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Transfusion-Transmissible Infections and Epidemiological Surveillance

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A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 29031

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Dr. Vincenzo De Angelis

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Guest Editor

National Blood Centre, Italian National Institute of Health, 00161 Rome, Italy
Interests: immunohaematology; quality systems in laboratory and clinical transfusion; haemostaseology
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Dr. Ilaria Pati

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Guest Editor

National Blood Centre, Italian National Institute of Health, 00161 Rome, Italy
Interests: transfusion risk; transfusion transmitted infection (TTI), pathogen reduction; neuroinflammation; neurological infection diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Transfusion-transmissible infectious agents are among the greatest threats to blood safety for transfusion recipients, and are a serious public health problem.

The safety of blood and blood components has dramatically increased over the last several decades thanks to the adoption of strict criteria for blood donor selection and the screening of all blood units for known transfusion-transmissible infections (TTIs), with the combined implementation of highly sensitive antigen/antibody-based assays and nucleic acid testing (NAT), the rational use of blood to avoid unnecessary transfusions, and the introduction of pathogen-reduction technologies (PRTs).

For the pathogens for which blood donors are currently screened, the risk of collecting an infectious donation that is not detectable by the currently used tests depends on the incidence of infection in blood donors and the length of the viral infection window (i.e., the time between infection, viraemia, and detection).

However, the last several decades have been characterized by the appearance of a significant number of emerging pathogens, and by the reappearance of infectious diseases with global impact, threatening transfusion safety. Blood donor screening tests may not be available for some of these pathogens.

Therefore, surveillance programs are a fundamental tool for monitoring new outbreaks of TTIs, for risk assessment, and for the implementation of strategies to guarantee transfusion safety.

These activities vary from country to country due to the different organisation of blood network surveillance systems, the strategic focus of transfusion safety programmes, and disease epidemiology.

As Guest Editors, we are excited to start a new challenge with this Special Issue. We hope that the document collection in this Issue will provide insights into the epidemiology of blood donors in different countries, as well as the best strategies for TTI risk reduction and ensuring blood donation safety, even during outbreaks from newly introduced or re-emerging pathogens.

The information can come from clinical practice and/or experimental research, as well as from accurate evaluations of data published in the literature.

We invite our colleagues to submit original research and review articles that provide interesting insights and new developments.

Dr. Vincenzo De Angelis
Dr. Ilaria Pati
Guest Editors

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

transfusion-transmissible infections
epidemiological surveillance
emerging and re-emerging pathogens

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Published Papers (9 papers)

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Research

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12 pages, 670 KiB

Open AccessArticle

Arylimidamides Have Potential for Chemoprophylaxis against Blood-Transmitted Chagas Disease

by Bruno Lisboa Timm, Aline Nefertiti Silva da Gama, Marcos Meuser Batista, Denise da Gama Jaén Batista, David W. Boykin, Harry P. De Koning and Maria de Nazaré Correia Soeiro

Pathogens 2023, 12(5), 701; https://doi.org/10.3390/pathogens12050701 - 12 May 2023

Cited by 1 | Viewed by 1482

Abstract

Chagas disease (CD) affects over 6 million people worldwide and can be transmitted iatrogenically. Crystal violet (CV) was previously used for pathogen reduction but has harmful side-effects. In the present study, three arylimidamides (AIAs) and CV were used to sterilize mice blood samples experimentally contaminated with bloodstream trypomastigotes (BT) of Trypanosoma cruzi, at non hemolytic doses. All AIAs were not toxic to mouse blood cells until the highest tested concentration (96 µM). The previous treatment of BT with the AIAs impaired the infection establishment of cardiac cell cultures. In vivo assays showed that pre-incubation of mouse blood samples with the AIAs and CV (96 µM) significantly suppressed the parasitemia peak, but only the AIA DB1831 gave ≥90% animal survival, while vehicle treated samples reached 0%. Our findings support further studies regarding the potential use of AIAs for blood bank purposes. Full article

(This article belongs to the Special Issue Transfusion-Transmissible Infections and Epidemiological Surveillance)

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17 pages, 2309 KiB

Open AccessArticle

Monitoring the SARS-CoV-2 Pandemic: Prevalence of Antibodies in a Large, Repetitive Cross-Sectional Study of Blood Donors in Germany—Results from the SeBluCo Study 2020–2022

by Ruth Offergeld, Karina Preußel, Thomas Zeiler, Konstanze Aurich, Barbara I. Baumann-Baretti, Sandra Ciesek, Victor M. Corman, Viktoria Dienst, Christian Drosten, Siegfried Görg, Andreas Greinacher, Marica Grossegesse, Sebastian Haller, Hans-Gert Heuft, Natalie Hofmann, Peter A. Horn, Claudia Houareau, Ilay Gülec, Carlos Luis Jiménez Klingberg, David Juhl, Monika Lindemann, Silke Martin, Hannelore K. Neuhauser, Andreas Nitsche, Julia Ohme, Sven Peine, Ulrich J. Sachs, Lars Schaade, Richard Schäfer, Heinrich Scheiblauer, Martin Schlaud, Michael Schmidt, Markus Umhau, Tanja Vollmer, Franz F. Wagner, Lothar H. Wieler, Hendrik Wilking, Malte Ziemann, Marlow Zimmermann and Matthias an der Heiden Show full author list Hide full author list

Pathogens 2023, 12(4), 551; https://doi.org/10.3390/pathogens12040551 - 2 Apr 2023

Cited by 4 | Viewed by 7299

Abstract

SARS-CoV-2 serosurveillance is important to adapt infection control measures and estimate the degree of underreporting. Blood donor samples can be used as a proxy for the healthy adult population. In a repeated cross-sectional study from April 2020 to April 2021, September 2021, and April/May 2022, 13 blood establishments collected 134,510 anonymised specimens from blood donors in 28 study regions across Germany. These were tested for antibodies against the SARS-CoV-2 spike protein and nucleocapsid, including neutralising capacity. Seroprevalence was adjusted for test performance and sampling and weighted for demographic differences between the sample and the general population. Seroprevalence estimates were compared to notified COVID-19 cases. The overall adjusted SARS-CoV-2 seroprevalence remained below 2% until December 2020 and increased to 18.1% in April 2021, 89.4% in September 2021, and to 100% in April/May 2022. Neutralising capacity was found in 74% of all positive specimens until April 2021 and in 98% in April/May 2022. Our serosurveillance allowed for repeated estimations of underreporting from the early stage of the pandemic onwards. Underreporting ranged between factors 5.1 and 1.1 in the first two waves of the pandemic and remained well below 2 afterwards, indicating an adequate test strategy and notification system in Germany. Full article

(This article belongs to the Special Issue Transfusion-Transmissible Infections and Epidemiological Surveillance)

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15 pages, 1103 KiB

Open AccessArticle

Evaluation of Molecular Methods to Identify Chagas Disease and Leishmaniasis in Blood Donation Candidates in Two Brazilian Centers

by Juliana de Jesus Guimarães Ferreira, Sandra Cecília Botelho Costa, Marcelo Addas-Carvalho, Mariane Barroso Pereira, Adriana de Oliveira França, Rodrigo Gonçalves de Lima, Paula Durante Andrade, Jamiro da Silva Wanderley, Luiz Cláudio Martins, Eros Antonio de Almeida and Gláucia Elisete Barbosa Marcon

Pathogens 2023, 12(4), 508; https://doi.org/10.3390/pathogens12040508 - 24 Mar 2023

Viewed by 1998

Abstract

In Brazil, blood donation is regulated by the Brazilian Ministry of Health, and all States follow the same protocol for clinical and laboratory screening. Brazil is an endemic country for Chagas disease (CD), caused by Trypanosoma cruzi, and for leishmaniasis, caused by a species of Leishmania spp. Screening for leishmaniosis is not routinely performed by blood banks. Given the antigenic similarity between T. cruzi and Leishmania spp., cross-reactions in serological tests can occur, and inconclusive results for CD have been found. The objective of this study was to apply molecular techniques, e.g., nPCR, PCR, and qPCR, to clarify cases of blood donation candidates with non-negative serology for CD and to analyze the difference between the melting temperature during real-time PCR using SYBR Green. Thirty-seven cases that showed non-negative results for CD using chemiluminescent microparticle immunoassay (CMIA) tests from blood banks in Campo Grande, MS, and Campinas, SP, were analyzed. In the serum samples, 35 samples were evaluated by ELISA, and 24.3% (9/35) showed positive results for CD. nPCR was able to detect 12 positive results in 35 samples (34.28%). qPCR for T. cruzi was quantifiable in the samples that showed a value ≥0.002 par eq/mL (parasite equivalents per milliliter), and in 35 samples, 11 (31.42%) were positive. Of all evaluated samples using the described tests (CMIA, ELISA, nPCR, and qPCR), 18 (48.6%) were positive for CD. For MCA by qPCR, the melting temperature was 82.06 °C ± 0.46 for T. cruzi and 81.9 °C ± 0.24 for Leishmania infantum. The Mann–Whitney test showed a significant value of p < 0.0001. However, the differentiation between T. cruzi and L. infantum could not be considered due to temperature overlap. For leishmaniasis, of the 35 samples with non-negative serology for CD tested by the indirect fluorescent antibody test (IFAT), only one sample (2.85%) was positive (1:80). The PCR for Leishmania spp. was performed on 36 blood samples from donation candidates, and all were negative. qPCR for L. infantum showed 37 negative results for the 37 analyzed samples. The data presented here show the importance of performing two different tests in CD screening at blood banks. Molecular tests should be used for confirmation, thereby improving the blood donation system. Full article

(This article belongs to the Special Issue Transfusion-Transmissible Infections and Epidemiological Surveillance)

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15 pages, 1078 KiB

Open AccessEditor’s ChoiceArticle

Hepatitis E Virus in Finland: Epidemiology and Risk in Blood Donors and in the General Population

by Jaana Mättö, Niina Putkuri, Ruska Rimhanen-Finne, Päivi Laurila, Jonna Clancy, Jarkko Ihalainen and Susanne Ekblom-Kullberg

Pathogens 2023, 12(3), 484; https://doi.org/10.3390/pathogens12030484 - 18 Mar 2023

Cited by 5 | Viewed by 2616

Abstract

Autochthonous hepatitis E (HEV) cases have been increasingly recognized and reported in Europe, caused predominantly by the zoonotic HEV genotype 3. The clinical picture is highly variable, from asymptomatic to acute severe or prolonged hepatitis in immunocompromised patients. The main route of transmission to humans in Europe is the ingestion of undercooked pork meat. Transfusion-transmitted HEV infections have also been reported. The aim of the study was to determine the HEV epidemiology and risk in the Finnish blood donor population. A total of 23,137 samples from Finnish blood donors were screened for HEV RNA from individual samples and 1012 samples for HEV antibodies. Additionally, laboratory-confirmed hepatitis E cases in 2016–2022 were extracted from national surveillance data. The HEV RNA prevalence data was used to estimate the risk of transfusion transmission of HEV in the Finnish blood transfusion setting. Four HEV RNA-positive were found, resulting in 1:5784 (0.02%) RNA prevalence. All HEV RNA-positive samples were IgM-negative, and genotyped samples represented genotype HEV 3c. HEV IgG seroprevalence was 7.4%. From the HEV RNA rate found in this study and data on blood component usage in Finland in 2020, the risk estimate for a severe transfusion-transmitted HEV infection is 1:1,377,000 components or one in every 6–7 years. In conclusion, the results indicate that the risk of transfusion-transmitted HEV (HEV TTI) in Finland is low. However, continuous follow-up of the HEV epidemiology in relation to the transfusion risk landscape in Finland is necessary, as well as promoting awareness in the medical community of the small risk for HEV TTI, especially for immunocompromised patients. Full article

(This article belongs to the Special Issue Transfusion-Transmissible Infections and Epidemiological Surveillance)

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8 pages, 649 KiB

Open AccessArticle

Chagas Disease and Transfusion Risk in Italy: The Results of a National Survey

by Ilaria Pati, Mario Cruciani, Francesca Masiello, Francesco Barone, Giacomo Silvioli, Massimo La Raja, Simonetta Pupella and Vincenzo De Angelis

Pathogens 2022, 11(11), 1229; https://doi.org/10.3390/pathogens11111229 - 25 Oct 2022

Cited by 4 | Viewed by 2287

Abstract

Background: Universal serological screening in endemic areas is essential for preventing Chagas disease transmission by transfusions, while in non-endemic areas, screening is provided only to donors exposed to the infection risk. In this respect, in order to ensure high and uniform standards of quality and safety of blood components, the Italian National Blood Centre conducted a survey to detect information on management of donors at risk of Chagas disease and on the current transfusion risk. Methods: The National Blood Centre conducted a survey on preventive measures for Chagas disease in the years 2020–2021. Results: Survey results are broadly representative of the national situation; out of 24,269 tested donors, only 15 donors were confirmed positive (0.4 out of 100,000 donors). This rate is lower than the number of positive donors (72/100,000) for transfusion transmissible infections (HIV, HBV, HCV, and T. pallidum) in the same period. Furthermore, the number of T. cruzi positive blood donors is lower than the T. cruzi positive subjects in the general population. Conclusions: In Italy, T. cruzi infection transfusion risk may be considered still very low, and this is confirmed by the absence of documented transfusion transmission. Full article

(This article belongs to the Special Issue Transfusion-Transmissible Infections and Epidemiological Surveillance)

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Review

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15 pages, 612 KiB

Open AccessReview

Emerging Pathogen Threats in Transfusion Medicine: Improving Safety and Confidence with Pathogen Reduction Technologies

by Marcia Cardoso, Izabela Ragan, Lindsay Hartson and Raymond P. Goodrich

Pathogens 2023, 12(7), 911; https://doi.org/10.3390/pathogens12070911 - 5 Jul 2023

Cited by 2 | Viewed by 2795

Abstract

Emerging infectious disease threats are becoming more frequent due to various social, political, and geographical pressures, including increased human–animal contact, global trade, transportation, and changing climate conditions. Since blood products for transfusion are derived from donated blood from the general population, emerging agents spread by blood contact or the transfusion of blood products are also a potential risk. Blood transfusions are essential in treating patients with anemia, blood loss, and other medical conditions. However, these lifesaving procedures can contribute to infectious disease transmission, particularly to vulnerable populations. New methods have been implemented on a global basis for the prevention of transfusion transmissions via plasma, platelets, and whole blood products. Implementing proactive pathogen reduction methods may reduce the likelihood of disease transmission via blood transfusions, even for newly emerging agents whose transmissibility and susceptibility are still being evaluated as they emerge. In this review, we consider the Mirasol PRT system for blood safety, which is based on a photochemical method involving riboflavin and UV light. We provide examples of how emerging threats, such as Ebola, SARS-CoV-2, hepatitis E, mpox and other agents, have been evaluated in real time regarding effectiveness of this method in reducing the likelihood of disease transmission via transfusions. Full article

(This article belongs to the Special Issue Transfusion-Transmissible Infections and Epidemiological Surveillance)

16 pages, 360 KiB

Open AccessReview

Transfusion-Transmitted Disorders 2023 with Special Attention to Bone Marrow Transplant Patients

by Miklós Udvardy, Árpád Illés, Lajos Gergely, László Imre Pinczés, Ferenc Magyari and Zsófia Simon

Pathogens 2023, 12(7), 901; https://doi.org/10.3390/pathogens12070901 - 1 Jul 2023

Cited by 2 | Viewed by 2437

Abstract

Transfusion medicine is traditionally a strong/fundamental part of clinical practice, saving hundreds of millions of lives. However, blood-borne or transmitted infections are a well-known and feared possibility, a risk we relentlessly mitigate. Pathogens are continuously and rather quickly changing, so during the last decade, many, sometimes exotic, new pathogens and diseases were recorded and analyzed, and some of them were proved to be transmitted with transfusions. Blood or blood component transfusions are carried out after cautious preparative screening and inactivation maneuvers, but in some instances, newly recognized agents might escape from standard screening and inactivation procedures. Here, we try to focus on some of these proven or potentially pathogenic transfusion-transmitted agents, especially in immunocompromised patients or bone marrow transplantation settings. These pathogens are sometimes new challenges for preparative procedures, and there is a need for more recent, occasionally advanced, screening and inactivation methods to recognize and eliminate the threat a new or well-known pathogen can pose. Pathogen transmission is probably even more critical in hemophiliacs or bone marrow transplant recipients, who receive plasma-derived factor preparations or blood component transfusions regularly and in large quantities, sometimes in severely immunosuppressed conditions. Moreover, it may not be emphasized enough that transfusions and plasma-derived product administrations are essential to medical care. Therefore, blood-borne transmission needs continued alertness and efforts to attain optimal benefits with minimized hazards. Full article

(This article belongs to the Special Issue Transfusion-Transmissible Infections and Epidemiological Surveillance)

15 pages, 1060 KiB

Open AccessReview

Hepatitis C and Thalassemia: A Story with (Almost) a Happy Ending

by Raffaella Origa

Pathogens 2023, 12(5), 683; https://doi.org/10.3390/pathogens12050683 - 5 May 2023

Cited by 2 | Viewed by 2192

Abstract

Donor screening has nearly eliminated the risk of hepatitis C virus post-transfusion transmission in resource-rich settings. Moreover, the use of direct antiviral agents made it possible to treat the majority of patients with thalassemia and hepatitis C. However, this achievement, while extremely significant, does not erase the effects of the virus in terms of fibrogenesis and mutagenic risk, and adult patients with thalassemia are facing the long-term consequences of the chronic infection both on the liver and extrahepatically. As in the general population, it is in mainly patients with cirrhosis who are increasing in age, even though they are now HCV RNA-negative, who are at risk of hepatocellular carcinoma, which continues to be statistically much more frequent in individuals with than without thalassemia. In certain resource-limited settings, the World Health Organization has estimated that up to 25 percent of blood donations do not undergo screening. It is therefore not surprising that hepatitis virus infection is still the most prevalent in patients with thalassemia worldwide. Full article

(This article belongs to the Special Issue Transfusion-Transmissible Infections and Epidemiological Surveillance)

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12 pages, 1364 KiB

Open AccessEditor’s ChoiceReview

The Evolution of the Safety of Plasma Products from Pathogen Transmission—A Continuing Narrative

by Albert Farrugia

Pathogens 2023, 12(2), 318; https://doi.org/10.3390/pathogens12020318 - 15 Feb 2023

Cited by 8 | Viewed by 3821

Abstract

Chronic recipients of plasma products are at risk of infection from blood-borne pathogens as a result of their inevitable exposure to agents which will contaminate a plasma manufacturing pool made up of thousands of individual donations. The generation of such a pool is an essential part of the large-scale manufacture of these products and is required for good manufacturing practice (GMP). Early observations of the transmission of hepatitis by pooled plasma and serum led to the incorporation of heat treatment of the albumin solution produced by industrial Cohn fractionation of plasma. This led to an absence of pathogen transmission by albumin over decades, during which hepatitis continued to be transmitted by other early plasma fractions, as well as through mainstream blood transfusions. This risk was decreased greatly over the 1960s as an understanding of the epidemiology and viral aetiology of transfusion-transmitted hepatitis led to the exclusion of high-risk groups from the donor population and the development of a blood screening test for hepatitis B. Despite these measures, the first plasma concentrates to treat haemophilia transmitted hepatitis B and other, poorly understood, forms of parenterally transmitted hepatitis. These risks were considered to be acceptable given the life-saving nature of the haemophilia treatment products. The emergence of the human immunodeficiency virus (HIV) as a transfusion-transmitted infection in the early 1980s shifted the focus of attention to this virus, which proved to be vulnerable to a number of inactivation methods introduced during manufacture. Further developments in the field obviated the risk of hepatitis C virus (HCV) which had also infected chronic recipients of plasma products, including haemophilia patients and immunodeficient patients receiving immunoglobulin. The convergence of appropriate donor selection driven by knowledge of viral epidemiology, the development of blood screening now based on molecular diagnostics, and the incorporation of viral inactivation techniques in the manufacturing process are now recognised as constituting a “safety tripod” of measures contributing to safety from pathogen transmission. Of these three components, viral inactivation during manufacture is the major contributor and has proven to be the bulwark securing the safety of plasma derivatives over the past thirty years. Concurrently, the safety of banked blood and components continues to depend on donor selection and screening, in the absence of universally adopted pathogen reduction technology. This has resulted in an inversion in the relative safety of the products of blood banking compared to plasma products. Overall, the experience gained in the past decades has resulted in an absence of pathogen transmission from the current generation of plasma derivatives, but maintaining vigilance, and the surveillance of the emergence of infectious agents, is vital to ensure the continued efficacy of the measures in place and the development of further interventions aimed at obviating safety threats. Full article

(This article belongs to the Special Issue Transfusion-Transmissible Infections and Epidemiological Surveillance)

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