Saturday, July 04, 2009

The ECDC On The Ferret Pathogenicity Study

 

 

# 3438

 

Earlier this week I highlighted 3 reports by Helen Branswell, Maryn McKenna/Lisa Schnirring, and the Revere’s on Effect Measure on the two pathogenesis and transmissibility studies published this past week conducted on ferrets.

 

The ECDC (European Centre of Disease Prevention and Control) has also published their own recap of these studies.  

 

They take a cautious stance, reminding us that ferret studies do not always match with what humans may experience with a virus.  

 

But they do acknowledge that this novel H1N1 virus appears to have slightly greater virulence than seasonal H1N1, with a propensity towards lodging in the lower lungs, and migrating to the intestinal tract.

 


I’ve reparagraphed their comments for readability.  A hat tip goes to Anne, who very kindly emailed me this link.

 

 

 

EECDC Comment (3/07/2009):


Understanding the pathogenesis and transmission of the influenza A/H1N1v is essential for planning of appropriate Public Health responses to the current pandemic.

 

In the two pandemicly published articles different influenza A/H1N1v isolates from patients with varying severity of their clinical symptoms have been compared with a contemporary seasonal H1N1 virus for their ability to cause disease in mice and ferrets. In addition, their ability to transmit to naïve ferrets has also been assessed.

 

To date, these are the first studies that have tried to analyse the pathogenicity and transmissibility characteristics of the influenza A(H1N1)v virus. The results of the first study (Maines et al.) might be considered more representative since they used three different strains of the pandemic virus as opposed to only one strain used in the second study (Munster et al.).

 

Additionally, the first study was carried out over a longer period (two versus one week). However there are important common findings for the pandemic virus:

 

  • Significant but not lethal pathogenicity from the pandemic A(H1N1)v – somewhat more than for seasonal A(H1N1) but considerably less than that seen for A(H5N1) (bird flu) in ferrets.
  • In contrast to the seasonal influenza A H1N1 confined to the nasal cavity the pandemic influenza A/H1N1v isolates also replicated in the trachea, bronchi and bronchioles. No ferrets died from their infection,
  • Droplet respiratory expression (but not transmission) occurring with the pandemic virus was higher than with seasonal influenza though not reaching the levels when using a 1918 pandemic virus.
  • Successful and efficient ferret to ferret transmission but,
  • Respiratory droplet transmission was significantly reduced compared to respiratory droplet transmission of the seasonal influenza virus.
  • No systemic replication of the A(H1N1)v
  • Pandemic viruses being found at higher levels in the lower respiratory tract of the infected individuals,
  • Pandemic viruses in the intestinal tracts of the animals, which is consistent with some report of a explains the higher frequency of gastrointestinal symptoms observed in individuals affected by the pandemic virus.
  • An ability of both viruses to infect the same cells in the respiratory tract (upper and lower) so increasing the risk of reassortment when co-infection occurs in humans.

 

It is possible to speculate that droplet respiratory transmission was diminished in ferrets infected with the influenza A(H1N1)v virus when compared to the normal seasonal influenza viruses in the US study at least might be encouraging.

 

However ferrets are ferrets and humans are humans and this study is not a replacement for human studies of viral expression. 

 

A conclusion from the Netherlands study that pandemic  A(H1N1)v virus is more pathogenic than seasonal A(H1N1) needs some interpretation before extending to humans.

 

The control used seasonal A(H1N1) which on a case by case basis is less pathogenic in humans than seasonal A(H3N2). Also the picture in humans is coloured by the welcome absence of infections in older people. More experience and data are  needed before similar conclusions can be drawn from humans.

 

What finally is evident, and we need to be vigilant of is that the pandemic virus is here to stay, co-circulating with seasonal influenza strains, maybe re-assorting with them or with more pathogenic strains like the avian influenza viruses, or even mutating by giving origin to (yet again) a pandemic influenza virus.

 

These publications confirm the clinical picture observed in humans with the pandemic strain and is suggestive that we will continue to see severe disease in some individuals even without any further genetic changes in the circulating influenza A/H1N1v strains.

 

Should a more significant genetic change to the circulating viral strains occur, the ferret and the mouse models may serve as appropriate models to assess any changed pathogenicity. A baseline has been established by these research groups.