A, C, Y, and W conjugated to diphtheria toxoid.
MCV4 (Menveo, Novartis): A single 0.5-mL dose contains serogroups A, C, Y, and W capsular polysaccharide, all of which is conjugated to CRM197, a nontoxic mutant of diphtheria toxoid.
Hib-MenCY-TT (MenHibrix, GlaxoSmithKline Biologicals): 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.
MPSV4 (Menomune-A/C/Y/W, sanofi pasteur): Each dose consists of 50 mcg each of the four bacterial capsular polysaccharides.
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.
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), and factor H binding protein (fHbp); and 25 mcg of outer membrane vesicles (OMV).
Dosage & Schedule of Administration
MCV4 is given as a single 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 a single intramuscular dose of 0.5 mL; MPSV4 as a single subcutaneous dose of 0.5 mL; MenB as a single 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, Hib-MenCY-TT, and MPSV4 are described previously. MenB vaccines are licensed for use in persons aged 10–25 years. Trumenba is a three-dose series given at 0, 2, and 6 months, and Bexsero is a two-dose series given at least 1 month apart. MenB should be given to persons age ≥ 10 years at increased risk of meningococcal disease (complement deficiencies, asplenia, microbiologists, or serogroup B outbreaks).
Contraindications & Precautions
MCV4 and MPSV4 are 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. Both MCV4 and MPSV4 can be given to individuals who are immunosuppressed. MPSV4 is thought to be safe during pregnancy; no information is available regarding the safety of MCV4 during pregnancy.
Both MCV4 products and MPSV4 are 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 and in 4%–6% of persons of the same age receiving MPSV4. 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 or above; 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 and 2.6% of MPSV4 recipients. Although cases of Guillain-Barré syndrome have been reported after MCV4, the current data does not suggest that the rate is above that which would be expected in the absence of vaccination.
CJ: Prevention of meningococcal infection in the United States: current recommendations and future considerations. J Adol Health 2016;59:S29
CDC: Use of serogroup B meningococcal vaccines in persons aged ≥10 years at increased risk for serogroup B meningococcal disease: Recommendations of the Advisory Committee on Immunization Practices, 2015. MMWR 2015;62(22):608–612.
CDC: Prevention and control of meningococcal disease. MMWR 2013;62(RR-2):1–22
et al: Emerging experience with meningococcal serogroup B protein vaccines. Expert Rev Vaccines 2017;16:433
TETANUS-REDUCED DIPHTHERIA-ACELLULAR PERTUSSIS VACCINATION (ADOLESCENTS & ADULTS)
Pertussis is increasingly recognized as a disease affecting older children and adults, including fully vaccinated persons with waning immunity. In the United States, the most dramatic increases in pertussis incidence are among adolescents and young adults, prompting development of booster pertussis vaccines for this population. FDA approval in 2005 of the tetanus-reduced dose diphtheria-acellular pertussis (Tdap) vaccine was based on comparable seroresponse to pertussis antigens and a safety profile similar to control Td. Adolescent, adult, and elderly immunization not only has the capacity to protect adolescents from pertussis, but also should limit spread of pertussis from adults to infants and decrease overall pertussis endemicity.
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.
Tdap (Adacel, sanofi pasteur) 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, instead of the tetanus and diphtheria toxoids (Td) vaccine for booster immunization. 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 less than 12 months. Women who are pregnant should receive a Tdap booster with each pregnancy, ideally during the third trimester. 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. If not administered at the same time, a minimum interval of 1 month between vaccines is suggested.
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, a progressive neurologic disorder, uncontrolled epilepsy, or progressive encephalopathy until the condition has stabilized.
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.
AAP; Committee on Infectious Diseases: Additional recommendations for use of tetanus toxoid, reduced-content diphtheria toxoid, and acellular pertussis vaccine (Tdap). Pediatrics 2011;128:809
CDC: Updated recommendations for the use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine from the Advisory Committee on Immunization Practices, 2010. MMWR Morb Mortal Wkly Rep 2011;60:13
CDC: Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in pregnant women, Advisory Committee on Immunization Practices (ACIP), 2012. MMWR Morb Mortal Wkly Rep 2013;62:131
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. Approximately 70% of cervical cancers and 80% of all HPV-associated cancers (also includes oral, vaginal, anal) are caused by the high cancer risk types 16 and 18. Over 90% of genital warts are caused by low cancer risk types 6 and 11.
Three HPV vaccines are licensed in the United States. Bivalent HPV vaccine (2vHPV) contains types 16 and 18 (Cervarix, GlaxoSmithKline) and is approved for females. Quadrivalent HPV vaccine (4vHPV) contains types 6, 11, 16, and 18 (Gardasil, Merck) and is approved for females and males. Nine-valent HPV vaccine adds types HPV 31, 33, 45, 52, and 58 to 4vHPV and is approved for females and males. The added serotypes provide protection against an additional 12% of HPV-related cancers. Routine HPV vaccination is recommended for females and males aged 11–12 years and may be given as early as age 9. Catch-up vaccination is recommended for females aged 13–26 years and males aged 13–21 years who were not previously vaccinated or have not completed the full vaccine series. HPV vaccination is also recommended through age 26 years for men who have sex with men, and for men with immunocompromising conditions (including HIV infection), if they were not previously vaccinated or had not completed the vaccine series. Females who might have been exposed to HPV, test positive for a high-risk HPV types, or have an abnormal Pap test are still likely to benefit from HPV vaccine by avoiding infection with other HPV types.
Quadrivalent HPV vaccine (Gardasil, Merck), a nonlive vaccine; a 0.5-mL dose contains HPV-6, 11, 16, and 18 L1 proteins.
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.
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.
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 or for persons with certain 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 dose 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. When feasible, the same HPV vaccine should be used for the complete series. However, if the HPV vaccine previously administered is unknown or not available, any HPV vaccine can be used to complete the series to protect against HPV types 16 and 18. There is currently no recommendation for repeat vaccination with 9vHPV for persons who have completed a vaccination series with 2vHPV or 4vHPV; the most current recommendations can be found at www.cdc.gov/vaccines.
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.
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. Postmarketing reports of syncope, which were reported after vaccination with HPV vaccine, may follow any vaccination, so vaccine recipients should be observed for 15 minutes after vaccination.
CDC: Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2014;63(RR-05):1
CDC: Use of a 2-dose schedule for human papillomavirus vaccination—updated recommendations of the Advisory Committee on immunization practices. MMWR 2016 Dec 16;65(49):1405–1408
CDC: Use of 9-Valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the Advisory Committee on Immunization Practices. MMWR 2015;64:300–304