Unwelcome return: analyzing the recent rise of measles cases in the United States

Abstract

Measles is a highly contagious viral illness mainly affecting the younger population worldwide despite the availability of a safe and effective vaccine. The disease is caused by measles virus, a member of the Paramyxoviridea family, which is transmitted through aerosols and respiratory droplets. Widespread vaccination has led to a significant decline in morbidity and mortality worldwide; however, recent years have witnessed a resurgence of outbreaks in the United States, highlighting barriers in achieving and sustaining elimination goals. The measles and rubella elimination initiative, under Immunization Agenda 2030, required at least 5 World Health Organization regions to achieve measles elimination by 2020, but none of the regions met these goals. Vaccine hesitancy, virus importation via international travel, and waning immunity are considered contributing factors to the recent surge of measles outbreaks. This review highlights the challenges in the pursuit of measles eradication and the importance of a multidimensional approach involving public health interventions.

The word measles is derived from the Dutch word masels, referring to the red rash (blemish) caused by the ancient febrile illness. The disease was first reported in the United States in 1657 in Boston, Massachusetts.¹ The 20th century witnessed many milestones against measles. These include the discovery of the viral nature of the pathogen in 1911, the isolation of the virus from infected hosts in 1954, and the development and rollout of the measles vaccine in the 1960s, which led to a significant decline in both morbidity and mortality. The introduction of double doses of the vaccine in 1988 led to the elimination of measles from the United States in 2000.^2,3 Measles is a single-stranded, negative-sense RNA virus belonging to the Paramyxoviridea family and is caused by the transmission of respiratory droplets or aerosols.⁴ The virus is considered serologically monogenetic but can be divided into genotypes based on the differences in the nucleotides encoding the H and N proteins. Twenty-four known genotypes of measles virus are grouped into eight clades from letters A to H; B3, D4, D8, and H1 are the only known genotypes noted in circulation since 2016.^5,6 The World Health Organization (WHO) defines elimination as a 12-month period free of endemic transmission of measles in a region or country with a well-performing surveillance system in place. Prior to the introduction of measles vaccines, measles accounted for around 500,000 cases and 500 deaths annually in the United States.⁷ Following successful elimination of measles in the United States in 2000, the incidence decreased significantly, with an average of 175 cases per year in the 21st century. The WHO estimates that nearly 56 million deaths have been averted because of widespread measles vaccination. Despite these advances, >128,000 measles cases were reported globally in 2022.⁸

The United States has experienced variable trends in measles outbreaks in the 21st century, with major outbreaks occurring in 2014–2015 and 2019 (Figure 1). The initial outbreak in 2014 was traced back to 42 individuals who contracted measles within 3 days, all from visiting a Disney theme park in California. This outbreak was attributed to a traveler from the Philippines infected with the B3 genotype.⁹ In 2019, the United States reported 1274 measles cases, the highest number since 1992. Of these cases, 7.2% were linked to international travel, underscoring a concerning trend of local transmission and rising vaccine hesitancy.¹⁰ In the first quarter of 2024, the number of cases has already surpassed the total cases in 2023. During the same period in 2023, only 10 cases were recorded. As of April 2024, 19 states have had 128 confirmed cases of measles, representing a 1180% rise in the number of cases compared to the same time frame. Thirty-three of these cases were reported during a single week starting on March 17, 2024 (Figure 2).¹¹ This article reviews the recent trends of measles cases in the United States and correlates it with the factors behind the increase in outbreaks. We aim to address current challenges and solutions for the path toward eradication of measles.

Figure 1.

Annual cases of measles in the United States.

Figure 2.

Weekly comparison of measles cases in the United States, 2023 to 2024.

PATHOPHYSIOLOGY AND CLINICAL FEATURES

Measles spreads through airborne transmission, infecting respiratory epithelial and immune cells. Following initial replication, the virus disseminates through intercellular membrane pores, bypassing the extracellular space where antibodies limit its spread. While measles typically confers lifelong immunity after the patient recovers, acute infection depletes CD150+ memory lymphocytes, leading to transient immune amnesia.^12,13 In susceptible individuals, immune suppression coincides with widespread epithelial damage and increases the risk of secondary bacterial infections, leading to complications such as diarrhea, pneumonia, or otitis media.¹⁴

Measles manifests as a self-limited, widespread rash and accompanying fever. Evaluation involves reviewing the patient’s immunization history and disease contacts and checking for past exanthematous illnesses.¹⁵ The course of measles is characterized by three phases: prodromal, eruptive, and convalescent phase. It begins with a prodromal phase, characterized by classical symptoms like cough, coryza, conjunctivitis, and fever. The pathognomonic Koplik spots—tiny, white spots on the buccal mucosa—appear 1 to 2 days before rash onset in up to 70% of cases.¹⁶ The eruptive phase, which has the maximum infectious potential, is marked by a distinctive erythematous maculopapular rash that originates behind the ears and at the hairline, subsequently spreading to the face, trunk, and limbs. The convalescent phase begins as the rash fades; fever and general malaise also resolve during this phase, signaling the end of the acute infectious period (Figure 3).¹⁷ The entire disease course, spanning approximately a week, is highlighted in Figure 4.

Figure 3.

Measles transmission and pathophysiology.

Figure 4.

Clinical course of measles.

DIAGNOSIS, PREVENTION, AND MANAGEMENT

Diagnosis should be suspected in the patient presenting with the aforementioned symptoms, especially in those who come in close contact with a suspected case or someone with a history of recent international travel.¹⁷ Laboratory confirmation involves one of the following: detection of IgM antibodies against measles, which start to peak 3 days after the onset of rash; a fourfold rise or fall of IgG antibody; or detection of measles RNA by reverse transcription polymerase chain reaction from nasopharyngeal aspirates or throat swabs. Viral cultures are not usually obtained, as they are expensive and time consuming. Measles is a nationally notifiable disease, and clinician reporting to health departments is mandatory in every state.¹⁸

The absence of any animal reservoir for the measles virus makes it an ideal candidate for eradication with vaccines, although the virus’s high transmissibility demands homogenous vaccine coverage above >95%.¹⁹ In children, the first dose is administered at 12 to 15 months and the second dose at 4 through 6 years of age.²⁰ A single dose of the measles vaccine administered at >12 months confers protection to >93% of individuals. Receiving a second dose of the measles vaccine can increase the protection rate to >97%.⁷ Adults born in 1957 or after and with evidence of incomplete immunity against measles should receive at least one dose of the measles vaccine.²¹ Health care professionals should have documentation of receiving two doses of the MMR vaccine.²² Postexposure prophylaxis in unimmunized contacts for measles includes either vaccination within 72 hours of exposure or administration of immunoglobulin within 6 days. Note that coadministration of the vaccine and immunoglobulin renders the prophylaxis ineffective.²³

Since no specific antiviral treatment is available for the measles virus, supportive care is the mainstay of management. Vitamin A supplementation is known to decrease disease severity and all-cause mortality in low- and middle-income countries. The WHO recommends administering vitamin A in age-appropriate dosages for all severe cases requiring hospitalization, even in countries where measles is not usually severe. The dosage is 200,000 IU for children ages ≥12 months and 100,000 for children ages 6 to 11 months for 2 consecutive days.²³

DISCUSSION

The number of measles cases in the United States in the first quarter of 2024 has already surpassed the total number of cases in the previous year. Over 81% of this infected population is unvaccinated or of unknown vaccination status, highlighting the critical challenge posed by vaccine hesitancy.¹¹ This term refers to “delay in acceptance or refusal of vaccination despite availability of vaccination services.”^24–26 While the decreased incidence of vaccine-preventable diseases in the 21st century is attributed largely to widespread immunization, parents might have a paradoxical response where they perceive the side effects of the vaccine to be more detrimental than the disease itself.²⁷ The common factors contributing to vaccine hesitancy are summarized in Table 1. The COVID-19 pandemic, in addition to disrupting global supply chains of vaccines, exacerbated polarization about vaccine safety, intensifying mistrust in recommendations of the Centers for Disease Control and Prevention. Overcoming vaccine hesitancy requires changes in policy and communication strategies. Social media can serve as a medium to not only gauge public perception about the vaccines but to also address specific concerns of parents.²⁸ The “I Immunize” social media campaign is an Australian example of achieving positive perceptions about vaccination by using testimonials from local residents.²⁹

Table 1.

Common parental concerns for vaccine administration

Vaccine safety	Necessity of vaccines
Too many vaccines Development of autism Vaccines additives (thimerosal, etc.) Overload of the immune system Serious adverse effects Inadequate research before licensure Potential for long-term side effects	Disease as more “natural” than vaccine Lack of perception of the real risk of the disease being prevented A view that vaccines do not work Freedom of choice Right to choose whether to immunize their child View that parents know what’s best for their child Lack of trust in government health authorities and pharmaceutical companies Philosophical, ethical, or religious reasons

Side effects of the measles vaccine are generally mild and rare and mostly occur with the first dose (Table 2). The Wakefield et al study linking autism with the measles vaccine started a robust antivaccine campaign. Despite the article’s retraction in 2010 after debunking by committees of the National Academy of Medicine, the misinformation still remains a strong source of concern for parents.^30,31 Another common misconception is about the simultaneous administration of multiple vaccines overwhelming the immune system, leading to immunosuppression and infections.³²

Table 2.

Rate of side effects with the measles vaccine

Side effect	Rate
Fever	5%–15%
Rashes	5%
Lymphadenopathy	5%–20%
Acute febrile seizures	25–34 seizures per 100,000 vaccines
Thrombocytopenia or immune thrombocytopenic purpura	1 per 100,000 vaccines
Anaphylaxis	5.14 cases per million vaccines

Over 80% of parents reported health care professionals to be a positive influence to vaccinate their child, and this group includes parents who were initially vaccine hesitant.³³ Nearly half of parents who are initially vaccine hesitant accept vaccines after receiving parental education in the form of vaccine information statements, but only 55% of physicians provide adequate reasoning behind the necessity of vaccines, thus highlighting a potential area where physicians could make changes in their behavior and enhance communication.³⁴ Prenatal and postnatal counseling regarding immunization is known to increase the rates of immunizations and can be used as an important moment to provide the correct information about vaccines when parents are most receptive.³⁵ Motivational interviewing is a communication strategy that has proven to be effective in improving vaccine acceptability, especially in the perinatal period. It relies on the use of understandable language by health care professionals, encouraging discussion and questions from the parents instead of direct delivery of information.²⁸ Another communication approach that has been effective is AIMS (announce, inquire, mirror, and secure). It starts with the presumption that the parent is willing to get the child vaccinated but does not rule out discussions³⁴ (Table 3). Measures should be aimed at improving health care professionals’ contribution toward overcoming vaccine hesitancy, such as having a sentinel network of health care professionals who can help monitor emerging local concerns regarding vaccines and help other practitioners be better prepared.^36,37

Table 3.

AIMS approach

AIMS	Description
Announce	Presume people are ready to vaccinate their children
Inquire	Use open-ended, nonjudgmental questions to understand concerns
Mirror	Reflect back your understanding of the concerns to make them feel heard
Secure	Consolidate each conversation by securing trust

In areas where communication strategies are unable to drive up immunization coverage, policy changes, ranging from mandatory vaccination for entry into kindergarten to limiting or discontinuing nonmedical exemptions for vaccines, might have to be used. States like New York and California successfully tried such measures after the outbreaks in 2014 and 2019.^9,38

Given the ongoing rise in measles cases, it is essential to understand determinants of measle vaccine immunogenicity. The HLA and non-HLA genotypes, along with environmental, demographic, and clinical variables, influence interindividual variation in measles vaccine–induced humoral immunity.³⁹ The outbreaks have revealed measles vaccine failure, which means the inability to either mount or sustain a protective immune response among individuals previously vaccinated with two doses of measles-containing vaccine.⁴⁰ While the most prevalent measles virus genotype in the United States is D8, California experienced similar numbers of genotypes B3 and D8 cases and outbreaks in 2019, which allowed the assessment of genotype-specific differences in patient demographics and clinical characteristics for measles cases. A high percentage (40.4%) of vaccine failures were observed, with a higher proportion among cases with the B3 genotype as compared to D8.¹⁰ Neutralizing titers were lower against B3 genotypes than the H1, D4, and A genotypes, suggesting that the protective efficacy of the vaccine varies with the virus strain. Variations in protective antibody titer among vaccinated individuals allow for the accumulation of susceptible individuals and lead to an outbreak when these individuals are exposed to the virus. Genome-based studies coupled with fine-mapping efforts will enhance our understanding of vaccine-induced immunity. Additionally, improved measles vaccine and vaccination practices along with novel vaccinomics will overcome existing vaccine limitations and aid in attaining better disease control.^41,42

Despite substantial global efforts to eradicate measles, the recent rise in the cases of measles can be attributed to a confluence of factors: pockets of populations with low herd immunity, importation of cases from areas experiencing their own outbreaks, and the chances of vaccine failure either due to waning immunity or failure associated with virus genotype. Addressing these issues requires a comprehensive approach that includes education for parents and health care providers, strategic policy adjustments, and effective use of social media for public engagement and accurate information dissemination. Additionally, understanding individual variations in vaccine-induced immunity, influenced by HLA genotypes among other factors, can enhance vaccine strategies and personalized medicine approaches. The issue of vaccine acceptability is interdisciplinary and dynamic. By implementing targeted strategies and fostering collaboration among stakeholders, we can work toward the goal of measles eradication and ensure a healthier future for all.

Disclosure statement/Funding

The authors report no funding or conflicts of interest.