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Article ; Online: Monitoring viral genomic sequences in transfusion-transmitted viruses.

Candotti, Daniel / Drews, Steven J / Faddy, Helen M

2023 Volume 118, Issue 7, Page(s) 551–558

Abstract: Background and objectives: Monitoring genomic sequences of blood-borne viruses infecting blood donors enables blood operators to undertake molecular epidemiology, confirm transfusion transmission and assess and characterize molecular and serological ... ...

Abstract	Background and objectives: Monitoring genomic sequences of blood-borne viruses infecting blood donors enables blood operators to undertake molecular epidemiology, confirm transfusion transmission and assess and characterize molecular and serological screening assays. The purpose of the study was to determine how blood operators globally value viral diversity surveillance and to assess its impact. Materials and methods: An electronic questionnaire was developed and circulated to members of the International Society of Blood Transfusion-transmitted infectious diseases working party. Responses were compiled and complete data sets were analysed. Results: Ninety-seven percent of respondents agreed that monitoring viral genomic sequences was important to blood operators and the transfusion community. However, only 47% of respondents are currently doing this monitoring. The main limitations reported were a lack of financial resources and expertise. Sequencing techniques, primarily next-generation sequencing and also Sanger sequencing, were considered most appropriate, with the preferred option for testing being regional or national reference centres. Respondents agreed that engagement with public health authorities needs to be enhanced. Conclusion: Monitoring genomic sequences of blood-borne viruses is widely considered important by the transfusion community because of its direct applications for transfusion safety, and beyond for public health in general. Therefore, there is a need to strengthen collaboration between blood operators and public health authorities. While national and regional reference centres may be the most appropriate structure for such testing, international collaborations should not be overlooked. Overcoming financial barriers will be an important hurdle for many.
MeSH term(s)	Humans ; Torque teno virus ; Transfusion Reaction ; Blood Transfusion ; Viruses/genetics ; Genomics ; Blood Donors
Language	English
Publishing date	2023-06-01
Publishing country	England
Document type	Journal Article
ZDB-ID	80313-3
ISSN	1423-0410 ; 0042-9007
ISSN (online)	1423-0410
ISSN	0042-9007
DOI	10.1111/vox.13444
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Article ; Online: Human Herpesvirus 8 in Australia: DNAemia and Cumulative Exposure in Blood Donors.

Speicher, David J / Fryk, Jesse J / Kashchuk, Victoria / Faddy, Helen M / Johnson, Newell W

Viruses

2022 Volume 14, Issue 10

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. ... ...

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% 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.
MeSH term(s)	Humans ; Herpesvirus 8, Human/genetics ; Blood Donors ; Australia/epidemiology ; Sarcoma, Kaposi/epidemiology ; Castleman Disease/complications ; Herpesviridae Infections
Language	English
Publishing date	2022-10-03
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14102185
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Article ; Online: Detection of Leishmania (Mundinia) macropodum (Kinetoplastida: Trypanosomatidae) and heterologous Leishmania species antibodies among blood donors in a region of Australia with marsupial Leishmania endemicity.

Panahi, Elina / Stanisic, Danielle I / Skinner, Eloise B / Faddy, Helen M / Young, Megan K / Herrero, Lara J

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases

2022 Volume 130, Page(s) 42–47

Abstract: Objectives: The Australian Leishmania (Mundinia) macropodum parasite causes cutaneous leishmaniasis among marsupial species. Although cutaneous leishmaniasis is a major public health burden worldwide, it is not clear if humans are naturally exposed to ... ...

Abstract	Objectives: The Australian Leishmania (Mundinia) macropodum parasite causes cutaneous leishmaniasis among marsupial species. Although cutaneous leishmaniasis is a major public health burden worldwide, it is not clear if humans are naturally exposed to the unique L. macropodum. To assess whether humans have an immunoglobulin (Ig) G response to L. macropodum, we examined anti-Leishmania antibodies among humans residing in a region of marsupial Leishmania endemicity in Australia. Methods: Using a serological enzyme-linked immunosorbent assay, we characterized Leishmania-specific IgG and IgG subclass responses to soluble Leishmania antigen from L. macropodum, and other Leishmania species (L. donovani, L. major, and L. mexicana) in 282 blood donor samples. Results: We found that 20.57% of individuals demonstrated a positive total IgG response to L. macropodum. For individuals with antibodies to soluble Leishmania antigen from one Leishmania species, there was no increased likelihood of recognition to other Leishmania species. For samples with detectable L. macropodum IgG, IgG1 and IgG2 were the prevalent subclasses detected. Conclusion: It is not yet clear whether the IgG antibody detection in this study reflects exposure to Leishmania parasites or a cross-reactive immune response that was induced against an unrelated immunogen. Future studies should investigate whether L. macropodum can result in a viable infection in humans.
MeSH term(s)	Humans ; Leishmania ; Kinetoplastida ; Blood Donors ; Australia/epidemiology ; Leishmaniasis, Cutaneous/epidemiology ; Leishmaniasis, Cutaneous/veterinary ; Leishmaniasis, Cutaneous/diagnosis ; Immunoglobulin G
Chemical Substances	Immunoglobulin G
Language	English
Publishing date	2022-10-12
Publishing country	Canada
Document type	Journal Article
ZDB-ID	1331197-9
ISSN	1878-3511 ; 1201-9712
ISSN (online)	1878-3511
ISSN	1201-9712
DOI	10.1016/j.ijid.2022.10.006
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Zs.A 4516: Show issues

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Article ; Online: Inactivation of SARS-CoV-2 infectivity in platelet concentrates or plasma following treatment with ultraviolet C light or with methylene blue combined with visible light.

Hobson-Peters, Jody / Amarilla, Alberto A / Rustanti, Lina / Marks, Denese C / Roulis, Eileen / Khromykh, Alexander A / Modhiran, Naphak / Watterson, Daniel / Reichenberg, Stefan / Tolksdorf, Frank / Sumian, Chryslain / Seltsam, Axel / Gravemann, Ute / Faddy, Helen M

Transfusion

2023 Volume 63, Issue 2, Page(s) 288–293

Abstract: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unlikely to be a major transfusion-transmitted pathogen; however, convalescent plasma is a treatment option used in some regions. The risk of transfusion-transmitted infections ... ...

Abstract	Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unlikely to be a major transfusion-transmitted pathogen; however, convalescent plasma is a treatment option used in some regions. The risk of transfusion-transmitted infections can be minimized by implementing Pathogen Inactivation (PI), such as THERAFLEX MB-plasma and THERAFLEX UV-Platelets systems. Here we examined the capability of these PI systems to inactivate SARS-CoV-2. Study design and methods: SARS-CoV-2 spiked plasma units were treated using the THERAFLEX MB-Plasma system in the presence of methylene blue (~0.8 μmol/L; visible light doses: 20, 40, 60, and 120 [standard] J/cm Results: Treatment of spiked plasma with the THERAFLEX MB-Plasma system resulted in an average ≥5.03 log Conclusions: SARS-CoV-2 infectivity was reduced in plasma and platelets following treatment with the THERAFLEX MB-Plasma and THERAFLEX UV-Platelets systems, to the limit of detection, respectively. These PI technologies could therefore be an effective option to reduce the risk of transfusion-transmitted emerging pathogens.
MeSH term(s)	Humans ; Methylene Blue/pharmacology ; SARS-CoV-2 ; COVID-19/therapy ; COVID-19 Serotherapy ; Light ; Ultraviolet Rays ; Blood Platelets ; Virus Inactivation
Chemical Substances	Methylene Blue (T42P99266K)
Language	English
Publishing date	2023-01-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.17238
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Zs.A 284: Show issues

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Article ; Online: Packed Red Blood Cell Transfusion Modulates Myeloid Dendritic Cell Activation and Inflammatory Response In Vitro.

Ki, Katrina K / Faddy, Helen M / Flower, Robert L / Dean, Melinda M

Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research

2018 Volume 38, Issue 3, Page(s) 111–121

Abstract: Transfusion of packed red blood cells (PRBCs) modulates patients' immune responses and clinical outcomes; however, the underpinning mechanism(s) remain unknown. The potential for PRBC to modulate myeloid dendritic cells (mDC) and blood DC antigen 3 was ... ...

Abstract	Transfusion of packed red blood cells (PRBCs) modulates patients' immune responses and clinical outcomes; however, the underpinning mechanism(s) remain unknown. The potential for PRBC to modulate myeloid dendritic cells (mDC) and blood DC antigen 3 was assessed using an in vitro transfusion model. In parallel, to model processes activated by viral or bacterial infection, toll-like receptor agonists polyinosinic:polycytidylic acid or lipopolysaccharide were added. Exposure to PRBC upregulated expression of CD83 and downregulated CD40 and CD80 on both DC subsets, and it suppressed production of interleukin (IL)-6, IL-8, IL-12, tumor necrosis factor-α, and interferon-gamma-inducible protein-10 by these cells. Similar effects were observed when modeling processes activated by concurrent infection. Furthermore, exposure to PRBC at date of expiry was associated with more pronounced effects in all assays. Our study suggests PRBC have an impact on recipient DC function, which may result in failure to establish an appropriate immune response, particularly in patients with underlying infection.
MeSH term(s)	Cytokines/blood ; Cytokines/immunology ; Dendritic Cells/immunology ; Erythrocyte Transfusion ; Erythrocytes/immunology ; Humans ; Inflammation/blood ; Inflammation/immunology
Chemical Substances	Cytokines
Language	English
Publishing date	2018-03-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1226675-9
ISSN	1557-7465 ; 1079-9907
ISSN (online)	1557-7465
ISSN	1079-9907
DOI	10.1089/jir.2017.0099
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Article ; Online: Low Genetic Diversity of Hepatitis B Virus Surface Gene amongst Australian Blood Donors.

Phan, Ngoc Minh Hien / Faddy, Helen M / Flower, Robert L / Dimech, Wayne J / Spann, Kirsten M / Roulis, Eileen V

Viruses

2021 Volume 13, Issue 7

Abstract: Variants in the small surface gene of hepatitis B virus (HBV), which codes for viral surface antigen (HBsAg), can affect the efficacy of HBsAg screening assays and can be associated with occult HBV infection (OBI). This study aimed to characterise the ... ...

Abstract	Variants in the small surface gene of hepatitis B virus (HBV), which codes for viral surface antigen (HBsAg), can affect the efficacy of HBsAg screening assays and can be associated with occult HBV infection (OBI). This study aimed to characterise the molecular diversity of the HBV small surface gene from HBV-reactive Australian blood donors. HBV isolates from 16 HBsAg-positive Australian blood donors' plasma were sequenced and genotyped by phylogenies of viral coding genes and/or whole genomes. An analysis of the genetic diversity of eight HBV small surface genes from our 16 samples was conducted and compared with HBV sequences from NCBI of 164 international (non-Australian) blood donors. Genotypes A-D were identified in our samples. The region of HBV small surface gene that contained the sequence encoding the 'a' determinant had a greater genetic diversity than the remaining part of the gene. No escape mutants or OBI-related variants were observed in our samples. Variant call analysis revealed two samples with a nucleotide deletion leading to truncation of polymerase and/or large/middle surface amino acid sequences. Overall, we found that HBV small surface gene sequences from Australian donors demonstrated a lower level of genetic diversity than those from non-Australian donor population included in the study.
MeSH term(s)	Australia/epidemiology ; Blood Donors/statistics & numerical data ; DNA, Viral/genetics ; Genetic Variation ; Genotype ; Hepatitis B/epidemiology ; Hepatitis B/virology ; Hepatitis B Surface Antigens/genetics ; Hepatitis B virus/classification ; Hepatitis B virus/genetics ; Humans ; Mutation
Chemical Substances	DNA, Viral ; Hepatitis B Surface Antigens
Language	English
Publishing date	2021-06-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13071275
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Article: Low Genetic Diversity of Hepatitis B Virus Surface Gene amongst Australian Blood Donors

Phan, Ngoc Minh Hien / Faddy, Helen M. / Flower, Robert L. / Dimech, Wayne J. / Spann, Kirsten M. / Roulis, Eileen V.

Viruses. 2021 June 30, v. 13, no. 7

2021

Abstract	Variants in the small surface gene of hepatitis B virus (HBV), which codes for viral surface antigen (HBsAg), can affect the efficacy of HBsAg screening assays and can be associated with occult HBV infection (OBI). This study aimed to characterise the molecular diversity of the HBV small surface gene from HBV-reactive Australian blood donors. HBV isolates from 16 HBsAg-positive Australian blood donors’ plasma were sequenced and genotyped by phylogenies of viral coding genes and/or whole genomes. An analysis of the genetic diversity of eight HBV small surface genes from our 16 samples was conducted and compared with HBV sequences from NCBI of 164 international (non-Australian) blood donors. Genotypes A–D were identified in our samples. The region of HBV small surface gene that contained the sequence encoding the ‘a’ determinant had a greater genetic diversity than the remaining part of the gene. No escape mutants or OBI-related variants were observed in our samples. Variant call analysis revealed two samples with a nucleotide deletion leading to truncation of polymerase and/or large/middle surface amino acid sequences. Overall, we found that HBV small surface gene sequences from Australian donors demonstrated a lower level of genetic diversity than those from non-Australian donor population included in the study.
Keywords	Hepatitis B virus ; amino acids ; genes ; genetic variation ; genotyping ; phylogeny ; sequence deletion ; surface antigens
Language	English
Dates of publication	2021-0630
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13071275
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Platelet concentrates modulate myeloid dendritic cell immune responses.

Ki, Katrina K / Faddy, Helen M / Flower, Robert L / Dean, Melinda M

Platelets

2017 Volume 29, Issue 4, Page(s) 373–382

Abstract: Platelet transfusion has been reported to modulate the recipients' immune system. To date, the precise mechanism(s) driving poor patient outcomes (e.g., increased rate of mortality, morbidity, infectious complications and prolonged hospital stays) ... ...

Abstract	Platelet transfusion has been reported to modulate the recipients' immune system. To date, the precise mechanism(s) driving poor patient outcomes (e.g., increased rate of mortality, morbidity, infectious complications and prolonged hospital stays) following platelet transfusion are largely undefined. To determine the potential for platelet concentrates (PC) to modulate responses of crucial immune regulatory cells, a human in vitro whole blood model of transfusion was established. Maturation and activation of human myeloid dendritic cells (mDC) and the specialized subset blood DC antigen (BDCA)3
MeSH term(s)	Blood Platelets/metabolism ; Dendritic Cells/immunology ; Humans ; Platelet Transfusion/methods
Language	English
Publishing date	2017-05-15
Publishing country	England
Document type	Journal Article
ZDB-ID	1034283-7
ISSN	1369-1635 ; 0953-7104
ISSN (online)	1369-1635
ISSN	0953-7104
DOI	10.1080/09537104.2017.1306045
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Zs.A 2888: Show issues

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Article ; Online: Estimation of mosquito-borne and sexual transmission of Zika virus in Australia: Risks to blood transfusion safety.

Viennet, Elvina / Frentiu, Francesca D / Williams, Craig R / Mincham, Gina / Jansen, Cassie C / Montgomery, Brian L / Flower, Robert L P / Faddy, Helen M

PLoS neglected tropical diseases

2020 Volume 14, Issue 7, Page(s) e0008438

Abstract: Background: Since 2015, Zika virus (ZIKV) outbreaks have occurred in the Americas and the Pacific involving mosquito-borne and sexual transmission. ZIKV has also emerged as a risk to global blood transfusion safety. Aedes aegypti, a mosquito well ... ...

Abstract	Background: Since 2015, Zika virus (ZIKV) outbreaks have occurred in the Americas and the Pacific involving mosquito-borne and sexual transmission. ZIKV has also emerged as a risk to global blood transfusion safety. Aedes aegypti, a mosquito well established in north and some parts of central and southern Queensland, Australia, transmits ZIKV. Aedes albopictus, another potential ZIKV vector, is a threat to mainland Australia. Since these conditions create the potential for local transmission in Australia and a possible uncertainty in the effectiveness of blood donor risk-mitigation programs, we investigated the possible impact of mosquito-borne and sexual transmission of ZIKV in Australia on local blood transfusion safety. Methodology/principal findings: We estimated 'best-' and 'worst-' case scenarios of monthly reproduction number (R0) for both transmission pathways of ZIKV from 1996-2015 in 11 urban or regional population centres, by varying epidemiological and entomological estimates. We then estimated the attack rate and subsequent number of infectious people to quantify the ZIKV transfusion-transmission risk using the European Up-Front Risk Assessment Tool. For all scenarios and with both vector species R0 was lower than one for ZIKV transmission. However, a higher risk of a sustained outbreak was estimated for Cairns, Rockhampton, Thursday Island, and theoretically in Darwin during the warmest months of the year. The yearly estimation of the risk of transmitting ZIKV infection by blood transfusion remained low through the study period for all locations, with the highest potential risk estimated in Darwin. Conclusions/significance: Given the increasing demand for plasma products in Australia, the current strategy of restricting donors returning from infectious disease outbreak regions to source plasma collection provides a simple and effective risk management approach. However, if local transmission was suspected in the main urban centres of Australia, potentially facilitated by the geographic range expansion of Ae. aegypti or Ae. albopictus, this mitigation strategy would need urgent review.
MeSH term(s)	Aedes/virology ; Animals ; Australia/epidemiology ; Blood Donors ; Blood Safety/standards ; Communicable Diseases, Emerging/epidemiology ; Disease Outbreaks ; Humans ; Models, Biological ; Mosquito Vectors/virology ; Public Health ; Reproducibility of Results ; Sexually Transmitted Diseases, Viral/blood ; Sexually Transmitted Diseases, Viral/epidemiology ; Sexually Transmitted Diseases, Viral/transmission ; Zika Virus/physiology ; Zika Virus Infection/epidemiology ; Zika Virus Infection/transmission ; Zika Virus Infection/virology
Language	English
Publishing date	2020-07-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2727
ISSN (online)	1935-2735
ISSN	1935-2727
DOI	10.1371/journal.pntd.0008438
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Article ; Online: Understanding occult hepatitis C infection.

An, Timothy / Dean, Melinda / Flower, Robert / Tatzenko, Tayla / Chan, Hiu Tat / Kiely, Philip / Faddy, Helen M

Transfusion

2020 Volume 60, Issue 9, Page(s) 2144–2152

Abstract: Background: Occult hepatitis C infection (OCI) is a type of hepatitis C virus (HCV) infection, defined as the presence of HCV RNA in hepatocytes or peripheral blood mononuclear cells (PBMCs) and the absence of HCV RNA in serum.: Study design and ... ...

Abstract	Background: Occult hepatitis C infection (OCI) is a type of hepatitis C virus (HCV) infection, defined as the presence of HCV RNA in hepatocytes or peripheral blood mononuclear cells (PBMCs) and the absence of HCV RNA in serum. Study design and methods: A literature review was conducted to identify articles that characterized OCI as a disease, including its epidemiology, mode of transmission, pattern of infection, progression, and treatment. Results: OCI patients experience a milder degree of inflammatory and cirrhotic changes than patients with chronic hepatitis C. OCI is transmissible parenterally both in vivo and in vitro, however the duration and outcome of OCI remains unclear. OCI is most consistently found in patients with previous hepatitis C disease and hemodialysis patients. Beyond the at-risk populations, OCI has also been demonstrated among healthy individuals and blood donors. Conclusions: This review summarises our current understanding of OCI and suggests areas for further research to improve our understanding of this phenomenon, including a better understanding of its epidemiology and full clinical course. The current understanding of OCI and its clinical implications remain limited. Further standardized detection methods, ongoing surveillance, and investigation of its potential transmissions are required.
MeSH term(s)	Blood Donors ; Hepacivirus/metabolism ; Hepatitis C, Chronic/blood ; Hepatitis C, Chronic/pathology ; Hepatitis C, Chronic/therapy ; Hepatocytes/metabolism ; Hepatocytes/pathology ; Hepatocytes/virology ; Humans ; Leukocytes, Mononuclear/metabolism ; Leukocytes, Mononuclear/pathology ; Leukocytes, Mononuclear/virology ; RNA, Viral/blood ; Renal Dialysis ; Risk Factors
Chemical Substances	RNA, Viral
Language	English
Publishing date	2020-08-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.16006
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