Harnessing the potential of blood donation archives for influenza surveillance and control

Abstract

Many blood donation services around the globe maintain large archives of serum and/or plasma specimens of blood donations which could potentially be used for serologic surveillance and risk assessment of influenza. Harnessing this potential requires robust evidence that the outcomes of influenza serology in plasma, which is rarely used, is consistent with that in serum, which is the conventional choice of specimens for influenza serology. We harvested EDTA-plasma specimens from the blood donation archives of Hong Kong Red Cross Transfusion Services, where EDTA is the type of anticoagulant used for plasma collection, compared their antibody titers and responses to that in serum. Influenza A/H1N1/California/7/2009 and A/H3N2/Victoria/208/2009 were the test strains. Our results showed that antibody titers in 609 matched serum/EDTA-plasma specimens (i.e. obtained from the same donor at the same time) had good agreement inferred by Intraclass Correlation Coefficient, the value of which was 0.82 (95% CI: 0.77-0.86) for hemagglutination inhibition assay and 0.95 (95% CI: 0.93-0.96) for microneutralization assay; seroconversion rates (based on hemagglutination inhibition titers) during the 2010 and 2011 influenza seasons in Hong Kong inferred from paired EDTA-plasma were similar to that inferred from paired sera. Our study provided the proof-of-concept that blood donation archives could be leveraged as a valuable source of longitudinal blood specimens for the surveillance, control and risk assessment of both pandemic and seasonal influenza.

Fig 1. Influenza activity in Hong Kong during 2009–2011 and the sources of specimens for comparative analyses.

(A) Influenza virus isolation [20]; (B) Specimens included sera from a serial cross-sectional influenza serosurvey [3], EDTA-plasma harvested from the HKRCBTS blood donation archives, and sera from a longitudinal influenza serosurvey [20]. Color codes indicate the specimens used for the different comparative analyses in this study: green indicates 609 matched serum/EDTA-plasma specimens for antibody titer comparison; purple indicates 340 paired sera and 376 paired EDTA-plasma for estimating seroconversion rate against A/H3N2 during the 2010 season; and orange indicates 190 paired sera and 392 paired EDTA-plasma for estimating seroconversion rate against A/H1N1 during the 2011 season.

Fig 2. Comparison of antibody titers in 609 matched serum/EDTA-plasma specimens.

Serum and EDTA-plasma specimens were collected from the same donor at the same time during 2009 (Fig 1). Color codes indicate the fold difference in antibody titers between the matched serum/EDTA-plasma specimens: blue, orange and red indicate no, one-fold and two-fold or more difference, respectively. Pink shades indicate p<0.05 in Stuart-Maxwell test (i.e. statistically significant lack of marginal homogeneity between serum and EDTA-plasma titer distributions).

Fig 3. Comparison of the age-standardized HI seroconversion rates in paired sera and paired EDTA-plasma.

(A) The 2010 H3N2 influenza season in Hong Kong caused by A/H3N2/Victoria/210/2009. (B) The 2011 H1N1 influenza season in Hong Kong caused by A/H1N1/California/7/2009. Color codes indicate the source of paired specimens used for calculating seroconversion rates: blue indicates paired EDTA plasma from HKRCBTS blood donation archives, while red indicates paired sera from Kwok et al. [20]. Square and circle indicate the conventional (≥4-fold rise and the latter titer ≥1:40) and alternative (≥4-fold rise) definition of seroconversion, vertical bars indicate 95% confidence intervals.