Casos de Síndrome de Gullain-Barré associados à infecção pelo Zika vírus no Brasil: uma revisão sistemática

Introduction: Zika is an arbovirus transmitted to humans mainly during the hematophagy of the Aedes aegypti and Aedes albopictus vectors. In most cases, the infection is accompanied by dengue-like symptoms, but studies have correlated it with Guillain-Barré syndrome. Objective: Elaborate a systematic review of cases of Guillain-Barré syndrome that were associated with Zika infections in Brazil from 2013 to 2018. Methods: A survey was conducted at PUBMED using the keywords Zika Virus, Gullain-Barré, Infection, Brazil and Epidemiology. In addition to these words, the following filters were used: study period from 2013 to 2018; full availability of work free of charge; works performed only with human beings; works published in English and Portuguese; and type of article, which included case reports, classic articles, clinical study, clinical trial, comparative study, controlled clinical trial, bibliographic reviews and systematic reviews. Results: Among the eight selected studies, 75% are review articles, one of which is a meta-analysis, 12.5% reported by cases and 12.5% study prospective observational cohort. 470 cases of Guillain-Barré Syndrome associated with Zika infection have been reported. The cases were defined clinically and / or by laboratory methods (serological and molecular). The main limitation for the association was the laboratory diagnosis. Conclusion: It is concluded that even with several difficulties in determining the possible relation-ship, the northeast and southeast were the regions that most published / reported on the cases of GBS associated with ZIKV infection in Brazil.Introdução: Zika é um arbovírus transmitido aos seres humanos principalmente durante a hematofagia dos vetores Aedes aegypti e Aedes albopictus. Na maioria dos casos a infecção é acompanhada por sintomas semelhantes ao da dengue, porém estudos a correlacionou à síndrome Guillain-Barré. Objetivo: Elaborar uma revisão sistemática sobre casos de síndrome Guillain-Barré que foram associadas as infecções por Zika no Brasil entre o período de 2013 a 2018. Métodos: Foi realizado um levantamento no PUBMED utilizando as palavras-chave Zika Vírus, Gullain-Barré, Infecção, Brasil e Epidemiologia. Além destas palavras, os seguintes filtros foram utilizados: período de estudo entre 2013 a 2018; disponibilidade completa do trabalho gratuitamente; trabalhos realizados somente com seres humanos; trabalhos publicados nos idiomas inglês e português; e tipo de artigo, os quais foram inclusos relatos de casos, artigos clássicos, estudo clínico, ensaio clínico, estudo comparativo, ensaio clínico controlado, revisões bibliográficas e revisões sistemáticas. Resultados: Dentre os oito trabalhos selecionados, 75% tratavam-se de artigos de revisão, sendo um deles metanálise, 12,5% relato de caso e 12,5 % estudo de coorte prospectivo observacional. Foram relatados 470 casos de Síndrome Guillain-Barré associados a infecção pelo Zika. A definição dos casos foi realizada clinicamente e/ou por métodos laboratoriais (sorológicos e moleculares). A principal limitação para a associação foi o diagnóstico laboratorial. Conclusão: Conclui-se que mesmo com várias dificuldades para determinar a possível relação, o nordeste e o sudeste foram as regiões que mais publicaram sobre os casos de GBS associados à infecção por ZIKV no Brasil

Polymorphisms in the MBL2 gene are associated with the plasma levels of MBL and the cytokines IL-6 and TNF-α in severe COVID-19

IntroductionMannose-binding lectin (MBL) promotes opsonization, favoring phagocytosis and activation of the complement system in response to different microorganisms, and may influence the synthesis of inflammatory cytokines. This study investigated the association of MBL2 gene polymorphisms with the plasma levels of MBL and inflammatory cytokines in COVID-19.MethodsBlood samples from 385 individuals (208 with acute COVID-19 and 117 post-COVID-19) were subjected to real-time PCR genotyping. Plasma measurements of MBL and cytokines were performed by enzyme-linked immunosorbent assay and flow cytometry, respectively.ResultsThe frequencies of the polymorphic MBL2 genotype (OO) and allele (O) were higher in patients with severe COVID-19 (p< 0.05). The polymorphic genotypes (AO and OO) were associated with lower MBL levels (p< 0.05). IL-6 and TNF-α were higher in patients with low MBL and severe COVID-19 (p< 0.05). No association of polymorphisms, MBL levels, or cytokine levels with long COVID was observed.DiscussionThe results suggest that, besides MBL2 polymorphisms promoting a reduction in MBL levels and therefore in its function, they may also contribute to the development of a more intense inflammatory process responsible for the severity of COVID-19

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Detection of Epstein-Barr virus in gastric adenocarcinoma: qPCR and fish comparison

Scientifc initiation scholarships were paid by National Council for Scientifc and Technological Development (CNPq). Salaries were paid by Evandro Chagas Institute (IEC) and Federal University of Pará. Equipment and supplies were provided by the IECMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, BrasilFederal University of Pará. Institute of Biological Sciences. Laboratory of Human Cytogenetics. Belém, PA, BrazilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, BrasilFederal University of Pará. Institute of Biological Sciences. Laboratory of Human Cytogenetics. Belém, PA , Brazil / Ophir Loyola Hospital. Molecular Biology Laboratory. Belém, PA, BrazilEBV-associated gastric cancer accounts for about 10% of all gastric carcinomas worldwide. We aimed to verify the prevalence of EBV in gastric adenocarcinoma samples using FISH and qPCR and comparing the results obtained by both techniques. Gastric cancer samples from 191 cases were analyzed. The FISH assay was performed to detect small EBV RNAs (EBER1) and qPCR was performed to detect the EBV-EBNA-1 gene region. Cohen's kappa index and the chi-square test were used to compare the methodologies and investigate correlations with the clinical-pathological data of the gastric adenocarcinoma patients. Most of the patients were men, and the average age was 60 years. The intestinal subtype cancer presented more aggressive stages with 90% of patients having a reactive FISH for EBV (EBV+), although the virus infection frequency in epithelial gastric tissue was only 1%. No positive association with clinicopathological features and EBV+ was found by FISH. Using qPCR analysis, the percentage of positive samples was lower (52.4%), and a positive association was found in samples from older patients (> 60 years). Interestingly, 71 qPCR-negative cases were detected by FISH in the presence of non-epithelial cells and in 10 qPCR-positive cases with no evidence of EBV according to FISH. The concordance between the two techniques was low, with only 57.6%. FISH is more informative for associating the gastric carcinoma with EBV positivity in tumor/epithelial cells; however, qPCR can provide relevant information regarding the progression and characteristics of neoplasia

Epstein–Barr Virus (EBV) Genotypes Associated with the Immunopathological Profile of People Living with HIV-1: Immunological Aspects of Primary EBV Infection

Background: The aim of the present study was to evaluate the immunological profile of adult HIV-1+ patients coinfected with primary Epstein–Barr virus (EBV) infection who were free of antiretroviral drugs and inhabitants of the Brazilian Amazon region. Materials and methods: Primary EBV infection was screened by the semiquantitative detection of IgM and IgG anti-VCA. Genotypes were determined by conventional PCR. EBV and HIV viral load (VL) were quantified by real-time PCR. Cytokine dosage and cell quantification were performed by cytometry. Results: Only HIV-1+ individuals had primary EBV infection (7.12%). The EBV-1 genotype was the most prevalent (47.37%). The VL of HIV-1 was lower in the HIV/EBV-2 group. CD4+ T lymphocytes were inversely proportional to the VL of EBV in HIV/EBV-1/2 multi-infected patients. The HIV/EBV-2 group had the lowest cytokine levels, especially IFN-γ and IL-4. Different correlations were proposed for each coinfection. The late search for specific care related to HIV infection directly affected the cytokine profile and the number of CD8+ T lymphocytes. Symptoms were associated with the increase in VL of both viruses and cytokine profile. Conclusions: Different immunological profiles were associated with EBV genotypes in primary infection, with EBV-2 being more frequent in patients with low levels of HIV viral load. With late infection monitoring and consequent delay in the initiation of HAART, clinical changes and effects on the maintenance of the immune response were observed

Epidemiological risk factors associated with primary infection by Epstein-Barr virus in HIV-1-positive subjects in the Brazilian Amazon region

Health Surveillance Department of the Brazilian Ministry of Health and Conselho Nacional de Desenvolvimento Científco e Tecnológico–CNPQ (#301869/2017-0). Coordination for the Improvement of Higher Education Personnel (CAPES) (process number: 88882.183970/2018-01).Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Vírus Epstein-Barr. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Vírus Epstein-Barr. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Vírus Epstein-Barr. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Departamento de Epidemiologia e Vigilância. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Departamento de Epidemiologia e Vigilância. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Vírus Epstein-Barr. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Retrovírus. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Vírus Epstein-Barr. Ananindeua, PA, Brasil / Federal University of Pará. School of Medicine. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Retrovírus. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Vírus Epstein-Barr. Ananindeua, PA, Brasil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil /Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.To identify the prevalence and risk factors for primary Epstein–Barr virus (EBV) infection in human immunodeficiency virus (HIV)-1-positive adult treatment-naïve patients between January 2018 and December 2019 in a state of the Brazilian Amazon region. A total of 268 HIV-1 positive patients and 65 blood donors participated in the study. Epidemiological data were obtained from medical records and through a designed questionnaire. EBV infection was screened by the semiquantitative detection of anti-viral capsid antigen (VCA) EBV IgM and IgG, followed by molecular detection of the EBNA-3C gene. The plasma viral loads of HIV-1 and EBV were quantified using a commercial kit. The prevalence of primary coinfection was 7.12%. The associated risk factors were education level, family income, history of illicit drug use and sexually transmitted infections, homosexual contact and condom nonuse. Approximately 58.5% had late initiation of highly active antiretroviral therapy, which influenced the risk of HIV-EBV 1/2 multiple infection (odds ratio (OR): 4.76; 95% CI 1.51–15.04) and symptom development (p = 0.004). HIV viral load was associated with patient age (OR: 2.04; 95% CI 2.01–2.07; p = 0.026) and duration of illicit drug use (OR: 1.57; 95% CI 1.12–2.22; p = 0.0548). EBV viral load was associated with younger age (OR: 0.82; 95% CI 0.79–1.03; p = 0.0579). The replication of both viruses was associated with symptom development (HIV = OR: 2.06; 95% CI 1.22–3.50; p = 0.0073; EBV = OR: 8.81; 95% CI 1–10; p = 0.0447). The prevalence of HIV/EBV coinfection was lower than that observed in other studies, and social vulnerability and promiscuous sexual behavior were associated risk factors. A long time of HIV-1 infection, without therapy, influenced the risk of coinfection and disease progression. The viral loads of both viruses may be associated with some epidemiological aspects of the population

Genotypes of Epstein–Barr virus (EBV1/EBV2) in individuals with infectious mononucleosis in the metropolitan area of Belém, Brazil, between 2005 and 2016

Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Pós-graduação em Virologia. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Estadual do Pará. Residência Médica. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Rotavírus. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Rotavírus. Ananindeua, PA, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Pós-graduação em Virologia. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Federal do Pará. Núcleo de Medicina Tropical. Belém, PA, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Pós-graduação em Virologia. Ananindeua, PA, Brasil.Two types of Epstein Barr virus (EBV1/EBV2) have been shown to infect humans. Although their genomes are similar, the regions containing the EBNA genes differ. This study aimed to characterize the EBV genotypes of infectious mononucleosis (IM) cases in the metropolitan region of Belém, Brazil, from 2005 to 2016. A total of 8295 suspected cases with symptoms/signs of IM were investigated by infectious disease physicians at Evandro Chagas Institute, Health Care Service, from January 2005 to December 2016. Out of the total, 1645 (19.8%) samples had positive results for EBV by enzyme immunoassay and 251 (15.3%) were submitted to polymerase chain reaction (PCR) technique, using the EBNA3C region, in order to determine the type of EBV. Biochemical testing involving aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase were also performed. EBV type was identified by PCR in 30.3% (76/251) of individuals; of those, 71.1% (54/76) were classified as EBV1, 17.1% (13/76) as EBV2, and 11.8% (9/76) as EBV1 + EBV2. The main symptoms/signs observed with EBV1 infection were cervical lymphadenopathy (64.8%, 35/54), fever (63%, 34/54), headache (20.4%, 11/54), arthralgia (20.4%, 11/54), and exanthema (18.5%, 10/54). EBV2 infection was detected in all but two age groups, with an average age of 24 years. The most common signs/symptoms of EBV2 were fever (76.9%, 10/13), average duration of 18 days, and lymphadenopathy (69.2%, 9/13). In contrast, EBV1 + EBV2 coinfections were more frequent in those aged five years or less (20.0%, 2/10). The symptoms of EBV1 + EBV2 coinfection included fever (66.7%, 6/9), and cervical lymphadenopathy and headache (33.3%, 3/9) each. The mean values of hepatic enzymes according to type of EBV was significantly different (p < 0.05) in those EBV1 infected over 14 years of age. Thus, this pioneering study, using molecular methods, identified the EBV genotypes in 30.3% of the samples, with circulation of EBV1, EBV2, and EBV1 + EBV2 co-infection in cases of infectious mononucleosis in the northern region of Brazil

Diagnostic evaluation of infections by Epstein-Barr virus, parvovirus B19, and human T-cell lymphotropic virus in patients with systemic lupus erythematosus from a reference hospital in Pará State, Brazil

Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Hospital Jean Bitar. Departamento de Clínica Médica. Belém, PA, Brasil.Hospital Jean Bitar. Departamento de Clínica Médica. Belém, PA, Brasil.O lúpus eritematoso sistêmico (LES) é uma doença autoimune crônica, cujo desenvolvimento pode estar associado à infecção por vírus, como o vírus Epstein-Barr (EBV), parvovírus B19 e vírus linfotrópico de células T humanas (HTLV). Durante o período de junho a setembro de 2014, foi realizado um estudo transversal, incluindo 85 pacientes oriundos do Hospital Jean Bitar, na Cidade de Belém, Estado do Pará, Brasil. Foi realizada a pesquisa de anticorpos específicos contra os agentes virais estudados, assim como pesquisa da presença do genoma para EBV e HTLV. Foram avaliadas também variáveis clínicas e epidemiológicas. A maioria dos pacientes eram mulheres, tinham média de idade de 30 anos e se declararam brancos. Para EBV, detectou-se positividade de 37,6% para IgM, 98,8% para IgG e 2,4% por qPCR, com quantificações de 85.028 e 298 cópias do genoma/mL de plasma. Para B19, a positividade para IgM foi 0% e para IgG 67,1%. Não houve detecção sorológica ou por qPCR de HTLV. Foi verificada relação estatisticamente significante entre a positividade para IgM anti-EBV e pacientes mais jovens. Esse achado pode estar relacionado com a maior eficiência na produção dessa imunoglobulina nas infecções primárias agudas, que ocorrem geralmente em indivíduos infantes ou adultos jovens. Adicionalmente, o resultado de IgG anti-B19 foi associado à idade avançada dos pacientes, provavelmente por um maior tempo de exposição ao vírus aliado à persistência desse marcador após o contato. A presença dos marcadores não esteve associada às variáveis clínicas e epidemiológicas. Entretanto, o percentual de positividade para o marcador de infecção aguda por EBV pode sugerir um envolvimento do vírus com o LES.Systemic lupus erythematosus (SLE) is a chronic autoimmune disease whose development may be associated with viral infections, such as Epstein-Barr virus (EBV), parvovirus B19, and human T-cell lymphotropic virus (HTLV). A cross-sectional study was performed between June and September 2014 involving 85 patients from the Hospital Jean Bitar, located in Belém, Pará State, Brazil. A survey of specific antibodies against the studied viral agents was conducted, in addition to a survey of the EBV and HTLV genomes. Clinical and epidemiologic variables were also evaluated. Most patients were female, approximately 30 years old, and declared themselves as Caucasians. The following positive results were detected for EBV: IgM = 37.6%, IgG = 98.8%, and qPCR = 2.4%, with 85,028 and 298 copies of the genome per milliliter of plasma. Positive results for B19 were: IgM = 0%, IgG = 67.1%. Serological or qPCR detection did not reveal HTLV. A significant statistical correlation was observed between anti-EBV IgM antibodies and younger patients. These findings may be related to the highly efficient production of this immunoglobulin during acute primary infections, which frequently occurs in children and young adults. Furthermore, the results for anti-B19 IgG were associated with the patients' advanced age, resulting from the longer exposure period to the virus combined with this marker's persistence after exposure. Presence of the marker was not associated with clinical and epidemiological variables. However, the percentage of cases of acute infection by the EBV marker suggests an association with SLE

Aspergillus fumigatus Transcription Factors Involved in the Caspofungin Paradoxical Effect

International audienceAspergillus fumigatus is the leading cause of pulmonary fungal diseases. Azoles have been used for many years as the main antifungal agents to treat and prevent invasive aspergillosis. However, in the last 10 years there have been several reports of azole resistance in A. fumigatus and new strategies are needed to combat invasive aspergillosis. Caspofungin is effective against other human-pathogenic fungal species, but it is fungistatic only against A. fumigatus. Resistance to caspofungin in A. fumigatus has been linked to mutations in the fksA gene that encodes the target enzyme of the drug β-1,3-glucan synthase. However, tolerance of high caspofungin concentrations, a phenomenon known as the caspofungin paradoxical effect (CPE), is also important for subsequent adaptation and drug resistance evolution. Here, we identified and characterized the transcription factors involved in the response to CPE by screening an A. fumigatus library of 484 null transcription factors (TFs) in CPE drug concentrations. We identified 11 TFs that had reduced CPE and that encoded proteins involved in the basal modulation of the RNA polymerase II initiation sites, calcium metabolism, and cell wall remodeling. One of these TFs, FhdA, was important for mitochondrial respiratory function and iron metabolism. The ΔfhdA mutant showed decreased growth when exposed to Congo red or to high temperature. Transcriptome sequencing (RNA-seq) analysis and further experimental validation indicated that the ΔfhdA mutant showed diminished respiratory capacity, probably affecting several pathways related to the caspofungin tolerance and resistance. Our results provide the foundation to understand signaling pathways that are important for caspofungin tolerance and resistance

HLA-B13, B35 and B39 alleles are closely associated with the lack of response to ART in HIV infection: a cohort study in a population of northern Brazil

Secretaria de Vigilancia em Saúde do Ministério da Saúde (Health Surveillance Secretariat of the Ministry of Health), Conselho Nacional de Desenvolvimento Cientıfíco e Tecnológico (National Council for Scientific and Technological Development; CNPQ) (no. 301869/ 2017-0) and Fundação Amazônia de Amparo a Estudos e Pesquisa – FAPESPA (ICAAF-60/2020). Coordenação de Aperfeiçoamento de Pessoal de Nıvel Superior ́ (Brazilian Federal Agency for the Support and Evaluation of Graduate Education; CAPES) for granting a scholarship (process number: 88882.183970/2018-01).Federal University of Pará. Institute of Biological Sciences. Virology Laboratory. Belém, PA, BrazilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de vírus Epstein-Barr. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de vírus Epstein-Barr. Ananindeua, PA, BrasilHemotherapy and Hematology Foundation of the State of Pará. Department of Immunogenetics. Belém, PA, BrazilHemotherapy and Hematology Foundation of the State of Pará. Department of Immunogenetics. Belém, PA, BrazilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de vírus Epstein-Barr. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Retrovirus. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de vírus Epstein-Barr. Ananindeua, PA, Brasil / Federal University of Pará. School of Medicine. Belém, PA, BrazilFederal University of Pará. Institute of Biological Sciences. Laboratory of Human and Medical Genetics. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, BrazilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Retrovirus. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de vírus Epstein-Barr. Ananindeua, PA, Brasil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, BrazilFederal University of Pará. Institute of Biological Sciences. Virology Laboratory. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, BrazilIntroduction Immune reconstitution failure after HIV treatment is a multifactorial phenomenon that may also be associated with a single polymorphism of human leukocyte antigen (HLA); however, few reports include patients from the Brazilian Amazon. Our objective was to evaluate the association of the immunogenic profile of the “classical” HLA-I and HLA-II loci with treatment nonresponse in a regional cohort monitored over 24 months since HIV diagnosis. Materials and Methods Treatment-free participants from reference centers in the state of Pará, Brazil, were enrolled. Infection screening was performed using enzyme immunoassays (Murex AG/AB Combination DiaSorin, UK) and confirmed by immunoblots (Bio-Manguinhos, FIOCRUZ). Plasma viral load was quantified by real-time PCR (ABBOTT, Chicago, Illinois, USA). CD4 ⁺ /CD8 ⁺ T lymphocyte quantification was performed by immunophenotyping and flow cytometry (BD Biosciences, San Jose, CA, USA). Infection was monitored via test and logistics platforms (SISCEL and SICLOM). Therapeutic response failure was inferred based on CD4 ⁺ T lymphocyte quantification after 1 year of therapy. Loci A, B and DRB1 were genotyped using PCR-SSO (One Lambda Inc., Canoga Park, CA, USA). Statistical tests were applied using GENEPOP, GraphPad Prism 8.4.3 and BioEstat 5.3. Results Of the 270 patients monitored, 134 responded to treatment (CD4 ⁺ ≥ 500 cells/µL), and 136 did not respond to treatment (CD4 ⁺ < 500 cells/µL). The allele frequencies of the loci were similar to heterogeneous populations. The allelic profile of locus B was statistically associated with treatment nonresponse, and the B*13, B*35 and B*39 alleles had the greatest probabilistic influence. The B*13 allele had the highest risk of treatment nonresponse, and carriers of the allele had a detectable viral load and a CD4+ T lymphocyte count less than 400 cells/µL with up to 2 years of therapy. The B*13 allele was associated with a switch in treatment regimens, preferably to efavirenz (EFZ)-based regimens, and among those who switched regimens, half had a history of coinfection with tuberculosis. Conclusions The allelic variants of the B locus are more associated with non-response to therapy in people living with HIV (PLHIV) from a heterogeneous population in the Brazilian Amazon