What is the risk of Subacute Sclerosing Panencephalitis (SSPE) when factoring in measles underreporting?

Risk of SSPE When Accounting for Measles Underreporting

The true risk of SSPE following measles infection is approximately 4-11 per 100,000 measles cases, but this substantially underestimates the actual risk because measles cases are dramatically underreported—before vaccination, virtually all children acquired measles (approximately 3.5 million cases annually in the US), yet only about 400,000 cases were officially reported, representing just 11% of actual infections. 1

Quantifying the True SSPE Risk

Reported vs. Actual Measles Incidence

• Before measles vaccine licensure in 1963, approximately 400,000 measles cases were reported annually in the United States, but the actual number of cases approached 3.5 million per year (essentially an entire birth cohort), meaning reported cases represented only about 11% of true infections 1
• This 9-fold underreporting means that risk calculations based on reported cases significantly overestimate the per-infection SSPE risk 1

Adjusted SSPE Risk Estimates

• When calculated against reported measles cases, the SSPE risk appears to be 4.0 per 100,000 cases 2, 3
• More recent estimates using broader surveillance suggest 6.5-11 per 100,000 measles cases 4
• However, when accounting for the actual infection rate (not just reported cases), the true population-level risk is proportionally lower, though still clinically significant 1

Age-Specific Risk Stratification

Highest Risk Population

• Children who contract measles under 1 year of age face a risk 16 times greater than those infected after age 5 years 2
• Measles contracted under 5 years of age carries the highest overall risk for developing SSPE 4
• In the England and Wales cohort, nearly half of SSPE cases had documented measles infection before age 2 years 2

Risk by Age at Measles Infection

• Measles under 1 year: approximately 18 per 100,000 cases (based on reported cases, so actual risk lower when accounting for underreporting) 3
• Measles over 5 years: baseline risk of approximately 4 per 100,000 reported cases 2, 3

Critical Context: Vaccination Impact

Vaccine Safety Profile

• The risk of SSPE after measles vaccination is 0.14 per 100,000 doses or less—approximately 28-fold lower than the risk following natural measles infection 2, 3
• The ACIP definitively states that MMR vaccine does not increase the risk for SSPE, even in persons who previously had measles or received prior measles vaccine 5, 6
• When rare SSPE cases have been reported in vaccinated children without known measles history, evidence indicates these children likely had unrecognized measles infection before vaccination 5, 6

Prevention Through Vaccination

• Widespread measles vaccination has essentially eliminated SSPE from the United States 1
• Countries with high vaccination coverage have achieved near elimination of SSPE cases 5
• Measles vaccination is the only effective prevention strategy for SSPE 5, 6

Additional Risk Factors Beyond Age

Immunocompromised Status

• Children with or exposed to HIV infection who contract measles may be at increased risk of SSPE 4
• Immunocompromised individuals can experience severe and prolonged measles infection 7

Geographic and Social Factors

• Children residing in areas with poor vaccination coverage face increased SSPE risk 4
• Higher incidence observed in northwest versus southeast regions (in England/Wales data) 2
• Excess cases noted in third and subsequent children within families 2

Clinical Implications of Underreporting

Why This Matters for Risk Communication

• When counseling families about measles risks, using the 4-11 per 100,000 figure based on reported cases actually overstates the individual per-infection risk but appropriately reflects the population burden 4, 2, 3
• The key message remains unchanged: natural measles infection carries a substantially higher SSPE risk than vaccination, regardless of how underreporting is factored 2, 3
• The latency period (median 8 years between measles and SSPE onset) means cases continue to emerge years after measles exposure 2

Recent Epidemiological Trends

• A recent surge in SSPE cases in developed countries has been attributed to reduced vaccination coverage, aggravated by misinformation and declining immunization rates after the COVID-19 pandemic 8, 9
• The age at SSPE onset has increased significantly over time, reflecting the transient effect of declining measles incidence following mass vaccination introduction 2, 3

Common Pitfalls to Avoid

• Do not confuse SSPE with acute post-vaccination encephalopathy, which if it occurs (extremely rare at approximately 1 per 2 million doses), presents around 10 days after vaccination, not years later 5
• Do not confuse SSPE with febrile seizures, which occur 5-12 days after MMR vaccination at approximately 1 per 3,000 doses and do not lead to residual neurologic disorders 5
• Do not assume that vaccination increases SSPE risk—the disease is caused by persistent wild-type measles virus infection, not by vaccination 5, 6