Óbito por dengue 4 no Brasil em paciente com púrpura trombocitopênica idiopática

Dengue é atualmente um importante problema de saúde pública. O vírus da dengue (DENV) é classificado em quatro sorotipos distintos, DENV 1-4. Após 28 anos de ausência, o DENV-4 foi detectado novamente no Brasil em 2010 no Estado de Roraima, e um ano depois, o vírus foi identificado em outros estados do norte do país, Amazonas e Pará, seguido pelos estados do Rio de Janeiro e São Paulo. Em Minas Gerais, o primeiro caso confirmado de DENV-4 ocorreu no município de Frutal em 2011 e, desde então, o sorotipo foi isolado em um número crescente de pacientes. Apesar do DENV-2 estar associado a um maior risco de formas graves e morte, o DENV-4 também tem sido associado a casos graves e a risco aumentado de manifestações hemorrágicas. Neste relato, descrevemos o primeiro caso fatal confirmado por DENV-4 no Brasil. A paciente era uma menina de 11 anos do município de Montes Claros, no norte de Minas Gerais, Brasil. Apresentava púrpura trombocitopênica idiopática e evoluiu de forma fulminante durante a infecção por dengue, com óbito associado a complicações hemorrágicas. O diagnóstico foi confirmado pela detecção de anticorpos IgM específicos para dengue, por método imunoenzimático, e por semi-nested RT-PCR. Médicos e outros profissionais de saúde devem estar cientes que infecções por DENV-4 também podem resultar em formas graves da doença com complicações hemorrágicas e óbito, principalmente em pacientes com comorbidades.Dengue is currently a major public-health problem. Dengue virus (DENV) is classified into four distinct serotypes, DENV 1-4. After 28 years of absence, DENV-4 was again detected in Brazil in 2010 in Roraima State, and one year later, the virus was identified in the northern Brazilian states of Amazonas and Pará, followed by Rio de Janeiro and São Paulo. In Minas Gerais, the first confirmed case of DENV-4 occurred in the municipality of Frutal in 2011 and has now been isolated from a growing number of patients. Although DENV-2 is associated with the highest risk of severe forms of the disease and death due to the infection, DENV-4 has also been associated with severe forms of the disease and an increasing risk of hemorrhagic manifestations. Herein, the first fatal case of confirmed DENV-4 in Brazil is reported. The patient was an 11-year-old girl from the municipality of Montes Claros in northern Minas Gerais State, Brazil. She had idiopathic thrombocytopenic purpura as a comorbid condition and presented with a fulminant course of infection, leading to death due to hemorrhagic complications. Diagnosis was confirmed by detection of Dengue-specific antibodies using IgM capture enzyme-linked immunosorbent assay and semi-nested RT-PCR. Primary care physicians and other health-care providers should bear in mind that DENV-4 can also result in severe forms of the disease and lead to hemorrhagic complications and death, mainly when dengue infection is associated with coexisting conditions

Promoting Responsible Research and Innovation (RRI) During Brazilian Activities of Genomic and Epidemiological Surveillance of Arboviruses

Zika infectio

Cocirculation of two dengue virus serotypes in individual and pooled samples of Aedes aegypti and Aedes albopictus larvae

INTRODUCTION: To detect dengue virus, eggs of Aedes sp were collected in the city of Belo Horizonte, Brazil, in 2007. METHODS: Egg samples were subsequently hatched and the larvae were tested for the presence of dengue virus RNA by RT-PCR. RESULTS: Among the Aedes aegypti larvae samples, 163 (37.4%) out of 435 were positive, including 32 (10.9%) of 293 individual larvae samples concomitantly positive for two serotypes. CONCLUSIONS: Virological surveillance detecting coinfected vectors in the field could represent an important strategy for understanding the numerous factors involved in the transmission and clinical presentation of dengue

Persistence of Yellow fever virus outside the Amazon Basin, causing epidemics in Southeast Brazil, from 2016 to 2018

<div><p>Background</p><p>Yellow fever (YF) is endemic in the Brazilian Amazon Basin, and sporadic outbreaks take place outside the endemic area in Brazil. Since 2016, YF epidemics have been occurring in Southeast Brazil, with more than 1,900 human cases and more than 1,600 epizooties of non-human primates (NHPs) reported until April 2018. Previous studies have demonstrated that Yellow fever virus (YFV) causing outbreaks in 2017 formed a monophyletic group.</p><p>Methodology/Principal findings</p><p>Aiming to decipher the origin of the YFV responsible for the recent epidemics, we obtained nucleotide sequences of YFV detected in humans (n = 6) and NHPs (n = 10) from Minas Gerais state during 2017–2018. Next, we performed evolutionary analyses and discussed the results in the light of epidemiological records (official numbers of YFV cases at each Brazilian Federative unit, reported by the Brazilian Ministry of Health). Nucleotide sequences of YFV from Southeast Brazil from 2016 to 2018 were highly conserved and formed a monophyletic lineage (BR-YFV_2016/18) within the genotype South America I. Different clusters were observed within lineage BR-YFV_2016/18, one containing the majority of isolates (from humans and NHPs), indicating the sylvatic transmission of YFV. We also detected a cluster characterized by two synapomorphies (amino acid substitutions) that contained YFV only associated with NHP what should be further investigated. The topology of lineage BR-YFV_2016/18 was congruent with epidemiological and temporal patterns of the ongoing epidemic. YFV isolates detected in 2016, in São Paulo state were located in the most basal position of the lineage, followed by the isolates from Minas Gerais and Espírito Santo obtained in 2017 and 2018. The most recent common ancestor of the lineage BR-YFV_2016/18 dated to 2015 (95% credible intervals = 2014–2016), in a period that was coincident with the reemergence of YFV in the Midwest region of Brazil.</p><p>Conclusions</p><p>The results demonstrated a single introduction of YFV in the Southeast region and the silent viral circulation before the onset of the outbreaks in 2016. Evolutionary analyses combined with epidemiological records supported the idea that BR-YFV_2016/18 was probably introduced from the Midwest into the Southeast region, possibly in São Paulo state. The persistence of YFV in the Southeast region, causing epidemics from 2016 to 2018, suggests that this region presents suitable ecological and climatic conditions for YFV maintenance during the epidemic and interepidemic seasons. This fact poses risks for the establishing of YF enzootic cycles and epidemics, outside the Amazon Basin in Brazil. YF surveillance and studies of viral dynamics deserve particular attention, especially in Midwest, Southeast and neighbor regions which are the main areas historically associated with YF outbreaks outside the Amazon Basin. YFV persistence in Southeast Brazil should be carefully considered in the context of public health, especially for public health decision-makers and researchers.</p></div

Low prevalence of influenza A strains with resistance markers in Brazil during 2017–2019 seasons

This project was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Programa Estratégico de Apoio à Pesquisa em Saúde (PAPES), Fundação Oswaldo Cruz, CNPq, and Coordenação Geral de Laboratórios de Saúde Pública (CGLAB) from the Brazilian Ministry of Health.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Laboratório Central de Saúde Pública de Sergipe. Aracaju, SE, Brazil.Laboratório Central de Saúde Pública de Sergipe. Aracaju, SE, Brazil.Laboratório Central do Estado do Paraná. Curitiba, PR, Brazil.Laboratório Central do Estado do Paraná. Curitiba, PR, Brazil.Secretaria de Saúde do Estado do Espírito Santo. Laboratório de Saúde Pública do Estado do Espírito Santo. Vitória, ES, Brazil / Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, Brazil.Secretaria de Saúde do Estado do Espírito Santo. Laboratório de Saúde Pública do Estado do Espírito Santo. Vitória, ES, Brazil / Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, Brazil.Laboratório Central de Saúde Pública do Rio de Janeiro. Rio de Janeiro, RJ, Brazil.Laboratório Central de Saúde Pública do Rio de Janeiro. Rio de Janeiro, RJ, Brazil.Secretaria de Saúde do estado do Rio Grande do Sul. Laboratório Central de Saúde Pública. Porto Alegre, RS, Brazil.Secretaria de Saúde do estado do Rio Grande do Sul. Laboratório Central de Saúde Pública. Porto Alegre, RS, Brazil.Fundação Ezequiel Dias. Laboratório Central de Saúde Pública de Minas Gerais. Belo Horizonte, MG, Brazil.Fundação Ezequiel Dias. Laboratório Central de Saúde Pública de Minas Gerais. Belo Horizonte, MG, Brazil.Laboratório Central da Saúde Pública do estado da Bahia. Salvador, BA, Brazil.Laboratório Central da Saúde Pública do estado da Bahia. Salvador, BA, Brazil.Laboratório Central de Santa Catarina. Florianópolis, SC, Brazil.Laboratório Central de Santa Catarina. Florianópolis, SC, Brazil.Ministério da Saúde. Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos. Instituto Evandro Chagas. Ananindeua, PA. Brasil.Ministério da Saúde. Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos. Instituto Evandro Chagas. Ananindeua, PA. Brasil.Instituto Adolfo Lutz. Laboratório Central de Saúde Pública do Estado de São Paulo. São Paulo, SP, Brazil.Instituto Adolfo Lutz. Laboratório Central de Saúde Pública do Estado de São Paulo. São Paulo, SP, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Imunização e Doenças Transmissíveis. Brasília, DF, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Imunização e Doenças Transmissíveis. Brasília, DF, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.The influenza A virus (IAV) is of a major public health concern as it causes annual epidemics and has the potential to cause pandemics. At present, the neuraminidase inhibitors (NAIs) are the most widely used anti-influenza drugs, but, more recently, the drug baloxavir marboxil (BXM), a polymerase inhibitor, has also been licensed in some countries. Mutations in the viral genes that encode the antiviral targets can lead to treatment resistance. Worldwide, a low prevalence of antiviral resistant strains has been reported. Despite that, this situation can change rapidly, and resistant strain surveillance is a priority. Thus, the aim of this was to evaluate Brazilian IAVs antiviral resistance from 2017 to 2019 through the identification of viral mutations associated with reduced inhibition of the drugs and by testing the susceptibility of IAV isolates to oseltamivir (OST), the most widely used NAI drug in the country. Initially, we analyzed 282 influenza A(H1N1)pdm09 and 455 A(H3N2) genetic sequences available on GISAID. The amino acid substitution (AAS) NA:S247N was detected in one A(H1N1)pdm09 strain. We also identified NA:I222V (n = 6) and NA:N329K (n = 1) in A(H3N2) strains. In addition, we performed a molecular screening for NA:H275Y in 437 A(H1N1)pdm09 samples, by pyrosequencing, which revealed a single virus harboring this mutation. Furthermore, the determination of OST IC50 values for 222 A(H1N1)pdm09 and 83 A(H3N2) isolates revealed that all isolates presented a normal susceptibility profile to the drug. Interestingly, we detected one A(H3N2) virus presenting with PA:E119D AAS. Moreover, the majority of the IAV sequences had the M2:S31N adamantanes resistant marker. In conclusion, we show a low prevalence of Brazilian IAV strains with NAI resistance markers, in accordance with what is reported worldwide, indicating that NAIs still remain an option for the treatment of influenza infections in Brazil. However, surveillance of influenza resistance should be strengthened in the country for improving the representativeness of investigated viruses and the robustness of the analysis