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The objective of this study was to examine the effects of polyethylene glycol (PEG) treated red blood cells (RBCs) on the microcirculation in a hamster back skin window chamber model. Donor hamster RBCs were PEGylated through an incubation with an activated PEG solution, washed, resuspended, and infused through a 10% volume top loading procedure into the carotid artery in an awake Syrian Golden hamster. Eight hamster groups were treated with activated PEG different sizes and concentrations: 0.05 mM-5 kDa PEG, 0.5 mM-5 kDa PEG, 1.1 mM-5 kDa PEG, 2.2 mM-5 kDa PEG, 22 mM-5 kDa PEG, 0.05 mM-20 kDa PEG, 0.5 mM-20 kDa PEG, and 5 mM-20 kDa PEG. Non-treated RBCs were used as control. The microvascular bed under observation was videotaped 30 min before the infusion and followed for 30 min post infusion. The diameter of individual blood vessels and blood flow velocities in selected vessels was measured. Hematocrit and hemoglobin concentration were recorded before infusion and at the end of experiment. Tissue pO2 was also monitored. Results showed the hamsters tolerated the PEGylated RBCs without apparent ill effects. No significant changes were recorded for the hematocrit, the hemoglobin concentration, the blood vessel diameters, blood flow velocities, and the interstitial partial oxygen pressure (pO2) before, during, and after the injections of PEG-RBCs (P > 0.05). Unlike most hemoglobin-based oxygen carrying compounds, which can cause vasoconstriction, the PEGylated RBCs did not produce any measurable vasoactivity. Together with the absence of rouleaux formation and the fact that PEG molecules can mask the surface antigens on RBCs, PEGylation appeared promising as a circulation enhancement treatment. [ABSTRACT FROM AUTHOR]

Background: Risk of transfusion-transmitted (TT) malaria is mainly associated with whole blood (WB) or red blood cell (RBC) transfusion. Risk mitigation relies mostly on donor deferral while a limited number of countries perform blood testing, both negatively impacting blood availability. This study investigated the efficacy of the pathogen reduction system using amustaline and glutathione (GSH) to inactivate Plasmodium falciparum in WB.Study Design and Methods: WB units were spiked with ring stage P. falciparum infected RBCs. Parasite loads were measured in samples at time of infection, after 24 hours at room temperature (RT), and after a 24-hour incubation at RT post-treatment with 0.2 mM amustaline and 2 mM GSH. Serial 10-fold dilutions of the samples were inoculated to RBC cultures and maintained up to 4 weeks. Parasitemia was quantified by cytometry.Results: The P. falciparum viability assay has a limit of detection of a single live parasite per sample. Input parasite titer was >5.7 log10 TCID50 per mL. A 24-hour incubation at RT paused parasite development in controls, but they retained viability and infectivity when tested in culture. In contrast, no infectious parasites were detected in the amustaline/GSH-treated sample after 4 weeks of culture.Conclusion: A robust level of P. falciparum inactivation was achieved in WB using amustaline/GSH treatment. Parasite log reduction was >5.7 log10 TCID50 per mL. Development of such a pathogen reduction system may provide an opportunity to reduce the risk of TT malaria and improve blood availability. [ABSTRACT FROM AUTHOR]

The ISBT Working Party on Transfusion‐Transmitted Infectious Diseases, Bacterial Subgroup (TTID‐WP‐BS) held a meeting during the 2017 ISBT Congress covering topics on safety of platelet components (PC), which are highlighted in this review. The TTID‐WP‐BS along with the Paul Ehrlich Institute have pioneered the development of bacterial strain repositories for PC and red blood cells (RBC) to be used for the validation of detection and pathogen reduction (PR) technologies. Results of the development of the RBC repository strains indicated that six bacterial strains were selected for further testing in international studies, complementing the previous study developed for PC. The THERAFLEX UV‐Platelets PR technology has used the bacterial strain repository for PC to test the effectiveness of the system with data presented in this report. Other PR studies described herein include a report of inactivation of Serratia marcescens by the INTERCEPT Blood System for PC at the levels of the PR claim. Furthermore, a summary of current and future developments of the Mirasol PR system was presented with emphasis on PR in whole blood. Advances in PC screening for bacterial contamination were covered by a comparative study of the BacT/ALERT 3D and BacT/ALERT VIRTUO systems, demonstrating that the latter has a shorter time to detection. Finally, data on septic transfusion reactions involving PC produced in plasma and platelet additive solutions indicated different clinical outcomes and screening results. The topics covered during the TTID‐WP‐BS meeting generated insightful scientific discussions and advanced knowledge, one of the most relevant activities of the Bacterial Subgroup. [ABSTRACT FROM AUTHOR]

Background and objectives: Chikungunya virus (CHIKV) infections have been reported in all continents, and the potential risk for CHIKV transfusion‐transmitted infections (TTIs) was demonstrated by the detection of CHIKV RNA‐positive donations in several countries. TTIs can be reduced by pathogen inactivation (PI) of blood products. In this study, we evaluated the efficacy of amustaline and glutathione (S‐303/GSH) to inactivate CHIKV in red‐blood‐cell concentrates (RBCs). Material and Methods: Red‐blood‐cells were spiked with high level of CHIKV. Infectious titres and RNA loads were measured before and after PI treatment. Residual CHIKV infectivity was also assessed after five successive cell culture passages. Results: The mean CHIKV titres in RBCs before inactivation was 5·81 ± 0·18 log10 50% tissue culture infectious dose (TCID50)/mL, and the mean viral RNA load was 10·49 ± 0·15 log10 genome equivalent (GEq)/mL. No CHIKV TCID was detected after S‐303 treatment nor was replicative CHIKV particles and viral RNA present after five cell culture passages of samples obtained immediately after S‐303 treatment. Conclusion: Chikungunya virus was previously shown to be inactivated by the PI technology using amotosalen and ultraviolet A light for the treatment of plasma and platelets. This new study demonstrates that S‐303/GSH can inactivate high titres of CHIKV in RBCs. [ABSTRACT FROM AUTHOR]

Background: Dengue virus (DENV) is an arbovirus primarily transmitted through mosquito bite; however, DENV transfusion-transmitted infections (TTIs) have been reported and asymptomatic DENV RNA-positive blood donors have been identified in endemic countries. DENV is considered a high-risk pathogen for blood safety. One of the mitigation strategies to prevent arbovirus TTIs is pathogen inactivation. In this study we demonstrate that the amustaline and glutathione (S-303/GSH) treatment previously found effective against Zika virus in red blood cells (RBCs) is also effective in inactivating DENV.Study Design and Methods: Red blood cells were spiked with high levels of DENV. Viral RNA loads and infectious titers were measured in the untreated control and before and after pathogen inactivation treatment of RBC samples. DENV infectivity was also assessed over five successive cell culture passages to detect any potential residual replicative virus.Results: The mean ± SD DENV titer in RBCs before inactivation was 6.61 ± 0.19 log 50% tissue culture infectious dose (TCID50 )/mL and the mean viral RNA load was 8.42 log genome equivalents/mL. No replicative DENV was detected either immediately after completion of treatment using S-303/GSH or after cell culture passages.Conclusion: Treatment using S-303/GSH inactivated high levels of DENV in RBCs to the limit of detection. In combination with previous studies showing the effective inactivation of DENV in plasma and platelets using the licensed amotosalen/UVA system, this study demonstrates that high levels of DENV can be inactivated in all blood components. [ABSTRACT FROM AUTHOR]

Background: With an increasing number of recognized transfusion-transmitted (TT) babesiosis cases, Babesia microti is the most frequently TT parasite in the United States. We evaluated the inactivation of B. microti in red blood cells (RBCs) prepared in Optisol (AS-5) using amustaline and glutathione (GSH) and in platelet components (PCs) in 100% plasma using amotosalen and low-energy ultraviolet A (UVA) light.Study Design and Methods: Individual RBCs and apheresis PCs were spiked with B. microti-infected hamster RBCs (iRBCs) to a final concentration of 106 iRBCs/mL and treated with the respective inactivation systems according to the manufacturer's instruction. Samples were collected before (control) and after (test) each treatment. Dilutions of the control samples to 10-6 were inoculated into hamsters, while the test samples were inoculated neat or at 10-1 dilution. At 3 and 5 weeks postinoculation, hamsters were evaluated for B. microti infection by microscopic observation of blood smears and 50% infectivity titers (ID50 ) were determined. Log reduction was calculated as control log ID50 minus test log ID50 .Results: Parasitemia was detected in hamsters injected with as low as 100,000-fold diluted control samples, while no parasites were detectable in the blood smears of any hamsters receiving neat test samples. Mean log reduction was more than 5 log/mL by amustaline/GSH for RBCs and more than 4.5 log/mL by amotosalen/UVA for PCs.Conclusion: B. microti was inactivated to the limit of detection in RBCs and PCs after the respective inactivation treatment. Complete inactivation of B. microti was achieved in this animal infectivity model, and pathogen reduction treatment inhibited transmission of infection. [ABSTRACT FROM AUTHOR]

Background: The potential for Zika virus (ZIKV) transfusion-transmission (TT) has been demonstrated in French Polynesia and Brazil. Pathogen inactivation (PI) of blood products is a proactive strategy to inactivate TT pathogens including arboviruses. Inactivation of West Nile, dengue, Zika, and chikungunya viruses was previously demonstrated by photochemical treatment with amotosalen and ultraviolet A (UVA) illumination. In this study, we evaluated ZIKV inactivation in red blood cell (RBC) components by a chemical approach that uses amustaline (S-303) and glutathione (GSH).Study Design and Methods: RBC components were spiked with a high titer of ZIKV. Viral titers (infectivity) and ZIKV RNA loads (reverse transcription-polymerase chain reaction) were measured in spiked RBCs before and after S-303 and GSH treatment and confirmed using repetitive passages in cell culture. A mock-treated arm validated the approach by demonstrating stability of the virus (infectivity and RNA load) during the process.Results: The mean ZIKV infectivity titer and RNA load in RBCs were 5.99 ± 0.2 log 50% tissue culture infectious dose (TCID50 )/mL and 7.75 ± 0.16 log genomic equivalents/mL before inactivation. No infectivity was detected immediately after S-303 and GSH treatment and after five serial passages in cell culture.Conclusion: Complete ZIKV inactivation of more than 5.99 log TCID50 /mL in RBCs was achieved using S-303 and GSH at levels higher than those found in asymptomatic ZIKV-infected blood donors. Therefore, the S-303 and GSH PI system is promising for mitigating the risk of ZIKV TT. [ABSTRACT FROM AUTHOR]

Abstract: Background: The presence of nucleated red blood cells (NRBCs) has been identified as a poor prognostic indicator. We investigated the relationship of NRBC trends in patients with and without trauma. Methods: We retrospectively reviewed surgical intensive care unit admissions over 4 years, categorizing trauma and nontrauma patients and subdividing them into 3 groups: group A, all-zero NRBC; group B, positive NRBC value returning to zero; and group C, positive NRBC value that did not return to zero. We analyzed all groups for outcomes of length of stay and mortality. Results: Group A was the largest and had the shortest length of stay and least mortality. Group C had the highest mortality rate. No statistical difference was observed with mortality. Conclusions: Any positive NRBC was associated with poor outcome, and increasing NRBC was associated with increasing mortality. Trends in NRBC values showed that returning to zero was protective. [Copyright &y& Elsevier]