A 13-year-old girl in British Columbia who was hospitalized with bird flu for several weeks late last year had a mutated version of the virus, according to a report published this week in the New England Journal of Medicine.
It is the first recorded human infection of bird flu in Canada, which has infected at least 66 people in the United States since last March, according to the Centers for Disease Control and Prevention. This includes the country’s first serious case, in Louisiana in December.
So far, almost all cases of bird flu in North America have been mild, with symptoms such as conjunctivitis, runny nose, chills, cough and sore throat.
“I think it’s concerning, but not entirely surprising, that we see some sporadic cases where there is severe disease. Even seasonal flu can occasionally cause very serious illness,” said Dr. Chanu Rhee, an infectious diseases and critical care physician at Brigham and Women’s Hospital and an associate professor of demographic medicine at Harvard Medical School.
So far, the Canadian teenager and the Louisiana patient are outliers, but they show the virus’s ability to cause severe illness and are also an example of how, during prolonged illness, the virus has the possibility of mutating to more strongly affect the humans.
In both cases, samples of the virus showed that once it was in the body, it changed in a way that allowed it to attach to cells in the mucous membrane lining the upper respiratory tract.
“The average bird flu virus is not very good at attaching to the cells of our mucous membrane, which is what it needs to do to cause a human infection,” explained Dr. William Schaffner, professor of infectious diseases at the School of Medicine. Vanderbilt University.
However, the presence of these mutations does not mean that the virus can definitely be transmitted from person to person.
“Just because there are mutations that allow the virus to spread between people doesn’t mean that’s the case,” said Angie Rasmussen, a virologist at the Vaccines and Infectious Diseases Organization at the University of Saskatchewan.
In both cases, no one else was infected, meaning the mutations do not appear to allow the virus to spread between humans, Rasmussen added.
Rhee, Rasmussen and Schaffner were not involved in any of the patients’ cases.
viral roulette
Mutations in the bird flu, or H5N1, viruses that caused severe infections in British Columbia and Louisiana occurred in a protein on the virus’s surface that allows it to attach to cells. Normally, the surface proteins of the H5N1 virus are designed to attach to the birds’ receptors, which is why the virus is so good at infecting poultry. But the mutations seen in both severe cases allowed these versions of the virus to attach to receptors on the human mucous membrane.
Viruses replicate in any body they infect, but they are more likely to do so in people who are immunocompromised or have underlying health problems that make it difficult for their immune system to fight a virus. As the virus persists, it replicates over and over again, occasionally creating mutations that can make the virus more adept at spreading.
“RNA viruses, like flu, have enzymes that basically can’t correct spelling on their own, so they make a lot of mistakes and mutations inevitably arise,” Rasmussen explained.
In addition to a mutation on the surface of the virus that allowed it to better infect humans, the British Columbia teen’s virus sample contained a mutation that allowed it to replicate rapidly once it infected cells, something the virus sample from the Louisiana patient did not have one.
However, more worrying than these mutations is that the virus infects humans at the same time as seasonal flu increases, Rasmussen noted.
“If you get infected with H5N1 and at the same time you get infected with seasonal flu, it’s like shuffling two sets of cards together when they replicate, that can be extremely dangerous,” he added.
This phenomenon is called genetic recombination. The 2009 swine flu outbreak is believed to have resulted from recombination between avian, swine and human flu viruses.
“We already know that genetic reassortment is sometimes really beneficial for the virus and allows it to make a big evolutionary leap much faster than random mutations. That’s why mutations don’t worry me as much as the growing number of human cases,” Rasmussen explained.
Rasmussen compared the possibility that a virus could create a pandemic to playing the lottery.
“Many times, worrying about whether a pandemic will emerge from this is like buying a lottery ticket. The odds are low, but if you buy enough tickets, eventually you will have a winner,” he said.
As the virus infects more humans, especially if those cases are not closely monitored, it creates more opportunities for the virus to mutate and mix with other viruses that are already effective at infecting people.
“We are basically giving the virus a lot of lottery tickets,” Rasmussen added.
serious illness
It’s still unclear where or how the Canadian girl was infected, but the version of the virus she had was “more closely related to viruses detected in wild birds in British Columbia around the same time,” according to the new report.
The Louisiana patient is also believed to have become infected through exposure to birds near her residence. Other cases in the United States have occurred from exposure to dairy cows or poultry.
“We are close to wild animals much more than we think,” Rasmussen said. “We are close to their feathers, their excrement. My suspicion was that it was probably a contact with birds that the person didn’t realize, but how they became infected may never be known.”
The girl, who had mild asthma and obesity, went to the emergency room on Nov. 4 for conjunctivitis and fever, but was sent home without treatment, according to the report.
However, he continued to get sick and soon developed cough, vomiting and diarrhea.
Three days later, he returned to the emergency room: he had difficulty breathing and his body could not get enough blood to his organs. The next day, November 8, she was transferred to the pediatric intensive care unit for respiratory failure, pneumonia, kidney injury, and low platelet and white blood cell counts. On Nov. 9, doctors put her on a ventilator to help her breathe and on extracorporeal membrane oxygenation, or ECMO, a life-saving machine that circulates and oxygenates blood when the lungs and heart are not working properly.
“That’s definitely an indicator of very serious illness,” Rhee said.
The rest of the month was a chaos of daily antiviral treatments and keeping the child intubated until finally, on November 28, her breathing tube was removed when doctors determined she could breathe on her own. Tests revealed that the virus, even with its mutations, was not resistant to available antivirals.
“Fortunately, this virus, like all other bird flu viruses, remains susceptible to the antivirals we have available,” Schaffner said.
Whether humans have immunity to bird flu is complicated and depends on a number of factors, including the flu strain a person was infected with for the first time in their life, Rasmussen explained.
“Viral immunologists think there may be some cross-protection that we’ve had from previous experiences with flu viruses, but if so, it’s not going to be much,” Schaffner said.
