57. Jahrestagung der Deutschen Gesellschaft für Transfusionsmedizin und Immunhämatologie

Vorsitz

Prof.

Establishing blood regulation in Africa: From 0 to 100 in …? – Insights into working globally

Quality Management and Regulatory Aspects

Regulation von Blut in Afrika: Von 0 auf 100 in …? – Einblicke in globale Arbeit

Blood and blood components for transfusion are essential medicines for which there is a high demand in African countries. Many children and mothers require transfusions to treat sickle cell disease, parasitic anemia or postpartum hemorrhage. However, although in most parts of sub-Saharan Africa, the national blood services are functional to a certain degree, both the amount and the quality of blood need improvement. Also, blood is mostly not subject to regulatory oversight.The establishment of regulatory oversight for blood will further improve its quality and safety. Many countries already regulate pharmaceuticals and vaccines. The BloodTrain project at the Paul-Ehrlich-Institut which is part of the Global Health Protection Programme supports the integration of blood into the regulatory system by developing and implementing the corresponding legal documents.The work of the project is based on three pillars: structure building through specialized technical support including the development of legal documents, capacity development through training workshops, and harmonization of regulation through the support of continental technical working groups.We also support the train-the-trainer principle and the establishment of so-called Regional Centers of Regulatory Excellence to further promote sustainability.However, setting up and supporting regulatory systems often presents very specific challenges.The intercultural challenges, political delays, and high staff turnover were already largely expected, but those can always happen at unexpected times. Moreover, some challenges only became obvious during the project: changing and/or contradicting mandates, strong hierarchical structures, and changing focus of the health system (i.e. during and after the pandemic).International work is subject to many challenges on the way from 0 to 100 % implementation. In this presentation we give insights into the global work of regulatory systems strengthening, the upcoming expected and unexpected challenges and how we meet these challenges to support the availability of safe and quality-assured blood in Africa.The views expressed in this presentation are the personal views of the presenter(s). They shall not be understood or cited as opinions of the Paul-Ehrlich-Institut. The presenter has not received any funding or grants from companies or from associations representing companies.We have no conflicts of interest to declare.

Abstract lecture

Prof. Dr. med.

Dose-dependent inactivation of Plasmodium falciparum in red blood cell concentrates by treatment with short wavelength ultraviolet light

Blood Safety and Transfusion Transmitted Infections

Dosisabhängige Inaktivierung von Plasmodium falciparum in Erythrozytenkonzentraten durch die Behandlung mit kurzwelligem ultraviolettem Licht

Plasmodium species are blood-borne pathogens that are naturally transmitted by female Anopheles mosquitos. The parasite infects red blood cells (RBCs) and can therefore be transfused with blood products. The risk of infection in non-endemic areas is limited to travellers coming back from malaria endemic regions. However, transfusion-transmitted malaria (TTM) constitutes a significant risk of infection in endemic countries. TTM may cause life-threatening complications in patients dependent on blood donations. This study investigates the effectivity of Plasmodium falciparum inactivation in RBC by treatment with short wavelength ultraviolet (UVC) light in the absence of photochemical additives.RBC suspended in the new developed additive solution PAGGS-C were diluted to a haematocrit of approximately 30% before UVC treatment. RBC (n=3) were spiked with Plasmodium falciparum to a final parasitemia of 0.1-1% and were irradiated with up to 4.5 J/cm2 UVC (254 nm) under agitation (300 rpm). Samples were taken at different time points and the parasitemia was determined by serial dilutions followed by either by GIEMSA staining or flow cytometry over three weeks post irradiation treatment.The lowest dose of 1.5 J/cm2 UVC led to a ≥ 3 log unit reduction in parasite load compared to the untreated control. The inactivation capacity was shown to be dose-dependent. Strikingly, 4.5 J/cm2 led to ≥ 5 log unit reduction, which was equivalent to a complete inactivation in two out of three experiments.Additive-free pathogen reduction with UVC light was previously shown to be effective for different bacteria and viruses, but the inactivation of parasites was not addressed until now. The present study provides evidence for significant inactivation of P. falciparum-infected RBCs by UVC light.SF, MR and BL have no conflict of interest to disclose.UG and AS received grants from the Research Foundation of the German Red Cross Blood Services (Deutsche Forschungsgemeinschaft der Blutspendedienste des Deutschen Roten Kreuzes) and Macopharma for the development of the UVC-based Pathogen inactivation technology for platelets. UG and AS filed a joint patent application for the UVC-based technology for RBC. BL acknowledges support from the Deutsche Forschungsgemeinschaft (LE 2498/9-1 to B.L.). We thank the Hannover Graduate School for Neurosciences, Infection Medicine and Veterinary Sciences (HGNI) for supporting the PhD project of which this manuscript was a part of. Illumination bags used in this study were kindly provided by Macopharma.

PD Dr.

Parvovirus b19 infection after transfusion of a pathogen-reduced platelet concentrate: a case report

Parvovirus B19-Infektion nach Transfusion enes Pathogen-inaktiviertes Thrombozytenkonzentrat: eine Fallvorstellung

Parvovirus B19 (B19) is moderately resistant to the inactivation methods used for platelet concentrates. Approximately 30% of donors are seronegative and susceptible for new B19 infections. B19 nucleic acid testing (NAT) is generally not required to release blood products. In Switzerland the Blood Transfusion Centers test B19 NAT for plasma fractionation. Results are normally available after the release of the blood products and, according to the national prescriptions, are handled by post donation information.We describe the case of a B19 primo-infection transmitted by transfusion of a UVA and Amotosalen-treated pooled platelet concentrate (PC) to a seronegative patient in treatment for aplastic anemia. In donor and patient samples before and after the transfusion we performed B19 NAT viremia, IgG and IgM serologies, and phylogenetic analyses in viremic samples. Additionally, we collected relevant clinical and laboratory data.At d0 the patient received a pathogen-reduced pooled PC including a B19 NAT-positive donation with a viral load of 9.1E+11 IU/mL, negative IgM, and negative IgG. The donor was a 42-y.o. asymptomatic male without recent history of B19 contact. At d 2 post transfusion B19 was detectable in the recipient, with a viral load of 36201 IU/mL. The highest viral load of 7.94E+09 IU/mL and a IgM seroconversion (9.2, index) were observed at d14. IgG seroconversion was observed at d26 (30, index). With i.v. immunoglobulin treatment at d14-15 the patient remained asymptomatic. At d39 the viral load has dropped to 19"040 IU/mL. Phylogenetic analysis demonstrated identity between the donor"s and patient"s B19 DNA sequences.This is, at our knowledge, the second case describing a direct transmission of B19 by a PC treated with a pathogen reduction technology, and the first case documenting the development of an infection in the recipient. B19 is not considered as a safety concern in transfusion medicine. However, it should be kept in mind that some pathogens may be transmitted by transfusion of pathogen reduced products, and procedures should be in place to detect these cases and take appropriate measures in the patients.No conflict of interests related to the present abstract.

The kinetics of asymptomatic hepatitis E virus infections in healthy individuals

Die Kinetik asymptomatischer Hepatitis-E-Virus-Infektionen bei gesunden Menschen

Transfusion-transmitted hepatitis E virus (HEV) infection has attracted increasing attention as a cause of complications in immunocompromised patients and organ donation recipients, while infection in apparently healthy people, such as blood donors, is usually asymptomatic. Although testing of blood products for HEV is mandatory in Germany since 2020, little is known about the course of asymptomatic infections due to the immediate restriction of donors.Samples from blood donations collected before initiation of mandatory testing were screened retrospectively for HEV RNA. Donations were made with few days distance, resulting in dense data on viral load progression. Screening involved pooling 96 samples for HEV RNA, followed by RNA extraction and polymerase chain reaction for nucleic acid detection. Viral load was quantified using internal kit standards, allowing calculation of doubling time in the first half of infection and half-life in the second half using the formula n=log(2)*log(Nt/N0). Seroconversion in HEV RNA-positive blood donors was traced by evaluating HEV IgM and IgG titers using HEV ELISA Kits.Viremia was analyzed in 32 HEV RNA-positive individuals with a median of four days between donations. A typical median infection proceeded as follows: detectable viremia lasted for 36 days (IQR 19 – 49 days) with a maximum viral load of 2.0 ×104 IU/ml (IQR 2.0×103 – 1.5×105 IU/ml) at day 22 (IQR 10 – 27 days). A weak correlation was observed between maximum viral load and duration of infection (r = 0.5642, p = 0.0018). The average doubling time was 2.4 days (IQR 1.7 – 3.7 days; n=21), the half-life 1.6 days (IQR 0.8 – 2.2 days; n=14). HEV IgM and IgG started to rise around day 32 to 33 (IQR 24 – 40 days) and peaked on day 36 (IQR 28 – 54 days) and 53 (IQR 32 – 72 days). While HEV IgG titers were stable, IgM titers became undetectable in 40 % of the cases on median at day 85 (IQR 59 – 108 days).Our data provide insight into the kinetics of asymptomatic HEV infections. While key characteristics such as humoral immune response, maximum and duration of viremia confirm previous studies, doubling time and half-life were additionally determined allowing a baseline evaluation of self-limiting HEV infection. By taking secondary factors (e.g. age or immune status) into account, we might determine risk factors influencing the kinetics of the infection in future studies.Funding statement: D.T. was supported by the German Federal Ministry of Education and Research (BMBF, project: VirBio, Grant number: 01KI2106). E.S. and T.V. were supported by the German Federal Ministry of Education and Research (BMBF, project HepEDiaSeq — FKZ 01EK2106A).

Prof. Dr. rer. nat.

A new lab-on-a-chip device to judge red blood cells

Ein neues lab-on-a-chip Gerät zur Beurteilung von Erythrozyten

Red blood cell transfusion is a life-saving action for patients in various situations. Besides numerous safety measures for pathogens, there is no quality control of red blood cells during storage. In contrast, it has been shown, that decreased red blood cell deformability impairs the transfusion outcome.Erysense is a novel microfluidic device, which characterises red blood cell flow properties. The point-of-care device assesses red blood cell shapes at various flow velocities. Shape classification is performed using neural networks. The resulting phase diagrams (shape classifications at different flow velocities) are characteristic for red blood cell properties such as their deformability.We show a continuous loss of red blood cell quality over the storage time of 10 weeks. The quality of the correlation between the assessed parameter and the storage time is better for parameters derived from artificial intelligence compared with analytical parameters. The severeness of quality loss is variable and donor-dependent.Microfluidic characterization on red blood cells by Erysense allows their quality control meeting the required activity by the SoHO EU directive. Additional studies with an increased number of donors are necessary to impose general guidelines. Furthermore, Erysense bears the potential to enable precision transfusion concepts.I'm a shareholder of Cysmic GmbH.

Did changes in deferral criteria impact on HIV infections in donors? Comparing donor epidemiology data from 2017, 2019 and 2023

Hatten die Änderungen der Spendeauswahlkriterien eine Auswirkung auf die Häufigkeit von HIV-Infektionen unter Spendenden? Vergleich der Daten der Spendeepidemiologie aus 2017, 2019 und 2023

Individuals with high risk sexual behaviour are not allowed to donate. Using population-based deferral criteria, men who have sex with men (MSM) were indefinitely deferred until 2017 when the deferral period was reduced to 12 months after the last sexual contact. Since 2023 an individual donor screening approach is mandated. We compare data on HIV infections in the blood donor population in Germany prior to the implementation of temporary deferral, after the introduction of the 12-month deferral and after the change to individual assessment.Donor epidemiology data reported to the RKI were used for the analysis. All blood donation services report the number of tests performed for prospective, first time (FTD) and repeat donors (RD), stratified for age group, sex and type of donation. Information on donors tested positive for HIV include donation history, laboratory results and mode of transmission.In 2023, the number of HIV infections decreased compared to 2017 and 2019. The HIV prevalence and incidence were 4.8, 5.7 and 2.5/100,000 in FTD and 1.6, 1.2 and 0.9/100,000 RD in 2017, 2019 and 2023, respectively. Male FTD and RD were more often found to be HIV-positive. The highest difference in HIV prevalence (factor of 9.4) was found in male FTD compared to female FTD in 2023. HIV infections were detected more often in younger age groups (18-34 years). No trend was seen in distribution of HIV infections with respect to sex or age group. The proportion of HIV infections with a reported mode of transmission was 47%, 50% and 46% in 2017, 2019 and 2023. Sexual contacts caused the majority of reported transmissions but the proportion of MSM and heterosexual exposures varied: In 2023, MSM accounted for 46% of the notifications (36% in 2017 and 17% in 2019) while heterosexual contacts (31%) were less often reported than in 2017 (48%) and 2019 (53%).HIV infections declined unrelated to the donor selection criteria. No change in age or sex distribution was observed. An increased reporting of MSM as transmission mode was seen in 2023. This can be due to more MSM presenting at blood services or to a more open recording of this exposure. As the individual risk assessment was only implemented in 2023, more research is necessary to interpret these early findings. Post donation interviews of positive donors are of utmost importance to identify changes in donor risk profiles.Both authors declare no conflicts of interest.

Raum 27

Safety and Quality Management in transfusion

Abstractsitzungen

Safety and Quality Management in transfusion

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