The Effects of Vaccination Status and Age on Clinical Characteristics and Severity of Measles Cases in the United States in the Post-Elimination Era, 2001-2022

Background Despite high vaccine-effectiveness, wild-type measles can occur in previously vaccinated persons. We compared the clinical presentation and disease severity of measles by vaccination status and age in the post-elimination era in the United States. Methods We included U.S. measles cases reported from 2001–2022. Breakthrough measles was defined as cases with ≥1 documented dose of measles-containing vaccine, classic measles as the presence of rash, fever, and ≥1 symptoms (cough, coryza, or conjunctivitis), and severe disease as the presence of pneumonia, encephalitis, hospitalization, or death. Vaccinated cases with low and high avidity IgG were classified as primary (PVF) and secondary (SVF) vaccine failures, respectively. Results Among 4,056 confirmed measles cases, 2,799 (69%) were unvaccinated, 475 (12%) were breakthrough infections, and 782 (19%) had unknown vaccination; 1,526 (38%), 1,174 (29%), and 1,355 (33%) were aged <5, 5–19, and ≥20 years, respectively. We observed a general decline in classic presentation and severe disease with an increase in the number of doses, and less complications among children aged 5–19 years compared to other age-groups. Among 93 breakthrough cases with avidity results, 11 (12%) and 76 (82%) were classified as PVF and SVF, respectively, with a higher proportion of PVFs having a classic measles presentation and severe disease than SVFs. Discussion Breakthrough measles cases tended to have milder disease with less complications. A small proportion of breakthrough infections were due to PVF than SVF. It is critical to maintain high MMR vaccination coverage in the United States to prevent serious measles illnesses.