Spread of Influenza A(H1N1) oseltamivir-resistant viruses in Africa in 2008 confirmed by multiple introductions in Senegal

Among Influenza neuraminidase inhibitors (NAIs), oseltamivir corresponds to the most widely used agent to treat influenza disease. However since 2001, several cases of resistance to NAIs have been reported for circulating seasonal A(H1N1) Influenza viruses. A direct resistance mechanism may be invok...

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Bibliographic Details
Published in:	BMC infectious diseases Vol. 13; no. 1; p. 106
Main Authors:	Dia, Ndongo, Niang, Mbayame N, Diadhiou, Saadiya A, Goudiaby, Déborah G, Faye, Abdourahmane, Kiori, Davy, Bâ, Mady, Michel, Rémy, Diop, Ousmane M
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 27-02-2013 BioMed Central
Subjects:	Adolescent Adult Analysis Antiviral Agents - pharmacology Child Child, Preschool Drug Resistance, Viral Genes Genetic aspects Genetic polymorphisms Hemagglutinin Glycoproteins, Influenza Virus - genetics Humans Infant Influenza Influenza A Virus, H1N1 Subtype - classification Influenza A Virus, H1N1 Subtype - drug effects Influenza A Virus, H1N1 Subtype - genetics Influenza A Virus, H1N1 Subtype - isolation & purification Influenza viruses Influenza, Human - epidemiology Influenza, Human - virology Microbial Sensitivity Tests Microbiology Middle Aged Mutation Oseltamivir - pharmacology Phylogeny Reverse Transcriptase Polymerase Chain Reaction Senegal - epidemiology Viral drug resistance Senegal United Kingdom Africa Norway Europe
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Summary:	Among Influenza neuraminidase inhibitors (NAIs), oseltamivir corresponds to the most widely used agent to treat influenza disease. However since 2001, several cases of resistance to NAIs have been reported for circulating seasonal A(H1N1) Influenza viruses. A direct resistance mechanism may be invoked, involving critical mutations in the viral NA gene that prevent the drug binding to its target. Same phenomenon is reported for adamantanes drugs and mutations in the M2 channel protein gene of Influenza viruses. Reverse-Transcription/Restriction Fragment Length Polymorphism (RT-PCR/RFLP) method, phenotypic testing for oseltamivir resistance, and sequencing of NA, HA and M2 genes were used in this study. Phylogenetic analyses were performed using BioEdit and Mega 5 softwares for alignment of sequences and phylogenetic trees building respectively. Using a simple RT-PCR/RFLP method, we found that the 86 seasonal A(H1N1) isolates from 2008 bear the oseltamivir resistance-associated mutation (H274Y) in the NA gene. In contrast all isolates isolated in Senegal in 2007 were sensitive to oseltamivir. These results were first confirmed by finding high IC50 values using a phenotypic testing for oseltamivir resistance, and secondly by sequencing the whole NA gene. Regarding M2 gene, no mutation associated to adamantanes resistance was characterized of the isolates. The present work provides evidence of circulation of drug-resistant seasonal A(H1N1) viruses during the 2008 influenza season (July to September) in Senegal. The results are in favor of multiple introductions of oseltamivir resistant viruses (ORV) A(H1N1) in Senegal.Phylogenetic analyses of isolates with complete sequences of N1 and HA1 genes showed that they belong to clade 2B and suggest sequential introductions in Africa.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1471-2334 1471-2334
DOI:	10.1186/1471-2334-13-106