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Open Access Research article

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

Ndongo Dia1, Mbayame N Niang1, Saadiya A Diadhiou2, Déborah G Goudiaby1, Abdourahmane Faye1, Davy Kiori1, Mady Bâ2, Rémy Michel3 and Ousmane M Diop14*

Author Affiliations

1 Institut Pasteur de Dakar, Unité de Virologie Médicale, Dakar, Sénégal

2 Ministère de la Santé et de la Prévention, Dakar, Sénégal

3 Institut Pasteur de Dakar, Unité d’Epidémiologie des maladies infectieuses, Dakar, Sénégal

4 Unit of Medical Virology, Institut Pasteur de Dakar, Dakar, BP 220, Senegal

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BMC Infectious Diseases 2013, 13:106  doi:10.1186/1471-2334-13-106

Published: 27 February 2013

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords:
Influenza; Oseltamivir; Resistance