Measles in a Modern World

Measles has been a common and often serious childhood illness for hundreds of years, with one of the first documented cases recorded by a 9th-century Persian physician. The United States began mandatory reporting of measles cases and monitoring trends related to the disease in 1912. In the first decade of reporting, around 6,000 measles-related deaths were reported yearly. By the 1950s, it was recognized that nearly all children experienced the disease by age 15. An estimated 3-4 million cases occurred in the United States yearly towards the end of the pre-vaccine era, with 400-500 deaths annually and over 1,000 cases of measles encephalitis, one of the most dangerous complications (Centers for Disease Control and Prevention, 2020b).

Over the last several decades, the development and wide distribution of the measles vaccine have dramatically decreased the prevalence of measles and its complications. However, the disease still exists and reappears in isolated outbreaks nationwide almost yearly. Measles spreads incredibly easily through unvaccinated or under-vaccinated populations, demonstrating the delicate balance of herd immunity that relies on high levels of vaccine compliance throughout the population.

The high transmission rate, paired with the quick onset of viral symptoms and hallmark rash, as well as the large list of potentially serious complications, emphasizes that healthcare professionals cannot afford to be careless in their knowledge of this disease. They must remain current in recent and local trends of vaccination and disease outbreaks, be familiar with symptoms to identify measles if they come across it, and serve as knowledgeable resources when advocating for vaccination for infants and children.

This course aims to ensure healthcare professionals are adequately prepared to recognize measles, care for patients experiencing complications of the disease, and combat misinformation to preserve the near-eradication of this disease afforded to the United States through vaccines.

Measles, historically, has been thought to be a disease of childhood. However, measles infection can occur in unvaccinated or partially vaccinated individuals or those with compromised immunity.

Unvaccinated young children are at the highest risk. Depending on local immunization practices and the incidence of the disease, age-specific infection rates may be highest in susceptible infants younger than 12 months, school-aged children, or young adults. In densely populated, underdeveloped countries, measles is most common in children younger than two years (World Health Organization [WHO], 2019).

Unvaccinated males and females are equally susceptible to infection by the measles virus. Following acute measles, increased mortality has been observed among females of all ages, but it is most marked in adolescents and young adults. Measles affects people of all races (WHO, 2023a).

There is some seasonal variation, and in temperate areas, the peak incidence of measles infection occurs during late winter and early spring. Humans are the only known host to measles, and it does not spread among animals.

Aside from being unvaccinated or under-vaccinated, risk factors for contracting and developing complications from measles include young age, being immunocompromised from HIV/AIDS, chemotherapy, organ transplant, or other reasons, living close to a large number of people, malnutrition, pregnancy, and international travel. Measles remains endemic in countries in five out of the six WHO regions of the world, which underscores the importance of ensuring age-appropriate vaccination for all individuals before international travel to any region (WHO, 2023a).

Development and distribution of the measles vaccine have been so overwhelmingly successful that patterns and prevalence of the disease should be divided into pre- and post-vaccine data. Between 2000 and 2018, there was a 73% decrease in the prevalence of measles worldwide, and the WHO estimates that over 23 million measles-related deaths were avoided during that time (WHO, 2023a).

In 1954, at a boarding school near Boston, Massachusetts, a measles outbreak gained attention from doctors at Boston Children's Hospital, who collected throat swabs and blood samples from infected students to try and isolate the virus. Dr. Thomas Peebles and Dr. John Enders did just that, with a blood sample from an adolescent student named David Edmonston, resulting in an isolated strain of the measles virus, known afterward as the "Edmonston B strain" (WHO, n.d.).

These doctors developed a vaccine from the Edmonston B strain and tested it on small groups of children between 1958 and 1960. Once those trials were successful, they began testing on larger groups, vaccinating thousands of children in New York City and Nigeria. The vaccine was wildly effective and licensed for widespread distribution to the public in 1963 (WHO, n.d.).

The early vaccine had many side effects, so in 1968, Dr. Maurice Hillman attempted to weaken the virus contained within the vaccine while maintaining its overall effectiveness. He accomplished this by passing the virus through chick embryo cells many times, reducing the severity of side effects while not affecting the vaccine's efficacy; this improved vaccine is the one we still use today (WHO, n.d.).

In 1971, Hillman also combined the measles vaccine with existing inoculations for mumps and rubella, so all three could be given in one injection, known as the MMR. The measles vaccine is always combined with mumps and rubella in the United States. Standalone measles vaccines are sometimes used in other countries (WHO, n.d.).

MMR Vaccine

The current recommendation for MMR vaccination is an initial dose at 12-15 months and a second dose between the ages of 4-6 before school entry. The MMR can be given as early as six months of age and is recommended earlier than the standard 12 months for children traveling outside of the United States, particularly to areas with high rates of measles, or also when outbreaks occur, especially if children are at high risk or living in a community affected by an outbreak (CDC, 2022).

A 2-dose series at least four weeks apart is recommended for previously unvaccinated children on a catch-up schedule. A single booster dose is recommended for adults who do not demonstrate immunity on titers. A two-dose series is recommended for adults with no immunity who are considered at high risk of exposure, such as healthcare professionals or those traveling internationally (CDC, 2022).

A combination vaccine for MMR and varicella (MMRV) was created in 2005 for school-aged children receiving their second dose to only receive one injection. For children younger than age four or older than age 12, the MMR and varicella components should be administered separately (CDC, 2022).

While measles is known for its hallmark red, macular rash spreading from the face down to the toes, it includes many other symptoms of varying severity that progress in a predictable fashion.

Incubation period:

• The first 10-14 days after exposure, the virus replicates and spreads throughout the body. There are no symptoms at this time.

First symptoms appear 7-14 days after initial exposure and include the following:

• High fever (may be greater than 104°F)
• Fatigue and malaise
• Cough
• Runny nose
• Sore throat
• Conjunctivitis 

2-3 days after initial symptoms:

• Koplik's spots (white spots inside the mouth) may develop

3-5 days after initial symptoms:

• Measles rash develops
  • Red macules beginning at the hairline and spreading downward to the thighs and feet
  • Macules may be so numerous that they blend together
  • Fever may spike up to 104-105°F as rash appears and spreads

Recovery:

• The rash may last seven days and fades in the order it appeared, with the face fading first and lower extremities fading last
• Cough and other symptoms may last for around ten days
• Peeling of the skin where the rash was may occur (CDC, 2020d)

Measles Rash

While the typical symptoms can be miserable and leave children and adults alike bedridden for up to 2 weeks, the real risk of measles is the numerous complications that can occur and affect around 30% of all measles cases (CDC, 2020a). Risk factors for complications include the following:

• Children under the age of five
• Adults over the age of 20
• Pregnancy
• Compromised immune system (such as HIV or leukemia)(CDC, 2020a)

Common complications include ear infections and diarrhea, with around 10% of all measles cases experiencing one or both (CDC, 2020a). More serious complications often require hospitalization and may result in long-term disabilities or death. Serious complications include the following:

• Hospitalization: Around 20% of unvaccinated measles cases require hospitalization.
• Pneumonia: This complication is the most common cause of measles-related death in children. 1 in 10 children experiences this complication.
• Encephalitis: This dangerous complication causes brain swelling, resulting in acute seizures or long-term disabilities such as permanent brain damage, learning disabilities, or deafness. 1 in every 1,000 children with measles experiences this complication.
• Death: Up to 3 of every 1,000 children with measles will die from respiratory or neurological complications.
• Pregnancy complications: Women who contract measles while pregnant are at an increased risk of miscarriage, premature birth, or low birth weight infants. Measles infection during pregnancy does not cause congenital disabilities in the fetus.
• Subacute sclerosing panencephalitis (SSPE): This long-term complication is very rare but can be fatal. SSPE typically develops seven to 10 years after the initial measles infection from long-term inflammation and irritation to the brain. People infected with measles during the first two years of life are most at risk for developing SSPE, usually as teenagers. When measles was more widely circulated, only around seven to 11 of every 100,000 cases would result in SSPE later in life. With the current low levels of measles in the United States annually, SSPE is seldom reported. (CDC, 2020a)

It is important for any healthcare professionals working in pediatrics, urgent care, or emergency departments to be familiar with the symptoms and disease progression of measles and to keep it on their differential list when encountering patients with a high fever and rash. Patients should be asked about their vaccination status and recent travel, particularly to developing countries, as up to 90% of measles outbreaks in the United States can be traced back to recent international travel (CDC, 2020c).

If measles is suspected, laboratory confirmation is essential. Several laboratory tests are used to confirm a measles diagnosis- a respiratory swab for real-time polymerase chain reaction (RT-PCR) provides quick and specific results, and a serum sample can be assessed for immunoglobulin M (IgM) antibodies, indicating a current measles infection. The virus may also be present in urine samples. When possible, a respiratory swab and urine sample increase the chances of detecting the virus for diagnosis confirmation (CDC, 2020c).

When measles outbreaks occur, molecular analysis of confirmed samples helps map the virus's genetic data and link cases together. In the United States, all suspected and confirmed measles cases must be reported to state public health departments, which report to the CDC (CDC, 2020c).

Treatment for measles is entirely supportive as there is no antiviral for the disease. Fever reducers such as Tylenol or ibuprofen, antibiotics for secondary pneumonia or ear infections, and even a concentrated dose of Vitamin A may be indicated to reduce symptom severity. Hospitalization for additional supportive care such as IV fluids, oxygen support, or neurologic monitoring and treatment is indicated for severe cases. Immunoglobulin therapy is available after measles exposure for special populations (such as pregnant women, unvaccinated infants, and immune-compromised individuals) to prevent or lessen the severity of illness after exposure (Mayo Clinic, 2022).

Unfortunately, the success of the measles vaccine has met challenges as the MMR, in particular, is at the center of the anti-vaccine movement that gained traction in the 1990s. Vaccine hesitancy is not new; the Anti-Vaccination Society of America was founded in 1879. However, the availability of the internet and social media in recent years has provided an easily accessible platform and means of connection for vaccine-hesitant families to connect and feel more confident in their resistance (Schwartz, 2012).

In the 1990s, then-doctor Andrew Wakefield (whose medical license has since been revoked) headed a publication in The Lancet that claimed a direct link between the MMR vaccine and the development of autism in children. There were many problems with this publication, and swift legal action against the authors occurred (10 of the 13 withdrew their opinion). There have since been many additional studies and thousands of research dollars spent investigating this potential link with no evidence found. Thimerosal, a preservative used in multidose vials, was supposedly the culprit in autism development, and despite this connection being repeatedly disproved, it was removed from vaccines in the 1990s. Additionally, most MMR vaccines are now single-dose vials that need not be preserved once open (Barrows et al., 2015).

Despite the time and money spent disproving this theory, the damage has been done, and the risk of autism and other neurologically damaging side effects remains a common ideology, among others, for vaccine hesitancy (Barrows et al., 2015). Unfortunately, because of the high transmissibility rate of measles, maintaining around 95% vaccination rate of the general population is needed to prevent easy virus transmission and large outbreaks. Even small drops in routine adherence to the recommended vaccine schedule, particularly when concentrated within the same geographic area, can lead to quick and devastating consequences that are difficult to control (WHO, 2023b).

Nonadherence is important to understand, not only because of pockets of anti-vaccine groups that have been at the center of the United States measles outbreaks in recent years but also because of the effects of the COVID-19 pandemic on routine well-child visits and vaccination rates. Particularly at the beginning of the pandemic, much routine well-care was being delayed or completed virtually as shelter-in-place orders were implemented or people avoided going to healthcare facilities for fear of coronavirus exposure. Up to 70% of children experienced delays in routine vaccinations during the first few months of the pandemic (Ota et al., 2021).

Three years later, data indicates that many children were able to catch up and are back on track with their vaccines. However, the full extent of the delays is still unfolding, and specific populations remain at risk of being under-vaccinated. At-risk populations include families of low socioeconomic status or who are unvaccinated or underinsured, those with disabilities, immigrant families, and those in rural locations or with difficult access to healthcare (Ota et al., 2021). The WHO has expressed great concern that improved data assessment and catch-up campaigns are needed to identify at-risk populations and implement policies that will help return vaccination rates to their pre-pandemic rate and prevent the resurgence of measles (WHO, 2023b).

Scenario:

Benjamin is a four-year-old male brought to the emergency department by his parents for chief complaints of a high fever, sore throat, and lethargy. His mother states he has had typical cold symptoms for 3-4 days now and slept for 13 hours the night before, which they hoped meant he would wake up rested and feeling better. Instead, he woke up crying and with an axillary temperature of 104°F.

Upon exam, the emergency department nurse practitioner noted rhinorrhea, injected sclera, and scattered red macules along the child's hairline. An exam of the pharynx reveals Koplik's spots. He is also noted to have an erythematous and bulging right tympanic membrane. Upon further questioning, the child's mother states another child was recently sent home sick from Benjamin's daycare with a bad rash and fever. This child had come home ill after visiting extended family in the Philippines. Benjamin's mother admits he is behind on his vaccinations, as he turned one just as the pandemic started. He has not been back to the pediatrician to catch up yet, as the mother planned to take him before he started kindergarten.

Interventions:

A respiratory swab and a serum draw are collected to assess for measles; both are positive. His lungs are clear, so a chest x-ray is not indicated. Vital signs are stable. He is prescribed an antibiotic for the secondary ear infection and sent home with instructions for supportive care and to follow up with his pediatrician in 2-3 days to reassess. Signs and symptoms that warrant concern and a return to the emergency department are reviewed. The case is reported to the public health department, which follows up with contact tracing and advice for isolating Benjamin at home.

Discussion:

The history information provided by the mother about Benjamin's ill peer and his recent travel, paired with Benjamin's unvaccinated status, made this diagnosis much more obvious. If the emergency department nurse practitioner had not had this information, the symptoms were still very early in their trajectory and not very obviously measles, especially with the rash starting at the hairline, the diagnosis may not have been accurate. This illustrates the importance of thorough history taking and being familiar with the signs and symptoms of measles and the progression of symptoms.

Strengths/Weaknesses:

Strength: The rapid identification of this child's measles infection, supportive care, and frequent follow-up helped Benjamin fully recover with no complications other than the ear infection.

Weakness: The case of measles was reported to public health as it should have been. However, more information should have been gathered about Benjamin's family at home and their vaccination status or health risks. Benjamin's mother is in her first trimester of pregnancy but did not mention it because she was vaccinated for measles as a child and assumed she was immune. While this is likely true, she is still at high risk for complications of measles, such as miscarriage or premature birth. Further assessment of these risks and education regarding who Benjamin needs to isolate from were needed.

Ideally, Benjamin would also have been identified by vaccine catch-up campaigns as a child needing additional vaccines in the post-pandemic era.

Also, the initial case from Benjamin's preschool should have been reported so that other families from the preschool could be notified of the exposure to measles.

Though the incidence of measles has significantly decreased, it has not fully disappeared. Many patients are diagnosed with this disease yearly, and some succumb to this diagnosis. It is important that healthcare practitioners continue to monitor for this disease, being aware of the signs and symptoms and researching evidence-based practices.

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