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Background Blood services in Africa operate at different levels of development from those comparable to the developed world to those operating at a basic level. In recent years, countries have improved their blood services but have found many international quality standards too stringent for most economies in the region. To address these challenges, the Africa Society for Blood Transfusion ( Af SBT) has developed blood transfusion standards relevant for Africa. The Af SBT Stepwise Accreditation Standards The Standards were drafted by an Af SBT Task Team with guidance from the AABB and input from a team of experts. There is one Standard with three progressively more rigorous steps of achievement. The Standards apply to facilities that perform any or all of the blood transfusion process chain activities from vein to vein. There is a guidance document that clarifies and enhances understanding of the requirements of some of the standards. Training and Implementation There is a training committee, tasked with supporting training for blood services. Piloting of the Standards was done in Namibia and Malawi. Next implementation steps include licensing, translation into French and Portuguese and development of the capacity of the Af SBT to become an accrediting body. Conclusion Stepwise accreditation programme is relevant in encouraging improvements for developing blood transfusion services. Accreditation standards need to be commensurate with local needs while safeguarding patient and blood donor safety. Training is important in helping blood services to become accredited. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization recommends not performing transfusions in African children hospitalized for uncomplicated severe anemia (hemoglobin level of 4 to 6 g per deciliter and no signs of clinical severity). However, high mortality and readmission rates suggest that less restrictive transfusion strategies might improve outcomes.Methods: In this factorial, open-label, randomized, controlled trial, we assigned Ugandan and Malawian children 2 months to 12 years of age with uncomplicated severe anemia to immediate transfusion with 20 ml or 30 ml of whole-blood equivalent per kilogram of body weight, as determined in a second simultaneous randomization, or no immediate transfusion (control group), in which transfusion with 20 ml of whole-blood equivalent per kilogram was triggered by new signs of clinical severity or a drop in hemoglobin to below 4 g per deciliter. The primary outcome was 28-day mortality. Three other randomizations investigated transfusion volume, postdischarge supplementation with micronutrients, and postdischarge prophylaxis with trimethoprim-sulfamethoxazole.Results: A total of 1565 children (median age, 26 months) underwent randomization, with 778 assigned to the immediate-transfusion group and 787 to the control group; 984 children (62.9%) had malaria. The children were followed for 180 days, and 71 (4.5%) were lost to follow-up. During the primary hospitalization, transfusion was performed in all the children in the immediate-transfusion group and in 386 (49.0%) in the control group (median time to transfusion, 1.3 hours vs. 24.9 hours after randomization). The mean (±SD) total blood volume transfused per child was 314±228 ml in the immediate-transfusion group and 142±224 ml in the control group. Death had occurred by 28 days in 7 children (0.9%) in the immediate-transfusion group and in 13 (1.7%) in the control group (hazard ratio, 0.54; 95% confidence interval [CI], 0.22 to 1.36; P = 0.19) and by 180 days in 35 (4.5%) and 47 (6.0%), respectively (hazard ratio, 0.75; 95% CI, 0.48 to 1.15), without evidence of interaction with other randomizations (P>0.20) or evidence of between-group differences in readmissions, serious adverse events, or hemoglobin recovery at 180 days. The mean length of hospital stay was 0.9 days longer in the control group.Conclusions: There was no evidence of differences in clinical outcomes over 6 months between the children who received immediate transfusion and those who did not. The triggered-transfusion strategy in the control group resulted in lower blood use; however, the length of hospital stay was longer, and this strategy required clinical and hemoglobin monitoring. (Funded by the Medical Research Council and Department for International Development; TRACT Current Controlled Trials number, ISRCTN84086586.). [ABSTRACT FROM AUTHOR]

Background and Objective: Despite the Malawi Blood Transfusion Service (MBTS) increasing the amount of blood collected since its inception in 2004, Malawi remains with a 27% deficit in required blood supplies nationally. We sought to understand the facilitators and barriers to blood donation among secondary school students in Malawi., Methods: We utilised a qualitative exploratory design, with a sample of 135 participants purposefully selected from 16 secondary schools across Malawi. Data collection methods included in-depth interviews with 20 participants (inclusive of first-time and repeat donors, lapsed and non-donors), 20 key informant interviews (including community leaders, policy-level stakeholders and MBTS staff), and 16 focus group discussions involving 95 participants (community stakeholders and all donor categories). We used the consolidated framework for implementation research (CFIR) to assess barriers and facilitators of blood donation, focusing only on four CFIR domains: internal and external factors; the implementation process and individual characteristics influencing blood donation., Results: Blood donation among students are facilitated by altruism, incentives including milestone awards, knowledge, motivation, transport, peer pressure and individual health status. Common barriers cited included: negative experiences with the blood donation process, fear, unsupported environment, poor incentives, privacy issues and the donation activities starting late than scheduled., Conclusion: While there have been efforts to motivate students to donate blood, significant barriers to blood donation still exist. Intensifying education and awareness campaigns may help dispel misconceptions and fears surrounding donation experiences and blood usage. Also, continuing with the provision of appropriate incentives including milestone awards may also encourage students., (© 2024 The Author(s). Transfusion Medicine published by John Wiley & Sons Ltd on behalf of British Blood Transfusion Society.)

The World Health Organization recommends that all blood donations be screened for transfusion transmissible infections; these data are currently not incorporated into national disease surveillance efforts. We set out to use routinely collected data from blood donors in Blantyre district, Malawi to explore HIV and syphilis prevalence and identify sero-conversions among repeat donors. We conducted a retrospective cohort analysis of blood donation data collected by the Malawi Blood Transfusion Service from 2015 to 2021. All blood donations were routinely screened for HIV and syphilis. We characterized donor demographics as well as screening outcomes, including identifying sero-conversions among repeat donors who previously tested negative on their last donation. A total of 23,280 donations from 5,051 donors were recorded, with a median frequency of donations of 3 (IQR:2-6). Most donors were male (4,294; 85%) and students (3,262; 64.6%). Prevalence of HIV at first donation was 1.0% (52/5,051) and prevalence of syphilis was 1.6% (80/5,051); 52 HIV sero-conversions and 126 syphilis sero-conversions were identified, indicating an incidence rate per 1,000 person-years of 5.9 (95% CI: 4.7, 7.4) and 13.3 (95% CI:11.4, 15.4) respectively. Students had a lower prevalence of HIV and syphilis but higher risk of syphilis seroconversion. While blood donors are generally considered a low-risk population for HIV and syphilis, we were able to identify relatively high rates of undiagnosed HIV and syphilis infections among donors. Routinely collected data from national blood donation services may be used to better understand local HIV and syphilis epidemiology, with the potential to enhance disease surveillance systems. These findings may be used to identify priority prevention areas and populations in Blantyre district that can inform targeted interventions for improved disease prevention, testing and treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Singogo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Voluntary non-remunerated blood donors (VNRBDs) are essential to sustain national blood supplies. Expanding testing capacity for the major transfusion-transmitted infections (TTI) is crucial to ensure safe blood products. Understanding trends in TTIs can inform prioritisation of resources., Methods: We conducted a retrospective cohort data analysis of routine blood donation data collected from VNRBDs by the Malawi Blood Transfusion Service from January 2015 to October 2021. Variables included age, occupation; and screening results of TTIs (HIV, Hepatitis B and C, and syphilis). We estimated both prevalence and incidence per person-year for each TTI using longitudinal and spatial logistic regression models., Results: Of the 213 626 donors, 204 920 (95.8%) donors were included in the final analysis. Most donors (77.4%) were males, baseline median age was 19.9 (IQR 18.0, 24.1), 70.9% were students, and over 80.0% were single at first donation. Overall TTI prevalence among donors was 10.7%, with HBV having the highest prevalence (3.4%), followed by syphilis (3.3%), then HIV (2.4%) and HCV (2.4%). Incidence per 1000 person-years for syphilis was 20.1 (19.0, 21.3), HCV was 18.4 (17.3, 19.5), HBV was 13.7 (12.8, 14.7), and HIV was 11.4 (10.6, 12.3). We noted geographical variations with the northern region having lower rates of both prevalence and incidence compared to central and southern regions., Conclusion: The individual TTI prevalence and incidence rates from this study are consistent with Southern African regional estimates. By identifying geographical variations of TTI prevalence and incidence, these findings could potentially inform prioritisation of blood collection efforts to optimise blood collection processes., (© 2023 The Authors. Transfusion Medicine published by John Wiley & Sons Ltd on behalf of British Blood Transfusion Society.)

Blood and blood products are listed as one of the essential medicines by the World Health Organization (WHO). In addition to inadequate supply, most sub-Saharan Africa (SSA) nations fail to meet their blood needs because many donated blood units are discarded because they are contaminated with transfusion-transmitted infections (TTIs). We sought to estimate the prevalence of TTIs, identify the risk factors for TTIs among blood donors, and identify the efforts and interventions that have been made to improve blood safety in Southern African nations, particularly the nations of the South African Development Community (SADC). We investigated the prevalence and risk factors for TTIs, blood safety interventions, and blood quality improvement in the SADC region from major PubMed/MEDLINE, Cochrane Library, and HINARI databases from 1 January 2011 to 31 April 2021. All investigations followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). In meta-analysis, we estimated the pooled TTIs prevalence and summarised the same using forest plots. A total of 180 articles published from the SSA region were identified covering our three targeted themes: TTI prevalence, risk factors for TTIs, and blood safety improvements. Of these 180 articles, only 27 (15%) focused on the SADC region. The overall pooled TTI prevalence estimate was 2.0% (95% CI: 1.0-3.0) and hepatitis B was the most prevalent TTI in the region (prevalence = 3.0; 95% CI: 2.0-5.0). The prevalence of HIV, HCV, and syphilis was 2.0% (95% CI: 1.0-4.0), 1.0% (95% CI: 0.0-2.0), and 2.0% (95% CI: 0.0-8.0), respectively. In general, replacement donors and first-time donors were more likely to be infected with TTIs than repeat donors. Twelve articles explored blood safety research in the region; however, they vary greatly highlighting the need for consistent and more comprehensive research. Few publications were identified that were from the SADC region, indicating lack of research or resources towards improving both quantity and quality of blood donation. TTI prevalence remains one of the highest in the world and blood safety recommendations vary across the region. More effort should be directed towards developing a cohesive regional blood transfusion policy and effective blood monitoring and evaluation strategies., (© 2023 British Blood Transfusion Society.)

Competing Interests: IB has received support from the British Society for Haematology for attending meetings and declares research grants from the National Institute for Health and Care Research. BM declares research grants paid to their institution from the National Heart, Lung, and Blood Institute (NHLBI) of the US National Institutes of Health (NIH). BA declares research grants paid to their institution from NHLBI-NIH. LA-A declares research grants paid to their institution from NHLBI-NIH and Global Blood Fund and support from The Harvard Radcliffe Institute for attending a meeting. MD declares research grants from the NIH and is chairperson for the BLOODSAFE research programme. MD declares honoraria for presenting at grand rounds and is a board member volunteer for Association for the Advancement of Blood & Biotherapies for which they receive no payment. CTT declares research grants from NIH, the University of California San Francisco, Vitalant Research Institute, Grifols, Institut de Recherche pour le Développement, and Roche. CTT declares consulting fees from the Africa Society for Blood Transfusion, Safe Blood for Africa Foundation, Swiss Red Cross, and WHO; honoraria for lectures from Universite libre de Bruxelles; support for attending meetings from Societe Francophone de Transfusion Sanguine (SFTS) and The Harvard Radcliffe Institute; and participation on an advisory board for SFTS.

Background: The supply of blood in many low- and middle-income nations in Sub-Saharan Africa (SSA) does not meet the patient care needs. Lack and delay of blood transfusion cause harm to patients and slow the rate of progress in other parts of the health system. Recognizing the power of implementation science, the BLOODSAFE Program was initiated which supports three SSA research study teams and one data coordinating center (DCC) with the goal to improve access to safe blood transfusion in SSA., Study Design and Methods: The study team in Ghana is focusing on studying and decreasing iron deficiency in blood donors and evaluating social engagement of blood donors through different approaches. The study team in Kenya is building a "vein to vein" workflow model to elucidate and devise strategies to overcome barriers to blood donation and improve infrastructural components of blood product production and use. The Malawi team is studying the infectious disease ramifications of blood donation as well as blood donor retention strategies aimed at blood donors who commence their donation career in secondary schools., Results and Discussion: Together the project teams and the DCC work as a consortium to support each other through a shared study protocol that will study donor motivations, outcomes, and adverse events across all three countries. The BLOODSAFE Program has the potential to lead to generalizable improvement approaches for increasing access to safe blood in SSA as well as mentoring and building the research capacity and careers of many investigators., (© 2022 AABB.)

Background: The recent worldwide increase in malaria cases highlights the need for renewed efforts to eliminate malaria. The World Health Organization advocates that malaria surveillance becomes a core intervention. Current methods to estimate the malaria burden rely on clinical malaria case reports and surveys of asymptomatic parasite infection mainly from children  < 5 years. In this study the hypothesis was that screening blood donors for malaria parasites would provide real-time information on the asymptomatic reservoir of parasites in the adult population and mirror other surveillance data., Methods: This study was conducted in Malawi, a high malaria burden country, at the Malawi Blood Transfusion Service, which collects blood units at donation sites countrywide. A secondary analysis was conducted on data obtained from a prior Sysmex XN-31 analyser malaria diagnostic evaluation study utilizing residual donor blood samples. XN-31 malaria results, donor age, sex, geographical location, and collection date, were analysed using standard statistical methods., Results: The malaria parasite prevalence in blood donors was 11.6% (614/5281 samples) increasing seasonally from December (8.6%) to April (18.3%). The median age was 21 years and 45.9% of donors were from urban areas, which showed a lower prevalence compared to non-urban regions. The Central administrative region had the highest and the Northern region the lowest malaria parasite prevalence. The donors were predominantly male (80.2%), 13.1% of whom had malaria parasites, which was significantly higher (p < 0.0001) than for female donors (7.4%). Multivariable logistic regression analysis showed that age, location, and collection month were significant predictors of malaria positivity in males, whereas in females only location was significant. There was no gender difference in parasite density nor gametocyte carriage., Conclusions: This study demonstrates the powerful utility of screening blood donors for malaria parasites using the XN-31, which not only improves the safety of blood transfusion, but provides valuable complementary surveillance data for malaria control, especially targeting males, who are generally excluded from periodic household surveys. Blood donations are sourced countrywide, year-round, and thus provide dynamic, real-time information on the malaria burden. Furthermore, the XN-31 identifies the asymptomatic human reservoir of infectious gametocytes, which must be targeted to eliminate malaria., (© 2022. The Author(s).)

Background: Postpartum haemorrhage (PPH) is the leading cause of maternal mortality in Malawi. Despite the presence of a centralized institution supplying blood and blood products for hospitals across the country, a lack of timely blood transfusion has been identified as a critical barrier to successful PPH management. This study aims to understand the factors that affect the blood delivery pipeline and adequate access to blood products for postpartum haemorrhage patients., Methods: Qualitative data were collected through in-depth interviews with key stakeholders across the blood delivery pipeline. Interviews were conducted from July 2020 to January 2021 at Queen Elizabeth Central Hospital and Mulanje District Hospital, a referral and district hospital respectively, as well as the Malawi Blood Transfusion Service. Line by line, open coding was used to perform a thematic analysis of the data using Nvivo and Atlas.ti software., Results: Five key themes were identified: 1) Lack of blood availability due to an inadequate donor pool, 2) Transportation of blood products and PPH patients is impeded by distance to target sites and competing interests for blood delivery vehicles, 3) The Malawi Blood Transfusion Service has difficulty meeting demand for blood products due to inadequate funding and difficulty retaining blood donors, 4) Current PPH management protocols and practices lead to delays due to inconsistent guidelines on delivery and analysis of patient samples, and 5) Communication between health cadres is inconsistent and affected by a lack of adequate resources., Conclusions: Barriers to timely blood transfusion for PPH patients exist across the blood delivery pipeline. While an investment of infrastructure would alleviate many obstacles, several solutions identified in this study can be implemented without additional resources, such as establishing joint department meetings to improve communication between health cadres. Ultimately, given a resource limited setting, it may be worth considering de-centralizing the blood supply., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: S.E.N. reports prior employment with MBTS and B.M. is currently employed at MBTS. R.F.S., G.M., A.J., A.S.M., B.J., P.B., L.G., S.C., E.S., and D.W. have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background and Objectives: Balancing blood supply safety and sufficiency is challenging in malaria-endemic countries where the risk of transfusion-transmitted malaria (TTM) is ever-present. In support of reducing this risk, our study aimed at evaluating the performance of the Sysmex XN-31 analyser in blood donor malaria screening, as compared with current practice in Malawi., Materials and Methods: This prospective observational study was conducted on remnant venous donor blood samples collected at Malawi Blood Transfusion Service donation sites countrywide for routine blood-borne pathogen screening. XN-31 results were compared with routine thick smear malaria microscopy, using expert microscopy (phase 1 and 2) plus qualitative malaria polymerase chain reaction (PCR) (phase 2) to adjudicate discrepancies., Results: XN-31 detected malaria in 614 (11.6%) of 5281 study samples compared with 341 (6.5%) for routine microscopy. Of the 273 discrepant samples, 60 smears (phase 1) could not be retrieved for expert microscopic review. Expert microscopy confirmed the XN-31 positivity in 78.8% (149/189) and 91.7% (22/24) of discrepant samples in phase 1 (n = 4416) and phase 2 (n = 975), respectively, with two cases requiring PCR testing, confirming one each as positive and negative, giving sensitivities of 100% and 75% and specificities of 99.9% and 100%, respectively, for XN-31 and routine microscopy., Conclusion: The automated Sysmex XN-31 analyser's high sensitivity and specificity, ability to detect all Plasmodium species and high throughput with rapid turnaround-time, overcomes many of the limitations of currently available diagnostic tests, making it well-suited for malaria screening of donated blood in malaria-endemic countries in support of TTM risk reduction., (© 2021 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Background: The TRACT trial established the timing of transfusion in children with uncomplicated anaemia (haemoglobin 4-6 g/dL) and the optimal volume (20 vs 30 mL/kg whole blood or 10 vs 15 mL/kg red cell concentrates) for transfusion in children admitted to hospital with severe anaemia (haemoglobin <6 g/dL) on day 28 mortality (primary endpoint). Because data on the safety of blood components are scarce, we conducted a secondary analysis to examine the safety and efficacy of different pack types (whole blood vs red cell concentrates) on clinical outcomes., Methods: This study is a secondary analysis of the TRACT trial data restricted to those who received an immediate transfusion (using whole blood or red cell concentrates). TRACT was an open-label, multicentre, factorial, randomised trial conducted in three hospitals in Uganda (Soroti, Mbale, and Mulago) and one hospital in Malawi (Blantyre). The trial enrolled children aged between 2 months and 12 years admitted to hospital with severe anaemia (haemoglobin <6 g/dL). The pack type used (supplied by blood banks) was based only on availability at the time. The outcomes were haemoglobin recovery at 8 h and 180 days, requirement for retransfusion, length of hospital stay, changes in heart and respiratory rates until day 180, and the main clinical endpoints (mortality until day 28 and day 180, and readmission until day 180), measured using multivariate regression models., Findings: Between Sept 17, 2014, and May 15, 2017, 3199 children with severe anaemia were enrolled into the TRACT trial. 3188 children were considered in our secondary analysis. The median age was 37 months (IQR 18-64). Whole blood was the first pack provided for 1632 (41%) of 3992 transfusions. Haemoglobin recovery at 8 h was significantly lower in those who received packed cells or settled cells than those who received whole blood, with a mean of 1·4 g/dL (95% CI -1·6 to -1·1) in children who received 30 mL/kg and -1·3 g/dL (-1·5 to -1·0) in those who received 20 mL/kg packed cells versus whole blood, and -1·5 g/dL (-1·7 to -1·3) in those who received 30 mL/kg and -1·0 g/dL (-1·2 to -0·9) in those who received 20 mL/kg settled cells versus whole blood (overall p<0·0001). Compared to whole blood, children who received blood as packed or settled cells in their first transfusion had higher odds of receiving a second transfusion (odds ratio 2·32 [95% CI 1·30 to 4·12] for packed cells and 2·97 [2·18 to 4·05] for settled cells; p<0·001) and longer hospital stays (hazard ratio 0·94 [95% CI 0·81 to 1·10] for packed cells and 0·86 [0·79 to 0·94] for settled cells; p=0·0024). There was no association between the type of blood supplied for the first transfusion and mortality at 28 days or 180 days, or readmission to hospital for any cause. 823 (26%) of 3188 children presented with severe tachycardia and 2077 (65%) with tachypnoea, but these complications resolved over time. No child developed features of confirmed cardiopulmonary overload., Interpretation: Our study suggests that the use of packed or settled cells rather than whole blood leads to additional transfusions, increasing the use of a scarce resource in most of sub-Saharan Africa. These findings have substantial cost implications for blood transfusion and health services. Nevertheless, a clinical trial comparing whole blood transfusion with red cell concentrates might be needed to inform policy makers., Funding: UK Medical Research Council (MRC) and the Department for International Development., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The phase III Transfusion and Treatment of severe anaemia in African Children Trial (TRACT) found that conservative management of uncomplicated severe anaemia [haemoglobin (Hb) 40-60 g/l] was safe, and that transfusion volume (20 vs. 30 ml/kg whole blood equivalent) for children with severe anaemia (Hb <60 g/l) had strong but opposing effects on mortality, depending on fever status (>37·5°C). In 2020 a stakeholder meeting of paediatric and blood transfusion groups from Africa reviewed the results and additional analyses. Among all 3196 children receiving an initial transfusion there was no evidence that nutritional status, presence of shock, malaria parasite burden or sickle cell disease status influenced outcomes or modified the interaction with fever status on volume required. Fever status at the time of ordering blood was a reliable determinant of volume required for optimal outcome. Elevated heart and respiratory rates normalised irrespective of transfusion volume and without diuretics. By consensus, a transfusion management algorithm was developed, incorporating three additional measurements of Hb post-admission, alongside clinical monitoring. The proposed algorithm should help clinicians safely implement findings from TRACT. Further research should assess its implementation in routine clinical practice., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Introduction: Collecting blood from voluntary non-remunerated blood donors from low risk populations is a key strategy for blood safety. Identifying such populations involves analysis of population and blood donor data to identify risk factors for transfusion transmissible infections (TTIs). There are no recent seroprevalence statistics for blood donors in Malawi. This study fills this gap by describing characteristics of blood donors, trend of annual prevalence of HIV, HBV, HCV and syphilis and factors associated with each TTI., Methods: Retrospective analysis of blood donors' records in the MBTS database from 2011 to 2015 was undertaken. Summary statistics were performed to describe characteristics of the blood donors. Univariable and multivariable logistic regression analyses were performed to determine association between prevalence of infections and socio-demographic factors. Time trend analysis was done to assess changes in prevalence. P-value <0.05 was considered statistically significant., Results: The number of blood donors screened over the 5 year period was 125,893. The mean number of donors donating blood per year was 39, 289; median age was 19 years; 82% were male, 87% single and 72% students and56% were repeat blood donors. Overall prevalence of each TTI decreased. The 2015 prevalence was: 3.6% for HBV; 1.9% for HIV; 2.6% for Syphilis and 1.0% for HCV while the 2011 prevalence was 4.7% for HBV; 3.5% for HIV 3.2% for syphilis and 2.4% for HCV.Repeat blood donors had significantly lower prevalence of TTIs than first time donors. Females were associated with lower risk for HBV, HCV and syphilis. Age ≥25 years and being out of school were associated with HIV. Age ≥25 years was associated with reduced risk for HCV and being self-employed and married were each associated with syphilis., Conclusion: The typical blood donor is a young single male student. Repeat blood donation improves safety of the blood supply.

Background and Objectives: Paediatric blood transfusion for severe anaemia in hospitals in sub-Saharan Africa remains common. Yet, reports describing the haematological quality of donor blood or storage duration in routine practice are very limited. Both factors are likely to affect transfusion outcomes., Materials and Methods: We undertook three audits examining the distribution of pack types, haematological quality and storage duration of donor blood used in a paediatric clinical trial of blood at four hospitals in Africa (Uganda and Malawi)., Results: The overall distribution of whole blood, packed cells (plasma-reduced by centrifugation) and red cell concentrates (RCC) (plasma-reduced by gravity-dependent sedimentation) used in a randomised trial was 40·7% (N = 1215), 22·4% (N = 669) and 36·8% (N = 1099), respectively. The first audit found similar median haematocrits of 57·0% (50·0,74·0), 64·0% (52·0,72·5; P = 0·238 vs. whole blood) and 56·0% (48·0,67·0; P = 0·462) in whole blood, RCC and packed cells, respectively, which resulted from unclear pack labelling by blood transfusion services (BTS). Re-training of the BTS, hospital blood banks and clinical teams led to, in subsequent audits, significant differences in median haematocrit and haemoglobins across the three pack types and values within expected ranges. Median storage duration time was 12 days (IQR: 6, 19) with 18·2% (537/2964) over 21 days in storage. Initially, 9 (2·8%) packs were issued past the recommended duration of storage, dropping to 0·3% (N = 7) in the third audit post-training., Conclusion: The study highlights the importance of close interactions and education between BTS and clinical services and the importance of haemovigilance to ensure safe transfusion practice., (© 2019 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Background: In sub-Saharan Africa, where infectious diseases and nutritional deficiencies are common, severe anaemia is a common cause of paediatric hospital admission, yet the evidence to support current treatment recommendations is limited. To avert overuse of blood products, the World Health Organisation advocates a conservative transfusion policy and recommends iron, folate and anti-helminthics at discharge. Outcomes are unsatisfactory with high rates of in-hospital mortality (9-10%), 6-month mortality and relapse (6%). A definitive trial to establish best transfusion and treatment strategies to prevent both early and delayed mortality and relapse is warranted., Methods/design: TRACT is a multicentre randomised controlled trial of 3954 children aged 2 months to 12 years admitted to hospital with severe anaemia (haemoglobin < 6 g/dl). Children will be enrolled over 2 years in 4 centres in Uganda and Malawi and followed for 6 months. The trial will simultaneously evaluate (in a factorial trial with a 3 x 2 x 2 design) 3 ways to reduce short-term and longer-term mortality and morbidity following admission to hospital with severe anaemia in African children. The trial will compare: (i) R1: liberal transfusion (30 ml/kg whole blood) versus conservative transfusion (20 ml/kg) versus no transfusion (control). The control is only for children with uncomplicated severe anaemia (haemoglobin 4-6 g/dl); (ii) R2: post-discharge multi-vitamin multi-mineral supplementation (including folate and iron) versus routine care (folate and iron) for 3 months; (iii) R3: post-discharge cotrimoxazole prophylaxis for 3 months versus no prophylaxis. All randomisations are open. Enrolment to the trial started September 2014 and is currently ongoing. Primary outcome is cumulative mortality to 4 weeks for the transfusion strategy comparisons, and to 6 months for the nutritional support/antibiotic prophylaxis comparisons. Secondary outcomes include mortality, morbidity (haematological correction, nutritional and infectious), safety and cost-effectiveness., Discussion: If confirmed by the trial, a cheap and widely available 'bundle' of effective interventions, directed at immediate and downstream consequences of severe anaemia, could lead to substantial reductions in mortality in a substantial number of African children hospitalised with severe anaemia every year, if widely implemented., Trial Registration: Current Controlled Trials ISRCTN84086586 , Approved 11 February 2013.

Background: In spite of the significant mortality associated with Plasmodium falciparum infection, the mechanisms underlying severe disease remain poorly understood. We have previously shown evidence of endothelial activation in Ghanaian children with malaria, indicated by elevated plasma levels of both von Willebrand factor (VWF) and its propeptide. In the current prospective study of children in Malawi with retinopathy confirmed cerebral malaria, we compared these markers with uncomplicated malaria, non malarial febrile illness and controls., Methods and Findings: Children with cerebral malaria, mild malaria and controls without malaria were recruited into the study. All comatose patients were examined by direct and indirect ophthalmoscopy. Plasma VWF and propeptide levels were measured by ELISA. Median VWF and propeptide levels were significantly higher in patients with uncomplicated malaria than in children with non-malarial febrile illness of comparable severity, in whom levels were higher than in non-febrile controls. Median concentrations of both markers were higher in cerebral malaria than in uncomplicated malaria, and were similar in patients with and without retinopathy. Levels of both VWF and propeptide fell significantly 48 hours after commencing therapy and were normal one month later., Conclusions: In children with malaria plasma VWF and propeptide levels are markedly elevated in both cerebral and mild paediatric malaria, with levels matching disease severity, and these normalize upon recovery. High levels of both markers also occur in retinopathy-negative 'cerebral malaria' cases, many of whom are thought to be suffering from diseases other than malaria, indicating that further studies of these markers will be required to determine their sensitivity and specificity.

Squalene synthetase (EC 2.5.1.21) and squalene epoxidase (EC 1.14 99.7) activities have been measured in cell-free extracts of wild type yeast grown in aerobic and semi-anaerobic conditions as well as in sterol-auxotrophic mutant strains grown aerobically. The results show that both enzymes are induced resulting in an almost two- to five-fold increase in enzymatic activities in mutant strains containing limited sterol amounts and are repressed in the wild type strain cultured in anaerobiosis in excess of sterol. The results show also that squalene epoxidase is repressed by lanosterol, and that the mevalonic acid pool may regulate squalene synthetase levels. The large change in the activities of the two enzymes, depending on the sterol needs of the cells, as well as their low specific activities in comparison with those of the enzymes involved in the early stages of sterol synthesis strongly suggests that squalene synthetase and squalene epoxidase are of importance in regulating the amount of sterol synthesized by yeast.

We describe a simple assay for measuring squalene epoxidase specific activity in Saccharomyces cerevisiae cell-free extracts, by using [14C] farnesyl pyrophosphate as substrate. Cofactor requirements for activity are FAD and NADPH or NADH, NADPH being the preferred reduced pyridine nucleotide. Squalene epoxidase activity is localized in microsomal fraction and no supernatant soluble factor is required for maximum activity. Microsomal fraction converted farnesyl pyrophosphate into squalene, squalene 2,3-epoxide and lanosterol, showing that squalene 2,3-epoxide-lanosterol cyclase is also a microsome-bound enzyme. We show also that squalene epoxidase activity is not inhibited by ergosterol or lanosterol, but that enzyme synthesis is induced by oxygen.