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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.

Results of genotyping with true high-throughput capability for MNSs antigens are underrepresented, probably because of technical issues, due to the high level of nucleotide sequence homology of the paralogous genes GYPA, GYPB and GYPE. Eight MNSs-specific single nucleotide polymorphisms (SNP) were detected using matrix-assisted laser desorption/ionization, time-of-flight mass spectrometry (MALDI-TOF MS) in 5800 serologically M/N and S/s pre-typed Swiss blood donors and 50 individuals of known or presumptive black African ethnicity. Comparison of serotype with genotype delivered concordance rates of 99·70% and 99·90% and accuracy of genotyping alone of 99·88% and 99·95%, for M/N and S/s, respectively. The area under the curve of peak signals was measured in intron 1 of the two highly homologous genes GYPB and GYPE and allowed for gene copy number variation estimates in all individuals investigated. Elevated GYPB:GYPE ratios accumulated in several carriers of two newly observed GYP*401 variants, termed type G and H, both encoding for the low incidence antigen St(a). In black Africans, reduced GYPB gene contents were proven in pre-typed S-s-U- phenotypes and could be reproduced in unknown specimens. Quantitative gene copy number estimates represented a highly attractive supplement to conventional genotyping, solely based on MNSs SNPs.

Background: High-frequency blood group antigens (HFA) are present in >90% of the human population, according to some reports even in >99% of individuals. Therefore, patients lacking HFA may become challenging for transfusion support because compatible blood is hardly found, and if the patient carries alloantibodies, the cross-match will be positive with virtual every red cell unit tested. Methods: In this study, we applied high-throughput blood group SNP genotyping on >37,000 Swiss blood donors, intending to identify homozygous carriers of low-frequency blood group antigens (LFA). Results: 326 such individuals were identified and made available to transfusion specialists for future support of patients in need of rare blood products. Conclusion: Thorough comparison of minor allele frequencies using population genetics revealed heterogeneity of allele distributions among Swiss blood donors which may be explained by the topographical and cultural peculiarities of Switzerland. Moreover, geographically localized donor subpopulations are described which contain above-average numbers of individuals carrying rare blood group genotypes.

Background: Ethnicities differ in prevalence of blood groups and antigens. Substantial donor-recipient mismatch within mixed-ethnic societies may render certain recipients at higher risk for alloimmunization. Data regarding antigen distribution within Switzerland by ethnicity is limited. We examined immigration patterns against the distribution of ABO blood groups using large cross-sectional Swiss samples spanning 70 years. Methods: Historical ABO blood group distribution data (1940-1945) from Swiss army personnel (n = 275,664) were sourced from the literature. Recent blood group phenotypes of 122,925 individuals who presented themselves at army recruitment centers (2004-2015) were obtained, alongside a validation sample of 175,202 patients from a university hospital. Two-sample tests with z-statistics assessing blood groups between samples were used. Results: The respective proportions of A (47.2% and 45.2%), B (8.4% and 9.8%), and AB (3.0 and 4.1) in the historical and recent army samples were significantly different (p < 0.001), while group O was not. Conclusion: ABO blood groups in Switzerland have remained stable despite substantial immigration with a changing foreign-national profile. Further research is needed to improve the understanding of antigen differences in newly introduced ethnic groups. Blood product requirements and public health initiatives aimed at recruiting blood donors would benefit from this information.

Glioblastoma is a deadly malignant brain tumor and one of the most incurable forms of cancer in need of new therapeutic targets. As some cancers are known to be caused by a virus, the discovery of viruses could open the possibility to treat, and perhaps prevent, such a disease. Although an association with viruses such as cytomegalovirus or Simian virus 40 has been strongly suggested, involvement of these and other viruses in the initiation and/or propagation of glioblastoma remains vague, controversial and warrants elucidation. To exhaustively address the association of virus and glioblastoma, we developed and validated a robust metagenomic approach to analyze patient biopsies via high-throughput sequencing, a sensitive tool for virus screening. In addition to traditional clinical diagnostics, glioblastoma biopsies were deep-sequenced and analyzed with a multistage computational pipeline to identify known or potentially discover unknown viruses. In contrast to the studies reporting the presence of viral signatures in glioblastoma, no common or recurring active viruses were detected, despite finding an antiviral-like type I interferon response in some specimens. Our findings highlight a discrete and non-specific viral signature and uncharacterized short RNA sequences in glioblastoma. This study provides new insights into glioblastoma pathogenesis and defines a general methodology that can be used for high-resolution virus screening and discovery in human cancers.

To conduct a study project on the inactivation of pathogens in whole blood using acridine derivatives in Africa, in order to prevent the transmission of pathogens, it is important to look for possible immunization to acridine in the blood donor population. It is therefore important to undertake an estimate of the prevalence in the sub-Saharan population in order to guide the design of the clinical study that will use the INTERCEPT Red Blood System procedure on whole blood for transfusion. to define the starting point in the evaluation of the immunological safety and transfusion safety of the product treated by this process. The objective of this study is to determine the prevalence of AAA among blood donors in sub-Saharan Africa. We conducted a multicenter prospective descriptive study of 902 blood donors collected in Cote d'Ivoire, Benin and Cameroon over the period from June 2015 to January 2017. Blood samples were collected from voluntary blood donors, of any sex, aged between 18 and 65, having given their consent for the study and having participated in the medical consultation for the donation of blood. The samples were analyzed according to the technique of the RAI gel card of the company BIORAD after centrifugation and incubation using test red cells treated with S-303 and glutathione. In the case of positive RAI results, to confirm the presence of anti-acridine, the donor plasma should be incubated with S-300. S-300 is a degradation product of S-303. The donor serum and S-300 are then incubated with the same red test cells. S-300 binds to the antibody and produces a negative result in the gel map in the presence of anti-acridin antibodies. Of the 903 samples tested both at the Abidjan laboratory in Cote D'Ivoire and at the Frankfurt laboratory, we found 1 positive sample and 8 reactive samples (positive for anti-erythrocyte antibodies). Positive donor plasma was incubated with S-300 which is the degradation product of S-303. The result is always positive, whereas according to the instructions of the reference laboratory of Frankfurt, it should be negative in case of presence of Locustacan. The results on AAA testing among 903 donors in three sub-Saharan countries show the absence of AAA in the sample of subjects included in the study according to the hypothesis emitted from this study. This opens the door to the prospect of conducting a clinical study on the inactivation of pathogens by acridine derivatives.

A part from any incompatible blood transfusion, anti-erythrocyte alloimmunization is observed to pregnant women. It is the result of the passage of red blood cells carrying antigens different from those of the mother during pregnancy and delivery. The Rhesus D system is the most involved; but there are also other systems involved in this alloimmunization. Non-transfusion alloimmunization is an extremely rare event in the order of 1 of 4000 to women in Europe and in most cases concerns the Rhesus D. In sub-Saharan Africa, there are no statistics collected on foeto-maternal alloimmunization. As part of our postgraduate thesis on the sensitization status of red blood cells to acridine, we used the technique of looking for irregular agglutinins. The goal was to find anti-erythrocyte alloimmunization to blood donors in sub-Saharan Africa. We conducted a two-year multicenter prospective and descriptive study of 903 blood donors in Cote d'Ivoire, Benin and Cameroon. The samples were analyzed in the laboratories of the National Blood Transfusion Center of Cote D'Ivoire and Frankfurt according to the technique of the RAI gel card of the BIORAD company after centrifugation and incubation using test red cells treated with S-303. In the case of a positive reaction, identification is made by a panel of red blood cells in the different blood group systems. In our study population, there is a male predominance with a male/female ratio of 7.42. We found a very low prevalence of alloimmunization to non-transfused blood donors (0.9% or 8 cases out of 902). 4 anti-erythrocyte antibodies have been identified (1 Ac anti D and 3 AC anti S); 2 pan-agglutination, 2 unidentified Ac (insufficient serum) and suspicion of anti-glutathione. Anti-erythrocyte alloimmunization to sub-Saharan Africa blood donor is about 0.9% in our series. It remains high compared to European data. This alloimmunization is mainly observed to women with low frequency antigens to black peoples.