There’s also a silver lining to the Tamiflu-resistant strains that Kawaoka identified. The mutation behind this resistance works by changing the shape of a protein on the virus’s surface—a protein that Tamiflu normally attacks. But the same protein is also part of the infection process; by changing its shape, the strains weaken themselves. They cause milder disease in both mice and ferrets (although they still spread with the same ease as the drug-sensitive strains).
That’s good news, but it’s no reason to rest on our laurels. In 1999, scientists discovered a mutation called H274Y that made H1N1 strains resistant to Tamiflu, but that also reduced their ability to infect mouse and ferrets. The scientists thought that this mutation was “unlikely to be of clinical consequence.” They were wrong. H1N1 picked up other mutations that compensated for H274Y, creating flu strains that were infective and resistant. By 2008, almost all the seasonal strains of H1N1 had become resistant to Tamiflu. With H7N9, history could well repeat itself.
But Tamiflu isn’t our only weapon against influenza. There’s an experimental new drug called Avigan (or favipiravir) that, rather than going after a surface protein, attacks an enzyme that the virus uses to copy its genetic material. Even Tamiflu-resistant strains of H7N9 fall to this drug, as do other kinds of flu that Kawaoka has looked at—at least in animals. “Whether that’s also the case in humans, we don’t know,” he says.
The viruses could eventually evolve to resist this new drug, too. But, Kawaoka says, “many people, including us, have looked for viruses that are resistant to favipiravir, and I don’t think anyone has found one yet.” And Barclay suggests that scientists should start running clinical trials that test both drugs together. “It still astonishes me that we continue to treat flu patients with a single drug when we know that the virus is highly mutable,” she says. “It’s almost inevitable that drug-resistant viruses can evolve.”
In the meantime, vaccines are being developed to match the viruses seen in the fifth and current epidemic. Other control measures have waxed and waned. When the first of the epidemics struck, Chinese health ministries closed markets and slaughtered birds. But as Helen Branswell reports in STAT, some of those containment efforts became more lax in 2015 and 2016.
Again, there is some good news: H7N9 infects chickens very well, but unlike H5N1, it seems to avoid ducks. That matters because Chinese ducks are often housed outside, and domestic birds can mingle with wild ones. Aboard ducks, bird flu can easily spread from one infected farm to other parts of the world. “That may be a major difference that may make it easier to control H7N9 compared to H5N1.”
It might also be a blessing in disguise that the high-path strains have emerged. The low-path strains were very hard to detect because they didn’t cause symptoms. But the high-path viruses kill infected birds, which means “they might be easier to eradicate from chickens since they can be more easily detected,” says Adolfo García-Sastre, from the Icahn School of Medicine at Mount Sinai in New York. “However, one would need a very well-organized eradication campaign to eliminate them from poultry before they spread to other areas beyond China. I’m afraid that this will not happen, since it did not happen with the H5N1 viruses, which were first detected in 1997, and finally disseminated to most of the rest of the world starting in 2003.”