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An Update on Avian Influenza in Dairy Cows, Poultry, and Humans

Outbreaks of H5N1 continue to rise in dairy cattle and poultry, as well as in other wild and domesticated animals, including the first confirmed infection in a pig. Human cases also continue to occur, primarily—but not exclusively—in people who had exposure to infected animals.

In this Q&A, adapted from the November 26 episode of Public Health On Call, Stephanie Desmon speaks with Meghan Davis, DVM, PhD ’12, MPH ’08, associate professor in Environmental Health and Engineering, and Andrew Pekosz, PhD, professor in Molecular Microbiology and Immunology, for an update on the spread of H5N1 in the U.S. They share updates on viral sequencing and patterns of spread, the potential for economic impacts and interruptions in the food supply, risks to the general public, and concerns about how a presidential administration change in January may impact public health’s ability to mount a sufficient response.

What is the state of bird flu in the U.S. at this moment?

Meghan Davis: When we last spoke in May, we were investigating a growing outbreak of H5N1 among dairy cows and poultry. A lot has happened since then. At this point, we have over 600 cow herds that have been confirmed positive, and that number is growing almost every day—particularly in California, which is the current epicenter.

Our last discussion was also before the big outbreak in Colorado that majorly impacted both dairy and poultry. We're seeing something similar in California now, where there’s been an explosion of cases within the dairy industry. California is the number one dairy producing state in the country, as well as a very large poultry producing state. A lot of different kinds of poultry flocks have been affected there, including turkeys.

There have been more than 50 confirmed human cases in the U.S., including a child in California with no known contact [with animals]. There’s also a case in Vancouver, British Columbia, where a teenager is in critical condition and didn't have any access to animals. What can you tell us about human cases?

Andy Pekosz: The good news is that the vast majority of these human infections are rather mild. Most of them can be traced back to people working on dairy farms or people who were involved in poultry farms where there was an outbreak of H5N1.

The bad news is that case numbers in humans keep increasing over time. That's always an opportunity for the virus to start adapting to be better at either infecting or transmitting among humans. We're seeing [new] cases in Oregon. The case in British Columbia is particularly concerning, because the individual had a very severe infection and was hospitalized in intensive care with respiratory symptoms.

Importantly, when researchers sequenced the virus, there were some ambiguities; the sequence wasn't very clear at three very critical amino acid positions that are important for infecting humans. What many scientists think is happening is that the virus is sort of a mixed population—it's starting to adapt to humans at those sites, hence the sequence is a little bit difficult for us to read.

The Oregon and B.C. cases are slightly different viruses from the [one in] dairy cows, so we're now seeing different kinds of H5N1 infect humans as well. All of this, as Megan says, just continues this explosion of cases among both humans and animals, and with different kinds of H5s infecting and with the signs of the virus adapting, it really does warrant being really cautious as we go forward.

The CDC is maintaining that the risk of human to human transmission among the general public is low. Can you tell us more about that?

AP: The good news is, so far, no clear person to person transmission of any significant nature has been documented or detected. There was a case in Missouri where an individual and a household contact did not have any known, easily tracked exposures to H5N1, but both had evidence of infection. The case in California and the case in B.C. are also cases where there is no clear connection to an infected animal, yet these people tested positive. But that's not necessarily uncommon.

As we look at H5N1 cases around the world, there are always some percentage of these cases that can't be attributed directly to a clear exposure. That's kind of epidemiology in general: Sometimes you can make all the connections, sometimes you can't. 

Would evidence of person to person transmission be a danger sign?

AP: Yes, if we start to detect people with H5N1 whose only contact was another person infected with H5N1—that would be a real danger sign.

MD: We should add that with dairy workers and poultry workers, a lot of their household contacts are also being approached, and where they consent, they're being monitored.

There was a study that looked at serology—evidence of prior infection, rather than just testing for active virus in symptomatic people—and there was a small proportion, 7%, who were seropositive and didn't recall having any symptoms. That suggests that it's possible to have asymptomatic infection, or at least not recognized by the person as being symptomatic.

Before this, we didn’t typically swab people who were not symptomatic, so now there is some expansion of looking at these contacts to make sure that there might not be a transmission chain of asymptomatic person to asymptomatic person. We've got a lot of reassurance, and now we're looking a little bit deeper.

What’s going on in the dairy and poultry industries from an economic perspective?

MD: You're going to have some regional consumer impacts—people who are purchasing dairy products or turkey, which is on everyone’s mind this time of year may see some potential shortages. On the other side, you have a lot of resiliency in this system, and you can see a shifting around of commodities. Right now, most of the impact is on the West Coast and along the Pacific Flyway.

For the poultry and dairy farmers, there are indemnification programs. They're being partially compensated for their losses by the USDA. They have a specific program of indemnification, usually by reimbursement. However, the reimbursements usually don’t quite match market value, and they may only be available for certain things. For example, if the farmer needs to discard milk because it’s considered infectious because the herd has H5N1, they'll get that covered, usually after some delay. Dairy farmers tend to be pretty close to the margin, meaning that when there’s a big, unexpected financial hit, they may not be able to be made completely whole [through indemnification]. 

There’s also the optics of this and its impact on consumer confidence in the product. These are things we need to put effort into understanding, so that we can make sure that [even with] our public health systems—herd quarantining, culling, disrupted food supplies—we're making it possible for farmers to keep their businesses going.

AP: It's important to note that these dairy cow farms can be infected for weeks, if not months, on end. These farmers are in a situation where they can't bring many of their products to market for extended periods of time. We have to make sure we're compensating them and that their efforts at minimizing disease spread aren't butting up with their desire to actually make some money and stay in existence. As we all know, when public health measures start to impact economics, it's the public health measures that usually get cut.

What can we do to boost public health efforts among the migrant workers on dairy and poultry farms?

MD: The CDC has put some efforts in with trusted groups that already have established relationships in these communities. Working through these existing groups is absolutely essential., especially given that these communities may have different experiences with government agencies, and not all of them may be positive ones. 

Among the goals of the CDC funding here is to increase vaccination rates among the workforce, specifically for seasonal flu, to prevent someone from being co-infected with both seasonal influenza and H5N1. We don't want the opportunity for this virus to encounter another virus like seasonal influenza that's well-adapted to human to human transmission.

Is there a vaccine for bird flu?

AP: Yes, but the vaccine for humans is experimental and hasn’t gone through many of the clinical trials that are needed to distribute it in this kind of response. BARDA has a stockpile of the vaccine, and they've gone so far as to put the vaccine into vials so that it can be easily distributed in case of emergency.

These stockpiles of H5N1 vaccines would still need some testing in large scale clinical trials before they could be considered for use in humans. A faster way they could be used is via Emergency Use Authorization, which would allow them to be used in humans based on their history of safety and efficacy, but this would only occur if the U.S. felt a pandemic was imminent and needed some sort of immediate response.

The NIH is planning to do some safety and efficacy studies to make sure that these vaccines actually work in humans. They've followed the regular flu vaccine protocol, but they need that final step of getting it in the arms of some people and making sure people are responding to the vaccine in the way that’s expected.

MD: Globally we have animal vaccines available, although those aren't a great match for this particular H5N1. There have been developed poultry vaccines that are either finishing field trials or pretty close. And there are now swine and bovine vaccines also in development.

The question is whether there’s going to be an economic push to use these vaccines. Some people may not know that there are trade barriers that you need to be able to Differentiate Infected from Vaccinated Animals (DIVA). The challenge is that a country may not allow imports if they can’t test a product and know that it was clearly vaccinated as opposed to infected. That can have real impacts in terms of commodity trade.

How should the general public feel right now about avian flu? Is the current H5N1 situation reminiscent of COVID?

AP: The general public is still relatively safe from H5N1. We have a lot of known risk factors for the cases [that have occurred] in humans. This is one of those situations where public health officials are scratching their heads a bit about how they can better limit the spread of this virus in some of these farm situations. We thought we had a good handle on how this virus was spreading from farm to farm, but that doesn't seem to be the case anymore, because of all the outbreaks that have been occurring in California and elsewhere. Scientists are trying to get their boots on the ground to figure out what else can be done to try to limit the spread of this virus.

MD: Most people are going to be at low risk because of the way we do food safety and prevent these products from coming to market. But we do recognize that milk, if it is raw and it is infected, could be highly infectious, not just to humans, but importantly to cats—which can get extremely severe disease—and other companion animals, like dogs and ferrets, which are especially susceptible. Some state-level regulations might permit raw milk for pet use only, even if they restrict it for human use.

Looking ahead to a new administration coming in in January, what are your concerns with regard to the virus?

AP: One concern is all the talk about cutting funding for science. You can't respond quickly if you don't have the people and the resources to do so. One of the many lessons we learned from COVID response is that when you've got a strong group of individuals who are ready to respond, you need to give them the resources, and they can respond very quickly to these situations. My worry is that we’ll get caught up in political maneuvering to reduce resources to those individuals, which is going to make us less prepared to respond.

MD: It's going to put more on the states. If federal agencies aren’t focusing as much on H5N1, responses are going to vary from one state to the next. But what's important to recognize about infectious diseases, which can cross state lines and cross national boundaries, is that high-level coordination is absolutely essential. That's where I am most worried.

There has also been some signaling around things like raw milk and valuation of vaccination, and there could even be consumer-based changes that could put more people at risk. We don't want to give this virus any more opportunities.

The FDA just cleared a clinical trial for a self-amplifying mRNA vaccine for H5N1. What is a self-amplifying mRNA vaccine?

AP: This is a type of mRNA vaccine based on RNA viruses. The mRNA is delivered via a shot, and your cells not only make the protein from the mRNA that’s injected, but that mRNA also replicates itself, making more copies that can be used to make more of the protein you want to make antibodies for.

When would this vaccine be widely available? Would it just be for farm workers and those who are at risk of coming into contact with the virus?

AP: This is in the early stages of development and would not be available for some time.

Source : jhu.edu

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