In November of 2014, a highly pathogenic strain of bird flu derived from Eurasia called H5N2 popped up in North America—in a Canadian turkey farm east of Vancouver, to be exact. From there, the virus quickly spread and mutated into new varieties, including H5N1, fanning fears it would vault to humans and cause a deadly pandemic. By March of 2015, it and its kin had swooped into 15 US states, causing 248 outbreaks in domestic birds and $5 billion worth of damages to poultry operations.

Then, it vanished.

“It’s very good news,” Robert Webster, prominent influenza expert at St. Jude Children’s Research Hospital, told Ars. He and colleagues published surveillance data in the Proceedings of the National Academy of Sciences on Monday that shows the swift and unexpected disappearing act by the noxious germ. But, he added, “it’s a mystery where it went.”

Its enigmatic exit may mean that coordinated efforts to defeat the viral spread worked, Webster speculated with optimism. And, in a controversial twist, it may mean that bird vaccines, which aren't used in the US, are boosting potential pandemic flu viruses in other places of the world. Either way, we have more to learn about how such lethal influenza viruses move around, particularly in birds.

“Every time we make predictions, nature will go and do something quite the opposite,” Webster said. Many experts thought that this variety of bird flu would spread to humans and spark massive worldwide outbreaks. But then it didn’t. And instead we saw a pandemic of H1N1 swine flu, he added. “So the thing that you have to do is be prepared."

In the study, Webster and colleagues tested nearly 23,000 wild US water fowl before, during, and after the 2014-2015 outbreaks. The team was looking in wild, migratory birds because researchers expected that the free-moving fliers would provide the virus rides to new locales. Once in a new place, the viruses could potentially wreak mass destruction on commercial and backyard poultry operations, mix and hybridize with distant viral relatives, and get introduced to humans. Such scenarios in domestic birds are known to create and bolster highly pathogenic flu viruses that can spark lethal outbreaks in humans.

Thus, many experts think that wild birds are key to influenza’s spread and cycles, Webster explained. But the new study seems to counter the hypothesis.

Fight or flight

Webster and his team didn’t find any of the high-pathogenic H5N2 viruses in the wild US birds, nor any of the virus’ hybrid offspring, which would be of the H5N-something variety. (The H stands for hemagglutinin and the N stands for neuraminidase, which are viral proteins that help the germ get into and out of, respectively, the cells of its victim. There are several varieties of each, hence the numbering systems. And the viral genes that code for the proteins can easily jumble to form new versions and combinations in descendent viruses, H5N2 to H5N1 or H5N8, for example.)

When the team looked back over influenza records, it noticed that wild water fowl in the US had not tested positive for a highly pathogenic H5N-something virus once in the 43 years prior to the outbreak. Yet they had tested positive for a whole slew of flu viruses that are considered "low pathogenic." Unlike the Eurasian H5N2, these viruses cause garden-variety infections or seasonal flu infections instead of life-threatening illnesses.

We need a lot more research on how and why H5N2 and other highly pathogenic flu viruses are fizzling out of wild birds, Webster said. But, he has a theory. Webster hypothesizes that the garden-variety flu viruses essentially elbow out the highly pathogenic ones. So, when those nasty varieties move into wild bird populations, they don’t stay long.

But, if Webster is right, it raises more questions about why and how some places, particularly in Asia, continually see the spread and maintenance of those highly pathogenic flu viruses in wild birds. And this is where vaccines come in to Webster’s hypothesis.

Flu vaccines for domestic birds don’t always completely block the virus. In a small number of vaccinated birds, highly pathogenic flu viruses can still get a foot in the door and cause an infection. But those infections are mild, more like seasonal flus—unnoticeable to poultry farmers and perhaps even the bird. However, those domestic birds will still poop and shed massive amounts of highly pathogenic viruses. And those viruses can then continually be picked up by wild birds.

In many places in Asia, poultry farmers clamor for vaccinations. But, in the US and Europe, which don’t see the same levels of highly pathogenic viruses, vaccines aren’t regularly used. Instead, the US Department of Agriculture adopted a system of monitoring, quarantining, and culling. That system is what racked up the $5 billion worth of damages in the 2014-2015 outbreak.

It’s expensive, Webster noted, but it may be the best way to squash a potential pandemic.

Proceedings of the National Academy of Sciences, 2016. DOI: 10.1073/pnas.1608853113 (About DOIs).