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Mem. Inst. Oswaldo Cruz ; 110(1): 101-105, 03/02/2015. tab, graf
Article in English | LILACS, ColecionaSUS, CONASS | ID: lil-741611


The 2009 pandemic influenza A virus outbreak led to the systematic use of the neuraminidase (NA) inhibitor oseltamivir (OST). Consequently, OST-resistant strains, carrying the mutation H275Y, emerged in the years after the pandemics, with a prevalence of 1-2%. Currently, OST-resistant strains have been found in community settings, in untreated individuals. To spread in community settings, H275Y mutants must contain additional mutations, collectively called permissive mutations. We display the permissive mutations in NA of OST-resistant A(H1N1)pdm09 virus found in Brazilian community settings. The NAs from 2013 are phylogenetically distinct from those of 2012, indicating a tendency of positive selection of NAs with better fitness. Some previously predicted permissive mutations, such as V241I and N369K, found in different countries, were also detected in Brazil. Importantly, the change D344N, also predicted to compensate loss of fitness imposed by H275Y mutation, was found in Brazil, but not in other countries in 2013. Our results reinforce the notion that OST-resistant A(H1N1)pdm09 strains with compensatory mutations may arise in an independent fashion, with samples being identified in different states of Brazil and in different countries. Systematic circulation of these viral strains may jeopardise the use of the first line of anti-influenza drugs in the future. (AU)

Humans , Male , Female , Adult , Middle Aged , Aged , Influenza A virus , Drug Resistance, Viral , Oseltamivir/pharmacology , Mutation/drug effects
Mem. Inst. Oswaldo Cruz ; 110(1): 148-150, 03/02/2015. tab
Article in English | LILACS | ID: lil-741618


The influenza A(H3N2) virus has circulated worldwide for almost five decades and is the dominant subtype in most seasonal influenza epidemics, as occurred in the 2014 season in South America. In this study we evaluate five whole genome sequences of influenza A(H3N2) viruses detected in patients with mild illness collected from January-March 2014. To sequence the genomes, a new generation sequencing (NGS) protocol was performed using the Ion Torrent PGM platform. In addition to analysing the common genes, haemagglutinin, neuraminidase and matrix, our work also comprised internal genes. This was the first report of a whole genome analysis with Brazilian influenza A(H3N2) samples. Considerable amino acid variability was encountered in all gene segments, demonstrating the importance of studying the internal genes. NGS of whole genomes in this study will facilitate deeper virus characterisation, contributing to the improvement of influenza strain surveillance in Brazil.

Adult , Aged , Female , Humans , Male , Middle Aged , Glucocorticoids/administration & dosage , Hepatitis B, Chronic/drug therapy , Prednisolone/administration & dosage , Severity of Illness Index , Acute Disease , Hepatitis B, Chronic/mortality , Hepatitis B, Chronic/pathology , Immunosuppressive Agents/administration & dosage , Necrosis , Treatment Outcome
Mem. Inst. Oswaldo Cruz ; 109(7): 912-917, 11/2014. tab, graf
Article in English | LILACS | ID: lil-728806


After the World Health Organization officially declared the end of the first pandemic of the XXI century in August 2010, the influenza A(H1N1)pdm09 virus has been disseminated in the human population. In spite of its sustained circulation, very little on phylogenetic data or oseltamivir (OST) resistance is available for the virus in equatorial regions of South America. In order to shed more light on this topic, we analysed the haemagglutinin (HA) and neuraminidase (NA) genes of influenza A(H1N1)pdm09 positive samples collected during the pandemic period in the Pernambuco (PE), a northeastern Brazilian state. Complete HA sequences were compared and amino acid changes were related to clinical outcome. In addition, the H275Y substitution in NA, associated with OST resistance, was investigated by pyrosequencing. Samples from PE were grouped in phylogenetic clades 6 and 7, being clustered together with sequences from South and Southeast Brazil. The D222N/G HA gene mutation, associated with severity, was found in one deceased patient that was pregnant. Additionally, the HA mutation K308E, which appeared in Brazil in 2010 and was only detected worldwide the following year, was identified in samples from hospitalised cases. The resistance marker H275Y was not identified in samples tested. However, broader studies are needed to establish the real frequency of resistance in this Brazilian region.

Female , Humans , Pregnancy , Hemagglutinins/genetics , Influenza A Virus, H1N1 Subtype/genetics , Influenza, Human/epidemiology , Neuraminidase/genetics , Pandemics , Antiviral Agents/therapeutic use , Biomarkers/analysis , Brazil/epidemiology , Drug Resistance, Viral/physiology , Gene Frequency/genetics , Influenza A Virus, H1N1 Subtype/classification , Influenza A Virus, H1N1 Subtype/pathogenicity , Influenza, Human/virology , Mutation/genetics , Oseltamivir/therapeutic use , Phylogeny , RNA, Viral/analysis , Sequence Analysis, DNA/methods , Virulence , Virulence Factors/genetics