Mitigating the risk of transfusion-transmitted infections with vector-borne agents solely by means of pathogen reduction

Abstract

Background: This study evaluated whether pathogen reduction technology (PRT) in plasma and platelets using amotosalen/ultraviolet A light (A/UVA) or in red blood cells using amustaline/glutathione (S-303/GSH) may be used as the sole mitigation strategy preventing transfusion-transmitted West Nile (WNV), dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) viral, and Babesia microti, Trypanosoma cruzi, and Plasmodium parasitic infections.

Methods: Antibody (Ab) status and pathogen loads (copies/mL) were obtained for donations from US blood donors testing nucleic acid (NAT)-positive for WNV, DENV, ZIKV, CHIKV, and B. microti. Infectivity titers derived from pathogen loads were compared to published PRT log₁₀ reduction factors (LRF); LRFs were also reviewed for Plasmodium and T. cruzi. The potential positive impact on donor retention following removal of deferrals from required questioning and testing for WNV, Babesia, Plasmodium, and T. cruzi was estimated for American Red Cross (ARC) donors.

Results: A/UVA and S-303/GSH reduced infectivity to levels in accordance with those recognized by FDA as suitable to replace testing for all agents evaluated. If PRT replaced deferrals resulting from health history questions and/or NAT for WNV, Babesia, Plasmodium, and T. cruzi, 27,758 ARC donors could be retained allowing approximately 50,000 additional donations/year based on 1.79 donations/donor for calendar year 2019 (extrapolated to an estimated 125,000 additional donations nationally).

Conclusion: Pathogen loads in donations from US blood donors demonstrated that robust PRT may provide an opportunity to replace deferrals associated with donor questioning and NAT for vector-borne agents allowing for significant donor retention and likely increased blood availability.

FIGURE 1

(A) West Nile viral loads in blood donations reactive by nucleic acid testing. Viral load distributions are shown for 1683 WNV‐RNA confirmed‐positive blood donations identified by blood donation screening from June 2003 to November 2017 in the continental United States. Viral loads are expressed in copies/mL and displayed by stage of infection beginning with donation samples testing individual donation nucleic acid test (IDNAT) positive (P) and antibody (AB) negative (N) (n = 152), mini‐pool NAT (MPNAT) P AB N (n = 1047), MPNAT P AB P (n = 150), and IDNAT P AB P (n = 334). Box and whisker plots include the median and 25th and 75th percentiles. Maximum viral load was 7.2 × 10⁵ copies/mL. (B) Dengue viral loads from blood donations reactive by nucleic acid testing. Viral load distributions are shown for 44 DENV confirmed‐positive blood donors identified by blood donation screening from June 2010 to June 2013 in Puerto Rico. Viral loads are expressed in copies/mL and displayed by stage of infection beginning with samples testing negative for anti‐DENV IgM antibodies (IgM Ab Neg) (n = 35) and those testing positive for anti‐DENV IgM antibodies (IgM Ab Pos) (n = 9). Box and whisker plots include the median and 25th and 75th percentiles. Maximum viral load was 7.79 × 10⁷copies/mL. (C) Zika viral loads from blood donations reactive by nucleic acid testing., Viral load distributions are shown for 246 ZIKV confirmed‐positive blood donors enrolled from April 2016 to May 2017 primarily in Puerto Rico but also including confirmed‐positive donations identified in the continental US. Viral loads are expressed in copies/mL and displayed by stage of infection beginning with samples testing IDNAT positive (P), IgM negative (AB N) (n = 14), MPNAT P, AB N (n = 192), MPNAT P, AB P (n = 26), and IDNAT P, AB P (n = 93). Box and whisker plots include the median and 25th and 75th percentiles. Maximum viral load was 8.3 × 10⁷ copies/mL. (D) Chikungunya viral loads from blood donations reactive by nucleic acid testing. Viral load distributions are shown for 56 CHIKV confirmed‐positive blood donors enrolled from the second half of 2014 to March 2015 in Puerto Rico. Viral loads are expressed in copies/mL and displayed by stage of infection beginning with samples testing IDNAT positive (P), IgM negative (AB N) (n = 2), MPNAT P, AB N (n = 11), MPNAT P, AB P (n = 10), and IDNAT P, AB P (n = 33). Positive samples with unquantifiable viral loads are plotted as being at the limit of quantification (3.16 copies/mL) and were included in calculation of medians (horizontal bars). Maximum viral load was 1.3 × 10⁸ copies/mL. (E) Babesia microti loads in blood donations. Parasite load distributions (parasites/mL) were measured in 89 B. microti confirmed‐positive blood donations collected from June 2012 to December 2017 in the US states of CT, MA, MN, and WI. Parasite load distributions are shown for donations testing B. microti positive by PCR only (PCR Pos) (n = 22) and by PCR and IFA (PCR and IFA Pos) (n = 67). Box and whisker plots include the median and 25th and 75th percentiles. Maximum parasite load was 2.99 × 10⁶ copies/mL. [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

(A) Comparing viral infectious titers with PRT log reduction factors. Maximum and 90% percentile infectivity levels and log reduction factors (LRF) for each pathogen obtained with the A/UVA treatment in plasma, platelets resuspended in 100% plasma or platelets resuspended in 65% platelet additive solution/35% plasma, and LRF for each pathogen obtained with the S‐303/GSH treatment in red blood cells expressed in log₁₀ copies/mL were compared. (B) Comparing Babesia microti infectious titers with PRT log reduction factors. Maximum and 90% percentile infectivity levels and LRF for B. microti obtained with the A/UVA treatment in plasma, platelets resuspended in 100% plasma or platelets resuspended in 65% platelet additive solution/35% plasma, and LRF for B. microti obtained with the S‐303/GSH treatment in red blood cells expressed in log₁₀ copies/mL were compared.