Declining measles antibodies in the era of elimination: Australia's experience

Abstract

Background: Australia is one of only a few countries with a long-standing and consistent serosurveillance program. We conducted a national serosurvey in 2012-2013 to estimate population seroprevalence of measles-specific IgG and the effective reproduction number, R, and compare the results with the three previous serosurveys (1996-1999, 2002 and 2007) to examine trends following a decade of sustained measles control.

Methods: 2729 residual sera from 1 to 49 year olds were tested using the Enzygnost anti-measles IgG enzyme immunoassay (EIA). All sera in the equivocal range by EIA on re-testing and a random sample of low positive and negative sera were later tested by a microneutralisation assay. R was calculated from weighted estimates of the proportion seronegative by age using a previously developed contact matrix.

Results: In the 2012-13 serosurvey, anti-measles IgG seropositivity for 1-49 year olds was 80.8% (95% CI: 79.4-82.3%) and 8.9% (95% CI: 7.8-10.0%) had equivocal antibody levels. The increasing proportion of seronegative and equivocal individuals in age groups 10-39 years continued a trend seen in previous serosurveys. There was also an increase in equivocal results among 2-4 and 5-9 year old children, >90% of whom were recently vaccinated. R increased from 0.57 in 1999 to above the epidemic threshold of 1 in 2012-13 (R = 1.7). All 20 EIA negative sera, 238/241 (98.8%) equivocal sera, and 89/92 (96.7%) low positive sera had a titre <10 (negative) in the measles microneutralisation assay.

Conclusions: A number of countries with sustained measles control have now demonstrated that measles-specific IgG antibodies decline with time since vaccination. As there is good epidemiologic evidence of population-level protection, the implications of declining measles-specific IgG antibody levels for maintaining measles elimination are unclear. Novel studies to determine correlates of protection against measles transmission and disease in the post-elimination era are needed to help answer this question.

Keywords: Immunity; Measles; Seroprevalence; Vaccination.