It takes two things to create a human influenza pandemic: the introduction of a novel virus for which the world’s population has no immune response, and the adaptation of that novel virus to spread easily from human to human.
According to Christopher Olsen, the interim vice provost for teaching and learning and professor of public health in the School of Veterinary Medicine at the University of Wisconsin-Madison, if these two criteria are met, it is very likely a human influenza pandemic will break out. And the world is currently watching one such novel virus.
A strain of avian influenza, identified as H7N9, has directed researchers’ and public health officials’ attention to China. According to the World Health Organization, as of May 16, there were 131 reported cases of H7N9 in six regions of China and Taiwan and 32 confirmed deaths.
For Olsen, H7N9 is reminiscent of an earlier avian influenza virus, H5N1, which still is the leading pandemic threat in the world. The fatality rate of H7N9 is currently close to 20 percent and, according to Olsen, “it’s similar to H5N1, where we’re still around 50 to 60 percent case fatality.”
“H7N9 … and H5N1, they’ve clearly distinguished themselves from other, very isolated examples of avian-to-human spread by their severity, and that’s what makes them very scary,” Olsen said.
The first case of H7N9 was reported to the WHO in February and, in the time since, several papers have been published on this particular strain of influenza. Yoshihiro Kawaoka, a professor of virology in the School of Veterinary Medicine at UW-Madison, published one of these papers on H7N9 in the April 11 issue of the journal Eurosurveillence. The paper found it was highly likely H7N9 had adapted to spread from birds to humans.
Kawaoka and his colleagues from the University of Tokyo in Japan observed in four cases of death in China, the isolated virus thought to be the cause appeared to be a 95 percent match to H7N3, a previously know strain of avian influenza found in isolated cases in humans. They concluded H7N9 to be a strain of avian influenza that had adapted to infect humans, and predicted H7N9 would be likely to continue to infect humans in the future.
“These viruses possess several characteristic features of mammalian influenza viruses, which are likely to contribute to their ability to infect humans and raise concerns regarding their pandemic potential,” Kawaoka wrote about H7N9.
Influenza viruses are characterized by two numbers, according to Olsen: an H number and an N number. The H refers to the form of the hemagglutinin protein in the virus and the N refers to the form of neuraminidase in the virus; there are 17 forms of H and nine forms of N in the world. In order for an influenza virus to create a pandemic, it would have to be a novel virus, meaning a virus would have to appear with an H number the world has never seen, or has seen in very isolated cases.
“If nobody in the world has been exposed to that [H number] before because it is a brand new virus coming into the human population, then everybody in the world is susceptible at once,” said Olsen, an expert in pandemics and animal to human viral infections.
Olsen explained, however, having a novel virus was just one of two criteria in created a pandemic, and one must also understand how a virus infects a host and adapts to humans.
Unlike bacterial infections, viruses cannot replicate outside of a living host, so they must continually attach themselves to receptors and hope to infect a cell in order to reproduce.
“Viruses can’t do anything except, at the very most, hope to survive within the environment long enough to reach and infect another host,” Olsen said. “They have to be infecting a host in order to increase their numbers, to replicate, to do anything.”
In order for a virus to infect a host, whether it be a human or other animal, it must attach itself to a receptor of a cell within that host. The receptor acts much like a cup that catches the virus. If the virus is the same shape as the cup, it will bind to the receptor, infecting the cell. In the case of influenza viruses, the receptor is often a type of sugar-coated compound called sialic acids.
However, a virus cannot infect just any host it encounters. The virus must be adapted to be able to bind with the specific receptors on the cells of the host. For avian influenza, birds and humans have different receptors the virus must bind to in order to cause an infection.
The difference between the receptors, according to Olsen, is in the structure of the sialic acids. For avian influenza to infect humans, the virus must bind to a different receptor than it does to infect birds. In order for a virus to move from an animal to a human, it must adapt to the specific receptor in humans, according to Olsen. As Kawaoka and his colleagues observed in their paper, it appears H7N9 has achieved this adaptation.
But, a pandemic requires human-to-human transmission. This adaptation to have the ability to transmit from animals to humans is not enough.
“What triggers a pandemic is when that person-to-person transmission is so efficient, it happens in a community setting,” Olsen said.
For the time being, it does not appear H7N9 has reached a pandemic stage. There is no strong evidence, according to Olsen, that H7N9 has fully adapted to human-to-human transmission. However, Olsen warns of the unpredictability of influenza viruses, saying, “The one thing that is predictable about influenza viruses is they’re unpredictable.”
The world is now just waiting to see if H7N9 makes that final jump to adapt to human-to-human transmission. If this occurs, we may find ourselves in the midst of the worst-case scenario: a widespread, human influenza pandemic.
“The person-to-person issue is the thing that everyone is watching very closely right now,” Olsen said.
