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Transfusion Transmitted Viral Infections
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Transfusion Transmitted Viral Infections

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (30 August 2022) | Viewed by 30607

Special Issue Editor

Dr. Daniel Candotti

E-Mail Website
Guest Editor
Department of Virology, Henri Mondor Hospital, Paris-Est University, INSERM U955 - IMRB - Team 18, 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France
Interests: virology; hepatitis viruses; viral persistence epidemiology; genetic variability; transfusion; blood screening
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Timely access to safe and adequate human blood products is primary concern of transfusion medicine. Despite decades of improvement in the prevention of transfusion-transmitted infectious diseases, blood safety remains challenged by continuous changes in the nature and the epidemiology of bloodborne viral infections related to the increasing global circulation of human and animal populations, human activities with increased risk of zoonotic infections, and the geographical expansion of viral vectors. Extended vaccination program, availability of efficient antiviral treatments, and changes in donor eligibility policies may also modify the viral infectious risk in the blood donor populations.

In this Special Issue, we would like to address the ongoing need to monitor residual threats from established viruses (HBV, HCV, HIV, WNV, etc.) and to identify new threats from emerging or re-emerging viruses (HEV, arboviruses, etc.). In addition, maintaining optimal blood safety requires the necessary adaptation of existing blood screening strategies and the implementation and evaluation of new strategies based on recent technological innovations (i.e., highly sensitive serological or molecular assays, next-generation sequencing, pathogen inactivation) and local resources. Risk-based decision making and cost-effective models are also needed to estimate infectious risks and place new interventions in context.

Dr. Daniel Candotti
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • blood-borne viruses
  • emergence
  • epidemiology
  • prevalence
  • transfusion transmission
  • blood donors
  • blood screening
  • infectious risk
  • pathogen inactivation
  • next-generation sequencing

Published Papers (16 papers)

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Editorial

Jump to: Research, Review

3 pages, 185 KiB  
Editorial
Viruses Special Issue “Transfusion-Transmitted Viral Infections”
by Daniel Candotti
Viruses 2023, 15(1), 86; https://doi.org/10.3390/v15010086 - 28 Dec 2022
Cited by 2 | Viewed by 1127
Abstract
Blood transfusion is a life-saving treatment that requires patients to have access to safe and adequate blood products that are available in a timely manner [...] Full article
(This article belongs to the Special Issue Transfusion Transmitted Viral Infections)

Research

Jump to: Editorial, Review

17 pages, 2743 KiB  
Article
Evolution of Blood Safety in Switzerland over the Last 25 Years for HIV, HCV, HBV and Treponema pallidum
by Christoph Niederhauser, Caroline Tinguely, Martin Stolz, Michael Vock, Soraya Amar El Dusouqui and Peter Gowland
Viruses 2022, 14(12), 2611; https://doi.org/10.3390/v14122611 - 23 Nov 2022
Cited by 6 | Viewed by 1430
Abstract
During the last few decades, efforts to increase the safety of blood and blood products have mainly focused on preventing the viral infections HCV, HIV, HBV and Treponema pallidum. The evolution of these approaches and the achieved increase in safety is shown [...] Read more.
During the last few decades, efforts to increase the safety of blood and blood products have mainly focused on preventing the viral infections HCV, HIV, HBV and Treponema pallidum. The evolution of these approaches and the achieved increase in safety is shown for the last 25 years in Switzerland. In detail, the prevalences and incidences of the infection disease and the theoretical estimated residual risks (RR) of these blood-borne infections are presented. Prevalences, incidences and, in particular, the RR have decreased considerably over the last 25 years. This was achieved primarily by the adoption of strict criteria for the selection of blood donors, refined questionnaires, the introduction of increasingly sensitive serological screening tests and the implementation of nucleic acid testing (NAT) for these blood-borne pathogens. These NAT assays have significantly shortened the window period between infection and the first detection of the infectious agent in the blood of an infected individual. A form of “real life” comparison or confirmation is provided by the reported lookback procedures (LBP) and the haemovigilance data of the Swiss competent authority, Swissmedic. These data are in agreement, and thus support the very low prevalences, incidences and RR. Full article
(This article belongs to the Special Issue Transfusion Transmitted Viral Infections)
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17 pages, 924 KiB  
Article
Insights on 21 Years of HBV Surveillance in Blood Donors in France
by Pierre Cappy, Laure Boizeau, Daniel Candotti, Sophie Le Cam, Christophe Martinaud, Josiane Pillonel, Martin Tribout, Claude Maugard, Josiane Relave, Pascale Richard, Pascal Morel and Syria Laperche
Viruses 2022, 14(11), 2507; https://doi.org/10.3390/v14112507 - 12 Nov 2022
Cited by 5 | Viewed by 1810
Abstract
Hepatitis B virus (HBV) infection is the most frequent viral infection found in blood donors (BDs) in France. We analyzed the epidemiological and sero-molecular data on HBV infection gathered over the past two decades by the French haemovigilance surveillance network, blood screening laboratories, [...] Read more.
Hepatitis B virus (HBV) infection is the most frequent viral infection found in blood donors (BDs) in France. We analyzed the epidemiological and sero-molecular data on HBV infection gathered over the past two decades by the French haemovigilance surveillance network, blood screening laboratories, and the national reference center for transfusion infectious risks (NRC). Between 2000 and 2020, 6149 of the 58,160,984 donations (1.06/10,000) tested HBV positive, 98% of them from first-time blood donors (FTBDs). In addition, 2212 (0.0071%) of the 30,977,753 donations screened for HBV DNA tested DNA positive, of which 25 (1.1%) were positive only for this marker. HBV prevalence decreased by 2.8-fold and the residual risk for transfusion-transmitted HBV infection decreased 13-fold and was divided by 13. The major risk factor for HBV infection was the origin of donors (endemic country, 66.5%), followed by parenteral exposure (10.7%). In the whole HBV-positive BD population, genotype D was predominant (41.8%), followed by genotypes A (26.2%) and E (20.4%), reflecting the geographical origin of donors. The low and decreasing prevalence and incidence of HBV infection in French BDs, coupled with a screening strategy using three HBV markers (HBsAg, anti-HBc and DNA), ensures a high level of blood safety, further reinforced by the implementation of pathogen-reduction measures. Full article
(This article belongs to the Special Issue Transfusion Transmitted Viral Infections)
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15 pages, 8984 KiB  
Article
SARS-CoV-2 Seroprevalence among Canadian Blood Donors: The Advance of Omicron
by Sheila F. O’Brien, Niamh Caffrey, Qi-Long Yi, Chantale Pambrun and Steven J. Drews
Viruses 2022, 14(11), 2336; https://doi.org/10.3390/v14112336 - 25 Oct 2022
Cited by 7 | Viewed by 1384
Abstract
With the emergence of the SARS-CoV-2 Omicron variant in late 2021, Canadian public health case/contact testing was scaled back due to high infection rates with milder symptoms in a highly vaccinated population. We monitored the seroprevalence of SARS-CoV-2 nucleocapsid (anti-N) and spike protein [...] Read more.
With the emergence of the SARS-CoV-2 Omicron variant in late 2021, Canadian public health case/contact testing was scaled back due to high infection rates with milder symptoms in a highly vaccinated population. We monitored the seroprevalence of SARS-CoV-2 nucleocapsid (anti-N) and spike protein (anti-S) antibodies in blood donors across Canada from September 2021 to June 2022 in 202,123 randomly selected samples. Multivariable logistic regression of anti-N positivity with month, age, sex, racialization, region, material and social deprivation (based on postal code) identified as independent predictors. Piece-wise logistic regression analysed the association between anti-S concentration and month, and anti-N/anti-S positivity. Infection-related seroprevalence (anti-N positive) was 4.38% (95% CI: 3.96, 4.81) in September reaching 50.70% (50.15, 52.16) in June; nearly 100% were anti-S positive throughout. Anti-N positivity was associated with younger age, male sex, the Alberta and Prairies regions, greater material deprivation and less social deprivation (p < 0.001). Anti-S concentration was high initially (3306 U/mL, IQR 4280 U/mL), increased to (13,659 U/mL, IQR 28,224 U/mL) by June (p < 0.001), following the pattern of deployment of the third and fourth vaccine doses and was higher in those that were anti-N positive (p < 0.001). Despite already high vaccination-related seroprevalence, infection-related seroprevalence increased dramatically with the emergence of the Omicron SARS-CoV-2 variant. Full article
(This article belongs to the Special Issue Transfusion Transmitted Viral Infections)
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11 pages, 1059 KiB  
Article
Blood Center Testing Allows the Detection and Rapid Treatment of Acute and Recent HIV Infection
by Karin van den Berg, Marion Vermeulen, Sonia Bakkour, Mars Stone, Genevieve Jacobs, Cynthia Nyoni, Coreen Barker, Christopher McClure, Darryl Creel, Eduard Grebe, Nareg Roubinian, Ute Jentsch, Brian Custer, Michael P. Busch, Edward L. Murphy and on behalf of the Recipient Epidemiology and Donor Evaluation Study (REDS)-III South Africa International Program
Viruses 2022, 14(11), 2326; https://doi.org/10.3390/v14112326 - 23 Oct 2022
Cited by 1 | Viewed by 1684
Abstract
Blood donations in South Africa are tested for HIV RNA using individual donation NAT (ID-NAT), allowing detection and rapid antiretroviral therapy (ART) of acute HIV infections. We enrolled a cohort of acute and recent HIV-infected blood donation candidates in South Africa in 2015–2018, [...] Read more.
Blood donations in South Africa are tested for HIV RNA using individual donation NAT (ID-NAT), allowing detection and rapid antiretroviral therapy (ART) of acute HIV infections. We enrolled a cohort of acute and recent HIV-infected blood donation candidates in South Africa in 2015–2018, measured HIV antibody, ID-NAT, and recency of infection <195 days (Sedia LAg) at enrollment and initiated early ART. A small cohort of HIV elite controllers was followed without treatment. HIV reservoir measurements included ultrasensitive plasma RNA, cell-associated HIV RNA, and total DNA. Enrollment of 18 Fiebig I–III and 45 Fiebig IV–VI HIV clade C subjects occurred a median of 18 days after index blood donation. ART was administered successfully and compliance with follow-up visits was excellent. There were only minimal differences in HIV reservoir between ART initiation in Fiebig stages I–III vs. IV–VI, but ART noncompliance increased HIV reservoir. In 11 untreated HIV elite controllers, HIV reservoir levels were similar to or higher than those seen in our early treated cohort. National blood services can identify acute HIV cohorts for subsequent HIV cure research studies. Among HIV clade C-infected donors, HIV reservoir differed little by Fiebig stage at treatment initiation, but was smaller than in chronically treated HIV and those with ART noncompliance. Full article
(This article belongs to the Special Issue Transfusion Transmitted Viral Infections)
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15 pages, 1907 KiB  
Article
Efficacy of Different Testing Scenarios in Reducing Transfusion-Transmitted Hepatitis B Virus (TT-HBV) Infection Risk
by Nico Lelie, Michael Busch and Steven Kleinman
Viruses 2022, 14(10), 2263; https://doi.org/10.3390/v14102263 - 15 Oct 2022
Cited by 2 | Viewed by 1507
Abstract
The efficacy of different screening scenarios in reducing hepatitis B virus (HBV) transmission risk as compared to the risk without screening was modeled in 9,337,110 donations from four geographical regions that had been subjected to hepatitis B surface antigen (HBsAg) and individual donation [...] Read more.
The efficacy of different screening scenarios in reducing hepatitis B virus (HBV) transmission risk as compared to the risk without screening was modeled in 9,337,110 donations from four geographical regions that had been subjected to hepatitis B surface antigen (HBsAg) and individual donation nucleic acid amplification testing (ID-NAT). We used the Weusten models for estimating infectivity risk for Red Blood Cell (RBC) transfusions in eight HBV infection stages and then evaluated multiple screening strategies based on minipool (MP) and ID-NAT options of different sensitivity for their efficacy in reducing this risk. The efficacy in reducing HBV transmission risk by screening scenarios across the regions varied between 81% (HBsAg only) and 99.2% (ID-NAT and anti-HBc). Highly sensitive ID-NAT alone achieved a slightly higher risk reduction (97.6–99.0%) than minipool of 6 donations (MP6)-NAT in combination with HBsAg and anti-HBc (96.3–98.7%). In ID-NAT screened lapsed and repeat donors, the additional risk removed by HBsAg testing was minimal (<0.1%). The modeling outcomes in this and two previous reports using this multi-regional database suggest that one could consider an ID-NAT alone testing scenario as an alternative to MP-NAT and serology-based testing algorithms and restrict serologic testing to first-time donors only. Full article
(This article belongs to the Special Issue Transfusion Transmitted Viral Infections)
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9 pages, 271 KiB  
Article
Human Herpesvirus 8 in Australia: DNAemia and Cumulative Exposure in Blood Donors
by David J. Speicher, Jesse J. Fryk, Victoria Kashchuk, Helen M. Faddy and Newell W. Johnson
Viruses 2022, 14(10), 2185; https://doi.org/10.3390/v14102185 - 3 Oct 2022
Cited by 2 | Viewed by 1988
Abstract
Human herpesvirus 8 (HHV-8), the causative agent of Kaposi’s sarcoma, multicentric Castleman’s disease and primary effusion lymphoma, predominantly manifests in immunocompromised individuals. However, infection in immunocompetent individuals does occur. The prevalence of HHV-8 exposure in blood donors from non-endemic countries ranges between 1.2% [...] Read more.
Human herpesvirus 8 (HHV-8), the causative agent of Kaposi’s sarcoma, multicentric Castleman’s disease and primary effusion lymphoma, predominantly manifests in immunocompromised individuals. However, infection in immunocompetent individuals does occur. The prevalence of HHV-8 exposure in blood donors from non-endemic countries ranges between 1.2% and 7.3%. Nothing was known about the prevalence in Australian blood donors. Therefore, this study investigated the active and cumulative exposure of HHV-8 in this cohort. Plasma samples (n = 480) were collected from eastern Australian blood donors and were tested for HHV-8 DNA by qPCR, and for HHV-8 antibodies by two different ELISAs. Samples initially positive on either ELISA were retested in duplicate on both, and on a mock-coated ELISA. Any samples positive two or three out of the three times tested on at least one ELISA, and repeat negative on the mock-coated ELISA, were assigned as repeat positive. None of the 480 samples tested contained HHV-8 DNA. Serological testing revealed 28 samples (5.83%; 95% CI: 3.74–7.93%) had antibodies to HHV-8. There was no difference (p > 0.05) in seropositivity between sex or with increasing age. This is the first study to show serological evidence of cumulative HHV-8 exposure and no HHV-8 DNAemia within a select blood donor population in Australia. Our molecular and serological data is consistent with published results for blood donors residing in HHV-8 non-endemic countries, which shows the prevalence to be very low. Full article
(This article belongs to the Special Issue Transfusion Transmitted Viral Infections)
12 pages, 273 KiB  
Article
HTLV-1/2 Infection in Blood Donors from a Non-Endemic Area (Catalonia, Spain) between 2008 and 2017: A 10-Year Experience
by Maria Piron, Fernando Salvador, Estrella Caballero, Adrián Sánchez-Montalvá, Marta Bes, Natàlia Casamitjana, Lluís Puig, Israel Molina and Silvia Sauleda
Viruses 2022, 14(9), 1975; https://doi.org/10.3390/v14091975 - 6 Sep 2022
Cited by 4 | Viewed by 1857
Abstract
Human T-cell lymphotropic virus type 1 and 2 (HTLV-1/2) screening is not mandatory in Spanish blood banks. In Catalonia, selective screening was introduced in 2008, followed by universal screening in 2011. We present herein a 10-year experience of HTLV testing in blood donors. [...] Read more.
Human T-cell lymphotropic virus type 1 and 2 (HTLV-1/2) screening is not mandatory in Spanish blood banks. In Catalonia, selective screening was introduced in 2008, followed by universal screening in 2011. We present herein a 10-year experience of HTLV testing in blood donors. HTLV-1/2 selective screening was performed using Ortho-Clinical Diagnostics HTLV-I/HTLV-II Ab-Capture ELISA between February 2008 and May 2009, then Abbott Prism HTLV-I/ HTLV-II assay until December 2010. Abbott Architect rHTLV-I/II assay was then used for HTLV-1/2 universal screening in pooled samples. INNO-LIA HTLV I/II Score (Fujirebio) and in-house HTLV-1/2 proviral DNA real-time PCR were used in reactive samples. Follow-up was offered to confirm HTLV-1/2 donors in Vall d’Hebron Hospital. Between 2008 and 2017, 51 blood donors were confirmed HTLV positive (46 HTLV-1, 4 HTLV-2 and 1 HTLV) out of 2,114,891 blood donations (1 in 41,468). Sixty-nine percent were female, median age was 40 years and most were born in Latin America (69%), followed by Europe (25%), Africa (4%) and Asia (2%). Screening of relatives and partners identified 12 additional HTLV-1 cases. Lookback studies did not show any HTLV-1/2 transmission. HTLV infections found in blood donors mirror epidemiological changes in the population of Spain. Consequently, HTLV should be considered a potential risk for recipients and calls for the design of optimal strategies to ensure transfusion safety. Full article
(This article belongs to the Special Issue Transfusion Transmitted Viral Infections)
17 pages, 1539 KiB  
Article
Early Dynamics of Hepatitis B Virus (HBV)-DNA and Surface Antigen (HBsAg) in Ramp-Up Phase of Viremia: Implications for Performance Evaluation of Blood Screening Assays
by Harry van Drimmelen and Nico Lelie
Viruses 2022, 14(9), 1942; https://doi.org/10.3390/v14091942 - 31 Aug 2022
Cited by 2 | Viewed by 1493
Abstract
The Common Specifications/EU 2017/746 regulation for market approval of class D in vitro diagnostic devices (IVDs) intended for detection of blood borne viruses requires testing of the International Standard and 10–30 seroconversion panels to demonstrate ‘state of the art’ assay performance. We examined [...] Read more.
The Common Specifications/EU 2017/746 regulation for market approval of class D in vitro diagnostic devices (IVDs) intended for detection of blood borne viruses requires testing of the International Standard and 10–30 seroconversion panels to demonstrate ‘state of the art’ assay performance. We examined whether these requirements for performance evaluation are reasonable for HBV-DNA and HBsAg assays. For this purpose, we quantified HBsAg and HBV-DNA (genotype A) in the ramp-up phase of five seroconversion panels and demonstrated a remarkably parallel increase in the Log concentration of both analytes over time. Testing of seroconversion panels by three nucleic acid amplification technology (NAT) methods in multiple replicates and probit analysis with sufficient critical samples from all five panels taken together showed detection limits in copies/mL that were comparable to those on a HBV-DNA genotype A standard dilution panel. This indicates that the viral doubling time in the ramp-up phase is equal above and below the quantification limit of the viral load assay. The geometric mean HBsAg (PRISM) cutoff crossing point was 20 days later than the 50% NAT (Ultrio Plus) conversion point equivalent to 1500 (range: 1100–2200) and 4.8 (CI: 3.7–6.4) HBV-DNA copies/mL, respectively. Analytical sensitivity data of different NAT assay versions obtained over a decade demonstrated that the detection limit on the International Standard is not representative of all genotyped reference samples. From our detailed mathematical analysis, we conclude that HBV-DNA and HBsAg standard dilution series are functionally equivalent to seroconversion panels. A general requirement of a 95% detection limit ≤100 HBV-DNA copies/mL for different viral genotypes would be a better-defined regulation for EU market approval of NAT blood screening assays than the testing of multiple seroconversion panels to claim ‘state of the art’ performance. Full article
(This article belongs to the Special Issue Transfusion Transmitted Viral Infections)
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12 pages, 15448 KiB  
Article
An Outbreak of Japanese Encephalitis Virus in Australia; What Is the Risk to Blood Safety?
by Veronica C. Hoad, Philip Kiely, Clive R. Seed, Elvina Viennet and Iain B. Gosbell
Viruses 2022, 14(9), 1935; https://doi.org/10.3390/v14091935 - 31 Aug 2022
Cited by 5 | Viewed by 2153
Abstract
A widespread outbreak of Japanese encephalitis virus (JEV) was detected in mainland Australia in 2022 in a previous non-endemic area. Given JEV is known to be transfusion-transmissible, a rapid blood-safety risk assessment was performed using a simple deterministic model to estimate the risk [...] Read more.
A widespread outbreak of Japanese encephalitis virus (JEV) was detected in mainland Australia in 2022 in a previous non-endemic area. Given JEV is known to be transfusion-transmissible, a rapid blood-safety risk assessment was performed using a simple deterministic model to estimate the risk to blood safety over a 3-month outbreak period during which 234,212 donors attended. The cumulative estimated incidence in donors was 82 infections with an estimated 4.26 viraemic components issued, 1.58 resulting in transfusion-transmission and an estimated risk of encephalitis of 1 in 4.3 million per component transfused over the risk period. Australia has initiated a robust public health response, including vector control, animal control and movement, and surveillance. Unlike West Nile virus, there is an effective vaccine that is being rolled-out to those at higher risk. Risk evaluation considered options such as restricting those potentially at risk to plasma for fractionation, which incorporates additional pathogen reduction, introducing a screening test, physicochemical pathogen reduction, quarantine, post donation illness policy changes and a new donor deferral. However, except for introducing a new deferral to potentially cover rare flavivirus risks, no option resulted in a clear risk reduction benefit but all posed threats to blood sufficiency or cost. Therefore, the blood safety risk was concluded to be tolerable without specific mitigations. Full article
(This article belongs to the Special Issue Transfusion Transmitted Viral Infections)
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10 pages, 1550 KiB  
Article
The Impact of Early Antiretroviral Treatment (ART) for HIV on the Sensitivity of the Latest Generation of Blood Screening and Point of Care Assays
by Marion Vermeulen, Cari van Schalkwyk, Genevieve Jacobs, Karin van den Berg, Mars Stone, Sonia Bakkour, Brian Custer, Ute Jentsch, Michael P. Busch, Edward Murphy and Eduard Grebe
Viruses 2022, 14(7), 1426; https://doi.org/10.3390/v14071426 - 29 Jun 2022
Cited by 6 | Viewed by 1798
Abstract
Introduction: Rapid initiation of antiretroviral therapy (ART) in early HIV infection is important to limit seeding of the viral reservoir. A number of studies have shown that if ART is commenced prior to seroconversion, the seroconversion may, or may not, occur. We aimed [...] Read more.
Introduction: Rapid initiation of antiretroviral therapy (ART) in early HIV infection is important to limit seeding of the viral reservoir. A number of studies have shown that if ART is commenced prior to seroconversion, the seroconversion may, or may not, occur. We aimed to assess whether seroreversion or no seroconversion occurs using samples collected during an early treatment study in South Africa. Methods: We tested 10 longitudinal samples collected over three years from 70 blood donors who initiated ART after detection of acute or early HIV infection during donation screening on fourth- and fifth-generation HIV antibody and RNA assays, and three point of care (POC) rapid tests. Donors were allocated to three treatment groups: (1) very early, (2) early, and (3) later. Longitudinal samples were grouped into time bins post-treatment initiation. Results: On all three high-throughput HIV antibody assays, no clear pattern of declining signal intensity was observed over time after ART initiation in any of the treatment initiation groups and 100% detection was obtained. The Abbott Determine POC assay showed 100% detection at all time points with no seroreversion. However, the Abbott ABON HIV1 and OraSure OraQuick POC assays showed lower proportions of detection in all time bins in the very early treated group, ranging from 50.0% (95% CI: 26.8–73.2%) to 83.1% (95% CI: 64.2–93.0%), and moderate detection rates in the early and later-treated groups. Conclusion: While our findings are generally reassuring for HIV detection when high-throughput serological screening assays are used, POC assays may have lower sensitivity for detection of HIV infection after early treatment. Findings are relevant for blood safety and other settings where POC assays are used. Full article
(This article belongs to the Special Issue Transfusion Transmitted Viral Infections)
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11 pages, 1443 KiB  
Article
Human Intramuscular Hyperimmune Gamma Globulin (hIHGG) Anti-SARS-CoV-2—Characteristics of Intermediates and Final Product
by Elzbieta Lachert, Joanna Lasocka, Artur Bielawski, Ewa Sulkowska, Katarzyna Guz, Krzysztof Pyrc, Agnieszka Dabrowska, Agata Wawryniuk-Malmon, Magdalena Letowska, Krzysztof Tomasiewicz and Piotr Grabarczyk
Viruses 2022, 14(6), 1328; https://doi.org/10.3390/v14061328 - 17 Jun 2022
Cited by 2 | Viewed by 2313
Abstract
This study aims to characterize the intermediates, and the final product (FP) obtained during the production of human intramuscular hyperimmune gamma globulin anti-SARS-CoV-2 (hIHGG anti-SARS-CoV-2) and to determine its stability. Material and methods: hIHGG anti-SARS-CoV-2 was fractionated from 270 convalescent plasma donations [...] Read more.
This study aims to characterize the intermediates, and the final product (FP) obtained during the production of human intramuscular hyperimmune gamma globulin anti-SARS-CoV-2 (hIHGG anti-SARS-CoV-2) and to determine its stability. Material and methods: hIHGG anti-SARS-CoV-2 was fractionated from 270 convalescent plasma donations with the Cohn method. Prior to fractionation, the plasma was inactivated (Theraflex MB Plasma). Samples were defined using enzyme immunoassays (EIA) for anti-S1, anti-RBD S1, and anti-N antibodies, and neutralization assays with SARS-CoV-2 (VN) and pseudoviruses (PVN, decorated with SARS-CoV-2 S protein). Results were expressed as a titer (EIA) or 50% of the neutralization titer (IC50) estimated in a four-parameter nonlinear regression model. Results: Concentration of anti-S1 antibodies in plasma was similar before and after inactivation. Following fractionation, the anti-S1, anti-RBD, and anti-N (total tests) titers in FP were concentrated approximately 15-fold from 1:4 to 1:63 (1800 BAU/mL), 7-fold from 1:111 to 1:802 and from 1:13 to 1:88, respectively. During production, the IgA (anti-S1) antibody titer was reduced to an undetectable level and the IgM (anti-RBD) titer from 1:115 to 1:24. The neutralizing antibodies (nAb) titer increased in both VN (from 1:40 to 1:160) and PVN (IC50 from 63 to 313). The concentration of specific IgG in the FP did not change significantly for 14 months. Conclusions: The hIHGG anti-SARS-CoV-2 was stable, with concentration up to approximately 15-fold nAb compared to the source plasma pool. Full article
(This article belongs to the Special Issue Transfusion Transmitted Viral Infections)
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19 pages, 4188 KiB  
Article
Activation of the Ca2+/NFAT Pathway by Assembly of Hepatitis C Virus Core Protein into Nucleocapsid-like Particles
by Priya Devi, Tanel Punga and Anders Bergqvist
Viruses 2022, 14(4), 761; https://doi.org/10.3390/v14040761 - 6 Apr 2022
Viewed by 2199
Abstract
Hepatitis C virus (HCV) is the primary pathogen responsible for liver cirrhosis and hepatocellular carcinoma. The main virion component, the core (C) protein, has been linked to several aspects of HCV pathology, including oncogenesis, immune evasion and stress responses. We and others have [...] Read more.
Hepatitis C virus (HCV) is the primary pathogen responsible for liver cirrhosis and hepatocellular carcinoma. The main virion component, the core (C) protein, has been linked to several aspects of HCV pathology, including oncogenesis, immune evasion and stress responses. We and others have previously shown that C expression in various cell lines activates Ca2+ signaling and alters Ca2+ homeostasis. In this study, we identified two distinct C protein regions that are required for the activation of Ca2+/NFAT signaling. In the basic N-terminal domain, which has been implicated in self-association of C, amino acids 1–68 were critical for NFAT activation. Sedimentation analysis of four mutants in this domain revealed that association of the C protein into nucleocapsid-like particles correlated with NFAT-activated transcription. The internal, lipid droplet-targeting domain was not required for NFAT-activated transcription. Finally, the C-terminal ER-targeting domain was required in extenso for the C protein to function. Our results indicate that targeting of HCV C to the ER is necessary but not sufficient for inducing Ca2+/NFAT signaling. Taken together, our data are consistent with a model whereby proteolytic intermediates of C with an intact transmembrane ER-anchor assemble into pore-like structures in the ER membrane. Full article
(This article belongs to the Special Issue Transfusion Transmitted Viral Infections)
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Review

Jump to: Editorial, Research

18 pages, 2025 KiB  
Review
Re-Entry Evaluation of Chinese Blood Donors with Unconfirmed Hepatitis B Screening Results
by Xuelian Deng, Liang Zang and Daniel Candotti
Viruses 2022, 14(11), 2545; https://doi.org/10.3390/v14112545 - 17 Nov 2022
Cited by 5 | Viewed by 1593
Abstract
The hepatitis B virus (HBV) remains a high priority for Chinese blood banks due to the high prevalence of infection. HBV blood safety has been significantly improved by the implementation of highly sensitive and specific serological and molecular HBV screening assays. The multiplication [...] Read more.
The hepatitis B virus (HBV) remains a high priority for Chinese blood banks due to the high prevalence of infection. HBV blood safety has been significantly improved by the implementation of highly sensitive and specific serological and molecular HBV screening assays. The multiplication of viral markers tested and the ever-increasing analytical sensitivity of the tests can make the interpretation of the results difficult. False-positive or indeterminate results may lead to permanent donor deferrals and conflicts between donors and blood banks. To avoid blood shortages, blood services aim to limit unnecessary donor losses by developing procedures for the re-entry of donors temporarily deferred due to an unconfirmed HBV reactivity. The development of such procedures based on donor follow-up and HBV confirmation remains limited. A review of the scarce data available revealed considerable heterogeneity in testing methods and re-entry algorithms, limited validation studies, and a lack of accurate assessment of the residual infectious risk potentially associated with donor re-entry. In conclusion, systematic and widely validated confirmatory testing and prolonged follow-up are essential for safe re-entry of temporary deferred donors. Standardization of HBV testing methods and the establishment of dedicated expert laboratories are needed because of the complexity of HBV infection in blood donors. Full article
(This article belongs to the Special Issue Transfusion Transmitted Viral Infections)
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10 pages, 605 KiB  
Review
Viral Metagenomics for Identification of Emerging Viruses in Transfusion Medicine
by Svetoslav Nanev Slavov
Viruses 2022, 14(11), 2448; https://doi.org/10.3390/v14112448 - 4 Nov 2022
Cited by 5 | Viewed by 3159
Abstract
Viral metagenomics has revolutionized our understanding for identification of unknown or poorly characterized viruses. For that reason, metagenomic studies gave been largely applied for virus discovery in a wide variety of clinical samples, including blood specimens. The emerging blood-transmitted virus infections represent important [...] Read more.
Viral metagenomics has revolutionized our understanding for identification of unknown or poorly characterized viruses. For that reason, metagenomic studies gave been largely applied for virus discovery in a wide variety of clinical samples, including blood specimens. The emerging blood-transmitted virus infections represent important problem for public health, and the emergence of HIV in the 1980s is an example for the vulnerability of Blood Donation systems to such infections. When viral metagenomics is applied to blood samples, it can give a complete overview of the viral nucleic acid abundance, also named “blood virome”. Detailed characterization of the blood virome of healthy donors could identify unknown (emerging) viral genomes that might be assumed as hypothetic transfusion threats. However, it is impossible only by application of viral metagenomics to assign that one viral agent could impact blood transfusion. That said, this is a complex issue and will depend on the ability of the infectious agent to cause clinically important infection in blood recipients, the viral stability in blood derivatives and the presence of infectious viruses in blood, making possible its transmission by transfusion. This brief review summarizes information regarding the blood donor virome and some important challenges for use of viral metagenomics in hemotherapy for identification of transfusion-transmitted viruses. Full article
(This article belongs to the Special Issue Transfusion Transmitted Viral Infections)
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14 pages, 1190 KiB  
Review
Lessons Learned from the COVID-19 Pandemic and How Blood Operators Can Prepare for the Next Pandemic
by Steven J. Drews and Sheila F. O’Brien
Viruses 2022, 14(10), 2126; https://doi.org/10.3390/v14102126 - 27 Sep 2022
Cited by 1 | Viewed by 1726
Abstract
Humans interact with virus-infected animal hosts, travel globally, and maintain social networks that allow for novel viruses to emerge and develop pandemic potential. There are key lessons-learned from the coronavirus diseases 2019 (COVID-19) pandemic that blood operators can apply to the next pandemic. [...] Read more.
Humans interact with virus-infected animal hosts, travel globally, and maintain social networks that allow for novel viruses to emerge and develop pandemic potential. There are key lessons-learned from the coronavirus diseases 2019 (COVID-19) pandemic that blood operators can apply to the next pandemic. Warning signals to the COVID-19 pandemic included outbreaks of Severe acute respiratory syndrome-related coronavirus-1 (SARS-CoV-1) and Middle East respiratory syndrome-related coronavirus (MERS-CoV) in the prior two decades. It will be critical to quickly determine whether there is a risk of blood-borne transmission of a new pandemic virus. Prior to the next pandemic blood operators should be prepared for changes in activities, policies, and procedures at all levels of the organization. Blood operators can utilize “Plan-Do-Study-Act” cycles spanning from: vigilance for emerging viruses, surveillance activities and studies, operational continuity, donor engagement and trust, and laboratory testing if required. Occupational health and donor safety issues will be key areas of focus even if the next pandemic virus is not transfusion transmitted. Blood operators may also be requested to engage in new activities such as the development of therapeutics or supporting public health surveillance activities. Activities such as scenario development, tabletop exercises, and drills will allow blood operators to prepare for the unknowns of the next pandemic. Full article
(This article belongs to the Special Issue Transfusion Transmitted Viral Infections)
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