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Laurence Corash - One of the best experts on this subject based on the ideXlab platform.

  • Amotosalen inactivated fresh frozen plasma is comparable to solvent detergent inactivated plasma to treat thrombotic thrombocytopenic purpura
    Transfusion and Apheresis Science, 2019
    Co-Authors: Olivier Garraud, Laurence Corash, Jeanmarc Payrat, Jin Sying Lin, Sandrine Malot, Raoul Herbrecht, Mario Ojedauribe, Agnes Veyradier, Kathy Liu, Paul Coppo
    Abstract:

    Abstract Background Therapeutic Plasma Exchange (TPE) is the primary therapy of immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP). Efficacy and safety data for TPE of iTTP have been assessed with Quarantine and Solvent-Detergent inactivated (SD) plasma. Here, Amotosalen-UVA pathogen inactivated (AI) plasma, also in routine use, was evaluated in iTTP. Methods We conducted a retrospective review of iTTP cases prospectively reported to the French national registry (2010–2013). Cases reviewed underwent TPE with ≥70% of either AI or SD plasma. The primary endpoint was time to platelet count recovery; secondary endpoints were related to follow-up (sustained remission, relapses, flare-ups and refractoriness). Results 30 Test patients were identified in the AI group which could be timely matched to 40 Control patients in the SD group. The groups were fairly comparable for clinical presentation. Major findings were: (i) iTTP patients were exposed to lower plasma volumes in the AI group than in the SD group; (ii) Recovery rates were comparable between the groups. Median time to platelet count recovery (>150 × 109/L) trended to be shorter in the AI group though non significantly. Tolerance of AI vs SD plasma was of comparable frequency and severity in either group. Conclusion TPE with Amotosalen-inactivated plasma demonstrated therapeutic efficacy and tolerability for iTTP patients. In view of the retrospective design, confirmation of these results is required in larger prospective studies.

  • transfusion de plaquettes traitees par Amotosalen conservees jusqu a 7 jours
    Transfusion Clinique Et Biologique, 2019
    Co-Authors: Laura Infanti, Laurence Corash, Richard J Benjamin, Jin Sying Lin, Jakob Passweg, Andreas Holbro, David Tappe, Andreas Buser
    Abstract:

    Contexte La reduction des agents pathogenes par Amotosalen/UVA (INTERCEPT™ (IA)) pour les concentres de plaquettes (CP) dont 80 a 90 % proviennent d’apherese, est utilisee en routine par notre institution. Les CP sont conserves pendant 7 jours maximums. Objectif Evaluer l’impact de la duree de conservation sur l’efficacite therapeutique des CP-IA pour les patients en hematologie-oncologie et ceux subissant une greffe de cellules souches hematopoietiques (GCSH) allogenique. Methodes Les increments plaquettaires (CI) et CI corriges (CCI) ont ete obtenus 1 a 4 heures apres la transfusion. Le risque d’echec de l’hemostase a ete evalue par la necessite d’une transfusion supplementaire de CP ou de concentres de globules rouges (CGR) le jour de la transfusion de CP ou le jour suivant. Resultats Voir Tableau 1 . De 2011 a 2016, 22578 CP ont ete transfuses a 2809 patients. 16,6 % des CP etaient âges de > 5 jours. Les GCSH representaient 14,8 % de la population (13,1 % allogreffes) et ont utilise 50,6 % des CP. La dose moyenne de plaquettes etait de 3,0 ± 0,4 × 10 11 , avec une duree de conservation moyenne de 4,1 ± 1,4 jours. Les CI et CCI ont diminue de facon lineaire avec l’âge des CP. L’utilisation de CP ou de CGR supplementaire(s) le jour meme ou le lendemain d’une transfusion de CP n’a pas augmente avec la duree de stockage. Le delai median avant la prochaine transfusion de CP (1,0 jour) n’etait pas affecte par la duree de conservation du CP. Conclusion L’augmentation de la duree de conservation des CP a ete associee a une diminution des CI et CCI mais n’affecte pas l’hemostase, comme en temoigne l’absence de besoin en CP ou de CGR supplementaires le jour meme ou suivant la transfusion de CP-IA.

  • Amotosalen uva treatment inactivates t cells more effectively than the recommended gamma dose for prevention of transfusion associated graft versus host disease
    Transfusion, 2018
    Co-Authors: Grace Castro, Laurence Corash, Patricia A Merkel, Hannah E Giclas, Andrew Gibula, Gillian Andersen, Jin Sying Lin, Jennifer Green, Vijaya Knight, Adonis Stassinopoulos
    Abstract:

    INTRODUCTION Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare complication after transfusion of components containing viable donor T cells. Gamma irradiation with doses that stop T-cell proliferation is the predominant method to prevent TA-GVHD. Treatment with pathogen inactivation methodologies has been found to also be effective against proliferating white blood cells, including T cells. In this study, T-cell inactivation was compared, between Amotosalen/ultraviolet A (UVA) treatment and gamma-irradiation (2500 cGy), using a sensitive limiting dilution assay (LDA) with an enhanced dynamic range. METHODS AND MATERIALS Matched plasma units (N = 8), contaminated with 1 × 106 peripheral blood mononuclear cells (PBMCs) per mL, were either treated with Amotosalen/UVA or gamma irradiation, or retained as untreated control. Posttreatment, cells were cultured under standardized conditions. T-cell proliferation was determined by the incorporation of 3 H-thymidine and correlated with microscopic detection. RESULTS Range-finding experiments showed that after gamma irradiation (2500 cGy), significant T-cell proliferation could be observed at a 1 × 107 cell culture density, some proliferation at 1 × 106 , and none at 1 × 105 cells/well. Based on these facts, a quantitative comparison was carried out between Amotosalen/UVA at the highest challenge of 1 × 107 PBMCs/well, and gamma irradiation at 1 × 106 and 1 × 105 PBMCs/well. Complete inactivation of the T cells after Amotosalen/UVA treatment was observed, equivalent to greater than 6.2 log inactivation. Complete inactivation of the T cells was also observed after gamma irradiation when 1 × 105 PBMCs/well were cultured (>4.2 log inactivation). Proliferation was observed when 1 × 106 PBMCs/well were cultured (≤5.2 log inactivation) after gamma irradiation. CONCLUSION Amotosalen/UVA treatment more effectively inactivates T cells than the current standard of gamma irradiation (2500 cGy) for the prevention of TA-GVHD.

  • hemovigilance monitoring of platelet septic reactions with effective bacterial protection systems
    Transfusion, 2017
    Co-Authors: Richard J Benjamin, Tina Weingand, Thomas Braschler, Laurence Corash
    Abstract:

    BACKGROUND Delayed, large-volume bacterial culture and Amotosalen/ultraviolet-A light pathogen reduction are effective at reducing the risk of bacterial proliferation in platelet concentrates (PCs). Hemovigilance programs continue to receive reports of suspected septic transfusion reactions, most with low imputability. Here, we compile national hemovigilance data to determine the relative efficacy of these interventions. STUDY DESIGN AND METHODS Annual reports from the United Kingdom, France, Switzerland, and Belgium were reviewed between 2005 and 2016 to assess the risk of bacterial contamination and septic reactions. RESULTS Approximately 1.65 million delayed, large-volume bacterial culture-screened PCs in the United Kingdom and 2.3 million Amotosalen/ultraviolet-A–treated PCs worldwide were issued with no reported septic fatalities. One definite, one possible, and 12 undetermined/indeterminate septic reactions and eight contaminated “near misses” were reported with delayed, large-volume bacterial cultures between 2011 and 2016, for a lower false-negative culture rate than that in the previous 5 years (5.4 vs. 16.3 per million: odds ratio, 3.0; 95% confidence interval, 1.4-6.5). Together, the Belgian, Swiss, and French hemovigilance programs documented zero probable or definite/certain septic reactions with 609,290 Amotosalen/ultraviolet-A–treated PCs (<1.6 per million). The rates were significantly lower than those reported with concurrently transfused, nonpathogen-reduced PCs in Belgium (<4.4 vs. 35.6 per million: odds ratio, 8.1; 95% confidence interval,1.1-353.3) and with historic septic reaction rates in Switzerland (<6.0 vs. 82.9 per million: odds ratio, 13.9; 95% confidence interval, 2.1-589.2), and the rates tended to be lower than those from concurrently transfused, nonpathogen-reduced PCs in France (<4.7 vs. 19.0 per million: odds ratio, 4.1; 95% confidence interval, 0.7-164.3). CONCLUSION Pathogen reduction and bacterial culture both reduced the incidence of septic reactions, although under-reporting and strict imputability criteria resulted in an underestimation of risk.

  • plasma attenue pour les agents pathogenes par Amotosalen conserve liquide
    Transfusion Clinique Et Biologique, 2017
    Co-Authors: Anna Erickson, Richard J Benjamin, Jeanmarc Payrat, Katie Waldhaus, Norman Huang, Nina Mufti, Laurence Corash
    Abstract:

    Contexte La reanimation precoce et agressive avec du plasma, des globules rouges et plaquettes est indiquee dans les protocoles de transfusion massive (PTM) en cas de traumatisme. Le plasma frais congele pourrait etre decongele et stocke a 1–6°C pour permettre une disponibilite rapide dans les PTM. L’attenuation des pathogenes permettrait alors de reduire le risque infectieux lie aux PTM. Objectif et methode Cette etude a pour but de mesurer les concentrations proteiques et la capacite a generer la thrombine dans les PFC-IA traites par Amotosalen/UVA compares a des PFC controles non traites (PFC-C), congeles 8 ou 24 heures apres collecte, stockes ∼3 a 12 mois, decongeles et maintenus a 1–6°C pendant 5 jours. Resultats Les PFC-IA decongeles ( n  = 24) presentaient jusqu’a J5 des taux en Facteurs I, II, V, VIII, IX, × , VWF:RCo, ATIII, proteine C et S comparables aux PFC-C. La capacite a generer la thrombine etait maintenue a J5 (voir Tableau 1 ) pour les PFC-IA. La plupart des facteurs a J5, etaient a > 90 % des taux mesures J0, sauf les facteurs V, VIII et proteine S. Toutes les unites contenaient > 0,4 â’â’UI/mL de proteine S et d’alpha-2 antiplasmine a j5. D’apres les marqueurs globaux (complexes TAT, temps de cephaline, pic de generation de thrombine), la coagulation ne semblait pas etre plus activee dans les PFC-IA que dans les PFC-C. Conclusion Le PFC-IA decongele demontre une activite procoagulante et antithrombotique comparable au plasma non-traite decongele apres 5 jours de stockage a 1–6°C. Ce plasma liquide (non approuve) representerait une alternative interessante pour les PTM tout en ameliorant la securite par rapport aux agents pathogenes transmissibles par le sang.

Lily Lin - One of the best experts on this subject based on the ideXlab platform.

  • the extent of Amotosalen photodegradation during photochemical treatment of platelet components correlates with the level of pathogen inactivation
    Transfusion, 2011
    Co-Authors: Weiqun Liu, Laurence Corash, George D Cimino, Lily Lin
    Abstract:

    BACKGROUND: Amotosalen plus ultraviolet A (UVA) light inactivates a broad range of bacteria, viruses, protozoa, and leukocytes in platelet (PLT) and plasma components. Upon UVA illumination a small fraction of Amotosalen reacts with the nucleic acid of contaminating pathogens and residual white blood cells and the remaining fraction undergoes photodegradation into defined photoproducts. The levels of Amotosalen and photoproducts can be accurately quantified. STUDY DESIGN AND METHODS: This study evaluated the relationship between the extent of photodegradation of Amotosalen and the level of pathogen inactivation in PLT components. PLT components containing of 3.78 × 1011 to 7.23 × 1011 PLTs in 300 to 450 mL of 35% to 50% plasma and 50% to 65% PLT additive solution and up to 5 × 106 red blood cells (RBCs)/mL were prepared. Each component was contaminated with 105 to 106 colony-forming units/mL Klebsiella pneumoniae and treated with 115 to 200 µmol/L Amotosalen and 0 to 3 J/cm2 UVA light. For each treatment condition, the level of K. pneumoniae inactivation (log-reduction) was measured by microbiologic methods. The initial and postillumination Amotosalen concentrations (µmol/L) were determined by high-performance liquid chromatography. RESULTS: For a defined set of treatment conditions, the extent of Amotosalen photodegradation was consistent and reproducible. The bacterial log-reduction correlated linearly with the extent of Amotosalen photodegradation with a regression correlation coefficient (r2) between 0.845 and 0.890 regardless of the treatment variables such as PLT content, component volume, plasma content, RBC content, initial Amotosalen concentration, and UVA dose. CONCLUSION: This study demonstrated that the extent of Amotosalen photodegradation can serve as an intrinsic actinometer which directly correlated with the level of pathogen inactivation.

  • assessment of safety in neonates for transfusion of platelets and plasma prepared with Amotosalen photochemical pathogen inactivation treatment by a 1 month intravenous toxicity study in neonatal rats
    Transfusion, 2009
    Co-Authors: Vic Ciaravino, Lily Lin, Jessica Hanover, Theresa Sullivan, Laurence Corash
    Abstract:

    BACKGROUND: It is estimated that approximately 300,000 neonates undergo transfusions annually. The neonatal immune system is immature, making such patients more susceptible to the effects associated with transfusion-transmitted bacteria, viruses, protozoa, and white blood cells (WBCs). The INTERCEPT Blood System is a photochemical process (PCT) utilizing Amotosalen and long-wavelength ultraviolet to inactivate pathogens and WBCs in both platelet (PLT) and plasma components for transfusion. A series of clinical studies has shown PCT PLTs and PCT plasma to be safe and effective for transfusion in adults and pediatric patients. Because clinical studies in neonates are technically difficult and ethically challenging, preclinical toxicologic studies were conducted in neonatal rats to evaluate the safety of PCT blood components for neonates. STUDY DESIGN AND METHODS: This study examined daily intravenous administration to neonatal rats of Amotosalen in 35 percent:65 percent plasma:InterSol from 1 µg per kg per day (representing 1-unit transfusion) to 457 µg per kg per day (representing multiple transfusions) from Postnatal Day 4 (PND4) to PND31. Rats were observed for viability, clinical signs, and body weights until PND31 and then subjected to pathology evaluation. Hematology, clinical chemistry, and urinalysis data were also collected on PND31. Toxicokinetic parameters were evaluated on PND4 and PND31. RESULTS: There were no Amotosalen-related effects on clinical signs, body weight, hematology, clinical chemistry, urinalysis, gross pathology, or histopathology, despite the exposure of neonatal rats to Amotosalen concentrations as high as approximately 48 times the standard exposure in adult patients. CONCLUSION: This study demonstrates the safety of PCT for transfusion in neonatal rats and augments data from other studies and clinical use supporting the use of PCT in neonatal patients.

  • evaluation of in vitro storage properties of prestorage pooled whole blood derived platelets suspended in 100 percent plasma and treated with Amotosalen and long wavelength ultraviolet light
    Transfusion, 2009
    Co-Authors: Stephen J Wagner, Andrey Skripchenko, Andrew Myrup, Helen Awatefe, Dedeene Thompsonmontgomery, Gary Moroff, Patrick Carmichael, Lily Lin
    Abstract:

    BACKGROUND: Amotosalen, a psoralen, has been utilized for photochemical treatment (PCT) of apheresis platelets (PLTs) and pooled buffy coat PLTs suspended in additive solution. In the United States, the source of many PLT transfusions is from whole blood–derived PLTs prepared by the PLT-rich plasma (PRP) method. This study investigated the in vitro PLT properties of Amotosalen-PCT of leukoreduced pools of PLTs prepared by the PRP method and suspended in 100 percent plasma. STUDY DESIGN AND METHODS: On Day 1 of storage, 12 leukoreduced (n = 6) or 10 leukoreplete (n = 6) ABO-identical PLT concentrates were pooled, separated into two pools of 6 or 5 units, respectively, and leukoreduced (leukoreplete pools only). Each pool of 5 or 6 units was then photochemically treated (designated “test”: Amotosalen plus 3.0 J/cm2 long-wavelength ultraviolet light followed by Amotosalen/photoproduct removal) while the remaining identical pool (designated “control”) was untreated. PLT in vitro assays were performed on test and control pools during 7-day storage. RESULTS: PCT resulted in slightly reduced pH in test pools compared to that of matched control pools after 5 days of storage (5-unit pools: test, 6.96 ± 0.12 vs. control, 7.15 ± 0.09, p = 0.0033; 6-unit pools: test, 6.90 ± 0.10 vs. control, 7.07 ± 0.09, p < 0.0001). Test pools adequately maintained many other in vitro properties including PLT morphology, hypotonic shock response, and extent of shape change parameters during 5-day storage, which, like pH, also differed from those of controls. The pH of test and control pools declined on Day 7, with 1 of 6 test pools (either 5 or 6 units) having a pH value of less than 6.20, while all control pools had pH values of more than 6.66. CONCLUSION: PCT of leukoreduced PLT pools of whole blood–derived PLTs in 100 percent plasma maintained adequate PLT in vitro variables through 5 days of storage.

  • photochemical inactivation with Amotosalen and long wavelength ultraviolet light of plasmodium and babesia in platelet and plasma components
    Transfusion, 2008
    Co-Authors: Philippe Grellier, Lily Lin, Ryan Alfonso, Jorge L Benach, Mehdi Labaied, Sebastien Charneau, Horacio Gil, Gloria Monsalve, Lynette Sawyer, Matthias Steiert
    Abstract:

    BACKGROUND: Transfusion-transmitted cases of malaria and babesiosis have been well documented. Current efforts to screen out contaminated blood products result in component wastage due to the lack of specific detection methods while donor deferral does not always guarantee safe blood products. This study evaluated the efficacy of a photochemical treatment (PCT) method with Amotosalen and long-wavelength ultraviolet light (UVA) to inactivate these agents in red blood cells (RBCs) contaminating platelet (PLT) and plasma components. STUDY DESIGN AND METHODS:Plasmodium falciparum– and Babesia microti–contaminated RBCs seeded into PLT and plasma components were treated with 150 µmol per L Amotosalen and 3 J per cm2 UVA. The viability of both pathogens before and after treatment was measured with infectivity assays. Treatment with 150 µmol per L Amotosalen and 1 J per cm2 UVA was used to assess the robustness of the PCT system. RESULTS: No viable B. microti was detected in PLTs or plasma after treatment with 150 mol per L Amotosalen and 3 J per cm2 UVA, demonstrating a mean inactivation of greater than 5.3 log in PLTs and greater than 5.3 log in plasma. After the same treatment, viable P. falciparum was either absent or below the limit of quantification in three of four replicate experiments both in PLTs and in plasma demonstrating a mean inactivation of at least 6.0 log in PLTs and at least 6.9 log in plasma. Reducing UVA dose to 1 J per cm2 did not significantly affect the level of inactivation. CONCLUSION:P. falciparum and B. microti were highly sensitive to inactivation by PCT. Pathogen inactivation approaches could reduce the risk of transfusion-transmitted parasitic infections and avoid unnecessary donor exclusions.

  • The efficacy of photochemical treatment with Amotosalen HCl and ultraviolet A (INTERCEPT) for inactivation of Trypanosoma cruzi in pooled buffy‐coat platelets
    Transfusion, 2007
    Co-Authors: Emma Castro, Lily Lin, Núria Gironès, José Luis Bueno, Javier Carrión, Manuel Fresno
    Abstract:

    BACKGROUND This study evaluated the efficacy of photochemical treatment (PCT) with Amotosalen and ultraviolet A (UVA) light to inactivate Trypanosoma cruzi in contaminated platelet (PLT) components. STUDY DESIGN AND METHODS Fifteen pools of buffy-coat PLTs (BC-PLTs) were inoculated with approximately 5 x 10(3) to 5 x 10(5) per mL of viable T. cruzi of the G, Tulahuen (T), or Y strains. Samples from BC-PLTs were assayed for infectivity before and after PCT with 150 micromol per L Amotosalen and 3 J per cm(2) UVA light. Infectivity was determined with three different methods: 1) in vitro culture to detect viable epimastigotes, 2) [(3)H]thymidine incorporation in culture, and 3) in vivo inoculation into interferon-gamma receptor (IFN-gammaR)-deficient mice. RESULTS The in vitro assay yielded viable parasite titers of 3.9 x 10(5), 2.8 x 10(4), and 5.6 x 10(3) per mL (corresponding to 5.6, 4.4, and 3.8 logs/mL) for the Y, T, and G strains, respectively. PCT was able to inactivate all three strains of T. cruzi to below the limit of detection (10 parasites/mL) in the sensitive in vivo assay. Because 10-mL samples, each concentrated into a 1-mL sample for inoculation, were tested in the in vivo assay, log reductions achieved were greater than 5.6, greater than 4.4, and greater than 3.8 for the Y, T, and G strains of T. cruzi, respectively. CONCLUSIONS The pathogen reduction system with Amotosalen HCl and UVA demonstrated robust efficacy for inactivation of high doses of three different strains of T. cruzi and offers the potential to make the PLT supply safer.

Ghazi A Damanhouri - One of the best experts on this subject based on the ideXlab platform.

  • Amotosalen and ultraviolet a light treatment efficiently inactivates severe acute respiratory syndrome coronavirus 2 sars cov 2 in human plasma
    Vox Sanguinis, 2021
    Co-Authors: Esam I Azhar, Salwa Hindawi, Sherif A Elkafrawy, Ahmed M Hassan, Ahmed M Tolah, Thamir A Alandijany, Leena H Bajrai, Ghazi A Damanhouri
    Abstract:

    Background and objectives During the ongoing pandemic of COVID-19, SARS-CoV-2 RNA was detected in plasma and platelet products from asymptomatic blood donors, raising concerns about potential risk of transfusion transmission, also in the context of the current therapeutic approach utilizing plasma from convalescent donors. The objective of this study was to assess the efficacy of Amotosalen/UVA light treatment to inactivate SARS-CoV-2 in human plasma to reduce the risk of potential transmission through blood transfusion. Methods Pools of three whole-blood-derived human plasma units (630-650 ml) were inoculated with a clinical SARS-CoV-2 isolate. Spiked units were treated with Amotosalen/UVA light (INTERCEPT Blood System™) to inactivate SARS-CoV-2. Infectious titres and genomic viral load were assessed by plaque assay and real-time quantitative PCR. Inactivated samples were subject to three successive passages on permissive tissue culture to exclude the presence of replication-competent viral particles. Results Inactivation of infectious viral particles in spiked plasma units below the limit of detection was achieved by Amotosalen/UVA light treatment with a mean log reduction of >3·32 ± 0·2. Passaging of inactivated samples on permissive tissue showed no viral replication even after 9 days of incubation and three passages, confirming complete inactivation. The treatment also inhibited NAT detection by nucleic acid modification with a mean log reduction of 2·92 ± 0·87 PFU genomic equivalents. Conclusion Amotosalen/UVA light treatment of SARS-CoV-2 spiked human plasma units efficiently and completely inactivated >3·32 ± 0·2 log of SARS-CoV-2 infectivity, showing that such treatment could minimize the risk of transfusion-related SARS-CoV-2 transmission.

  • efficient inactivation of sars cov 2 in human plasma with Amotosalen and ultraviolet a light treatment
    Transfusion, 2020
    Co-Authors: Esam I Azhar, Marcus Picardmaureau, Salwa Hindawi, Sherif A Elkafrawy, Ahmed M Hassan, Ahmed M Tolah, Thamir A Alandijany, Qossay Abunada, Ghazi A Damanhouri
    Abstract:

    Background/Case Studies: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was identified in January 2020 as the responsible agent for COVID-19 First recognized in late 2019, the COVID-19 epidemic developed into a pandemic with, as of July 23, 2020, more than 15 million cases and 600,000 deaths reported globally SARS-CoV-2 RNA was detected in blood samples and blood components from asymptomatic blood donors including frozen plasma units and platelet concentrates This suggests that SARS-CoV-2 may be a potential bloodborne pathogen and pathogen reduction offers potential to reduce the risk of transfusion transmission We investigated the efficacy of Amotosalen/UVA light to inactivate SARS-CoV-2 in human plasma Study Design/Methods: Five pools of whole-blood derived human plasma units (630-650 mL each) were inoculated with a local clinical isolate (SARS-CoV-2/ human/SAU/85791C/2020) with a 1:100 dilution Spiked pools were used to evaluate the efficacy of Amotosalen/ UVA treatment (INTERCEPT® Blood System, Cerus Corporation, Concord, U S A ) to inactivate SARS-CoV-2 in plasma Infectious and genomic viral titers were assessed by plaque assay and quantitative PCR (Altona Diagnostics, Hamburg, Germany), respectively, in spiked and treated samples in parallel with positive and negative controls Results/Findings: Treatment of spiked plasma (titer of the viral stock: 5 6±0 2 log10 pfu/mL) with Amotosalen/ UVA light resulted in complete inactivation of infectious viral titer with mean log reduction of >3 3±0 2 log10 pfu/mL No viral replication or cytopathic effect (CPE) was observed in cells inoculated with inactivated samples even after 9 days of incubation and three successive passages Evaluation of genomic titer expressed in genome equivalent (GEq/mL) in inactivated samples showed equivalent reduction to the limit of detection of 7 10±0 2 log10 GEq/mL Conclusions: Complete and efficient inactivation of SARS-CoV-2 was observed with Amotosalen/UVA light treatment of spiked human plasma units suggesting that treatment of plasma with this pathogen reduction technology could reduce the risk of transfusion-transmitted SARS-CoV-2 infection These findings are consistent with prior inactivation data with Amotosalen/UVA for other human-pathogenic coronaviruses (SARS-CoV-1 and MERS-CoV) in platelets and plasma

  • Amotosalen and ultraviolet a light efficiently inactivate mers coronavirus in human platelet concentrates
    Transfusion Medicine, 2019
    Co-Authors: Anwar M Hashem, Marcus Picardmaureau, Sherif A Elkafrawy, Ahmed M Hassan, Ahmed M Tolah, Qossay Abunada, Esam I Azhar, Ghazi A Damanhouri, M A Alsaadi, Salwa Hindawi
    Abstract:

    Objective This study aimed to assess the efficacy of the INTERCEPT™ Blood System [Amotosalen/ultraviolet A (UVA) light] to reduce the risk of Middle East respiratory syndrome-Coronavirus (MERS-CoV) transmission by human platelet concentrates. Background Since 2012, more than 2425 MERS-CoV human cases have been reported in 27 countries. The infection causes acute respiratory disease, which was responsible for 838 deaths in these countries, mainly in Saudi Arabia. Viral genomic RNA was detected in whole blood, serum and plasma of infected patients, raising concerns of the safety of blood supplies, especially in endemic areas. Methods Four apheresis platelet units in 100% plasma were inoculated with a clinical MERS-CoV isolate. Spiked units were then treated with Amotosalen/UVA to inactivate MERS-CoV. Infectious and genomic viral titres were quantified by plaque assay and quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR). Inactivated samples were successively passaged thrice on Vero E6 cells to exclude the presence of residual replication-competent viral particles in inactivated platelets. Results Complete inactivation of MERS-CoV in spiked platelet units was achieved by treatment with Amotosalen/UVA light with a mean log reduction of 4·48 ± 0·3. Passaging of the inactivated samples in Vero E6 showed no viral replication even after nine days of incubation and three passages. Viral genomic RNA titration in inactivated samples showed titres comparable to those in pre-treatment samples. Conclusion Amotosalen and UVA light treatment of MERS-CoV-spiked platelet concentrates efficiently and completely inactivated MERS-CoV infectivity (>4 logs), suggesting that such treatment could minimise the risk of transfusion-related MERS-CoV transmission.

  • inactivation of middle east respiratory syndrome coronavirus in human plasma using Amotosalen and ultraviolet a light
    Transfusion, 2018
    Co-Authors: Salwa Hindawi, Sherif A Elkafrawy, Ahmed M Hassan, Ahmed M Tolah, Ghazi A Damanhouri, Anwar M Hashem, Esam I Azhar
    Abstract:

    Background Middle East respiratory syndrome-coronavirus (MERS-CoV) is a novel zoonotic pathogen. Although the potential for MERS-CoV transmission through blood transfusion is not clear, MERS-CoV was recognized as a pathogen of concern for the safety of the blood supply especially after its detection in whole blood, serum, and plasma of infected individuals. Here we investigated the efficacy of Amotosalen and ultraviolet A light (UVA) to inactivate MERS-CoV in fresh-frozen plasma (FFP). Study design and methods Pooled FFP units were spiked with a recent clinical MERS-CoV isolate. Infectious and genomic viral titers were determined in plasma before and after inactivation with Amotosalen/UVA treatment by plaque assay and reverse transcription-quantitative polymerase chain reaction, respectively. In addition, residual replicating or live virus after inactivation was examined by passaging in the permissive Vero E6 cells. Results The mean MERS-CoV infectious titer in pretreatment samples was 4.67 ± 0.25 log plaque-forming units (pfu)/mL, which was reduced to undetectable levels after inactivation with Amotosalen/UVA demonstrating a mean log reduction of more than 4.67 ± 0.25 pfu/mL. Furthermore, inoculation of inactivated plasma on Vero E6 cells did not result in any cytopathic effect (CPE) even after 7 days of incubation and three consecutive passages, nor the detection of MERS RNA compared to pretreatment samples which showed complete CPE within 2 to 3 days postinoculation and log viral RNA titer ranging from 9.48 to 10.22 copies/mL in all three passages. Conclusion Our data show that Amotosalen/UVA treatment is a potent and effective way to inactivate MERS-CoV infectious particles in FFP to undetectable levels and to minimize the risk of any possible transfusion-related MERS-CoV transmission.

Adonis Stassinopoulos - One of the best experts on this subject based on the ideXlab platform.

  • inactivation of a broad spectrum of viruses and parasites by photochemical treatment of plasma and platelets using Amotosalen and ultraviolet a light
    Transfusion, 2020
    Co-Authors: Marion C Lanteri, Adonis Stassinopoulos, Andrew Laughhunn, Felicia Santamaria, Yvette A Girard, Marcus Picardmaureau, Jeanmarc Payrat, Johannes Irsch, Peter Bringmann
    Abstract:

    Background The INTERCEPT Blood System pathogen reduction technology (PRT), which uses Amotosalen and ultraviolet A light treatment (Amotosalen/UV-PRT), inactivates pathogens in plasma and platelet components (PCs). This review summarizes data describing the inactivation efficacy of Amotosalen/UVA-PRT for a broad spectrum of viruses and parasites. Methods Twenty-five enveloped viruses, six nonenveloped viruses (NEVs), and four parasites species were evaluated for sensitivity to Amotosalen/UVA-PRT. Pathogens were spiked into plasma and PC at high titers. Samples were collected before and after PRT and assessed for infectivity with cell cultures or animal models. Log reduction factors (LRFs) were defined as the difference in infectious titers before and after Amotosalen/UV-PRT. Results LRFs of ≥4.0 log were reported for 19 pathogens in plasma (range, ≥4.0 to ≥7.6), 28 pathogens in PC in platelet additive solution (PC-PAS; ≥4.1-≥7.8), and 14 pathogens in PC in 100% plasma (PC-100%; (≥4.3->8.4). Twenty-five enveloped viruses and two NEVs were sensitive to Amotosalen/UV-PRT; LRF ranged from >2.9 to ≥7.6 in plasma, 2.4 or greater to greater than 6.9 in PC-PAS and >3.5 to >6.5 in PC-100%. Infectious titers for four parasites were reduced by >4.0 log in all PC and plasma (≥4.9 to >8.4). Conclusion Amotosalen/UVA-PRT demonstrated effective infectious titer reduction for a broad spectrum of viruses and parasites. This confirms the capacity of this system to reduce the risk of viral and parasitic transfusion-transmitted infections by plasma and PCs in various geographies.

  • pathogen reduction with Amotosalen uva reduces platelet refractoriness in a dog platelet transfusion model
    Vox Sanguinis, 2019
    Co-Authors: Sherrill J. Slichter, Grace Castro, Jennifer M. Green, Lawrence S Bailey, Irena Gettinger, Esther Pellham, Todd Christoffel, Adonis Stassinopoulos
    Abstract:

    Background and objectives Pathogen reduction of donor platelets with Amotosalen/UVA has been shown to effectively inactivate pathogens and also contaminating white blood cells (WBCs). We wanted to determine whether WBC inactivation could also decrease alloimmune refractoriness to donor platelets. Materials and methods Platelets were prepared from a donor dog's whole blood, and the platelets were either transfused without modification [standard (STD) platelets] or treated with Amotosalen/UVA under conditions modelling the Amotosalen/UVA Blood System for human platelets (APR) using either 4 or 3 J/cm2 of UVA exposure. Platelets were transfused weekly from a single donor dog for 8 weeks or until the recipient dog became refractory to their donor's platelets. Antibody samples were drawn weekly and tested against the donor dog's platelets and WBCs (CD8 and B cells). Results Only 1/7 (14%) dogs that received STD platelets accepted 8 weeks of donor transfusions. Following APR 4 J/cm2 donor transfusions, 3/9 (33%) recipients accepted their donor's transfusions, but only one recipient remained antibody negative. Following APR 3 J/cm2 donor transfusions, the same dose as used for human platelet transfusions, 7/10 (70%) recipients accepted their donor's transfusions, but only two remained antibody negative. Conclusion As a very high percentage of recipient dogs (70%) accepted APR 3 J/cm2 donor transfusions, these data suggest that preventing alloimmune platelet refractoriness may be another benefit of pathogen reduction using Amotosalen/UVA.

  • Amotosalen uva treatment inactivates t cells more effectively than the recommended gamma dose for prevention of transfusion associated graft versus host disease
    Transfusion, 2018
    Co-Authors: Grace Castro, Laurence Corash, Patricia A Merkel, Hannah E Giclas, Andrew Gibula, Gillian Andersen, Jin Sying Lin, Jennifer Green, Vijaya Knight, Adonis Stassinopoulos
    Abstract:

    INTRODUCTION Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare complication after transfusion of components containing viable donor T cells. Gamma irradiation with doses that stop T-cell proliferation is the predominant method to prevent TA-GVHD. Treatment with pathogen inactivation methodologies has been found to also be effective against proliferating white blood cells, including T cells. In this study, T-cell inactivation was compared, between Amotosalen/ultraviolet A (UVA) treatment and gamma-irradiation (2500 cGy), using a sensitive limiting dilution assay (LDA) with an enhanced dynamic range. METHODS AND MATERIALS Matched plasma units (N = 8), contaminated with 1 × 106 peripheral blood mononuclear cells (PBMCs) per mL, were either treated with Amotosalen/UVA or gamma irradiation, or retained as untreated control. Posttreatment, cells were cultured under standardized conditions. T-cell proliferation was determined by the incorporation of 3 H-thymidine and correlated with microscopic detection. RESULTS Range-finding experiments showed that after gamma irradiation (2500 cGy), significant T-cell proliferation could be observed at a 1 × 107 cell culture density, some proliferation at 1 × 106 , and none at 1 × 105 cells/well. Based on these facts, a quantitative comparison was carried out between Amotosalen/UVA at the highest challenge of 1 × 107 PBMCs/well, and gamma irradiation at 1 × 106 and 1 × 105 PBMCs/well. Complete inactivation of the T cells after Amotosalen/UVA treatment was observed, equivalent to greater than 6.2 log inactivation. Complete inactivation of the T cells was also observed after gamma irradiation when 1 × 105 PBMCs/well were cultured (>4.2 log inactivation). Proliferation was observed when 1 × 106 PBMCs/well were cultured (≤5.2 log inactivation) after gamma irradiation. CONCLUSION Amotosalen/UVA treatment more effectively inactivates T cells than the current standard of gamma irradiation (2500 cGy) for the prevention of TA-GVHD.

  • inactivation of chikungunya virus in blood components treated with Amotosalen ultraviolet a light or amustaline glutathione
    Transfusion, 2018
    Co-Authors: Andrew Laughhunn, Marion C Lanteri, Yanjang S Huang, Dana L Vanlandingham, Adonis Stassinopoulos
    Abstract:

    Background Chikungunya virus, a mosquito-borne arbovirus, often co-circulates with the Zika, dengue, and yellow fever viruses in Aedes mosquito-infested areas where cases of arbovirus transfusion-transmitted infections have been reported. Building on past experience to help maintain the availability of safe components during major outbreaks of chikungunya virus in La Reunion, Italy, and Thailand and of Zika virus in the Pacific, the Caribbean, and the Americas, pathogen inactivation is a mitigation strategy to reduce the risk of transfusion-transmitted infection. Inactivation of chikungunya virus was investigated for platelets in 100% plasma using Amotosalen/ultraviolet A light, and in red blood cells using amustaline/glutathione. Study design and methods Platelets in 100% plasma and red blood cells (RBCs) were spiked with chikungunya virus. Infectious chikungunya virus titers were measured in contaminated blood products before and after treatment with Amotosalen/ultraviolet A light for platelets in 100% plasma and after treatment with amustaline/glutathione for RBCs. Viral infectivity was quantified by plaque assay. Results The mean chikungunya virus infectivity titers before inactivation were 6.50 log10 plaque-forming units/mL for platelets in 100% plasma and 7.60 log10 plaque-forming units/mL for RBCs. No infectivity was detected after Amotosalen/ultraviolet A light or amustaline/glutathione treatment, corresponding to greater than 6.5 log10 plaque-forming units/mL and greater than 7.1 log10 plaque-forming units/mL of inactivation, respectively. Conclusion Robust levels of chikungunya virus inactivation were achieved for platelets in 100% plasma and for RBC components. The licensed Amotosalen/ultraviolet A light technology and the amustaline/glutathione pathogen-reduction system under development may provide an opportunity for comprehensive mitigation of the risk of chikungunya virus transfusion-transmitted infection by plasma, platelets, and RBCs.

  • inactivation of babesia microti in red blood cells and platelet concentrates
    Transfusion, 2017
    Co-Authors: Laura Tonnetti, Kent Dupuis, Adonis Stassinopoulos, Aaron M Thorp, Andrew Laughhunn, Irina Vasilyeva, Susan L Stramer
    Abstract:

    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.

Esam I Azhar - One of the best experts on this subject based on the ideXlab platform.

  • Amotosalen and ultraviolet a light treatment efficiently inactivates severe acute respiratory syndrome coronavirus 2 sars cov 2 in human plasma
    Vox Sanguinis, 2021
    Co-Authors: Esam I Azhar, Salwa Hindawi, Sherif A Elkafrawy, Ahmed M Hassan, Ahmed M Tolah, Thamir A Alandijany, Leena H Bajrai, Ghazi A Damanhouri
    Abstract:

    Background and objectives During the ongoing pandemic of COVID-19, SARS-CoV-2 RNA was detected in plasma and platelet products from asymptomatic blood donors, raising concerns about potential risk of transfusion transmission, also in the context of the current therapeutic approach utilizing plasma from convalescent donors. The objective of this study was to assess the efficacy of Amotosalen/UVA light treatment to inactivate SARS-CoV-2 in human plasma to reduce the risk of potential transmission through blood transfusion. Methods Pools of three whole-blood-derived human plasma units (630-650 ml) were inoculated with a clinical SARS-CoV-2 isolate. Spiked units were treated with Amotosalen/UVA light (INTERCEPT Blood System™) to inactivate SARS-CoV-2. Infectious titres and genomic viral load were assessed by plaque assay and real-time quantitative PCR. Inactivated samples were subject to three successive passages on permissive tissue culture to exclude the presence of replication-competent viral particles. Results Inactivation of infectious viral particles in spiked plasma units below the limit of detection was achieved by Amotosalen/UVA light treatment with a mean log reduction of >3·32 ± 0·2. Passaging of inactivated samples on permissive tissue showed no viral replication even after 9 days of incubation and three passages, confirming complete inactivation. The treatment also inhibited NAT detection by nucleic acid modification with a mean log reduction of 2·92 ± 0·87 PFU genomic equivalents. Conclusion Amotosalen/UVA light treatment of SARS-CoV-2 spiked human plasma units efficiently and completely inactivated >3·32 ± 0·2 log of SARS-CoV-2 infectivity, showing that such treatment could minimize the risk of transfusion-related SARS-CoV-2 transmission.

  • efficient inactivation of sars cov 2 in human plasma with Amotosalen and ultraviolet a light treatment
    Transfusion, 2020
    Co-Authors: Esam I Azhar, Marcus Picardmaureau, Salwa Hindawi, Sherif A Elkafrawy, Ahmed M Hassan, Ahmed M Tolah, Thamir A Alandijany, Qossay Abunada, Ghazi A Damanhouri
    Abstract:

    Background/Case Studies: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was identified in January 2020 as the responsible agent for COVID-19 First recognized in late 2019, the COVID-19 epidemic developed into a pandemic with, as of July 23, 2020, more than 15 million cases and 600,000 deaths reported globally SARS-CoV-2 RNA was detected in blood samples and blood components from asymptomatic blood donors including frozen plasma units and platelet concentrates This suggests that SARS-CoV-2 may be a potential bloodborne pathogen and pathogen reduction offers potential to reduce the risk of transfusion transmission We investigated the efficacy of Amotosalen/UVA light to inactivate SARS-CoV-2 in human plasma Study Design/Methods: Five pools of whole-blood derived human plasma units (630-650 mL each) were inoculated with a local clinical isolate (SARS-CoV-2/ human/SAU/85791C/2020) with a 1:100 dilution Spiked pools were used to evaluate the efficacy of Amotosalen/ UVA treatment (INTERCEPT® Blood System, Cerus Corporation, Concord, U S A ) to inactivate SARS-CoV-2 in plasma Infectious and genomic viral titers were assessed by plaque assay and quantitative PCR (Altona Diagnostics, Hamburg, Germany), respectively, in spiked and treated samples in parallel with positive and negative controls Results/Findings: Treatment of spiked plasma (titer of the viral stock: 5 6±0 2 log10 pfu/mL) with Amotosalen/ UVA light resulted in complete inactivation of infectious viral titer with mean log reduction of >3 3±0 2 log10 pfu/mL No viral replication or cytopathic effect (CPE) was observed in cells inoculated with inactivated samples even after 9 days of incubation and three successive passages Evaluation of genomic titer expressed in genome equivalent (GEq/mL) in inactivated samples showed equivalent reduction to the limit of detection of 7 10±0 2 log10 GEq/mL Conclusions: Complete and efficient inactivation of SARS-CoV-2 was observed with Amotosalen/UVA light treatment of spiked human plasma units suggesting that treatment of plasma with this pathogen reduction technology could reduce the risk of transfusion-transmitted SARS-CoV-2 infection These findings are consistent with prior inactivation data with Amotosalen/UVA for other human-pathogenic coronaviruses (SARS-CoV-1 and MERS-CoV) in platelets and plasma

  • Amotosalen and ultraviolet a light efficiently inactivate mers coronavirus in human platelet concentrates
    Transfusion Medicine, 2019
    Co-Authors: Anwar M Hashem, Marcus Picardmaureau, Sherif A Elkafrawy, Ahmed M Hassan, Ahmed M Tolah, Qossay Abunada, Esam I Azhar, Ghazi A Damanhouri, M A Alsaadi, Salwa Hindawi
    Abstract:

    Objective This study aimed to assess the efficacy of the INTERCEPT™ Blood System [Amotosalen/ultraviolet A (UVA) light] to reduce the risk of Middle East respiratory syndrome-Coronavirus (MERS-CoV) transmission by human platelet concentrates. Background Since 2012, more than 2425 MERS-CoV human cases have been reported in 27 countries. The infection causes acute respiratory disease, which was responsible for 838 deaths in these countries, mainly in Saudi Arabia. Viral genomic RNA was detected in whole blood, serum and plasma of infected patients, raising concerns of the safety of blood supplies, especially in endemic areas. Methods Four apheresis platelet units in 100% plasma were inoculated with a clinical MERS-CoV isolate. Spiked units were then treated with Amotosalen/UVA to inactivate MERS-CoV. Infectious and genomic viral titres were quantified by plaque assay and quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR). Inactivated samples were successively passaged thrice on Vero E6 cells to exclude the presence of residual replication-competent viral particles in inactivated platelets. Results Complete inactivation of MERS-CoV in spiked platelet units was achieved by treatment with Amotosalen/UVA light with a mean log reduction of 4·48 ± 0·3. Passaging of the inactivated samples in Vero E6 showed no viral replication even after nine days of incubation and three passages. Viral genomic RNA titration in inactivated samples showed titres comparable to those in pre-treatment samples. Conclusion Amotosalen and UVA light treatment of MERS-CoV-spiked platelet concentrates efficiently and completely inactivated MERS-CoV infectivity (>4 logs), suggesting that such treatment could minimise the risk of transfusion-related MERS-CoV transmission.

  • inactivation of middle east respiratory syndrome coronavirus in human plasma using Amotosalen and ultraviolet a light
    Transfusion, 2018
    Co-Authors: Salwa Hindawi, Sherif A Elkafrawy, Ahmed M Hassan, Ahmed M Tolah, Ghazi A Damanhouri, Anwar M Hashem, Esam I Azhar
    Abstract:

    Background Middle East respiratory syndrome-coronavirus (MERS-CoV) is a novel zoonotic pathogen. Although the potential for MERS-CoV transmission through blood transfusion is not clear, MERS-CoV was recognized as a pathogen of concern for the safety of the blood supply especially after its detection in whole blood, serum, and plasma of infected individuals. Here we investigated the efficacy of Amotosalen and ultraviolet A light (UVA) to inactivate MERS-CoV in fresh-frozen plasma (FFP). Study design and methods Pooled FFP units were spiked with a recent clinical MERS-CoV isolate. Infectious and genomic viral titers were determined in plasma before and after inactivation with Amotosalen/UVA treatment by plaque assay and reverse transcription-quantitative polymerase chain reaction, respectively. In addition, residual replicating or live virus after inactivation was examined by passaging in the permissive Vero E6 cells. Results The mean MERS-CoV infectious titer in pretreatment samples was 4.67 ± 0.25 log plaque-forming units (pfu)/mL, which was reduced to undetectable levels after inactivation with Amotosalen/UVA demonstrating a mean log reduction of more than 4.67 ± 0.25 pfu/mL. Furthermore, inoculation of inactivated plasma on Vero E6 cells did not result in any cytopathic effect (CPE) even after 7 days of incubation and three consecutive passages, nor the detection of MERS RNA compared to pretreatment samples which showed complete CPE within 2 to 3 days postinoculation and log viral RNA titer ranging from 9.48 to 10.22 copies/mL in all three passages. Conclusion Our data show that Amotosalen/UVA treatment is a potent and effective way to inactivate MERS-CoV infectious particles in FFP to undetectable levels and to minimize the risk of any possible transfusion-related MERS-CoV transmission.