As China's H7N9 avian influenza outbreak draws to a close, scientists are exploring how this new strain of bird flu started an epidemic in the first place. A study published today in Science suggests the virus prefers traveling by direct contact between mammals rather than airborne transmission. The investigation was conducted by an international collaboration of scientists from China, Canada, and the U.S.

The world held its collective breath after the first cases of the new, deadly H7N9 strain were announced at the end of March. At the height of the outbreak, news media struggled to keep up with the virus's staggering rate of infection, and public officials raced to contain its rapid spread.

Poultry markets were shuttered, as chickens and ducks - possible carriers of the virus - were slaughtered by the thousands. The latest figures estimate the H7N9 flu outbreak has cost $6.5 billion so far in lost business.

The pace of the outbreak has recently tapered off, with the latest confirmed case being recorded on May 7. Scientists are now conducting retrospective analysis of the deadly virus to ascertain how the pathogen managed to spread so quickly in Eastern China and Taiwan.

In this study, a biological sample of the virus from one of the first human cases was used to test for transmission between laboratory ferrets.

Ferrets, a popular animal model for influenza, can provide clues into how flu viruses affect mammalian organs, and the reseachers were surprised to find that H7N9 is found in the brain as well as the lungs.

"It may be advisable to examine human cases for signs of central nervous system affects," wrote the authors.

Ferrets were also picked because efficient transmission between these furry creatures is considered by some to be a good predictor for how flu will spread in humans. For instance, ferrets were used to confirm the 2009 H1N1 swine influenza virus could hop between mammals.

Two scenarios were tested, with both situations matching three infected animals with three ferrets lacking the virus. The first setup had H7N9-positive ferrets mingle with uninfected animals in the same room. In the other experiment, ferrets with and without the flu were separated by a four-inch barrier with holes in it, so as to allow for airborne transmission without direct contact.

All three ferrets exposed to H7N9 via direct contact developed symptoms of flu and mounted a immune response, which is a positive indicator of infection. In contrast, only one ferret exposed via the airborne route had clinical signs of flu.

While their findings suggest H7N9 prefers to travel by direct contact in mammals, their conclusion that "under appropriate conditions human to human transmission of the H7N9 virus may be possible" could be an overstatement.

Limited conclusions can be drawn with regards to human disease, given the ferrets do not develop severe symptoms, while humans do.

"The paper has a good example of the disconnect between ferrets and humans: infection of ferrets with H7N9 results in quite mild disease, and no mortality," said Dr. Vincent Racaniello, a virus expert and immunologist at Columbia University.

"As of 16 May, there were 32 deaths out of 131 confirmed human cases. Clearly, there is a difference in H7N9 pathogenesis in ferrets and humans."

One of their findings does address a major question surrounding H7N9: did pigs contribute to its origins?

Right before the virus was discovered, thousands of dead pigs were found floating in Shanghai's Huangpu River. This massive pig die-off had Laurie Garrett, a Pulitzer-prize winning virus tracker and senior fellow at the Council on Foreign Relations asking "Is This a Pandemic Being Born?"

While her concerns were warranted - pigs have played key roles in infecting humans during prior influenza outbreaks, such as 2009's H1N1 swine flu pandemic.

This study observed that while H7N9 can infect pigs, it doesn't easily pass between pigs or from pigs to ferrets.

Source: Zhu H, Wang D, Kelvin DJ, et al. Infectivity, Transmission, and Pathology of Human H7N9 Influenza in Ferrets and Pigs. Science. 2013.