Abstract：
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.
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 + UVA light [INTERCEPT], riboflavin + UV light [Mirasol], methylene blue + visible light/UVC light [THERAFLEX], solvent detergent, amustaline [INTERCEPT] and PEN110 [Inactine]), 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.
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 load-mean 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, THERAFLEX and INTERCEPT; and in red blood cells/whole blood, PEN110 (Inactine).
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.
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 + UVA light [INTERCEPT], riboflavin + UV light [Mirasol], methylene blue + visible light/UVC light [THERAFLEX], solvent detergent, amustaline [INTERCEPT] and PEN110 [Inactine]), 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.
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 load-mean 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, THERAFLEX and INTERCEPT; and in red blood cells/whole blood, PEN110 (Inactine).
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.
摘要：
目的：虫媒病毒正在成为输血安全的相关威胁。病原体灭活方法可以降低通过输血传播的风险，只要他们达到最低的有效性标准。本研究旨在评估不同病原体灭活方法实现的病毒载量的对数减少，根据他们使用的血液产品和虫媒病毒的目标。
方法：系统文献综述和荟萃分析。在MEDLINE和Embase中进行搜索。研究方案在PROSPEROCRD42022312061中注册。我们选择了报告主要病原体灭活方法（amotosalen+UVA光[INTERCEPT]，核黄素+紫外光[Mirasol]，亚甲基蓝+可见光/UVC光[THERAFLEX]，溶剂洗涤剂,amustaline[INTERCEPT]和PEN110[Inactine]），适用于任何血液制品(血浆，血小板,红细胞或全血）和任何虫媒病毒。通过获得平均对数减少因子(LRF)来评估病毒载量的对数减少。我们使用统计方法对不同技术的LRF进行了比较和分类。
结果：我们纳入了59篇出版物，报告了17种虫媒病毒的LRF结果。对于13种虫媒病毒，包括基孔肯雅病毒,登革热病毒,西尼罗河病毒,和寨卡病毒,至少一种方法实现了病毒载量的充分或最佳对数减少-平均LRF≥4。用核黄素+紫外光实现的LRF不如其他技术，无论是整体还是特别是等离子体，保存在血小板添加剂溶液（PAS）/血浆中的血小板，和红细胞/全血。使用Mirasol实现的LRF在灭活基孔肯雅病毒方面也较低，登革热病毒,和寨卡病毒。对于西尼罗河病毒，我们没有发现显著差异.在等离子体中，达到最高LRF的方法是溶剂/洗涤剂；在血小板中，治疗和中断;在红细胞/全血，PEN110（Inactine）。
结论：并非所有病原体灭活方法都能获得相同的LRF，这在不同的虫媒病毒或血液制品之间也不等同。总的来说,使用核黄素+UV光(Mirasol)获得的LRF劣于用其余病原体灭活方法获得的那些。关于其他人,LRF因虫媒病毒和血液制品而异。鉴于不同虫媒病毒的威胁，血液机构应该已经验证了病原体灭活方法，并在后勤上做好准备以迅速实施这些技术。
方法：系统文献综述和荟萃分析。在MEDLINE和Embase中进行搜索。研究方案在PROSPEROCRD42022312061中注册。我们选择了报告主要病原体灭活方法（amotosalen+UVA光[INTERCEPT]，核黄素+紫外光[Mirasol]，亚甲基蓝+可见光/UVC光[THERAFLEX]，溶剂洗涤剂,amustaline[INTERCEPT]和PEN110[Inactine]），适用于任何血液制品(血浆，血小板,红细胞或全血）和任何虫媒病毒。通过获得平均对数减少因子(LRF)来评估病毒载量的对数减少。我们使用统计方法对不同技术的LRF进行了比较和分类。
结果：我们纳入了59篇出版物，报告了17种虫媒病毒的LRF结果。对于13种虫媒病毒，包括基孔肯雅病毒,登革热病毒,西尼罗河病毒,和寨卡病毒,至少一种方法实现了病毒载量的充分或最佳对数减少-平均LRF≥4。用核黄素+紫外光实现的LRF不如其他技术，无论是整体还是特别是等离子体，保存在血小板添加剂溶液（PAS）/血浆中的血小板，和红细胞/全血。使用Mirasol实现的LRF在灭活基孔肯雅病毒方面也较低，登革热病毒,和寨卡病毒。对于西尼罗河病毒，我们没有发现显著差异.在等离子体中，达到最高LRF的方法是溶剂/洗涤剂；在血小板中，治疗和中断;在红细胞/全血，PEN110（Inactine）。
结论：并非所有病原体灭活方法都能获得相同的LRF，这在不同的虫媒病毒或血液制品之间也不等同。总的来说,使用核黄素+UV光(Mirasol)获得的LRF劣于用其余病原体灭活方法获得的那些。关于其他人,LRF因虫媒病毒和血液制品而异。鉴于不同虫媒病毒的威胁，血液机构应该已经验证了病原体灭活方法，并在后勤上做好准备以迅速实施这些技术。
