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1.
Higher Risk of HEV Transmission and Exposure among Blood Donors in Europe and Asia in Comparison to North America: A Meta-Analysis
Wolski A, Pischke S, Ozga AK, Addo MM, Horvatits T
Pathogens (Basel, Switzerland). 2023;12(3)
Abstract
BACKGROUND AND AIMS The increasing number of diagnosed hepatitis E virus (HEV) infections in Europe has led to the implementation of the testing of blood products in various countries. Many nations have not yet implemented such screening. To assess the need for HEV screening in blood products worldwide, we conducted a systematic review and meta-analysis assessing HEV RNA positivity and anti-HEV seroprevalence in blood donors. METHODS Studies reporting anti-HEV IgG/IgM or HEV RNA positivity rates among blood donors worldwide were identified via predefined search terms in PubMed and Scopus. Estimates were calculated by pooling study data with multivariable linear mixed-effects metaregression analysis. RESULTS A total of 157 (14%) of 1144 studies were included in the final analysis. The estimated HEV PCR positivity rate ranged from 0.01 to 0.14% worldwide, with strikingly higher rates in Asia (0.14%) and Europe (0.10%) in comparison to North America (0.01%). In line with this, anti-HEV IgG seroprevalence in North America (13%) was lower than that in Europe (19%). CONCLUSIONS Our data demonstrate large regional differences regarding the risk of HEV exposure and blood-borne HEV transmission. Considering the cost-benefit ratio, this supports blood product screening in high endemic areas, such as Europe and Asia, in contrast to low endemic regions, such as the U.S.
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2.
The Medical Relevance of Toxoplasma Infections in Terms of the Safety of Blood Recipients under Immunosuppression-A Meta-Analysis
Wesołowski, R., Pawłowska, M., Mila-Kierzenkowska, C.
Microorganisms. 2023;11(8)
Abstract
Laboratory diagnosis of Toxoplasma gondii infection plays a crucial role in ensuring the safety of blood recipients, especially in the case of immunosuppressed people, such as organ transplant patients. Toxoplasmosis, caused by the parasite Toxoplasma gondii, is a potential threat to people with weakened immune systems, and blood transfusions from infected donors can lead to severe complications. In this publication, we analyze the medical relevance of Toxoplasma infection in the context of the safety of blood recipients, focusing on the immunosuppressed patient population. We present various diagnostic methods, such as serological, molecular, and microscopic tests, which can detect the presence of Toxoplasma gondii in donors' blood. We also discuss the importance of adequately interpreting diagnostic results, considering risk factors, and detectability of the infection. We pay special attention to high-sensitivity and -specificity diagnostic techniques, which allow us to minimize the risk of Toxoplasma gondii transmission to blood recipients. Our findings have important implications for clinical practice and organ transplantation guidelines, emphasizing the need to diagnose and monitor Toxoplasma infections in blood donors and recipients.
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3.
Meta-analysis of bacterial growth characteristics in platelet components: Refining the inputs of a simulation analysis comparing the relative safety of testing strategies
Walker, B. S., Schmidt, R. L., White, S. K., Metcalf, R. A.
Transfusion. 2023
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Editor's Choice
Abstract
BACKGROUND The relative safety of bacterial risk control strategies for platelets that include culture with or without rapid testing has been compared using simulation analysis. A wide range of bacterial lag and doubling times were included. However, published data on growth rates are available and these data have not been synthesized. We conducted a systematic review and meta-analysis to estimate growth rates and used these estimates to refine a comparative safety analysis of bacterial risk control strategies in the FDA guidance STUDY DESIGN AND METHODS Data were extracted from published studies on bacterial growth rates in platelet components during storage. These data were used to estimate the practical range of growth rates. This refined the inputs for a simulation model comparing the safety of the testing strategies. RESULTS In total, 108 growth curves for 11 different aerobic organisms were obtained. Doubling times ranged from 0.8 to 12 h, but the lower 90% range was approximately 1-5 h. The revised comparative safety simulation using the narrower 1-5-h range showed similar rankings to the prior simulation, with 48-h large-volume delayed sampling with 7-day expiration (48C-7) demonstrating the lowest-ranking relative performance at the 10(3) and 10(5) colony forming unit (CFU)/mL exposure thresholds. DISCUSSION This was a two-step study. First, meta-analysis of published data on aerobic bacterial growth rates in stored platelets showed the vast majority of doubling times were 1-5 h. Next, an updated comparative safety simulation yielded similar results to a prior study, with 48C-7 showing the least favorable relative safety performance.
PICO Summary
Population
Recipients of platelet transfusions (12 studies).
Intervention
Systematic review and meta-analysis to estimate growth rates and used these estimates to refine a comparative safety analysis of bacterial risk control strategies in the FDA guidance.
Comparison
Outcome
Data were extracted from published studies on bacterial growth rates in platelet components during storage. These data were used to estimate the practical range of growth rates. This refined the inputs for a simulation model comparing the safety of the testing strategies. In total, 108 growth curves for 11 different aerobic organisms were obtained. Doubling times ranged from 0.8 to 12 h, but the lower 90% range was approximately 1-5 h. The revised comparative safety simulation using the narrower 1-5-h range showed similar rankings to the prior simulation, with 48-h large-volume delayed sampling with 7-day expiration (48C-7) demonstrating the lowest-ranking relative performance at the 10(3) and 10(5) colony forming unit (CFU)/mL exposure thresholds.
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4.
Pathogen inactivation methods to prevent transfusion-transmissible arboviruses
Giménez-Richarte Á, Ortiz de Salazar MI, Giménez-Richarte MP, Larrea L, Arbona C, Marco P, Ramos-Rincón JM
Tropical medicine & international health : TM & IH. 2023
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Editor's Choice
Abstract
OBJECTIVE Arboviruses are emerging as a relevant threat to transfusion safety. Pathogen inactivation methods may reduce the risk of transmission through transfusion, as long as they meet minimum standards for effectiveness. This study aims to assess the log reduction of viral load achieved with different pathogen inactivation methods, according to the blood product they are used on and the arbovirus targeted. METHODS Systematic literature review and meta-analysis. Searches were conducted in MEDLINE and Embase. The study protocol was registered in PROSPERO CRD42022312061. We selected records reporting the log reduction of viral load achieved with the main pathogen inactivation methods (amotosalen + UVA light [INTERCEPT], riboflavin + UV light [Mirasol], methylene blue + visible light/UVC light [THERAFLEX], solvent detergent, amustaline [INTERCEPT] and PEN110 [Inactine]), applied to any blood product (plasma, platelets, red blood cells or whole blood) and for any arbovirus. The log reduction of viral loads was assessed by obtaining the mean log reduction factor (LRF). We compared and classified the LRF of different techniques using statistical methods. RESULTS We included 59 publications reporting LRF results in 17 arboviruses. For 13 arboviruses, including Chikungunya virus, Dengue virus, West Nile virus, and Zika virus, at least one of the methods achieves adequate or optimal log reduction of viral load - mean LRF ≥4. The LRF achieved with riboflavin + UV light is inferior to the rest of the techniques, both overall and specifically for plasma, platelets preserved in platelet additive solution (PAS)/plasma, and red blood cells/whole blood. The LRF achieved using Mirasol is also lower for inactivating chikungunya virus, dengue virus, and Zika virus. For West Nile virus, we found no significant differences. In plasma, the method that achieves the highest LRF is solvent/detergent; in platelets, THERAFLEX and INTERCEPT; and in red blood cells/whole blood, PEN110 (Inactine). CONCLUSION Not all pathogen inactivation methods achieve the same LRF, nor is this equivalent between the different arboviruses or blood products. Overall, the LRFs achieved using riboflavin + UV light (Mirasol) are inferior to those achieved with the rest of the pathogen inactivation methods. Regarding the others, LRFs vary by arbovirus and blood product. In light of the threat of different arboviruses, blood establishments should have already validated pathogen inactivation methods and be logistically prepared to implement these techniques quickly.
PICO Summary
Population
Whole blood or human blood products from blood donors (59 studies).
Intervention
Systematic literature review and meta-analysis assessing the log reduction of viral load achieved with different pathogen inactivation methods, according to the blood product they were used on and the arbovirus targeted.
Comparison
Outcome
The included studies reported log reduction factor (LRF) results in 17 arboviruses. For 13 arboviruses, including Chikungunya virus, Dengue virus, West Nile virus, and Zika virus, at least one of the methods achieved adequate or optimal log reduction of viral load - mean LRF ≥4. The LRF achieved with riboflavin + UV light was inferior to the rest of the techniques, both overall and specifically for plasma, platelets preserved in platelet additive solution (PAS)/plasma, and red blood cells/whole blood. The LRF achieved using Mirasol was also lower for inactivating Chikungunya virus, Dengue virus, and Zika virus. For West Nile virus, no significant differences were found. In plasma, the method that achieved the highest LRF was solvent/detergent; in platelets, THERAFLEX and INTERCEPT; and in red blood cells/whole blood, PEN110 (Inactine).
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5.
Efficacy and Safety of Pathogen-Reduced Platelets Compared with Standard Apheresis Platelets: A Systematic Review of RCTs
Pati I, Masiello F, Pupella S, Cruciani M, De Angelis V
Pathogens (Basel, Switzerland). 2022;11(6)
Abstract
In this systematic review, we evaluate the efficacy and safety of blood components treated with pathogen reduction technologies (PRTs). We searched the Medline, Embase, Scopus, Ovid, and Cochrane Library to identify RCTs evaluating PRTs. Risk of bias assessment and the Mantel-Haenszel method for data synthesis were used. We included in this review 19 RCTs evaluating 4332 patients (mostly oncohematological patients) receiving blood components treated with three different PRTs. Compared with standard platelets (St-PLTs), the treatment with pathogen-reduced platelets (PR-PLTs) does not increase the occurrence of bleeding events, although a slight increase in the occurrence of severe bleeding events was observed in the overall comparison. No between-groups difference in the occurrence of serious adverse events was observed. PR-PLT recipients had a lower 1 and 24 h CI and CCI. The number of patients with platelet refractoriness and alloimmunization was significantly higher in PR-PLT recipients compared with St-PLT recipients. PR-PLT recipients had a higher number of platelet and RBC transfusions compared with St-PLT recipients, with a shorter transfusion time interval. The quality of evidence for these outcomes was from moderate to high. Blood components treated with PRTs are not implicated in serious adverse events, and PR-PLTs do not have a major effect on the increase in bleeding events. However, treatment with PRTs may require a greater number of transfusions in shorter time intervals and may be implicated in an increase in platelet refractoriness and alloimmunization.
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6.
Bacterial culture time to detection in platelet components: An evidence synthesis and estimation of detection failures
Walker BS, Schmidt RL, Moore RA, White SK, Fisher MA, Metcalf RA
Transfusion. 2022
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Editor's Choice
Abstract
BACKGROUND Non-pathogen reduction platelet bacterial risk control strategies in the US FDA guidance include at least one culture. Almost all of these strategies have a culture hold time of ≥12 h. Studies have reported time to detection (TTD) of bacterial cultures inoculated with bacteria from contaminated platelets, but these data and estimates of risk associated with detection failures have not been synthesized. METHODS We performed a literature search to identify studies reporting TTD for samples obtained from spiked platelet components. Using extracted data, regression analysis was used to estimate TTD for culture bottles at different inoculum sizes. Detection failures were defined as events in which contaminated components are transfused to a patient. We then used published data on time of transfusion (ToT) to estimate the risk of detection failures in practice. RESULTS The search identified 1427 studies, of which 16 were included for analysis. TTD data were available for 16 different organisms, including 14 in aerobic cultures and 11 in anaerobic cultures. For inocula of 1 colony forming unit (CFU), the average TTD for aerobic organisms was 19.2 h while it was 24.9 h in anaerobic organisms, but there was substantial overall variation. A hold time of 12 versus 24 h had minimal effect for most organisms. CONCLUSION TTD variation occurs between bacterial species and within a particular species. Under typical inventory management, the relative contribution of culture detection failures is much smaller than the residual risk from sampling failures. Increasing the hold period beyond 12 h has limited value.
PICO Summary
Population
Spiked platelets inoculated into bacterial cultures (16 studies).
Intervention
Systematic review to obtain summary estimates of the time to detection (TTD) for the most common contaminating organisms, and to estimate the risk of detection failures.
Comparison
Outcome
Regression analysis was used to estimate TTD for culture bottles at different inoculum sizes. Detection failures were defined as events in which contaminated components were transfused to a patient. Published data was used on time of transfusion to estimate the risk of detection failures in practice. TTD data were available for 16 different organisms, including 14 in aerobic cultures and 11 in anaerobic cultures. For inocula of 1 colony forming unit, the average TTD for aerobic organisms was 19.2 hours while it was 24.9 hours in anaerobic organisms, but there was substantial overall variation. A hold time of 12 vs. 24 hours had minimal effect for most organisms.
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7.
Pathogen Reduction Technologies and Their Impact on Metabolic and Functional Properties of Treated Platelet Concentrates: A Systematic Review
Tsalas S, Petrou E, Tsantes AG, Sokou R, Loukopoulou E, Houhoula D, Mantzios PG, Kriebardis AG, Tsantes AE
Seminars in thrombosis and hemostasis. 2022
Abstract
Pathogen reduction technologies (PRTs) such as Mirasol and Intercept were developed to eliminate transfusion-transmitted infections. The impact of PRTs on platelet function during the storage period, their effect on platelet storage lesions, and the optimal storage duration following PRTs have not been clearly defined. The aim of this study was to systematically review the existing literature and investigate the impact of PRTs on functional alterations of PRT-treated platelets during the storage period. The authors identified 68 studies suitable to be included in this review. Despite the high heterogeneity in the literature, the results of the published studies indicate that PRTs may increase platelet metabolic activity, accelerate cell apoptosis, and enhance platelet activation, which can subsequently lead to a late exhaustion of activation potential and reduced aggregation response. However, these effects have a minor impact on platelet function during the early storage period and become more prominent beyond the fifth day of the storage period. Large in vivo trials are required to evaluate the effectiveness of PRT-treated platelets during the storage period and investigate whether their storage can be safely extended to more than 5 days, and up to the traditional 7-day storage period.
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8.
Filariasis and transfusion-associated risk: a literature review
Drews SJ, Spencer BR, Wendel S, Bloch EM
Vox sanguinis. 2021
Abstract
BACKGROUND AND OBJECTIVES Filariae are parasitic worms that include the pathogens Loa loa, Onchocerca volvulus, Wuchereria bancrofti, Brugia spp. and Mansonella spp. which are endemic in parts of Africa, Asia, Asia-Pacific, South and Central America. Filariae have a wide clinical spectrum spanning asymptomatic infection to chronic debilitating disease including blindness and lymphedema. Despite successful eradication programmes, filarial infections remain an important -albeit neglected - source of morbidity. We sought to characterize the risk of transfusion transmission of microfilaria with a view to guide mitigation practices in both endemic and non-endemic countries. MATERIALS AND METHODS A scoping review of scientific publications as well as grey literature was carried out by a group of domain experts in microbiology, transfusion medicine and infectious diseases, representing the parasite subgroup of the International Society of Blood Transfusion. RESULTS Cases of transfusion-transmitted filariasis are rare and confined to case reports of variable quality. Transfusion-associated adverse events related to microfilariae are confined to isolated reports of transfusion reactions. Serious outcomes have not been reported. No known strategies have been implemented, specifically, to mitigate transfusion-transmitted filariasis yet routine blood donor screening for other transfusion-transmissible infections (e.g. hepatitis B, malaria) may indirectly defer donors with microfilaremia in endemic areas. CONCLUSION Rare examples of transfusion-transmitted filariasis, without serious clinical effect, suggest that filariasis poses low transfusion risk. Dedicated mitigation strategies against filarial transfusion transmission are not recommended. Given endemicity in low-resource regions, priority should be on the control of filariasis with public health measures.
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9.
Molecular and serological markers of human parvovirus B19 infection in blood donors: A systematic review and meta-analysis
Farahmand M, Tavakoli A, Ghorbani S, Monavari SH, Kiani SJ, Minaeian S
Asian journal of transfusion science. 2021;15(2):212-222
Abstract
BACKGROUND Human parvovirus B19 (B19V) is one of the blood-borne viruses. The virus can be transmitted to susceptible individuals by blood or blood products. The virus is not associated with significant disease in general population, while people with underlying problems such as immunodeficiency can cause anemia and arthritis. The current systematic review and meta-analysis aimed to estimate the overall prevalence of B19V DNA, anti-B19V IgG, and anti-B19V IgM antibodies in blood donors worldwide. METHODS A systematic search was carried out in online databases for relevant studies from inception until March 30, 2019. Study selection was performed based on predesigned eligibility criteria. The proportion of B19V DNA, anti-B19V IgG, and anti-B19V IgM antibodies were pooled using the inverse variance method. All statistical analyses were performed using the R version 3.5.3, package "meta." RESULTS According to the random-effects model, the pool prevalence of B19V DNA, anti-B19V IgM, and anti-B19V IgG among blood donors was calculated to be 0.4% (95% confidence interval [CI] =0.3%-0.6%), 2.2% (95% CI = 1.3%-3.7%), and 50.1% (95% CI = 43.1%-57.1%), respectively. CONCLUSION For the transmission of B19V through blood, the presence of the virus genome is required, and the present study showed that the prevalence of the virus genome in blood donors is <1%. Therefore, there is no need to screen donated blood for B19V infection.
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10.
Bacterial contamination rate of platelet components by primary culture: a systematic review and meta-analysis
White SK, Schmidt RL, Walker BS, Metcalf RA
Transfusion. 2020;60(5):986-996
Abstract
BACKGROUND Platelets have the highest bacterial contamination risk of all blood components, and septic transfusion reactions remain a problem. A good estimate of contamination rates could provide information about residual risk and inform optimal testing strategies. We performed a systematic review and meta-analysis of platelet contamination rates by primary culture. STUDY DESIGN AND METHODS A literature search in December 2019 identified articles on platelet contamination rates using primary culture. We used meta-analysis to estimate the overall rate of contamination and meta-regression to identify heterogeneity. We studied the following sources of heterogeneity: collection method, sample volume, positivity criteria, and study date. Contamination rate estimates were obtained for apheresis (AP), platelet rich plasma (PRP), and buffy coat (BC) collection methods. RESULTS The search identified 6102 studies, and 22 were included for meta-analysis. Among these 22 studies, there were 21 AP cohorts (4,072,022 components), 4 PRP cohorts (138,869 components), and 15 BC cohorts (1,474,679 components). The overall mean contamination rate per 1000 components was 0.51 (95% CI: 0.38-0.67) including AP (0.23, 95% CI: 0.18-0.28), PRP, (0.38, 95% CI: 0.15-0.70), and BC (1.12, 95% CI: 0.51-1.96). There was considerable variability within each collection method. Sample volume, positivity criteria, and publication year were significant sources of heterogeneity. CONCLUSION The bacterial contamination rate of platelets by primary culture is 1 in 1961. AP and PRP components showed a lower contamination rate than BC components. There is clinically significant between-study variability for each method. Larger sample volumes increased sensitivity, and bacterial contamination rates have decreased over time.
