Validating the use of EDTA-plasma for influenza seroepidemiology

Abstract

Antibody response to influenza viruses are critical for protection, serology is the most reliable method for measuring the immune response and inferring previous history of exposure. Influenza seroepidemiology aim to yield accurate estimate on infection attack rate and severity for mitigating the impact of an emerging pandemic or epidemic. Blood transfusion service in many countries typically archive serum and/or plasma specimens, instrumental in monitoring blood safety. Though serum is the choice of specimen for influenza serology, plasma has been used for serologic studies in recent years. However, there is lack of evidence on the validity of plasma influenza serology as anticoagulant (i.e. citrate, heparin, EDTA) is known to interfere with the antigen-antibody reactions. If the outcomes of plasma influenza serology are consistent with that in serum, blood donation archives could potentially be a valuable source of specimens for influenza seroepidemiologic study.

The validity of EDTA-plasma specimens from blood donation archives maintained by Hong Kong Red Cross Blood Transfusion Service for influenza seroepidemiology was evaluated via the following analysis: (i) compared antibody titres in EDTA-plasma with that in serum; (ii) compared seroconversion rates from paired EDTA-plasma with those in paired sera during 2010–2011 epidemics; (iii) regression analysis of antibody response in EDTA-plasma specimen; (iv) estimate infection attack rate using longitudinal donation archive during 2010–2011 epidemic.

The excellent agreement of MN titres between matched serum and EDTA-plasma suggested EDTA-plasma can be a substitute for serum in MN assay. While HI titres in matched samples were correlated in an additive way because of the systematic error/difference. During 2010–2011 epidemics, seroconversion rates in paired EDTA-plasma were comparable with that in paired sera from an independent cohort study. Given the results of regression analysis, age had the impact on the correlation of HI and MN antibody titres in the post-epidemic of A/H3N2, and seroconversion rate inferred from MN titre had a good agreement with that in HI titres. While MN titre of 1:20 should be considered the seropositive threshold for pandemic A/H1N1, so that the agreement of seroconversion rates between HI and MN titres would be improved. Longitudinal donation archive was composed of donation series from repeat donors, including bracketing pairs that is typically used for seroconversion rate in paired serology and non-bracketing pairs that is not intentionally available for longitudinal serologic study. To account for the effect from the non-bracketing properties of longitudinal donations, influenza surveillance data was incorporated in the inference of serologic data from longitudinal donation archive. The infection attack rate of pandemic A/H1N1 using longitudinal donation archive was around 17% to 22% among healthy adults aged 16–65 years during 2010–2011 epidemic in Hong Kong.

In summary, this is the first study to provide comprehensive evidence on the validity of EDTA-plasma from blood donation archives for influenza serological study, suggesting the archived EDTA-plasma specimens from the Hong Kong Red Cross Blood Transfusion Service can be leveraged as a valuable source of specimens for the surveillance and risk assessment of influenza.