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Background Brazilian blood banks encourage donors to report postdonation information (PDI) regarding conditions that would lead to deferral in an attempt to retrieve distributed nonconforming blood. Objectives This study evaluated the profile of donors reporting PDI, the impact on transfusion safety, and the possible impact on the discard of blood products. Subjects and methods We analyzed 115 consecutive PDIs between May 2014 and July 2015, a period comprising two dengue-like syndrome (DLS) outbreaks. Results These PDIs accounted for 87,780 blood donations. The average time for PDIs since donation was 4 (0-23) days and 190 blood components were discarded. DLS accounted for 21.7% of the PDIs analyzed; 11 of the 23 samples tested were nucleic acid test (NAT) positive for dengue and 2 positive for Zika virus (ZIKV). Six of these PDIs were reported after blood components have been transfused: After NAT testing, one of these recipients was diagnosed with dengue and another one with ZIKV infection, both possible transfusions transmitted but without clinical consequences. Conclusion The high number of recovered blood components due to PDI suggests that PDI remains a great ally in the fight against transfusion-transmitted infections and may be particularly useful during outbreaks of emerging potentially blood-borne pathogens.

Currently, there are no evidence-based treatment options for long COVID-19, and it is known that SARS-CoV-2 can persist in part of the infected patients, especially those with immunosuppression. Since there is a robust secretion of SARS-CoV-2-specific highly-neutralizing IgA antibodies in breast milk, and because this immunoglobulin plays an essential role against respiratory virus infection in mucosa cells, being, in addition, more potent in neutralizing SARS-CoV-2 than IgG, here we report the clinical course of an NFκB-deficient patient chronically infected with the SARS-CoV-2 Gamma variant, who, after a non-full effective treatment with plasma infusion, received breast milk from a vaccinated mother by oral route as treatment for COVID-19. After such treatment, the symptoms improved, and the patient was systematically tested negative for SARS-CoV-2. Thus, we hypothesize that IgA and IgG secreted antibodies present in breast milk could be useful to treat persistent SARS-CoV-2 infection in immunodeficient patients.

Even after two years of the pandemic, a completely effective treatment against SARS-CoV-2 has not yet been established. Considering this fact and the emergence of successive new viral variants, the development of therapies based on natural polyclonal antibodies recovered from convalescent plasma remains relevant. This study presents a comparison between different methods of screening antibodies in samples of 41 individuals previously diagnosed with COVID-19. We found a significant correlation between Abbot Architect anti-SARS-CoV-2 IgG and Abbott Allinity SARS-CoV-2 IgG II Quantitative assay intensity of reactivity and neutralizing antibody (nAb) titers. Thus, we propose an initial antibody screening with IgG anti-N Abbott Architect test, with an index of, for example, 3.25 or SARS-CoV-2 IgG II Quantitative Abbott Allinity assay 137.65 AU/mL as good predictors of Nab ≥ 1:80. For the quantitative method, this threshold demonstrated a 100 % sensitivity and 80 % specificity, with 97.3 % accuracy. An interesting observation was the increase in the neutralizing activity of the anti-SARS-CoV-2 antibodies with the longest interval between the end of the symptoms and the collection, demonstrating that the delay in plasma collection does not affect the achievement of adequate nAbs levels. These results demonstrate the possibility of using faster and more widely available commercial serological tests with a good correlation with viral neutralization tests in culture, allowing for optimized large-scale donor selection, which will be of utmost importance for the development of therapies such as hyperimmune immunoglobulin.

Background Mutations accrued by SARS-CoV-2 lineage P.1—first detected in Brazil in early January, 2021—include amino acid changes in the receptor-binding domain of the viral spike protein that also are reported in other variants of concern, including B.1.1.7 and B.1.351. We aimed to investigate whether isolates of wild-type P.1 lineage SARS-CoV-2 can escape from neutralising antibodies generated by a polyclonal immune response. Methods We did an immunological study to assess the neutralising effects of antibodies on lineage P.1 and lineage B isolates of SARS-CoV-2, using plasma samples from patients previously infected with or vaccinated against SARS-CoV-2. Two specimens (P.1/28 and P.1/30) containing SARS-CoV-2 lineage P.1 (as confirmed by viral genome sequencing) were obtained from nasopharyngeal and bronchoalveolar lavage samples collected from patients in Manaus, Brazil, and compared against an isolate of SARS-CoV-2 lineage B (SARS.CoV2/SP02.2020) recovered from a patient in Brazil in February, 2020. Isolates were incubated with plasma samples from 21 blood donors who had previously had COVID-19 and from a total of 53 recipients of the chemically inactivated SARS-CoV-2 vaccine CoronaVac: 18 individuals after receipt of a single dose and an additional 20 individuals (38 in total) after receipt of two doses (collected 17–38 days after the most recent dose); and 15 individuals who received two doses during the phase 3 trial of the vaccine (collected 134–230 days after the second dose). Antibody neutralisation of P.1/28, P.1/30, and B isolates by plasma samples were compared in terms of median virus neutralisation titre (VNT50, defined as the reciprocal value of the sample dilution that showed 50% protection against cytopathic effects). Findings In terms of VNT50, plasma from individuals previously infected with SARS-CoV-2 had an 8·6 times lower neutralising capacity against the P.1 isolates (median VNT50 30 [IQR Interpretation SARS-CoV-2 lineage P.1 might escape neutralisation by antibodies generated in response to polyclonal stimulation against previously circulating variants of SARS-CoV-2. Continuous genomic surveillance of SARS-CoV-2 combined with antibody neutralisation assays could help to guide national immunisation programmes. Funding São Paulo Research Foundation, Brazilian Ministry of Science, Technology and Innovation and Funding Authority for Studies, Medical Research Council, National Council for Scientific and Technological Development, National Institutes of Health. Translation For the Portuguese translation of the abstract see Supplementary Materials section.

Despite being initially considered at higher risk for severe COVID‐19, sickle cell disease (SCD) patients have mostly presented clinical severity similar to the general population. As their vulnerability to become infected remains uncertain, we assessed the seroreactivity for SARS‐CoV‐2 to estimate the prevalence of infection and possible phenotypic and socioeconomic determinants for their contagion. Serologic evaluation was performed on 135 patients with an overall prevalence of 11%; positivity was associated with older age and use of public transportation. We speculate that social distancing instructions recommended by our clinic may have contributed to lower levels of infection, but potential protection factors need further investigation.

Le Bresil est un pays continental compose de differents biomes, ainsi que de zones urbaines a forte densite de population. Ces caracteristiques demographiques et climatiques conduisent a l'apparition d'un grand nombre de maladies infectieuses, souvent susceptibles de transmettre des transfusions sanguines. Le ministere de la Sante considere la securite transfusionnelle comme une priorite depuis les annees 1980, integrant progressivement les exigences legales. En plus d'evaluer l'exposition au risque ITT realisee par une evaluation medicale ou paramedicale avant tous les dons de sang, les tests de laboratoire obligatoires comprennent les tests de depistage suivants : syphilis (treponemique ou non treponemique), hepatite B (HBsAg, anti-HBc et NAT), hepatite C (anti-HCV et NAT), VIH/SIDA (anti-VIH 1/2/O/Agp24 et NAT), la m. de Chagas et anti-HTLV 1/2. En Amazonie, un test de detection du plasmodium, des antigenes plasmodiaux ou du materiel genomique capable de detecter une infection active par P. falciparum, vivax et malariae doit etre effectue pour tous les dons. La definition de l'endemicite des zones se fait au moyen d'un indicateur de la positivite des tests d'investigation (IPA). Plus recemment, lors de l'emergence arbovirus (ZIKV, CHKV et DENV), la legislation a defini de nouveaux criteres et strategies pour l'evaluation du risque transfusionnel. La pandemie COVID-19 a declenche des strategies pour reduire le risque de transmission de maladies infectieuses par transfusion. Une surveillance constante permet d'evaluer les risques et de definir des strategies dans des pays aux ressources limitees, tels que le Bresil. (French) [ABSTRACT FROM AUTHOR] Copyright of Transfusion Clinique et Biologique is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background Common variable immunodeficiency is the most prevalent symptomatic primary immunodeficiency in adults. Affected patients fail to mount an appropriate humoral response against community acquired infectious diseases and recent reports have provided data supporting the increased susceptibility of these patients to severe SARS-CoV-2 infections. In this context, the infusion of COVID-19 convalescent plasma could represent an effective therapeutic strategy. Case presentation 25-year old woman diagnosed with common variable immunodeficiency in 2013, developed severe COVID-19 that rapidly progressed to pneumonia presenting with multiple bilateral lung opacities that were both central and peripheral and presented as ground-glass and consolidation types involving all lobes, bilaterally. As blood oxygen saturation decayed and lung abnormalities were not responsive to large spectrum antibiotics and corticosteroids, patient was placed on mechanical ventilation and compassionate-use of approved COVID-19 convalescent donor plasma was introduced. The patient presented a rapid response to the approach and mechanical ventilation could be interrupted 24 h after first dose of COVID-19 convalescent donor plasma. As a whole, the patient received four doses of 200 mL convalescent plasma during a period of 6 days. There was rapid improvement of clinical status, with interruption of supplemental oxygen therapy after 6 days and reduction of lung abnormalities as evidence by sequential computed tomography scans. Conclusions This is a single patient report that adds to other few reports on common variable immunodeficiency and agammaglobulinemia, suggesting that COVID-19 convalescent donor plasma could be a valuable therapeutic approach to treat patients affected by dysgammaglobulinemias and presenting severe COVID-19.

Background: Some studies have determined that the SARS-CoV-2 B.1.1.7 variant of concern (VOC) has been associated with increased transmissibility, hospitalization, and mortality. This study aimed to explore the factors associated with B.1.1.7 VOC infection in the context of vaccination with adenovirus-vectored and inactivated vaccines. Methods: We analyzed epidemiological, clinical, and laboratory data from simultaneous COVID-19 outbreaks in a convent (Outbreak A) and in a long-term care facility (Outbreak B) in individuals vaccinated with a single dose of ChAdOx1 or two doses of the CoronaVac vaccine, respectively. First, we identified the viral lineages associated with these outbreaks by genome sequencing. Then, we assessed the relationship of viral load, specific immunoglobulin antibody levels, neutralization antibodies, case characteristics (age, vaccine type, and presence or absence of symptoms), and associations with risk of developing COVID-19. Findings: On March 2021, we detected SARS-CoV-2 RNA in nasopharyngeal samples from 14 of 22 of the ChAdOx1 vaccine recipients (Outbreak A, n=26), and 22 of 42 of the CoronaVac-vaccinated individuals (Outbreak B, n=52) for breakthrough infection rates for ChAdOx1 of 63·6% and 52·4% for CoronaVac. Vaccinated individuals from Outbreak A received a single dose at least 23 days before the outbreak, and the Outbreak B was involved virus detection 5 to 27 days after a second dose. In these outbreaks, the median ages were 73 and 77 years old, respectively. The median viral loads were 3·4×101 and 2·3×103 RNA copies per mL in Outbreaks A and B, respectively. In total for both outbreaks, 12 people had mild-COVID-19 while 26 were asymptomatic, but one case involving a person from Outbreak B was fatal. Based on analysis of SARS-CoV-2 genome sequences, we determined that outbreaks A and B were caused by two independent clusters of the B.1.1.7 VOC. Interestingly, the serum of PCR-positive symptomatic SARS-CoV-2-infected individuals had ~1·8 to 3·4-fold more neutralizing capacity against B.1.1.7 compared to the serum of asymptomatic, SARS-CoV-2-infected individuals, indicating that the levels of neutralizing antibodies induced by ChAdOx1 and CoronaVac were not correlated with protection against symptomatic infection. Interpretation: These data suggest that the B.1.1.7 variant can escape from the immune response elicited by immunization with a single dose of an adenovirus-vectored vaccine or two doses of an inactivated vaccine. However, partial immunization with ChAdOx1 and the complete series of CoronaVac seemed to provide protection against severe COVID-19 and death in the large majority of individuals. Continued and rapid immunization combined with nonpharmaceutical interventions (e.g., masking and physical distancing), are necessary to break the SARS-CoV-2 transmission until herd immunity improves. Funding Information: Sao Paulo Research Foundation, Brazilian Ministry of Science, Technology and Innovation and Funding Authority for Studies, Coordination for the Improvement of Higher Education Personnel, Wellcome Trust, Medical Research Council, National Institutes of Health, and Brazilian National Council for Scientific and Technological Development. Declaration of Interests: All other authors declare no competing interests. Ethics Approval Statement: All procedures followed the ethical standards of the responsible committee on human experimentation and were approved by the ethics committees from the University of Campinas, Brazil (Approval number: CAEE 31170720.3.0000.5404).

Background: A new SARS-CoV-2 lineage, named P.1 (20J/501Y.V3), has recently been detected in Brazil. Mutations accrued by the P.1 lineage include amino acid changes in the receptor-binding domain of the spike protein that also are reported in variants of concern in the United Kingdom (B.1.1.7) and South Africa (B.1.325). Methods: We isolated two P.1-containing specimens from nasopharyngeal and bronchoalveolar lavage samples of patients of Manaus, Brazil. We measured neutralization of the P.1 virus after incubation with the plasma of 19 COVID-19 convalescent blood donors and recipients of the chemically-inactivated CoronaVac vaccine and compared these results to neutralization of a SARS-CoV-2 B-lineage previously circulating in Brazil. Findings: The immune plasma of COVID-19 convalescent blood donors had 6-fold less neutralizing capacity against the P.1 than against the B-lineage. Moreover, five months after booster immunization with CoronaVac, plasma from vaccinated individuals failed to efficiently neutralize P.1 lineage isolates. Interpretation: These data indicate that the P.1 lineage may escape from neutralizing antibodies generated in response to polyclonal stimulation against previously circulating variants of SARS-CoV-2. Funding: Sao Paulo Research Foundation, MCTI/FINEP, Medical Research Council, National Council for Scientific and Technological Development, National Institutes of Health. Conflict of Interest: M.S.D. is a consultant for Inbios, Vir Biotechnology, NGMBiopharmaceuticals, and Carnival Corporation, and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. Ethical Approval: All procedures followed the ethical standards of the responsible committee on humanexperimentation and approved by the ethics committees from the University of Campinas, Brazil (Approval number CONEP 4.021.484 for plasma collection of blood donors, CAEE32078620.4.0000.5404 and 30227920.9.0000.5404 for the sampling of vaccinated and viral genome sequencing, respectively). All patient data were anonymized before study inclusion.Informed consent was obtained from all subjects for being included in the study.

The relationship between the recent Zika virus (ZIKV) outbreak and the increase in the incidence of microcephaly in newborns prompted the declaration of a public health emergency in many countries. As ZIKV was identified in the blood of healthy blood donors and survives blood processing techniques and storage conditions, its transmission through transfusion was plausible and raised concerns about the safety of blood inventories and recipients at risk, such as immunosuppressed patients and pregnant women. This chapter provides an updated review of the prevalence of ZIKV infection in blood donors and transfusion recipients around the world and discusses the possible measures for preventing its transfusion transmission, including the clinical and laboratory screening of potential donors and the inactivation of pathogens in blood components. The coordination of research and public policy efforts against the threat of new emerging pathogens is also discussed.

A SARS-CoV-2 B.1.1.7 variant of concern (VOC) has been associated with increased transmissibility, hospitalization, and mortality. This study aimed to explore the factors associated with B.1.1.7 VOC infection in the context of vaccination. On March 2021, we detected SARS-CoV-2 RNA in nasopharyngeal samples from 14 of 22 individuals vaccinated with a single-dose of ChAdOx1 (outbreak A, n = 26), and 22 of 42 of individuals with two doses of the CoronaVac vaccine (outbreak B, n = 52) for breakthrough infection rates for ChAdOx1 of 63.6% and 52.4% for CoronaVac. The outbreaks were caused by two independent clusters of the B.1.1.7 VOC. The serum of PCR-positive symptomatic SARS-CoV-2-infected individuals had ~1.8–3.4-fold more neutralizing capacity against B.1.1.7 compared to the serum of asymptomatic individuals. These data based on exploratory analysis suggest that the B.1.1.7 variant can infect individuals partially immunized with a single dose of an adenovirus-vectored vaccine or fully immunized with two doses of an inactivated vaccine, although the vaccines were able to reduce the risk of severe disease and death caused by this VOC, even in the elderly.

Objetivos: Avaliar a incidência e evolução clínica da COVID-19 em pacientes com leucemia mieloide crônica (LMC) acompanhados em dois centros. Materiais e métodos: Estudo prospectivo, observacional, em andamento. Os pacientes responderam a dois questionários com 6 meses de intervalo. Foram incluídas perguntas relacionadas a sintomas, comorbidades, incidência e suspeita de COVID-19, contatos com pessoas infectadas, comportamento durante a pandemia, gravidade da infecção e vacinação. Cada questionário avaliou dados referentes aos últimos 6 meses. Adicionalmente, foram obtidos dados clínicos, laboratoriais e de tratamento dos prontuários médicos.Os dados foram coletados e armazenados no sistema REDCap. Resultados: Entre setembro de 2020 e julho de 2021, 225 pacientes responderam ao primeiro questionário e 121 também responderam ao segundo. Dos analisados, 127 (56,4%) eram homens. A mediana de idade 56,5 anos (19-90). A maioria estava em tratamento com inibidores de tirosina quinase (88.5%) e 11.5% sem tratamento, em protocolo de descontinuação. 80% dos pacientes realizaram distanciamento social e 30% dos avaliados tiveram algum familiar ou contato próximo com COVID-19. Nos 6 meses anteriores à aplicação do primeiro questionário, 49 (21,9%) tiveram sintomas respiratórios, 30 (13,4%) febre, 7 (3,1%) pneumonia e 45 (20,1%) falta de ar ou tosse seca. Comorbidades: 79 (35,6%) hipertensão, 34 (15,3%) diabetes, 15 (6,8%) insuficiência renal, 13 (5,9%) doença pulmonar, 37 (16,7%) cardiopatia e 43 (19,4%) outra doença crônica. No total, 28 (12,4%) pacientes foram diagnosticados com COVID-19, enquanto 10 foram suspeitos. A mediana de idade foi 47 anos, 67,9% eram homens; 10 (37,0%) não estavam respeitando o distanciamento social. 36% tinham comorbidades: 12% diabetes, 28% hipertensão, 4% insuficiência renal, 24% cardiopatia e 12% outra doença crônica. 12 tiveram algum familiar ou contato próximo diagnosticado com COVID-19. Vinte e seis (92%) pacientes tiveram forma leve, sem necessidade de internação, um paciente de 71 anos em uso de nilotinibe e em RMM teve quadro grave, com óbito. 27 pacientes estavam na fase crônica e um em fase acelerada. Treze apresentavam resposta molecular maior, um resposta hematológica, 4 resposta citogenética completa, 3 MR4.0 e 7 MR4.5. Tratamento vigente: imatinibe (16), dasatinibe(5), nilotinibe (5) e um sem tratamento. Houve um caso de reinfecção. Até o momento, 84 (37%) dos pacientes receberam vacinas para a COVID-19 (32 CoronaVac, 51 Oxford/AstraZeneca e um da Pfizer). Dentre os pacientes vacinados, 22 apresentaram reações adversas: 8 apresentaram febre, 6 dor de cabeça e 20 outros (dores no corpo, calafrios ou dores no local da injeção). Discussão: Pacientes com neoplasias hematológicas tem quadro mais grave e maior mortalidade associada a COVID-19. Na LMC a mortalidade parece ser levemente superior à da população geral, com pior evolução nas fases mais avançadas e em pacientes com comorbidades. Tivemos um caso de óbito e um de reinfecção, onde não podemos descartar a hipótese de uma variante. Conclusão: A incidência de COVID-19 na população de LMC estudada foi de 12,4%, mais frequente em homens, com menor mediana de idade e menor taxa de isolamento social, com predomínio de casos leves e moderados. Todos os casos descritos ocorreram antes da vacinação.

BACKGROUND The reason for the difference in susceptibility to red blood cell (RBC) alloimmunization among patients with sickle cell disease (SCD) is not clearly understood and is probably the result of multiple factors. Our hypothesis is that genetic polymorphisms are associated with RBC alloimmunization. STUDY DESIGN AND METHODS We investigated the possible association of susceptibility to RBC alloimmunization with polymorphisms of HLA and cytokines genes in 161 SCD patients prior exposed to RBC transfusion. Cytokine gene polymorphisms were analyzed by polymerase chain reaction (PCR) and TaqMan assays. HLA Class I genotyping was performed using PCR-specific sequence of oligonucleotides. Polymorphism frequencies were compared using the Fisher's exact test. RESULTS Our results revealed increased percentage of the A allele and the GA genotype of the TNFA −308G/A cytokine among alloimmunized patients when compared to nonalloimmunized patients (A allele, 16.4% vs. 6.8%, p = 0.004; GA genotype, 32.8% vs. 11.7%, p = 0.0021). In addition, the IL1B −511T allele and the IL1B −511TT and CT genotype frequencies were overrepresented among alloimmunized patients (T allele, 53.0% vs. 37.5%, p = 0.0085; CT + TT genotypes, 81.82% vs. 60.87%, p = 0.0071). In relation to HLA Class I, we found a higher frequency of HLA-DRB1*15 among patients alloimmunized to Rh antigens when compared to nonalloimmunized patients (15.63% vs. 6.98%, p = 0.044). CONCLUSION Brazilian SCD patients with the TNFA, IL1B, and HLA-DRB1 gene polymorphisms were at increased risk of becoming alloimmunized by RBC transfusions. These findings may contribute to the development of future therapeutic strategies for patients with SCD with higher susceptibility of alloimmunization.

The potential for transfusion transmission of dengue virus (DENV), chikungunya virus (CHIKV), and Zika virus (ZIKV) has raised concerns about the safety of the blood supply in endemic areas. In this study, nucleic acid testing (NAT) for ZIKV, DENV, and CHIKV RNA was performed in asymptomatic blood donor samples in the city of Campinas, located in the southeast region of Brazil (1962 in 2015 and 1775 in 2016). The prevalence of reactive NAT was 0.15% in 2015 and 0.62% in 2016 for dengue, 0.05% in 2015 and 0.17% in 2016 for Zika, and 0% in both years for chikungunya. These results demonstrate the weakness of the clinical interview in screening these blood donors. Furthermore, positivity for ZIKV was detected in March 2015, 1 year before the first reported cases in the region. These data attest the feasibility of using donor samples held in library as a tool for retrospective epidemiological evaluation, which is particularly interesting considering emerging pathogens, for which data on their spread and penetrance are initially scarce.

Background: Zika, a disease caused by Zika virus infections, has recently emerged and caused outbreaks in many parts of the world. The clinical manifestations of Zika are usually mild, mostly presenting as an exanthematic febrile disease, but on some occasions, it might be associated with microcephaly after intrauterine infection, and Guillain-Barré Syndrome. Zika virus is primarily transmitted by mosquito bites, but other means of transmission have been described, and potential risk for blood transmission has been reported in French Polynesia and Brazil. Methods: To investigate the risk of Zika virus infection after a blood transfusion in an area of Brazil where a possible transmission by a platelet concentrate has been described. Using a mini-pool format, 1857 blood donations were evaluated by real-time reverse transcriptase polymerase chain reaction designed to detect Zika virus RNA. Results: After testing samples individually from positive mini-pools, the prevalence of Zika virus RNA was only 0.16%, a result probably associated to the low circulation of this virus in the study area. In addition, it was evident that the implementation of post-surveillance programs is important to detect Zika virus infections in blood donors, as the post-donation surveillance program detected two blood donors with the disease in this study. Conclusion: This study shows that the risk for Zika virus transmission by blood transfusion is real, even in regions with a low circulation of the disease, but the combination of the detection of Zika virus RNA by polymerase chain reaction and post-donation surveillance might reduce the risk of transmission by blood transfusions. Keywords: Zika, Blood transfusion, Transfusion risk, ZIKV

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by decreased activity of ADAMTS13, resulting in reduced clearance of ultralarge von Willebrand factor (VWF) multimers. Treatment of TTP is therapeutic plasma exchange (TPE) with replacement with fresh frozen plasma (FFP). Cryoprecipitate-poor plasma (CPP) is a plasma product with lower concentrations of large VWF multimers, and similar amounts of ADAMTS13. CPP is regarded as at least as efficacious as FFP in TTP but evidence of additional benefits has not been demonstrated. Furthermore, there are limited data on the frequency of adverse events associated with CPP. Material and methods: In our center, the choice between CPP and FFP is performed before the 1st TPE session at the physicians' discretion. Here, we retrospectively evaluated the efficacy and safety of CPP based on the number of sessions, volume of plasma exposure, frequency of exacerbations/relapses, and adverse events. Results: Fourteen patients with newly diagnosed TTP were included in this analysis. The proportion of CPP:FFP use was 5:9. There were no significant differences in age, gender, initial hemoglobin, platelet count, LDH, or etiology of TTP between groups. We observed a trend toward a higher number of TPE sessions and higher plasma exposure in CPP, compared to FFP-treated patients. Acute exacerbations were more frequent among patients treated with CPP (OR 26.6; 95%CI 1.01–703.51; P = 0.03). Mild allergic reactions were the most common treatment-related adverse event in both groups. Discussion: Our data suggest that CPP should not be used as 1st line treatment for newly diagnosed TTP patients. J. Clin. Apheresis 29:311–315 2014. © 2014 Wiley Periodicals, Inc.

Le Bresil est un pays continental qui realise environ 3,5 dons de sang volontaires par an. Il est forme de plusieurs biomes, ainsi que de zones urbaines a forte densite de population. Ces caracteristiques demographiques et climatiques conduisent a l’apparition d’un grand nombre de maladies infectieuses, souvent susceptibles de transmettre des transfusions sanguines. Le ministere de la sante considere la securite transfusionnelle comme une priorite depuis les annees 1980, integrant progressivement les exigences legales en matiere de selection des donneurs et de tests de laboratoire. En plus d’evaluer l’exposition au risque d’infections transmissibles par transfusion (ITT) realisee par une evaluation medicale avant tous les dons de sang, les tests de laboratoire obligatoires comprennent les tests de depistage suivants : syphilis, hepatite B (HBsAg, anti-HBc et NAT), hepatite C (anti-HCV et NAT), VIH/SIDA (anti-VIH 1/2/O/p24 et NAT), la maladie de Chagas (CLIA ou EIA) et anti-HTLV1/2 (CLIA ou EIA). En Amazonie, un test de detection du plasmodium, des Ag plasmodiaux ou NAT, capable de detecter P. falciparum, vivax et malariae doit etre effectue pour tous les dons. La definition de l’endemicite des zones se fait au moyen d’un indicateur de la positivite des tests d’investigation (IPA). Le sang recueilli dans ces regions ne peut etre mis a la disposition de regions non endemiques. Plus recemment, lors de l’emergence de certains arbovirus, la legislation a defini de nouveaux criteres et strategies pour l’evaluation du risque transfusionnel. Une surveillance constante permet d’evaluer les risques et de definir des strategies dans des pays aux ressources limitees, comme le Bresil.

The blood center is the focus unit of a blood supply chain; and it has among its main assignments, the following activities: blood collection from donors, blood processing and blood components distribution to hospitals and healthcare institutions. It is surely the nervous center of the chain where planning, monitoring and controlling of these activities must be efficiently performed in order to prevent the stockout or outdate of blood components. All efficiency performance provided by a blood center will depend on the quality of its planning process, which starts with a good accuracy of forecasting required for blood supply and blood components. In this paper, a computational environment, which is oriented for forecasting of blood components, is presented. The idea is to improve the planning of the inventory balance process of the blood supply chain.

We report here the genome sequence of Zika virus, strain ZikaSPH2015, containing all structural and nonstructural proteins flanked by the 5′ and 3′ untranslated region. It was isolated in São Paulo state, Brazil, in 2015, from a patient who received a blood transfusion from an asymptomatic donor at the time of donation.

Sickle cell disease is a chronic inflammatory condition characterized by elevated levels of inflammatory cytokines, which may be regulated by genetic polymorphisms and could be associated with diverse disease presentations and alloimmunization. The aim of this study was to evaluate Treg and Th17 cell frequencies, cytokine gene polymorphisms, and their association with cytokine expression profile in patients with sickle cell disease. For that purpose, we evaluated the IL intron 3 variable number tandem repeat (VNTR, genotypes 1.1, 1.2, 2.2, and 2.3), IL4-T590C>T, IL6-174G>C, TNFα-308G>A, IL10-819T>C, IL10-592A>C, and IL10-1082A>G polymorphisms and their correlation with TGFβ, IL4, IL6, and IL10 gene expression in sickle cell patients. We observed a significant decrease in Treg frequency together with a substantial increase in Th17 response in patients with sickle cell disease compared with healthy controls (p

SUMMARY . Cytokines are associated with inflamma-tory responses including febrile non-hemolytic trans-fusion reactions (FNHTR). Moreover, there aresome polymorphisms of these cytokine genes asso-ciated with different levels of gene expression. Theaim of the present study was to investigate the asso-ciation of inflammatory cytokine gene polymorph-isms with the occurrence of FNHTR inmultitransfused patients. We studied two groups oftransfused patients: one presenting FNHTR before20 transfusions of red blood cells concentrates andthe other which never presented FNHTR even after20 transfusions. The gene polymorphisms studiedwere IL1B 511C/T and þ3953C/T, IL1RN (intron 2,variable number tandem repeat), IL6–174G/C, IL10 1082G/A and 819C/T, TNF-308G/A andLTAþ253G/A using polymerase chain reaction andrestriction digestion or sequencing methods. An asso-ciation of IL1RN*2 2 genotype with the occurrenceof precocious FNHTR (P < 0 025) was detected.This allele and this genotype have been related withhigher serum levels of interleukin (IL)-1b in vivo andhigher promoter activity. No other association wasdemonstrated. The association of gene polymorph-isms related with the increase of inflammatory cyto-kine gene expression may be a relevant factor inFNHTR and requires confirmation.Key words: blood transfusion, cytokine, gene poly-morphism, transfusion reaction.Although blood and blood component transfusion isusually a safe and an effective form of therapy, thereare risks of adverse effects. The immediate effects arecalled transfusion reactions, and the most commonlyrecognized is the febrile non-hemolytic transfusionreaction (FNHTR). This manifestation is character-ized by fever, with or without chills, without haemo-lysis. The fever can be mild or severe and is morefrequent in blood recipients who have been pregnantor transfused repeatedly (multitransfused) (Jenner H Heddle & Kelton, 1996). The occur-rence of FNHTR is unpredictable, and individualcharacteristics of each patient may be involved. Twomechanisms are described: one involving the whiteblood cell (WBC) antibodies present in the plasmaof multitransfused or previously pregnant womenwhich reacted with donor WBC contaminating bloodcomponents, causing endogenous pyrogens releasefrom patient macrophages or from donor WBC(Dzik, 1992; Dzik et al., 1992); and the other invol-ving an increase of cytokines in platelet concen-trates during storage. This cytokine accumulation issecondary to WBC activation associated with thecontact of these cells, mainly mononuclear cells(MNC), with the bag material. The main criticalfactors in determining cytokine accumulation areconsidered to be the WBC content and the age ofthe blood component (Heddle et al., 1993; Muylleet al., 1993; Aye et al., 1995; Muylle et al., 1996).These two mechanisms do not explain all cases ofFNHTR, and individual characteristics of patients,such as clinical conditions, immunologic diseases andassociation with infections may be associated withthe gravity and occurrence of FNHTR.The endogenous pyrogens are cytokines or chemo-kines, and those most related with the occurrence offever are interleukin (IL)-1, IL-6, IL-8 and tumournecrosis factor (TNF). They appear to be associatedwith the occurrence of FNHTR and other

Background : Transfusion-transmitted infections (TTI) continue to be a problem in many parts of the world, and multi-transfused patients (MTP) are at a particularly increased risk of TTI. Objectives : to estimate the prevalence of TTI among multi-transfused patientsin Brazil, and to understand the epidemiological characteristics of TTI among these patients. Study design : cross-sectional study of 353 MTP, who were interviewed using a structured questionnaire and tested for serological markers of hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infection. Results : the overall prevalence of HCV, HIV, HBV and co-infection among MTP were 16.7%, 1.7%, 0.8% and 1.7% respectively. A dose-effect relationship could be detected between the number of units transfused and HCV infection. Other non-transfusion related (NTR) risk factors for HCV did not confer any excess risk of HCV infection to MTP. Conclusions : HCV infection was the most prevalent TTI among MTP, and remains a major health problem for these patients.A dose-effect relationship could be detected between HCV and the number of units transfused. The implementation of measures such as donor education programs, standards for donor selection criteria, and of improved serological screening protocols, paralleled the decline in the prevalence of TTI, specially of HCV, observed in MTP, underscoring the importance of such measures for the reduction of the residual risk of TTI.

Chronic idiopathic neutropenia of adults (CINA) is a granulocytic disorder characterised by the "unexplained" decrease in the number of circulating neutrophils. Serum inflammatory cytokines and chemokines are increased in CINA. In addition, cytokines gene polymorphisms are associated with increased levels of respective products and related with inflammatory diseases. The aim of the present study was to investigate the association of polymorphisms of IL1B-511C/T and +3953C/T, IL1RN intron 2, IL6-174G/C and TNF-308G/A genes with CINA. We analysed 29 CINA and controls by polymerase chain reaction and restriction fragment length polymorphism. Statistical analyses were performed using chi2 test, and the Hardy-Weinberg equilibrium (HWE) was investigated. All alleles analysed were in HWE in both populations. Similar frequencies of IL1B-511C/T, IL1B+3953C/T, IL1RN, IL6-174G/C and TNF-308G/A genotypes were observed in CINA and controls. These results suggest that cytokine polymorphisms associated with control of gene expression and protein levels were not associated with occurrence of CINA and were not responsible for the increased cytokine in CINA patients.

BACKGROUND: Cytokines (IL-1 b and TNF) generated by WBCs during storage of PLT concentrates have been associated with febrile nonhemolytic transfusion reactions. STUDY DESIGN AND METHODS: This study was undertaken to investigate whether there is an association between the polymorphisms of IL1B -511C/T and + 3953C/T, IL1RN intron 2 VNTR and TNFA -308G/A genes and the increase of cytokines during the storage of PLT concentrates produced by plasma-rich PLTS (PRP-PC) or apheresis PLTs. RESULTS: Thirty PRP-PCs were studied and a progressive increase of IL-1 b and TNF during storage was revealed. IL1- b and TNF levels were inversely correlated with the content of PLTs in PRP-PCs detected on Day 3 (p = 0.004) and Day 5 (p = 0.019), but not on Day 7. There was association of IL1B -511T polymorphism and IL-1 b levels (Day 5, p = 0.063, only tendency and on Day 7, p = 0.038, significant). There was no association of the other polymorphisms ( IL1B + 3953C/T, IL1RN intron 2 and TNFA -308G/A) with their respective cytokines. CONCLUSION: The great variation of cytokine levels in the plasma of PLT concentrates (PCs) during storage may also be caused by cytokine gene polymorphisms, as well as WBC contamination, material that the bags are made of, and storage time, as previously described. ytokines are soluble polypeptides with the function of intercellular signaling molecules for a wide range of local and systemic responses, including immunologic and inflammatory effects. IL-1, IL-6, IL-8, and TNF increase in PC concentrates during storage, and this fact appears to be associated with the occurrence of febrile nonhemolytic transfusion reaction (FNHTR) and other transfusion reactions such as urticaria, hypotension, anaphylaxis, TRALI. 1 The main critical factors in determining the cytokines accumulation are considered to be the WBC content and the age of the blood component; moreover, it is heterogeneous and there is a large interindividual (donors) variation. 2-6 The genes of the IL-1 complex are polymorphic and code for three proteins: IL-1 a , IL-1 b , and IL-1 receptor antagonist (IL-1RA), of which the first two are potent inducers of inflammation, while IL-1RA binds to the IL-1 receptors with high affinity, developing an antagonist function. 7,8 The IL-1 b molecule is, contrary to the a form, readily secreted by the cells, and its plasma levels are commonly associated with various diseases and inflammation C

A polymorphism at codon 129 of the prion protein gene has been shown to confer genetic susceptibility to prion diseases, and to influence the epidemic course of variant Creutzfeldt-Jakob disease. We employed a PCR-endonuclease digestion-based assay to investigate this genetic trait in Brazil, and then compared our results to previously published data from several European and Asian countries.

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by decreased activity of ADAMTS13, resulting in reduced clearance of ultralarge von Willebrand factor (VWF) multimers. Treatment of TTP is therapeutic plasma exchange (TPE) with replacement with fresh frozen plasma (FFP). Cryoprecipitate-poor plasma (CPP) is a plasma product with lower concentrations of large VWF multimers, and similar amounts of ADAMTS13. CPP is regarded as at least as efficacious as FFP in TTP but evidence of additional benefits has not been demonstrated. Furthermore, there are limited data on the frequency of adverse events associated with CPP.In our center, the choice between CPP and FFP is performed before the 1st TPE session at the physicians' discretion. Here, we retrospectively evaluated the efficacy and safety of CPP based on the number of sessions, volume of plasma exposure, frequency of exacerbations/relapses, and adverse events.Fourteen patients with newly diagnosed TTP were included in this analysis. The proportion of CPP:FFP use was 5:9. There were no significant differences in age, gender, initial hemoglobin, platelet count, LDH, or etiology of TTP between groups. We observed a trend toward a higher number of TPE sessions and higher plasma exposure in CPP, compared to FFP-treated patients. Acute exacerbations were more frequent among patients treated with CPP (OR 26.6; 95%CI 1.01-703.51; P = 0.03). Mild allergic reactions were the most common treatment-related adverse event in both groups.Our data suggest that CPP should not be used as 1st line treatment for newly diagnosed TTP patients.

Background Blood transfusion has always been an important route for Chagas Disease (CD) transmission. The high prevalence of CD in Latin America and its lifelong asymptomatic clinical picture pose a threat for the safety of the blood supply. The outcome of measures designed to improve transfusion safety can be assessed by evaluating the prevalence of CD among multitransfused patients Methods In order to assess the impact of CD control measures on the safety of the blood supply, an observational cross-sectional study was designed to determine the prevalence of CD in 351 highly transfused patients, in which vectorial transmission was excluded. This study compared patients that received transfusion products before (n = 230) and after (n = 121) 1997, when measures to control transfusion-transmitted CD were fully implemented in Brazil. Results The study group consisted of 351 patients exposed to high numbers of blood products during their lifetime (median number of units transfused = 51, range 10–2086). A higher prevalence of transfusion-transmitted CD (1.30%) was observed among multitransfused patients that received their first transfusion before 1997, compared with no cases of transfusion-transmitted CD among multitransfused patients transfused after that year. The magnitude of the exposure to blood products was similar among both groups (mean number of units transfused per year of exposure = 25.00 ± 26.46 and 23.99 ± 30.58 respectively; P = 0.75, Mann-Whitney test). Conclusion Multiple initiatives aimed to control vector and parental transmission of CD can significantly decrease transfusion-transmitted CD in Brazil. Our data suggest that mandatory donor screening for CD represents the most important measure to interrupt transmission of CD by blood transfusions.

Sickle cell disease (SCD) is a chronic inflammatory condition, even in steady state, as indicated by elevated levels of inflammatory cytokines and increased Th17 responses, compared with healthy controls. These inflammatory pathways may be directly regulated by genetic polymorphisms and could be associated to different outcomes of the disease. High levels of a number of different circulating cytokines were found in SCD patients in several studies, and changes in the cytokine balance in SCD patients are an important risk factor for the occurrence of clinical events. Moreover, inter-patient variations in cytokine levels could be attributed to gene polymorphisms. To investigate cytokine polymorphisms and their association with cytokines expression we evaluated the IL4 intron3 VNTR (genotypes 1.1, 1.2, 2.2, 2.3), IL4T590C/T, IL6174G/C and TNFA308A/G polymorphisms and their correlation with TGFB, IL-4, IL-6 and IL-10 expression in steady-state SCD patients. Methods. Fourth-nine patients (24 male and 25 female; 39.8 ± 9.59 years) with SCD and 28 (22 male and 6 female; 35.5 ± 10.2 years) healthy blood donors were evaluated. The polymorphisms were performed by PCR-RFLP analysis described as [individuals (genotype frequencies)] and the expression of TGFB, IL-4, IL-6 and IL-10 by q-PCR expressed as [median (max-min)]. Results. A higher frequency of 1.2, 2.2 and 2.3 genotypes was found in SCD patients compared with normal controls [34(0.69) vs 12 (0.44), P=0.03]; higher expression of IL-4 was found in the ones carrying the 1.1 genotype [0.31 (2.53-0.01) vs 0.05 (0.95-0.0), P=0.047] and although no differences were found in the IL4T590C/T, IL6174G/C and TNFA308A/G polymorphism frequencies, a significantly greater expression of TGFB, IL6 and IL10 was observed in the patients cohort compared to normal individuals [1.55 (9.02-0.0) vs 0.97 (5.46-0.0), P=0.019]; [0.18 (45.45-0.0) vs 0.0 (8.14-0.0), P=0.03] and [0.98 (22.84-0.0) vs 0.0 (9.95-0.0), P Conclusion: A unique distribution of IL-4 genotypes was observed in our cohort of patients and controls, probably related to the miscellaneous ethnic background of our population. The highest prevalence of the IL4intron3 polymorphism in sickle cell patients suggests a less secretory phenotype associated with increased expression of inflammatory cytokines. IL-4 plays an important role in tissue adhesion and inflammation, including induction of adhesion molecules on vascular endothelial cells and could be responsible for a more “inflammatory” phenotype. Despite the small number of patients enrolled, our study brings insights and new data regarding the deregulation in immune system affecting SCD patients and this information must be investigated in larger cohorts, and may help to better characterize individual variations in immune responses and new markers for disease morbidity. Disclosures No relevant conflicts of interest to declare.