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J Antimicrob Chemother. 2014 Sep;69(9):2458-69. doi: 10.1093/jac/dku146. Epub 2014 May 19.

Evaluation of oseltamivir prophylaxis regimens for reducing influenza virus infection, transmission and disease severity in a ferret model of household contact.

Author information

1
WHO Collaborating Centre for Reference and Research on Influenza, North Melbourne, Victoria, Australia.
2
Australian Animal Health Laboratory, Geelong, Victoria, Australia.
3
Vaccine and Immunisation Research Group, Murdoch Childrens Research Institute, Royal Childrens Hospital, Parkville, Victoria, Australia Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
4
WHO Collaborating Centre for Reference and Research on Influenza, North Melbourne, Victoria, Australia School of Applied Sciences and Engineering, Monash University, Churchill, Victoria, Australia.
5
WHO Collaborating Centre for Reference and Research on Influenza, North Melbourne, Victoria, Australia School of Applied Sciences and Engineering, Monash University, Churchill, Victoria, Australia aeron.hurt@influenzacentre.org.

Abstract

OBJECTIVES:

The emergence of the pandemic influenza A(H1N1)pdm09 virus in 2009 saw a significant increase in the therapeutic and prophylactic use of neuraminidase inhibitors (NAIs) to mitigate the impact of this highly transmissible virus. Prior to the pandemic, many countries stockpiled NAIs and developed pandemic plans for the use of antiviral drugs, based on either treatment of high-risk individuals and/or prophylaxis of contacts. However, to date there has been a lack of in vivo models to test the efficacy of treatment or prophylaxis with NAIs, for influenza-infected individuals or exposed contacts, in a household setting.

METHODS:

A ferret model of household contact was developed to study the efficacy of different prophylaxis regimens in preventing infection in contact ferrets exposed to influenza A(H1N1)pdm09-infected index ferrets.

RESULTS:

Among the different prophylactic regimens, contact ferrets receiving oseltamivir prophylaxis twice daily showed better outcomes than those receiving oseltamivir once daily. Benefits included a significant delay in the time to secondary infection, lower weight loss and higher activity levels. The treatment of index ferrets at 36 h post-infection did not influence either secondary infection rates or clinical symptoms in exposed contact ferrets. Neither prophylaxis nor treatment prevented infection or reduced the duration of viral shedding, although clinical symptoms did improve in infected animals receiving prophylaxis.

CONCLUSIONS:

Different oseltamivir prophylaxis regimens did not prevent infections, but consistently resulted in a reduction in symptoms in infected ferrets. However, oseltamivir prophylaxis failed to reduce viral titres, which warrants further investigation in humans.

KEYWORDS:

A(H1N1)pdm09; antiviral; neuraminidase inhibitors; pandemic

PMID:
24840623
PMCID:
PMC4130381
DOI:
10.1093/jac/dku146
[Indexed for MEDLINE]
Free PMC Article
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