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

Stramer, Susan L.; Lanteri, Marion C.; Brodsky, Jaye P.; Foster, Gregory A.; Krysztof, David E.; Groves, Jamel A.; Townsend, Rebecca L.; Notari, Edward P.; Bakkour, Sonia; Stone, Mars; Simmons, Graham; Spencer, Bryan R.; Tonnetti, Laura; Busch, Michael P.

doi:10.1111/trf.16950

Cited by 11 publications

(8 citation statements)

References 63 publications

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“…In this sense, another limitation is that pre‐inactivation titres might not correlate with viremia in actual ongoing infections in volunteer donors. However, recently Stramer et al have shown viral titres in infected blood donors similar to those shown in studies using spiking techniques (West Nile virus 3.25 log 10 copies/ml, dengue virus 3.89 log 10 copies/ml, Zika virus 4.92 log10 copies/ml, Chikungunya virus 6.11 log 10 copies/ml) [20].…”

Section: Discussionmentioning

confidence: 68%

Pathogen inactivation methods to prevent transfusion‐transmissible arboviruses: A systematic review and meta‐analysis

Giménez-Richarte¹,

Salazar²,

Giménez-Richarte

et al. 2023

Tropical Med Int Health

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Objective: Arboviruses are emerging as a relevant threat to transfusion safety. Pathogen inactivation methods (PIMs) may reduce the risk of transmission through transfusion, as long as they meet minimum standards for effectiveness. This study aims to assess the log reduction of viral load achieved with different PIMs, according to the blood product they are used on and the arbovirus targeted. Methods: Systematic literature review and meta-analysis. Searches were conducted in MEDLINE and Embase. The study protocol was registered in PROSPERO CRD42022312061. We selected records reporting the log reduction of viral load achieved with the main PIMs (amotosalen), applied to any blood product (plasma, platelets, red blood cells or whole blood) and for any arbovirus. The log reduction of viral loads was assessed by obtaining the mean log reduction factor (LRF). We compared and classified the LRF of different techniques using statistical methods. Results: We included 59 publications reporting LRF results in 17 arboviruses. For 13 arboviruses, including Chikungunya virus, Dengue virus, West Nile virus and Zika virus, at least one of the methods achieves adequate or optimal log reduction of viral loadÀmean LRF ≥4. The LRF achieved with riboflavin + UV light is inferior to the rest of the techniques, both overall and specifically for plasma, platelets preserved in platelet additive solution (PAS)/plasma, and red blood cells/whole blood. The LRF achieved using Mirasol is also lower for inactivating Chikungunya virus, Dengue virus and Zika virus. For West Nile virus, we found no significant differences. In plasma, the method that achieves the highest LRF is solvent/detergent; in platelets, THERA-FLEX and INTERCEPT; and in red blood cells/whole blood, PEN110 (Inactine). Conclusion: Not all PIMs achieve the same LRF, nor is this equivalent between the different arboviruses or blood products. Overall, the LRFs achieved using riboflavin + UV light (Mirasol) are inferior to those achieved with the rest of the PIMs. Regarding the others, LRFs vary by arbovirus and blood product. In light of the threat of different arboviruses, blood establishments should have already validated PIMs and be logistically prepared to implement these techniques quickly.

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Section: Discussionmentioning

confidence: 68%

Pathogen inactivation methods to prevent transfusion‐transmissible arboviruses: A systematic review and meta‐analysis

Giménez-Richarte¹,

Salazar²,

Giménez-Richarte

et al. 2023

Tropical Med Int Health

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“…The highest VLs in seronegative blood donors during the epidemic approached 10 8 IU RNA/ml, 23 with 2% (4 out of 209) of Puerto Rican ZIKV RNA reactive/seronegative donors identified in 2016/2017 having viral loads above 10 7 IU 9 . Using an average of the in vitro infectivity to VL ratio for our three human plasmas (183 IU RNA/PFU), ~10 8 IU of ZIKV RNA would equate to ~5 × 10 5 PFU/ml although in the current and previous 14 studies, it is important to note that RNA/PFU ratios are not consistent over the course of acute infection.…”

Section: Discussionmentioning

confidence: 95%

Plasma transfusion–transmission of Zika virus in mice and macaques

et al. 2023

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Background Zika virus (ZIKV) epidemics with infections in pregnant women are associated with severe neurological disease in newborns. Although an arbovirus, ZIKV is also blood transfusion‐transmitted (TT). Greater knowledge of the efficiency of ZIKV TT would aid decisions on testing and pathogen reduction technologies (PRT). Study Design and Methods Plasma units from ZIKV RNA‐reactive blood donors were used to study infectivity in vitro, in mice, and in macaques. Furthermore, plasma units were subjected to PRT using amotosalen/ultraviolet light A (A/UVA) before transfusion. Results In vitro infectivity of ZIKV RNA‐reactive plasma varied between 100 and 1000 international units (IU) of ZIKV RNA. Immunodeficient mice were more sensitive with as low as 32 IU sufficient to infect 50% of mice. 50–5500 IU of RNA led to TT in macaques using dose escalation of three different RNA‐positive, seronegative plasma units. In contrast, RNA‐reactive units collected postseroconversion were not infectious in macaques, even at a dose of 9 million IU RNA. After A/UVA PRT, transfusion of plasma containing up to 18 million IU was no longer infectious in vitro and did not result in ZIKV TT in macaques. Conclusion Significant risks of ZIKV TT are likely confined to a relatively short viremic window before seroconversion, and that sensitive nucleic acid amplification testing likely identifies the majority of infectious plasma. PRT was demonstrated to be effective at preventing ZIKV TT. Considering that there is no approved ZIKV vaccine, these data are relevant to mitigate the risk of TT during the future ZIKV outbreaks.

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“…Such risk may be further mitigated by applying PR technology. In addition, applying PR to platelets in the setting of arboviruses outbreaks, notably those associated with a transfusion risk such as West Nile virus [14], allows for an immediately available alternative to specific testing or targeted donor deferral [15].…”

Section: Discussionmentioning

confidence: 99%

Implementation of amotosalen plus ultraviolet A‐mediated pathogen reduction for all platelet concentrates in France: Impact on the risk of transfusion‐transmitted infections

Richard,

Pouchol,

Sandid

et al. 2023

Vox Sanguinis

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Background and ObjectivesPathogen reduction (PR) technology may reduce the risk of transfusion‐transmitted infections (TTIs), notably transfusion‐transmitted bacterial infection (TTBI) associated with platelet concentrates (PCs). PR (amotosalen/UVA treatment) was implemented for all PCs transfused in France in November 2017. No bacterial detection was in place beforehand. The study aimed to assess the impact of PR PC on TTI and TTBI near‐miss occurrences.Materials and MethodsTTI and TTBI near‐miss occurrences were compared before and after 100% PR implementation. The study period ran from 2013 to 2022. Over 300,000 PCs were transfused yearly.ResultsNo PC‐related transmission of human immunodeficiency virus, hepatitis C virus, hepatitis B virus and human T‐cell lymphotropic virus was reported throughout the study period. PC‐mediated hepatitis E virus and hepatitis A virus infections occurred irrespective of PR implementation. Mean PC‐mediated TTBI occurrence before PR‐PC implementation was 3/year (SD: 1; n = 15; 1/92,687 PC between 2013 and 2016) with a fatal outcome in two patients. Since PR implementation, one TTBI has been reported (day 4 PC, Bacillus cereus) (1/1,645,295 PC between 2018 and 2022; p < 0.001). Two PR PC quarantined because of a negative swirling test harboured bacteria: a day 6 PC in 2021 (B. cereus and Staphylococcus epidermidis) and a day 7 PC in 2022 (Staphylococcus aureus). Five similar occurrences with untreated PC were reported between 2013 and 2020.ConclusionTransfusion of 100% PR PC resulted in a steep reduction in TTBI occurrence. TTBI may, however, still occur. Pathogen‐reduced PC‐related TTI involving non‐enveloped viruses occurs as well.

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

Cited by 11 publications

References 63 publications

Pathogen inactivation methods to prevent transfusion‐transmissible arboviruses: A systematic review and meta‐analysis

Pathogen inactivation methods to prevent transfusion‐transmissible arboviruses: A systematic review and meta‐analysis

Plasma transfusion–transmission of Zika virus in mice and macaques

Implementation of amotosalen plus ultraviolet A‐mediated pathogen reduction for all platelet concentrates in France: Impact on the risk of transfusion‐transmitted infections

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