For the past 3 decades, I have cared for transplant candidates and recipients, who receive immunosuppressive drugs to prevent rejection but which place them at risk of infections. More than most other patients, they need vaccinations, per national guidelines,1,2 but their vaccination rates remain suboptimal, both here and in other countries.3,4 Personally, I’m encountering many patients who decline some and occasionally all vaccinations, something that rarely occurred just 10 years ago.
My experience reflects a disturbing global trend toward vaccine hesitancy, defined as delaying or refusing available vaccinations,5 or indecisiveness regarding a vaccination decision, independent of behavior.6 Reflecting an extreme form of vaccine hesitancy, anti-vaxxers or antivaccinationists are fundamentally and actively opposed to vaccination,7 often using social media to advance their views.8
Not long ago, we hailed vaccination as one of the top 10 public health achievements in the 20th century.9 Now, the World Health Organization lists vaccine hesitancy among the top 10 threats to global health.10
HOW DID WE GET HERE?
Vaccination skeptics appeared soon after Edward Jenner began advocating vaccination against smallpox at the turn of the 19th century.11 Nobody likes to be told what to do, and riots broke out in several towns in the United Kingdom when the first mandatory smallpox vaccination program was implemented.12 Antivaccination attitudes increased in Europe before gaining ground in the United States toward the end of the 19th century.13 Little did the skeptics know that this vaccine would eradicate this deadly infection from the face of the earth in less than 200 years.
Now, vaccine hesitancy is encountered among different countries, economies, religions, and cultures, and its scope varies depending on the extent of misinformation circulating in a given setting, as misinformation results in distrust, ultimately manifesting as “infodemics.”14–16 The United Nations Children’s Fund has reported that perception of the importance of childhood vaccines declined in 52 of 55 countries during the COVID-19 pandemic, and confidence in these vaccines declined by up to 44% in some countries.17
The messenger RNA (mRNA) vaccines against COVID-19 aroused special skepticism and conspiracy theories. This skepticism emerged even though these vaccines underwent rigorous studies conducted in multiple countries around the world; the technology underlying mRNA vaccines has been studied in other settings for 3 decades; and there is ample evidence for the safety, immunogenicity, efficacy, and effectiveness18,19 of mRNA vaccines compared with other vaccine production methods (Table 1). Patients opposed to mRNA COVID-19 vaccines can now receive Novavax’s Nuvaxovid protein-based subunit vaccine. The estimated prevalence of COVID-19 vaccine hesitancy in the United States varies widely by area, ranging from 2.6% to 26%.20
Messenger RNA (mRNA) vaccines vs other types of vaccines
In addition to the 2 mRNA COVID-19 vaccines, an mRNA respiratory syncytial virus vaccine is approved by the US Food and Drug Administration. A recently published randomized blinded study in healthy adults demonstrated the immunogenicity and efficacy of an mRNA influenza vaccine compared with inactivated influenza vaccine in preventing laboratory-confirmed influenza-like illness, with higher local and systemic reactogenicity within 7 days with the mRNA influenza vaccine but similar serious, severe, and life-threatening adverse events, including those leading to withdrawal from the study.21
Altogether more than 100 vaccines are licensed for use in the United States.22 In development are several more addressing common infections such as urinary tract infections23 and global infections such as malaria,24 dengue,25 chikungunya,26 and Salmonella enterica Paratyphi A.27
Nonetheless, the current state of affairs in vaccination is chaotic and evolving. On September 3, 2025, Florida became the first state to eliminate all vaccination mandates, including those for school children.28 Just 2 weeks later, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) moved from recommending COVID-19 vaccine for everyone to an individualized decision-making approach.29 In response, national and local medical societies issued declarations opposing this move,30 warning of politicization of the Department of Health and Human Services,31 and intensifying public-facing statements and programs supporting evidence-based vaccination guidelines.31–33 On December 4, 2025, the ACIP changed its recommendation for hepatitis B vaccination for newborns—formerly recommended for all, it is now optional if the mother tests negative for hepatitis B.34
WHAT’S AT STAKE?
What’s at stake is not only the reversal of vaccine-associated life-expectancy gains but also the reversal of noncommunicable diseases, particularly cardiovascular disease–associated life expectancy. To put it bluntly, people could die.
Measles is back
In 2000, the World Health Organization declared that measles had been eliminated in the United States. But it is back.
As of December 9, 2025, a total of 1,912 confirmed cases of measles had been reported in the United States in 2025; 92% of these cases were in people who were unvaccinated or of unknown vaccination status.35 Some 47 outbreaks had been reported in 43 jurisdictions, with 88% of confirmed cases being outbreak associated. These numbers are up from past years. Texas reported the highest number of confirmed cases (803), and New Mexico, Arizona, and Utah each reported more than 100 cases. Three quarters of cases in 2025 occurred in people older than 5 years, and 12% of patients required hospitalization. Three people have died.
The mumps, measles, and rubella vaccine is very safe, but it is most effective when more than 95% of people in a community are vaccinated. Unfortunately, only 10 states achieved this herd immunity target in 2023–2024, leaving 280,000 unvaccinated kindergartners at risk and serving as sources of further spread to adults with no or waning immunity. Pockets of unvaccinated people exist even in states with high vaccination coverage, such as New Mexico, leading to outbreaks.35
COVID-19, flu, and respiratory syncytial virus harm the heart
About two thirds of US adults have at least 1 risk factor for cardiovascular diseases.36 To the traditional risk factors such as high blood pressure we should add vaccine-preventable acute viral respiratory infections, including COVID-19, influenza, and respiratory syncytial virus.37 Deaths from noncommunicable diseases are continuing to decline around the world,38 but vaccine hesitancy could slow or reverse this trend.
COVID-19 is receding but not gone
Life expectancy decreased globally during the COVID-19 pandemic, then returned to prepandemic levels in 2023.39 In 2021, COVID-19 became the second-leading cause of death worldwide, particularly impacting lower-middle-income and high-income countries.40 In the United States, COVID-19 moved down to the tenth leading cause of death in 2023.41
Flu is an eternal threat, and bird flu looms
The influenza-associated hospitalization rate in the 2024–2025 influenza season was the highest since the 2009 influenza pandemic. Of those hospitalized with the flu, most had at least 1 underlying medical condition or were age 75 years or older, 17% were admitted to an intensive care unit, 6% received invasive mechanical ventilation, and 3% died during hospitalization.42
In the same season, pediatric influenza-associated encephalopathy occurred in 109 children, 19% of whom died, including 41% of those with acute necrotizing encephalopathy.43 Only 16% of these children had received an influenza vaccine earlier that season.
H5 bird flu is widespread in wild birds worldwide, and for the fourth year in a row it has caused outbreaks in US poultry and dairy cows and sporadic human cases, mostly in poultry and dairy workers, posing low risk to the public.44 The US Centers for Disease Control and Prevention is using surveillance systems to monitor H5 bird flu activity in humans, particularly in those with animal exposures. This virus can mutate and become more transmissible from animals to humans.45 Currently, the risk of transmission to people in the United States is mainly in those in contact with infected animals or contaminated surfaces, and the risk to the general population or of human-to-human transmission is low.46
WHAT PHYSICIANS CAN DO ABOUT VACCINE HESITANCY
Identifying causes of any problem, particularly potentially reversible causes, is the first step in attempting to find solutions.15,16,47,48
Identify and address external barriers to vaccination, such as misinformation, access, cost, and lack of community support.
Present vaccination as the default, rather than optional. Some patients are “hesitant adopters”49 who say they are hesitant but do not actually hold the opinion strongly and get the shot anyway. Sociodemographic factors affect hesitant adopters to different degrees. Clinician recommendations, conversations with friends and family, professional network interactions, workplace recommendations and requirements, and perceived social norms are important factors persuading those who are hesitant to become hesitant adopters (Table 2).
10 Reasons to get vaccinated
Humans cherish their freedom to make their own decisions. In general, positive reinforcement and incentives are more successful than negative reinforcement and punitive actions.
In any event, most people are not hesitant: 84% of Americans are extremely or somewhat confident in the effectiveness of childhood vaccines, and 75% extremely or somewhat agree that they have been tested enough for safety.50
Be equipped to answer our patients’ questions about vaccinations,51,52 using simple infographics, tailored to specific communities and cultures to facilitate conversations. Our recommendations must always be rooted in evidence-based data.53,54
Honestly present how the benefits dwarf potential risks. This builds trust, arguably the most important ingredient in establishing a healthy relationship between clinicians and their patients. Some vaccines decrease the risk of hospitalization and death from infection, even if they do not decrease the risk of acquiring infection. This is still valuable and clinically relevant! Also, vaccination can benefit not only the recipient but also the family and community at large, an argument that appeals to one’s sense of altruism and citizenship.
All approved vaccines have side effects to some degree, but objectively their benefits clearly outweigh their risks. Reassure patients that the preapproval and postapproval vaccine safety system is robust.55,56
Find allies and resources. Providing vaccines at a variety of places in addition to traditional medical offices and vaccination clinics, including emergency departments, schools, and places of work, at no or minimal cost and at extended hours, has been extensively studied and proven effective in increasing vaccination rates.
In an effort to protect their grandchildren through vaccines, grandparents have united in a volunteer-led movement to share personal stories of how vaccines developed before and during their lifetime changed their world (grandparentsforvaccines.com). Training community vaccination champions, such as public officeholders, clergy, teachers, and industry leaders, increases public trust in the value of vaccinations.
With the increasing demands on clinicians’ time,57 we need to use all available resources to stem the tide of vaccine hesitancy and change course from where we could be heading to where we should be heading.
DISCLOSURES
The author reports no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.
- Copyright © 2026 The Cleveland Clinic Foundation. All Rights Reserved.
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