July 19, 2013
Ferret Study Shows H7N9 Could Transmit Between Humans
Lawrence LeBlond for redOrbit.com - Your Universe Online
The H7N9 bird flu strain that broke out in China earlier this year, sickening more than 130 and resulting in at least 43 deaths, has so far remained largely non-transmissible between humans. Regardless, that has been one of the most pressing questions to date, with fears that a move to human-to-human transmissions could spark a global pandemic.
But a recent study, published online in the journal Science, has shown that the virus does have the ability to become airborne between mammals, after three experiments involving ferrets have shown positive transmission results.
Ferret models are typically regarded as the most accurate ways to assess human-to-human transmission and the researchers had intentionally infected the animals to test their theory.
Hualan Chen, of China's Harbin Veterinary Research Institute, and colleagues report that they have isolated a sample of the H7N9 strain that was shown to be "highly transmissible" via respiratory droplets.
When Chen and his team inoculated three ferrets in one cage with the sample strain from a person who fell ill in the Anhui province, three ferrets in an adjacent cage all became infected. After analyzing the strains, the team found that all three infected ferrets in the separate cage had the same strain as those in the first. The team had similar results in two subsequent tests, although in the first follow-up, only one of the three ferrets in the separate cage fell ill, and only one in the third cage fell ill using a sample strain taken from a bird.
While some may argue that ferret models have limitations, Chen and colleagues noted that their findings show that H7N9 could in fact become a future problem.
"Currently, implementation of compulsory control measures in H7N9 virus-positive live poultry markets is preventing further human infections; however, the elimination of the H7N9 virus from nature is a huge and long-term challenge," they wrote. "Its replication in humans will provide further opportunities for the virus to acquire more mutations and become more virulent and transmissible in the human population."
Chen's results were not duplicated in a different control setting use the same Anhui sample. A group of researchers from the US Centers for Disease Control and Prevention (CDC) came to a much different conclusion in their study.
After inoculating two groups of three ferrets, the team found that the disease spread to only two of six ferrets in an adjacent cage. The CDC team reported in the 10 July issue of Nature that their virus "did not transmit readily by respiratory droplets."
The CDC team emphasizes "that additional virus adaptation in mammals would be required to reach the high-transmissible phenotypes observed by the respiratory droplet route with pandemic and seasonal influenza A viruses." They noted this was in sharp contrast to Chen's findings.
In a second study also published in the same issue of Nature, a team led by Yoshihiro Kawaoka, a virologist at the University of Wisconsin, Madison, and the University of Tokyo, reported that the Anhui sample infected one in three ferrets -- the same percentage as what was seen in the CDC study.
However, Kawaoka concurs with Chen's team that the virus poses "a formidable threat to public health" due to respiratory transmission.
Although Chen's findings are somewhat different than what was found in the CDC and Kawaoka findings, virologist Ron Fouchier of Erasmus MC in Rotterdam, the Netherlands, said the results were more similar than it seemed.
"H7N9 clearly transmits via aerosol or respiratory droplets in ferrets," says Fouchier, whose own studies with ferrets inoculated with the H5N1 subtype drew worldwide criticism when he intentionally made the bird flu virus transmit through respiratory droplets to tease out responsible mutations. "In general, human flu viruses transmit in 100 percent of ferrets, avian in 0 percent, and this one is in between."
It is likely the debate is not over on transmissibility in H7N9. Fouchier noted that the experiments in these studies included too few ferrets to draw definitive conclusions on transmissibility between humans.
"Do you say the glass is half full or half empty?" Fouchier asks. The CDC researchers "are the optimists, while the other groups are more pessimistic." He said right now the bottom line is that we are fortunate that the disease is not being spread efficiently between humans. But all it will take is a few mutations and we could see it easily adapt into a full-blown pandemic via human-to-human transmissions.
This H7N9 outbreak still requires close monitoring to see how it behaves in birds and humans.