Current approaches to increase blood donations in resource-limited countries.

BACKGROUND: Low- and middle-income countries (LMIC) suffer from chronic or seasonal blood shortage. The first review was published in 2007. METHODS: The review of literature since 2005 presented here uncovered a fairly large number of articles justifying the grouping of blood donation issues into five geographical areas sharing common background. These are Sub-Saharan Africa (SSA), Muslim countries, India, China/South East Asia and Latin America/Caribbean islands (LA&C). RESULTS: SSA countries start collecting at 16-18 years of age in schools where female donors can be reached better than in other settings. Community-oriented culture favours family donors who need, similar to volunteer non-remunerated donors (VNRD), to be actively induced to repeat donation. Muslim countries share the contradiction of religion encouraging blood donation but restrain women from donating. The active involvement of religious leaders and the progressive easing of female participation are the keys to increasing blood donation. In India, 'social duty' is a major inducement to blood donation but also benefits and rewards. Ways of involving female donors by reducing the donation age to 16 years and providing donor education in schools need to be considered. In China and East Asia, the option of small-volume donation impairs blood collection without being justified by scientific evidence but is a concession to culture. Reducing the donation age would also help the supply. In LA&C, the concept of 'social capital' was developed as a complement or alternative to the theory of planned behaviour. CONCLUSIONS: Strategies to improve blood donation and repeat donation should be innovative and adapted to local or regional culture and environment.

Incidence of hepatitis B virus infection in young Chinese blood donors born after mandatory implementation of neonatal hepatitis B vaccination nationwide.

This study was carried out to determine the incidence of hepatitis B virus (HBV) infection in the young generation born after mandatory implementation of hepatitis B vaccination since 1992. Repeat blood donors born between 1992 and 1997 were enrolled, who gave blood at least twice during the past 3 years. Donors were tested for HBV infection markers of HBsAg, anti-HBc, anti-HBs and viral DNA by immunoassays (EIAs) and nucleic acid tests (NAT). A total of 14 937 pre-donation screening qualified young repeat donors aged 18-23 years were tested with 9 (0.06%) being HBsAg by EIA and 10 (1:1494) HBV DNA positive by Ultrio NAT (10.4 IU/mL), respectively. HBV DNA was further detected in 1:192 (9/1732) anti-HBc+ repeat donors with Ultrio Plus NAT (3.4 IU/mL). Most cases were identified as occult HBV infection (OBI). Of 14 937 repeat donors, 20.9% were anti-HBc+ positive, while approximately 50% of 12 024 repeat donors were anti-HBs negative or had levels <100 IU/L. HBsAg+ or OBI strains were classified as wild type of genotype B or genotype C. Incident HBV infection in repeat donors was approximately 1:18.5 person-years (1.1%/year) but significantly less frequent in donors with confirmed HBV vaccination (2.4%-3.3%) than those unsure of vaccination status (10.5%; P = .0023). Hepatitis B virus vaccination appears largely protective of HBV infection, but incidence of infections increases in young adults with mostly undetectable or low anti-HBs or occasionally high anti-HBs. A boost of hepatitis B vaccine for adolescents prior to age 18 years may reduce HBV infection, and implementation of more sensitive NAT in blood donation screening may improve HBV safety in blood transfusion.

Pathogen reduction of whole blood: utility and feasibility.

OBJECTIVES: To collect information on pathogen reduction applied to whole blood. BACKGROUND: Pathogen reduction (PR) of blood components has been developed over the past two decades, and pathogen-reduced fresh-frozen plasma and platelet concentrates are currently in clinical use. High cost and incomplete coverage of components make PR out of reach for low- and middle-income countries (LMIC). However, should PR become applicable to whole blood (WB), the main product transfused in sub-Saharan Africa, and be compatible with the preparation of clinically suitable components, cost would be minimised, and a range of safety measures in place at high cost in developed areas would become redundant. METHODS: All articles called with "pathogen reduction", "pathogen inactivation" and "whole blood" were retrieved from Medline. References in articles were utilised. RESULTS: One such PR technology (PRT) applied to WB has been developed and has shown efficacious against viruses, bacteria and parasites in vitro; and has been able to inactivate nucleated blood cells whilst retaining the ability to prepare components with acceptable characteristics. The efficacy of this WB PRT has been demonstrated in vivo using the inactivation of Plasmodium falciparum as a model and showing a high degree of correlation between in vitro and in vivo data. Obtaining further evidence of efficacy on other suitable targets is warranted. Shortening of the process, which is currently around 50 min, or increasing the number of units simultaneously processed would be necessary to make PRT WB conducive to LMIC blood services' needs. CONCLUSIONS: Even if not 100% effective against agents that are present in high pathogen load titres, WB PRT could massively impact blood safety in LMIC by providing safer products at an affordable cost.

Characterization of major histocompatibility complex class I allele polymorphisms in common marmosets.

Currently, little information is available for major histocompatibility complex (MHC)-I that conditions the T-cell response of marmosets. In this study, 471 clones of MHC-I cDNA sequences were isolated from 12 marmosets. Twenty full-length sequences of class I G (Caja-G) alleles were obtained from these marmosets, 15 of them were novel. Among these 20 Caja-G alleles, 10 were found in individual animals while the rests were in two to four marmosets, but none was common to all animals. Ten marmosets possessed one to three Caja-G alleles, and two marmosets carried five or six alleles, which suggested that the Caja-G locus was duplicated in marmoset's genome. The high polymorphisms of Caja-G sequences provided important information helpful for understanding the cellular immune response in virus-infected marmosets.

Deuterium uptake in magnetic-fusion devices with lithium-conditioned carbon walls.

Lithium wall conditioning has lowered hydrogenic recycling and dramatically improved plasma performance in many magnetic-fusion devices. In this Letter, we report quantum-classical atomistic simulations and laboratory experiments that elucidate the roles of lithium and oxygen in the uptake of hydrogen in amorphous carbon. Surprisingly, we show that lithium creates a high oxygen concentration on a carbon surface when bombarded by deuterium. Furthermore, surface oxygen, rather than lithium, plays the key role in trapping hydrogen.

Hepatitis E virus infection in Ghanaian blood donors - the importance of immunoassay selection and confirmation.

BACKGROUND AND OBJECTIVES: Hepatitis E virus (HEV) infection is emerging as a potential new threat to blood safety after several cases of transfusion-transmission were reported from non-epidemic countries. On the basis of seroprevalence data, HEV is endemic in Ghana where poor sanitary conditions and regular flooding are prevalent. However, no data are available for HEV prevalence in blood donors. MATERIALS AND METHODS: Plasma samples from 239 Ghanaian blood donors were tested for anti-HEV IgG and IgM by ELISA (two and three assays, respectively) and Western blot (recomLine) and for HEV-RNA by RT-qPCR. RESULTS: All donors were RNA negative. Results from the different serological assays were discrepant: reactivity in two of the three IgM assays was correlated with elevated IgM levels, but the discrepancies between IgG assays were unrelated to the donors' IgG levels and more likely related to assay sensitivity. Fourteen samples (5·9%) were anti-HEV IgM reactive and 11 samples (4·6%) anti-HEV IgG reactive in at least two serological assays from different manufacturers. CONCLUSIONS: (a) In the absence of accepted confirmatory assays, it is crucial to confirm anti-HEV reactive samples with an alternative assay, especially when the population tested carries high levels of immunoglobulin M. (b) Although asymptomatic HEV infections are common in Ghanaian blood donors, currently, it does not seem to be a major risk to blood safety.

Appropriateness of blood product transfusion in the Obstetrics and Gynaecology (O&G) department of a tertiary hospital in West Africa.

BACKGROUND: Misuse of blood by clinicians was suggested to explain blood shortage in sub-Saharan Africa although based on little evidence. This study evaluated whether routine halving (restricted) of blood requests was justified. STUDY DESIGN AND METHODS: On alternated days for 3 months in 2011-2012, restricted or full blood product supply [whole blood (WB), red cell concentrate (RCC)] was provided to the Obstetrics & Gynaecology department (O&G). Patient age, haemoglobin (Hb) level pre- and post-transfusion, clinical condition, blood products request and supply, transfused and returned, clinical outcome were collated. RESULTS: Five hundred and nineteen patients (249 restricted and 270 full supply) received 1001 blood products (94.6% WB, 6.4% RCC). Clinical conditions were severe peri-partum bleeding (72.4%) requiring emergency transfusion (82%) whilst 27.6% of total transfusion was for anaemia, 18% being moderate (8-10 g dL(-1) ). Pre-transfusion Hb level was <6 g dL(-1) in 36.7%, 6-8 g dL(-1) 29.1% and ≥ 8 g dL(-1) in 33.2% of cases. Fifty-five percent of the transfused blood was stored ≤ 1 week. Restricted supply triggered additional request (40%) compared to 10% in full supply mode. Whether with restricted or full supply, blood requests, supply and units transfused/patient were similar (restricted 2.3 and 2.1 unit patient(-1) and full 2.9 and 2.3 unit patient(-1) , respectively). Fatal clinical outcome was 3.1% evenly distributed between supply modes and transfusion reactions 0.8%. CONCLUSIONS: O&G clinicians order blood according to clinical need and transfuse 85% of the products supplied. Product supply did not significantly affect use although appropriateness of transfusion was difficult to assess.

A liquid metal dropper for experiments on the wettability of liquid metals on plasma facing components.

A liquid metal dropper has been developed as a part of the Ion-Gas-Neutral Interactions with Surfaces 2 (IGNIS-2) facility at The Pennsylvania State University. The dropper has the capability of directly applying drops to candidate plasma facing materials for nuclear fusion reactors to enable measurements of their liquid metal wetting properties. The results presented here are specific to the use of lithium in the dropper. This paper discusses the design choices of the liquid metal dropper and its chamber, including the heating and temperature control and the dropper's motorized operation. Lithium drops of masses ranging from 0.05 g up to 0.13 g, equivalent to drop diameters between 5.6 mm to 1 cm, have been consistently dispensed by the dropper. A new algorithm is developed and used to automate the analysis of the contact angle between the liquid drops and substrate material for efficient analysis of video data recorded to study the wetting properties of candidate plasma-facing components.

Current incidence and residual risk of HIV, HBV and HCV at Canadian Blood Services.

Estimates of the viral residual risk should be updated to reflect current incidence of infection in blood donors. Incidence rates were estimated for allogeneic whole-blood donations made to Canadian Blood Services from 2006 to 2009 based on transmissible disease conversions of repeat donations within a 3-year period. Residual risk was estimated as the incidence multiplied by the window period. The residual risk of HIV was 1 per 8 million donations, HCV 1 per 6·7 million donations and HBV 1 per 1·7 million donations. The residual risk remains low and has decreased for HCV since our previous estimates due to reduced incidence.

Diversity of hepatitis B virus infecting Malaysian candidate blood donors is driven by viral and host factors.

Malaysia is a medium endemic country for hepatitis B virus (HBV) infection but little is known about HBV strains circulating in Malaysian blood donors. Viral load, HBsAg concentrations and nested PCR products from 84 HBV surface antigen (HBsAg) positive samples were analysed in detail. Median viral load was 3050 IU/mL and median HBsAg 1150 IU/mL. Fifty-six full genome, 20 pre-S/S, 1 S gene and six basic core promoter/precore-only sequences were obtained. Genotypes B and C were present at a ratio of 2:1, and two genotype D samples were obtained, both from donors of Indian background. Phylogenetically, genotype B was more diverse with subgenotypes B2-5, B7 and B8 present, while most genotype C strains were from subgenotype C1. Genotypes B and C were equally frequent in ethnic Malays, but 80% of strains from Chinese were genotype B. HBsAg concentrations were higher in genotype C than in genotype B, in Chinese than Malays and in donors under the age of 30. HBV vaccine escape substitutions (P120S/T, I126N and G145G) were present in six strains. In the large surface protein, immuno-inactive regions were more mutated than CD8 epitopes and the major hydrophilic region. Strains of genotype B or from ethnic Malays had higher genetic diversity than strains of genotype C or from Chinese donors. Hence HBV strains circulating in Malaysia are phylogenetically diverse reflecting the ethnic mix of its population. Ethnic Malays carry lower HBsAg levels and higher genetic diversity of the surface antigen, possibly resulting in more effective immune control of the infection.

Development of the materials analysis and particle probe for Proto-MPEX.

The Prototype Material Plasma Exposure eXperiment (Proto-MPEX) is a linear plasma device being used in plasma source research and development (R&D) for the proposed MPEX. Once the R&D is completed, this device can also be used to perform plasma-material interaction studies. To perform these studies, a new materials analysis and particle probe (MAPP) has been constructed. The MAPP's components are a sample holder and manipulator and a custom vacuum chamber with ports to facilitate surface chemistry diagnostics. The MAPP's overall design enables rapid sample turnaround and in vacuo surface characterization. The surface analysis vacuum chamber has ports for x-ray photoelectron spectroscopy, thermal desorption spectroscopy, back-scatter ion scattering spectroscopy, forward-scatter ion scattering spectroscopy, and direct recoil spectroscopy. The sample manipulator and holder is a Lesker/UHV Multi-Centre Analytical Stage, which is used to place the samples in the exposure region of the Proto-MPEX or the analysis position in the MAPP vacuum chamber. The sample holder has a heating capability of up to 1200 °C for heated exposure and for desorption studies. In this work, we present the MAPP's design and the first tungsten sample exposure with ex situ analysis that shows a surface deposition layer on the exposed target, highlighting the need for additional in situ measurements on the Proto-MPEX.

HBV reactivation after fludarabine chemotherapy identified on investigation of suspected transfusion-transmitted Hepatitis B virus.

BACKGROUND & AIMS: Multi-transfused patients often receive treatments inducing various levels of immunodeficiency. Acute viral infections may then be attributed either to transfusion-transmitted infection (TTI) or reactivation of a past infection. METHODS: A patient with chronic lymphocytic leukemia (CLL) who had >250 blood donor exposures developed acute Hepatitis B virus (HBV) infection. Routine donor testing for HB core antibodies (anti-HBc) was in place in the relevant period and investigations undertaken on the blood donors were negative. RESULTS: Review of historical, molecular, and antigenic evidence demonstrated reactivation of a recovered HBV infection dating >30 years and the selection of a rare escape mutant that briefly replicated and caused acute liver disease. This mutant was unreactive with several HBsAg assays and poorly reactive with an HBV vaccine plasma. Correcting the C139Y substitution by site directed mutagenesis of recombinant surface proteins re-established assay reactivity. CONCLUSIONS: Fludarabine, but not Chlorambucil, appeared sufficiently immunosuppressive to trigger reactivation despite low levels of neutralizing antibodies. Differentiating between TTI and reactivation of HBV becomes more challenging with the increasing frequency of immunocompromised blood recipients. Chemotherapy with Fludarabine alone should be considered as carrying high risk of viral reactivation. Pre-treatment testing and peripheral blood sample archiving may be indicated in HBsAg negative patients.

Molecular and serological characterization of hepatitis B virus genotype A and D infected blood donors in Poland.

Hepatitis B virus (HBV) genotypes have distinct geographical distributions and influence severity of clinical outcome and response to antiviral therapies. HBV polymorphism in HBV surface antigen (HBsAg) positive first time blood donors from Poland was examined. HBV serological markers and HBV DNA were tested in 170 samples. Whole genome (n = 53) or specific region sequences: pre-S/S and basic core promoter/precore (BCP/PC) region (91 and 154 samples, respectively) were phylogenetically analyzed. The median age of infected donors was 21 years. Anti-HBs, anti-HBe and hepatitis B e antigen were detected in 5%, 92.4% and 10.5% of tested donors, respectively. The HBV DNA load ranged between unquantifiable and 3.1 x 10(10) IU/mL (median: 4.10 x 10(3) IU/mL). Genotypes A2 (81.2%) and D (18.8%) co-circulated. Phylogenetic analyses revealed differences between the genotypes. Viral load and level of HBsAg tended to be lower in genotype D. The median HBsAg/HBV DNA ratio expressed in IU/mL was one for both genotypes, but very low or very high ratios appeared more frequent in genotype D infections. Higher amino acid variability in the surface proteins (median: 4%vs 1.5%; P = 0.01) and in the major hydrophilic region was observed in genotype D (P = 0.01). BCP/PC region analysis revealed the double mutation 1762T/1764A in 49/125 (39.2%) genotype A2 and 6/29 (20.7%) genotype D strains (P = 0.08). Mutations in PC and BCP regions correlated neither with HBsAg nor HBV DNA levels. HBV genotype A2 is dominant in HBsAg positive donors in Poland. Minority genotype D strains are significantly more substituted than genotype A2 strains potentially affecting the course of infection.

Fatal outcome of a hepatitis B virus transfusion-transmitted infection.

BACKGROUND AND OBJECTIVES: In 2008, hepatitis B virus (HBV) DNA testing was not yet mandatory for the screening of blood donations in Switzerland. At that time, HBsAg was the only specific mandatory marker for HBV. The importance of high sensitivity for HBV NAT screening is shown. MATERIALS AND METHODS: Donor and recipient of a transfusion-transmitted HBV infection were followed up. Multiple samples were tested for HBV serological and molecular markers. RESULTS: At donation, the donor appeared healthy, HBsAg was negative and had a normal ALAT level. Ten weeks later, clinical symptoms suggested acute HBV infection as was confirmed with positive HBsAg, HBeAg, anti-HBc IgG, anti-HBc IgM and anti-HBe. The archived sample from the original donation was negative for anti-HBc, but positive for HBV DNA (17 IU/ml). A recipient transfused with the red cell concentrate was HBV DNA positive (3100 IU/ml) 3 months post-transfusion. After five months, HBsAg, HBeAg, anti-HBc and HBV DNA (1.1 x 10(11) IU/ml) were positive. Two weeks later, the patient died from complications associated with HBV infection and his underlying bone marrow disease. CONCLUSIONS: The present case illustrates the importance of introducing highly sensitive HBV NAT screening strategy to prevent possible HBV transfusion-transmitted infections from donors with low viral load.

Fostering repeat donations in Ghana.

INTRODUCTION: Most African countries are challenged in recruiting and retaining voluntary blood donors by cost and other complexities and in establishing and implementing national blood policies. The availability of replacement donors who are a cheaper source of blood has not enhanced repeat voluntary donor initiatives. METHODS: An overview of activities for recruiting and retaining voluntary blood donors was carried out. Donor records from mobile sessions were reviewed from 2002 to 2008. RESULTS AND DISCUSSION: A total of 71,701 blood donations; 45,515 (63.5%) being voluntary donations with 11,680 (25%) repeat donations were collected during the study period. Donations from schools and colleges contributed a steady 60% of total voluntary whilst radio station blood drives increased contribution from 10 to 27%. Though Muslim population is less than 20%, blood collection was above the 30-donation cost-effectiveness threshold with a repeat donation trend reaching 60%. In contrast Christian worshippers provided <25 unit/session and 30% repeat donations. Repeat donation trends amongst school donors and radio blood drives were 20% and 70% respectively. CONCLUSION: Repeat donations rates have been variable amongst different blood donor groups in Kumasi, Ghana. The impact of community leaders in propagating altruism cannot be overemphasized. Programs aiming at motivating replacement donors to be repeat donors should be developed and assessed.

Publisher Correction: Effect of deuterium irradiation on graphite boronized in the NSTX-U tokamak.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

In vivo activity against HIV and favorable toxicity profile of 2',3'-dideoxyinosine.

The purine analog 2',3'-dideoxyinosine (ddI), which has anti-retroviral activity in vitro was administered for up to 42 weeks to 26 patients with acquired immunodeficiency syndrome (AIDS) or severe AIDS-related complex (ARC). Ten of these individuals were AZT-intolerant. Eight dose regimens were studied. The drug was orally bioavailable and penetrated into the cerebrospinal fluid (CSF). Comparatively little evidence of an effect against human immunodeficiency virus (HIV) was seen at the lowest four doses. However, patients in the four highest dose groups (ddI at 1.6 milligrams per kilogram intravenously and then greater than or equal to 3.2 milligrams per kilogram orally at least every 12 hours or higher) had increases in their circulating CD4+ T cells (P less than 0.0005), increased CD4/CD8 T cell ratios (P less than 0.01), and, where evaluable, more than an 80% decrease in serum HIV p24 antigen (P less than 0.05). The patients also had evidence of improved immunologic function, had reduced viremic symptomatology, and gained a mean of 1.6 kilogram with these comparatively infrequent dosing schedules (every 8 or 12 hours). The most notable adverse effects directly attributable to ddI administration at the doses used in this study included increases in serum uric acid (due to hypoxanthine release) and mild headaches and insomnia. These results suggest that serious short-term toxicity at therapeutic doses is not an inherent feature in the profile of agents with clinical anti-HIV activity. Further controlled studies to define the safety and efficacy of this agent may be worth considering.

Effect of deuterium irradiation on graphite boronized in the NSTX-U tokamak.

Boronization has been used in the National Spherical Torus-Upgrade (NSTX-U) as first wall conditioning technique. The technique decreased the oxygen impurities in the plasma and the O% on the Plasma Facing Components (PFC) as measured with an in-vacuo probe. Samples were extracted from tiles removed from the tokamak for post-mortem and controlled studies. Ex-vessel low energy and fluence D2+ and Ar+ irradiations were characterized in-situ to elucidate surface evolution of a cored graphite sample with an intrinsic concentration of boron from a tokamak environment. In addition, quadrupole mass spectrometer measurements of emitted D-containing species during irradiation, indicate potential retention of D by the boronized graphite interface and correlated back to the surface chemistry evolution. Classical Molecular Dynamics (CMD) simulations were used to investigate the chemistry of the B-C-O-D system. The results suggest that boron coatings retain oxygen by forming oxidized boron states in the presence of deuterium plasmas and corroborate empirical findings. A four times increase in the O% of the boron coatings was observed following in-situ deuterium exposures, in contrast with a reduction of equal magnitude observed after Ar irradiations. These results illustrate the complex chemistry driven by energetic ions at the edge of tokamaks plasmas on the PFCs.

Evidence for persistent hepatitis C virus (HCV) infection in hemophiliacs.

Hepatitis C virus (HCV) is the major etiologic agent associated with non-A, non-B hepatitis. This study was designed to assess virologic and serologic markers in hemophiliacs exposed to non-heat-treated and/or virus-inactivated plasma derivatives. Serial bleeds from 48 hemophilic patients were analyzed for the presence of HCV viral RNA sequences as detected by polymerase chain reaction (PCR) and antibodies to structural (core) and nonstructural (C-100 and 33C) proteins by specific dot immunoblot assay. All patients exposed to non-heat-treated products, and four of six patients exposed only to virus inactivated products, had evidence of HCV infection. However, over the 5-yr study period, six exposed patients (13%) consistently lacked detectable anti-C-100 and seven (15%) lost this antibody. HCV viremia (PCR positive) was found in 91% of exposed patients, and was significantly more frequent in HIV seropositive hemophiliacs (P less than 0.05). Six patients had high antibody level to HCV and elevated ALT, but appeared to clear viremia. Four hemophiliacs were HCV seropositive but lacked detectable viremia. These data indicate that hemophiliacs remain persistently infected by HCV and that antibody to the core antigen of HCV is a reliable marker of this transfusion transmissible agent.

IMPACT: a facility to study the interaction of low-energy intense particle beams with dynamic heterogeneous surfaces.

The Interaction of Materials with Particles and Components Testing (IMPACT) experimental facility is furnished with multiple ion sources and in situ diagnostics to study the modification of surfaces undergoing physical, chemical, and electronic changes during exposure to energetic particle beams. Ion beams with energies in the range between 20 and 5000 eV can bombard samples at flux levels in the range of 10(10)-10(15) cm(-2) s(-1); parameters such as ion angle of incidence and exposed area are also controllable during the experiment. IMPACT has diagnostics that allow full characterization of the beam, including a Faraday cup, a beam imaging system, and a retarding field energy analyzer. IMPACT is equipped with multiple diagnostics, such as electron (Auger, photoelectron) and ion scattering spectroscopies that allow different probing depths of the sample to monitor compositional changes in multicomponent and/or layered targets. A unique real-time erosion diagnostic based on a dual quartz crystal microbalance measures deposition from an eroding surface with rates smaller than 0.01 nm/s, which can be converted to a sputter yield measurement. The monitoring crystal can be rotated and placed in the target position so that the deposited material on the quartz crystal oscillator surface can be characterized without transfer outside of the vacuum chamber.