Transfusion-transmitted diseases: risks,prevention and perspectives

Abstract: During the past decades major improvements in blood safety have been achieved, both in developed and developing countries. The introduction of donor counseling and screening for different pathogens has made blood a very safe product, especially in developed countries. However, even in these countries, there is still a residual risk for the transmission of several pathogens. For viruses such as the human immunodeficiency virus (HIV), and the hepatitis viruses B and C, this is due mainly to window-period donations. Furthermore, the threat of newly emerging pathogens which can affect blood safety is always present. For example, the implications of the agent causing new variant Creutzfeld-Jakob disease for transfusion practice are not yet clear. Finally, there are several pathogens, e.g. CMV and parvo B19, which are common in the general donor population, and might pose a serious threat in selected groups of immunosuppressed patients. In the future, further improvements in blood safety are expected from the introduction of polymerase chain reaction for testing and from the implementation of photochemical decontamination for cellular blood products. The situation in transfusion medicine in the developing world is much less favorable, due mainly to a higher incidence and prevalence of infectious diseases.     

降钙素原检测在细菌感染中的应用研究

目的探讨血清降钙素原(procalcitonin, PCT)定量检测在细菌感染患者中的诊断价值。方法选取2016年9月—2018年5月在我院住院治疗并发生医院细菌感染者131例,比较血清PCT水平在不同年龄、不同感染严重程度患者之间以及革兰阳性菌和革兰阴性菌感染患者之间的差异。结果 131例患者血清PCT水平均高于正常值;年龄<60岁组与年龄≥60岁组PCT水平比较,差异无统计学意义(P> 0.05);脓毒症组血清PCT水平明显高于局部感染组(P <0.05);革兰阴性菌感染组血清PCT水平明显高于革兰阳性菌感染组(P <0.05)。结论 PCT可以作为细菌感染的重要诊断指标,并能够对患者感染严重程度进行评估。     

Pathogen reduction and blood transfusion safety in Africa: strengths,limitations and challenges of implementation in low‐resource settings

Transfusion‐transmitted infection risk remains an enduring challenge to blood safety in Africa. A high background incidence and prevalence of the major transfusion‐transmitted infections (TTIs), dependence on high‐risk donors to meet demand, suboptimal testing and quality assurance collectively contribute to the increased risk. With few exceptions, donor testing is confined to serological evaluation of human immunodeficiency virus (HIV), hepatitis B and C (HBV and HCV) and syphilis. Barriers to implementation of broader molecular methods include cost, limited infrastructure and lack of technical expertise. Pathogen reduction (PR), a term used to describe a variety of methods (e.g. solvent detergent treatment or photochemical activation) that may be applied to blood following collection, offers the means to diminish the infectious potential of multiple pathogens simultaneously. This is effective against different classes of pathogen, including the major TTIs where laboratory screening is already implemented (e.g. HIV, HBV and HCV) as well pathogens that are widely endemic yet remain unaddressed (e.g. malaria, bacterial contamination). We sought to review the available and emerging PR techniques and their potential application to resource‐constrained parts of Africa, focusing on the advantages and disadvantages of such technologies. PR has been slow to be adopted even in high‐income countries, primarily given the high costs of use. Logistical considerations, particularly in low‐resourced parts of Africa, also raise concerns about practicality. Nonetheless, PR offers a rational, innovative strategy to contend with TTIs; technologies in development may well present a viable complement or even alternative to targeted screening in the future.     

Pathogen reduction technologies: The pros and cons for platelet transfusion

The transfusion of platelets is essential for diverse pathological conditions associated with thrombocytopenia or platelet disorders. To maintain optimal platelet quality and functions, platelets are stored as platelet concentrates (PCs) at room temperature under continuous agitation—conditions that are permissive for microbial proliferation. In order to reduce these contaminants, pathogen reduction technologies (PRTs) were developed by the pharmaceutical industry and subsequently implemented by blood banks. PRTs rely on chemically induced cross-linking and inactivation of nucleic acids. These technologies were initially introduced for the treatment of plasma and, more recently, for PCs given the absence of a nucleus in platelets. Several studies verified the effectiveness of PRTs to inactivate a broad array of bacteria, viruses, and parasites. However, the safety of PRT-treated platelets has been questioned in other studies, which focused on the impact of PRTs on platelet quality and functions. In this article, we review the literature regarding PRTs, and present the advantages and disadvantages related to their application in platelet transfusion medicine.     

Pathogen inactivation technology: cleansing the blood supply

The calculated residual infectious risk of HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) from blood transfusion is extremely low. However, the risk of bacterial contamination remains and a variety of other agents including emerging viruses, protozoa and tick-borne agents threaten blood supplies and undermine public confidence in blood safety. Traditional methods of donor screening and testing have limited ability to further reduce disease transmission and cannot prevent an emerging infectious agent from entering the blood supply. Pathogen inactivation technologies have all but eliminated the infectious risks of plasma-derived protein fractions, but as yet no technique has proved sufficiently safe and effective for traditional blood components. Half-way technologies can reduce the risk of pathogen transmission from fresh frozen plasma and cryoprecipitate. Traditional methods of mechanical removal such as washing and filtration have limited success in reducing the risk of cell-associated agents, but methods aimed at sterilizing blood have either proved toxic to the cells or to the recipients of blood components. Several promising methods that target pathogen nucleic acid have recently entered clinical testing.     

Effects of pathogen reduction systems on platelet microRNAs,mRNAs, activation,and function

Pathogen reduction (PR) systems for platelets, based on chemically induced cross-linking and inactivation of nucleic acids, potentially prevent transfusion transmission of infectious agents, but can increase clinically significant bleeding in some clinical studies. Here, we documented the effects of PR systems on microRNA and mRNA levels of platelets stored in the blood bank, and assessed their impact on platelet activation and function. Unlike platelets subjected to gamma irradiation or stored in additive solution, platelets treated with Intercept (amotosalen?+?ultraviolet-A [UVA] light) exhibited significantly reduced levels of 6 of the 11 microRNAs, and 2 of the 3 anti-apoptotic mRNAs (Bcl-xl and Clusterin) that we monitored, compared with platelets stored in plasma. Mirasol (riboflavin?+?UVB light) treatment of platelets did not produce these effects. PR neither affected platelet microRNA synthesis or function nor induced cross-linking of microRNA-sized endogenous platelet RNA species. However, the reduction in the platelet microRNA levels induced by Intercept correlated with the platelet activation (p?<?0.05) and an impaired platelet aggregation response to ADP (p?<?0.05). These results suggest that Intercept treatment may induce platelet activation, resulting in the release of microRNAs and mRNAs from platelets. The clinical implications of this reduction in platelet nucleic acids secondary to Intercept remain to be established.     

The long and winding road to pathogen reduction of platelets,red blood cells and whole blood

Pathogen reduction technologies (PRTs) have been developed to further reduce the current very low risks of acquiring transfusion-transmitted infections and promptly respond to emerging infectious threats. An entire portfolio of PRTs suitable for all blood components is not available, but the field is steadily progressing. While PRTs for plasma have been used for many years, PRTs for platelets, red blood cells (RBC) and whole blood (WB) were developed more slowly, due to difficulties in preserving cell functions during storage. Two commercial platelet PRTs use ultra violet (UV) A and UVB light in the presence of amotosalen or riboflavin to inactivate pathogens’ nucleic acids, while a third experimental PRT uses UVC light only. Two PRTs for WB and RBC have been tested in experimental clinical trials with storage limited to 21 or 35 days, due to unacceptably high RBC storage lesion beyond these time limits. This review summarizes pre-clinical investigations and selected outcomes from clinical trials using the above PRTs. Further studies are warranted to decrease cell storage lesions after PRT treatment and to test PRTs in different medical and surgical conditions. Affordability remains a major administrative obstacle to PRT use, particularly so in geographical regions with higher risks of transfusion-transmissible infections.     

44例新生儿败血症病原菌及耐药性分析

目的 探讨新生儿败血症病原学特点及致病菌耐药情况.方法 分析我院NICU 44例血培养阳性新生儿败血症培养检出菌及药敏结果.结果 检出病原菌44株,其中革兰阳性菌为34株（77.27%）,革兰阴性菌为8株（18.18%）;真菌2株（4.55%）.革兰阳性菌以凝固酶阴性葡萄球菌（CONS）为主,革兰阴性菌以大肠埃希菌为常见;CONS对青霉素G、红霉素、头孢唑啉的耐药率高,对万古霉素未发现产生耐药.结论 我院NICU新生儿败血症病原菌以CONS 为主,重视病原菌耐药性检测,根据药敏选用抗菌药物,可减少细菌耐药性的产生.     

Health risks and interventions in prediabetes: A review

Prediabetes is a condition which appears prior to the development of diabetes in which blood glucose is abnormally high but do not reach the diagnostic threshold of type 2 diabetes mellitus. It is characterized by a cluster of metabolic abnormalities viz. dysglycemia, dyslipidemia, hypertension, physical inactivity, obesity, insulin resistance, procoagulant state, endothelial dysfunction, oxidative stress and inflammation, placing prediabetic subjects to an increased risk for diabetes and its complications. Recent studies demonstrate that complications of diabetes i.e. microvascular and macrovascular complications may manifest in some prediabetic subjects. This article reviews prediabetes-related risk factors and health issues. In addition, this article also highlights the interventions to prevent the development of diabetes in prediabetic subjects.     

Influence of blood prestorage conditions and white blood cell filtration on the bacterial load of blood deliberately inoculated with Gram-positive and Gram-negative pathogens

BACKGROUND AND OBJECTIVES: Currently, the bacterial contamination of blood constitutes one of the major infectious risks of transfusion. The aim of this study was to evaluate the bactericidal effect of blood on various bacterial species and to determine the influence of prestorage conditions and white blood cell (WBC) filtration on the reduction of the bacterial load in isolated red blood cells (RBCs). MATERIALS AND METHODS: The growth kinetics of eight different species of bacteria were studied at 20 degrees C in deliberately contaminated RBC units. Further experiments evaluated the effect of prestorage conditions and WBC filtration on the viability of two model bacteria (Klebsiella oxytoca and Staphylococcus epidermidis) in comparison to previous results obtained with Yersinia enterocolitica. RESULTS: For bacteria susceptible to the bactericidal effect of blood (mainly Gram-negative rods), a reduction of the bacterial load was obtained within 2 h of prestorage at 20 degrees C. When the prestorage period was prolonged beyond 3 h at 20 degrees C, rapid growth was observed with some Enterobacteriaceae. Whereas WBC filtration reduced dramatically the viability of Y. enterocolitica, it had only a minimal effect on the viability of S. epidermidis and K. oxytoca. However, the two latter species of bacteria did not survive prolonged storage at 4 degrees C. CONCLUSIONS: Experiments conducted under realistic conditions are needed to determine whether it would be worthwhile recommending the rapid storage of RBCs at 4 degrees C after WBC reduction of the blood product.     

Clinical and laboratory practices in investigation of suspected transfusion-transmitted bacterial infection: a survey of Canadian hospitals

Transfusion of a bacterially contaminated blood product can have serious consequences. We undertook an electronic survey of representative Canadian hospitals to determine current clinical and laboratory practices for investigating such reactions, prior to the development of national guidelines. There was considerable variability in symptoms and signs that would trigger investigation of possible contamination. The most frequent laboratory investigations performed were aerobic blood cultures of recipients and the residual component. If there is no residual product in the component bag, 36% of respondents would use a segment to perform testing. Guidelines could be helpful in improving and standardizing these practices.     

Rejuvenation of allogenic red cells: benefits and risks

Background and objectives

To review preclinical and clinical studies that have evaluated the effects of red cell rejuvenation in vivo and in vitro and to assess the potential risks and benefits from their clinical use.

Materials and methods

A systematic review and narrative synthesis of the intervention of red cell rejuvenation using a red cell processing solution containing inosine, pyruvate, phosphate and adenine. Outcomes of interest in vitro were changes in red cell characteristics including adenosine triphosphate (ATP), 2,3‐diphosphoglycerate (2,3‐DPG), deformability and the accumulation of oxidized lipids and other reactive species in the red cell supernatant. Outcomes in vivo were 24‐h post‐transfusion survival and the effects on oxygen delivery, organ function and inflammation in transfused recipients.

Results

The literature search identified 49 studies evaluating rejuvenated red cells. In vitro rejuvenation restored cellular properties including 2,3‐DPG and ATP to levels similar to freshly donated red cells. In experimental models, in vivo transfusion of rejuvenated red cells improved oxygen delivery and myocardial, renal and pulmonary function when compared to stored red cells. In humans, in vivo 24‐h survival of rejuvenated red cells exceeded 75%. In clinical studies, rejuvenated red cells were found to be safe, with no reported adverse effects. In one adult cardiac surgery trial, transfusion of rejuvenated red cells resulted in improved myocardial performance.

Conclusion

Transfusion of rejuvenated red cells reduces organ injury attributable to the red cell storage lesion without adverse effects in experimental studies in vivo. The clinical benefits of this intervention remain uncertain.     

New antibiotic strategies in patients with cirrhosis and bacterial infection

Early diagnosis and adequate empirical antibiotic treatment of bacterial infections in advanced cirrhosis is essential to improve outcomes given the high risk of developing severe sepsis, multiple organ failure and death. β-lactams and quinolones are nowadays frequently ineffective in nosocomial and healthcare associated infections, due to the increasing prevalence of multidrug resistant (MDR) bacteria reported across different geographical areas. Recent antibiotic exposure also increases the risk of developing MDR bacterial infections. Initial antibiotic strategies should therefore be tailored according to the presence or absence of risk factors of MDR bacteria and to the severity of infection and should consider the local epidemiology. Empirical treatment in the population at high risk of MDR bacterial infections requires the use of broad-spectrum antibiotics (carbapenems or tigecycline) and of drugs active against specific resistant bacteria (glycopeptides, linezolid, daptomycin, amikacin, colistin). Early de-escalation policies are recommended to prevent the spread of MDR bacteria in cirrhosis.     

Relative values of the interventions of diversion and improved donor-arm disinfection to reduce the bacterial risk from blood transfusion

BACKGROUND AND OBJECTIVES: The aim of this study was to demonstrate the efficiency of diverting the initial 20-ml donation from the collection bag and of an improved donor-arm disinfection procedure in reducing bacterial contamination in blood. MATERIALS AND METHODS: Donations were collected in bags specially manufactured for the study. These bags incorporated two satellite pouches into each of which 20 ml of blood was collected. Blood initially flowed into sample pouch P1, representing a diversion pouch. Pouch P2 was then filled with 20 ml of blood, which allowed us to sample the collection bag after diversion was complete. Blood then flowed into the standard collection bag. The contents of the pouches were aerobically and anaerobically cultured on the BacT/ALERT automated culture system for 7 days. Two procedures were investigated in the study (each involving 1409 blood donations): one analysed the current disinfection procedure; and the other analysed an improved donor-arm disinfection procedure. RESULTS: The use of diversion alone resulted in a 47% reduction in contamination, and improved donor-arm disinfection alone resulted in a 57% reduction in contamination. Diversion plus improved donor-arm disinfection produced a predicted 77% reduction in contamination. CONCLUSIONS: The study validates diversion and an improved donor-arm disinfection procedure. In combination, these two interventions produced a substantial reduction in contamination. These procedures are to be introduced by the English National Blood Service to enhance the safety of the blood supply.