Surveillance for Zika, Chikungunya, and Dengue Virus Incidence and RNAemia in Blood Donors at 4 Brazilian Blood Centers During 2016-2019.

BACKGROUND: Except for public health case reports, the incidence of Zika virus (ZIKV), chikungunya virus (CHIKV), and dengue virus (DENV) infection are not available to assess the potential blood transfusion safety threat in Brazil. METHODS: Pools of 6 donation samples (MP6) left over from human immunodeficiency virus, hepatitis B virus, and hepatitis C virus nucleic acid testing were combined to create MP18 pools (3 MP6 pools). Samples were tested using the Grifols triplex ZIKV, CHIKV, and DENV real-time transcription mediated amplification assay to estimate prevalence of RNAemia and incidence, and to compare these results to case reports in São Paulo, Belo Horizonte, Recife, and Rio de Janeiro, from April 2016 through June 2019. RESULTS: ZIKV, CHIKV, and DENV RNAemia were found from donors who donated without overt symptoms of infection that would have led to deferral. The highest RNAemic donation prevalence was 1.2% (95% CI, .8%-1.9%) for DENV in Belo Horizonte in May 2019. Arbovirus infections varied by location and time of year, and were not always aligned with annual arbovirus outbreak seasons in different regions of the country. CONCLUSIONS: Testing donations for arboviruses in Brazil can contribute to public health. Transfusion recipients were likely exposed to ZIKV, CHIKV, and DENV viremic blood components during the study period.

Prevalence and Risk Factors for Human T-Cell Lymphotropic Virus (HTLV) in Blood Donors in Brazil-A 10-Year Study (2007-2016).

It is unknown whether HTLV-1/2 prevalence has been stable or changing with time in Brazil. We present a 10-year (2007-2016) analysis of HTLV-1/2 infection in first-time blood donors from four blood banks in Brazil. The Brazilian blood centers participating in this multicenter Recipient Epidemiology and Donor Evaluation Study (REDS) are located in Recife in the Northeast and in São Paulo, Rio de Janeiro and Belo Horizonte located in the Southeast of the country. A previous REDS study using the same database from 2007 to 2009 showed that the prevalence per 100,000 donors was 222 in Recife, 83 in Belo Horizonte and 101 in São Paulo. From 2007 to 2016, HTLV-1/2 prevalence was calculated by year, blood center and birth cohort. Covariates included age, gender, schooling, self-reported skin color and type of donation. From 1,092,174 first-blood donations, in the general analysis, HTLV-1/2 infection predominated in females, donors over 50 years of age, black skin color and less educated. The average prevalence was 228 per 100,000 donors in Recife, 222 in Rio de Janeiro, 104 in Belo Horizonte and 103 in São Paulo. In the 10-year analysis, HTLV-1/2 prevalence was stable, but a trend was observed toward an increase in HTLV-1/2 infection among younger people (p < 0.001), males (p = 0.049), those with white skin color (p < 0.001), and higher education (p = 0.014). Therefore, this 10-year surveillance of the infection showed stable HTLV-1/2 prevalence overall but a trend toward increased prevalence among the younger and more educated donors despite Brazilian policies to control sexually transmitted infections being in place for more than 10 years.

Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial.

The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset ( NCT04348656 ). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm-relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94-1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02-1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57-0.95 and OR = 0.66, 95% CI 0.50-0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14-2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

Convalescent plasma for adults with acute COVID-19 respiratory illness (CONCOR-1): study protocol for an international, multicentre, randomized, open-label trial.

BACKGROUND: Convalescent plasma has been used for numerous viral diseases including influenza, severe acute respiratory syndrome, Middle East respiratory syndrome and Ebola virus; however, evidence to support its use is weak. SARS-CoV-2 is a novel coronavirus responsible for the 2019 global pandemic of COVID-19 community acquired pneumonia. We have undertaken a randomized controlled trial to assess the efficacy and safety of COVID-19 convalescent plasma (CCP) in patients with SARS-CoV-2 infection. METHODS: CONCOR-1 is an open-label, multicentre, randomized trial. Inclusion criteria include the following: patients > 16 years, admitted to hospital with COVID-19 infection, receiving supplemental oxygen for respiratory complications of COVID-19, and availability of blood group compatible CCP. Exclusion criteria are : onset of respiratory symptoms more than 12 days prior to randomization, intubated or imminent plan for intubation, and previous severe reactions to plasma. Consenting patients are randomized 2:1 to receive either approximately 500 mL of CCP or standard of care. CCP is collected from donors who have recovered from COVID-19 and who have detectable anti-SARS-CoV-2 antibodies quantified serologically. The primary outcome is intubation or death at day 30. Secondary outcomes include ventilator-free days, length of stay in intensive care or hospital, transfusion reactions, serious adverse events, and reduction in SARS-CoV-2 viral load. Exploratory analyses include patients who received CCP containing high titre antibodies. A sample size of 1200 patients gives 80% power to detect a 25% relative risk reduction assuming a 30% baseline risk of intubation or death at 30 days (two-sided test; α = 0.05). An interim analysis and sample size re-estimation will be done by an unblinded independent biostatistician after primary outcome data are available for 50% of the target recruitment (n = 600). DISCUSSION: This trial will determine whether CCP will reduce intubation or death non-intubated adults with COVID-19. The trial will also provide information on the role of and thresholds for SARS-CoV-2 antibody titres and neutralization assays for donor qualification. TRIAL REGISTRATION: Clinicaltrials.gov NCT04348656 . Registered on 16 April 2020.

Effect of Convalescent Plasma in Critically Ill Patients With COVID-19: An Observational Study.

Background: Convalescent plasma is a potential therapeutic option for critically ill patients with coronavirus disease 19 (COVID-19), yet its efficacy remains to be determined. The aim was to investigate the effects of convalescent plasma (CP) in critically ill patients with COVID-19. Methods: This was a single-center prospective observational study conducted in Rio de Janeiro, Brazil, from March 17th to May 30th, with final follow-up on June 30th. We included 113 laboratory-confirmed COVID-19 patients with respiratory failure. Primary outcomes were time to clinical improvement and survival within 28 days. Secondary outcomes included behavior of biomarkers and viral loads. Kaplan-Meier analyses and Cox proportional-hazards regression using propensity score with inverse-probability weighing were performed. Results: 41 patients received CP and 72 received standard of care (SOC). Median age was 61 years (IQR 48-68), disease duration was 10 days (IQR 6-13), and 86% were mechanically ventilated. At least 29 out of 41CP-recipients had baseline IgG titers ≥ 1:1,080. Clinical improvement within 28 days occurred in 19 (46%) CP-treated patients, as compared to 23 (32%) in the SOC group [adjusted hazard ratio (aHR) 0.91 (0.49-1.69)]. There was no significant change in 28-day mortality (CP 49% vs. SOC 56%; aHR 0.90 [0.52-1.57]). Biomarker assessment revealed reduced inflammatory activity and increased lymphocyte count after CP. Conclusions: In this study, CP was not associated with clinical improvement or increase in 28-day survival. However, our study may have been underpowered and included patients with high IgG titers and life-threatening disease. Clinical Trial Registration: The study protocol was retrospectively registered at the Brazilian Registry of Clinical Trials (ReBEC) with the identification RBR-4vm3yy (http://www.ensaiosclinicos.gov.br).

Lateral Sesamoid Position Relative to the Second Metatarsal in Feet with and without Hallux Valgus.

Objective To determine if the sesamoids migrate laterally in the feet with hallux valgus or if they only appear to move, maintaining their relationship with the other forefoot structures. Methods Anteroposterior radiographs of 80 patients (94 feet, all weight-bearing), from the period between 2015 and 2016, were evaluated. Forty-eight had a valgus hallux angle greater than 15° (hallux valgus group) and 46 presented a hallux valgus angle lower than 15° (control group). The distances from the first metatarsus head and the lateral sesamoid bone to the second metatarsus axis were measured. Subsequently, the coefficients of these distances were determined by the length of the second metatarsus to adjust it for different foot sizes. Results Both the absolute and the relative measures from the first metatarsus head to the second metatarsus axis were significantly different between the groups, with a positive correlation with hallux valgus and intermetatarsal angles. However, neither the absolute nor the relative distance of the lateral sesamoid bone to the second metatarsus was different between the groups, as they did not correlate with hallux valgus or intermetatarsal angles. Conclusion Despite the medial deviation of the first metatarsus in hallux valgus, the sesamoid bone maintains its relationship with the second metatarsus in the transverse plane. This apparent lateral displacement may lead to misinterpretation of these radiographs. This fact is of paramount importance in the pre-, intra-, and postoperative period of patients with hallux valgus.

Lateral Sesamoid Position Relative to the Second Metatarsal in Feet with and without Hallux Valgus / Posição do sesamoide lateral em relação ao segundo metatarso em pés com e sem hálux valgo

Abstract Objective To determine if the sesamoids migrate laterally in the feet with hallux valgus or if they only appear to move, maintaining their relationship with the other forefoot structures. Methods Anteroposterior radiographs of 80 patients (94 feet, all weight-bearing), from the period between 2015 and 2016, were evaluated. Forty-eight had a valgus hallux angle greater than 15° (hallux valgus group) and 46 presented a hallux valgus angle lower than 15° (control group). The distances from the firstmetatarsus head and the lateral sesamoid bone to the secondmetatarsus axis weremeasured. Subsequently, the coefficients of these distances were determined by the length of the second metatarsus to adjust it for different foot sizes. Results Both the absolute and the relativemeasures from the firstmetatarsus head to the second metatarsus axis were significantly different between the groups, with a positive correlationwith hallux valgus and intermetatarsal angles. However, neither the absolute nor the relative distance of the lateral sesamoid bone to the second metatarsus was different between the groups, as they did not correlate with hallux valgus or intermetatarsal angles. Conclusion Despite the medial deviation of the first metatarsus in hallux valgus, the sesamoid bone maintains its relationship with the second metatarsus in the transverse plane. This apparent lateral displacement may lead to misinterpretation of these radiographs. This fact is of paramount importance in the pre-, intra-, and postoperative period of patients with hallux valgus.

Resumo Objetivo Determinar se os sesamoides migramlateralmente nos pés comhálux valgo ou se apenas aparentam deslocar-se, mantendo sua relação com as demais estruturas do antepé. Métodos Foram avaliadas radiografias na incidência anteroposterior com carga dos pés de 80 pacientes (94 pés) entre o período de 2015 e 2016. Dessas, 48 tinham ângulo de hálux valgo maior do que 15º (grupo hálux valgo) e 46 tinham ângulo de hálux valgo menor do que 15º (grupo controle). Foram medidas as distâncias da cabeça do primeiro metatarso e do sesamoide lateral ao eixo do segundo metatarso. Posteriormente, forammedidos os coeficientes dessas distâncias pelo comprimento do segundo metatarso, a fim de se ajustarem aos diferentes tamanhos de pés. Resultados Tanto a medida absoluta quanto a medida relativa da cabeça do primeiro metatarso ao segundo metatarso foram significativamente diferentes nos dois grupos, tiveram correlação positiva com os ângulos de hálux valgo e intermetatarsal. Contudo, nem a distância absoluta nem a relativa do sesamoide lateral ao segundo metatarso foram diferentes nos dois grupos, bem como não se correlacionaram com os ângulos de hálux valgo e inter-metatarsal. Conclusão Apesar do desvio medial do primeiro metatarso no hálux valgo, o sesamoide mantém sua relação com o segundo metatarso no plano transverso. Esse aparente deslocamento lateral pode levar a interpretação equivocada dessas radiografias. Tal fato é de suma importância no pré-, peri- e pós-operatório dos pacientes com hálux valgo.

In-Hospital Onset of Pseudothrombocytopenia Days before Surgery.

Automated cell counters often produce spuriously low platelet counts due to laboratory artifacts. These in vitro phenomena may lead to erroneous treatments, surgical delays, and unnecessary platelet transfusions. An overlooked case of newly developed anticoagulant-induced platelet aggregation diagnosed in a preoperative visit is discussed and diagnostic clues are presented.

Plasma fractionation issues.

Procurement and processing of human plasma for fractionation of therapeutic proteins or biological medicines used in clinical practice is a multi-billion dollar international trade. Together the private sector and public sector (non-profit) provide large amounts of safe and effective therapeutic plasma proteins needed worldwide. The principal therapeutic proteins produced by the dichotomous industry include gamma globulins or immunoglobulins (including pathogen-specific hyperimmune globulins, such as hepatitis B immune globulins) albumin, factor VIII and Factor IX concentrates. Viral inactivation, principally by solvent detergent and other processes, has proven highly effective in preventing transmission of enveloped viruses, viz. HBV, HIV, and HCV.

Effect of the extracts and fractions of Baccharis trimera and Syzygium cumini on glycaemia of diabetic and non-diabetic mice.

In the present study, we investigated the effects of extracts and fractions of Baccharis trimera and Syzygium cumini on glycaemia of diabetic and non-diabetic mice. Crude ethanolic extracts and aqueous and butanolic fractions of the aerial parts of Baccharis trimera and leaves of Syzygium cumini were evaluated. None of the extracts or fractions (200 or 2000 mg/kg, per os) induced any effect after acute administration. Seven-day treatment with crude ethanolic and aqueous and butanolic fractions (200-2000 mg/kg, twice daily, per os) of Syzygium cumini reduced glycaemia of non-diabetic mice. However, this effect was associated with a reduction of food intake and body weight, indicating that this may not be a genuine hypoglycaemic effect. In diabetic mice, only the aqueous fraction of Baccharis trimera (2000 mg/kg, twice daily, per os) reduced the glycaemia after a 7-day treatment. This effect was not associated with a body weight reduction. The results suggest that Baccharis trimera presents a potential antidiabetic activity and indicate that food intake and body weight must be determined when evaluating metabolic parameters after prolonged administration of plant extracts.

Serological surveillance of measles in blood donors in Rio de Janeiro, Brazil

OBJETIVOS: Determinar la proporción de personas seronegativas a anticuerpos contra el sarampión entre los donantes de un banco de sangre de la ciudad de Río de Janeiro, Brasil, y describir sus características sociales y demográficas, con el fin de explorar el uso eventual de los bancos de plasma para complementar la vigilancia serológica con datos que permitan apoyar el programa de erradicación del sarampión en la ciudad de Río de Janeiro y en otras localidades. MÉTODOS: Se estudió la presencia de inmunoglobulinas G contra el sarampión en muestras de plasma de 1 101 donaciones de sangre consecutivas realizadas en noviembre de 2000 en HEMORIO, el mayor banco de sangre del estado de Río de Janeiro, mediante un ensayo inmunoenzimático comercial y una prueba de neutralización por reducción de placas. Se calculó la proporción (y el intervalo de confianza (IC) de 95 por ciento) de las muestras negativas a anticuerpos contra el sarampión en la totalidad de las donaciones y en subgrupos conformados según la edad, el sexo, el vecindario de residencia, la educación y la ocupación laboral. La significación estadística de las diferencias entre las proporciones y entre sus tendencias lineales se determinó mediante la prueba de ji al cuadrado. RESULTADOS: Del total de donantes de sangre, el 6,9 por ciento (IC95 por ciento: 5,4 a 8,4 por ciento) resultó seronegativo al sarampión. Las mujeres tuvieron una mayor proporción de resultados seronegativos (10,1 por ciento; IC95 por ciento: 6,8 a 13,4 por ciento) que los hombres (5,6 por ciento; IC95 por ciento: 4,0 a 7,2 por ciento). En relación con la edad, 86,8 por ciento de las personas seronegativas nacieron entre 1971 y 1982. La seronegatividad fue inversamente proporcional a la edad (ji al cuadrado = 58,0; P < 0,0001). En cuanto a la ocupación laboral, los estudiantes presentaron la mayor proporción de seronegativos (17,8 por ciento), mientras que en lo referente a la educación, la mayoría de las personas susceptibles a la enfermedad se encontraban en la categoría de "estudios universitarios incompletos" o "estudios secundarios incompletos". La proporción de seronegativos entre las diferentes áreas de residencia estuvo entre 2,1 por ciento y 11,4 por ciento. CONCLUSIONES: El plasma de los bancos de sangre puede ser una fuente útil y conveniente de datos complementarios para la vigilancia serológica en adultos, tanto de sarampión como de otras enfermedades infecciosas para las que se hayan implementado...

Hemophilia care in the state of Rio de Janeiro, Brazil.

In the developing countries of the world, few people with hemophilia receive adequate care. Nevertheless, Brazil has made significant advances in the treatment of hemophilia over the last decade. The provision of factor concentrates imported by the Government of Brazil is gradually increasing, and patients receive the concentrates for free. A national register was established as well as a coordinated program for comprehensive care. Of the 6 297 persons with hemophilia in Brazil who were registered as of January 2001, 689 of them (11.1%) were registered in the state of Rio de Janeiro. Of those 689, 664 of them were being monitored at the state's coordinating blood transfusion center, which is located in the city of Rio de Janeiro. Among those 664, factor VIII inhibitors were identified in 81 of them (12.2%). Among 653 of the Rio de Janeiro patients who were tested for transfusion-transmitted diseases, the overall prevalence found was 41.5%, with the specific rates being 13.3% for human immunodeficiency virus (HIV), 2.9% for hepatitis B virus (HBV), and 39.4% for hepatitis C virus (HCV). The state of Rio de Janeiro has adopted a comprehensive hemophilia management approach that includes medical, psychological, and social care. As a result, the quality of life of hemophilia patients has improved noticeably. For example, the rate of hospitalization among patients fell by 30% between 1998 and 2001, and there has also been a decline in the school and work activities that they have missed.

Hemophilia care in the state of Rio de Janeiro, Brazil

In the developing countries of the world, few people with hemophilia receive adequate care. Nevertheless, Brazil has made significant advances in the treatment of hemophilia over the last decade. The provision of factor concentrates imported by the Government of Brazil is gradually increasing, and patients receive the concentrates for free. A national register was established as well as a coordinated program for comprehensive care. Of the 6 297 persons with hemophilia in Brazil who were registered as of January 2001, 689 of them (11.1 percent) were registered in the state of Rio de Janeiro. Of those 689, 664 of them were being monitored at the state's coordinating blood transfusion center, which is located in the city of Rio de Janeiro. Among those 664, factor VIII inhibitors were identified in 81 of them (12.2 percent). Among 653 of the Rio de Janeiro patients who were tested for transfusion-transmitted diseases, the overall prevalence found was 41.5 percent, with the specific rates being 13.3 percent for human immunodeficiency virus (HIV), 2.9 percent for hepatitis B virus (HBV), and 39.4 percent for hepatitis C virus (HCV). The state of Rio de Janeiro has adopted a comprehensive hemophilia management approach that includes medical, psychological, and social care. As a result, the quality of life of hemophilia patients has improved noticeably. For example, the rate of hospitalization among patients fell by 30 percent between 1998 and 2001, and there has also been a decline in the school and work activities that they have missed

Serological surveillance of measles in blood donors in Rio de Janeiro, Brazil.

OBJECTIVES: To estimate the proportion of individuals seronegative for measles antibody among blood donors from a blood bank in the city of Rio de Janeiro, Brazil, and to describe their social and demographic characteristics, with the goal of exploring the potential use of plasma banks to supplement serological surveillance with relevant data in order to support the program of measles elimination in the city of Rio de Janeiro and elsewhere. METHODS: Plasma samples from 1 101 consecutive blood donations made in November 2000 at HEMORIO, the largest blood bank in the state of Rio de Janeiro, were tested for measles immunoglobulin G, using a commercial enzyme immunoassay and a plaque reduction neutralization test. We calculated the proportion (and 95% confidence interval (CI)) of samples seronegative for measles antibody for the total sample of blood donors and also for subgroups categorized by age, sex, neighborhood of residence, education, and occupation. We used the chi-square test to assess the statistical significance of differences in proportions and linear trends in proportions. RESULTS: Of the total group of blood donors, 6.9% of them (95% CI: 5.4%-8.4%) were seronegative for measles. Women had a higher proportion (10.1%; 95% CI: 6.8%-13.4%) of seronegative results than did men (5.6%; 95% CI: 4.0%-7.2%). In terms of age, 86.8% of seronegative individuals were born between 1971 and 1982. Seronegativity was inversely proportional to age (chi-square = 58.0; P < 0.0001). With regard to occupation, students had the highest proportion of seronegative individuals (17.8%). In terms of education, most of the susceptible persons were in the categories of "incomplete university degree" or "incomplete high school." For the various areas of residence the proportions ranged from 2.1% to 11.4%. CONCLUSIONS: Blood bank plasma may constitute a useful and convenient source of complementary data for serological surveillance in adults of measles and other infections for which immunization and surveillance activities are implemented. This approach could be beneficial to other areas in Brazil and other countries where plasma from blood donors is available for surveillance. The use of residual sera from patients and plasma from blood donors represents a tradeoff between representativeness and timeliness as well as economy of resources.