Performance of the Elecsys Rubella IgG assay in the diagnostic laboratory setting for assessment of immune status

Abstract

Rubella in early pregnancy bears a high risk for congenital defects (e.g., cataracts, hearing loss, and heart disease) and for long-term sequelae in the newborn. Despite implementation of vaccination programs in many regions, the threat of devastating consequences from congenital rubella virus infection remains and careful screening of maternal immune status before and during pregnancy helps to reduce the risk. This study compared the performance of the Elecsys Rubella IgG assay with that of other assays routinely used for screening. Samples from 1,090 women undergoing routine antenatal care were tested using the Elecsys and Enzygnost Rubella IgG assays and the hemagglutination inhibition test. Samples with hemagglutination inhibition titers of <32 (n = 148) were additionally tested using the Vidas, AxSYM, Liaison, and Architect Rubella IgG assays. Agreement of qualitative results from the Elecsys, Enzygnost, and hemagglutination inhibition assays was good in all samples. All assays showed 100.0% specificity. In samples with hemagglutination inhibition titers of <32, the Elecsys, AxSYM, and Enzygnost assays showed higher sensitivity (>90.0%) than the other immunoassays (78.6 to 82.4%). The Elecsys assay reported significantly higher rubella virus IgG levels than the other immunoassays across the whole set of 1,090 samples, with the largest bias and deviation from limits of agreement in Bland-Altman analysis. In conclusion, the Elecsys assay is highly sensitive and specific with regard to qualitative results and suitable for routine automated screening. However, given the considerable variation between quantitative results from different immunoassays, testing methods should be documented and the same assay used throughout an individual's antenatal follow-up wherever possible.

Fig 1

(A) Distribution of rubella HI titers in the sample of pregnant women (n = 1,090). The histogram shows the absolute number of pregnant women for each HI titer. The dashed curve is the density of a fitted zero-inflated lognormal distribution with goodness-of-fit P = 0.4689. (B) Age distribution of the sample of pregnant women (n = 1,090; left axis) together with the percentage with rubella HI titers of <32 (right axis). The observed percentages are shown together with their exact 95% confidence intervals. The dashed lines are the fitted percentages in a piecewise linear model with a negative slope up to age 34 years and a subsequent positive slope.

Fig 2

Mosaic plot of rubella virus IgG levels in IU/ml comparing all six tests for the 148 pregnant women with HI titers of <32.

Fig 3

Bland-Altman plots for all 15 pairs of the six tests. The vertical axis is the dimensionless ratio of the numerator test divided by the denominator test. The horizontal axis is the geometric mean of the two tests in IU/ml. The central continuous line is the linear regression of the ratio versus the geometric mean. The continuous lines below and above the central lines represent the limits of acceptability (obtained by multiplying or dividing the central line by a factor of 2). The dashed lines below and above the central lines are obtained by taking into account 1.96 times the standard deviations of the residuals at the logarithmic scale.