Standard childhood vaccines: Caregiver hesitancy or refusal

INTRODUCTION — This topic reviews the reasons why some caregivers refuse or are hesitant to have their child(ren) immunized, the consequences of vaccine refusal, and an approach to the management of caregivers who refuse vaccines for their children. Standard childhood immunizations for children are discussed separately. (See "Standard immunizations for children and adolescents: Overview".)

DEFINITION — According to the World Health Organization Strategic Advisory Group of Experts Working Group on Vaccine Hesitancy [1]:

●Vaccine hesitancy refers to "a delay in acceptance or refusal of vaccination despite availability of vaccination services. Vaccine hesitancy is complex and context specific, varying across time, place, and vaccines. It is influenced by factors such as complacency, convenience, and confidence."

•Complacency refers to the perception that the risks of vaccine-preventable diseases are low.

•Convenience refers to the availability, affordability, and accessibility of vaccines.

•Confidence refers to trust in the safety and effectiveness of vaccines, the health care system, and policymakers who recommend vaccines.

Vaccine hesitancy is a concern worldwide [2]. In 2019, the World Health Organization named vaccine hesitancy as one of the top 10 threats to global health [3].

STATE LAWS REGARDING VACCINATION — Laws that require immunization for school entry are associated with increased rates of immunization and decreased rates of vaccine-preventable diseases [4].

Every state in the United States requires some immunizations for school entry (typically for kindergarten, seventh grade, and college entry). However, caregivers can elect to exempt their children from immunizations for three reasons:

●Medical exemptions – For children with a valid medical contraindication to a vaccine or vaccine component (eg, history of anaphylaxis to a previous dose of vaccine)

●Religious exemptions – For individuals whose religious beliefs oppose immunizations

●Philosophical exemptions – For individuals with a personal, moral, or philosophical belief against some or all immunizations

All states allow medical exemptions, nearly all states allow exemptions based upon religious beliefs, and approximately one-third allow philosophical exemptions [5]. The National Conference of State Legislatures and the Immunization Action Coalition provide a comprehensive list of state exemption statutes. The American Academy of Pediatrics (AAP) provides an interactive map that provides state-by-state information about nonmedical exemptions.

The ease with which exemptions can be obtained affects exemption rates within communities [6-9]. States that allow philosophical and religious exemptions have higher exemption rates than those with religious exemptions only [10-12]. They also have higher rates of vaccine-preventable diseases [13-17]. When states eliminate philosophical exemptions, religious exemptions appear to increase [18]. (See 'Consequences of vaccine refusal' below.)

The AAP [19], the Pediatric Infectious Diseases Society [20], the Infectious Diseases Society of America [21], the American Academy of Family Physicians [22], the American College of Physicians [23], and the American Medical Association [24] support elimination of nonmedical exemptions to immunizations.

Legislation that eliminates nonmedical exemptions is strengthened by requiring a standardized review of medical exemptions to ensure that they are valid. After California passed legislation eliminating nonmedical exemptions that was not accompanied by standardized review of medical exemptions, there was an increase in medical exemption claims that were not true contraindications to immunization [25,26].

EPIDEMIOLOGY

●Prevalence – The primary measure of the prevalence of vaccine refusal in the United States is the proportion of children who are exempted from school immunization requirements for nonmedical reasons [27]. The rate of nonmedical exemptions at kindergarten entry varies among states. For the 2021-2022 school year, it ranged from 0.1 to 9.8 percent among states that allow religious or philosophic exemptions [28]. Additionally, 2.6 percent of kindergartners had an exemption for one or more required vaccines (0.2 and 2.3 percent with medical and nonmedical exemptions, respectively). Compared with the prior year, exemptions increased 0.4 percent. Individual states may have even greater within-state variation (figure 1) [29,30]. State-specific vaccine exemption information is available from the Centers for Disease Control and Prevention.

Although the overall prevalence of complete vaccine refusal remains low (approximately 1 percent of United States children <3 years of age [31]), substantial numbers of caregivers refuse one or more vaccines or request that they be administered on an alternative schedule (eg, limiting the number of vaccines per visit or omitting a particular vaccine altogether) [27,32-37]. Many caregivers have concerns about vaccines, even if they ultimately choose to vaccinate their children [33,38,39]. In a nationwide online survey, 6 percent of caregivers reported hesitancy about routine childhood vaccines and 25 percent reported hesitancy about influenza vaccines [40]. Undervaccination is more common in children with autism spectrum disorder (ASD) and their younger siblings than in children without ASD and their younger siblings [41].

●Vaccine belief categorization – Scientific characterization of caregivers according to vaccine beliefs has been attempted in many ways. Surveys and interviews have identified a spectrum of caregiver attitudes and beliefs about vaccines, ranging from "immunization advocate" to "immunization refuser," depending upon how strongly they agree or disagree that vaccines are necessary and safe [1,42-45].

Prior to the coronavirus disease 2019 (COVID-19) pandemic, approximately 50 to 60 percent of caregivers agreed or strongly agreed that vaccines are necessary and safe [42-45]. Approximately 40 percent had concerns about necessity or safety; this group may vaccinate their children despite their concerns or may choose to delay or refuse one or more vaccines. In a study conducted prior to the COVID-19 pandemic, predictors for caregiver vaccine hesitancy were younger caregiver age, lower levels of caregiver education, and greater religiosity [46]. Vaccine-hesitant caregivers also had lower trust in physicians. As the COVID-19 pandemic wanes, vaccine attitudes continue to evolve. While most caregivers hold largely positive views of childhood vaccines, COVID-19-specific vaccine concerns may negatively impact routine childhood vaccine uptake in the future [47].

WHY CAREGIVERS REFUSE VACCINES — Caregivers may choose to delay or altogether refuse some or all vaccines for their child for a variety of reasons or beliefs. Some of these belief patterns are simple to address, while others are more complex.

Underestimation of risks of natural infection — Poor understanding of the risks of natural infection is the unintended consequence of the success of childhood immunization programs (figure 2). As more diseases are successfully prevented by immunization, caregivers have little familiarity with the devastating effects of vaccine-preventable diseases [48]. They may be unaware of the risks to their child and the community at large if they refuse vaccines. For caregivers who are unfamiliar with vaccine-preventable diseases, potential adverse effects of vaccines may seem more important than potential benefits. (See 'Consequences of vaccine refusal' below.)

Vaccine-hesitant caregivers may attempt to seek information regarding their vaccine concerns solely from sources that confirm their existing beliefs. This phenomenon, known as confirmation bias, may strengthen mistaken beliefs [49].

The potentially serious consequences of vaccine-preventable diseases are discussed separately:

●Hepatitis B (see "Clinical manifestations and diagnosis of hepatitis B virus infection in children and adolescents", section on 'Hepatocellular carcinoma')

●Diphtheria (see "Clinical manifestations, diagnosis, and treatment of diphtheria", section on 'Clinical manifestations')

●Tetanus (see "Tetanus", section on 'Clinical features')

●Pertussis (see "Pertussis infection in infants and children: Clinical features and diagnosis", section on 'Clinical features' and "Pertussis infection in adolescents and adults: Clinical manifestations and diagnosis", section on 'Complications')

●Polio (see "Poliomyelitis and post-polio syndrome", section on 'Clinical manifestations')

●Haemophilus influenzae type b and Streptococcus pneumoniae (see "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Clinical features' and "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Complications' and "Epiglottitis (supraglottitis): Clinical features and diagnosis", section on 'Clinical presentation')

●Rotavirus (see "Clinical manifestations and diagnosis of rotavirus infection", section on 'Clinical manifestations')

●Influenza (see "Seasonal influenza in children: Clinical features and diagnosis", section on 'Complications')

●Measles (see "Measles: Clinical manifestations, diagnosis, treatment, and prevention", section on 'Complications')

●Mumps (see "Mumps", section on 'Complications')

●Rubella (see "Rubella", section on 'Clinical manifestations')

●Varicella (see "Clinical features of varicella-zoster virus infection: Chickenpox", section on 'Complications of varicella')

●Hepatitis A (see "Overview of hepatitis A virus infection in children", section on 'Clinical manifestations')

●Human papillomavirus (see "Virology of human papillomavirus infections and the link to cancer", section on 'HPV Genotypes and risk of cancer' and "Epidemiology, staging, and clinical presentation of human papillomavirus associated head and neck cancer")

●Meningococcal disease (see "Clinical manifestations of meningococcal infection", section on 'Meningitis and acute meningococcemia')

Vaccine safety misinformation — Some caregivers have concerns that vaccines are unsafe or the risks outweigh the benefits. While some safety concerns have a factual basis (eg, rotavirus vaccine and intussusception), most others are misconceptions that lack scientific proof (eg, that multiple vaccines overwhelm the immune system) [50,51]. (See "Rotavirus vaccines for infants", section on 'Intussusception'.)

Concerns about safety and side effects account for approximately 60 to 70 percent of vaccine exemption requests [52-54].

Vaccines that are recommended for children in the United States are fully tested in large numbers of subjects before they are licensed by the US Food and Drug Administration (FDA) [55,56]. After licensure, adverse events associated with vaccines are monitored by the Centers for Disease Control and Prevention (CDC) and the FDA through the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink. When concerns are identified, the FDA issues news releases and may temporarily or permanently suspend the use of a specific vaccine (eg, the RotaShield rotavirus vaccine was withdrawn from the market in 1999) [57]. (See "Rotavirus vaccines for infants", section on 'Intussusception'.)

Most vaccine-associated adverse events are minor and self-limited (eg, local skin reactions, transient low-grade fever). Serious adverse events are rare and should be discussed in the context of the risks associated with natural infection [58].

Safety concerns may include specific side effects (eg, Guillain-Barré syndrome, intussusception, pain), as well as more general concerns [52,59-62]. Concerns about safety are intensified by negative word of mouth and media messages [54,62-64].

Some caregivers may worry that receiving multiple vaccines on the same day overwhelms the immune system, possibly causing autism spectrum disorder (ASD), autoimmune disease, or increased susceptibility to infections [51,61,65-67]. However, evidence of adverse effects related to exposure to multiple antigens is lacking. In a cohort of 1047 children who were exposed to an average of >10,000 antigens by age 24 months (predominantly through whole cell pertussis vaccine), there was no association between increasing antigen exposure and adverse neuropsychologic outcomes [68]. With manufacturing advances that have occurred since publication of this study and the discontinuation of smallpox immunization, children younger than two years are exposed to fewer antigens than they were in 1980 (approximately 125 versus >3000) [68-70].

Furthermore, the infant immune system can respond to multiple antigens (conservative estimates suggest thousands) simultaneously [50,69]. As examples:

●Mild to moderate illness does not interfere with an infant's ability to generate protective immune responses to vaccines.

●The immune response induced by combination vaccines is comparable to the response when the vaccines are administered separately.

Avoiding vaccines does not improve a child's response to infections for which there are no vaccines (eg, enterovirus, Candida) [71-73]. In addition, in a small study, completely immunized and unimmunized children appeared to have equivalently robust innate and adaptive immune responses to nonantigen-specific stimuli [74].

In a nested case-control study of children aged 24 to 47 months, there was no association between vaccine antigen exposure and development of infections for which there are no vaccines [51]. These findings support the safety of the routine immunization schedule, which often requires multiple vaccines at a single visit (figure 3A), and suggest that the schedule does not weaken the immune system.

Misinterpretation of the risk-benefits ratio — Although scientific studies have clearly shown that the benefits of vaccines clearly outweigh the risks, some people persist in their beliefs that vaccines are not needed or are unsafe. Just as some may misinterpret that airplane flight is riskier than transportation by car (the opposite being true), some caregivers may believe that natural disease is safer than vaccination [75]. Confirmation bias may reinforce erroneous risk-benefit interpretation [76].

Vaccine-specific misinformation — Caregivers may choose to vaccinate against diseases that they believe to be more severe (eg, H. influenzae type b) and forego vaccines against diseases that they believe are not dangerous (eg, influenza, COVID-19) [27]. Unfortunately, providers may inadvertently reinforce these beliefs by more strongly emphasizing vaccines for some diseases over others.

MMR vaccine misinformation — The major concern about the combination measles-mumps-rubella (MMR) vaccine, which is unfounded, is belief that MMR causes ASD. This concern can be traced to a 1998 study in 12 children alleging that MMR damaged the intestinal lining, allowing encephalopathic proteins to enter the bloodstream and brain, thereby leading to the development of ASD [77]. The paper was retracted from the public record in 2010 and exposed as fraudulent in 2011 [78-83]. Despite overwhelming evidence disproving this theory, it still is highlighted in media reports and on the internet [84]. The absence of a causal association between MMR vaccine and ASD is discussed separately. (See "Autism spectrum disorder and chronic disease: No evidence for vaccines or thimerosal as a contributing factor", section on 'MMR vaccine and ASD'.)

Another concern related to MMR vaccine, which is also unfounded, is the belief that measles vaccine should be avoided because measles infection protects against cancer [85]. Although there is evidence that oncolytic measles virotherapy (ie, using engineered measles virus to treat cancer) may be helpful, evidence that wild-type measles virus prevents cancer is lacking [85-88]. In addition, studies of oncolytic measles virotherapy suggest that vaccination against measles will increase rather than decrease the potential benefits [85].

HPV vaccine misinformation — Concerns regarding the human papillomavirus (HPV) vaccine are related to the erroneous belief that it may encourage sexual activity [89,90], belief that it is unnecessary [91], perceived excessive influence by the pharmaceutical industry [92,93], and misinformation regarding its safety [61,94-96], including the mistaken belief that it caused the death of a girl whose autopsy demonstrated that she died of an undiagnosed tumor [97].

The media focus on these concerns may have contributed to the number of adverse events reported to the VAERS between June 2006 and December 2008 [98,99]. However, analysis of postlicensure VAERS reports indicates that adverse events were similar to those identified in prelicensure trials [99]. In addition, the rates of adverse events were similar to background rates of other vaccine-associated adverse events, except for syncope, which is more common in the age-group for which HPV vaccine is recommended [100]. Other adverse events that appeared to be vaccine-related have not been substantiated.

The safety of HPV vaccine is discussed separately. (See "Human papillomavirus vaccination", section on 'Vaccine safety'.)

Meningococcal conjugate vaccine misinformation — The major concern about the quadrivalent meningococcal conjugate vaccine is a possible association with Guillain-Barré syndrome [101]. Although Guillain-Barré syndrome has been temporally associated with vaccination, a causal association has not been proven. (See "Meningococcal vaccination in children and adults", section on 'Adverse events'.)

Influenza vaccine misinformation — Caregiver concerns about influenza vaccines include Guillain-Barré syndrome, thimerosal exposure from multidose influenza vaccine vials, inadequate testing to ensure safety in children, and the belief that there is no need for protection against what may be mistakenly considered a "mild type" of influenza [102], a belief strengthened by the false characterization of other respiratory viral illnesses as influenza or "flu."

Concerns about influenza vaccine-associated Guillain-Barré syndrome and other neurologic complications were highlighted by the media during the 2009 H1N1 influenza pandemic. Some commentators erroneously compared the rapid development of monovalent pandemic H1N1 influenza vaccines to the effort for rapid development of a swine flu vaccine in 1976, which was associated with Guillain-Barré syndrome.

However, monovalent H1N1 vaccine was developed using the same methods that are used for seasonal influenza vaccine, and the increased risk of Guillain-Barré syndrome following seasonal influenza vaccine was found to be small or nonexistent [103-105]. (See "Seasonal influenza in children: Prevention with vaccines", section on 'Adverse effects' and "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis", section on 'Vaccinations'.)

Thimerosal has been hypothesized to result in mercury-related neurologic effects, including the development of ASD. Numerous studies refute this hypothesis, but some caregivers remain unconvinced. Thimerosal-free preparations of influenza vaccine are available for families who remain concerned about thimerosal exposure. (See "Seasonal influenza in children: Prevention with vaccines", section on 'Types of vaccine' and "Autism spectrum disorder and chronic disease: No evidence for vaccines or thimerosal as a contributing factor".)

COVID-19 vaccines misinformation — Caregiver concerns related to COVID-19 vaccines may include [106-109]:

●COVID-19 vaccine safety – Misinformation regarding the safety of messenger ribonucleic acid (mRNA) vaccines is prominent. While several of the COVID-19 vaccines are associated with a slight increased rick of myocarditis and pericarditis in young males, the benefits of vaccination greatly outweigh the risks. Other rumors, including negative impact on fertility and alterations to the recipient's deoxyribonucleic acid (DNA), are unfounded. (See "COVID-19: Vaccines", section on 'Rare but serious associated events'.)

●Necessity of COVID-19 vaccine in children – COVID-19 can cause significant morbidity and mortality in children. Since the beginning of the pandemic, tens of thousands of children have been hospitalized and over 1000 children have died [110]. Additionally, children are at risk for multisystem inflammatory syndrome in children (MIS-C), which can be fatal [111]; importantly, vaccination may be protective against MIS-C. As with adults, children are at risk for long COVID. COVID-19 infection in children may be associated with an increased risk of new-onset diabetes in persons <18 years [112-114]. (See "COVID-19: Vaccines", section on 'Children'.)

●COVID-19 vaccines testing in children – Following successful clinical trials in adults, which demonstrated strong efficacy and safety, bridging studies were conducted in adolescents and children. These demonstrated similar safety and efficacy for both mRNA vaccines available in the United States.

●COVID-19 vaccine approval process – mRNA vaccine technology has been under development for several decades [115]. All authorized vaccines in the United States were required to undergo all phases of clinical trials. Given the ongoing, significant morbidity and mortality caused by COVID-19, phases of the clinical trials occurred in an overlapping fashion to eliminate delays. Delays in review by the FDA were also minimized [116].

●COVID-19 vaccine after a COVID-19 infection – Several studies demonstrate that protection against future severe COVID-19 is enhanced when previously infected persons are vaccinated [117].

Adjuvant misinformation — Adjuvants are materials added to vaccines to improve the immune response [118]. One of the most common adjuvants is aluminum, which is used in many inactivated vaccines (eg, hepatitis B vaccine, diphtheria-tetanus-acellular pertussis vaccine, pneumococcal conjugate vaccine). Aluminum adjuvants are considered to be both safe and effective, with rare adverse effects [119,120]. There has been concern that the cumulative dose of aluminum from childhood vaccines exceeds safe levels [121]. However, during the first year of life, the total body burden of aluminum from diet and vaccines is lower than the minimal risk level determined by the Agency for Toxic Substances and Disease Registry [121,122]. In a cross-sectional study of children age 9 to 13 months, no correlation was found between blood and hair aluminum levels and immunization history [123].

Although aluminum has been hypothesized to play a role in the development of autoimmune diseases (eg, macrophagic myofasciitis, autoimmune autoinflammatory syndrome induced by adjuvants) [124-126], evidence does not support the hypothesis [61,127-130]. In a population-based study, the risk of autoimmune disease was lower among patients who received aluminum-containing allergen-specific immunotherapy (which contains more aluminum than vaccines) than among patients receiving conventional allergy treatment [131].

Poor trust — Vaccines, especially vaccines recommended by government officials or large organizations, may be negatively impacted by poor trust. The Tuskegee Study, which harmed hundreds of Black men between 1932 and 1972, continues to negatively impact medical trust. Since that time, patient safety has been enhanced by the implementation of institutional review boards, data safety monitoring boards, and hospital quality assurance programs. Despite these safeguards, some people may continue to fear that vaccines are experimental or that safety was not adequately studied in people of their racial or ethnic group. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients without HIV", section on 'Introduction'.)

Caregivers who seek vaccine exemptions may have a low level of trust in the government and health care professionals and may turn to complementary or alternative medicine professionals whom they consider to be reliable sources of vaccine information [52,132]. They also may refuse other medical interventions (eg, neonatal vitamin K) [46,47,133].

Fear of vaccines and/or vaccine ingredients — Some people may have a profound dislike for medical interventions or procedures, such as vaccines. These individuals may have a heightened fear of needles, blood, or hospitals. To avoid these triggers, they may adopt attitudes or behaviors to avoid encountering these experiences. Even though vaccines could help them or their child avoid considerable medical intervention should they acquire natural infection, they persist in their desire to avoid vaccination [134].

Nonconformist or individualist identity — Some individuals will refuse some or all vaccines based on general skepticism of consensus views [134]. In other words, they will reject vaccines if the prevailing view is that vaccines are good or important. Similarly, these individuals may make decisions based on what is best for themselves without regard to what is best for others or the community. Thus, the importance of herd immunity is not important to them. Nonconformists may reject the idea of any vaccine which is mandatory (ie, vaccines required by law for school entry).

Conspiracy theory beliefs — The COVID-19 pandemic brought vaccine-related conspiracy theories to the forefront [135,136]. Examples of conspiracy theories that have been popularized by social media include: COVID-19 vaccines insert microchips in vaccine recipients; pharmaceutical companies created COVID-19 to increase the sales of vaccines and drugs; and COVID-19 vaccines are attempts to genetically modify humans. Some people will latch onto these conspiracy theories as they offer a simplified explanation for a complex event. If exposure to these conspiracy theories occurs repeatedly, people may begin to trust these messages despite their lack of a factual basis.

CONSEQUENCES OF VACCINE REFUSAL

For the individual — Vaccine refusal increases the risk of vaccine-preventable diseases among unvaccinated individuals [137].

●Risks of vaccine refusal – Unvaccinated children have a greater risk of acquiring vaccine-preventable disease than their vaccinated peers. In observational studies and mathematical modeling, the magnitude of the increased risk is approximately 9-fold for varicella, as high as 35-fold for measles, and ranges from 6- to 28-fold for pertussis [138-143]. Similarly, people fully vaccinated against COVID-19 experience risk reduction of infection and severe disease compared with unvaccinated people [144,145].

A systematic review evaluated the association between vaccine refusal and measles infection in the United States between 2015 and 2020 [17]. Among the 1392 people with measles, 71 percent had no history of measles vaccination, 11 percent had a history of measles vaccination, and 18 percent had unknown vaccination status. Although the reason for lack of vaccination (eg, medical exemption, religious exemption) was not consistently documented, 82 percent of those who were unvaccinated were old enough to have received a measles vaccine.

●Risks of vaccine delay – The risks of delaying immunization have not been well studied [27]. As a general rule, vaccine-preventable diseases (eg, pertussis, influenza) are more severe in infants and young children than in older children. Delaying immunizations increases the duration of vulnerability for these young children.

For the community — Vaccine refusal increases the risk of outbreaks of vaccine-preventable diseases in the general population [137,146]. The World Health Organization considers vaccine hesitancy a threat to global health [3]. In addition to causing preventable illness in the community, outbreaks of vaccine-preventable diseases unnecessarily consume public health resources (eg, for laboratory testing, contact investigation, control measures) [147-149].

In observational studies, unvaccinated individuals tend to cluster geographically, making some communities more vulnerable [6,14,75,147,150-152].

These outbreaks may affect individuals who are unvaccinated due to religious or philosophical objections to vaccines, children too young to be vaccinated, people with contraindications to vaccines, and vaccinated individuals with suboptimal immune response or waning immunity [140,147,153,154]. The rates of disease among vaccinated individuals increase as vaccinated and unvaccinated individuals mix in communities [14,16,140,141].

Multiple outbreaks of vaccine-preventable diseases (measles, polio, rubella, pertussis, H. influenzae type b) have been related to religious groups or communities opposed to immunization [147,149,151,154-163]. In 2019, the United States experienced the highest number of measles cases since the United States was declared measles free in 2000 [164,165]. The Centers for Disease Control and Prevention provides information about measles outbreaks in the United States and around the world.

Importantly, the COVID-19 pandemic increased the risks of measles outbreaks globally due to the postponed or missed measles vaccination, thus increasing the risks of larger measles outbreaks around the world [166].

APPROACH TO MANAGEMENT — Our approach to the management of vaccine hesitancy involves establishing a positive dialogue, identifying caregiver concerns, providing education targeted to those concerns, maintaining a relationship with the family, and making every effort to follow the recommended immunization schedule, as described in the sections below. Our approach is consistent with that of the American Academy of Pediatrics (AAP) Committees on Infectious Diseases, Practice and Ambulatory Medicine, and Bioethics [55,167,168].

A 2015 systematic review of strategies for addressing vaccine hesitancy found few strategies explicitly designed to address vaccine hesitancy or to quantify the impact of the intervention and wide variation in effect size, settings, and target populations [169]. However, multicomponent and dialogue-based interventions appeared to be most effective. Previsit screening for vaccine hesitancy has not been shown to improve on-time immunization [170].

Establish a positive dialogue — Establishing a positive, nonconfrontational dialogue that presumes that the caregivers will ultimately vaccinate the child is essential to ensuring a successful outcome [55,171]. The dialogue should begin at the first provider-caregiver encounter and continue at every subsequent interaction. Having the dialogue and establishing/maintaining trust is more important than the outcome at any one visit [172]. The goals are to identify specific caregiver concerns and the forces that influence the caregivers' knowledge and attitudes toward vaccines [173,174].

Key points in establishing the dialogue include [55,172,175]:

●Acknowledging a shared goal (ie, what is best for the child)

●Acknowledging the large volume of information and/or misinformation about vaccine benefits and safety

●Offering to help caregivers to gather and interpret the best information to make an informed decision (table 1)

Provide a strong vaccine recommendation — The health care provider has an important influence on decisions about immunization, even among vaccine-hesitant caregivers [176-180]. Surveys suggest that approximately one-third to one-half of vaccine-hesitant caregivers eventually vaccinate their children [38,171,181,182]. The strength and quality of the provider recommendation plays a key role in the caregiver decision to vaccinate [183-185].

How the provider initiates the conversation about vaccines may play a role in vaccine acceptance. In observational studies, a presumptive approach (eg, "He is due for three shots today") was associated with less caregiver resistance to immunizations than a participatory approach (eg, "What would you like to do about shots?") [171,186-189]. However, the presumptive approach was also associated with lower ratings for visit experience, suggesting that further study is needed to determine the optimal use of this approach.

Additional information about communicating with vaccine-hesitant caregivers and sample scripts are available through the AAP, the World Health Organization (WHO), the Autism Science Foundation, and in reference [43] (free full text available through BioMed Central).

Identify concerns — A major goal of the dialogue is to identify caregiver concerns and the forces that influence caregiver concerns about vaccines (eg, family members, religious community, the media, etc). Alternatively, some caregivers may hold strong beliefs in conspiracy theories, suffer extreme fear of or aversion to medical interventions, or prefer to take an individualist or nonconformist approach to medical recommendations [134].

Regardless of the source of vaccine concerns, providers may inadvertently make incorrect assumptions about caregiver attitudes and beliefs (eg, mistaking lack of knowledge for hesitancy or overestimating the strength of caregiver beliefs) [173,174]. Once the concerns are identified, the provider can establish a plan for targeted education to address them. (See 'Why caregivers refuse vaccines' above and 'Target education' below.)

Some concerns may not be immediately obvious. Caregivers who are concerned that their infant may suffer during vaccine administration may fear committing harm (eg, giving an unsafe vaccine) more than permitting harm (eg, taking a chance that their child will develop a disease) [175]. Providers must listen carefully and respectfully to understand these concerns, even if it is time consuming.

Respectful listening is also critical to identifying the source of caregiver concerns. Caregivers may receive vaccine information from mainstream media or the internet [62]. The mainstream media has a limited ability to adequately communicate scientific information about vaccines, and internet sites are not subject to constraints regarding scientific accuracy or the fairness of their reporting.

Mainstream media reports are designed to gain attention, present information that is easy to understand, and highlight pro- and antivaccine viewpoints in a limited span of time. They may give equal or greater weight to ill-informed opinions or anecdotal claims about the dangers of vaccines than to the rigorous scientific studies that prove vaccines are safe and effective [48,63,84,190]. Erroneous impressions from the media (including social media) may be reinforced by stories from family members, friends, or the internet [54,62,191,192]. The resulting misinformation leads to unnecessary caregiver concerns. Health care providers need to understand these concerns to effectively address them.

Target education — Many caregiver concerns about vaccines are amenable to dialogue and discussion. The provider must address relevant concerns while emphasizing that vaccines are safe and effective and that serious disease can occur if the child and family are not vaccinated, realizing that some caregivers may need information from a variety of resources (table 1) [55].

Providers should target education to specific caregiver concerns and/or beliefs. Potential topics include:

●Vaccine benefits and limitations – While communicating the benefits of vaccines, it is also important to acknowledge their limitations. They are neither 100 percent effective nor completely risk free. Provision of this information helps to establish credibility but must be placed in proper context, particularly for caregivers who tend to overestimate the risks of vaccines and underestimate the risks from vaccine-preventable diseases [48]. For such caregivers, it may be helpful to define the options in terms of benefits with risks rather than focusing on risks alone [50]. For example, the risk of acquiring measles during an outbreak may be 35 times higher in an unvaccinated than in a vaccinated person [141]. The risk of measles-associated encephalopathy or subacute sclerosing panencephalitis following natural measles is much higher than the risk of encephalopathy from measles vaccine.

●Vaccine safety and adverse events – Patients and caregivers are often looking to their provider to reassure them about the risk-benefit balance. For this reason, providers should clearly state the overwhelming benefit of vaccination and that most side effects are minor and short lived.

●Risks of natural infection – In the context of provider-caregiver discussion, visual imagery and anecdotes from caregivers who are vaccine advocates, and with whom other caregivers can identify, may be used to support the educational message that serious disease can occur if the child and family are not immunized [55]. Without the associated discussion, preferably with a trusted provider, these educational messages may not have the intended effect (ie, increased vaccination), particularly among caregivers with the least favorable view of vaccines [193]. Visual imagery and anecdotes from caregivers who are vaccine advocates are available from Families Fighting Flu, Meningitis Angels, National Meningitis Association, and Vaccine-preventable disease: The forgotten story.

●Correcting misconceptions – It is important to dispel myths, correct misinformation, and direct caregivers to scientifically sound information (table 1) [50,55,194]. Providers should avoid using ambiguous language or complicated scientific terms when discussing the evidence supporting vaccine safety and effectiveness. The WHO suggests that providers emphasize core facts, keep the message simple, make explicit warnings, explain why the myth is wrong, use graphics (eg, to demonstrate the number of children who will develop measles if they are vaccinated compared with if they are not vaccinated), and avoid strong language (which can paradoxically increase the perception of risk) [195,196]. It may be necessary to explain the difference between an antigen and a vaccine or shot. For caregivers who struggle to understand the difference between an antigen and a vaccine, providers can explain that an antigen is a tiny piece of a germ. A vaccine contains either a group of antigens from a killed germ or a weakened germ that allows the body to form protection against that germ the next time the body is exposed that germ [197].

●Injection pain – Providers can allay caregiver concerns about pain by offering one or more of the available methods to reduce injection pain. (See "Standard immunizations for children and adolescents: Overview", section on 'Reducing injection pain'.)

●Autism spectrum disorder – The most common vaccine myth is that vaccines, particularly the combined measles-mumps-rubella vaccine and thimerosal-containing vaccines, cause autism spectrum disorder. These myths are discussed separately. (See "Autism spectrum disorder and chronic disease: No evidence for vaccines or thimerosal as a contributing factor".)

●Vaccines are not necessary – As vaccine-preventable diseases become less common and caregivers have little familiarity with the devastating effects of vaccine-preventable diseases, some caregivers may believe that vaccines are not necessary [48]. These caregivers must be educated regarding the persistence of vaccine-preventable diseases, the potential for a rapid increase in vaccine-preventable disease incidence when immunization rates decline, and the potential complications of vaccine-preventable diseases [50]. (See 'Consequences of vaccine refusal' above.)

●Vaccines and aborted fetal cells – Several vaccines (varicella, rubella, hepatitis A, one rabies vaccine, and one COVID-19 vaccine [Johnson and Johnson]) are made using cells, either fibroblast or retinal cells, that were obtained from three terminations that occurred between 1960 and 1980. In the laboratory, human cells are needed as these viruses grow better in cells from humans than from other animal cell lines. Once the viruses are grown in the aborted fetal cell lines, the cells are killed as the replicating viruses are released from the cell. During the vaccine manufacturing and purification process, remnant cellular debris is removed. The COVID-19 mRNA vaccines were not manufactured using fetal cell lines; however, both Pfizer and Moderna report that fetal cell lines were used during the testing of mRNA vaccines. The use of vaccines made in this way has been approved by multiple major religions [67,198].

Several strategies incorporating the above elements offer a framework for providers to engage in conversations about vaccine hesitancy [199].

●The CASE method – Developed by Allison Singer, the CASE method aims to establish common ground between the provider and the patient, establish trust, correct vaccine misinformation, and offer an opportunity for the provider to deliver a strong recommendation for vaccination [200]. Following active listening, during which the provider elicits the source of the vaccine concerns, the provider offers the following:

•Corroborating statement – The purpose of the corroborating statement is to find common ground with the patient/caregiver. Examples of corroborating statements include: "Other caregivers have shared similar concerns with me," or "I saw that on social media, too." When offering a corroboratory statement, the provider must be careful not to accidently confirm vaccine misinformation as truth.

•About me – The provider should identify and explain the source of their knowledge about vaccines to establish trust.

•Science – The provider corrects the vaccine misinformation with evidence-based facts. Information should be shared in a way to be most easily understood by the patient or caregiver.

•Explain/Advise – Once the vaccine misinformation has been corrected, the provider should emphasize the importance of vaccination and should offer a strong recommendation for vaccination.

●The Ask-Tell-Ask method – Providers may consider using this streamlined technique, during which the provider follows this simple framework [201]:

•Ask – Provider asks the source of the vaccine concern.

•Tell – Provider tells the patient or caregiver what they want them to know.

•Ask – Provider inquires about understanding and asks what else they would like to learn.

●The OARS method – Alternatively, providers may prefer the OARS method, which emphasizes affirming the families' values and thoughts. The components of OARS are as follows [202-204]:

•O – Open-ended questions help elucidate caregiver's position on vaccination and their specific concerns (ie, What concerns do you have about the HPV vaccine? What do you know about HPV vaccine?).

•A – Affirming families' strengths, values, and positive qualities helps to establish a strong rapport and shows respect (ie, I know that you want what is best for your child).

•R – Reflecting the caregiver's thoughts demonstrates active listening by the provider and further strengthens rapport (ie, I hear how concerned you are about what you read on social media).

•S – Summarizing what was discussed and bridging back to the possibility of vaccine acceptance; providers should show appreciation and consider offering further educational materials while indicating the opportunity for future discussions [205].

Maintain relationship whenever possible — We encourage providers to make continuous and strident efforts towards educating caregivers who are vaccine hesitant, maintaining the relationship whenever possible. The decision to vaccinate ultimately belongs to the caregivers. The benefits of immunization must be weighed against those of the provider maintaining a positive relationship with the family. Maintenance of the relationship permits time for ongoing dialogue and targeted education and ensures that the child has a medical home. Ethical arguments for and against continuing care for children of vaccine-hesitant caregivers can be made [206,207]. (See 'Establish a positive dialogue' above and 'Target education' above.)

Although we encourage providers to maintain relationships with vaccine-hesitant families, we recognize that providers may have no option but to dismiss a family from their practice when poor communication and distrust are insurmountable [181,208]. This decision is not one that should be made lightly and should be made only after considering and respecting the caregiver's point of view. Factors influencing this decision include lack of shared goals, absence of trust in the clinician-family relationship, and concern that the child may subsequently contract a vaccine-preventable disease or transmit a vaccine-preventable disease to an individual who has vaccine contraindications or is too young to be immunized [206,209]. These concerns are particularly salient if community immunization rates are low and disease prevalence is high, or if the child has a medical predisposition to disease.

The 2016 AAP Clinical Report on countering vaccine hesitancy, which was reaffirmed in 2022, suggests that dismissal of a family should be an option of last resort, used only when [55,167,210]:

●The clinician has exhausted all means of education.

●The family has been made aware of the policy regarding dismissal of nonvaccinators.

●The geographic area is not in short supply of pediatric providers.

●The practice provides sufficient information to help the family find another provider and continues to provide health care until the family does so (usually 30 days).

Alternative schedules — Alternative vaccine schedules are those that deviate from the recommended vaccine schedule (eg, in the United States, the schedule recommended by the Centers for Disease Control and Prevention (CDC), AAP, and American Academy of Family Physicians (figure 3A-B)). Examples include the "selective vaccine schedule" and "alternative vaccine schedule" published by Dr. Robert Sears [211], as well as individual caregiver requests to postpone or skip one or more vaccines.

Unlike the CDC United States Recommended Immunization Schedule, alternative vaccine schedules offer incomplete and delayed protection against life-threatening diseases. For this reason, they should be considered only after other options have failed and the family would otherwise refuse vaccination entirely. Although alternative schedules may allay caregiver fears enough to permit immunization, they should not be used as a substitute for establishing caregiver dialogue or targeted education [48,55]. (See 'Establish a positive dialogue' above and 'Target education' above.)

Alternative schedules increase the duration of vulnerability to vaccine-preventable diseases that continue to cause outbreaks (eg, measles, pertussis), increase the risk of undervaccination, and may increase the risk of adverse effects [212-215]. They may require extra visits (ie, visits for immunization outside of the routine well-child visit schedule) that may be cumbersome and time consuming.

A committee convened by the Institute of Medicine (now the National Academy of Medicine) to study the health outcomes related to the recommended childhood immunization schedule in the United States concluded that the schedule is safe and found no definitive evidence of adverse events related to multiple immunizations [216]. The schedules for individual vaccines have been demonstrated to be safe and effective.

Timely receipt of vaccines during the first year of life has no adverse effect on neuropsychologic outcomes. Review of data from the Vaccine Safety Datalink study, which included 1047 children, indicates that the 47 percent of children who received their vaccines on time (≥2 hepatitis B, three diphtheria-tetanus-pertussis, three H. influenzae type b, and two polio vaccines within 30 days of the recommended age) performed as well or better at age 7 to 10 years on every measure of neuropsychologic outcome than the 23 percent of children who received all of the recommended vaccines, but not on time, and the 30 percent of children who did not receive all of the recommended vaccines [217].

Precautions for unimmunized children — Children who have not been immunized are at risk of developing or transmitting vaccine-preventable diseases. When they are ill, it is important for their caregivers to tell the health care provider that the child is unimmunized, particularly providers who are not familiar with their child's medical history or lack of immunizations (eg, on-call clinicians, emergency department clinicians). Determining the current immunization status is a necessary part of health care provider history-taking and assessment during every sick-child encounter. This information allows the provider to consider vaccine-preventable diseases in the differential diagnosis and to prevent spread of vaccine-preventable diseases to other patients.

The CDC, AAP, and American Academy of Family Physicians have developed a handout to remind caregivers of the risks and responsibilities of refusing immunization [218]. Another handout is available from the Immunization Action Coalition (IAC).

Documentation — Providers should document each discussion with caregivers about the risks of not immunizing [167]. The AAP has developed guidelines for documentation and provides a sample "Refusal to Vaccinate" form (available through the AAP). Another sample form is available through the IAC [219].

PREVENTION — Strategies to prevent vaccine hesitancy have not been well studied. However, given that health care providers are an influential source of vaccine information, it is helpful for clinicians to establish open, honest, nonconfrontational dialogue about the importance of childhood vaccinations at the first interaction (ideally at the prenatal visit) [52,220,221]. We encourage providers to share their own or their practice's philosophy or policy for delaying or refusing vaccination to avoid the potential for future disagreements. Providers may want to consider offering evidence-based, accurate vaccine-related information in advance of vaccine decision-making. Known as prebunking, this technique may help minimize the later impact of vaccine misinformation on caregivers and their children [67,222,223].

The dialogue should be continued at subsequent well-child visits. At each encounter, providers should listen to caregiver concerns to identify sources of misinformation or other factors that may lead to vaccine hesitancy. Providers can then provide individualized education to address specific concerns or misconceptions. (See 'Target education' above.)

Education should be multifaceted, with providers answering questions unambiguously, avoiding complicated statistics, and providing information that is easily understood and "personal." Some caregivers may find the information in the Vaccine Information Statements adequate to address their needs, but others may require more detailed scientific information or may find simple question-and-answer pamphlets or personal testimonials from vaccine advocates more helpful (table 1) [48,224]. (See 'Resources' below.)

Support for early vaccine education is provided by a randomized trial in which vaccine-hesitant caregivers (defined by a score of ≥25 on the Parent Attitudes about Childhood Vaccines [PACV] survey) who received educational information (a video, written information, and written instructions for finding accurate information on the internet) at the two-week health supervision visit had decreased PACV scores at the two-month visit compared with those who received usual care [225].

RESOURCES

●For vaccine-hesitant caregivers – Caregivers who need more information than the clinician can provide during an office visit can be directed to a number of reputable vaccine websites (table 1).

Focus groups suggest that most caregivers trust information from the Centers for Disease Control and Prevention (CDC) or American Academy of Pediatrics (AAP) [226].

Caregiver/family groups may be particularly helpful for vaccine-hesitant caregivers because they highlight identifiable, serious, and sometimes fatal consequences of refusing immunization, using anecdotes and visual imagery to counter those of children allegedly injured by vaccines [227].

●For health care providers – The CDC, in partnership with the AAP and the American Academy of Family Physicians, has developed Provider Resources for Vaccine Conversations with Parents. This website provides communication tips, vaccine safety information, and answers to common questions. A related website provides specific information about vaccine-preventable diseases and the vaccines that prevent them that can supplement Vaccine Information Statements and guide caregiver risk-benefit discussions [48].

●The Vaccine Education Center at the Children's Hospital of Philadelphia provides a library of references that discuss vaccine safety and disprove claims made against vaccines.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Immunizations in children and adolescents".)

SUMMARY AND RECOMMENDATIONS

●Definition – Vaccine hesitancy is a term used to describe refusal of vaccination or a delay in acceptance of vaccination. (See 'Definition' above.)

●Epidemiology – Although the overall prevalence of complete vaccine refusal remains low (<2 percent), substantial numbers of caregivers refuse one or more vaccines or request that vaccines be administered on an alternative schedule. (See 'Epidemiology' above.)

●Why caregivers refuse vaccines – Concern about vaccine safety is the most common reason for vaccine refusal. Other caregiver concerns may focus on the belief that vaccines are not necessary or in freedom of choice. (See 'Vaccine safety misinformation' above and 'Nonconformist or individualist identity' above and 'Underestimation of risks of natural infection' above.)

●Consequences of vaccine refusal – Vaccine refusal may result in vaccine-preventable disease in the individual and/or outbreaks of vaccine-preventable disease in unvaccinated and vaccinated individuals. (See 'Consequences of vaccine refusal' above.)

●Approach to management

•Our approach to the management of vaccine hesitancy involves (see 'Approach to management' above):

-Establishing a positive dialogue – Approaching each patient encounter using positive, nonconfrontational dialogue that presumes that the caregivers will ultimately vaccinate their child. (See 'Establish a positive dialogue' above.)

-Identifying caregiver concerns – Listening carefully and respectfully to identify caregiver concerns and the forces that influence caregiver concerns. (See 'Identify concerns' above.)

-Targeting education to address caregiver concerns – Targeted education may include education about vaccine effectiveness (figure 2), acknowledgment of vaccine limitations, providing accurate estimates of the risks of adverse events in the context of the risks of natural infection, correction of misconceptions, and discussion of techniques to alleviate injection pain. (See 'Target education' above and 'Resources' above.)

•We encourage providers to maintain relationships with families who refuse immunization but recognize that a provider may have no option but to dismiss a family from their practice when poor communication and distrust have become insurmountable. (See 'Maintain relationship whenever possible' above.)

•In the United States, we strongly support following the immunization schedule provided by the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American Academy of Family Physicians (figure 3A-B). Alternative schedules increase the duration of vulnerability to vaccine-preventable diseases. (See 'Alternative schedules' above.)