Evaluation of oseltamivir prophylaxis regimens for reducing influenza virus infection, transmission and disease severity in a ferret model of household contact.
OBJECTIVE
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.
WHO Collaborating Centre for Reference and Research on Influenza, North Melbourne, Victoria, Australia.
Ding Yuan
DY
Oh
Australian Animal Health Laboratory, Geelong, Victoria, Australia.
Sue
S
Lowther
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.
James M
JM
McCaw
WHO Collaborating Centre for Reference and Research on Influenza, North Melbourne, Victoria, Australia.
Sheena G
SG
Sullivan
WHO Collaborating Centre for Reference and Research on Influenza, North Melbourne, Victoria, Australia.
Sook-Kwan
SK
Leang
Australian Animal Health Laboratory, Geelong, Victoria, Australia.
Jessica
J
Haining
Australian Animal Health Laboratory, Geelong, Victoria, Australia.
Rachel
R
Arkinstall
WHO Collaborating Centre for Reference and Research on Influenza, North Melbourne, Victoria, Australia.
Anne
A
Kelso
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.
Jodie
J
Mcvernon
WHO Collaborating Centre for Reference and Research on Influenza, North Melbourne, Victoria, Australia School of Applied Sciences and Engineering, Monash University, Churchill, Victoria, Australia.
Ian G
IG
Barr
Australian Animal Health Laboratory, Geelong, Victoria, Australia.
Deborah
D
Middleton
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.
Aeron C
AC
Hurt
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D005260:Female; D005289:Ferrets; D006801:Humans; D007251:Influenza, Human / Q000473:pathology* / Q000517:prevention & control* / Q000635:transmission; D008297:Male; D053139:Oseltamivir / Q000008:administration & dosage*; D065129:Pre-Exposure Prophylaxis / Q000379:methods*; D012720:Severity of Illness Index; D019562:Viral Load; D017201:Virus Shedding
D000998:Antiviral Agents; D053139:Oseltamivir
A(H1N1)pdm09; antiviral; neuraminidase inhibitors; pandemic