RESUMO

BACKGROUND: The Amazonas state/AM and Manaus rank among the highest AIDS detection rates in Brazil. High proportion of HIV infected blood donors and transmission clusters of multidrug antiretroviral/ARV resistant viruses were described in HEMOAM blood donors, a main Amazonas public blood bank. Recent and long-term infections among previously genotyped donors are reported. METHODS/MATERIALS: The recency immunoassay Lag Avidity EIA (Maxim, USA) was employed. Clinical/CD4/viral load medical file data of the main local HIV management center (FMT-HVD) and ARV treatment/ART data were reviewed. RESULTS: Among 142 HIV-blood donors, chronic infection predominated (n = 87; 61.3 %), 79 based on LAg EIA and 8 undisclosed HIV identified in FMT-HVD records, mostly young adult, single males, 4 repeat donors, all ART-naive. Recent infections represented 30.3 % (n = 43), 39 identified by LAg EIA and 4 immunologic windows (antibody negative/NAT/RNA positive). The overall profile of recent and long-term infections was similar, including moderate rate of transmitted drug resistance/TDR, however with multiple resistance mutations to more than one ARV-class, suggesting ART/failure. DISCUSSION: Recent/acute and undisclosed/long-term HIV infections represent blood safety alerts suggesting test-seeking behavior of at-risk populations. Early ART use in Brazil, can turn HIV diagnosis more challenging representing a blood transfusion risk in the highly endemic Brazilian Amazon.

Assuntos

Doadores de Sangue , Infecções por HIV , Humanos , Doadores de Sangue/estatística & dados numéricos , Masculino , Brasil/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Adulto , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Doença Aguda , Carga Viral , Adolescente , Doenças Endêmicas , Contagem de Linfócito CD4 , HIV-1/genética , Doença Crônica

RESUMO

Sickle Cell Disease (SCD) is a hereditary disease characterized by extravascular and intravascular hemolysis and clinical variability, from mild pain to potentially life-threatening. Arboviruses include mainly Zika (ZIKV), Chikungunya (CHKV), and Dengue (DENV) virus, and are considered a public and social health problem. The present cross-sectional observational study aimed to investigate the prevalence of arbovirus infection in SCD patients from two Brazilian cities, Salvador and Manaus located in Bahia and Amazonas states respectively. A total of 409 individuals with SCD were included in the study, and 307 (75.06 %) patients tested positive for DENV-IgG, 161 (39.36 %) for ZIKV-IgG, and 60 (14.67 %) for CHIKV-IgG. Only one individual was positive for DENV-NS1 and another for DENV-IgM, both from Salvador. No individuals had positive serology for ZIKV-IgM or CHIKV-IgM. Arbovirus positivity by IgG testing revealed that the SCD group presented high frequencies in both cities. Interestingly, these differences were only statistically significant for ZIKV-IgG (p = 0.023) and CHIKV-IgG (p = 0.005) among SCD patients from Manaus. The reshaping of arbovirus from its natural habitat by humans due to disorderly urban expansion and the ease of international Mobility has been responsible for facilitating the spread of vector-borne infectious diseases in humans. We found the need for further studies on arboviruses in this population to elucidate the real association and impact, especially in acute infection. We hope that this study will contribute to improvements in the personalized clinical follow-up of SCD patients, identifying the influence of arbovirus infection in severe disease manifestations.

Assuntos

Anemia Falciforme , Infecções por Arbovirus , Arbovírus , Humanos , Brasil/epidemiologia , Anemia Falciforme/epidemiologia , Anemia Falciforme/complicações , Estudos Transversais , Masculino , Feminino , Adulto , Prevalência , Infecções por Arbovirus/epidemiologia , Infecções por Arbovirus/virologia , Adulto Jovem , Adolescente , Arbovírus/isolamento & purificação , Imunoglobulina G/sangue , Criança , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/complicações , Anticorpos Antivirais/sangue , Pessoa de Meia-Idade , Dengue/epidemiologia , Imunoglobulina M/sangue , Vírus da Dengue/imunologia , Zika virus/imunologia , Zika virus/isolamento & purificação , Pré-Escolar , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/complicações

RESUMO

BCR::ABL1-negative myeloproliferative neoplasms are hematopoietic disorders characterized by panmyelosis. JAK2 V617F is a frequent variant in these diseases and often occurs in the 46/1 haplotype. The G allele of rs10974944 has been shown to be associated with this variant, specifically its acquisition, correlations with familial cases, and laboratory alterations. This study evaluated the association between the 46/1 haplotype and JAK2 V617F in patients with myeloproliferative neoplasms in a population from the Brazilian Amazon. Clinical, laboratory and molecular sequencing analyses were considered. Carriers of the G allele of rs10974944 with polycythemia vera showed an increase in mean corpuscular volume and mean corpuscular hemoglobin, while in those with essential thrombocythemia, there was an elevation in red blood cells, hematocrit, and hemoglobin. Associations were observed between rs10974944 and the JAK2 V617F, in which the G allele (OR 3.4; p < 0.0001) and GG genotype (OR 4.9; p = 0.0016) were associated with JAK2 V617F + and an increase in variant allele frequency (GG: OR 15.8; p = < 0.0001; G: OR 6.0; p = 0.0002). These results suggest an association between rs10974944 (G) and a status for JAK2 V617F, JAK2 V617F + _VAF ≥ 50%, and laboratory alterations in the erythroid lineage.

Assuntos

Janus Quinase 2 , Transtornos Mieloproliferativos , Polimorfismo de Nucleotídeo Único , Humanos , Brasil , Feminino , Masculino , Janus Quinase 2/genética , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/genética , Idoso , Adulto , Frequência do Gene , Alelos , Haplótipos , Policitemia Vera/genética , Policitemia Vera/sangue , Genótipo , Predisposição Genética para Doença , Idoso de 80 Anos ou mais

RESUMO

ABSTRACT Sickle Cell Disease (SCD) is a hereditary disease characterized by extravascular and intravascular hemolysis and clinical variability, from mild pain to potentially life-threatening. Arboviruses include mainly Zika (ZIKV), Chikungunya (CHKV), and Dengue (DENV) virus, and are considered a public and social health problem. The present cross-sectional observational study aimed to investigate the prevalence of arbovirus infection in SCD patients from two Brazilian cities, Salvador and Manaus located in Bahia and Amazonas states respectively. A total of409 individuals with SCD were included in the study, and 307 (75.06 %) patients tested positive for DENV-IgG, 161 (39.36 %) for ZIKV-IgG, and 60 (14.67 %) for CHIKV-IgG. Only one individual was positive for DENV-NS1 and another for DENV-IgM, both from Salvador. No individuals had positive serology for ZIKV-IgM or CHIKV-IgM. Arbovirus positivity by IgG testing revealed that the SCD group presented high frequencies in both cities. Interestingly, these differences were only statistically significant for ZIKV-IgG (p = 0.023) and CHIKV-IgG (p = 0.005) among SCD patients from Manaus. The reshaping of arbovirus from its natural habitat by humans due to disorderly urban expansion and the ease of international Mobility has been responsible for facilitating the spread of vector-borne infectious diseases in humans. We found the need for further studies on arboviruses in this population to elucidate the real association and impact, especially in acute infection. We hope that this study will contribute to improvements in the personalized clinical follow-up of SCD patients, identifying the influence of arbovirus infection in severe disease manifestations.

RESUMO

Background: Children with B-cell acute lymphoblastic leukemia (B-ALL) have an immune imbalance that is marked by remodeling of the hematopoietic compartment, with effects on peripheral blood (PB). Although the bone marrow (BM) is the main maintenance site of malignancy, the frequency with which immune cells and molecules can be monitored is limited, thus the identification of biomarkers in PB becomes an alternative for monitoring the evolution of the disease. Methods: Here, we characterize the systemic immunological profile in children undergoing treatment for B-ALL, and evaluate the performance of cell populations, chemokines and cytokines as potential biomarkers during clinical follow-up. For this purpose, PB samples from 20 patients with B-ALL were collected on diagnosis (D0) and during induction therapy (days 8, 15 and 35). In addition, samples from 28 children were used as a control group (CG). The cellular profile (NK and NKT-cells, Treg, CD3+ T, CD4+ T and CD8+ T cells) and soluble immunological mediators (CXCL8, CCL2, CXCL9, CCL5, CXCL10, IL-6, TNF, IFN-γ, IL-17A, IL- 4, IL-10 and IL-2) were evaluated via flow cytometry immunophenotyping and cytometric bead array assay. Results: On D0, B-ALL patients showed reduction in the frequency of cell populations, except for CD4+ T and CD8+ T cells, which together with CCL2, CXCL9, CXCL10, IL-6 and IL-10 were elevated in relation to the patients of the CG. On D8 and D15, the patients presented a transition in the immunological profile. While, on D35, they already presented an opposite profile to D0, with an increase in NKT, CD3+ T, CD4+ T and Treg cells, along with CCL5, and a decrease in the levels of CXCL9, CXCL10 and IL-10, thus demonstrating that B-ALL patients present a complex and dynamic immune network during induction therapy. Furthermore, we identified that many immunological mediators could be used to classify the therapeutic response based on currently used parameters. Conclusion: Finally, it is noted that the systemic immunological profile after remission induction still differs significantly when compared to the GC and that multiple immunological mediators performed well as serum biomarkers.

RESUMO

OBJECTIVE/BACKGROUND: Sickle cell anemia (SCA) is associated with increased levels of extracellular heme, which is a key mediator of inflammation in this condition. Despite abundant evidence supporting this concept in cell and animal models, few studies addressed the association between heme levels and the development and severity of acute vasoocclusive crises (VOC) in humans. METHODS: A cross-sectional study was conducted in patients with acute VOC. Total extracellular heme levels were measured in both plasma and serum at admission and after convalescence, and correlated with other clinical and laboratory markers of SCA severity. RESULTS: A total of 28 episodes of VOC in 25 patients were included. Heme levels were similar between admission and convalescence, and correlated with the difference between pre and post hemoglobin, and SCA severity estimated by a composite score of clinical and laboratory markers. Heme levels were neither associated with VOC severity nor with markers of hemostasis activation, and were similar to those reported in an independent population of SCA patients at steady state. DISCUSSION: Acute VOC are not characterized by significant increases in total extracellular heme levels. Studies measuring the fraction of free extracellular heme unbound to proteins are warranted to further refine our understanding of the role of heme in acute VOC.

Assuntos

Anemia Falciforme , Compostos Orgânicos Voláteis , Humanos , Heme , Estudos Transversais , Convalescença , Anemia Falciforme/complicações , Biomarcadores

RESUMO

The present study aimed at estimating the prevalence of structural hemoglobinopathies in newborn and describing the hematological and biochemical characteristics between postpartum women (PW) and their respective newborns (NB) at a public maternity hospital in Manaus, Amazonas state, Brazil. In total, 825 NB and 820 PW were included in the study. Hematological and biochemical analysis and screening of structural hemoglobinopathies were performed and compared in groups of individuals (NICU or not; hemoglobin genotypes; gestational age and prenatal). The age of PW ranged from 13 to 44 years old (mean of 23.7 ± 6.6 years), with 45.9% pregnant for the first time and 54.1% multiparous. Reported receiving prenatal care 88% and regarding the type of delivery, 47.7% had delivered by cesarean section. Among the births, 19.4% were born premature and 8.3% were admission to the neonatal intensive care unit (NICU). The male NB represented 53.4% of the total. Sickle cell trait (FAS) was found in 16 (1.94%) and heterozygous for D hemoglobin (FAD) in 6 (0.73%) newborns. A statistically significant values was found between the previous history of miscarriage and increase of Mean corpuscular volume (MCV) (p < .001), Red blood cell distribution width (RDW) (p = .003), total and indirect bilirubin concentration (p < .001) and LDL cholesterol (p = .004). Hemoglobin levels below 13.5 g/dL was found in 66% black newborns, compared with 15% of Afro-Brazilian and 5% of whites. The frequency of structural hemoglobinopathies was higher in African-Brazilian newborn babies (78%) and those who with low birth weight had a higher frequency of NICU (35.7%). Interestingly, underage mothers had a higher frequency of NB with low birth weight and premature birth. Postpartum women who had children carriers of FAS and FAD had a higher frequency of urinary tract infection (65.2%) and moderate anemia (23.8%). This study estimated for the first time the prevalence of structural hemoglobinopathies in NB in Manaus, Amazonas, Brazil. Despite the small prevalence of, we highlight the importance of early diagnosis of hemoglobin variants, contributing to the improvement of the quality of life of PW and your NB, reinforce the need to implement educational and prevention programs to raise awareness among the population and in order to counsel parents regarding the probability of having a child with abnormal hemoglobins homozygous as HbSS or HbCC.

Assuntos

Cesárea , Hemoglobinopatias , Lactente , Criança , Recém-Nascido , Feminino , Masculino , Humanos , Gravidez , Adolescente , Adulto Jovem , Adulto , Brasil/epidemiologia , Qualidade de Vida , Flavina-Adenina Dinucleotídeo , Hemoglobinopatias/epidemiologia , Hemoglobinopatias/genética , Hemoglobinopatias/diagnóstico , Período Pós-Parto

Assuntos

Doadores de Sangue , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Brasil/epidemiologia , Glucosefosfato Desidrogenase/genética , Deficiência de Glucosefosfato Desidrogenase/genética , Humanos , Polimorfismo de Nucleotídeo Único

RESUMO

Sickle Cell Anemia (SCA) is the most common genetic disorder around the world. The mutation in the ß-globin gene is responsible for a higher hemolysis rate, with further involvement of immunological molecules, especially cytokines, chemokines, growth factors, and anaphylatoxins. These molecules are responsible for inducing and attracting immune cells into circulation, thus contributing to increases in leukocytes and other pro-inflammatory mediators, and can culminate in a vaso-occlusive crisis (VOC). This study aimed to characterize the levels of these molecules in SCA patients in different clinical conditions in order to identify potential hallmarks of inflammation in these patients. An analytical prospective study was conducted using the serum of SCA patients in steady-state (StSt; n = 27) and VOC (n = 22), along with 53 healthy donors (HD). Samples from the VOC group were obtained on admission and on discharge, in the convalescent phase (CV). Levels of chemokines (CXCL8, CXCL10, CL2, CLL3, CCL4, CL5, and CCL11), cytokines (IL-1ß, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12p70, IL-13, IL-17A, TNF-α, and IFN-γ) and growth factors (VEGF, FGFb, PDGF-BB, GM-CSF, and G-CSF) were measured using a Luminex assay, and anaphylatoxins (C3a, C4a, and C5a) were measured using Cytometric Bead Array. SCA patients in StSt showed a pro-inflammatory profile, and were indicated as being higher producers of CCL2, IL-1ß, IL-12p70, IFN-γ, IL-17A, and GM-CSF, while VOC is highlighted by molecules IL-4 and IL-5, but also IL-2, IL-7, PDGF-BB, and G-CSF. PDGF-BB and IL-1ra seemed to be two important hallmarks for the acute-to-chronic stage, due to their significant decrease after crisis inflammation and statistical difference in VOC and CV groups. These molecules show higher levels and a strong correlation with other molecules in VOC. Furthermore, they remain at higher levels even after crisis recovery, which suggest their importance in the role of inflammation during crisis and participation in immune cell adhesion and activation. These results support a relevant role of cytokines, neutrophil and monocytes, since these may act as markers of VOC inflammation in SCA patients.

Assuntos

Anemia Falciforme/imunologia , Citocinas/imunologia , Mediadores da Inflamação/imunologia , Inflamação/imunologia , Doenças Vasculares/imunologia , Adolescente , Adulto , Anemia Falciforme/metabolismo , Quimiocinas/imunologia , Quimiocinas/metabolismo , Citocinas/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Modelos Imunológicos , Monócitos/imunologia , Monócitos/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Mapas de Interação de Proteínas/imunologia , Doenças Vasculares/metabolismo , Adulto Jovem

RESUMO

An amendment to this paper has been published and can be accessed via the original article.