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Vaccine safety in infants and children

Barbel, Paula PhD, RN, CPNP-PC

doi: 10.1097/01.NURSE.0000604724.58449.ad
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Abstract: Immunization is crucial to maintaining public health. This article addresses the benefits of childhood vaccinations and educates parents on the myths surrounding possible adverse reactions.

Immunization is crucial to maintaining children's health. Read about the benefits of childhood vaccinations, weigh the risks, and dispel myths that may drive vaccine hesitancy in parents.

Paula Barbel is an associate professor of nursing at the College at Brockport, State University of New York.

The author has disclosed no financial relationships related to this article.

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VACCINES ARE AN ESSENTIAL part of public health, having prevented serious disease and mortality in millions of children globally.1 They are highly effective in disease prevention and have reduced the incidence of rubella (German measles), measles (rubeola), and mumps (parotitis) by 96% to 99%.1,2 This article sheds light on the benefits of childhood immunization and how they outweigh the potential for adverse reactions.

Unless otherwise indicated, the information below is intended for pediatric patients receiving immunizations and their parents. Consult with a pharmacist, review product inserts, and look over the prescriber instructions for more information on each vaccine.

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Preventable diseases on the rise

Recently, vaccine-preventable diseases have been increasing in the US, with 1,250 documented cases of measles in 2019 as of this writing.3 Globally, approximately 19 cases of measles per 1 million individuals are reported, resulting in 89,780 to 110,000 deaths annually.4-7 In the US, the rise of vaccine-preventable disease is largely attributed to vaccine refusals and hesitancy by parents or guardians, exposure to unvaccinated children, and the exposure of unvaccinated children to travelers from regions of the world where these diseases remain endemic.8

Vaccine hesitancy is characterized as a “delay in acceptance or refusal of vaccination despite availability of vaccination services.”9 It may vary depending on context, including the time, place, and specific vaccine, as well as parental complacency, convenience, and confidence.9 (See Understanding parental hesitancy.)

The Advisory Committee on Immunization Practices at the CDC recommends that children receive several vaccines before their second birthday.10 Given the increase in outbreaks of vaccine-preventable diseases that had been virtually eradicated in the US, nurses must educate patients and/or their parents or guardians about the safety of vaccines and address the spectrum of hesitancy from indecision to outright refusal.11

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Safety and monitoring

Vaccines are highly effective and safe.12,13 To ensure safety, they undergo a rigorous testing process before FDA approval. This includes clinical trials to establish safety in animals, followed by trials to establish safety and effectiveness in humans. The FDA evaluates the trial results and inspects manufacturing sites and vaccine lots both pre- and post-licensure.14 Each vaccine must meet strict FDA standards and regulations for safety, efficacy, potency, and purity.14 Once a vaccine has met FDA standards and demonstrated that the benefits outweigh any risks, it is approved for public use and licensed.

During the postapproval period, the CDC continues to monitor safety via the Vaccine Adverse Event Reporting System (VAERS), the Vaccine Safety Datalink (VSD), the Clinical Immunization Safety Assessment (CISA) Project, and the emergency preparedness for vaccine safety regulations. The VAERS collects reports on adverse reactions following vaccination, all of which are examined to determine patterns and the need for further studies or investigation.15 The VSD is a database of more than 9.2 million people used to conduct research on whether reported adverse reactions are related to a specific vaccine.14

The CISA is a network of vaccine safety experts from the CDC, medical research centers, and other organizations that addresses issues regarding vaccine safety, examines complex clinical adverse reactions, and conducts research.15 Providers and nurses can also consult the CISA project for vaccine safety issues and questions.14-16 Additionally, emergency preparedness for vaccinesafety regulations ensure “robust systems are in place to rapidly monitor vaccine safety in the event of an emergency vaccination program.”15

Parents or guardians and patients are encouraged to report any vaccine-associated adverse reactions through VAERS. Under the National Childhood Vaccine Injury Act, nurses and other healthcare professionals are mandated to report vaccine-associated adverse reactions.17 To ensure accurate reporting, nurses must document the manufacturer information, lot number, and expiration date of every administered vaccine. Additionally, vaccine manufacturers must report adverse reactions according to federal regulations; failure to do so can result in a loss of licensure for that vaccine.18

All vaccines carry a small risk of a hypersensitivity reaction to a specific component. As such, vaccine-specific contraindications include severe allergic reactions, such as anaphylaxis, to any component of a vaccine or after a previous dose. In patients experiencing moderate to severe illness, immunization should be deferred until the acute illness has been resolved.19

The following discussion focuses on the measles, mumps, and rubella (MMR); diphtheria-tetanus and pertussis (DTaP); rotavirus; influenza; and human papillomavirus (HPV) vaccines.

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Measles, mumps, and rubella vaccine

The MMR vaccine is a safe and effective way to prevent measles, mumps, and rubella. It is a live attenuated virus, administered subcutaneously.20 The first dose is recommended for infants ages 12 months to 15 months, with a second dose administered between ages 4 and 6 years.21 Localized tenderness, erythema, swelling, and mild fever are the most common adverse reactions. These usually resolve in 1 or 2 days without intervention. Febrile seizures are a rare adverse reaction associated with the MMR vaccine, with a rate of approximately 1 case per every 3,000 to 4,000 doses. Other rare adverse reactions include anaphylaxis, aseptic meningitis, immune thrombocytopenia, and lymphadenopathy.1,22,23

Based on a fraudulent study, the myth that the MMR vaccine is associated with autism continues to contribute to vaccine hesitancy.9 Multiple studies have discredited this myth, concluding that there is no causal relationship between the MMR vaccine and autism spectrum disorder.24 For example, a large cohort study of 657,461 children who received the MMR vaccine in Denmark showed no increased risk for the development of autism spectrum disorder.25 Additionally, some parents may avoid immunization due to the unfounded notion that the measles infection may protect against cancer.9 However, delaying administration of the MMR vaccine is associated with an increased risk of febrile seizures after age 16 months.10,26

Contraindications to MMR vaccine administration include a history of anaphylactic reactions to neomycin or any other components, as well as a known severe immunodeficiency.27 Precautions that may increase the chance or severity of a serious adverse reaction or compromise the vaccine's ability to produce immunity include moderate or severe acute illness with or without fever, the recent receipt of an antibody-containing blood product (within 11 months), a history of thrombocytopenia or thrombocytopenic purpura, the need for tuberculin skin testing, and a patient or family history of seizures.

Before the licensure of the measles vaccine in 1963, there were approximately 500,000 cases of measles annually in the US, resulting in 500 deaths. Measles vaccinations have led to a reduction of more than 95% in incidences since their introduction. Globally, vaccinations have decreased measles-related deaths by 80%, preventing an estimated 21.1 million deaths.6,27

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Diphtheria-tetanus and pertussis vaccine

Five doses of the DTaP vaccine are recommended for infants and children. It is administered I.M. at ages 2, 4, and 6 months, again between ages 15 and 18 months, and once more between 4 and 6 years.28 Common adverse reactions include erythema and tenderness at the injection site and a low-grade fever.29 More serious adverse reactions, including seizures and fever greater than or equal to 40.5° C (105° F), are associated with the whole-cell pertussis vaccine.29 However, several studies examining postlicensure safety found no increased risk for neurologic complications or seizures following vaccination with DTaP.30,31

Patients who have had a severe allergic reaction such as anaphylaxis after a previous dose or who have severe allergies to any vaccine components should not receive the DTaP vaccine.32 Additional contraindications include encephalopathy, including coma, decreased level of consciousness, or prolonged seizures that are not attributable to another identifiable cause within 7 days of the administration of a previous dose.32

Precautions to DTaP vaccine administration include a moderate or severe acute illness with or without fever, Guillain-Barré syndrome (GBS) within 6 weeks following a previous dose of tetanus toxoid-containing vaccines, and a history of Arthus-type hypersensitivity reactions after a previous dose of tetanus or diphtheria toxoid-containing vaccines.32,33 Arthus reactions are characterized as localized type III hypersensitivity, resulting in inflammation, infiltration of neutrophils, and skin necrosis.33

With approximately 24.1 million annual cases of pertussis, 7,100 annual cases of diphtheria, and 15,103 annual cases of tetanus globally, the benefits of the DTaP vaccine outweigh the small risk of adverse reactions given its established safety.34

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Rotavirus vaccine

The rotavirus vaccine is administered either in two doses at ages 2 months and 4 months or in three doses at ages 2 months, 4 months, and 6 months (depending on the brand) to prevent viral gastroenteritis in pediatric patients.22,35,36 Both vaccines are administered via the oral route, and the efficacy ranges from 85% to 100% against various viral strains.10 The most common adverse reactions include diarrhea, vomiting, irritability, otitis media, nasopharyngitis, bronchospasm, fussiness or irritability, cough or runny nose, fever, and anorexia.37

Contraindications to rotavirus vaccine administration include a severe (life-threatening) allergic reaction to a previous dose, a severe (life-threatening) allergy to any component, severe combined immunodeficiency, or a previous episode of intussusception.37 Conditions commonly misperceived as contraindications for the rotavirus vaccine may include prematurity, household members who are immunosuppressed, and those who are pregnant.37

At a rate of 5.3 infants per 100,000, a small risk of intussusception is associated with the monovalent rotavirus vaccine postlicensure.38 This must be weighed against the fact that rotavirus is the leading cause of diarrhea in children and the second leading cause of mortality in children under 5 years old globally.39 Since the introduction of the vaccine, rotavirus-associated hospitalizations have decreased 63% to 94% in the US.4

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Seasonal influenza vaccine

Several inactivated influenza vaccines (IIVs) and a live attenuated influenza vaccine (LAIV) are licensed for use in children in the US.40 IIVs for children age 18 years and under are administered I.M.; the LAIV is administered intranasally. IIVs are recommended annually for patients age 6 months and older, and the LAIV is approved and recommended annually for children age 2 years and older.

Children ages 6 months to 35 months may receive one of four quadrivalent IIVs (IIV4s) licensed for this age group. Alternatively, healthy children age 2 years and older may receive quadrivalent LAIV (LAIV4) intranasally, but it is not licensed for those under 2 years.41

For optimal protection, children between ages 6 months and 8 years require 2 doses of the influenza vaccine, which are administered a minimum of 4 weeks apart during their first vaccination season. The number of necessary doses is determined based on their age at the time of the first dose of the 2019-2020 influenza vaccine and the number of doses they have received in previous influenza seasons:41

  • Children age 9 years and older require only one dose for the 2019-2020 influenza season.
  • For children between ages 6 months and 8 years, the number of required doses for the 2019-2020 influenza season is determined as follows:
    • Those who received two or more total doses of trivalent or quadrivalent influenza vaccine before July 1, 2019, separated by a period of 4 weeks or more, require only one dose for 2019-2020 season. The two previous doses do not need to have been administered in the same season or in consecutive seasons.
    • Those who have not received two or more doses of trivalent or quadrivalent influenza vaccine before July 1, 2019, or whose previous influenza vaccination history is unknown, require two doses for the 2019-2020 season. The two doses should be separated by an interval of 4 weeks or more, and these are recommended even if the child turns 9 between the first and second dose.41

Common adverse reactions to IIVs include injection site erythema, fever, myalgia, headache, fatigue, and nausea.42 The estimated risk of GBS is 1 to 2 individuals per 1 million.43 Studies have found no evidence of elevated risk for adverse reactions to the influenza vaccine, specifically GBS, in 1,195,552 doses administered to children under age 18.44,45 Manufacturer package inserts and updated CDC/Advisory Committee on Immunization Practices (ACIP) guidance should be consulted for information on contraindications and precautions for individual influenza vaccine products.

In general, a history of severe allergic reactions to the vaccine or any of its components, such as an egg allergy, is a labeled contraindication to most IIVs (see ACIP's statement on egg allergies). As such, the influenza vaccine is not recommended for individuals who are allergic to the vaccine or its components other than egg. More information on vaccine components can be found in the package inserts for each vaccine. Precautions include moderate or severe acute illness with or without fever, as well as a history of GBS within 6 weeks of a previous dose.41

LAIV4 is contraindicated for patients with a history of severe allergic reactions to any components or previous doses of any influenza vaccine, as well as for children receiving concomitant aspirin- or salicylate-containing medications. In addition to the labeled contraindications (other than egg allergies), ACIP recommends that LAIV4 not be administered to:41

  • children between ages 2 and 4 years who have received an asthma diagnosis, whose parents or caregivers report a healthcare provider telling them that their child had wheezing or asthma in the past 12 months, or whose medical record indicates a wheezing episode within the past 12 months
  • immunocompromised patients
  • patients in close contact with severely immunocompromised patients who require a protected environment.

Like IIVs, precautions for the LAIV4 include moderate or severe acute illness with or without fever, as well as a history of GBS within 6 weeks of a previous dose. Additional LAIV4-specific precautions include asthma in individuals age 5 years and older and the presence of an underlying medical condition that might predispose patients to severe illness with wild-type influenza virus infection. Wild-type influenza viruses are naturally occurring, but they are typically unsuitable for vaccine production.41,46

Parents and caregivers may refuse the flu vaccine for various reasons, including the belief that influenza is a mild illness, concerns about ingredients such as thimerosal, or doubt regarding the vaccine's effectiveness.47 It highlights the importance of educating parents and guardians that IIVs and the LAIV prevent millions of cases of influenza annually, significantly decrease hospitalization and admissions to the pediatric ICU, and decrease the overall risk of mortality.48 An estimated 25.5 to 29.3 million individuals became sick with the influenza virus from October 2018 to March 2019, resulting in 21,500 to 35,500 deaths. The benefits of vaccination clearly outweigh the risks.4

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Human papillomavirus vaccine

The CDC recommends vaccinations for girls and boys age 11 or 12 years to protect against cancers caused by HPV infections, but vaccination can be started as early as age 9.49 HPV vaccines are administered as a two-dose series separated by 6 to 12 months for most children between ages 9 and 14 years, as well as in a three-dose series separated by periods of 1 to 2 months and then again after 6 months for those ages 15 to 26 years and those who are immunocompromised.50 These should be administered I.M.

Common adverse reactions to the HPV vaccine include erythema, nausea, dizziness, syncope, headache, and pain or swelling at the injection site.51 Syncope is rare, but the CDC recommends monitoring patients for 15 minutes after vaccine administration.51 One study of 600,558 administered quadrivalent HPV vaccines demonstrated no statistically significant increase in the risk of GBS, stroke, venous thromboembolism, appendicitis, seizures, syncope, allergic reactions, or anaphylaxis.52

A severe allergic reaction, such as anaphylaxis, to a vaccine component or following a prior dose is a contra-indication to the HPV vaccine.53 Anaphylactic allergies to latex are contraindications to the bivalent HPV vaccine, as the tip cap of the prefilled syringe may contain natural rubber latex.53 Quadrivalent and 9-valent HPV vaccines are produced in Saccharomyces cerevisiae (baker's yeast) and are contraindicated for those with a history of immediate hypersensitivity to yeast.53

A moderate or severe acute illness is a precaution to vaccination, and vaccinations should be deferred until the signs and symptoms improve.53 Minor acute illnesses, such as diarrhea or mild upper respiratory tract infection with or without fever, are not a reason to defer vaccination.53

Parents and caregivers may hesitate or refuse the HPV vaccine because they think it will encourage their child to engage in sexual activity or believe that a child who is not sexually active does not need it.47 Several studies have shown that children who receive the HPV vaccine do not engage in sexual activity any earlier than those who did not receive it.47

Since the introduction of the vaccine in 2006, there has been a 29% decrease in HPV-related cancers in females.54 A recent meta-analysis of 65 studies on HPV vaccine administration, including data from 60 million individuals from 14 high-income countries, found an 83% reduction for female patients between ages 13 and 19 and a 66% reduction for those between ages 20 and 24 in the two types of HPV most often associated with cervical cancers and anogenital warts, HPV 16 and 18. There was also a significant reduction in anogenital warts in female patients ages 15 to 29 and male patients ages 15 to 24, as well as a significant reduction in precancerous lesions in female patients.55

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Nursing considerations

Nurses play an important role in vaccine safety by following specific guidelines on storage, administration, and documentation. Any facility or agency administering vaccinations requires a designated professional who is knowledgeable on CDC guidelines to manage storage and handling. Policies and procedures on both routine storage and emergency management in situations such as a power outage, an equipment malfunction, or an anaphylactic reaction following vaccination should be in place and updated regularly. For anaphylactic reactions, these include but are not limited to practices such as the administration of epinephrine and, if appropriate, endotracheal intubation due to an obstructed airway.56

Vaccines should be stored separately at the recommended temperature using an up-to-date, calibrated temperature-monitoring device checked twice daily.14 The device should include an alarm to alert the nursing staff if temperatures fall outside of the established parameters.

As with any drug, nurses are also responsible for safely administering vaccines. They assess which immunizations are due, ensure the proper time interval requirements, and complete the necessary documentation. Additionally, they screen patients for precautions and contraindications, check expiration dates, prepare vaccines using sterile technique, and administer dosages via the appropriate route.14

Education is vital in addressing vaccination refusal and/or hesitancy. Nurses help parents to understand the benefits of vaccination, the risk of serious complications associated with each vaccine-preventable disease, and the low risk of serious adverse reactions to vaccines. Additionally, they can assure parents that vaccines, specifically the MMR immunization, are not associated with any risk for development of autism spectrum disorder.

By partnering with parents, listening to their concerns, and trying to understand the underlying reasons for their hesitancy or refusal, nurses avoid an adversarial relationship. They must stress to skeptical parents that they are on the same team, with the ultimate concern being the health and well-being of the young patient.57,58

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Understanding parental hesitancy6,9,47,59,60

There are several reasons for parental vaccine hesitancy and refusal, including:

  • objections based on religious beliefs
  • safety concerns
  • potential for adverse reactions
  • potentially harmful vaccine components, including ingredients such as aluminum
  • the perception that vaccines or their components cause harm, learning disabilities, or autism spectrum disorders; for example, unfounded fears surrounding the MMR vaccine
  • autoimmune disorders and concern over receiving too many vaccinations in a short period, “overloading” the immune system
  • distrust of the medical community, pharmaceutical industry, and government
  • the belief that a child has a low probability of getting the disease and/or a preference for natural immunity through exposure.
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ACIP statement on egg allergies

Egg allergies can be confirmed by a consistent medical history of adverse reactions to eggs and egg-containing foods, as well as skin or blood testing. Patients with egg allergies may tolerate their presence as ingredients in baked products, but this does not exclude the possibility of an adverse reaction.

The following egg-allergic individuals should receive any licensed, recommended influenza vaccine appropriate to their age and health status:

  • those who have experienced only urticaria
  • those who have reported other reactions, such as angioedema, respiratory distress, lightheadedness, or recurrent vomiting
  • those who required epinephrine or another emergency medical intervention.

The influenza vaccine is contraindicated for egg-allergic patients who:

  • have experienced a severe allergic reaction to the influenza vaccine, regardless of the suspected component responsible for the reaction.

Vaccines should be administered and supervised:

  • in inpatient or outpatient medical settings, such as hospitals, clinics, health departments, and physician offices
  • by a healthcare provider able to recognize and manage severe allergic reactions.

No postvaccination observation period is recommended specifically for egg-allergic persons, but vaccine providers should consider observing patients for minutes after the administration of any vaccine for possible injury and syncope.

Adapted with permission from: Grohskopf LA, Alyanak E, Broder KR, Walter EB, Fry AM, Jernigan DB. Prevention and control of seasonal influenza with vaccines: recommendations of the advisory committee on immunization practices—United States, 2019-20 influenza season. MMWR Recomm Rep. 2019;68(3):1-21.

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Resources

Excellent resources are available for nurses and parents discussing vaccine safety and hesitancy.

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REFERENCES

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54. Guo F, Cofie LE, Berenson AB. Cervical cancer incidence in young U.S. females after human papillomavirus vaccine introduction. Am J Prev Med. 2018;55(2):197–204.
55. Schnirring L. Experts expand HPV vaccine recs as study finds high impact. University of Minnesota, Center for Infectious Disease Research and Policy. 2019. http://www.cidrap.umn.edu/news-perspective/2019/06/experts-expand-hpv-vaccine-recs-study-finds-high-impact.
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Keywords:

childhood vaccination; diphtheria-tetanus and pertussis vaccine; DTaP vaccine; human papillomavirus vaccine; HPV vaccine; influenza vaccine; measles, mumps, and rubella vaccine; MMR vaccine; rotavirus vaccine; Vaccine Adverse Event Reporting System; VAERS; vaccine hesitancy; vaccine refusal

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