What are the potential sequelae of measles in unvaccinated (Measles, Mumps, and Rubella) individuals?

Measles Sequelae in Unvaccinated Individuals

Unvaccinated individuals face severe and potentially fatal complications from measles infection, including acute encephalitis (1 per 1,000 cases), pneumonia, subacute sclerosing panencephalitis (SSPE), and death (1-2 per 1,000 cases), with children under 5 years and adults over 20 years at highest risk. 1, 2

Acute Neurological Complications

Measles Encephalitis

• Occurs in approximately 1 per 1,000 measles cases, presenting with fever, altered mental status, seizures, and potential permanent CNS impairment 1
• Symptoms typically appear during or shortly after the acute measles illness, around 10 days after initial infection 1
• Survivors often suffer permanent brain damage and mental retardation, making this a devastating complication beyond the acute illness 1
• Encephalitis is one of the two most common causes of death from measles, along with pneumonia 1

Historical Burden

• Before vaccine introduction in 1963, approximately 3.5 million measles cases occurred annually in the United States, translating to approximately 3,500 cases of measles encephalitis per year in children 1

Subacute Sclerosing Panencephalitis (SSPE)

Disease Characteristics

• SSPE is a rare but invariably fatal late complication appearing years after the initial measles infection, caused by persistent mutant measles virus in the CNS 1, 3
• Risk is approximately 4-11 per 100,000 measles-infected individuals, particularly those infected at young ages 4, 1
• Typically presents 6-8 years after the initial measles infection, with onset generally between ages 5-15 years 4

Clinical Presentation

• Insidious personality changes and intellectual decline progressing to dementia 1
• Myoclonic jerks with characteristic 1:1 EEG periodic complexes 1
• Progressive motor deterioration, coma, and death 1
• CSF shows measles-specific antibody with intrathecal synthesis 1

Critical Prevention Point

• The only effective prevention strategy for SSPE is measles vaccination, which has essentially eliminated SSPE in highly vaccinated populations 4, 1
• The false notion that measles after age 5 carries negligible SSPE risk is definitively refuted by the ACIP 4

Respiratory Complications

Pneumonia

• One of the two most common causes of death from measles 1
• Complication rates are higher in children under 5 years old 2

Croup

• More common in children under 2 years old 2

Other Organ System Complications

Ophthalmologic

• Measles remains a common cause of blindness in developing countries 2

Otitis Media

• More common in children under 2 years old 2

Age-Specific Risk Stratification

Highest Risk Groups

• Children under 5 years old have higher complication rates 2
• Adults over 20 years old have higher complication rates 2
• Croup and otitis media are more common in those under 2 years 2
• Encephalitis is more common in older children and adults 2

Risk-Modifying Factors

Factors Increasing Complication Rates

• Immune deficiency disorders 2
• Malnutrition 2
• Vitamin A deficiency 2
• Intense exposures to measles 2
• Lack of previous measles vaccination 2

Mortality

Case-Fatality Rate

• Overall case-fatality rate is 1-2 per 1,000 cases in the United States 1
• Case-fatality rates remain high in developing countries despite improvements in socioeconomic status in many regions 2

Special Population: Immunocompromised Individuals

Measles Inclusion Body Encephalitis (MIBE)

• Occurs in immunocompromised patients approximately 6 months after primary infection 3
• Measles inclusion bodies found directly in brain tissue 3
• Often presents without the typical rash 3

Severe and Prolonged Disease

• Measles can be severe and prolonged in immunocompromised persons, particularly those with leukemias, lymphomas, or HIV infection 4
• Atypical presentations and prolonged viral shedding occur 4

Contemporary Outbreak Data

Recent U.S. Experience

• Among confirmed measles cases from 2001-2022, 69% were unvaccinated 5
• Outbreaks continue to occur primarily among unvaccinated persons 6, 7, 8
• Over 80% of cases in 2015 occurred among persons who were unvaccinated or had unknown vaccination status 8

Disease Severity by Vaccination Status

• Unvaccinated cases demonstrate higher rates of classic presentation (rash, fever, and cough/coryza/conjunctivitis) 5
• Severe disease (pneumonia, encephalitis, hospitalization, or death) is more common in unvaccinated individuals 5

Critical Clinical Pitfall

The most important pitfall is failing to recognize that vaccination is the only proven prevention strategy for these sequelae. Natural measles infection provides no protective benefit against complications and carries substantial morbidity and mortality risk 4, 1. The CDC recommends all children receive two doses of MMR vaccine: the first at 12-15 months and the second at 4-6 years 4.