U.S. health officials have run into obstacles in their efforts to determine whether a Missouri person infected with H5N1 bird flu passed the virus on to others, causing a delay that will likely fuel concerns about the possibility that there has been human-to-human transmission.
The Centers for Disease Control and Prevention has blood samples from several health workers and a household contact of the Missouri case that it plans to test for antibodies that would indicate whether they too had been infected with the virus, an agency official told STAT.
But the CDC has had to develop a new test to look for those antibodies because key genetic changes to the main protein on the exterior of the virus found in the Missouri case meant the agency’s existing tests might not have been reliable, Demetre Daskalakis, director of the CDC’s National Center on Immunization and Respiratory Diseases, said in an interview. He suggested it will be mid-October before the work can be completed.
“The antibodies that would grow in the person exposed to that virus would then be different then the antibodies that would grow in a person who had a virus without those mutations,” Daskalakis said.
Developing the new test has been challenging because the sample from the patient contained so little viral material that the CDC was not able to grow whole viruses from it. Instead its scientists have had to reverse engineer H5N1 viruses that contain the changes to use them as the basis for the new serology test, he said.
There is still no explanation of how the individual contracted the virus. The unidentified individual was hospitalized for other health problems on Aug. 22, and was released three days later. While in hospital the person was tested for a panel of respiratory viruses and tested positive for influenza.
The state’s ongoing investigation into the case has retrospectively turned up six health workers who cared for the patient who went on to experience respiratory symptoms. One tested negative for flu at the time she or he was ill but the other five were not tested when they were sick. Neither was the household contact. Blood from those six individuals will be tested for H5N1 antibodies.
There are fears in some quarters that this represents a cluster of cases, which infectious disease experts agree would be concerning. Although there have been a few times where person-to-person spread of the virus probably took place outside the U.S., in the main H5N1 is a virus that can’t easily infect humans or spread from one person to another. Were that to change, the risk of a pandemic would be dramatically higher. That possibility has sparked an understandable desire for answers about the Missouri case, fast.
But that isn’t possible in this case, Daskalakis said. “Biology takes time,” he said.
Jesse Bloom, an evolutionary virologist at the Fred Hutchinson Cancer Center in Seattle, recently commented on the mutations of the Missouri virus on the social media site X, noting that one is sufficiently important that it might erode the effectiveness of some of the candidate vaccine viruses that have been create to be the starting material for H5 vaccines, if mass production is needed.
Bloom told STAT the mutation is not present in the candidate virus that was used to produce 4.8 million doses of vaccine that are currently held in the Department of Health and Human Services’ National Pre-Pandemic Influenza Vaccine Stockpile.
The mutation in the Missouri virus could also affect a serology test’s ability to detect antibodies in blood samples, if the test did not look for antibodies that recognize it, Bloom said. The result could be a false negative test, or test results that are hard to read.
“If you’re getting serology that’s kind of at this ambiguous level, where it’s a little bit hard to be super confident whether it’s positive or negative, certainly this type of mutation could make you want to then redo the assays with a virus that contained that mutation,” Bloom said.
The CDC is also concerned about the possibility that antibodies to seasonal flu strains — which virtually every adult alive would have — could trigger a false positive result when the H5N1 serology test is run. So the agency’s labs will also take the additional step of depleting each sample of antibodies to H1N1, one of the human flu strains, before it tests the Missouri blood samples for H5N1 antibodies, Daskalakis said.
All this work adds to the time it is taking to reach answers. But Bloom saw it as defensible, though he stressed he did not have details of the approaches the CDC is taking to test the Missouri samples.
“As someone who’s very interested, I hope they’re able to do it as quickly as possible,” he said. But he noted that in a case such as this, “serology can be a little bit more tricky if you’re trying to reach a really highly confident conclusion.”
“I’m sure they don’t want to put out something prematurely that’s inaccurate. So if they’re not getting a super clear answer they may want to spend more time working on positive and negative controls and really making sure they’re correct in terms of whatever they end up saying,” Bloom said.
Michael Osterholm, director of the University of Minnesota’s Center for Infectious Diseases Research and Policy, also said he can understand the delay, though he expressed concern that some people have already concluded that transmission did occur in Missouri.
While it is possible that serology testing will show some of the patient’s contacts were infected, it’s also possible that those individuals had Covid-19 or another respiratory bug, he said.
“We are all just going to have to wait and see,” said Osterholm.
Meanwhile the CDC continues to monitor multiple data streams for any evidence of unusual flu activity in Missouri, Daskalakis said. To date, there has been nothing that has triggered any alarms.
“We’re not seeing anything that looks like any flu signal,” he said. “All of the systems are firing at full steam to make sure that we see [it] if there’s anything going on.”
Correction: A previous version of this story incorrectly suggested the mutation in the Missouri patient’s virus might have eroded the effectiveness of all H5 vaccines the U.S. government has stockpiled.
