An analysis of the ferret co-infection paper

A new study of the pandemic flu virus using ferrets as experimental animals has received a great deal of attention from the press today. Unfortunately, the headlines suggest some things that are not true and leave out an important finding.

Rationale

The purpose of this study was to compare the relative fitness of seasonal influenza with the new H1N1 virus. The investigators wished to experimentally test the hypothesis that the new H1N1 virus would replace seasonal flu as the dominant influenza circulating in humans.

Methods

Ferrets, animals that reproduce many of the symptoms and pathologies observed in humans after flu infections, were experimentally infected with seasonal H3N2 influenza (A/Brisbane/10/07), seasonal H1N1 influenza (A/Brisbane/59/07) and pandemic H1N1 influenza (A/California/04/09) either alone or in combination (co-infection). Transmission from experimentally infected ferrets to other ferrets by direct contact or respiratory droplets was also examined.

Results

Pandemic H1N1 influenza caused more severe symptoms (pneumonia), replicated to higher levels and transmitted more efficiently to other ferrets than seasonal influenza. When ferrets were co-infected with both pandemic flu and either of the two seasonal flu viruses, more severe symptoms were seen in some ferrets than in any of the single infections. In fact, one ferret that acquired its infection from respiratory contact with an experimentally infected ferret needed to be euthanised because its symptoms were so severe (intestinal hemorrhage). In addition to infections of normal flu targets, nose, trachea and lungs, this animal was also found to have an infection in the brain (olfactory bulbs).

No evidence of reassortment between pandemic flu and the two seasonal flu viruses was observed, in either the directly infected ferrets or respiratory droplet infected ferrets.

Analysis

Many of the headlines describing this experiment draw incorrect conclusions from this study. For example:

Swine Flu May Be Less Dangerous Than Predicted: Study

Swine flu outcompetes seasonal flu, unlikely to get more lethal

H1N1 not likely to mutate into superbug: study

None of these headlines is accurate. As discussed above, this study found that the new H1N1 virus is more dangerous than seasonal flu. Further, co-infection with pandemic flu and seasonal flu may lead to more severe symptoms, including death, than infection with either virus alone. Although it is true that the seasonal and pandemic flu viruses did not reassort in this experiment, there is little comfort in this result. Only a small number of animals were involved. Reassortment was never likely to be observed in such a small sample size. The population of humans who are likely to be co-infected with multiple flu viruses is much, much larger. Further, pandemic H1N1 and seasonal flu co-infections are not the only possibilities. The new H1N1 and H5N1 could also co-infect people (and likely will sometime within the next 12 months).

Every time a co-infection occurs, there is a possibility that reassortment or recombination will happen. To avoid disaster, we have to be lucky every time this happens. The virus only has to be lucky once.

Reference

Perez et al. (2009) Fitness of Pandemic H1N1 and Seasonal influenza A viruses during Co-infection. PLoS Currents.

Previous ferret study blogs:

Ferreting out the dangers of swine flu: A discussion of two animal model studies of the new H1N1 flu virus

More evidence that the new H1N1 virus is more dangerous than seasonal flu: The new Kawaoka paper

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