Transfusion medicine research in Africa: Insights from investigators in the field.

BACKGROUND AND OBJECTIVES: Research in low-resource settings is inherently challenging. We sought to assess the factors that have impeded or facilitated transfusion medicine (TM) research in various African settings. MATERIALS AND METHODS: A qualitative case study was conducted of selected investigators in Africa; selection was based on productivity-spanning publication, leadership and research in TM. We designed a questionnaire to explore the factors impeding or facilitating TM research to understand the impact on the investigators' careers. Written responses were independently coded and double-checked for precision. Qualitative analysis was conducted, whereby responses were grouped thematically and clustered by relationship. The initial findings were discussed with respondents to validate and refine the interpretations. The recorded transcript was analysed and incorporated into the final analysis. RESULTS: Six investigators participated in the study. Their responses yielded 471 coded comments: 389 from the questionnaires and 82 from the ensuing discussion. The most frequently cited factors described included knowledge and intellectual abilities (n = 104), personal effectiveness (n = 99), research and governance structure (n = 97), and engagement, influence and impact (n = 75). Four relationship clusters emerged from the facilitators (n = 42), barriers (n = 28), and common approaches (n = 26) to research, informing summary themes of adaptation, collaboration, perseverance, and resiliency. CONCLUSION: Individual attributes were found to be central to a successful TM research career in African settings. However, given other public health priorities and constraints, interpersonal relationships, organizational structures and the broader research context were important to TM researchers. Overcoming complexities demands adaptation, collaboration, perseverance and resiliency.

Hepatitis B Virus Chronic Infection in Blood Donors from Asian and African High or Medium Prevalence Areas: Comparison According to Sex.

Immune control of various infectious diseases, particularly viral, was shown to be more efficient for females than males. Response to viral vaccines (HAV, HBV) was higher in females. Data on hepatitis B virus (HBV) markers accumulated over 15 years in blood donors was stratified according to sex, including HBsAg, HBV viral load and levels of anti-HBs in areas where genotypes B and C (China), genotype D (Iran, Lebanon, Tunisia) and genotype E (Ghana, Burkina Faso, Gabon) were prevalent. HBsAg was screened by either ELISA or rapid tests, anti-HBc and anti-HBs by ELISA, HBV DNA load by a standardized method across sites. In Ghanaian children less than 5 years, HBV DNA load was significantly lower in females than in males (p = 0.035). In China, Ghana, Burkina Faso and Gabon blood donors, median HBsAg prevalence was ~5% and 3% in China, ~8.5% and 4.5% in Gabon, ~16% and 11% in Burkina Faso and ~11% and 7% in Ghana for male and female donors, respectively (p < 0.001). In HBsAg+ Ghanaian blood donors, distribution and median viral load were not significantly different between sexes; occult hepatitis B infections (OBI) were significantly more frequent in males. In Chinese blood donor anti-HBc+ and anti-HBs+, anti-HBs levels tended to be higher in males but vaccinated donors' anti-HBs+ only, while anti-HBs levels were females > males. In areas where genotypes B-E are dominant, the prevalence of chronic HBV infection (HBsAg+) seems better controlled before age 16−18 by females infected vertically or horizontally. OBIs appear considerably more frequent in men, suggesting lower efficacy of HBV infection control. Female blood donors appear significantly safer from HBV than males, and their donation should be encouraged.

Cost-effectiveness and budget impact of whole blood pathogen reduction in Ghana.

BACKGROUND: Despite the promise of pathogen reduction for reducing transfusion-associated adverse events in sub-Saharan Africa, no health-economic assessment is publicly available. STUDY DESIGN AND METHODS: We developed a mathematical risk reduction model to estimate the impact of nationwide whole blood pathogen reduction in Ghana on the incidence of six infectious and one non-infectious transfusion-associated adverse events. We estimated the lifetime direct healthcare costs and disability-adjusted life years lost for each adverse event. For HIV, HCV, and HBV, we simulated disease progression using Markov models, accounting for the likelihood and timing of clinical detection and treatment. We performed probabilistic and univariate sensitivity analysis. RESULTS: Adding whole blood pathogen reduction to Ghana's blood safety portfolio would avert an estimated 19,898 (11,948-27,353) adverse events and 38,491 (16,444-67,118) disability-adjusted life years annually, primarily by averting sepsis (49%) and malaria (31%) infections. One year of pathogen reduction would cost an estimated $8,037,191 ($6,381,946-$9,880,760) and eliminate $8,656,389 ($4,462,614-$13,469,448) in direct healthcare spending on transfusion-associated adverse events. We estimate a 58% probability that the addition of pathogen reduction would reduce overall direct healthcare spending. Findings were most sensitive to uncertainty in the probability that a bacterially contaminated blood donation causes sepsis. CONCLUSION: Whole blood pathogen reduction would substantially reduce the burden of known transfusion-associated adverse events in Ghana and may reduce overall healthcare spending. Additional benefits not captured by this analysis may include averting secondary transmission of infectious diseases, reducing non-medical costs, and averting new or re-emerging transfusion-transmitted infections.

Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a group of inherited disorders that result in haemoglobin abnormalities and other complications. Injury to the spleen, among other factors, contribute to persons with SCD being particularly susceptible to infection. Infants and very young children are especially vulnerable. The 'Co-operative Study of Sickle Cell Disease' observed an incidence rate for pneumococcal septicaemia of 10 per 100 person-years in children under the age of three years. Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimens may be advisable for this population. This is an update of a Cochrane Review which was first published in 2002, and previously updated, most recently in 2017.  OBJECTIVES: To compare the effects of antibiotic prophylaxis against pneumococcus in children with SCD receiving antibiotic prophylaxis compared to those without in relation to: 1. incidence of Streptococcus pneumoniae infection; 2. mortality (as reported in the included studies); 3. drug-related adverse events (as reported in the included studies) to the individual and the community; 4. the impact of discontinuing at various ages on incidence of infection and mortality. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which is comprised of references identified from comprehensive electronic database searches and also two clinical trials registries: ClinicalTrials.gov and the WHO International Registry Platform (not in 2020 given access issues relating to Covid-19 pandemic). Additionally, we carried out hand searching of relevant journals and abstract books of conference proceedings. Date of the most recent search: 25 January 2021. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing prophylactic antibiotics to prevent pneumococcal infection in children with SCD with placebo, no treatment or a comparator drug. DATA COLLECTION AND ANALYSIS: The standard methodological procedures expected by Cochrane were used. Both authors independently extracted data and assessed trial quality. The authors used the GRADE criteria to assess the certainty of the evidence. MAIN RESULTS: Six trials were identified by the searches, of which three trials were eligible for inclusion. A total of 880 children, who were between three months to five years of age at randomization were included. The included studies were conducted in centres in the USA and in Kingston, Jamaica. In trials that investigated initiation of penicillin on risk of pneumococcal infection, the odds ratio was 0.37 (95% confidence interval 0.16 to 0.86) (two trials, 457 children) (low-certainty evidence), while for withdrawal the odds ratio was 0.49 (95% confidence interval 0.09 to 2.71) (one trial, 400 children) (low-certainty evidence). Adverse drug effects were rare and minor. Rates of pneumococcal infection were found to be relatively low in children over the age of five years. Overall, the certainty of the evidence for all outcomes was judged to be low. The results from the risk of bias assessment undertaken identified two domains in which the risk of bias was considered to be high, these were incomplete outcome data (attrition bias) (two trials) and allocation concealment (selection bias) (one trial). Domains considered to have a low risk of bias for all three trials were selective reporting (reporting bias) and blinding (performance and detection bias). AUTHORS' CONCLUSIONS: The evidence examined was determined to be of low certainty and suggests that prophylactic penicillin significantly reduces risk of pneumococcal infection in children with homozygous SCD, and is associated with minimal adverse reactions. Further research may help to determine the ideal age to safely withdraw penicillin.

Microchimerism in Ghanaian children recipients of whole blood transfusion for severe anaemia.

BACKGROUND AND OBJECTIVES: Transfusion-acquired microchimerism (TA-Mc) has been reported in major trauma but not in young children despite relative immunodeficiency who, in sub-Saharan Africa, often suffer severe anaemia related to haemoglobinopathies or primary malaria infections. We examined the hypothesis that such massive red cell destructions might provide conditions favourable to TA-Mc, particularly when exposed to massive amounts of parasite antigens. MATERIALS AND METHODS: Twenty-seven female children <5 years transfused with male whole blood for severe anaemia (13 with acute malaria and 14 with other causes) were retrospectively identified, and a blood sample was collected >6 months post-transfusion. Four whole blood samples from paediatric females transfused with blood from female donors and five secondary school female students never pregnant, never transfused were used as negative controls. RESULTS: Nineteen patients (70%) carried male Mc with four (15%) having high levels of Mc (>100 genome equivalent of male cells/million of host cells) compared to three controls (37·5%). There was no difference in frequency or quantity of male Mc between paediatric patients with severe malaria and paediatric patients with other causes of severe anaemia. TA-Mc was not correlated with patient age, duration of whole blood storage or lymphocyte load transfused. After a median of 7 months post-transfusion, acute malaria did not increase the frequency of TA-Mc. One negative control appeared to carry low-level male cells. CONCLUSION: Transfusion-acquired microchimerism appears frequent in young children transfused with whole blood for severe anaemia.

Blood transfusion in sub-Saharan Africa: understanding the missing gap and responding to present and future challenges.

Blood transfusion in sub-Saharan Africa (SSA) is at a crossroad. Significant recent developments may help meet local needs in safe blood products and fulfil a global health target, as highlighted by the World Health Organization (WHO) Millennium and Sustainable Development Goals, in improving supply and safety, and ensuring the gradual implementation of selective haemotherapy. When WHO recommended the evaluation of convalescent blood or plasma to treat Ebola-infected patients during the recent epidemics, substantial gaps in local blood collection, testing and technology infrastructure and safety, as compared to best accepted quality standards, became evident. This evidence should now serve as an 'electro-shock'/awakening call used to highlight the needs for local governments to support National Blood Transfusion Services and establish robust national regulatory authorities that are mandated to bear regulatory responsibilities of blood establishments. A nationally co-ordinated blood programme is the best tool to gather reliable epidemiological data, address local needs in blood and blood products and serve public health. A literature review using WHO website and PubMed was conducted in this article to outline the current clinical use of blood products and plasma derivatives in SSA. This text also intends to highlight the gaps to be filled in the coming years with respect to quality, safety, supply and efficacy of blood and plasma products, in line with WHO guidelines for transfusion.

Splenectomy versus conservative management for acute sequestration crises in people with sickle cell disease.

BACKGROUND: Acute splenic sequestration crises are a complication of sickle cell disease, with high mortality rates and frequent recurrence in survivors of first attacks. Splenectomy and blood transfusion, with their consequences, are the mainstay of long-term management used in different parts of the world. This is a 2017 update of a Cochrane Review first published in 2002, and previously updated, most recently in 2015. OBJECTIVES: To assess whether splenectomy (total or partial), to prevent acute splenic sequestration crises in people with sickle cell disease, improved survival and decreased morbidity in people with sickle cell disease, as compared with regular blood transfusions. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and handsearching relevant journals and abstract books of conference proceedings. We also searched clinical trial registries. Additional trials were sought from the reference lists of the trials and reviews identified by the search strategy.Date of the most recent search: 14 August 2017. SELECTION CRITERIA: All randomized or quasi-randomized controlled trials comparing splenectomy (total or partial) to prevent recurrence of acute splenic sequestration crises with no treatment or blood transfusions in people with sickle cell disease. DATA COLLECTION AND ANALYSIS: No trials of splenectomy for acute splenic sequestration were found. MAIN RESULTS: No trials of splenectomy for acute splenic sequestration were found. AUTHORS' CONCLUSIONS: Splenectomy, if full, will prevent further sequestration and if partial, may reduce the recurrence of acute splenic sequestration crises. However, there is a lack of evidence from trials showing that splenectomy improves survival and decreases morbidity in people with sickle cell disease. There is a need for a well-designed, adequately-powered, randomized controlled trial to assess the benefits and risks of splenectomy compared to transfusion programmes, as a means of improving survival and decreasing mortality from acute splenic sequestration in people with sickle cell disease.There are no trials included in the review and we have not identified any relevant trials up to August 2017. We will continue to run searches to identify any potentially relevant trials; however, we do not plan to update other sections of the review until new trials are published.

Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease.

BACKGROUND: Persons with sickle cell disease (SCD) are particularly susceptible to infection. Infants and very young children are especially vulnerable. The 'Co-operative Study of Sickle Cell Disease' observed an incidence rate for pneumococcal septicaemia of 10 per 100 person years in children under the age of three years. Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimens may be advisable for this population. This is an update of a Cochrane Review first published in 2002, and previously updated, most recently in 2014. OBJECTIVES: To assess the effects of antibiotic prophylaxis against pneumococcus in children with SCD in relation to:1. incidence of infection;2. mortality;3. drug-related adverse events (as reported in the included studies) to the individual and the community;4. the impact of discontinuing at various ages on incidence of infection and mortality. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which is comprised of references identified from comprehensive electronic database searches and also two clinical trials registries: ClinicalTrials.gov and the WHO International Registry Platform. Additionally, we carried out handsearching of relevant journals and abstract books of conference proceedings.Date of the most recent search: 19 December 2016. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing prophylactic antibiotics to prevent pneumococcal infection in children with SCD with placebo, no treatment or a comparator drug. DATA COLLECTION AND ANALYSIS: Both authors independently extracted data and assessed trial quality. The authors used the GRADE criteria to assess the quality of the evidence. MAIN RESULTS: Five trials were identified by the searches, of which three trials (880 children randomised) met the inclusion criteria. All of the included trials showed a reduced incidence of infection in children with SCD (SS or Sß0Thal) receiving prophylactic penicillin. In trials which investigated initiation of penicillin on risk of pneumococcal infection, the odds ratio was 0.37 (95% confidence interval 0.16 to 0.86) (two trials, 457 children) (low-quality evidence), while for withdrawal the odds ratio was 0.49 (95% confidence interval 0.09 to 2.71) (one trial, 400 children) (low-quality evidence). Adverse drug effects were rare and minor. Rates of pneumococcal infection were found to be relatively low in children over the age of five.Overall, the quality of the evidence for all outcomes was judged to be low. The results from the risk of bias assessment undertaken identified two domains in which the risk of bias was considered to be high, these were incomplete outcome data (attrition bias) (two trials) and allocation concealment (selection bias) (one trial). Domains considered to have a low risk of bias for all three trials were selective reporting (reporting bias) and blinding (performance and detection bias). AUTHORS' CONCLUSIONS: The evidence examined suggests that prophylactic penicillin significantly reduces risk of pneumococcal infection in children with homozygous SCD, and is associated with minimal adverse reactions. Further research may help to determine the ideal age to safely withdraw penicillin.

Characterization of posttransfusion Plasmodium falciparum infection in semi-immune nonparasitemic patients.

BACKGROUND: Transfusion-transmitted malaria (TTM) has not been studied with molecular means in hyperendemic areas where it is assumed to occur frequently. The African Investigation of the Mirasol System (AIMS) trial provided the opportunity to study TTM from standard whole blood (WB) units. STUDY DESIGN AND METHODS: The Plasmodium genome in transfused WB units and patient samples both before transfusion and 1, 3, 7, and 28 days after transfusion was screened and quantified using real-time polymerase chain reaction. Parasitemic samples were confirmed, three alleles were sequenced, and the percentage homology was determined between paired WB units and patient samples. Anti-Plasmodium titers were quantified by serial dilution. Clinical symptoms and microscopic detection of malaria were monitored. RESULTS: Microscopy was negative below 3 × 10(6) genome copies/mL. Thirty-seven patients who were nonparasitemic before transfusion were exposed to parasitemic WB. The amount of Plasmodium genome load transfused ranged between 0.1 × 10(6) and 2.0 × 10(9) copies. The parasite load received through transfusion by 13 patients with TTM was higher than that received by patients without TTM (p = 0.01). Patients with a single parasitemic posttransfusion sample were not considered to have TTM. Four elements critical to predict outcome emerged: parasite load, patient anti-Plasmodium titer pretransfusion, percentage clearance of parasites at Day 1, and level of anti-Plasmodium humoral immune response. Four patients with TTM became parasite-free at Day 28 (effective control), four patients with TTM maintained relatively stable levels of parasitemia (uncertain control), and five patients reached high levels of parasitemia at Day 28 posttransfusion, indicating ineffective control of malarial infection by semi-immune individuals. CONCLUSIONS: TTM in endemic areas is relatively frequent (13 of 112 donations; 11.6%) and, although largely controlled by semi-immunity in recipient patients, may require antimalarial treatment.

Effect of Plasmodium inactivation in whole blood on the incidence of blood transfusion-transmitted malaria in endemic regions: the African Investigation of the Mirasol System (AIMS) randomised controlled trial.

BACKGROUND: Transfusion-transmitted malaria is a frequent but neglected adverse event in Ghana. We did a randomised controlled clinical trial to assess the efficacy and safety of a whole blood pathogen reduction technology at preventing transfusion transmission of Plasmodium spp parasites. METHODS: For this randomised, double-blind, parallel-group clinical trial, eligible adult patients (aged ≥ 18 years) with blood group O+, who required up to two whole blood unit transfusions within 3 days of randomisation and were anticipated to remain in hospital for at least 3 consecutive days after initial transfusion, were enrolled from Komfo Anokye Teaching Hospital in Kumasi, Ghana. The main exclusion criteria were symptoms of clinical malaria, antimalaria treatment within 7 days before randomisation, fever, and haemorrhage expected to require transfusion with up to two units of whole blood during the 3 days following study entry. Eligible patients were randomly assigned 1:1 by computer-generated permuted block randomisation (block size four) list to receive transfusion with either pathogen-reduced whole blood (treated) or whole blood prepared and transfused by standard local practice (untreated). Patients, health-care providers, and data collectors were masked to treatment allocation. Patients in both groups received up to two whole blood unit transfusions that were retrospectively tested for parasitaemia. Pre-transfusion and post-transfusion blood samples (taken on days 0, 1, 3, 7, and 28) were tested for presence and amount of parasite genome, and assessed for haematological and biochemical parameters. The primary endpoint was the incidence of transfusion-transmitted malaria in non-parasitaemic recipients exposed to parasitaemic whole blood, defined as two consecutive parasitaemic post-transfusion samples with parasite allelic matching, assessed at 1-7 days after transfusion. Secondary endpoints included haematological parameters and a safety analysis of adverse events in patients. This study is registered with ClinicalTrials.gov, number NCT02118428, and with the Pan African Clinical Trials Registry, number PACTR201406000777310. FINDINGS: Between March 12, 2014, and Nov 7, 2014, 227 patients were enrolled into the study, one of whom was subsequently excluded because she did not meet the inclusion criteria. Of the 226 randomised patients, 113 were allocated to receive treated whole blood and 113 to receive standard untreated whole blood. 223 patients (111 treated and 112 untreated) received study-related transfusions, whereas three patients (two treated and one untreated) did not. 214 patients (107 treated and 107 untreated) completed the protocol as planned and comprised the per-protocol population. Overall, 65 non-parasitaemic patients (28 treated and 37 untreated) were exposed to parasitaemic blood. The incidence of transfusion-transmitted malaria was significantly lower for the pathogen-reduced (treated) patients (1 [4%] of 28 patients) than the untreated group (8 [22%] of 37 patients) in this population (p=0.039). Overall, 92 (41%) of 223 patients reported 145 treatment-related emergent adverse events during the conduct of the study, with a similar incidence of adverse events between groups receiving untreated or treated whole blood. No transfusion-related deaths occurred in the trial. INTERPRETATION: Treatment of whole blood with the Mirasol pathogen reduction system for whole blood reduced the incidence of transfusion-transmitted malaria. The primary endpoint of the study was achieved in the population of non-parasitaemic patients receiving parasitaemic whole blood. The safety profile and clinical outcomes were similar across the two treatment groups. FUNDING: Terumo BCT Inc.

Syphilis screening practices in blood transfusion facilities in Ghana.

OBJECTIVES: The primary objective of this study was to compare laboratory practices for screening blood donors for syphilis at blood transfusion facilities in Ghana with the recommendations of the World Health Organization and the National Blood Service, Ghana (NBSG). The prevalence of syphilis antibodies in blood donors in Ghana was also estimated. METHODS: Over an 11-month period, from February 2014 to January 2015, a semi-structured questionnaire was administered to 122 laboratory technical heads out of a total of 149 transfusion facilities in Ghana. The response rate was 81.9%. RESULTS: A total of 58 (48%) transfusion facilities tested donors for syphilis, with an estimated 3.7% seroprevalence (95% confidence interval 3.6-3.8%). A total of 62782 out of 91386 (68.7%) donations were tested with assays that are not recommended. The estimated syphilis seroprevalence in voluntary donations was 2.9%, compared to 4.0% in family donations (p=0.001). Only 6.9% of the health facilities were using standard operating procedures (SOPs). CONCLUSIONS: Despite international and national recommendations, more than half of the studied health facilities that provide blood transfusions in Ghana are not screening blood donations for syphilis. These data show a considerable mismatch between recommendations and practice, with serious consequences for blood safety and public health.

Next-Generation Sequencing Reveals Frequent Opportunities for Exposure to Hepatitis C Virus in Ghana.

Globally, hepatitis C Virus (HCV) infection is responsible for a large proportion of persons with liver disease, including cancer. The infection is highly prevalent in sub-Saharan Africa. West Africa was identified as a geographic origin of two HCV genotypes. However, little is known about the genetic composition of HCV populations in many countries of the region. Using conventional and next-generation sequencing (NGS), we identified and genetically characterized 65 HCV strains circulating among HCV-positive blood donors in Kumasi, Ghana. Phylogenetic analysis using consensus sequences derived from 3 genomic regions of the HCV genome, 5'-untranslated region, hypervariable region 1 (HVR1) and NS5B gene, consistently classified the HCV variants (n = 65) into genotypes 1 (HCV-1, 15%) and genotype 2 (HCV-2, 85%). The Ghanaian and West African HCV-2 NS5B sequences were found completely intermixed in the phylogenetic tree, indicating a substantial genetic heterogeneity of HCV-2 in Ghana. Analysis of HVR1 sequences from intra-host HCV variants obtained by NGS showed that three donors were infected with >1 HCV strain, including infections with 2 genotypes. Two other donors share an HCV strain, indicating HCV transmission between them. The HCV-2 strain sampled from one donor was replaced with another HCV-2 strain after only 2 months of observation, indicating rapid strain switching. Bayesian analysis estimated that the HCV-2 strains in Ghana were expanding since the 16th century. The blood donors in Kumasi, Ghana, are infected with a very heterogeneous HCV population of HCV-1 and HCV-2, with HCV-2 being prevalent. The detection of three cases of co- or super-infections and transmission linkage between 2 cases suggests frequent opportunities for HCV exposure among the blood donors and is consistent with the reported high HCV prevalence. The conditions for effective HCV-2 transmission existed for ~ 3-4 centuries, indicating a long epidemic history of HCV-2 in Ghana.

Splenectomy versus conservative management for acute sequestration crises in people with sickle cell disease.

BACKGROUND: Acute splenic sequestration crises are a complication of sickle cell disease, with high mortality rates and frequent recurrence in survivors of first attacks. Splenectomy and blood transfusion, with their consequences, are the mainstay of long-term management used in different parts of the world. This is a 2015 update of a Cochrane review first published in 2002, and previously updated in 2013. OBJECTIVES: To assess whether splenectomy (total or partial), to prevent acute splenic sequestration crises in people with sickle cell disease, improved survival and decreased morbidity in people with sickle cell disease, as compared with regular blood transfusions. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and handsearching relevant journals and abstract books of conference proceedings.Additional trials were sought from the reference lists of the trials and reviews identified by the search strategy.Date of the most recent search: 10 June 2015. SELECTION CRITERIA: All randomized or quasi-randomized controlled trials comparing splenectomy (total or partial) to prevent recurrence of acute splenic sequestration crises with no treatment or blood transfusions in people with sickle cell disease. DATA COLLECTION AND ANALYSIS: No trials of splenectomy for acute splenic sequestration were found. MAIN RESULTS: No trials of splenectomy for acute splenic sequestration were found. AUTHORS' CONCLUSIONS: Splenectomy, if full, will prevent further sequestration and if partial, may reduce the recurrence of acute splenic sequestration crises. However, there is a lack of evidence from trials showing that splenectomy improves survival and decreases morbidity in people with sickle cell disease. There is a need for a well-designed, adequately-powered, randomized controlled trial to assess the benefits and risks of splenectomy compared to transfusion programmes, as a means of improving survival and decreasing mortality from acute splenic sequestration in people with sickle cell disease.There are no trials included in the review and we have not identified any relevant trials up to June 2015. We will continue to run searches to identify any potentially relevant trals; however, we do not plan to update other sections of the review until new trials are published.

Treatment of Whole Blood With Riboflavin and UV Light: Impact on Malaria Parasite Viability and Whole Blood Storage.

BACKGROUND: Sub-Saharan African countries utilize whole blood (WB) to treat severe anemia secondary to severe blood loss or malaria on an emergency basis. In many areas with high prevalence of transfusion-transmissible agents, blood safety measures are insufficient. Pathogen reduction technology applied to WB might considerably improve blood safety. METHODS: Whole blood from 40 different donors were treated with riboflavin and UV light (pathogen reduction technology) in order to inactivate malaria parasite replication. The extent of parasite inactivation was determined using quantitative polymerase chain reaction methods and was correlated to studies evaluating the replication of malaria parasites in culture. Products were also stored for 21 days at +4°C and monitored for cell quality throughout storage. RESULTS: Plasmodium amplicon was present in 21 samples (>100 copies/mL), doubtful in four (10-100 genome equivalents [gEq]/mL), and negative in 15 U. The majority of asymptomatic parasitemic donors carried low parasite levels, with only six donors above 5,000 copies/mL (15%). After treatment with riboflavin and UV light, these six samples demonstrated a 0.5 to 1.2 log reduction in quantitative polymerase chain reaction amplification. This correlated to equal to or greater than 6.4 log reductions in infectivity. In treated WB units, cell quality parameters remained stable; however, plasma hemoglobin increased to 0.15 g/dL. All markers behaved similarly to published data for stored, untreated WB. CONCLUSIONS: Pathogen reduction technology treatment can inactivate malaria parasites in WB while maintaining adequate blood quality during posttreatment cold storage for 21 days.

High frequency of active HCV infection among seropositive cases in west Africa and evidence for multiple transmission pathways.

BACKGROUND: Sub-Saharan Africa (SSA) has one of the highest global hepatitis C virus (HCV) prevalence estimates. However, reports that suggest high rates of serologic false positives and low levels of viremia have led to uncertainty regarding the burden of active infection in this region. Additionally, little is known about the predominant transmission risk factors in SSA. METHODS: We prospectively recalled 363 past blood donors (180 who were rapid screen assay [RSA] positive and 183 who were RSA negative at time of donation) to identify the level of active infection and risk factors for infection at a teaching hospital in Kumasi, Ghana. Participants had repeat blood testing and were administered a questionnaire on risk factors. RESULTS: The frequency of HCV active infection ranged from 74.4% to 88% depending on the criteria used to define serologically positive cases. Individuals with active disease had biochemical evidence of liver inflammation and median viral loads of 5.7 log copies/mL. Individuals from the northern and upper regions of Ghana had greater risks of infection compared with participants from other areas. Additional risk factors included traditional circumcision, home birth, tribal scarring, and hepatitis B virus coinfection. CONCLUSIONS: Viremic infection was common among serologically confirmed cases. Attention to testing algorithms is needed in order to define the true HCV burden in SSA. These data also suggest that several transmission modes are likely contributing to the current HCV epidemic in Ghana and that the distribution of these practices may result in substantial regional variation in prevalence.

Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease.

Background This is an update of a Cochrane Review first published in 2002, and previously updated in 2012. People with sickle cell disease are particularly susceptible to infection. Infants and very young children are especially vulnerable, and the 'Co-operative Study of Sickle Cell Disease' observed an incidence rate of 10 per 100 patient years of pneumococcal septicaemia in children under the age of three.Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimens may be advisable for this population.Objectives To assess the effects of prophylactic antibiotic regimens for preventing pneumococcal infection in children with sickle cell disease.Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which is comprised of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 26 June 2014.Selection criteria All randomised or quasi-randomised controlled trials comparing prophylactic antibiotics to prevent pneumococcal infection in children with sickle cell disease with placebo, no treatment or a comparator drug.Data collection and analysis Both authors independently extracted data and assessed trial quality.Main results Five trials were identified by the initial search, of which three trials met the inclusion criteria. All of the included trials showed a reduced incidence of infection in children with sickle cell disease (SS or Sß0Thal) receiving prophylactic penicillin. In trials which investigated initiation of penicillin on risk of pneumococcal infection, the odds ratio was 0.37 (95% CI 0.16 to 0.86), while for withdrawal the odds ratio was 0.49 (95% CI 0.09 to 2.71). Adverse drug effects were rare and minor. Rates of pneumococcal infection were found to be relatively low in children over the age of five.Authors' conclusions Prophylactic penicillin significantly reduces risk of pneumococcal infection in children with homozygous sickle cell disease, and is associated with minimal adverse reactions. Further research may help to determine the ideal age to safely withdraw penicillin.

Fourteen-year experience of a tertiary hospital transfusion committee in West Africa.

BACKGROUND: Hospital transfusion committees (HTCs) have been established in the United States to link producers and users as well as to ensure appropriate use of blood. The HTC has been little reported in sub-Saharan Africa (SSA), although it has been established in some hospitals. STUDY DESIGN AND METHODS: The minutes of three to four HTC meetings per year in a tertiary hospital hosting its own blood service have been reviewed to examine the HTC role over a period of 14 years. Minutes were broken down into themes and indexes, and incomplete data were reinforced by other information sources. Specific data on progress over time were reviewed. RESULTS: The HTC systematically scrutinized the blood supply, blood safety, donor care, clinical use of blood products, and costs. It operated more as a blood transfusion service supervisory board than the limited function allocated to western HTCs. Clinicians and hospital administration were directly involved in decision making and directing investigations to support potential changes and advances in the role and function of the blood transfusion service. The close relation with a UK major blood center and university laboratory provided the impetus and support for research and investigations preliminary to decision making. Data collected and analyzed were reported in the international literature and contributed to disseminate progress made. CONCLUSIONS: The HTC in a major SSA tertiary hospital inclusive of all sections of hospital organization was critically instrumental in decision making, funding, and implementing measures improving the amount and quality of blood products on the basis of evidence collected despite lack of resources. Steps are taken to ensure sustainability of the HTC.

Can family or replacement blood donors become regular volunteer donors?

BACKGROUND: In sub-Saharan Africa (SSA) confirmed viral marker prevalence between family donors (FDs) and first-time volunteer nonremunerated donors (VNRDs) is similar. In a blood service collecting 10 units/1000 inhabitants, a questionnaire examined FD donation conditions and willingness of becoming repeat VNRDs. STUDY DESIGN AND METHODS: Four areas were explored: circumstances of visit to hospital, external pressure, experience of donating, and potential repeat donation. After donation and consent, research assistants administered 25 questions and, according to literacy, helped with translation and completion. RESULTS: Of 513 FDs, three-fourths were males (median age, 27 years). Only 1.3% were unemployed and more than 50% were students or teachers. Ties with hospitalized patient were family (76%), friends (13%), colleagues, or sharing place of worship (10%). Donating blood was the reason for visiting in 16.8% and 20.9% had previously donated blood probably as FDs. In one-third of FDs, the family asked for donation of which 10% was pressured by the unjustified reason that not donating was endangering the patient's life. For two-thirds of FDs, donation was given "because individuals were asked." Donation was a positive experience for 77% of donors, 62% being interested in predonation testing. Repeating donation was acceptable for 99% of 79% FDs answering. DISCUSSION: FDs are active in the population, are willing to donate blood if asked, are submitted to little pressure, do not receive incentives, and accept repeat donation. Except for circumstances of donation, FDs are not different from VNRDs and more directly motivated. They constitute a legitimate and important source to improve the blood supply in SSA.

Splenectomy versus conservative management for acute sequestration crises in people with sickle cell disease.

BACKGROUND: Acute splenic sequestration crises are a complication of sickle cell disease, with high mortality rates and frequent recurrence in survivors of first attacks. Splenectomy and blood transfusion, with their consequences, are the mainstay of long-term management used in different parts of the world. OBJECTIVES: To assess whether splenectomy (total or partial), to prevent acute splenic sequestration crises in people with sickle cell disease, improved survival and decreased morbidity in people with sickle cell disease, as compared with regular blood transfusions. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and handsearching relevant journals and abstract books of conference proceedings.Additional trials were sought from the reference lists of the trials and reviews identified by the search strategy.Date of the most recent search: 06 December 2012. SELECTION CRITERIA: All randomized or quasi-randomized controlled trials comparing splenectomy (total or partial) to prevent recurrence of acute splenic sequestration crises with no treatment or blood transfusions in people with sickle cell disease. DATA COLLECTION AND ANALYSIS: No trials of splenectomy for acute splenic sequestration were found. MAIN RESULTS: No trials of splenectomy for acute splenic sequestration were found. AUTHORS' CONCLUSIONS: Splenectomy, if full, will prevent further sequestration and if partial, may reduce the recurrence of acute splenic sequestration crises. However, there is a lack of evidence from trials showing that splenectomy improves survival and decreases morbidity in people with sickle cell disease. There is a need for a well-designed, adequately-powered, randomized controlled trial to assess the benefits and risks of splenectomy compared to transfusion programmes, as a means of improving survival and decreasing mortality from acute splenic sequestration in people with sickle cell disease.

Investigating the prevalence of transfusion transmission of Plasmodium within a hyperendemic blood donation system.

BACKGROUND: Prevention of transfusion-transmitted malaria in at-risk children and pregnant women in endemic areas with inexpensive chloroquine is no longer effective due to widespread drug resistance. There is an urgent need for devising new strategies for transfusion malarial safety. We investigated the frequency of transfusion transmission of malaria within the Ghanaian blood donation system using blood donations from 106 asymptomatic adult Ghanaian blood donors. STUDY DESIGN AND METHODS: Paired samples from 106 blood donations and recipients (before and after transfusion) were tested for anti-merozoite surface protein-1/2 using the commercial Lab21 malaria enzyme immunoassay (EIA), four antigen-specific in-house EIAs, and Plasmodium lactate dehydrogenase (pLDH) EIA. Additionally, Plasmodium DNA was screened for using a species-specific nested polymerase chain reaction (PCR) and a Pan-Plasmodium quantitative PCR. Donor-recipient parasite identity was defined by two concordant genotyping strategies. RESULTS: Plasmodium antibody prevalence was 100% in both donors and recipients, with at least one antigen. Parasitemia prevalence was 54.7% in both donors and recipients with median levels of 20 and 5.3 copies/µL, respectively, the difference being correlated to age (p = 0.0001). Multiple species infections were frequent (8.5%). Twenty-four units of parasitemic blood were transfused to nonparasitemic recipients, of which 10 (41.7%) became infected after transfusion. Molecular genotyping with 13 distinct markers (antigenic genes and microsatellite loci) identified three to nine parasitemic recipients after transfusion with level of allelic identity suggesting 14% to 28% definite or possible transfusion-related parasitemia. CONCLUSION: None of the currently available screening assays appear suitable to minimize transfusion malaria without compromising the blood supply in endemic areas.