From Seroprevalence to Measles Outbreak Risk: A Multicountry Epidemiological Proof of Concept

Background: High national vaccination coverage may conceal age-specific and spatially concentrated measles susceptibility. Objective: To assess whether published age-specific seropositivity results can be converted into a time-updated susceptibility profile that corresponds with subsequent measles incidence, while distinguishing susceptibility from infectious introductions and transmission conditions. Methods: For Israel, published 2015 age-specific seropositivity estimates were mapped to monthly birth cohorts and projected to 1 March 2018, accounting for births, aging, maternal antibody, routine vaccination, vaccine effectiveness, and uncertainty in assay interpretation. The primary outcome was reported age-specific incidence during the 2018-2019 outbreak; national and Jerusalem District case burdens were secondary outcomes. Published evidence from the Netherlands, Czechia, and Australia was compared using a common framework covering age distribution, assay classification, vaccination, importation, spatial concentration, and transmission context. Results: The estimated number susceptible in Israel on 1 March 2018 ranged from approximately 0.55 million (6.3% of the modelled population) to 1.92 million (22.4%), with a central estimate of 1.22 million (14.2%). Children aged <1 year had the highest central susceptible proportion (75.7%) and the highest later incidence (196.0 per 100,000). Jerusalem District accounted for 2,202 of 4,311 reported national cases, consistent with susceptibility concentrated in communities with lower first-dose coverage. The external comparisons showed that clustering amplified Dutch outbreak risk, survey design affected Czech estimates, and importation dominated Australian activity. Conclusions: Published seropositivity can identify immunity gaps, but useful outbreak-risk assessment must also represent susceptible density and distribution, introduction pressure, and local transmission conditions. Although the model was not designed to compare alternative vaccination schedules directly, its identification of substantial susceptibility during early childhood provides epidemiological support for Israel's recent decision to advance the second routine MMRV dose from 6 years to 18 months of age, thereby shortening the period during which young children remain dependent on single-dose protection.