The European Sero-Epidemiology Network 2 (ESEN2): standardization of assay results for hepatitis A virus (HAV) to enable comparisons of seroprevalence data across 15 countries

Abstract

SUMMARYThe European Sero-Epidemiology Network 2 (ESEN2) aimed to compare serological results of vaccine-preventable diseases across Europe. To ensure direct inter-country comparability of hepatitis A virus antibody (anti-HAV) measurements, a standardization panel of 150 sera was developed by a designated reference laboratory and tested by participating national laboratories using assays of choice ; each country's results were subsequently regressed against those of the reference laboratory. Quantitatively, the assays were generally highly correlated (R 2 >0 . 90). Nevertheless, qualitative comparisons indicated that results obtained with different assays may differ despite the usage of well-established international and local standards. To a great extent standardization successfully alleviated such differences. The generated standardization equations will be used to convert national serological results into common units to enable direct international comparisons of HAV seroprevalence data. The results of this study are expected to contribute to the evaluation and potential improvement of the currently employed immunization strategies for hepatitis in Europe.

Regression models for censored serological data

“…For validating linear equations, the same example was used excluding the quadratic term. For this example, any data below 0.005 IU ml 21 (22.3 on the log 10 scale) were treated as censored, whereas the reference cut-off was 0.01 (Anastassopoulou et al, 2009).…”

Epidemiology of hepatitis A in Finland in 1990–2007

“…Serum samples (3,217) collected in connection with the ESEN (European Seroepidemiology Network) study during 1997-1998 [Anastassopoulou et al, 2009] were used to determine antibody levels for hepatitis A in Finnish individuals aged 0-88 years. Sera were collected in different areas covering most of the country.…”

Estimating seroprevalence of vaccine-preventable infections: is it worth standardizing the serological outcomes to adjust for different assays and laboratories?

“…The Italian laboratory used a different assay (DiaSorin, Italy) than the reference centre (Abbott Laboratories, USA) to test against HAV ( Table 6). Although both assays shared the same cutoff value (10 mIU/ml), a large number of samples were re-classified following standardization, which meant that there was a large difference in seroprevalence following standardization [7,21]. The estimated HAV seroprevalences for the Italian serosurvey results tested against HAV before and after standardization are shown in Figure 2.…”

“…However, the variety of assays and laboratory methods used by the national laboratories can result in non-comparable serological outcomes and hence, seroprevalence estimates. Inter-laboratory variation is not uncommon even when the same assay method and international standards are used [7][8][9][10][11][12][13][14]. For the ESEN and ESEN2 projects, a statistical method was developed to adjust for this variation by standardizing the serological quantitative data [9,15,16].…”

“…For the ESEN and ESEN2 projects, a statistical method was developed to adjust for this variation by standardizing the serological quantitative data [9,15,16]. The equations used for standardizing the serological outcomes for the ESEN2 project have been presented in previous papers [7,11,13,14,17,18]. The final seroprevalence estimates have also been presented elsewhere [17][18][19][20][21][22][23][24].…”