Biomarkers of transfusion transmitted occult hepatitis B virus infection: Where are we and what next?

Blood transfusion is a vital procedure, where transfusion-transmitted infection of hepatitis B virus (HBV) remains an important issue, especially from blood donors with occult hepatitis B virus infection (OBI). Occult hepatitis B virus infection is a complex entity to detect using surrogate blood biomarkers for intrahepatic viral transcriptional activity, requiring a continually refined battery of tests utilised for screening. This review aims to critically evaluate the latest advances in the current blood biomarkers to guide the identification of OBI donors and discuss novel HBV markers that could be introduced in future diagnostic practice. Challenges in detecting low HBV surface antigen levels, mutants, and complexes necessitate ultrasensitive multivalent dissociation assays, whilst HBV DNA testing requires improved sensitivity but worsens inaccessibility. Anti-core antibody assays defer almost all potentially infectious donations but have low specificity, and titres of anti-surface antibodies that prevent infectivity are poorly defined with suboptimal sensitivity. The challenges associated with these traditional blood HBV markers create an urgent need for alternative biomarkers that would help us better understand the OBI. Emerging viral biomarkers, such as pre-genomic RNA and HBV core-related antigen, immunological HBV biomarkers of T-cell reactivity and cytokine levels, and host biomarkers of microRNA and human leucocyte antigen molecules, present potential advances to gauge intrahepatic activity more accurately. Further studies on these markers may uncover an optimal diagnostic algorithm for OBI using quantification of various novel and traditional blood HBV markers. Addressing critical knowledge gaps identified in this review would decrease the residual risk of transfusion-transmitted HBV infection without compromising the sustainability of blood supplies

Genetic characterisation of human Coxsackievirus A6 variants associated with atypical hand, foot and mouth disease; a potential role of recombination in emergence and pathogenicity

Human coxsackievirus A6 (CVA6) is an enterically transmitted enterovirus. Until recently, CVA6 infections were considered as being of minor clinical significance, and only rarely aetiologically linked with hand, foot and mouth disease (HFMD) associated with other species A enteroviruses (particularly EV71 and CVA16). From 2008 onwards, however, CVA6 infections have been associated with several outbreaks worldwide of atypical HFMD (aHFMD) accompanied by a varicelliform rash. We recently reported CVA6-associated eczema herpeticum occurring predominantly in children and young adults in Edinburgh in January and February 2014. To investigate genetic determinants of novel clinical phenotypes of CVA6, we genetically characterized and analysed CVA6 variants associated with eczema herpeticum in Edinburgh in 2014 and those with aHFMD in CAV isolates collected from 2008. A total of eight recombinant forms (RFs) have circulated worldwide over the past 10 years, with the particularly recent appearance of RF-H associated with eczema herpeticum cases in Edinburgh in 2014. Comparison of phylogenies and divergence of complete genome sequences of CVA6 identified recombination breakpoints in 2A–2C, within VP3, and between 5′ untranslated region and VP1. A Bayesian temporal reconstruction of CVA6 evolution since 2004 provided estimates of dates and the actual recombination events that generated more recently appearing recombination groups (RF-E, -F, -G and -H). Associations were observed between recombination groups and clinical presentations of herpangina, aHFMD and eczema herpeticum, but not with VP1 or other structural genes. These observations provided evidence that NS gene regions may potentially contribute to clinical phenotypes and outcomes of CVA6 infection

Absence of detectable monkeypox virus DNA in 11,000 English blood donations during the 2022 outbreak

BACKGROUND: A large, worldwide outbreak of mpox (formerly referred to as monkeypox) involving mainly men who have sex with men commenced in May 2022. We evaluated the frequency of positivity for the causative agent, monkeypox virus (MPXV), in blood donations collected in August 2022, during the outbreak period in Southern England. METHODS/MATERIALS: The sensitivity and specificity of an MPXV-specific PCR and a generic non-variola orthopoxvirus (NVO) PCR were evaluated using samples from mpox cases and synthetic DNA standards. Residual minipools from nucleic acid testing were obtained from 10,896 blood donors in Southern England, with 21% from London. RESULTS: MPXV and NVO PCRs were both capable of detection of single copies of target sequence with calculated limits of detection (LOD)90  s of 2.3 and 2.1 DNA copies and analytical sample sensitivities of 46 and 42 MPXV DNA copies/ml, respectively. 454 minipools produced from 10,896 unique donors were assayed for MPXV DNA by both methods. No positive minipools were detected by either PCR. CONCLUSIONS: Although blood donors are unrepresentative of the UK population in terms of MPXV infection risk, the uniformly negative MPXV DNA testing results provide reassurance that MPXV viraemia and potential transmission risk were rare or absent in donors during the outbreak period. Minipools from blood donors allow rapid implementation of large-scale population-based screening for emerging pathogens and represent an important resource for pandemic preparedness

Blood donation screening for hepatitis B virus core antibodies: The importance of confirmatory testing and initial implication for rare blood donor groups

Background and Objectives: Exclusion of blood donors with hepatitis B virus (HBV) core antibodies (anti‐HBc) prevents transfusion‐transmitted HBV infection but can lead to significant donor loss. As isolated anti‐HBc positivity does not always indicate true past HBV infection, we have investigated the effectiveness of confirmatory anti‐HBc testing and the representation of rare blood groups in anti‐HBc‐positive donors. Materials and Methods: Three hundred ninety‐seven HBV surface antigen‐negative and anti‐HBc initially reactive blood donor samples were tested by five different anti‐HBc assays. Results: Eighty percentage of samples reactive in Architect anti‐HBc assay were positive by the Murex assay and anti‐HBc neutralization. Eleven out of 397 samples showed discordant results in supplementary testing from the Murex confirmatory test result, and five remained undetermined following extensive serological testing. Thirty‐eight percentage of anti‐HBc‐positive donors identified as minority ethnic groups compared with 11% representation in anti‐HBc‐negative donors (p < 0.0001); the frequency of the Ro blood group in anti‐HBc‐positive donors was 18 times higher in non‐white ethnic groups. Conclusion: Using two anti‐HBc assays effectively enabled the identification of HBV‐exposed and potentially infectious donors, their deferral and potential clinical follow‐up. However, the exclusion of confirmed anti‐HBc‐positive donors will still impact the supply of rare blood such as Ro

The Relationship Between SARS-CoV-2 Neutralizing Antibody Titers and Avidity in Plasma Collected From Convalescent Nonvaccinated and Vaccinated Blood Donors

Convalescent plasma (CP) treatment of coronavirus disease 2019 (COVID-19) has shown significant therapeutic effect when administered early (eg, Argentinian trial showing reduced hospitalization) but has in general been ineffective (eg, REMAP-CAP trial without improvement during hospitalization). To investigate whether the differences in CP used could explain the different outcomes, we compared neutralizing antibodies, anti-spike IgG, and avidity of CP used in the REMAP-CAP and Argentinian trials and in convalescent vaccinees. We found no difference between the trial plasmas, emphasizing initial patient serostatus as treatment efficacy predictor. By contrast, vaccinee CP showed significantly higher titers and avidity, being preferable for future CP treatment. Clinical Trials Registration. NCT02735707 and NCT04479163

Reconstruction of the historic time course of blood‐borne virus contamination of clotting factor concentrates, 1974–1992

Factor VIII and IX clotting factor concentrates manufactured from pooled plasma have been identified as potent sources of virus infection in persons with hemophilia (PWHs) in the 1970s and 1980s. To investigate the range and diversity of viruses over this period, we analysed 24 clotting factor concentrates for several blood‐borne viruses. Nucleic acid was extracted from 14 commercially produced clotting factors and 10 from nonremunerated donors, preserved in lyophilized form (expiry dates: 1974–1992). Clotting factors were tested by commercial and in‐house quantitative PCRs for blood‐borne viruses hepatitis A, B, C and E viruses (HAV, HBV, HCV, HEV), HIV‐ types 1/2, parvoviruses B19V and PARV4, and human pegiviruses types 1 and 2 (HPgV‐1,‐2). HCV and HPgV‐1 were the most frequently detected viruses (both 14/24 tested) primarily in commercial clotting factors, with frequently extremely high viral loads in the late 1970s–1985 and a diverse range of HCV genotypes. Detection frequencies sharply declined following introduction of virus inactivation. HIV‐1, HBV, and HAV were less frequently detected (3/24, 1/24, and 1/24 respectively); none were positive for HEV. Contrastingly, B19V and PARV4 were detected throughout the study period, even after introduction of dry heat treatment, consistent with ongoing documented transmission to PWHs into the early 1990s. While hemophilia treatment is now largely based on recombinant factor VIII/IX in the UK and elsewhere, the comprehensive screen of historical plasma‐derived clotting factors reveals extensive exposure of PWHs to blood‐borne viruses throughout 1970s‐early 1990s, and the epidemiological and manufacturing parameters that influenced clotting factor contamination

Convalescent plasma therapy for persistent hepatitis E virus infection

No abstract available

High Seroprevalence of Enterovirus Infections in Apes and Old World Monkeys

To estimate population exposure of apes and Old World monkeys in Africa to enteroviruses (EVs), we conducted a seroepidemiologic study of serotype-specific neutralizing antibodies against 3 EV types. Detection of species A, B, and D EVs infecting wild chimpanzees demonstrates their potential widespread circulation in primates