A second health care worker in Missouri reported respiratory illness symptoms—but was not tested—after being exposed to a hospitalized person who tested positive for the H5N1 strain of avian influenza a few weeks ago, the Centers for Disease Control and Prevention announced last week. H5N1 has recently been infecting U.S. dairy cows and several farm workers. Previously in the case in Missouri, another health care worker and a household contact of the infected person developed symptoms, although that health care worker tested negative. The household contact wasn’t tested but got sick at the same time as the person who had tested positive. Details of the Missouri case remain somewhat mysterious—and experts say the lack of information being shared about the investigation is troubling.
It’s certainly possible that the second health care worker was sick with a different respiratory virus; a lot of COVID has been going around. But there hasn’t been much transparency into the Missouri Department of Health & Senior Services’ efforts to rule out possible human-to-human transmission of H5N1, a highly pathogenic bird flu strain that has raised fears of a potential pandemic. In last week’s announcement, the CDC said blood samples from the infected person in Missouri and their household contact are being sent to the agency to test for antibodies to the virus (a lab process called serology). It also said that the second health care worker “will be offered” serological testing. That person and any additional contacts of the individual who had bird flu should definitely be tested for previous infection, says Seema Lakdawala, an associate professor of microbiology and immunology at the Emory University School of Medicine.
Delays in public information about the Missouri case make it hard to know whether things could have been handled better, says Angela Rasmussen, a virologist at the Vaccine and Infectious Disease Organization (VIDO) at the University of Saskatchewan. “I don’t want to second-guess the decision not to test [the additional health care worker] at the time,” she says. “My big issue is what has happened since.” It’s unclear how Missouri’s health department is investigating the case. The CDC is providing assistance, but to send a response team, it must be invited by the state—and so far, that doesn’t appear to have happened. Scientific American has reached out to the Missouri Department of Health & Senior Services for comment and will update this story with any response.
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We spoke with Lakdawala and Rasmussen about what is known about the Missouri case so far and what public health officials need to know to prevent bird flu from becoming another pandemic.
[An edited transcript of the interviews follow.]
What do we know about the second health care worker in Missouri?
SEEMA LAKDAWALA: There was a subsequent health care worker who had some interaction with this H5-positive case in Missouri. The interaction was not clear; the duration was not clear. And it’s unclear how long after that interaction the worker developed symptoms but was never tested. It’s unclear whether this is an influenza infection or just some other respiratory infection. There is a lot of COVID still transmitting around the country right now, so I don’t think we can rule out another respiratory infection.
ANGELA RASMUSSEN: It’s a really disturbing and also puzzling situation. We still actually just don’t have a lot of information about the time line here. The initial patient was identified through the state [influenza] surveillance program. So when they were in the hospital, they tested positive for influenza A, and then it was sent out to determine the viral subtype, which returned the H5 diagnosis. It’s not clear what time line that happened on. When these health care workers were ill, if they weren’t that sick, it’s hard to say if they would have been tested for flu because it’s not clear that it was known that the patient initially had bird flu. You can second-guess that everybody should have been tested, but that’s not really routinely how it works when somebody just has influenza. And I don’t think anybody expected to identify that this patient was infected with H5.
Is there a way to test this person for previous exposure to H5N1?
LAKDAWALA: We really need to understand how many people potentially were exposed or became infected from this individual. And I think serology is our best bet at this point for all contacts, not just those who reported symptoms—both health care workers as well as the housemates of this individual and any other people they had possible interactions with for prolonged periods of time—just to ensure that there weren’t suspected infections or that these were real forward transmission events or not.
RASMUSSEN: Missouri said that they are considering doing serological testing. I mean that is a situation where, when you hear about this and there was no test performed, you are getting that patient’s blood, and you are driving it to [the CDC’s headquarters in] Atlanta yourself. I mean, that is a really serious thing.
Why has there been such a delay in getting information about this case?
LAKDAWALA: So my understanding from that case is that [the original patient] tested positive because they arrived at the hospital, and it took a few weeks to determine that it was H5 in their sample. It was a few weeks because the case [was logged] in the novel influenza surveillance network that the person tested positive for influenza A, but it was not subtyped. Then they kept going to figure out what the subtype was, and that took a few weeks. But by the time it was caught, the patient had a very low level of virus. They were hospitalized for some of their other underlying conditions, and presumably the virus was made more severe because of that.
RASMUSSEN: In my view, here’s what should have happened. I mean, nobody was notified about the initial patient until weeks after they had been in the hospital. And some of that may have been delays, just because they weren’t expecting to get it, and it takes some time to get results back. But for this surveillance program to work, especially for things like rare human cases of H5N1, a lot of this testing needs to happen more expediently, and there needs to be more rapid disclosure of cases that are testing positive for H5.
What does this say about the U.S. response to a potentially major public health threat?
LAKDAWALA: What I have been amazed to learn in all of this is how much role state public health agencies have in these sorts of cases when there’s a novel influenza virus. At least on the agricultural side, the U.S. Department of Agriculture cannot go in and test every farm. It has to be invited.
Are we not getting any information out of Missouri because the Missouri public health department isn’t well equipped? Or maybe they didn’t initiate something quickly enough? Or maybe they are doing it, but they’re just not giving that information.
The investigation relies on state public health funds, and some states may be better equipped than other states. But if we aren’t, as a society, prioritizing public health readiness for pandemics—which we all should be, because as we learned in 2019 and 2020, they do not know any state boundaries—we are all susceptible. We really need to do better about funding our public health agencies so that they are well equipped to respond in a case of an outbreak.
The person in Missouri who tested positive for H5N1 reportedly had no contact with animals, and Missouri hasn’t reported any cow herds that are positive. But do we really know no cows there are infected?
LAKDAWALA: How do we how many cattle herds have even been tested in Missouri? We’re saying that there are no known ones because they haven’t been reported.
What should happen now?
LAKDAWALA: The thing that is bothering me the most is that, this many months after the first cases in Texas, we do not know how many herds are infected in this country. We have no idea about the scope of the outbreak in cattle. Not only do we not know how many herds are positive, but we’re not [always] testing individual cows.
Sick cows may just be mixing in with the herds, so you’re getting continuous spread of the virus on the farm because we’re not identifying cows that are infected and then isolating them. If you isolated them because you knew they were infected, you could then take better precautions to prevent cattle-to-cattle transmission on the farm and spillover to humans.
RASMUSSEN: It’s entirely possible that the health care worker in Missouri does not have H5, but that can easily be determined with serological testing, and that needs to happen, like, yesterday. Because if this does represent human-to-human transmission of H5N1, then time is of the essence in terms of containing it. There needs to be a detailed epidemiological investigation done. There needs to be way more testing of contacts, both testing for flu directly, as well as testing doing serology testing to see if people have been exposed in the past—because if there is a cluster of undetected community transmission, we’re in real trouble unless that can be contained as fast as possible.
In order to do this testing and to do it in a reasonable way, there needs to be adequate communication between the Missouri Department of Health & Senior Services and the CDC. And there needs to be rapid and timely disclosure of this because this is certainly not creating a lot of confidence in terms of how this response is going to go if this is the worst-case scenario, and there is human-to-human transmission of H5. If you can detect the outbreak while it’s still limited in terms of its geography and the number of people who might have been exposed to it, then you can use isolation and quarantine to contain the outbreak and prevent it from spreading. But if you don’t hurry to do that, then you end up with undetected community transmission. And by the time you realize what’s going on, the outbreak might be too big to contain.
The U.S. has a stockpile of H5N1 vaccines. Why are we not giving them to dairy farm workers? Instead the CDC has merely recommended that workers get the seasonal flu vaccine.
RASMUSSEN: One thing that I and many of my colleagues are sort of perplexed about is that dairy workers and people who are extremely high-risk are not being offered vaccines. What’s not clear is what the criteria are for deploying human H5N1 vaccines. I think that there is plenty of justification scientifically. There’s plenty of evidence that this should be offered to dairy workers, but it’s not.
And also, why isn’t there a discussion on the table of vaccinating the cows? I realize that we do have a lot of chickens and cows in the U.S., but veterinary vaccines also have a much lower bar for regulatory approval. So it does seem to me that that’s something that should be more on the table than it is. [Editor’s note: The U.S. Department of Agriculture has approved field studies to test H5N1 vaccines in cows, but these are in the early stages.]
I do think it’s a good idea that the CDC is launching this campaign to encourage seasonal flu vaccination among dairy workers—not because that would necessarily protect against H5N1, though there is potentially some protection that they would get from boosting N1 antibodies, but because it might reduce the risk of reassortment. [Editor’s Note: Such reassortment is the shuffling of pieces of influenza virus that happens when a person is coinfected with two different flu strains, which can result in a more virulent and transmissible virus.] I think offering high-risk people seasonal flu vaccines does offer some protection against that sort of nightmare scenario where a fully pandemic-capable reassortment emerges from a coinfected person—but it still doesn’t really offer them protection against H5.
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