The news that a person in Missouri has contracted H5 bird flu despite having no known contact with infected animals or birds — in other words, no apparent route of infection — raises pressing questions that public health officials are certainly rushing to answer.
The rationale for that urgency is this: an unexplained H5 infection raises the possibility of person-to-person spread of an influenza virus that has never before circulated among humans and to which humans would have no immunity. And this with a dangerous flu virus that scientists have long feared could one day cause a pandemic.
After all, the 2009 AH1N1 pandemic was first noticed when two children in California who had no contact with pigs or each other were diagnosed with influenza infections caused by a virus previously circulating among pigs.
To be clear, it is far too early to conclude that this infection cannot be linked to direct or indirect exposure to infected animals or birds, or to an agricultural product contaminated with the virus.
But there are, as we have noted, questions that need to be answered, and the sooner the better. Here are five.
What is being done to investigate the situation?
News of the infection emerged late Friday when the Missouri Department of Health and Senior Services issued a notice a press releasefollowed shortly afterwards by A statement from the Centers for Disease Control and Prevention; neither provided much information. The CDC statement said Missouri was conducting the on-site investigation to find the source of the individual’s infection.
Flu experts watching from a distance are puzzled by the apparent lack of urgency. They wonder why the CDC hasn’t sent a team to the state, and why health officials waited so long to make the case public.
Their concerns add to criticism that the entire US response to the outbreak of H5N1 viruses in dairy cattle has been lethargic; A number of critics have suggested that if this outbreak occurred elsewhere, the US would be in turmoil over the scope of the response. The concern is that if the virus, which is genetically wired to infect birds, adapts to spread efficiently among mammals, it will come a big step closer to transmission among humans.
“I would like to see a ‘better safe than sorry’ study,” Marion Koopmans, head of the viroscience department at the Erasmus Medical Center in Rotterdam, Netherlands, said of the response to the Missouri case.
What Koopmans is doing to unravel the mystery of how this person became infected is at the top of the list of questions that need to be answered. “I would like to see a broad net here,” she said, for example to see if there is any evidence of hidden chains of transmission of the virus from person to person. It “doesn’t all have to be in the public eye, but I would like to know that it is [being] taken very seriously.”
The fact that the case was only publicly announced two weeks after the individual was admitted to hospital and after the person had recovered and been discharged seems like a missed opportunity for Angela Rasmussen, a virologist who specializes in emerging infectious diseases at the University of Saskatchewan. and Infectious Disease Organization in Saskatoon, Canada. Local doctors should have been alerted quickly so they could look for more similar cases, she said.
“If there is human-to-human transmission, it is critical to carry it out [epidemiologic] investigation as quickly and efficiently as possible, so the choice to drag out and not provide details on follow-up is puzzling and very poorly reflects the capacity and practice of both the state of Missouri and the federal epidemic response,” Rasmussen told STAT in an email.
Thomas Peacock would like to know if people investigating the case have or plan to take blood samples from close contacts of the infected person to look for evidence of H5 infections that may have gone undetected. Peacock is an influenza virologist at Britain’s Pirbright Institute, which focuses on controlling viral diseases in animals.
He believes there will eventually be another explanation, but if this case turns out to involve human-to-human transmission, “the U.S. can no longer just sit on its thumbs.”
Is this the same H5 virus spreading among cows?
The outbreak among dairy cattle has infected nearly 200 herds in 14 states – as far as we know. Missouri has not reported any infections in cows. However, farmers in many places have refused to test their cows. So there could be much more of the virus in the country than is currently known.
The virus causing the outbreak in cows is the highly pathogenic bird flu – sometimes abbreviated to HPAI – of the H5N1 subtype. That’s a family of viruses. The specific version in cows is called clade 2.3.4.4b, genotype B3.13.
As of Friday, all that was known about the Missouri case was that the person was infected with an H5 virus. The CDC was still trying to figure out the virus’s neuraminidase, the N in its name. Sometimes this is not possible, for example if there is not much virus in the patient’s sample.
The CDC is also working to capture the genetic sequence of the virus. A sequence could help resolve the source of the virus by allowing a comparison of the person’s virus with other known versions of the virus.
“To be honest, I assume it will be a high path H5N1. And if so, it’s probably the beef because there’s a lot of that out there right now,” Peacock said.
Rasmussen noted that knowing the N number of the virus is important because influenza A viruses – H5N1 is an influenza A virus – can exchange genes with each other, creating so-called reassortants. That process could create a new virus that is better at infecting people, she said.
How sick was this person? Was he or she hospitalized because of flu symptoms, or for other reasons?
The press release from Missouri provides very scant details about the infected individual and says no additional information will be released due to patient privacy.
The person who tested positive went to the hospital on August 22. The person had “underlying medical conditions” – although there are no details on how many or how serious these are. There is no indication of the person’s age, but if it had been a child, the press release would likely have mentioned this. It says the person recovered and was released from the hospital. It does not indicate how long the person was in the hospital or whether some of that time was spent in intensive care.
Why does it matter how sick the person was, and whether the flu prompted the hospitalization or something else? There have been thirteen other H5 cases in the US this year, all directly or indirectly linked to the outbreak in cows. All these people had very mild illnesses.
If this person’s H5 infection was severe enough to require hospitalization, that broadens the picture of the spectrum of disease that 2.3.4.4b B3.13 viruses can cause. And it would suggest that we shouldn’t assume that we know how this virus would behave if it starts spreading among people.
“It’s important to know what this is [illness] looks like in humans, and to understand underlying medical conditions that can change a patient’s risk profile,” said Rasmussen.
Has this person really had no contact with infected animals or birds? Does this person have a cat that can go outside?
The state and CDC press releases emphasize that this is the nation’s first H5 case in a person with no occupational exposure to infected cows or poultry. “The patient reported no exposure to animals,” Missouri said.
But is it possible that the person was indirectly exposed, for example through contact with farm workers who may have been exposed to infected poultry or cows? Some suspected H5N1 transmission events between people in other countries have occurred among people whose close household contacts interacted with infected animals, Peacock noted.
Other experts question whether the person had bird feeders, which could have exposed him or her to wild bird droppings. They also wondered if there were cats in the household. There have been a number of reports of infected cats on farms with H5N1 infected dairy cows, probably caused by the consumption of contaminated milk. Cats can also become infected through encounters with infected wild birds.
Did this person consume raw milk?
One of the big questions in social media discussions among scientists this weekend is whether this person drank raw milk or consumed raw milk products. Unpasteurized milk from infected cows contains extremely high levels of the virus. Laboratory experiments have shown that feeding contaminated raw milk to mice can cause serious illness. Many of the farms with infected cats have reported deaths among the animals.
It is not known what risks drinking H5N1 milk poses to humans, but scientists worry it could cause illness. For example, Peacock is surprised that infections linked to raw milk consumption have not yet been identified.
‘The obvious question I would ask is: have you ruled out that this isn’t someone who has a large tub of raw milk in the fridge? Because that just seems like such an obvious route for a cryptic infection,” he said.
Rasmussen agreed that exploring this possibility is critical, saying, “If this is [due to] consumption of raw milk, this would be very valuable information on the feasibility and risk of this route of exposure.”