Additional Evidence on Serological Correlates of Protection against Measles: An Observational Cohort Study among Once Vaccinated Children Exposed to Measles.

To assess correlates of protection against measles and against subclinical measles virus (MV) infection, we recruited once-vaccinated children from geographic regions associated with increased MV circulation and/or at schools with low vaccination coverage in the Netherlands. Paired blood samples were collected shortly after onset of the measles outbreak and after the outbreak. A questionnaire was used to document the likelihood of exposure to MV and occurrence of measles-like symptoms. All blood samples were tested for MV-specific antibodies with five different assays. Correlates of protection were assessed by considering the lowest neutralizing antibody levels in children without MV infection, and by ROC analyses. Among 91 participants, two seronegative children (2%) developed measles, and an additional 19 (23%) experienced subclinical MV infection. The correlate of protection against measles was lower than 0.345 IU/mL. We observed a decreasing attack rate of subclinical MV infection with increasing levels of specific antibodies until 2.1 IU/mL, above which no subclinical MV infections were detected. The ROC analyses found a correlate of protection of 1.71 IU/mL (95% CI 1.01-2.11) for subclinical MV infection. Our correlates of protection were consistent with previous estimates. This information supports the analyses of serosurveys to detect immunity gaps that require targeted intervention strategies.

Rubella outbreak in the Netherlands, 2004-2005: high burden of congenital infection and spread to Canada.

BACKGROUND: In The Netherlands and Canada the measles, mumps, rubella vaccine coverage is high. In 2004 a rubella outbreak started in the Netherlands in a population subgroup with low coverage, with subsequent spread to Canada. METHODS: We examined data on rubella cases in the Netherlands and Canada reported between September 2004 and July 2005. In The Netherlands we established enhanced surveillance for congenital rubella while in Canada we carried out a cohort study to estimate vaccine effectiveness. RESULTS: In The Netherlands and Canada, 387 and 309 rubella cases were reported, respectively. Of these, 97% were in unvaccinated individuals of orthodox protestant denomination. Reported consequences of rubella in pregnancy were 2 fetal deaths and 14 infants with congenital infection. Of the latter, 11 had clinical defects including deafness in all but eye defects in none. The estimated vaccine effectiveness was 99.3% (95% CI: 95.3%-99.9%). Closely related strains of rubella virus genotype 1G were found in Dutch and Canadian cases. CONCLUSIONS: A large rubella outbreak occurred in The Netherlands with spread to Canada in a population subgroup with religious objections to vaccination. Its major public health importance was due to the high burden of congenital disease, international spread and implications for measles and rubella surveillance and elimination. Congenital deafness occurred more frequently and eye defects less frequently than expected. The estimated rubella vaccine effectiveness was very high. Our results demonstrate the risks associated with heterogeneity in rubella vaccine coverage. High rubella vaccine coverage in all population subgroups and sensitive surveillance are crucial for elimination of rubella and CRS.