Can Dangerous Bird Flu Virus Fly Between Humans?

Since a new bird flu virus began sickening and killing people in China in March, one of the most pressing questions has been whether the virus, H7N9, would easily spread from human to human, possibly kicking off a global pandemic. Fortunately, no convincing signs of such transmission surfaced, and the outbreak—which led affected Chinese cities to close poultry markets and cull birds—seems to have ground to a halt. But three new studies in ferrets show that the virus can spread in the air between mammals, reawakening worries of human-to-human transmission.

Today, a team led by virologist Hualan Chen of China's Harbin Veterinary Research Institute reports online in Science that in experiments with ferrets, an H7N9 virus isolated from a human was what the researchers described as "highly transmissible" by respiratory droplets. In the ferret model, widely regarded as one of the best ways to assess human-to-human transmission, researchers intentionally infect animals in one cage and determine whether the virus spreads to others in an adjacent cage. When Chen and colleagues inoculated three ferrets in one cage with H7N9 virus samples from a person who fell ill with the disease in Anhui province, all three ferrets in an adjacent cage became infected, and the viruses isolated from them matched the ones used in the test. The researchers repeated the experiment and found the same outcome. Two other viral samples from different patients spread to only one of three exposed animals, as did one taken from a bird.

Although the ferret model has its limitations, Chen and co-workers conclude that their findings portend future problems. "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 write. "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."

But a group at the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta that performed a similar experiment with the same Anhui province sample came to a different conclusion. After inoculating two groups of three ferrets, they found that it spread to two of six ferrets in adjacent cages. A different human sample had the same transmission frequency by the respiratory route. As the CDC researchers conclude in the 10 July issue of Nature, the virus "did not transmit readily by respiratory droplets." In contrast to Chen's team, they emphasize "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." CDC did not respond to a request for an interview.

A second study published in the same issue of Nature, led by Yoshihiro Kawaoka, a virologist at the University of Wisconsin, Madison, and the University of Tokyo, reported the Anhui sample infected one in three ferrets—the same percentage as CDC found. However, the researchers drew a different conclusion from the CDC group, writing that the respiratory transmission they observed contributes to their assessment that H7N9 viruses pose "a formidable threat to public health."

Although the Chen group's findings differ from those of the CDC and Kawaoka teams—and those two labs appear to reach different conclusions about the severity of the threat—virologist Ron Fouchier of Erasmus MC in Rotterdam, the Netherlands, notes that the results are not as disparate as they may seem. "H7N9 clearly transmits via aerosol or respiratory droplets in ferrets," says Fouchier, whose own ferret studies with the H5N1 subtype caused an international uproar when he intentionally made that bird flu virus transmit through the air to help tease out responsible mutations. "In general, human flu viruses transmit in 100% of ferrets, avian in 0%, and this one is in between."

Nor are the studies likely to be the end of the debate. Statistically, Fouchier says, the experiments included too few ferrets to arrive at conclusions about the likelihood of transmission to exposed animals. "Do you say the glass is half full or half empty?" Fouchier asks. "CDC are the optimists, while the other groups are more pessimistic." Fortunately, the bottom line at the moment is that H7N9 has not spread efficiently between humans—although a few mutations could tip the scale in the virus's favor, which warrants close monitoring of how it behaves in birds and us.