Transfusion-associated graft-versus-host disease, transfusion-associated hyperkalemia, and potassium filtration: advancing safety and sufficiency of the blood supply.

Irradiation of cellular blood components is well established as a countermeasure against transfusion-associated graft-versus-host disease (TA-GVHD). Unintended consequences of ionizing radiation are also well established. The red cell "storage lesion" - a progression of metabolic, functional, and morphological changes - may be exacerbated by irradiation rates and doses typically used for TA-GVHD prophylaxis. With or without irradiation, a storage lesion change of clinical concern is the accelerated egress of intracellular potassium. ATP depletion during storage limits the activity of the red cell membrane's sodium-potassium pump (Na,K-ATPase), which normally maintains intracellular potassium (K+) at levels 30-40 times higher than the extracellular milieu. The natural diffusion of potassium down this concentration gradient proceeds faster if the cell membrane is damaged, and oxidative damage to cellular membranes and membrane proteins - including Na,K-ATPase - is an effect of ionizing radiation. Preventing transfusion-related hyperkalemia is a reason for limiting the shelf life of irradiated red cells. In the absence of specific measurements to assess storage lesion in a particular unit of blood, and in the absence of specific interventions at the time of transfusion to mitigate effects of storage lesion, it is consistent with the precautionary principle to put conservative limits on a blood component's shelf life. On the other hand, both the safety and sufficiency of a nation's blood supply might be improved by interventions that benefit specific recipients when they are transfused, and benefit future patients by extending the allowable shelf life of blood components. Potassium filtration of irradiated red blood cell components is one such intervention.

Population-based prevalence of human T-lymphotropic virus type 1 in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1), the causative agent of adult T-cell leukaemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), is endemic in sub-Saharan Africa (SSA) and poses a high morbidity and mortality risk. Its prevalence in the general population is poorly understood. The potential for prevention motivated us to do a systematic review and meta-analysis of population-based studies to estimate the prevalence of HTLV-1 in SSA. METHODS: A comprehensive, no-limit search was conducted in EMBASE, PubMed, Web of Science and the Cochrane Library from their inception dates to March 2019. Population-based studies presenting data on HTLV-1 in sub-Saharan Africa were included. Pooled prevalence was estimated using a random-effects meta-analysis. RESULTS: A total of 21 studies were included, representing 42 297 participants. The pooled HTLV-1 seroprevalence was 3.19% (95% CI 2.36-4.12%) with variations across year of study. Prevalence of HTLV-1 positively correlated with year of study (ß = 0.0036, P = 0.007). Participants from Central, Western and Southern Africa had a seroprevalence of 4.16% (95% CI 2.43-6.31%), 2.66% (95% CI 1.80-3.68%) and 1.56% (95% CI 0.48-3.15%), respectively. CONCLUSIONS: Our findings suggest that HTLV-1 infection is a public health concern in SSA and highlight the need to implement effective preventive programmes and interventions aimed at reducing the burden of this common yet neglected infection.

PRÉVALENCE DANS LA POPULATION DU VIRUS T-LYMPHOTROPIQUE HUMAIN DE TYPE 1 (HTLV-1) EN AFRIQUE SUBSAHARIENNE: OBJECTIF: Le virus lymphotropique T humain 1 (HTLV-1), l'agent causal de la leucémie T de l'adulte/lymphome (ATL) et la myélopathie associée à HTLV-1/paraparésie spastique tropicale (HAM/TSP), est endémique en Afrique subsaharienne (ASS) et présente un risque élevé de morbidité et de mortalité. Sa prévalence dans la population générale est mal comprise. Le potentiel de prévention nous a incité à procéder à une revue systématique et à une méta-analyse des études basées sur la population afin d'estimer la prévalence du HTLV- 1 en ASS. MÉTHODES: Une recherche approfondie et sans limite a été effectuée dans EMBASE, PUBMED, Web of Science et dans la Cochrane Library, depuis leur création jusqu'à mars 2019. Des études basées sur la population présentant des données sur HTLV-1 en ASS ont été incluses. La prévalence poolée a été estimée à l'aide d'une méta-analyse à effet aléatoire. RÉSULTATS: Un total de 21 études ont été incluses, représentant 42.297 participants. La séroprévalence poolée du HTLV-1 était de 3,19% (IC95%: 2,36% à 4,12%), avec des variations au cours de l'année de l'étude. La prévalence du HTLV-1 était corrélée positivement avec l'année d'étude (bêta = 0,0037, p = 0,007). Les participants d'Afrique centrale, de l'Ouest et Australe présentaient une séroprévalence de 4,16% (IC95%: 2,43% à 6,31%), de 2,66% (IC95%: 1,80% à 3,68%) et 1,56% (IC95%: 0,48% à 3,15%), respectivement. CONCLUSIONS: Nos résultats suggèrent que l'infection au HTLV-1 est une préoccupation de santé publique en ASS et soulignent la nécessité de mettre en œuvre des programmes et des interventions préventives efficaces visant à réduire la charge de cette infection commune mais négligée.

Seroprevalence of human T-lymphotropic virus (HTLV) in blood donors in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Human T-cell lymphotropic viruses (HTLV) 1 and 2 are endemic in sub-Saharan Africa (SSA), transfusion-transmissible and causally linked to various severe diseases. However, even in SSA countries with moderate to high endemicity, routine blood donor screening for HTLV is rarely, if ever, performed. Information on seroprevalence is limited. The aim of this review is to establish the prevalence of HTLV-1 and HTLV-1/2 among blood donors in sub-Saharan Africa. MATERIALS AND METHODS: We systematically reviewed databases including EMBASE, MEDLINE and the Cochrane database library from their inception to June 2018. Studies presenting data on HTLV prevalence among blood donors in sub-Saharan Africa were included. A random-effect meta-analysis was conducted on all eligible studies. RESULTS: A total of 25 studies were included, representing 74 119 blood donors, of whom over 80% (61 002) were only tested for HTLV-1. The evidence base was high and moderate in quality. The pooled prevalence of the 17 studies that screened only for HTLV-1 and the nine studies that screened for HTLV-1/2 was 0·68 (95% CI: 0·29-1·60) and 1·11 (95% CI: 0·47-2·59) per 100 blood donors, respectively. CONCLUSION: The prevalence of HTLV-1 infection among blood donors is relatively low. The current review is intended to inform debates and decisions about best practices to prevent transfusion-transmitted HTLV in sub-Saharan Africa. Further work is required to determine the risk of infections by transfusion and the cost-effectiveness of any new measures such as routine screening.

Red blood cell alloimmunization in transfused patients in sub-Saharan Africa: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Previous studies of Sub-Saharan Africans show significant alloimmunization to red blood cell (RBC) antigens, but country-specific data are limited. Thus, the aim of this study was to estimate, by meta-analysis, the overall proportion of red blood cell alloantibodies among transfused patients. METHODS: We systematically searched Medline, Embase, and the Africa-Wide Information database to identify relevant studies in any language. Case reports, comments, letters, conference abstracts, editorials, and review articles were excluded. Of the 269 potentially relevant articles, 11 studies fulfilled our selection criteria. RESULTS: Overall proportions of alloimmunization were 6.7 (95% CI: 5.7, 7.8) per 100 transfused patients. With regard to antibody specificity, among clinically significant antibodies, anti-E ranked as the most common, followed by anti-K, anti-C and anti-D. CONCLUSION: Meta-analysis of available literature quantifies and qualifies the clinical challenge of RBC alloimmunization among transfused patients in Sub-Saharan Africa. These results should drive policy decisions in favour of routine testing of RBC antigens and irregular antibodies for transfused patients as a standard of care throughout Sub-Saharan Africa.

CD4+ T cells in aged or thymectomized recipients of allogeneic stem cell transplantations.

BACKGROUND: CD4+CD25highFOXP3+ regulatory T (Treg) cells, which include thymus-derived and peripherally induced cells, play a central role in immune regulation, and are therefore crucial to prevent graft-versus-host disease (GVHD). The increasing use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for elderly patients with thymus regression, and our case of allo-HSCT shortly after total thymectomy, raised questions about the activity of thymus-derived Treg cells and peripherally induced Treg cells, which are otherwise indistinguishable. RESULTS: We found that despite pre-transplant thymectomy or older age, both naïve and effector Treg cells, as well as naïve and effector conventional T cells, proliferated in allo-HSCT recipients. Higher proportions of total Treg cells 1 month post allo-HSCT, and naïve Treg cells 1 year post allo-HSCT, appeared in patients achieving complete chimera without developing significant chronic GVHD, including our thymectomized patient, compared with patients who developed chronic GVHD. CONCLUSIONS: Treg cells that modulate human allogeneic immunity may arise peripherally as well as in the thymus of allo-HSCT recipients.

Risk factors for early fatal outcomes among children with hemophagocytic lymphohistiocytosis (HLH): a single-institution case-series in Vietnam.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and fatal hematological syndrome that causes a disturbance of the immune system. Overall mortality of HLH is greater than 50% and the majority of patients who die do so within the first 8 weeks of chemotherapy treatment. To find clinical parameters relating to high-risk HLH patients, this study examined associations between an early fatal outcome and potential prognostic clinical factors and laboratory findings on admission. Eighty-nine pediatric HLH patients were prospectively recruited in Children's Hospital No. 1, Ho-Chi-Minh City, Vietnam, during the period from January 2010 to August 2012. Associations between early fatal outcome and clinical and laboratory findings, including a cerebrospinal fluid examination and virological test on admission, were examined. During the 8-week therapy, 25 (28%) HLH patients died. Persistent fever (>2 weeks), severe thrombocytopenia (<75 × 10(9)/L), hyperbilirubinemia, and prolonged activated partial thromboplastin time (APTT) (>33 sec) were significant risk factors of early fatal outcome. Multivariate logistic regression analysis revealed that thrombocytopenia and prolonged APTT (P for trend was 0.054 and 0.013, respectively) were independently associated with the early fatal outcome. Persistent fever, severe thrombocytopenia, hyperbilirubinemia, and prolonged APTT on admission will be useful and practical predictors to determine high-risk HLH patients.

Prevalence and Molecular Epidemiology of Human T-Lymphotropic Virus Type 1 among Women Attending Antenatal Clinics in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

Human T-cell lymphotropic virus type 1 (HTLV-1) imposes a substantial disease burden in sub-Saharan Africa (SSA), which is arguably the world's largest endemic area for HTLV-1. Evidence that mother-to-child transmission persists as a major mode of transmission in SSA prompted us to estimate the pooled prevalence of HTLV-1 among pregnant women throughout the region. We systematically reviewed databases including EMBASE, MEDLINE, Web of Science, and the Cochrane Database of Systemic Reviews from their inception to November 2018. We selected studies with data on HTLV-1 prevalence among pregnant women in SSA. A random effect meta-analysis was conducted on all eligible data and heterogeneity was assessed through subgroup analyses. A total of 18 studies, covering 14,079 pregnant women, were selected. The evidence base was high to moderate in quality. The pooled prevalence, per 100 women, of the 18 studies that screened HTLV-1 was 1.67 (95% CI: 1.00-2.50), a figure that masks regional variations. In Western, Central, Southern, and Eastern Africa, the numbers were 2.34 (1.68-3.09), 2.00 (0.75-3.79), 0.30 (0.10-0.57), and 0.00 (0.00-0.21), respectively. The prevalence of HTLV-1 infection among pregnant women in SSA, especially in Western and Central Africa, strengthens the case for action to implement routine screening of pregnant women for HTLV-1. Rigorous studies using confirmatory testing and molecular analysis would characterize more accurately the prevalence of this infection, consolidate the evidence base, and further guide beneficial interventions.

Platelet-, leucocyte- and red cell-derived microparticles in stored whole blood, with and without leucofiltration, with and without ionising radiation.

BACKGROUND: Storage lesion, including microparticle formation, has been partially characterised in whole blood, but not in all combinations of pre-storage leucofiltration and/or irradiation. MATERIALS AND METHODS: Single-donor whole blood products were processed into four subunits: with and without leucofiltration, with and without X-irradiation (25 Gy). Platelet-, leucocyte-, and erythrocyte-derived microparticles and free haemoglobin were measured periodically throughout 42 days of storage. RESULTS: Pre-storage leucofiltration substantially reduced platelet- and leucocyte-derived microparticle counts throughout storage. Irradiation, in contrast, had no significant effect on microparticle counts. A gate for all microparticles showed a substantial time-dependent increase in unfiltered whole blood. A time-dependent increase in free haemoglobin was greatest in unfiltered, irradiated whole blood. DISCUSSION: This study indicates that leucofiltration can prevent the formation of leucocyte- and platelet-derived microparticles, and might reduce haemolysis in irradiated whole blood, either by removing factors that provoke haemolysis, or by selective retention of senescent or effete red cells most prone to haemolysis.

Support-seeking behavior among Japanese mothers at high-risk of mental health problems: a community-based study at a city health center.

AIM: The aim of this small-scale study is to explore support-seeking behavior among mothers at high-risk of mental health problems on community basis in Japan. METHODS: A survey using one month home visit data was conducted among mothers who registered their pregnancy at Shirakawa City Health Center, Fukushima, from April to September 2010. Probable postpartum depression at one month postpartum was assessed using the Japanese version of the Edinburgh Postnatal Depression Scale and the mother's bonding to her child at one month postpartum was measured by the Bonding Questionnaire. RESULTS: A total of 118 out of 217 registered mothers were available for analysis. The proportion of probable depression among first time and experienced mothers was 12% and 3%, and that of low bonding was 43% and 13%, respectively. Factors that showed significant associations with probable depression and/or low-bonding among first-time mothers were financial difficulty, obstetrical problems, unhappy feeling towards pregnancy, younger maternal age, later gestational week at registration; associated factors among experienced mothers were financial difficulty and obstetrical problems. At the time of pregnancy, 35 (90%) of first-time mothers and 22 (31%) of experienced mothers expressed the intention to attend antenatal classes. None of the risk factors for probable depression or low-bonding were associated with the mother's intention to attend antenatal classes in this study. CONCLUSION: Pregnancy history, obstetrical problems, sociodemographic information and maternal feeling toward pregnancy should be carefully screened in antenatal phase, and those at risk of postpartum mental health problems should be screened and actively invited to antenatal classes.

Impaired regulatory T cell reconstitution in patients with acute graft-versus-host disease and cytomegalovirus infection after allogeneic bone marrow transplantation.

To elucidate the correlation between regulatory T cells (Tregs) and acute graft-versus-host disease (aGVHD) or cytomegalovirus infection following allogeneic bone marrow transplantation (allo-BMT), we evaluated either CD4⁺CD25(high) or FOXP3⁺ Treg-enriched cells in peripheral blood (PB) from 20 patients who received allo-BMT, and in biopsies of skin with aGVHD. Proportions of CD4⁺CD25(high)FOXP3⁺ cells in total lymphocytes, but not other types of T cells, were lower in patients who eventually developed grades II-IV aGVHD (n = 13) than in others (n = 7, P < 0.001). Proportions of CD62L⁺ cells in CD4⁺CD25(high) cells at day +30 were lower (P < 0.01) in patients who eventually showed cytomegalovirus viremia (n = 6) than in others (n = 14). Incidence of aGVHD (P < 0.05) or cytomegalovirus viremia (P < 0.05) was higher in patients without these complications, but with lower proportions of PB CD4⁺CD25(high)FOXP3⁺ cells at day +30 (n = 8) than in others (n = 8). However, in skin with aGVHD (n = 5), there was marked or slightly increased infiltration of CD8⁺ cells (P < 0.001) or CD3⁺FOXP3⁺ cells (P < 0.05), respectively, when compared with control (n = 5), resulting in threefold higher ratio of CD8⁺/CD3⁺FOXP3⁺ cells in aGVHD relative to controls (P < 0.05). Thus, impaired reconstitution of Tregs may be associated with aGVHD and CMV infection. Moreover, imbalance of Tregs and CD8⁺ cells may play a role in aGVHD tissue.

CD4+ T cells in aged or thymectomized recipients of allogeneic stem cell transplantations

BACKGROUND: CD4+CD25highFOXP3+ regulatory T (Treg) cells, which include thymus-derived and peripherally induced cells, play a central role in immune regulation, and are therefore crucial to prevent graft-versus-host disease (GVHD). The increasing use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for elderly patients with thymus regression, and our case of allo-HSCT shortly after total thymectomy, raised questions about the activity of thymus-derived Treg cells and peripherally induced Treg cells, which are otherwise indistinguishable. RESULTS: We found that despite pre-transplant thymectomy or older age, both naïve and effector Treg cells, as well as naïve and effector conventional T cells, proliferated in allo-HSCT recipients. Higher proportions of total Treg cells 1 month post allo-HSCT, and naïve Treg cells 1 year post allo-HSCT, appeared in patients achieving complete chimera without developing significant chronic GVHD, including our thymectomized patient, compared with patients who developed chronic GVHD. CONCLUSIONS: Treg cells that modulate human allogeneic immunity may arise peripherally as well as in the thymus of allo-HSCT recipients.