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Congres Quebecois en Sante respiratoire 14 et 15 novembre 2013 • Montreal, Quebec


ABSTRACT: BACKGROUND: Neuraminidase inhibitors (NAIs) such as oseltamivir (O) and zanamivir (Z) play a central role in the control of influenza infections. However, the emergence and dissemination of antiviral resistance threaten the efficacy of this intervention and advocate for innovative therapeutic strategies. The objective of this study was to evaluate in mice the efficacy of O-Z combination compared to that of monotherapy, for the treatment of experimental infections with influenza A(H1N1)pdm09 viruses. METHODS: Recombinant A(H1N1)pdm09 wild-type (WT) and O-resistant H275Y NA mutant viruses were generated by reverse genetics. Groups of twelve C57BL/6 mice were inoculated intranasally with saline, the WT or H275Y viruses. To mimic the clinical condition, infected mice were treated 48h p.i. with either saline, O by gavage, Z intranasally, or an O-Z combination, twice daily for 5 days. Weight loss and mortality were monitored for 14 days. On day 4 p.i., four mice were sacrificed to determine lung viral titers (LVT) by plaque assay in ST6GalI-MDCK cells. RESULTS: In mice infected with the WT virus, treatment with Z or O-Z resulted in 100% survival, vs 50% for the O group and 12.5% for the untreated group. Z monotherapy also led to a significant reduction in weight loss compared to O as well as lower LVT (5.7E^6 vs 1.7E^7 PFU mL, respectively). Intermediate values were observed for the O-Z combination. In the H275Y group, the efficacy of O-Z was comparable to that of Z and significantly higher than that of O in terms of survival (85.7% and 100% vs 12.5%, respectively), weight loss and LVT (5.4E^6 and 3.5E^6 vs 2.8E^8 PFU/mL, respectively). The evaluation of these treatments in mice infected with influenza A(H3N2) is in progress. CONCLUSIONS: Z monotherapy had greater efficacy than O in mice infected with A(H1N1)pdm09. O-Z bitherapy conferred no significant advantage over Z monotherapy. Development of new molecules and synergistic combined therapies are a necessity.

SUBMITTER: Pizzorno A 

PROVIDER: S-EPMC4128466 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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